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17.2k
22,705,952
2013-06-11
2022-04-08
1532-8651
Regional anesthesia and pain medicine
Perioperative nerve injury after total shoulder arthroplasty: assessment of risk after regional anesthesia.
Sviggum Hans P, Jacob Adam K, Mantilla Carlos B, Schroeder Darrell R, Sperling John W, Hebl James R
eng
null
Journal Article, Research Support, Non-U.S. Gov't
null
IM
22705952, 10.1097/AAP.0b013e31825c258b
One of the most debilitating complications after total shoulder arthroplasty (TSA) is perioperative nerve injury (PNI). Interscalene blockade (ISB) improves clinical outcomes after TSA, but it may increase the risk for PNI. The objective of this large-scale, single-institution cohort study was to test the hypothesis that the use of ISB increases the risk for PNI after elective TSA.
Adolescent, Adult, Aged, Aged, 80 and over, Anesthesia, Conduction, Arthroplasty, Replacement, Cohort Studies, Female, Follow-Up Studies, Humans, Male, Middle Aged, Peripheral Nerve Injuries, Postoperative Complications, Registries, Risk Factors, Shoulder, Young Adult
null
22,705,965
2012-11-05
2022-03-11
1873-2976
Bioresource technology
Harvesting Nannochloris oculata by inorganic electrolyte flocculation: effect of initial cell density, ionic strength, coagulant dosage, and media pH.
Garzon-Sanabria Andrea J, Davis Ryan T, Nikolov Zivko L
eng
null
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.
Culture Media, Electrolytes, Sodium Chloride
IM
22705965, S0960-8524(12)00662-1, 10.1016/j.biortech.2012.04.057
Process variables affecting harvesting efficiency of Nannochloris oculata by AlCl(3) flocculation such as, cell density, ionic strength, coagulant dosage, media pH, and cell surface charge were investigated. Initial cell density and coagulant dosage had a significant effect on the removal efficiency; however, levels of ionic strength tested were not significant. Best flocculation conditions of investigated variables were: 0.0016 ng of AlCl(3)/cell, 3.0×10(7) cell/mL, and pH 5.3. Removal efficiency at optimum conditions and salt concentrations of: 0, 15, and 30 g/L NaCl was 96, 98, and 97 %, respectively. Low cell density cultures ∼10(6) cell/mL, required five times greater AlCl(3) dosage to achieve the same removal efficiency. Destabilization of algal cultures using 0.0032 ng of AlCl(3)/cell was observed by reducing the zeta potential to -22 mV. Acidification with HCl for conducting flocculation at pH 5.3 could be a significant cost burden unless is mitigated by selecting a low-buffering-capacity media.
Cell Count, Chlorophyta, Culture Media, Electrolytes, Flocculation, Fresh Water, Hydrogen-Ion Concentration, Osmolar Concentration, Sodium Chloride, Software, Static Electricity
null
22,705,966
2012-11-05
2012-07-04
1873-2976
Bioresource technology
A new thermostable β-glucosidase mined from Dictyoglomus thermophilum: properties and performance in octyl glucoside synthesis at high temperatures.
Zou Zheng-Zheng, Yu Hui-Lei, Li Chun-Xiu, Zhou Xin-Wen, Hayashi Chihiro, Sun Jie, Liu Bao-Hong, Imanaka Tadeyuki, Xu Jian-He
eng
null
Journal Article, Research Support, Non-U.S. Gov't
Glucosides, octyl-beta-D-glucoside, beta-Glucosidase
IM
22705966, S0960-8524(12)00645-1, 10.1016/j.biortech.2012.04.040
A new β-glucosidase (DtGH) representing 40% identity with an apple seed glycosidase (ASG) was cloned from Dictyoglomus thermophilum. DtGH showed extremely high thermostability in aqueous solution, with half-lives of 533, 44, and 5 h measured at 70, 80 and 90 °C, respectively. Therefore it was used for direct glycosylation of n-octanol at 70 °C instead of 50 °C as usually. As a result, the glucose based conversion was increased by 27%, but the time spent to reach equilibrium was decreased from 7 d to 3 d. This enzyme also exhibited excellent stability under the reaction environment, retaining 70-80% of its initial activity after 7 d of incubation at 70 °C in either 1.7 M glucose solution or octanol-aqueous (85:15, v/v) system. It could retain part of synthetic activity even in boiling water. Owing to the strong glucose-tolerance and extremely high thermostability, DtGH should be promising for various glucosides synthesis.
Bacteria, Enzyme Stability, Genes, Bacterial, Glucosides, Hot Temperature, Hydrolysis, Kinetics, beta-Glucosidase
null
22,705,968
2012-09-27
2022-03-11
1471-6771
British journal of anaesthesia
Can regional anaesthesia for lymph-node dissection improve the prognosis in malignant melanoma?
Gottschalk A, Brodner G, Van Aken H K, Ellger B, Althaus S, Schulze H-J
eng
null
Journal Article, Research Support, Non-U.S. Gov't
null
IM
22705968, S0007-0912(17)32897-0, 10.1093/bja/aes176
Optimized anaesthetic management might improve the outcome after cancer surgery. A retrospective analysis was performed to assess the association between spinal anaesthesia (SpA) or general anaesthesia (GA) and survival in patients undergoing surgery for malignant melanoma (MM).
Adolescent, Adult, Aged, Aged, 80 and over, Anesthesia, General, Anesthesia, Spinal, Child, Child, Preschool, Female, Humans, Kaplan-Meier Estimate, Lymph Node Excision, Lymphatic Metastasis, Male, Melanoma, Middle Aged, Neoplasm Staging, Prognosis, Retrospective Studies, Skin Neoplasms, Treatment Outcome, Young Adult
null
22,705,967
2012-10-25
2012-06-20
1361-6560
Physics in medicine and biology
Radioactive bone cement for the treatment of spinal metastases: a dosimetric analysis of simulated clinical scenarios.
Kaneko T S, Sehgal V, Skinner H B, Al-Ghazi M S A L, Ramsinghani N S, Marquez Miranda M, Keyak J H
eng
null
Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.
Bone Cements
IM
22705967, 10.1088/0031-9155/57/13/4387
Vertebral metastases are a common manifestation of many cancers, potentially leading to vertebral collapse and neurological complications. Conventional treatment often involves percutaneous vertebroplasty/kyphoplasty followed by external beam radiation therapy. As a more convenient alternative, we have introduced radioactive bone cement, i.e. bone cement incorporating a radionuclide. In this study, we used a previously developed Monte Carlo radiation transport modeling method to evaluate dose distributions from phosphorus-32 radioactive cement in simulated clinical scenarios. Isodose curves were generally concentric about the surface of bone cement injected into cadaveric vertebrae, indicating that dose distributions are relatively predictable, thus facilitating treatment planning (cement formulation and dosimetry method are patent pending). Model results indicated that a therapeutic dose could be delivered to tumor/bone within ∼4 mm of the cement surface while maintaining a safe dose to radiosensitive tissue beyond this distance. This therapeutic range should be sufficient to treat target volumes within the vertebral body when tumor ablation or other techniques are used to create a cavity into which the radioactive cement can be injected. With further development, treating spinal metastases with radioactive bone cement may become a clinically useful and convenient alternative to the conventional two-step approach of percutaneous strength restoration followed by radiotherapy.
Bone Cements, Bone Neoplasms, Female, Humans, Radiometry, Radiotherapy Dosage, Spine
null
22,705,970
2013-04-26
2021-10-21
1872-7492
Virus research
Viral modulation of stress granules.
Valiente-Echeverría Fernando, Melnychuk Luca, Mouland Andrew J
eng
MOP-38111 (Canadian Institutes of Health Research, Canada)
Journal Article, Research Support, Non-U.S. Gov't, Review
RNA, Viral, Ribonucleoproteins
IM
22705970, S0168-1702(12)00201-8, 10.1016/j.virusres.2012.06.004, PMC7114395, 16221671, 20106928, 10823864, 10882126, 12486012, 9049243, 15721257, 10613902, 12642610, 22258263, 20427534, 19710141, 14715275, 22623775, 6633535, 12388085, 19825938, 15937477, 20844027, 12704645, 21752908, 16177138, 17490409, 15225984, 19467203, 9418880, 20133758, 15014438, 12414941, 15890928, 21994324, 18032499, 15371533, 21957303, 15355306, 22002165, 21377708, 15743837, 16306610, 10866656, 18005751, 20053637, 21532619, 18407064, 20440748, 11809833, 11752661, 22202676, 18836437, 15280467, 21106737, 20962086, 11756670, 16630668, 2836606, 12515382, 21561913, 21543503, 3031658, 9755181, 18775331, 20813183, 22172946, 16951406, 15967811, 12140254, 11836384, 18291657, 21715487, 16520386, 15546618, 17923231, 21813702, 17502609, 18079183, 19193871, 20429927, 17183357, 15930128, 16439558, 22405519, 16870703, 11726526, 20004716, 22163347
Following viral infection, the host responds by mounting a robust anti-viral response with the aim of creating an unfavorable environment for viral replication. As a countermeasure, viruses have elaborated mechanisms to subvert the host response in order to maintain viral protein synthesis and production. In the last decade, several reports have shown that viruses modulate the assembly of stress granules (SGs), which are translationally silent ribonucleoproteins (RNPs) and sites of RNA triage. This review discusses recent advances in our understanding of the interactions between viruses and the host response and how virus-induced modulations in SG abundance play fundamental roles in dictating the success of viral replication.
Animals, Cytoplasmic Granules, Host-Pathogen Interactions, Humans, Models, Biological, Plants, RNA, Viral, Ribonucleoproteins, Virus Physiological Phenomena, Virus Replication, Viruses
null
22,705,969
2013-01-14
2021-10-21
1559-2308
Epigenetics
Trans-chromosomal methylation.
Greaves Ian, Groszmann Michael, Dennis Elizabeth S, Peacock W James
eng
null
Journal Article, Review
RNA, Small Interfering
IM
22705969, 20820, 10.4161/epi.20820, PMC3427274, 10230403, 21030647, 16855589, 22438023, 20444233, 22269081, 17128275, 18278030, 21266545, 22131875, 21566194, 11090618, 17188398, 20725042, 21459171, 20616013, 21321601, 17105345, 20142834, 17720610, 19390088, 20086188, 21041414, 18423832, 17702644, 12154122, 17144899, 19805056, 20622146, 16949657, 22331882, 19557164, 12121623, 19179494, 21765458, 22046144, 14988555
The epigenome plays a vital role in helping to maintain and regulate cell functions in all organisms. Alleles with differing epigenetic marks in the same nucleus do not function in isolation but can interact in trans to modify the epigenetic state of one or both alleles. This is particularly evident when two divergent epigenomes come together in a hybrid resulting in thousands of alterations to the methylome. These changes mainly involve the methylation patterns at one allele being changed to resemble the methylation patterns of the other allele, in processes we have termed trans-chromosomal methylation (TCM) and trans-chromosomal demethylation (TCdM). These processes are primarily modulated by siRNAs and the RNA directed DNA methylation pathway. Drawing from other examples of trans-allelic interactions, we describe the process of TCM and TCdM and the effect such changes can have on genome activity. Trans-allelic epigenetic interactions may be a common occurrence in many biological systems.
Animals, Arabidopsis, Chromosomes, Mammalian, Chromosomes, Plant, DNA Methylation, Epigenesis, Genetic, Genome, Plant, Hybridization, Genetic, RNA, Small Interfering
null
22,705,972
2013-01-10
2012-07-24
1872-8308
Behavioural processes
Cooperative vigilance: the guanaco's (Lama guanicoe) key antipredator mechanism.
Taraborelli Paula, Gregorio Pablo, Moreno Pablo, Novaro Andrés, Carmanchahi Pablo
eng
null
Journal Article
null
IM
22705972, S0376-6357(12)00137-4, 10.1016/j.beproc.2012.06.002
The concept of sociality has been associated with the effectiveness of antipredator mechanisms, like cooperative vigilance and the dilution effect. Lama guanicoe (guanaco) is a social native herbivore in South America and a social species. The objectives of this study were to evaluate the antipredator responses of different-sized groups of guanacos in areas with varying predation risks and to determine antipredator mechanisms in guanacos. For this, we measured different antipredator responses to a potential predator (human subjects). Detection of predator and flight distances from predator both increased with a greater number of guanacos per group and with greater distances among guanacos within the social group. Both buffer distance and flight time decreased with a greater number of guanacos per group, but increased with greater distances among guanacos inside the social group. Solitary adult males moved shorter distance and mixed groups moved greater distances. Flight distances were greater in areas with tall and dense vegetation than in areas with low vegetation. Buffer distance and flight time were shorter in undulating land than on flat lands, and groups were usually observed on hill slopes. Our results suggest that the benefit of social grouping in guanacos is the increased probability of avoiding predator with cooperative vigilance and not with the dilution effect. This means that a predator could be detected earlier when approaching a guanaco group than when approaching a solitary individuals and could thus be avoided.
Animals, Arousal, Camelids, New World, Cooperative Behavior, Escape Reaction, Female, Male, Predatory Behavior
null
22,705,971
2013-04-26
2022-01-29
1872-7492
Virus research
The HIV-1 matrix protein does not interact directly with the protein interactive domain of AP-3δ.
Kyere Sampson K, Mercredi Peter Y, Dong Xinhong, Spearman Paul, Summers Michael F
eng
R01-AI40338 (NIAID NIH HHS, United States); R25 GM056833 (NIGMS NIH HHS, United States); R01 AI040338 (NIAID NIH HHS, United States); R25 GM055036 (NIGMS NIH HHS, United States); R01-AI30917 (NIAID NIH HHS, United States); F31-GM076979 (NIGMS NIH HHS, United States); R37 AI030917 (NIAID NIH HHS, United States)
Journal Article, Research Support, N.I.H., Extramural
AP3D1 protein, human, Adaptor Protein Complex 3, Adaptor Protein Complex delta Subunits, HIV Antigens, gag Gene Products, Human Immunodeficiency Virus, p17 protein, Human Immunodeficiency Virus Type 1
IM
22705971, S0168-1702(12)00204-3, 10.1016/j.virusres.2012.06.007, PMC3469251, NIHMS387766, 12885763, 12947040, 18799574, 14617360, 7966331, 18682304, 19828619, 18369466, 16840558, 21613397, 19861549, 19297499, 16683918, 18657545, 19383519, 18785842, 21762797, 15766529, 14722309, 17989173, 18005723, 19594910, 17507489, 17003132, 16699598, 11454451, 11907283, 18474355, 14561735, 19602278, 9151686, 12230470, 11717449, 17381240, 17438075, 21552427, 14617353, 18500329, 19284574, 19458002, 19779568, 10954568, 15465916, 17108326, 9400603, 20374631, 14745134, 16682056, 17147474, 17522207, 18034776, 18439901, 9624176, 16139599, 20510745
During the late phase of the Human Immunodeficiency Virus Type-1 (HIV-1) replication cycle, viral Gag proteins and the intact RNA genome are trafficked to specific sub-cellular membranes where virus assembly and budding occurs. Targeting to the plasma membranes of T cells and macrophages is mediated by interactions between the N-terminal matrix (MA) domain of Gag and cellular phosphatidylinositol-4,5-bisphosphate [PI(4,5)P(2)] molecules. However, in macrophages and dendritic cells, a subset of Gag proteins appears to be targeted to tetraspanin enriched viral compartments, a process that appears to be mediated by MA interactions with the Delta subunit of the cellular Adaptor Protein AP-3 (AP-3δ). We cloned, overexpressed and purified the protein interactive domain of AP-3δ and probed for MA binding by NMR. Unexpectedly, no evidence of binding was observed in these in vitro experiments, even at relatively high protein concentrations (200μM), suggesting that AP-3δ plays an alternative role in HIV-1 assembly.
Adaptor Protein Complex 3, Adaptor Protein Complex delta Subunits, Cloning, Molecular, Gene Expression, HIV Antigens, HIV-1, Humans, Magnetic Resonance Spectroscopy, Protein Binding, Protein Interaction Mapping, Virus Assembly, gag Gene Products, Human Immunodeficiency Virus
null
22,705,973
2012-11-12
2012-09-11
1470-7926
Occupational and environmental medicine
Occupational allergic contact dermatitis to acrylic fingernails in beauticians.
Patruno Cataldo, Ayala Fabio, Napolitano Maddalena, Bianca Dario, Balato Nicola
eng
null
Letter
Acrylates, Cosmetics
IM
22705973, oemed-2012-100901, 10.1136/oemed-2012-100901
null
Acrylates, Cosmetics, Dermatitis, Allergic Contact, Dermatitis, Occupational, Female, Humans, Occupational Exposure
null
22,705,974
2012-11-16
2020-12-31
1364-548X
Chemical communications (Cambridge, England)
Protodecarboxylation of benzoic acids under radical conditions.
Seo Sangwon, Taylor John B, Greaney Michael F
eng
null
Journal Article
null
null
22705974, 10.1039/c2cc33306f
A new approach to protodecarboxylation is described that enhances the substrate scope for benzoic acids. The reaction uses oxidative radical conditions to decarboxylate a variety of acids in acetonitrile.
null
null
22,705,975
2013-01-14
2021-10-21
1559-2308
Epigenetics
Global DNA methylation levels in white blood cell DNA from sisters discordant for breast cancer from the New York site of the Breast Cancer Family Registry.
Delgado-Cruzata Lissette, Wu Hui-Chen, Perrin Mary, Liao Yuyan, Kappil Maya A, Ferris Jennifer S, Flom Julie D, Yazici Hulya, Santella Regina M, Terry Mary Beth
eng
K07 CA131094 (NCI NIH HHS, United States); U01 CA069398 (NCI NIH HHS, United States); L30 HG004809 (NHGRI NIH HHS, United States); U01 CA69398 (NCI NIH HHS, United States); P30 CA013696 (NCI NIH HHS, United States); CA-06-503 (NCI NIH HHS, United States); P30 CA13696 (NCI NIH HHS, United States); P30 ES009089 (NIEHS NIH HHS, United States)
Journal Article, Research Support, N.I.H., Extramural
DNA
IM
22705975, 20830, 10.4161/epi.20830, PMC3427282, 10665836, 21669556, 21445976, 20442803, 454420, 17998810, 9683174, 20179218, 20920744, 20099281, 21636973, 9260521, 22678115, 18566018, 8323540, 19680444, 16985021, 8918229, 15217505, 20237504, 12730865, 3233245, 16736000, 18813801, 17220338, 10424731, 16009939, 19663042, 20890131, 21188491, 18166347, 9872311, 18339581, 15657342, 19750115, 6192902, 18577732, 18314632, 19339271, 15350988, 16624287, 17921400, 19584139
Lower global DNA methylation is associated with genomic instability and it is one of the epigenetic mechanisms relevant to carcinogenesis. Emerging evidence for several cancers suggests that lower overall levels of global DNA methylation in blood are associated with different cancer types, although less is known about breast cancer. We examined global DNA methylation levels using a sibling design in 273 sisters affected with breast cancer and 335 unaffected sisters from the New York site of the Breast Cancer Family Registry. We measured global DNA methylation in total white blood cell (WBC) and granulocyte DNA by two different methods, the [ ( 3) H]-methyl acceptance assay and the luminometric methylation assay (LUMA). Global methylation levels were only modestly correlated between sisters discordant for breast cancer (Spearman correlation coefficients ranged from -0.08 to 0.24 depending on assay and DNA source). Using conditional logistic regression models, women in the quartile with the lowest DNA methylation levels (as measured by the [ ( 3) H]-methyl acceptance assay) had a 1.8-fold (95% CI = 1.0-3.3) higher relative association with breast cancer than women in the quartile with the highest DNA methylation levels. When we examined the association on a continuous scale, we also observed a positive association (odds ratio, OR = 1.3, 95% CI = 1.0-1.7, for a one unit change in the natural logarithm of the DPM/μg of DNA). We observed no association between measures by the LUMA assay and breast cancer risk. If replicated in prospective studies, this study suggests that global DNA methylation levels measured in WBC may be a potential biomarker of breast cancer risk even within families at higher risk of cancer.
Adult, Breast Neoplasms, DNA, DNA Methylation, Female, Humans, Leukocytes, Middle Aged, New York, Registries, Siblings
null
22,705,980
2013-05-15
2012-12-03
1873-7870
Evaluation and program planning
Concept maps as network data: analysis of a concept map using the methods of social network analysis.
McLinden Daniel
eng
null
Journal Article
null
IM
22705980, S0149-7189(12)00045-6, 10.1016/j.evalprogplan.2012.05.001
Concept mapping is a method that creates a visual representation that illustrates the thoughts, ideas, or planned actions that arise from a group of stakeholders on a particular issue. Social network analysis is a method that likewise creates a visual representation of data; a network map typically represents people and the connections, or lack thereof, between these people regarding a particular issue. While the goals of these two methods differ, the underlying data structures are similar; a network of relationships between data elements. Social network analysis is explored here as a supplement to concept mapping. A secondary analysis of a concept map to define to leadership needs was conducted using social network analysis. The methods and the implications for supplementing the analysis of concept maps and debriefing results with stakeholders are discussed.
Cluster Analysis, Group Processes, Humans, Qualitative Research, Social Support, Software Design, Systems Analysis
null
22,705,979
2013-05-15
2014-11-20
1873-7870
Evaluation and program planning
Evaluating local food programs: the case of Select Nova Scotia.
Knight Andrew J
eng
null
Journal Article
null
IM
22705979, S0149-7189(12)00057-2, 10.1016/j.evalprogplan.2012.05.003
This study evaluated the effectiveness of the buy local food program Select Nova Scotia; a government program with the goal to increase awareness and consumption of Nova Scotia produced and processed agri-food products by Nova Scotians and visitors. The evaluation methodology was based on prior evaluation resources and local food consumer research. Data were gathered through a web panel survey; 877 respondents completed the survey in June 2010. The results suggest that the program is reaching a wider audience than just those predisposed to local food initiatives. In addition, awareness of Select Nova was related to perceptions of local benefits and barriers, as well as purchase motivation and behavior. Respondents who were aware of Select Nova Scotia rated societal benefits as more important and viewed location and price as less of a barrier; they were also more likely to be highly motivated to purchase local foods. This study also informs results found in previous consumer research studies and identifies marketing opportunities to enhance the effectiveness of local food programs. The results suggest that societal benefits might be used as a way to differentiate products with similar attributes.
Adolescent, Adult, Awareness, Child, Child, Preschool, Consumer Behavior, Female, Food Supply, Humans, Male, Middle Aged, Motivation, Nova Scotia, Program Evaluation, Social Marketing, Socioeconomic Factors, Systems Analysis, Young Adult
null
22,705,981
2013-01-03
2021-10-21
1554-8635
Autophagy
Interactions between enteroviruses and autophagy in vivo.
Alirezaei Mehrdad, Flynn Claudia T, Whitton J Lindsay
eng
R01 AI042314 (NIAID NIH HHS, United States); R01 HL093177 (NHLBI NIH HHS, United States)
Journal Article, Research Support, N.I.H., Extramural
null
IM
22705981, 20160, 10.4161/auto.20160, PMC3427263
Autophagy plays a protective role during many viral and bacterial infections. Predictably, evolution has led to several viruses developing mechanisms by which to evade the inhibitory effects of the pathway. However, one family of viruses, the picornaviruses, has gone one step further, by actively exploiting autophagy. Using mice in which Atg5 has been conditionally deleted in pancreatic acinar cells, we have studied the outcome of infection by coxsackievirus B3 (CVB3), a member of the enterovirus genus and picornavirus family. Two key findings emerged: disruption of autophagy (1) dramatically compromised virus replication in vivo, and (2) significantly limited pancreatic disease.
Animals, Autophagy, Coxsackievirus Infections, Enterovirus, Humans, Mice, Models, Biological, Virus Replication
null
22,705,982
2012-11-29
2021-12-03
1878-5875
The international journal of biochemistry & cell biology
Reelin and its complex involvement in brain development and function.
Lakatosova Silvia, Ostatnikova Daniela
eng
null
Journal Article, Review
Cell Adhesion Molecules, Neuronal, Extracellular Matrix Proteins, Nerve Tissue Proteins, Reelin Protein, RELN protein, human, Serine Endopeptidases
IM
22705982, S1357-2725(12)00193-8, 10.1016/j.biocel.2012.06.002
Reelin is a neuroprotein with crucial role during neurodevelopment and also in postnatal period. It regulates neuronal migration and positioning in developing neocortex and cerebellar cortex. Postnatally it participates in regulation of dendritic and axonal growth, synaptogenesis, neurotransmission and it contribute to synaptic plasticity necessary for learning and memory functions. Role of Reelin seems to be rather complex, profound research gradually uncovers its further functions. Deficits of Reelin were detected in neuropsychiatric disorders such as schizophrenia, bipolar disorder and autism. Pathogenesis of these disorders is far from being clearly understood. Reelin contribution to these diseases seems to be vital, since genetic variants of Reelin were associated with these diseases and often influence symptom severity. Reelin is a promising candidate molecule with potential future use in diagnostics and therapy, however further detailed research is essential.
Animals, Brain, Cell Adhesion Molecules, Neuronal, Disease, Extracellular Matrix Proteins, Gene Expression Regulation, Humans, Nerve Tissue Proteins, Reelin Protein, Serine Endopeptidases
null
22,705,983
2012-10-15
2024-06-29
1872-7905
Journal of immunological methods
TCR/pMHC Optimized Protein crystallization Screen.
Bulek Anna M, Madura Florian, Fuller Anna, Holland Christopher J, Schauenburg Andrea J A, Sewell Andrew K, Rizkallah Pierre J, Cole David K
eng
BB/H001085/1 (Biotechnology and Biological Sciences Research Council, United Kingdom); WT095767 (Wellcome Trust, United Kingdom)
Journal Article, Research Support, Non-U.S. Gov't
Peptides, Receptors, Antigen, T-Cell
IM
22705983, S0022-1759(12)00168-8, 10.1016/j.jim.2012.06.007, PMC3404460, 17259989, 9250664, 21124993, 19605354, 11877480, 11060013, 15572765, 18243322, 18094462, 9586631, 11017099, 22245737, 17442956, 15837811, 12530975, 15805601, 15299374, 8906788, 16079912, 16186824, 9427737, 15664161, 15821740, 1565634, 12414723, 17644531, 22044041, 14560057, 12563259, 12796775, 10435578, 16551255, 8824178
The interaction between the clonotypic αβ T cell receptor (TCR), expressed on the T cell surface, and peptide-major histocompatibility complex (pMHC) molecules, expressed on the target cell surface, governs T cell mediated autoimmunity and immunity against pathogens and cancer. Structural investigations of this interaction have been limited because of the challenges inherent in the production of good quality TCR/pMHC protein crystals. Here, we report the development of an 'intelligently designed' crystallization screen that reproducibly generates high quality TCR/pMHC complex crystals suitable for X-ray crystallographic studies, thereby reducing protein consumption. Over the last 2 years, we have implemented this screen to produce 32 T cell related protein structures at high resolution, substantially contributing to the current immune protein database. Protein crystallography, used to study this interaction, has already extended our understanding of the molecular rules that govern T cell immunity. Subsequently, these data may help to guide the intelligent design of T cell based therapies that target human diseases, underlining the importance of developing optimized approaches for crystallizing novel TCR/pMHC complexes.
Crystallization, Crystallography, X-Ray, Humans, Major Histocompatibility Complex, Peptides, Protein Conformation, Receptors, Antigen, T-Cell, T-Lymphocytes
null
22,705,977
2013-06-12
2022-04-22
1872-6356
Mechanisms of development
Delayed fusion and altered gene expression contribute to semicircular canal defects in Chd7 deficient mice.
Hurd Elizabeth A, Micucci Joseph A, Reamer Elyse N, Martin Donna M
eng
R01 DC009410 (NIDCD NIH HHS, United States); DC009410 (NIDCD NIH HHS, United States); T35 HL007690 (NHLBI NIH HHS, United States); T32 DC00011 (NIDCD NIH HHS, United States); T32 DC000011 (NIDCD NIH HHS, United States)
Journal Article, Research Support, N.I.H., Extramural
Chd7 protein, mouse, DNA-Binding Proteins, NTN1 protein, human, Nerve Growth Factors, Tumor Suppressor Proteins, Netrin-1
IM
22705977, S0925-4773(12)00055-X, 10.1016/j.mod.2012.06.002, PMC3477510, NIHMS391305, 15084464, 10225993, 17891716, 15846349, 15300250, 18404215, 12435365, 12761848, 18693263, 17952062, 10837119, 9435283, 12200165, 10654596, 19855134, 11181574, 15280215, 16971610, 16207732, 12453462, 8841200, 17701983, 9547240, 11259677, 19913004, 1794322, 7657163, 15499560, 20637105, 11919684, 21532573, 10588886, 17891714, 10660898, 19247974, 8405678, 10354604, 20736290, 19251738, 9326634, 10190809, 17891717, 17334657, 16600992, 17053809, 11861162
Proper morphogenesis of inner ear semicircular canals requires precise regulation of cellular proliferation, epithelial-to-mesenchymal transition, and fusion of epithelial plates. Epigenetic regulation of these processes is not well understood, but is likely to involve chromatin remodeling enzymes. CHD7 is a chromodomain-containing, ATP dependent helicase protein that is highly expressed in the developing ear and is required for semicircular canal development in both humans and mice. Here we report that mice with heterozygous loss of Chd7 function exhibit delayed semicircular canal genesis, delayed Netrin1 expression and disrupted expression of genes that are critical for semicircular canal formation (Bmp2, Bmp4, Msx1 and Fgf10). Complete loss of Chd7 results in aplasia of the semicircular canals and sensory vestibular organs, with reduced or absent expression of Otx1, Hmx3, Jagged1, Lmo4, Msx1 and Sox2. Our results suggest that Chd7 may have critical selector gene functions during inner ear morphogenesis. Detailed analysis of the epigenetic modifications underlying these gene expression changes should provide insights into semicircular canal development and help in the design of therapies for individuals with inner ear malformations.
Animals, Cell Proliferation, DNA-Binding Proteins, Epigenesis, Genetic, Epithelium, Gene Expression Regulation, Developmental, Heterozygote, Mesoderm, Mice, Morphogenesis, Mutation, Nerve Growth Factors, Netrin-1, Semicircular Canals, Tumor Suppressor Proteins
null
22,705,984
2012-12-17
2016-11-25
2159-8290
Cancer discovery
Janus kinase 3-activating mutations identified in natural killer/T-cell lymphoma.
Koo Ghee Chong, Tan Soo Yong, Tang Tiffany, Poon Song Ling, Allen George E, Tan Leonard, Chong Soo Ching, Ong Whee Sze, Tay Kevin, Tao Miriam, Quek Richard, Loong Susan, Yeoh Kheng-Wei, Yap Swee Peng, Lee Kuo Ann, Lim Lay Cheng, Tan Daryl, Goh Christopher, Cutcutache Ioana, Yu Willie, Ng Cedric Chuan Young, Rajasegaran Vikneswari, Heng Hong Lee, Gan Anna, Ong Choon Kiat, Rozen Steve, Tan Patrick, Teh Bin Tean, Lim Soon Thye
eng
null
Journal Article, Research Support, Non-U.S. Gov't
Piperidines, Pyrimidines, Pyrroles, STAT5 Transcription Factor, tofacitinib, JAK3 protein, human, Janus Kinase 3
IM
22705984, 2159-8290.CD-12-0028, 10.1158/2159-8290.CD-12-0028
The molecular pathogenesis of natural killer/T-cell lymphoma (NKTCL) is not well understood. We conducted whole-exome sequencing and identified Janus kinase 3 (JAK3) somatic-activating mutations (A572V and A573V) in 2 of 4 patients with NKTCLs. Further validation of the prevalence of JAK3 mutations was determined by Sanger sequencing and high-resolution melt (HRM) analysis in an additional 61 cases. In total, 23 of 65 (35.4%) cases harbored JAK3 mutations. Functional characterization of the JAK3 mutations support its involvement in cytokine-independent JAK/STAT constitutive activation leading to increased cell growth. Moreover, treatment of both JAK3-mutant and wild-type NKTCL cell lines with a novel pan-JAK inhibitor, CP-690550, resulted in dose-dependent reduction of phosphorylated STAT5, reduced cell viability, and increased apoptosis. Hence, targeting the deregulated JAK/STAT pathway could be a promising therapy for patients with NKTCLs.
Adult, Aged, Aged, 80 and over, Animals, Blotting, Western, Cell Line, Tumor, Cell Proliferation, DNA Mutational Analysis, Enzyme Activation, Female, Humans, Janus Kinase 3, Lymphoma, T-Cell, Male, Middle Aged, Mutation, Natural Killer T-Cells, Phosphorylation, Piperidines, Pyrimidines, Pyrroles, RNA Interference, STAT5 Transcription Factor
null
22,705,976
2014-01-24
2013-05-31
1933-6942
Fly
Plastic flies: the regulation and evolution of trait variability in Drosophila.
Shingleton Alexander W, Tang Hui Yuan
eng
null
Journal Article, Research Support, Non-U.S. Gov't
null
IM
22705976, 20323, 10.4161/fly.20323
Individuals within species and populations vary. Such variation arises through environmental and genetic factors and ensures that no two individuals are identical. However, it is clear that not all traits show the same degree of intraspecific variation. Some traits, in particular secondary sexual characteristics used by males to compete for and attract females, are extremely variable among individuals in a population. Other traits, for example brain size in mammals, are not. Recent research has begun to explore the possibility that the extent of phenotypic variation (here referred to as "variability") may be a character itself and subject to natural selection. While these studies support the concept of variability as an evolvable trait, controversy remains over what precisely the trait is. At the heart of this controversy is the fact that there are very few examples of developmental mechanisms that regulate trait variability in response to any source of variation, be it environmental or genetic. Here, we describe a recent study from our laboratory that identifies such a mechanism. We then place the study in the context of current research on the regulation of trait variability, and discuss the implications for our understanding of the developmental regulation and evolution of phenotypic variation.
Animal Nutritional Physiological Phenomena, Animals, Biological Evolution, Drosophila, Environment, Phenotype, Selection, Genetic
allometry, canalization, developmental stability, environmental variation, exaggerated traits, genetic variation, genic capture, morphological scaling, phenotypic plasticity, variability
22,705,985
2012-09-25
2012-07-17
1879-0038
Gene
Comparative transcriptomics of two pathogenic pinewood nematodes yields insights into parasitic adaptation to life on pine hosts.
Yan Xia, Cheng Xin-Yue, Wang Yun-Sheng, Luo Ji, Mao Zhen-Chuan, Ferris Virginia R, Xie Bing-Yan
eng
null
Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
Helminth Proteins
IM
22705985, S0378-1119(12)00629-4, 10.1016/j.gene.2012.05.041
Bursaphelenchus xylophilus and Bursaphelenchus mucronatus are migratory endoparasitic nematodes that live in pine trees. To gain insight into their molecular similarities and differences, transcriptomes of the two nematodes were analysed. A total of 23,765 and 21,782 contigs (>300 bp) were obtained from B. xylophilus and B. mucronatus, respectively. More than 80% of the contigs could map to each other's transcriptome reciprocally. A total of 23,467 and 21,370 Open Reading Frames were predicted, respectively. Besides those known parasitism-related proteins, six new venom allergen-like proteins (VAPs) were found, which were not homologous to known VAPs. Enzymes involved in xenobiotic biodegradation were abundant in the two transcriptomes based on KEGG functional annotation. Metabolism of xenobiotics by cytochrome P450 comprised the main detoxification pathways. The mRNA expression levels of detoxification genes in nematodes living in the host were higher than those in nematodes feeding on fungus. However, there were fewer enzymes involved in the α-pinene degradation. Our results indicate that the two pinewood nematodes have evolved similar molecular mechanisms to adapt to life on pine hosts.
Adaptation, Physiological, Animals, Evolution, Molecular, Gene Expression Regulation, Genes, Helminth, Helminth Proteins, Host-Parasite Interactions, Nematoda, Pinus, Transcriptome
null
22,705,986
2012-10-25
2021-10-21
1361-6560
Physics in medicine and biology
A nephron-based model of the kidneys for macro-to-micro α-particle dosimetry.
Hobbs Robert F, Song Hong, Huso David L, Sundel Margaret H, Sgouros George
eng
R01 CA116477 (NCI NIH HHS, United States); R01 CA157542 (NCI NIH HHS, United States); UL1 TR000064 (NCATS NIH HHS, United States)
Journal Article
null
IM
22705986, 10.1088/0031-9155/57/13/4403, PMC3640368, NIHMS453474, 20150265, 19920193, 4571744, 9935083, 15930310, 22080442, 1546799, 20847171, 17332322, 9399706, 18077533, 19258258, 10565792, 8130358, 20124656, 15653658, 1848692, 16778112, 18722269, 8679269, 18927342, 18483272, 12843230, 1162032, 9724387, 12396708, 19525452, 11516878, 20025544, 17921029, 17089844, 19580472, 15937315, 21815364, 15235063, 12732682, 11903800, 10947126, 15987754, 11085533, 21220845, 16503385, 12571218, 19580473, 12149203, 12036923, 1213044, 20080889
Targeted α-particle therapy is a promising treatment modality for cancer. Due to the short path-length of α-particles, the potential efficacy and toxicity of these agents is best evaluated by microscale dosimetry calculations instead of whole-organ, absorbed fraction-based dosimetry. Yet time-integrated activity (TIA), the necessary input for dosimetry, can still only be quantified reliably at the organ or macroscopic level. We describe a nephron- and cellular-based kidney dosimetry model for α-particle radiopharmaceutical therapy, more suited to the short range and high linear energy transfer of α-particle emitters, which takes as input kidney or cortex TIA and through a macro to micro model-based methodology assigns TIA to micro-level kidney substructures. We apply a geometrical model to provide nephron-level S-values for a range of isotopes allowing for pre-clinical and clinical applications according to the medical internal radiation dosimetry (MIRD) schema. We assume that the relationship between whole-organ TIA and TIA apportioned to microscale substructures as measured in an appropriate pre-clinical mammalian model also applies to the human. In both, the pre-clinical and the human model, microscale substructures are described as a collection of simple geometrical shapes akin to those used in the Cristy-Eckerman phantoms for normal organs. Anatomical parameters are taken from the literature for a human model, while murine parameters are measured ex vivo. The murine histological slides also provide the data for volume of occupancy of the different compartments of the nephron in the kidney: glomerulus versus proximal tubule versus distal tubule. Monte Carlo simulations are run with activity placed in the different nephron compartments for several α-particle emitters currently under investigation in radiopharmaceutical therapy. The S-values were calculated for the α-emitters and their descendants between the different nephron compartments for both the human and murine models. The renal cortex and medulla S-values were also calculated and the results compared to traditional absorbed fraction calculations. The nephron model enables a more optimal implementation of treatment and is a critical step in understanding toxicity for human translation of targeted α-particle therapy. The S-values established here will enable a MIRD-type application of α-particle dosimetry for α-emitters, i.e. measuring the TIA in the kidney (or renal cortex) will provide meaningful and accurate nephron-level dosimetry.
Alpha Particles, Animals, Humans, Mice, Models, Biological, Monte Carlo Method, Nephrons, Phantoms, Imaging, Radiometry
null
22,705,987
2013-04-03
2018-12-01
1557-3265
Clinical cancer research : an official journal of the American Association for Cancer Research
Predictive value of XRCC1 gene polymorphisms on platinum-based chemotherapy in advanced non-small cell lung cancer patients: a systematic review and meta-analysis.
Wu Junjie, Liu Jie, Zhou Yuhao, Ying Jun, Zou Houdong, Guo Shicheng, Wang Lei, Zhao Naiqing, Hu Jianjun, Lu Daru, Jin Li, Li Qiang, Wang Jiu-Cun
eng
null
Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't, Systematic Review
DNA-Binding Proteins, X-ray Repair Cross Complementing Protein 1, XRCC1 protein, human, Platinum
IM
22705987, 1078-0432.CCR-11-1531, 10.1158/1078-0432.CCR-11-1531
Published data have shown conflicting results about the relationship between X-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms (Arg399Gln and Arg194Trp) and clinical outcome of platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). A meta-analysis is needed to provide a systematic review of the published findings.
Alleles, Carcinoma, Non-Small-Cell Lung, DNA-Binding Proteins, Follow-Up Studies, Genetic Predisposition to Disease, Humans, Lung Neoplasms, Neoplasm Staging, Platinum, Polymorphism, Genetic, Prognosis, Treatment Outcome, X-ray Repair Cross Complementing Protein 1
null
22,705,989
2013-07-01
2024-06-10
1600-0641
Journal of hepatology
A renaissance in medical biochemistry - Hepatology and Endocrinology kick it up a Notch!
Anania Frank A
eng
I01 BX001746 (BLRD VA, United States); R01 DK062092 (NIDDK NIH HHS, United States); R56 DK062092 (NIDDK NIH HHS, United States); R01DK062092 (NIDDK NIH HHS, United States)
Comment, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.
null
null
22705989, S0168-8278(12)00433-3, 10.1016/j.jhep.2012.06.007, PMC3808188, NIHMS491665, 17767907, 18590693, 21804540, 22344295
null
null
null
22,705,991
2013-01-24
2015-11-19
1476-5551
Leukemia
Long-term follow-up of FIP1L1-PDGFRA-mutated patients with eosinophilia: survival and clinical outcome.
Pardanani A, D'Souza A, Knudson R A, Hanson C A, Ketterling R P, Tefferi A
eng
null
Letter
Benzamides, FIP1L1 protein, human, Piperazines, Pyrimidines, mRNA Cleavage and Polyadenylation Factors, Imatinib Mesylate, Receptor, Platelet-Derived Growth Factor alpha
IM
22705991, leu2012162, 10.1038/leu.2012.162
null
Adult, Aged, Benzamides, Eosinophilia, Female, Follow-Up Studies, Humans, Imatinib Mesylate, Male, Middle Aged, Mutation, Piperazines, Pyrimidines, Receptor, Platelet-Derived Growth Factor alpha, Survival Analysis, Treatment Outcome, mRNA Cleavage and Polyadenylation Factors
null
22,705,988
2012-12-21
2012-08-01
1557-3265
Clinical cancer research : an official journal of the American Association for Cancer Research
IGKV3 proteins as candidate "off-the-shelf" vaccines for kappa-light chain-restricted B-cell non-Hodgkin lymphomas.
Martorelli Debora, Guidoboni Massimo, De Re Valli, Muraro Elena, Turrini Riccardo, Merlo Anna, Pasini Elisa, Caggiari Laura, Romagnoli Luca, Spina Michele, Mortarini Roberta, Gasparotto Daniela, Mazzucato Mario, Carbone Antonino, Rosato Antonio, Anichini Andrea, Dolcetti Riccardo
eng
null
Journal Article, Research Support, Non-U.S. Gov't
Cancer Vaccines, Epitopes, T-Lymphocyte, HLA Antigens, HLA-A2 Antigen, Immunoglobulin kappa-Chains
IM
22705988, 1078-0432.CCR-12-0763, 10.1158/1078-0432.CCR-12-0763
An increasing set of B-cell non-Hodgkin lymphomas (B-NHL) show a biased usage of IGKV3-20 and IGKV3-15 immunoglobulin genes, a feature that could be exploited for the development of ready-to-use, broadly applicable cancer vaccines.
Adult, Aged, Amino Acid Sequence, Animals, Cancer Vaccines, Cell Line, Tumor, Cross Reactions, Enzyme-Linked Immunosorbent Assay, Epitopes, T-Lymphocyte, Female, Flow Cytometry, HLA Antigens, HLA-A2 Antigen, Humans, Immunity, Humoral, Immunoglobulin kappa-Chains, Lymphoma, B-Cell, Male, Mice, Mice, SCID, Mice, Transgenic, Middle Aged, T-Lymphocytes, T-Lymphocytes, Cytotoxic, Xenograft Model Antitumor Assays
null
22,705,990
2013-02-28
2021-10-21
1476-5551
Leukemia
Improvement in long-term outcomes with successive Total Therapy trials for multiple myeloma: are patients now being cured?
Usmani S Z, Crowley J, Hoering A, Mitchell A, Waheed S, Nair B, AlSayed Y, Vanrhee F, Barlogie B
eng
P01 CA055819 (NCI NIH HHS, United States); CA 55813 (NCI NIH HHS, United States)
Comparative Study, Journal Article, Research Support, N.I.H., Extramural
null
IM
22705990, leu2012160, 10.1038/leu.2012.160, PMC3744094, NIHMS496179, 21402611, 15976175, 17975015, 16525139, 11157506, 922731, 21628408, 17105813, 19344415, 21778345, 21410373, 20508167, 17489983, 20124509, 16939489, 21900099, 17593024, 17296972, 10204198, 20574050, 18318761, 14695639, 17023574, 19389881, 12430902, 19515721, 16728703, 19443657, 18056185, 21791430, 21732930, 16407512, 5910392, 11238092, 2647015, 19020545, 21292775, 20072152, 19702643, 8231256, 21880640, 13596417, 19657360, 12623842, 21482708, 20962323
The concept of applying all active therapeutic agents in Total Therapy (TT) clinical trials for newly diagnosed multiple myeloma was pursued with the intent of developing curative treatment. The results of TT1 (n=231), TT2 (n=668) without or with thalidomide and TT3 with added bortezomib (n=303) have been reported. An update with median follow-up times of 17.1, 8.7 and 5.5 years, respectively, is provided. Conditional overall survival (OS) analysis from a 4-year landmark was applied to account for earlier protocol failure owing to disease aggressiveness and toxicities. Cumulative relative survival was computed in the context of age- and gender-matched US population, and interval-specific relative survival ratios were estimated to determine times to normal survival expectation. Based on Cox model-adjusted statistics, OS, progression-free survival and complete-response duration all improved with the transitions from TT1 to TT2 to TT3; improvement was also evident from time-to-progression estimates, 4-year conditional survival data and cumulative relative survival. Interval-specific relative survival normalized progressively sooner, reaching near-normal levels with TT3 in patients who attained complete response. Thus, a strategy using all myeloma-effective agents up-front seems effective at preventing, in progressively larger patient cohorts over time, the outgrowth of resistant tumor cells that account for ongoing relapses.
Aged, Antineoplastic Combined Chemotherapy Protocols, Clinical Trials, Phase II as Topic, Clinical Trials, Phase III as Topic, Combined Modality Therapy, Follow-Up Studies, Humans, Multiple Myeloma, Neoplasm Staging, Prognosis, Randomized Controlled Trials as Topic, Survival Rate
null
22,705,992
2013-01-24
2022-04-19
1476-5551
Leukemia
Prognostic significance of FLT3 mutational status and expression levels in MLL-AF4+ and MLL-germline acute lymphoblastic leukemia.
Chillón M C, Gómez-Casares M T, López-Jorge C E, Rodriguez-Medina C, Molines A, Sarasquete M E, Alcoceba M, Miguel J D G-S, Bueno C, Montes R, Ramos F, Rodríguez J N, Giraldo P, Ramírez M, García-Delgado R, Fuster J L, González-Díaz M, Menendez P
eng
null
Journal Article, Research Support, Non-U.S. Gov't
KMT2A protein, human, Myeloid-Lymphoid Leukemia Protein, Histone-Lysine N-Methyltransferase, FLT3 protein, human, fms-Like Tyrosine Kinase 3
IM
22705992, leu2012161, 10.1038/leu.2012.161
There is barely any information about the prognostic significance of FLT3 expression and mutational status in cytogenetically distinct subgroups of acute lymphoblastic leukemia (ALL). We analyzed the presence of FLT3-tyrosine kinase domain (TKD) and FLT3-internal tandem duplication (ITD) mutations as well as FLT3 expression levels in 54 newly diagnosed patients with B-ALL (n=49) or T-ALL (n=5). All B/T-ALL samples tested negative for the presence of FLT3-TKD or FLT3-ITD. None of the T-ALL and E2A-PBX1+ B-ALL overexpressed FLT3. In contrast, mainly MLL-AF4+ B-ALL but also ETV6-RUNX1+, BCR-ABL+ or B-ALL displaying normal cytogenetics exhibited significantly higher FLT3 expression levels than normal bone marrow, supporting that aberrantly increased transcription of FLT3, rather than activating FLT3 mutations, contributes to the pathogenesis of these B-ALL. Using the median FLT3 expression as cut-off value we found that high-level FLT3 expression is associated with an extremely poor 1-year overall survival (OS; 0 vs 71%; P=0.002) and disease-free survival (DFS; 0 vs 43%; P=0.03) in MLL-AF4+ B-ALL but not in MLL-germline B-ALL. Cox regression analysis with OS/DFS as end points showed that age>14 years and high-level FLT3 expression were independent prognostic factors when all ALL patients were analyzed together. Importantly, when the MLL-AF4+ B-ALL subgroup was analyzed separately, high-level FLT3 expression was the only independent prognostic factor for OS and treatment outcome. These findings indicate that high FLT3 expression identifies MLL-AF4+ ALL patients at very high risk of treatment failure and poor survival, emphasizing the value of ongoing/future clinical trials for FLT3 inhibitors.
Histone-Lysine N-Methyltransferase, Humans, Mutation, Myeloid-Lymphoid Leukemia Protein, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Prognosis, fms-Like Tyrosine Kinase 3
null
22,705,993
2013-01-24
2022-04-19
1476-5551
Leukemia
Impact of minimal residual disease kinetics during imatinib-based treatment on transplantation outcome in Philadelphia chromosome-positive acute lymphoblastic leukemia.
Lee S, Kim D-W, Cho B-S, Yoon J-H, Shin S-H, Yahng S-A, Lee S-E, Eom K-S, Kim Y-J, Chung N-G, Kim H-J, Min C-K, Lee J-W, Min W-S, Park C-W
eng
null
Journal Article, Research Support, Non-U.S. Gov't
Antineoplastic Agents, Benzamides, Piperazines, Pyrimidines, Imatinib Mesylate
IM
22705993, leu2012164, 10.1038/leu.2012.164
We conducted a systemic evaluation to describe the effect of minimal residual disease (MRD) kinetics on long-term allogeneic transplantation outcome by analyzing 95 adult transplants with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) who received first-line two courses of imatinib-based chemotherapy (median follow-up 5 years). MRD monitoring was centrally evaluated by real-time quantitative PCR (4.5 log sensitivity). After the first course of imatinib-based chemotherapy, 33 patients (34.7%) achieved at least major molecular response. On the basis of MRD kinetics by the end of two courses of imatinib-based chemotherapy, we stratified entire patients into four subgroups: early-stable molecular responders (EMRs, n=33), late molecular responders (LMRs, n=35), intermediate molecular responders (IMRs, n=9) and poor molecular responders (PMRs, n=18). Multivariate analysis showed that the most powerful factor affecting long-term transplantation outcome was MRD kinetics. Compared with EMRs, IMRs or PMRs had significantly higher risk of treatment failure in terms of relapse and disease-free survival (DFS). LMRs had a tendency toward a lower DFS. Quantitative monitoring of MRD kinetics during the first-line imatinib-based chemotherapy course is useful in identifying subgroups of Ph-positive ALL transplants at a high risk of relapse.
Adolescent, Adult, Antineoplastic Agents, Benzamides, Combined Modality Therapy, Female, Hematopoietic Stem Cell Transplantation, Humans, Imatinib Mesylate, Male, Middle Aged, Neoplasm, Residual, Philadelphia Chromosome, Piperazines, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Prognosis, Pyrimidines, Real-Time Polymerase Chain Reaction, Young Adult
null
22,705,994
2013-02-28
2013-03-04
1476-5551
Leukemia
Hairy cell leukemia cell lines expressing annexin A1 and displaying B-cell receptor signals characteristic of primary tumor cells lack the signature BRAF mutation to reveal unrepresentative origins.
Weston-Bell N J, Hendriks D, Sugiyarto G, Bos N A, Kluin-Nelemans H C, Forconi F, Sahota S S
eng
null
Letter, Research Support, Non-U.S. Gov't
Annexin A1, RNA, Messenger, Receptors, Antigen, B-Cell, BRAF protein, human, Proto-Oncogene Proteins B-raf
IM
22705994, leu2012163, 10.1038/leu.2012.163
null
Annexin A1, B-Lymphocytes, Blotting, Western, Flow Cytometry, Humans, Immunoenzyme Techniques, Leukemia, Hairy Cell, Mutation, Proto-Oncogene Proteins B-raf, RNA, Messenger, Real-Time Polymerase Chain Reaction, Receptors, Antigen, B-Cell, Reverse Transcriptase Polymerase Chain Reaction, Tumor Cells, Cultured
null
22,705,995
2012-11-19
2012-07-13
1531-698X
Current opinion in pediatrics
Primary care for children and adolescents living with HIV.
Monge Maria C, Samples Cathryn L
eng
T71MC00009 (PHS HHS, United States)
Journal Article, Research Support, U.S. Gov't, P.H.S., Review
Anti-HIV Agents
IM
22705995, 10.1097/MOP.0b013e328355413f
Advances in HIV treatment, including simplified and better tolerated antiretroviral drug regimens, have led to increasing numbers of HIV-positive children and adolescents surviving into adulthood. Effective pediatric and adolescent primary care provided by pediatricians working together with an HIV specialist can help to optimize their current and future health.
Acquired Immunodeficiency Syndrome, Adolescent, Adolescent Health Services, Anti-HIV Agents, Atherosclerosis, Child, Child Health Services, Child, Preschool, Counseling, Female, Humans, Immunization Schedule, Insulin Resistance, Male, Primary Health Care, United States, Vaginal Smears
null
22,705,996
2012-11-19
2012-07-13
1531-698X
Current opinion in pediatrics
Endocrinology and metabolism 2012.
Root Allen W
eng
null
Editorial, Introductory Journal Article
fibroblast growth factor 21, Fibroblast Growth Factors
IM
22705996, 10.1097/MOP.0b013e3283557ceb
null
Adolescent, Carney Complex, Child, Child, Preschool, Endocrine System Diseases, Female, Fibroblast Growth Factors, Growth Disorders, Humans, Infant, Male, Marfan Syndrome, Peutz-Jeghers Syndrome, Sertoli Cell Tumor, Testicular Neoplasms, Wolfram Syndrome
null
22,705,997
2012-11-19
2012-07-13
1531-698X
Current opinion in pediatrics
Overgrowth syndromes.
Neylon Orla M, Werther George A, Sabin Matthew A
eng
null
Journal Article, Research Support, Non-U.S. Gov't, Review
null
IM
22705997, 10.1097/MOP.0b013e3283558995
Human growth ensues from a complex interplay of physiological factors, in the wider setting of varying genetic traits and environmental influences. Intensive research in these divergent areas, and particularly in the field of genetics, continues to clarify the molecular basis of disorders which result in overgrowth, and it is therefore timely to provide a review of these findings.
Abnormalities, Multiple, Adolescent, Child, Child, Preschool, Congenital Hypothyroidism, Craniofacial Abnormalities, Female, Fetal Macrosomia, Growth Disorders, Hand Deformities, Congenital, Humans, Infant, Male, Mutation, Phenotype, Prognosis, Proteus Syndrome, Wilms Tumor
null
22,705,998
2012-11-19
2016-11-25
1531-698X
Current opinion in pediatrics
Marfan syndrome: from gene to therapy.
Bolar Nikhita, Van Laer Lut, Loeys Bart L
eng
null
Journal Article, Research Support, Non-U.S. Gov't, Review
FBN1 protein, human, Fbn1 protein, mouse, Fibrillin-1, Fibrillins, Microfilament Proteins, Transforming Growth Factor beta
IM
22705998, 10.1097/MOP.0b013e3283557d4c
Although historically Marfan syndrome (MFS) has always been considered as a condition caused by the deficiency of a structural extracellular matrix protein, fibrillin-1, the study of Marfan mouse models and Marfan-related conditions has shifted our current understanding to a pathogenic model that involves dysregulation of the cytokine-transforming growth factor beta (TGF-β) signaling.
Acromegaly, Adolescent, Aortic Aneurysm, Thoracic, Child, Child, Preschool, Female, Fibrillin-1, Fibrillins, Humans, Loeys-Dietz Syndrome, Male, Marfan Syndrome, Microfilament Proteins, Mutation, Signal Transduction, Transforming Growth Factor beta
null
22,705,999
2012-11-19
2018-12-01
1531-698X
Current opinion in pediatrics
For both the doctor and the patient, what we see is important.
Chaudhari Jennifer Eggers, Dinulos James G H
eng
null
Journal Article, Portrait
null
IM
22705999, 10.1097/MOP.0b013e328355a381
null
Attitude of Health Personnel, Female, Humans, Male, Paintings, Physician's Role, Physician-Patient Relations
null
22,706,000
2012-09-24
2016-11-25
1473-5571
AIDS (London, England)
25 years of AIDS.
Adler Michael
eng
null
Historical Article, Journal Article
null
IM
22706000, 10.1097/QAD.0b013e328353efc3, 00002030-201206190-00002
null
Acquired Immunodeficiency Syndrome, HIV Infections, History, 20th Century, History, 21st Century, Humans, Journal Impact Factor, Periodicals as Topic, United Kingdom
null
22,706,001
2012-09-24
2012-06-18
1473-5571
AIDS (London, England)
AIDS: reflections on 1987-1992.
Weber Jonathan
eng
null
Historical Article, Journal Article
null
IM
22706001, 10.1097/QAD.0b013e328353f3b6, 00002030-201206190-00003
null
Acquired Immunodeficiency Syndrome, History, 20th Century, Humans, Journal Impact Factor, Periodicals as Topic
null
22,706,002
2012-09-24
2012-06-18
1473-5571
AIDS (London, England)
'…one man in his time plays many parts'.
Gold Jonathan W M
eng
null
Biography, Historical Article, Journal Article
null
IM
22706002, 10.1097/QAD.0b013e328353efab, 00002030-201206190-00004
null
Acquired Immunodeficiency Syndrome, History, 20th Century, History, 21st Century, Humans, Male, Research
null
22,706,003
2012-09-24
2012-06-18
1473-5571
AIDS (London, England)
Much progress, still many challenges.
Groopman Jerome E
eng
null
Journal Article
null
IM
22706003, 10.1097/QAD.0b013e328353f3ce, 00002030-201206190-00005
null
Acquired Immunodeficiency Syndrome, Female, HIV, HIV Infections, Humans, Male, Research
null
22,706,004
2012-09-24
2012-06-18
1473-5571
AIDS (London, England)
The next 25 years: the need for a long-term view.
Piot Peter
eng
null
Journal Article
null
IM
22706004, 10.1097/QAD.0b013e328353e1c6, 00002030-201206190-00006
null
Acquired Immunodeficiency Syndrome, HIV Infections, Health Services Needs and Demand, Humans, International Cooperation, Interprofessional Relations
null
22,706,005
2012-09-24
2016-11-25
1473-5571
AIDS (London, England)
Experiences as an editor.
Johnson Anne M
eng
null
Journal Article
null
IM
22706005, 10.1097/QAD.0b013e328354b378, 00002030-201206190-00007
null
Delivery of Health Care, HIV Infections, Homosexuality, Male, Humans, Male, United Kingdom
null
22,706,006
2012-09-24
2014-11-20
1473-5571
AIDS (London, England)
Epidemiological research in the HIV field: towards understanding what we do not know.
Buvé Anne, Laga Marie
eng
null
Journal Article
null
IM
22706006, 10.1097/QAD.0b013e328353bc36, 00002030-201206190-00008
null
Africa South of the Sahara, Epidemiologic Studies, Female, Global Health, HIV Infections, Humans, Male, Risk Factors
null
22,706,007
2012-09-24
2022-03-17
1473-5571
AIDS (London, England)
The evolving epidemiology of HIV/AIDS.
De Cock Kevin M, Jaffe Harold W, Curran James W
eng
null
Historical Article, Journal Article, Review
Anti-Retroviral Agents
IM
22706007, 10.1097/QAD.0b013e328354622a, 00002030-201206190-00009
Following its recognition in 1981, the HIV/AIDS epidemic has evolved to become the greatest challenge in global health, with some 34 million persons living with HIV worldwide. Early epidemiologic studies identified the major transmission routes of the virus before it was discovered, and enabled the implementation of prevention strategies. Although the first identified cases were in MSM in the United States and western Europe, the greatest impact of the epidemic has been in sub-Saharan Africa, where most of the transmission occurs between heterosexuals. Nine countries in southern Africa account for less than 2% of the world's population but now they represent about one third of global HIV infections. Where broadly implemented, HIV screening of donated blood and antiretroviral treatment (ART) of pregnant women have been highly effective in preventing transfusion-associated and perinatally acquired HIV, respectively. Access to sterile equipment has also been a successful intervention for injection drug users. Prevention of sexual transmission has been more difficult. Perhaps the greatest challenge in terms of prevention has been in the global community of MSM in which HIV remains endemic at high prevalence. The most promising interventions are male circumcision for prevention of female-to-male transmission and use of ART to reduce infectiousness, but the extent to which these interventions can be brought to scale will determine their population-level impact.
Africa, Anti-Retroviral Agents, Disease Outbreaks, Europe, Female, Global Health, HIV Infections, HIV-1, HIV-2, History, 20th Century, History, 21st Century, Homosexuality, Male, Humans, Infectious Disease Transmission, Vertical, Male, Pregnancy, Pregnancy Complications, Infectious, Prevalence, Risk Factors, United States
null
22,706,008
2012-09-24
2012-06-18
1473-5571
AIDS (London, England)
Prevention of sexual transmission of HIV: real results, science progressing, societies remaining behind.
Laga Marie, Piot Peter
eng
null
Journal Article, Review
Anti-HIV Agents, Anti-Retroviral Agents
IM
22706008, 10.1097/QAD.0b013e32835462b8, 00002030-201206190-00011
HIV spread has reached a turning point following decades of increasing and sustained incidence. An effective vaccine has not been developed, but critical breakthroughs with prevention based on antiretroviral treatment are promising. The new prevention technologies will have to be combined with condoms and incorporated into the mixes of combination prevention approaches that are tailored to the local epidemic and context. To address the implementation gap, more political will and leadership will be needed to overcome the socio-cultural, legal or religious barriers to prevention. We have learned that the generation of demand for HIV prevention is not easy, as for health promotion in general. Despite optimism about treatment as prevention, many western countries are facing an increase in new HIV cases, and HIV is no longer a collective concern. If we manage to find common ground on combination prevention, customize approaches to people's needs and exercise technical and political leadership, our decade may see the beginning of the end of the epidemic.
Anti-HIV Agents, Anti-Retroviral Agents, Circumcision, Male, Condoms, Developing Countries, Female, HIV Infections, Health Promotion, Humans, Male, Sexual Behavior, Sexually Transmitted Diseases
null
22,706,009
2012-09-24
2022-03-11
1473-5571
AIDS (London, England)
The history of antiretroviral therapy and of its implementation in resource-limited areas of the world.
Vella Stefano, Schwartländer Bernard, Sow Salif Papa, Eholie Serge Paul, Murphy Robert L
eng
null
Historical Article, Journal Article, Review
Anti-Retroviral Agents, Dideoxynucleosides, HIV Protease Inhibitors, Reverse Transcriptase Inhibitors
IM
22706009, 10.1097/QAD.0b013e32835521a3, 00002030-201206190-00012
HIV/AIDS not only represents the most severe epidemic in modern times, but also the greatest public health challenge in history. The response of the scientific community has been impressive and in just a few years, turned an inevitably fatal disease into a chronic manageable although not yet curable condition. The development of antiretroviral therapy is not only the history of scientific advancements: it is the result of the passionate 'alliance' towards a common goal between researchers, doctors and nurses, pharmaceutical industries, regulators, public health officials and the community of HIV-infected patients, which is rather unique in the history of medicine. In addition, the rapid and progressive development of antiretroviral therapy has not only proven to be life-saving for many millions but has been instrumental in unveiling the inequities in access to health between rich and poor countries of the world. Optimal benefits indeed, are not accessible to all people living with HIV, with challenges to coverage and sustainability in low and middle income countries. This paper will review the progress made, starting from the initial despairing times, till the current battle towards universal access to treatment and care for all people living with HIV.
Anti-Retroviral Agents, Antiretroviral Therapy, Highly Active, Developed Countries, Developing Countries, Dideoxynucleosides, HIV Infections, HIV Protease Inhibitors, History, 20th Century, History, 21st Century, Humans, Reverse Transcriptase Inhibitors
null
22,706,010
2012-09-24
2022-01-29
1473-5571
AIDS (London, England)
On HIV diversity.
Ndung'u Thumbi, Weiss Robin A
eng
G0801176 (Medical Research Council, United Kingdom)
Journal Article, Review
null
IM
22706010, 10.1097/QAD.0b013e32835461b5, 00002030-201206190-00014
HIV type 1 (HIV-1) displays a greater degree of genetic and antigenic variability than any other virus studied. This diversity reflects a high mutation rate during viral replication with a large turnover of virus, and a high tolerance of variation while maintaining reproductive capacity. Generation of diversity is a common property of lentiviruses such as HIV. Differences in virulence and in transmissibility are seen between different HIV-1 strains which may have clinical implications. The great degree of HIV diversity presents challenges to maintaining sensitivity to antiretroviral therapy and to the development of preventive strategies such as microbicides and vaccines.
HIV Infections, HIV-1, Humans, Mutation Rate, Virus Replication
null
22,706,013
2012-09-24
2015-11-19
1473-5571
AIDS (London, England)
Raltegravir-induced nephrolithiasis: a case report.
Vassallo Matteo, Dunais Brigitte, Naqvi Alissa, Garaffo Rodolphe, Durant Jacques
eng
null
Case Reports, Letter
Anti-HIV Agents, Pyrrolidinones, Raltegravir Potassium
IM
22706013, 10.1097/QAD.0b013e328353fda1, 00002030-201206190-00022
null
Adult, Anti-HIV Agents, Female, HIV Infections, Humans, Nephrolithiasis, Pyrrolidinones, Raltegravir Potassium, Recurrence
null
22,706,014
2012-10-16
2013-11-21
1464-0333
Journal of environmental monitoring : JEM
Critical analysis of the potential of Ipomoea nil'Scarlet O'Hara' for ozone biomonitoring in the sub-tropics.
Ferreira Maurício Lamano, Nobre Esposito Jéssica Bordotti, de Souza Silvia Ribeiro, Domingos Marisa
eng
null
Journal Article, Research Support, Non-U.S. Gov't
Air Pollutants, Ozone, Peroxidases, Superoxide Dismutase
IM
22706014, 10.1039/c2em30026e
This study aimed to analyze critically the potential of Ipomoea nil'Scarlet O'Hara' for O(3) biomonitoring in the sub-tropics. Four field experiments (one in each season of 2006) were carried out in a location of the city of São Paulo mainly polluted by O(3). Each experiment started with 50 plants, and lasted 28 days. Sub-lots of five plants were taken at intervals between three or four days long. Groups of four plants were also exposed in closed chambers to filtered air or to 40, 50 or 80 ppb of O(3) for three consecutive hours a day for six days. The percentage of leaf injury (interveinal chloroses and necroses), the concentrations of ascorbic acid (AA) and the activity of superoxide dismutase (SOD) and peroxidases (POD) were determined in the 5th, 6th and 7th oldest leaves on the main stem of the plants taken in all experiments. Visible injury occurred in the plants from all experiments. Seasonality in the antioxidant responses observed in plants grown under field conditions was associated with meteorological variables and ozone concentrations five days before leaf analyses. The highest levels of antioxidants occurred during the spring. The percentage of leaf injury was explained (R(2) = 0.97, p < 0.01) by the reduction in the levels of AA and activity of POD five days before the leaf analyses and by the reduction in the levels of particulate matter, and enhancement of temperature and global radiation 10 days before this same day. Although I. nil may be employed for qualitative O(3) biomonitoring, its efficiency for quantitative biomonitoring in the sub-tropics may be compromised, depending on how intense the oxidative power of the environment is.
Air Pollutants, Environmental Monitoring, Ipomoea nil, Ozone, Peroxidases, Plant Leaves, Superoxide Dismutase
null
22,706,012
2012-09-24
2022-03-16
1473-5571
AIDS (London, England)
Transitioning HIV care and treatment programs in southern Africa to full local management.
Vermund Sten H, Sidat Mohsin, Weil Lori F, Tique José A, Moon Troy D, Ciampa Philip J
eng
D43 TW001035 (FIC NIH HHS, United States); D43TW001035 (FIC NIH HHS, United States)
Journal Article, Research Support, N.I.H., Extramural
Anti-Retroviral Agents
IM
22706012, 10.1097/QAD.0b013e3283552185, 00002030-201206190-00019, PMC3576840, NIHMS439069, 18669420, 20825666, 20606571, 19947830, 19349625, 21047913, 15234864, 20941553, 21641026, 21628350, 21084990, 19858931, 25097450, 20562630, 18981769, 18382737, 21372723, 19491291, 12560007, 16776020, 21763938, 20180975, 21546845, 21745705, 21725246, 19858938, 21569533, 16392633, 22026289, 20841719, 21999776, 20934597, 17984757, 21767103, 21505317, 21266912, 18156161, 19901624, 20939909, 21846344, 20707698, 20529358, 21068674, 20516523, 3055286, 21967983, 21223546, 20540795, 21317587, 20588171, 20397956
Global AIDS programs such as the US President's Emergency Plan for AIDS Relief (PEPFAR) face a challenging health care management transition. HIV care must evolve from vertically-organized, externally-supported efforts to sustainable, locally controlled components that are integrated into the horizontal primary health care systems of host nations. We compared four southern African nations in AIDS care, financial, literacy, and health worker capacity parameters (2005 to 2009) to contrast in their capacities to absorb the huge HIV care and prevention endeavors that are now managed with international technical and fiscal support. Botswana has a relatively high national income, a small population, and an advanced HIV/AIDS care program; it is well poised to take on management of its HIV/AIDS programs. South Africa has had a slower start, given HIV denialism philosophies of the previous government leadership. Nonetheless, South Africa has the national income, health care management, and health worker capacity to succeed in fully local management. The sheer magnitude of the burden is daunting, however, and South Africa will need continuing fiscal assistance. In contrast, Zambia and Mozambique have comparatively lower per capita incomes, many fewer health care workers per capita, and lower national literacy rates. It is improbable that fully independent management of their HIV programs is feasible on the timetable being contemplated by donors, nor is locally sustainable financing conceivable at present. A tailored nation-by-nation approach is needed for the transition to full local capacitation; donor nation policymakers must ensure that global resources and technical support are not removed prematurely.
Acquired Immunodeficiency Syndrome, Anti-Retroviral Agents, Botswana, Delivery of Health Care, Developing Countries, Disease Management, HIV Infections, Humans, Mozambique, South Africa, Zambia
null
22,706,011
2012-09-24
2021-10-21
1473-5571
AIDS (London, England)
The design and evaluation of HIV-1 vaccines.
Saunders Kevin O, Rudicell Rebecca S, Nabel Gary J
eng
Z01 AI005002 (Intramural NIH HHS, United States)
Journal Article, Research Support, N.I.H., Intramural, Review
AIDS Vaccines, Vaccines, Synthetic
IM
22706011, 10.1097/QAD.0b013e32835474d2, 00002030-201206190-00018, PMC7480282, NIHMS1625192, 17409160, 17269929, 10846155, 19448633, 17109336, 10196297, 15613305, 20978378, 22237895, 16107949, 14985706, 12829775, 20978384, 22139420, 16357854, 20048702, 15519278, 19133809, 11797011, 21893538, 22229122, 19620962, 21732792, 3644145, 20168203, 21091279, 15166541, 20822348, 21562493, 15860590, 20350494, 21389135, 10403029, 12478295, 17721546, 20636279, 21501363, 20537376, 1531159, 20463069, 22217938, 21998254, 18987148, 21164527, 19414559, 12072528, 9641684, 12163597, 20010788, 22475592, 20080564, 19729618, 21899447, 15483468, 22315717, 11251383, 10644378, 8568294, 17301785, 21988996, 20876137, 16474158, 10490767, 20200250, 22113616, 19487423, 15700617, 20132004, 15834403, 16731926, 18724414, 15688278, 21543722, 18668044, 19843557, 17921999, 21395355, 12743287, 21764753, 21767103, 7848602, 20978375, 15367639, 20978385, 19012954, 17230414, 20978379, 16306625, 17109337, 18393601, 19620961, 18481459, 20042512, 9927688, 20643915, 20616231, 21508308, 17580087, 19372381, 22229123, 21849977, 18922865, 1470917, 19525965, 20299194, 20616233
There is renewed optimism that the goal of developing a highly effective AIDS vaccine is attainable. The HIV-1 vaccine field has seen its first trial of a vaccine candidate that prevents infection. Although modest in efficacy, this finding, along with the recent discovery that the human immune system can produce broadly neutralizing antibodies capable of inhibiting greater than 90% of circulating viruses, provides a guide for the rational design of vaccines and protection by passive immunization. Together, these findings will help shape the next generation of HIV vaccines.
AIDS Vaccines, Animals, Clinical Trials as Topic, Clinical Trials, Phase III as Topic, Drug Design, HIV Infections, HIV-1, Humans, Research Design, Treatment Outcome, Vaccines, Synthetic
null
22,706,015
2013-04-23
2018-12-01
1873-6750
Environment international
The 'take home' burden of workplace sensitizers: flour contamination in bakers' families.
Tagiyeva Nara, Anua Siti Marwanis, Semple Sean, Dick Finlay, Devereux Graham
eng
null
Journal Article, Research Support, Non-U.S. Gov't
Air Pollutants, Occupational, Allergens, Antigens, Fungal, Dust, alpha-Amylases
IM
22706015, S0160-4120(12)00103-1, 10.1016/j.envint.2012.04.014
Exposure to flour/flour constituents is a leading cause of occupational asthma. Paternal occupational exposure to flour has been associated with increased likelihood of childhood asthma, raising the possibility of para-occupational exposure whereby family members are exposed to sensitizers 'taken home' on contaminated skin/clothing.
Adult, Air Pollutants, Occupational, Air Pollution, Indoor, Allergens, Antigens, Fungal, Asthma, Automobiles, Clothing, Cross-Sectional Studies, Dust, Female, Flour, Fungi, Housing, Humans, Inhalation Exposure, Male, Middle Aged, Occupational Exposure, Scotland, Skin, Triticum, Workplace, Young Adult, alpha-Amylases
null
22,706,016
2013-04-23
2025-01-03
1873-6750
Environment international
Organic micropollutants in coastal waters from NW Mediterranean Sea: sources distribution and potential risk.
Sánchez-Avila Juan, Tauler Romà, Lacorte Silvia
eng
null
Journal Article, Research Support, Non-U.S. Gov't
Benzhydryl Compounds, Halogenated Diphenyl Ethers, Pesticides, Phenols, Phthalic Acids, Waste Water, Water Pollutants, Chemical, Polychlorinated Biphenyls, bisphenol A
IM
22706016, S0160-4120(12)00102-X, 10.1016/j.envint.2012.04.013
This study provides a first estimation on the sources, distribution and risk of organic micropollutants (OMPs) in coastal waters from NW Mediterranean Sea. Polycyclic aromatic hydrocarbons, polychlorinated biphenyls, organochlorinated pesticides, polybrominated diphenyl ethers, phthalates and alkylphenols were analyzed by solid phase extraction and gas chromatography coupled to tandem mass spectrometry (SPE-GC-EI-MS/MS). River waters and wastewater treatment plant effluents discharging to the sea were identified as the main sources of OMPs to coastal waters, with an estimated input amount of around of 25,800 g d(-1). The concentration of ΣOMPs in coastal areas ranged from 17.4 to 8442 ng L(-1), and was the highest in port waters, followed by coastal and river mouth seawaters. A summarized overview of the patterns and sources of OMP contamination on the investigated coastal sea waters of NW Mediterranean Sea, as well as of their geographical distribution was obtained by Principal Component Analysis of the complete data set after its adequate pretreatment. Alkylphenols, bisphenol A and phthalates were the main contributors to ΣOMPs and produced an estimated significant pollution risk for fish, algae and the sensitive mysid shrimp organisms in seawater samples. The combination of GC-MS/MS, chemometrics and risk analysis is proven to be useful for a better control and management of OMP discharges.
Animals, Benzhydryl Compounds, Decapoda, Environmental Monitoring, Fishes, Fresh Water, Gas Chromatography-Mass Spectrometry, Halogenated Diphenyl Ethers, Mediterranean Sea, Microalgae, Pesticides, Phenols, Phthalic Acids, Polychlorinated Biphenyls, Principal Component Analysis, Rivers, Seawater, Solid Phase Extraction, Tandem Mass Spectrometry, Wastewater, Water Pollutants, Chemical, Zooplankton
null
22,706,017
2013-02-05
2012-09-26
1878-5832
Drug discovery today
Improving drug penetration to curb tumor drug resistance.
Marcucci Fabrizio, Corti Angelo
eng
null
Journal Article, Research Support, Non-U.S. Gov't, Review
Antineoplastic Agents
IM
22706017, S1359-6446(12)00197-3, 10.1016/j.drudis.2012.06.004
Several classes of drugs that we refer to here as 'promoter drugs' can improve tumor uptake and penetration of other drugs that we refer to as 'effector drugs', which exert direct antitumor effects. In this review we discuss the main therapeutic advantages that can be obtained by using promoter drugs. First, tumor-specific enhancement of effector drug accumulation but unaltered accumulation in normal tissues with improvement of the therapeutic index. Second, we propose that curbing tumor drug resistance is another important consequence of using promoter drugs. In particular, we discuss evidence suggesting that promoter drugs can (i) prevent induction of new resistance by paracrine factors released in response to effector drugs, and (ii) reverse existing drug resistance induced by mechanical cues and tumor-cell-extracellular-matrix interactions.
Animals, Antineoplastic Agents, Biological Availability, Drug Resistance, Humans, Neoplasms, Pharmacokinetics
null
22,706,018
2013-11-12
2012-12-03
1878-5832
Drug discovery today
Rethinking leadership in drug discovery projects.
Schneider Andreas, Erden Zeynep, Widmer Hans, Koch Guido, Billy Christine, von Krogh Georg
eng
null
Journal Article
null
IM
22706018, S1359-6446(12)00198-5, 10.1016/j.drudis.2012.06.005
Great efforts have been dedicated to rebuilding the engine of pharmaceutical R&D. However, one potential area of improvement has received limited attention in the literature and in practice: namely, leadership. In this article, we enrich the traditional views of leadership, which consider leadership a responsibility of a few centrally placed authorities, with the concept of distributed leadership. Distributed leadership reflects a group-based capability driven by everyday activities and the key scientific questions at hand. We identify three leadership challenges faced by R&D teams that could be addressed by implementing distributed leadership. Furthermore, we provide some suggestions as to how to foster distributed leadership in drug discovery projects.
Decision Support Techniques, Drug Discovery, Leadership, Organizational Innovation
null
22,706,019
2012-09-06
2012-06-18
1540-0514
Shock (Augusta, Ga.)
Shock supports the use of animal research reporting guidelines.
Reynolds Penny, Wall Piper, van Griensven Martijn, McConnell Kevin, Lang Charles, Buchman Timothy
eng
null
Editorial
null
IM
22706019, 10.1097/SHK.0b013e31825f396c, 00024382-201207000-00001
null
Animal Experimentation, Animal Welfare, Animals, Disclosure, Guidelines as Topic, Periodicals as Topic, Publishing
null
22,706,020
2012-09-06
2013-11-21
1540-0514
Shock (Augusta, Ga.)
Enhanced steroid response of a human glucocorticoid receptor splice variant.
Baker Aaron C, Green Tajia L, Chew Victoria W, Tung Kelly, Amini Amir, Lim Debora, Cho Kiho, Greenhalgh David G
eng
null
Journal Article, Research Support, Non-U.S. Gov't
Anti-Inflammatory Agents, Glucocorticoids, Protein Isoforms, Receptors, Glucocorticoid, Hydrocortisone, Methylprednisolone
IM
22706020, 10.1097/SHK.0b013e318257c0c0, 00024382-201207000-00003
Glucocorticoids remain a recommended therapy in advanced septic shock despite the often unpredictable response, and our understanding of the mechanisms regulating the steroid and stress response remains limited. Since the initial sequencing of the human glucocorticoid receptor α and β gene (hGRα and hGRβ), only three additional splice variants have been identified--all of which have been postulated to contribute to steroid resistance. During a survey of 97 healthy humans' blood, we identified two novel hGR splice isoforms (hGR-S1 and hGR-S1(-349A) retaining intron H between exons 8 and 9. Human GR-S1(-349A) contained a base deletion causing an early termination and a truncated protein of 118 amino acids, whereas hGR-S1 had an early termination occurring within intron H and resulted in a 745-amino acid protein. Both isoforms had decreased transactivation potentials compared with hGRα when tested in the absence of exogenous steroids. However, after treating with exogenous steroids, dose-response studies showed hGR-S1(-349A) had a substantial augmentation in activity at higher concentrations of hydrocortisone and methylprednisolone when compared with hGRα, whereas hGR-S1 did not. Removal of the 3' untranslated region (3'UTR) of the hGR-S1(-349A) mRNA sequence resulted in a loss of the augmented response. The isoform hGR-S1(-349A) augments the response to steroids, and this significant response appears to be critically regulated by the 3'UTR. The identification and evaluation of these unique hGR isoforms helps further the understanding of the complex genetic regulation of the stress and steroid response.
Adult, Aged, Alternative Splicing, Anti-Inflammatory Agents, Base Sequence, Cells, Cultured, Dose-Response Relationship, Drug, Female, Glucocorticoids, Humans, Hydrocortisone, Inteins, Male, Methylprednisolone, Middle Aged, Molecular Sequence Data, Open Reading Frames, Protein Isoforms, Receptors, Glucocorticoid, Transcriptional Activation, Young Adult
null
22,706,021
2012-09-06
2012-06-18
1540-0514
Shock (Augusta, Ga.)
A comparison of the time from sepsis to inception of continuous renal replacement therapy versus RIFLE criteria in patients with septic acute kidney injury.
Chon Gyu Rak, Chang Jai Won, Huh Jin Won, Lim Chae-Man, Koh Younsuck, Park Su Kil, Park Jung Sik, Hong Sang-Bum
eng
null
Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
null
IM
22706021, 10.1097/SHK.0b013e31825adcda, 00024382-201207000-00006
We hypothesized that the time from sepsis to inception of continuous renal replacement therapy (CRRT) can be used to predict survival rates in patients with septic acute kidney injury (AKI). The survival predictability of CRRT inception time was compared with that of RIFLE criteria, which were previously used in clinical practice. We retrospectively analyzed outcomes in 55 patients with septic AKI admitted to the medical intensive care unit at Asan Medical Center (Seoul, Korea) between April 2009 and October 2010. These patients were stratified by the time of inception of CRRT from sepsis (early: ≤ 24 h and late: >24 h) and also by the RIFLE criteria (RIFLE-I and RIFLE-F). The primary outcome was 28-day mortality. Of the 55 patients, 38 (69.1%) were male. Patients' mean age was 62.6 years, the most common infection site was the lung (32, 58.2%), and 47 patients (85.5%) were on mechanical ventilation. Thirty patients (54.5%) were in the RIFLE-I, and the others were in the RIFLE-F. Twenty-eight-day mortality rates were lower in the early group than in the late group (19.4% vs. 47.4%; P = 0.03), but did not differ between RIFLE-I and RIFLE-F. Ventilator-free day at day 28 was longer in the early group than that in the late group (7.5 vs. 0 d; P = 0.033). After adjustment for covariates, we found that the late group (hazard ratio, 3.106; 95% confidence interval, 1.066-9.047) and Sequential Organ Failure Assessment at sepsis (hazard ratio, 1.410; 95% confidence interval, 1.108-1.796) were independent factors associated with 28-day mortality. This study suggests that the time interval from sepsis to CRRT inception may be a more useful predictor of 28-day mortality than RIFLE criteria in patients with septic AKI.
Acute Kidney Injury, Aged, Female, Humans, Intensive Care Units, Kaplan-Meier Estimate, Length of Stay, Male, Middle Aged, Prognosis, Renal Replacement Therapy, Retrospective Studies, Sepsis, Severity of Illness Index, Time Factors
null
22,706,022
2012-09-06
2021-10-21
1540-0514
Shock (Augusta, Ga.)
Syndecan 1 plays a novel role in enteral glutamine's gut-protective effects of the postischemic gut.
Peng Zhanglong, Ban Kechen, Sen Aritra, Grill Raymond, Park Pyong, Costantini Todd W, Kozar Rosemary
eng
R01 GM077282 (NIGMS NIH HHS, United States); R01 GM107482 (NIGMS NIH HHS, United States); UL1 RR024148 (NCRR NIH HHS, United States)
Journal Article, Research Support, N.I.H., Extramural
Syndecan-1, Glutamine, Caspases
IM
22706022, 10.1097/SHK.0b013e31825a188a, 00024382-201207000-00010, PMC3391586, NIHMS386013, 18762209, 1386982, 20884886, 16807246, 19540488, 12016132, 12198707, 20080249, 16257923, 19073610, 22237752, 15087819, 19875451, 8394371, 10220304, 12235282, 11333985, 16020957, 20128996, 18165444, 19638625, 21046201, 12744489, 18064305, 12904296, 12069183, 17383525, 21346161, 10406379, 18596315
Syndecan 1 is the predominant heparan sulfate proteoglycan found on the surface of epithelial cells and, like glutamine, is essential in maintaining the intestinal epithelial barrier. We therefore hypothesized that loss of epithelial syndecan 1 would abrogate the gut-protective effects of enteral glutamine. Both an in vitro and in vivo model of gut ischemia-reperfusion (IR) was utilized. In vitro, intestinal epithelial cells underwent hypoxia-reoxygenation to mimic gut IR with 2 mM (physiologic) or 10 mM glutamine supplementation. Permeability, caspase activity, cell growth, and cell surface and shed syndecan 1 were assessed. In vivo, wild-type and syndecan 1 knockout (KO) mice received ± enteral glutamine followed by gut IR. Intestinal injury was assessed by fluorescent dye clearance and histopathology, permeability as mucosal-to-serosal clearance ex vivo in everted sacs, and inflammation by myeloperoxidase (MPO) activity. In an in vitro model of gut IR, glutamine supplementation reduced epithelial cell permeability and apoptosis and enhanced cell growth. Shed syndecan 1 was reduced by glutamine without an increase in syndecan 1 mRNA. In vivo, intestinal permeability, inflammation, and injury were increased after gut IR in wild-type mice and further increased in syndecan 1 KO mice. Glutamine's attenuation of IR-induced intestinal hyperpermeability, inflammation, and injury was abolished in syndecan 1 KO mice. These results suggest that syndecan 1 plays a novel role in the protective effects of enteral glutamine in the postischemic gut.
Animals, Caspases, Cell Division, Cell Hypoxia, Cells, Cultured, Epithelial Cells, Glutamine, Intestinal Diseases, Intestinal Mucosa, Intestines, Mice, Mice, Inbred C57BL, Mice, Knockout, Permeability, Rats, Reperfusion Injury, Syndecan-1
null
22,706,024
2013-01-23
2013-11-21
1089-8638
Journal of molecular biology
pH-dependent dimerization of spider silk N-terminal domain requires relocation of a wedged tryptophan side chain.
Jaudzems Kristaps, Askarieh Glareh, Landreh Michael, Nordling Kerstin, Hedhammar My, Jörnvall Hans, Rising Anna, Knight Stefan D, Johansson Jan
eng
null
Journal Article, Research Support, Non-U.S. Gov't
Silk, Tryptophan, Fibroins
IM
22706024, S0022-2836(12)00466-4, 10.1016/j.jmb.2012.06.004
Formation of spider silk from its constituent proteins-spidroins-involves changes from soluble helical/coil conformations to insoluble β-sheet aggregates. This conversion needs to be regulated to avoid precocious aggregation proximally in the silk gland while still allowing rapid silk assembly in the distal parts. Lowering of pH from about 7 to 6 is apparently important for silk formation. The spidroin N-terminal domain (NT) undergoes stable dimerization and structural changes in this pH region, but the underlying mechanisms are incompletely understood. Here, we determine the NMR and crystal structures of Euprosthenops australis NT mutated in the dimer interface (A72R). Also, the NMR structure of wild-type (wt) E. australis NT at pH7.2 and 300 mM sodium chloride was determined. The wt NT and A72R structures are monomers and virtually identical, but they differ from the subunit structure of dimeric wt NT mainly by having a tryptophan (W10) buried between helix 1 and helix 3, while W10 is surface exposed in the dimer. Wedging of the W10 side chain in monomeric NT tilts helix 3 approximately 5-6Å into a position that is incompatible with that of the observed dimer structure. The structural differences between monomeric and dimeric NT domains explain the tryptophan fluorescence patterns of NT at pH7 and pH6 and indicate that the biological function of NT depends on conversion between the two conformations.
Amino Acid Sequence, Animals, Crystallography, X-Ray, Fibroins, Hydrogen-Ion Concentration, Magnetic Resonance Spectroscopy, Molecular Sequence Data, Protein Multimerization, Protein Structure, Secondary, Protein Structure, Tertiary, Silk, Spiders, Tryptophan
null
22,706,023
null
2021-10-21
null
Journal of health behavior and public health
Does Gender Moderate Associations Between Social Capital and Smoking? An Asian American Study.
Li Shijian, Delva Jorge
eng
P60 MD000538 (NIMHD NIH HHS, United States); U58 DP001022 (NCCDPHP CDC HHS, United States)
Journal Article
null
null
22706023, PMC3374585, NIHMS374886, 11860392, 14759946, 15719530, 19910909, 19443815, 11720409, 14675936, 18207227, 15450705, 16809581, 18158512, 12590993, 15199009, 19616270, 11854334, 19008791, 11854332, 16276539, 18667260, 16971030, 3602283, 15719529, 12721139, 15970227, 14749612, 22013026, 15252073, 16507645, 15917070
Growing research finds that social capital is associated with smoking. However, most studies focus on white populations and do not take into account potential differences between genders. The present study examines the associations between social capital and self-report smoking status and assesses the moderating role of gender among a national representative sample of Asian American adults. Social capital consisted of measures of individual social connectedness (i.e. social ties with relatives and friends) and subjective evaluation of family and neighborhood environment (i.e. family and neighborhood cohesion, family conflict). Asian men were almost three times more likely to be current smokers than women (20.1% vs. 7.0%). Results of multivariate logistic regression analyses showed that family conflicts or higher levels of connectedness with family members were associated with increased odds of being a current smoker among Asian Americans as a whole. Further stratified analysis revealed significant gender differences in several aspects of social capital: there were stronger effects of social connectedness with family members on increasing the odds of smoking for women than for men. In addition, women who had closer connections to friends had greater odds of being current smokers, whereas the opposite was true for men. The findings of this study provide new evidence for the differential effects of social capital by gender, suggesting that more studies are needed to understand social capital's effects in different racial/ethnic populations and the mechanisms by which the effects vary with gender.
null
null
22,706,025
2013-01-23
2024-07-27
1089-8638
Journal of molecular biology
Autoproteolytic activation of ThnT results in structural reorganization necessary for substrate binding and catalysis.
Buller Andrew R, Labonte Jason W, Freeman Michael F, Wright Nathan T, Schildbach Joel F, Townsend Craig A
eng
R01 AI014937 (NIAID NIH HHS, United States); R01 GM061017 (NIGMS NIH HHS, United States); R37 AI014937 (NIAID NIH HHS, United States); GM61017 (NIGMS NIH HHS, United States)
Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
GPI-Linked Proteins, Thienamycins, Amidohydrolases, pantetheinase, thienamycin
IM
22706025, S0022-2836(12)00485-8, 10.1016/j.jmb.2012.06.012, PMC3428426, NIHMS387021, 7725107, 20223213, 21913298, 7477383, 18678912, 8280057, 10490104, 17159900, 21576250, 12746549, 17599357, 20858215, 22308359, 8576176, 15358003, 15299374, 10673442, 10377256, 12538265, 17157318, 9642094, 16860823, 7816145, 9667864, 16369486, 12475205, 8068658, 20017478, 15572765, 14696379, 11206054, 19476497, 10500183, 17737951, 19461840, 952885, 17107958, 11706000, 19105697, 20800597, 15150276
cis-Autoproteolysis is a post-translational modification necessary for the function of ThnT, an enzyme involved in the biosynthesis of the β-lactam antibiotic thienamycin. This modification generates an N-terminal threonine nucleophile that is used to hydrolyze the pantetheinyl moiety of its natural substrate. We determined the crystal structure of autoactivated ThnT to 1.8Å through X-ray crystallography. Comparison to a mutationally inactivated precursor structure revealed several large conformational rearrangements near the active site. To probe the relevance of these transitions, we designed a pantetheine-like chloromethyl ketone inactivator and co-crystallized it with ThnT. Although this class of inhibitor has been in use for several decades, the mode of inactivation had not been determined for an enzyme that uses an N-terminal nucleophile. The co-crystal structure revealed the chloromethyl ketone bound to the N-terminal nucleophile of ThnT through an ether linkage, and analysis suggests inactivation through a direct displacement mechanism. More importantly, this inactivated complex shows that three regions of ThnT that are critical to the formation of the substrate binding pocket undergo rearrangement upon autoproteolysis. Comparison of ThnT with other autoproteolytic enzymes of disparate evolutionary lineage revealed a high degree of similarity within the proenzyme active site, reflecting shared chemical constraints. However, after autoproteolysis, many enzymes, like ThnT, are observed to rearrange in order to accommodate their specific substrate. We propose that this is a general phenomenon, whereby autoprocessing systems with shared chemistry may possess similar structural features that dissipate upon rearrangement into a mature state.
Amidohydrolases, Catalysis, Catalytic Domain, Crystallography, X-Ray, Enzyme Activation, GPI-Linked Proteins, Hydrolysis, Protein Processing, Post-Translational, Proteolysis, Substrate Specificity, Thienamycins
null
22,706,028
2012-11-28
2012-07-03
1096-0856
Journal of magnetic resonance (San Diego, Calif. : 1997)
Anisotropy in high-resolution diffusion-weighted MRI and anomalous diffusion.
Hanyga A, Seredyńska M
eng
null
Journal Article
null
IM
22706028, S1090-7807(12)00177-2, 10.1016/j.jmr.2012.05.001
It is shown below that complex diffusion anisotropy observed in diffusion-weighted MRI can be fully accounted for by allowing for non-locality of the spatial operator in the diffusion equation. The anisotropy is represented by a distribution over directions on a sphere. It allows recognition of fiber tracts crossing at arbitrary angles. A simple generalization of the Stejskal-Tanner equation for the determination of the ODF is presented. Furthermore, an explicit solution of the Bloch-Torrey equation for an anisotropic time-fractional diffusion equation is obtained in terms of a generalized Mittag-Leffler type function.
Algorithms, Anisotropy, Artifacts, Diffusion Magnetic Resonance Imaging, Image Enhancement, Image Interpretation, Computer-Assisted, Reproducibility of Results, Sensitivity and Specificity
null
22,706,027
2012-12-11
2022-04-09
1096-1186
Pharmacological research
β-Catenin pathway is required for TGF-β1 inhibition of PPARγ expression in cultured hepatic stellate cells.
Qian Jingjing, Niu Minghui, Zhai Xuguang, Zhou Qian, Zhou Yajun
eng
null
Journal Article, Research Support, Non-U.S. Gov't
Collagen Type I, PPAR gamma, Transforming Growth Factor beta1, beta Catenin, Glycogen Synthase Kinase 3 beta, Gsk3b protein, rat, Glycogen Synthase Kinase 3, Matrix Metalloproteinases
IM
22706027, S1043-6618(12)00121-1, 10.1016/j.phrs.2012.06.003
Hepatic stellate cell (HSC) activation is a key step in process of liver fibrosis. Transforming growth factor-β1 (TGF-β1) is the most powerful mediator of HSC activation and plays a central role in liver fibrosis. Peroxisome proliferator-activated receptor-γ (PPARγ) is an important regulator of adipocyte differentiation and has been proposed as a crucial factor for inhibition of HSC activation. The effect of TGF-β1 on PPARγ in HSCs is largely unknown. This study is aimed to examine whether TGF-β1 can influence PPARγ expression, focusing on the role of β-catenin pathway, a key pathway linked to adipogenesis, in TGF-β1 regulation of PPARγ in cultured HSCs. Our results demonstrated that TGF-β1 evidently inhibited PPARγ expression and activity in cultured HSCs, which were mediated through β-catenin pathway. TGF-β1 promoted β-catenin expression and also increased the stability of β-catenin protein through ERK1/2/glycogen synthase kinase-3β (GSK-3β) axis in cultured HSCs. Moreover, TGF-β1 inhibition of PPARγ expression by β-catenin pathway caused the increase in alpha1(1) collagen and tissue inhibitor of matrix metalloproteinase expression. These results indicated for the first time that TGF-β1 could down-regulate PPARγ expression through β-catenin pathway and subsequently contributed to the increase in alpha1(1) collagen level in cultured HSCs.
Adipogenesis, Animals, Cell Differentiation, Collagen Type I, Down-Regulation, Glycogen Synthase Kinase 3, Glycogen Synthase Kinase 3 beta, Hepatic Stellate Cells, Liver Cirrhosis, MAP Kinase Signaling System, Matrix Metalloproteinases, PPAR gamma, Rats, Rats, Sprague-Dawley, Signal Transduction, Transforming Growth Factor beta1, beta Catenin
null
22,706,026
2013-01-23
2021-10-21
1089-8638
Journal of molecular biology
Triepitopic antibody fusions inhibit cetuximab-resistant BRAF and KRAS mutant tumors via EGFR signal repression.
Spangler Jamie B, Manzari Mandana T, Rosalia Elizabeth K, Chen Tiffany F, Wittrup K Dane
eng
R01 CA096504 (NCI NIH HHS, United States); R01 CA101830 (NCI NIH HHS, United States); CA96504 (NCI NIH HHS, United States)
Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.
Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Fibronectins, KRAS protein, human, Proto-Oncogene Proteins, Recombinant Fusion Proteins, EGFR protein, human, ErbB Receptors, BRAF protein, human, Proto-Oncogene Proteins B-raf, Proto-Oncogene Proteins p21(ras), ras Proteins, Cetuximab
IM
22706026, S0022-2836(12)00487-1, 10.1016/j.jmb.2012.06.014, PMC4041985, NIHMS387350, 17704420, 22160867, 17895366, 16618717, 20068188, 9843701, 2543678, 7612182, 11096108, 20616078, 18593896, 6263497, 15994311, 19737224, 7488034, 1667084, 19001320, 1309762, 17646646, 19809433, 19278030, 11597399, 9219684, 15684082, 12653668, 15837620, 8735249, 11252954, 18316791, 10068277, 21125676, 2997213, 15857286, 21520037, 17041261, 9006938, 15035987, 19156131, 8951178, 9815926
Dysregulation of epidermal growth factor receptor (EGFR) is a hallmark of many epithelial cancers, rendering this receptor an attractive target for cancer therapy. Much effort has been focused on the development of EGFR-directed antibody-based therapeutics, culminating in the clinical approval of the drugs cetuximab and panitumumab. Unfortunately, the clinical efficacy of these drugs has been disappointingly low, and a particular challenge to targeting EGFR with antibody therapeutics has been resistance, resulting from mutations in the downstream raf and ras effector proteins. Recent work demonstrating antibody cocktail-induced synergistic downregulation of EGFR motivated our design of cetuximab-based antibody-fibronectin domain fusion proteins that exploit downregulation-based EGFR inhibition by simultaneously targeting multiple receptor epitopes. We establish that, among our engineered multiepitopic formats, trans-triepitopic antibody fusions demonstrate optimal efficacy, inducing rapid EGFR clustering and internalization and consequently ablating downstream signaling. The combined effects of EGFR downregulation, ligand competition, and immune effector function conspire to inhibit tumor growth in xenograft models of cetuximab-resistant BRAF and KRAS mutant cancers. Our designed triepitopic constructs have the potential to enhance the efficacy and expand the scope of EGFR-directed therapies, and our multiepitopic may be readily applied to other receptor targets to formulate a new class of antibody-based therapeutics.
Animals, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Cell Line, Tumor, Cetuximab, Down-Regulation, Drug Resistance, Neoplasm, ErbB Receptors, Female, Fibronectins, HCT116 Cells, HEK293 Cells, HT29 Cells, Humans, Mice, Mutation, Neoplasms, Proto-Oncogene Proteins, Proto-Oncogene Proteins B-raf, Proto-Oncogene Proteins p21(ras), Recombinant Fusion Proteins, Signal Transduction, ras Proteins
null
22,706,029
2012-11-28
2024-03-17
1096-0856
Journal of magnetic resonance (San Diego, Calif. : 1997)
A large volume double channel 1H-X RF probe for hyperpolarized magnetic resonance at 0.0475 T.
Coffey Aaron M, Shchepin Roman V, Wilkens Ken, Waddell Kevin W, Chekmenev Eduard Y
eng
5R00 CA134749-03 (NCI NIH HHS, United States); P50 CA128323 (NCI NIH HHS, United States); 5P50CA128323-03 (NCI NIH HHS, United States); 3R00CA134749-02S1 (NCI NIH HHS, United States); R25 CA136440 (NCI NIH HHS, United States); R01 CA140220 (NCI NIH HHS, United States); R00 CA134749 (NCI NIH HHS, United States)
Journal Article, Research Support, N.I.H., Extramural
Protons
IM
22706029, S1090-7807(12)00158-9, 10.1016/j.jmr.2012.04.012, PMC3510702, NIHMS381593, 20472478, 20171034, 10033824, 19319902, 16828566, 21141960, 22188975, 17174130, 21207591, 19067008, 17920316, 18486008, 22352377, 15671161, 19067009, 21981529, 22152352, 19256566, 17627856, 19848401, 15719973, 14652180, 21590996, 21403835
In this work we describe a large volume 340 mL (1)H-X magnetic resonance (MR) probe for studies of hyperpolarized compounds at 0.0475 T. (1)H/(13)C and (1)H/(15)N probe configurations are demonstrated with the potential for extension to (1)H/(129)Xe. The primary applications of this probe are preparation and quality assurance of (13)C and (15)N hyperpolarized contrast agents using PASADENA (parahydrogen and synthesis allow dramatically enhanced nuclear alignment) and other parahydrogen-based methods of hyperpolarization. The probe is efficient and permits 62 μs (13)C excitation pulses at 5.3 W, making it suitable for portable operation. The sensitivity and detection limits of this probe, tuned to (13)C, are compared with a commercial radio frequency (RF) coil operating at 4.7 T. We demonstrate that low field MR of hyperpolarized contrast agents could be as sensitive as conventional high field detection and outline potential improvements and optimization of the probe design for preclinical in vivo MRI. PASADENA application of this low-power probe is exemplified with (13)C hyperpolarized 2-hydroxyethyl propionate-1-(13)C,2,3,3-d(3).
Equipment Design, Equipment Failure Analysis, Magnetic Resonance Spectroscopy, Magnetics, Protons, Transducers
null
22,706,030
2012-12-14
2018-12-01
1873-3476
International journal of pharmaceutics
Jonathan Hadgraft--a Festschrift.
Lane Majella E
eng
null
Biography, Editorial, Historical Article, Portrait
null
IM
22706030, S0378-5173(12)00618-7, 10.1016/j.ijpharm.2012.06.021
null
England, History of Pharmacy, History, 20th Century, History, 21st Century
null
22,706,031
2012-10-25
2016-11-25
1361-6560
Physics in medicine and biology
Automatic delineation of body contours on cone-beam CT images using a delineation booster.
Stippel G, van Rooijen D C, Crezee J, Bel A
eng
null
Journal Article, Research Support, Non-U.S. Gov't
null
IM
22706031, 10.1088/0031-9155/57/13/N225
In radiotherapy, cone-beam computerized tomography (CBCT) scans are used for position correction for various tumour sites. At the start of the treatment, a CT scan that serves as input for a treatment planning is acquired. A CBCT scan is made prior to the irradiation of the tumour. Because there might be significant interfractional tumour movement, online recalculation of the dose improves decision making on how to proceed. A prerequisite for such recalculation is an accurately delineated body contour. In this note, we present an automatic delineation method for the body contour in the unprocessed CBCT scans, that employs a novel delineation boosting technique. The main idea of this technique is to construct an accurate delineation by combining the strength of several edge detectors in an innovative way. Quantitative validation reveals that the algorithm performs comparably with the manual delineations of two trained observers. Furthermore, because of the generic nature of the delineation boosting procedure, the algorithm can easily be extended with additional edge detectors to further increase the accuracy. Finally, the processing time of one scan when delineated manually is 3 h, and the total processing time is 24 min for one scan if the algorithm is used in its present form. Current investigation includes the conversion of the Matlab algorithm to C++ and the development of a visual tool to quickly detect which automatically delineated slices need manual correction. From this we expect further speeding up of the process, allowing online computation.
Algorithms, Artifacts, Automation, Cone-Beam Computed Tomography, Humans, Image Processing, Computer-Assisted, Neoplasms, Radiotherapy Dosage
null
22,706,032
2013-04-25
2012-08-14
1471-9053
Plant & cell physiology
Transcriptome analysis of age-related gain of callus-forming capacity in Arabidopsis hypocotyls.
Chen Chi-Chien, Fu Shih-Feng, Lee Yung-I, Lin Chung-Yi, Lin Wan-Chen, Huang Hao-Jen
eng
null
Journal Article, Research Support, Non-U.S. Gov't
Cytokinins, Plant Growth Regulators
IM
22706032, pcs090, 10.1093/pcp/pcs090
Callus-forming capacity is enhanced with hypocotyl maturity in Arabidopsis. However, the genetic regulation of age-related gain in capacity for callus formation is unclear. We used a gene expression microarray assay to characterize the underlying mechanisms during callus formation in young and mature hypocotyl explants of Arabidopsis. As expected, genes involved in photosynthesis and cell wall thickening showed altered expression during hypocotyl maturation. In addition, genes involved in cytokinin perception were enriched in mature hypocotyl tissues. Phytohormone-induced callus formation in hypocotyl explants was accompanied by increased expression of genes mainly related to the cell cycle, histones and epigenetics. The induction level of these genes was higher in mature hypocotyl explants than young explants during callus formation. We identified a number of genes, including those with unknown function, potentially involved in age-related gain in callus formation. Our results provide insight into the effect of hypocotyl age on callus formation. Altered cytokinin signaling components, cell cycle regulation and epigenetics may work in concert to lead to gain of callus-forming capacity in hypocotyls with age.
Arabidopsis, Cell Division, Cytokinins, Epigenesis, Genetic, Gene Expression Profiling, Gene Expression Regulation, Plant, Hypocotyl, Plant Growth Regulators, Time Factors, Tissue Culture Techniques
null
22,706,033
2013-04-25
2017-11-16
1471-9053
Plant & cell physiology
UV-A light induces anthocyanin biosynthesis in a manner distinct from synergistic blue + UV-B light and UV-A/blue light responses in different parts of the hypocotyls in turnip seedlings.
Wang Yu, Zhou Bo, Sun Mei, Li Yuhua, Kawabata Saneyuki
eng
null
Journal Article, Research Support, Non-U.S. Gov't
Anthocyanins, Basic Helix-Loop-Helix Transcription Factors, Cryptochromes, Pancreatitis-Associated Proteins, Plant Proteins, REG3A protein, human, Reactive Oxygen Species, Transcription Factors, Alcohol Oxidoreductases, dihydroflavanol 4-reductase, Acyltransferases, flavanone synthetase
IM
22706033, pcs088, 10.1093/pcp/pcs088
The effects of irradiating blue, UV-A, UV-B and a combination of the lights on anthocyanin accumulation at different hypocotyl positions were investigated in seedlings of the purple top turnip 'Tsuda'. The location of anthocyanin accumulation varied depending on different light spectra. Stronger accumulation of anthocyanin was induced (i) at the upper hypocotyl positions by blue light; (ii) mainly at the upper position, but also at the middle position by UV-B light; and (iii) at the upper to lower position by UV-A light. There were synergistic effects between blue and UV-B, while such effects were not observed for the other light combinations. Among the six chalcone synthase (CHS) genes identified in the 'Tsuda' turnip, BrCHS1, 4 and 5 exhibited light-dependent expression patterns, while the other three showed no apparent light responses. The expression of BrCHS1, 4 and 5 was increased particularly by UV-A and blue + UV-B irradiation at the middle to lower hypocotyl positions, in accordance with anthocyanin accumulation patterns. The highest induction of gene expression was observed for BrCHS4 upon blue + UV-B co-irradiation. In contrast, CHS expression was induced only slightly at higher hypocotyl positions by blue light. The R2R3-type MYB transcription factor genes PAP1, MYB4, MYB12 and MYB111 exhibited differential expression patterns at different hypocotyl positions; these patterns were unique for different light spectra. These unique anthocyanin accumulation patterns and gene expression profiles depending on hypocotyl positions and light sources demonstrate that there is a distinct UV-A response, blue + UV-B synergistic response and blue/UV-A light response for anthocyanin biosynthesis in turnip. UV-A light-dependent anthocyanin biosynthesis appeared to be regulated in a manner that is distinct from that mediated by cryptochromes and UV-B photoreceptors.
Acyltransferases, Alcohol Oxidoreductases, Anthocyanins, Basic Helix-Loop-Helix Transcription Factors, Brassica napus, Cryptochromes, Dose-Response Relationship, Radiation, Gene Expression Regulation, Plant, Hypocotyl, Light, Pancreatitis-Associated Proteins, Plant Proteins, Reactive Oxygen Species, Seedlings, Time Factors, Transcription Factors, Ultraviolet Rays
null
22,706,034
2012-09-19
2012-07-17
2042-7670
The Veterinary record
Use of low-field MRA to presurgically screen for medial meniscus lesions in 30 dogs with cranial cruciate deficient stifles.
McCartney W T, McGovern F
eng
null
Journal Article
null
IM
22706034, vr.100671, 10.1136/vr.100671
null
Animals, Anterior Cruciate Ligament, Dog Diseases, Dogs, Female, Joint Diseases, Magnetic Resonance Imaging, Male, Menisci, Tibial, Preoperative Period, Prospective Studies, Stifle
null
22,706,035
2012-09-24
2012-07-23
2042-7670
The Veterinary record
Laparoscopic ovariectomy in dogs using a single-port multiple-access device.
Manassero M, Leperlier D, Vallefuoco R, Viateau V
eng
null
Journal Article
null
IM
22706035, vr.100060, 10.1136/vr.100060
The aim of this case series was to describe a novel technique of single-incision laparoscopic ovariectomy in dogs using the SILS Port (Covidien), a single-port multiple-access device, in 40 client-owned dogs. A single 3 cm incision was made caudal to the umbilicus and the SILS Port device was bluntly introduced. Three cannulae were inserted in the SILS Port through the access channels. In the first 20 cases, a transabdominal suspension suture was used to transfix the ovaries. In all cases, ovariectomy was performed using a standard straight non-roticulated laparoscopic grasper and a vessel sealer/divider device. Mean (sd) duration of the ovarian resection was 25.1 (6.1) minutes (range 16 to 39 minutes). In five dogs (with transabdominal suspension suture), minor bleeding in the mesovarium or in the spleen was observed. Since the SILS Port allows simultaneous use of two instruments and a telescope through a single incision, the suspension suture is not mandatory. The lack of a transabdominal suspension suture increased collision between instruments and the telescope, but triangulation capabilities remained sufficient to achieve visualisation, sufficient manoeuvrability and safe vessel sealer/divider device application. The time to perform ovarian resection remained unaltered with or without suspension suture and regardless of the fat score of the ovarian ligament. Complications were less frequent without a suspension suture.
Animals, Dogs, Female, Laparoscopes, Laparoscopy, Ovariectomy, Time Factors, Treatment Outcome, Umbilicus
null
22,706,036
2012-10-09
2019-12-10
2042-7670
The Veterinary record
Protothecal pyogranulomatous meningoencephalitis in a dog without evidence of disseminated infection.
Márquez M, Ródenas S, Molin J, Rabanal R M, Fondevila D, Añor S, Pumarola M
eng
null
Case Reports, Journal Article
null
IM
22706036, vr.100661, 10.1136/vr.100661
null
Animals, Brain, Dog Diseases, Dogs, Fatal Outcome, Infections, Male, Meningoencephalitis, Prototheca
null
22,706,037
2012-10-09
2012-08-08
2042-7670
The Veterinary record
Pig-shed air polluted by α-haemolytic cocci and ammonia causes subclinical disease and production losses.
Murphy T, Cargill C, Rutley D, Stott P
eng
null
Journal Article, Research Support, Non-U.S. Gov't
Ammonia
IM
22706037, vr.100413, 10.1136/vr.100413
There is mounting evidence that bacteria originating from pigs degrade the environment of the pig shed and adversely affect the health of the animals and the pig-shed workers. α-haemolytic cocci (AHC) occur in pig-shed environments, but are regarded as commensals. Ammonia is also a component of the pig-shed environment, and is known to damage upper respiratory tract epithelia. The aim of this study was to determine whether polluted air in pig sheds adversely affected performance indicators in pigs. Modelling revealed a direct effect of AHC on voluntary feed intake and hence AHC are not commensal. No direct effect of ammonia on the pigs was detected, but the combination of AHC and ammonia stimulated the immune system in a progressive manner, and there were direct effects of immune stimulation on food intake and growth resulting in poorer feed-conversion efficiency, even though the effects remained subclinical. The authors conclude that exposure of the respiratory epithelia of pigs to viable AHC in the presence of ammonia redirects nutrients away from production and towards the immune system, explaining the impact of poor pig-shed hygiene on production parameters.
Aerococcus, Air Microbiology, Ammonia, Animal Husbandry, Animal Welfare, Animals, Female, Housing, Animal, Humans, Hygiene, Streptococcus, Swine
null
22,706,038
2012-09-18
2015-11-19
2042-7670
The Veterinary record
Serum gastrin concentrations in dogs with liver disorders.
Mazaki-Tovi M, Segev G, Yas-Natan E, Lavy E
eng
null
Journal Article
Biomarkers, Gastrins
IM
22706038, vr.100627, 10.1136/vr.100627
Dogs with liver disorders often display gastrointestinal signs that may be triggered by ulceration. The liver is important for inactivation of some forms of gastrin. Therefore, hypergastrinaemia has been implicated in the pathogenesis of gastrointestinal ulcerations related to liver dysfunction. The aim of this study was to determine serum gastrin concentrations in dogs with liver disease. Fasted blood samples were collected from 15 dogs with newly diagnosed liver disease and 18 healthy dogs. Gastrin concentrations were significantly lower in dogs with congenital portosystemic shunt compared with healthy dogs (P=0.003). No significant difference (P=0.6) in gastrin concentration was revealed between dogs with hepatocellular disease and healthy dogs. Serum gastrin concentrations were not significantly associated with the occurrence of vomiting, anorexia, diarrhoea, or melaena in dogs with liver disorders. These findings did not provide support for the role of hypergastrinaemia in the development of gastrointestinal signs associated with liver disease in dogs. Decreased serum concentrations of gastrin in a dog with liver disease may suggest the presence of portosystemic shunt. Further investigation is warranted to determine the importance of hyopogastrinaemia in congenital postosystemic shunts in dogs and to evaluate potential alterations in serum gastrin concentrations in specific hepatocellular diseases.
Animals, Biomarkers, Case-Control Studies, Dog Diseases, Dogs, Female, Gastrins, Gastrointestinal Diseases, Liver Diseases, Male, Ulcer
null
22,706,040
2012-09-19
2016-11-25
2042-7670
The Veterinary record
Prevalence and some clinical characteristics of equine cheek teeth diastemata in 471 horses examined in a UK first-opinion equine practice (2008 to 2009).
Walker H, Chinn E, Holmes S, Barwise-Munro L, Robertson V, Mould R, Bradley S, Shaw D J, Dixon P M
eng
null
Journal Article
null
IM
22706040, vr.100829, 10.1136/vr.100829
Cheek teeth (CT) diastemata are now recognised as a clinically significant equine disorder, but their prevalence in the general equine population is unknown. There is also limited information on the signalment of affected horses; the more commonly affected Triadan sites; and the shape and clinical characteristics of CT diastemata. During the 12-month study period (2008 to 2009), standardised records were obtained during routine dental examinations performed by five veterinarians in a first-opinion equine practice. Cheek teeth diastemata were identified in 49.9 per cent of all horses (n=471) of mean age 11 years (range one to 30 years), with 83.5 per cent of all diastemata affecting mandibular CT and 16.5 per cent affecting maxillary CT. The mean number of diastemata per case was 1.7 (range one to 20) and the mandibular 07 to 08 position was most commonly affected. Valve diastemata were more common (72.1 per cent prevalence) than open diastemata (27.9 per cent). Food trapping was present in 91.4 per cent of diastemata, with gingivitis and periodontal pockets adjacent to 34.2 per cent and 43.7 per cent, respectively. Halitosis was present in 45.5 per cent of affected horses. There was an age-related increase in both the prevalence of diastemata, and in the numbers of diastemata per affected horse, and horses over 15 years old had a significantly increased proportion of open diastemata.
Age Factors, Animals, Dentistry, Diastema, Female, Horse Diseases, Horses, Male, Prevalence, Tooth Diseases, United Kingdom
null
22,706,041
2012-12-28
2012-07-23
1873-5169
Peptides
Effects of cyclopeptide C*HSDGIC* from the cyclization of PACAP (1-5) on the proliferation and UVB-induced apoptosis of the retinal ganglion cell line RGC-5.
Ding Yong, Cheng Huanhuan, Yu Rongjie, Tang Cuicui, Liu Xiaofei, Chen Jiansu
eng
null
Journal Article, Research Support, Non-U.S. Gov't
Peptides, Cyclic, Pituitary Adenylate Cyclase-Activating Polypeptide, Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
IM
22706041, S0196-9781(12)00265-3, 10.1016/j.peptides.2012.06.003
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that confers potent neurotrophic and neuroprotective effects. Cyclopeptide C*HSDGIC* (CHC), which results from the cyclization of PACAP (1-5) with disulfide, has been demonstrated to represent a potent agonist for the PACAP-specific receptor PAC1 which mediates the majority of PACAP's effects. In this study, the expression of PAC1 in a rat retinal ganglion cell line (RGC-5) was confirmed using a western blot analysis, and it was determined that CHC promoted the proliferation of RGC-5 cells using the cell counting kit-8 (CCK8) assay and flow cytometry. Furthermore, the treatment of CHC attenuated the decrease of cell viability in cells exposed to UVB irradiation. Flow cytometry and a JC-1 assay revealed that the CHC treatment protected the RGC-5 cells against UVB-induced apoptosis. In addition, similar to PACAP, the anti-apoptotic effect of CHC was related to the down-regulation of caspase-3. In summary, these results demonstrate for the first time that PAC1 is present in RGC-5 cells and that CHC, a cyclopeptide from PACAP, promotes RGC-5 cell proliferation and attenuates UVB-induced apoptosis.
Animals, Apoptosis, Cell Line, Cell Proliferation, Peptides, Cyclic, Pituitary Adenylate Cyclase-Activating Polypeptide, Rats, Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I, Retinal Ganglion Cells, Ultraviolet Rays
null
22,706,039
2012-09-19
2019-12-10
2042-7670
The Veterinary record
Importance of infectious bovine reproductive diseases: an example from Ghana.
Adu-Addai B, Koney E B, Addo P, Kaneene J, Mackenzie C, Agnew D W
eng
null
Journal Article
Antibodies, Bacterial, Antibodies, Protozoan, Antibodies, Viral
IM
22706039, vr.100789, 10.1136/vr.100789
null
Abortion, Veterinary, Animals, Antibodies, Bacterial, Antibodies, Protozoan, Antibodies, Viral, Bovine Virus Diarrhea-Mucosal Disease, Cattle, Cattle Diseases, Causality, Diarrhea Viruses, Bovine Viral, Female, Ghana, Herpesviridae, Herpesviridae Infections, Herpesvirus 1, Bovine, Infections, Infectious Bovine Rhinotracheitis, Infertility, Female, Pregnancy, Pregnancy Complications, Infectious, Pregnancy Complications, Parasitic, Protozoan Infections, Animal, Uterine Diseases
null
22,706,044
2012-11-28
2024-01-09
1098-5336
Applied and environmental microbiology
Influence of the plant defense response to Escherichia coli O157:H7 cell surface structures on survival of that enteric pathogen on plant surfaces.
Seo Suengwook, Matthews Karl R
eng
null
Journal Article
Antigens, Surface
IM
22706044, AEM.01095-12, 10.1128/AEM.01095-12, PMC3406135, 17612061, 9572940, 8173808, 9573197, 16704355, 15199967, 8692856, 20936140, 15282131, 16204476, 8385664, 15829201, 16959575, 19777884, 19343953, 16164566, 15498873, 10377992, 16123135, 12933841, 16497589, 11319125, 15720086, 17876517, 21541320, 9611172, 15358511, 12857819, 3327686, 15895720, 18509467, 17419843, 7507102, 16353558, 17513585, 17849711, 9366597, 12244227, 15085136, 19681282, 15283665, 16332780, 9724702
Consumption of fresh and fresh-cut fruits and vegetables contaminated with Escherichia coli O157:H7 has resulted in hundreds of cases of illness and, in some instances, death. In this study, the influence of cell surface structures of E. coli O157:H7, such as flagella, curli fimbriae, lipopolysaccharides, or exopolysaccharides, on plant defense responses and on survival or colonization on the plant was investigated. The population of the E. coli O157:H7 ATCC 43895 wild-type strain was significantly lower on wild-type Arabidopsis plants than that of the 43895 flagellum-deficient mutant. The population of the E. coli O157:H7 43895 flagellum mutant was greater on both wild-type and npr1-1 mutant (nonexpressor of pathogenesis-related [PR] genes) plants and resulted in less PR gene induction, estimated based on a weak β-glucuronidase (GUS) signal, than did the 43895 wild-type strain. These results suggest that the flagella, among the other pathogen-associated molecular patterns (PAMPs), made a substantial contribution to the induction of plant defense response and contributed to the decreased numbers of the E. coli O157:H7 ATCC 43895 wild-type strain on the wild-type Arabidopsis plant. A curli-deficient E. coli O157:H7 86-24 strain survived better on wild-type Arabidopsis plants than the curli-producing wild-type 86-24 strain did. The curli-deficient E. coli O157:H7 86-24 strain exhibited a GUS signal at a level substantially lower than that of the curli-producing wild-type strain. Curli were recognized by plant defense systems, consequently affecting bacterial survival. The cell surface structures of E. coli O157:H7 have a significant impact on the induction of differential plant defense responses, thereby impacting persistence or survival of the pathogen on plants.
Antigens, Surface, Arabidopsis, Colony Count, Microbial, Escherichia coli O157, Microbial Viability, Organelles
null
22,706,046
2012-12-11
2021-10-21
1098-5336
Applied and environmental microbiology
Microsatellite markers for characterization of native and introduced populations of Plasmopara viticola, the causal agent of grapevine downy mildew.
Rouxel Mélanie, Papura Daciana, Nogueira Marilise, Machefer Virginie, Dezette Damien, Richard-Cervera Sylvie, Carrere Sébastien, Mestre Pere, Delmotte François
eng
null
Journal Article, Research Support, Non-U.S. Gov't
DNA, Fungal
IM
22706046, AEM.01255-12, 10.1128/AEM.01255-12, PMC3416634, 20007741, 17463017, 19317661, 21926208, 21676194, 1350188, 17659989, 21466660, 17586672
We reported 31 microsatellite markers that have been developed from microsatellite-enriched and direct shotgun pyrosequencing libraries of Plasmopara viticola, the causal agent of grapevine downy mildew. These markers were optimized for population genetics applications and used to characterize 96 P. viticola isolates from three European and three North American populations.
DNA, Fungal, Europe, Microsatellite Repeats, Molecular Sequence Data, Molecular Typing, Mycological Typing Techniques, North America, Oomycetes, Plant Diseases, Sequence Analysis, DNA, Vitis
null
22,706,045
2012-11-28
2021-10-21
1098-5336
Applied and environmental microbiology
Archaeal abundance across a pH gradient in an arable soil and its relationship to bacterial and fungal growth rates.
Bengtson Per, Sterngren Anna E, Rousk Johannes
eng
null
Journal Article, Research Support, Non-U.S. Gov't
RNA, Archaeal, RNA, Ribosomal, 16S, Soil
IM
22706045, AEM.01476-12, 10.1128/AEM.01476-12, PMC3406126, 21470255, 16915287, 12116647, 17391330, 15240332, 19453522, 19732147, 16177789, 18707610, 22611550, 11055931, 20445636, 19151179, 17334387, 15006809, 16909343, 20703315, 16407148, 3994368, 19236445, 16872405, 22158986, 21085198, 17334967, 270744, 19794413, 16000830, 21525411, 18978075, 22003023, 16505362, 19719676, 19583788, 19725866
Soil pH is one of the most influential factors for the composition of bacterial and fungal communities, but the influence of soil pH on the distribution and composition of soil archaeal communities has yet to be systematically addressed. The primary aim of this study was to determine how total archaeal abundance (quantitative PCR [qPCR]-based estimates of 16S rRNA gene copy numbers) is related to soil pH across a pH gradient (pH 4.0 to 8.3). Secondarily, we wanted to assess how archaeal abundance related to bacterial and fungal growth rates across the same pH gradient. We identified two distinct and opposite effects of pH on the archaeal abundance. In the lowest pH range (pH 4.0 to 4.7), the abundance of archaea did not seem to correspond to pH. Above this pH range, there was a sharp, almost 4-fold decrease in archaeal abundance, reaching a minimum at pH 5.1 to 5.2. The low abundance of archaeal 16S rRNA gene copy numbers at this pH range then sharply increased almost 150-fold with pH, resulting in an increase in the ratio between archaeal and bacterial copy numbers from a minimum of 0.002 to more than 0.07 at pH 8. The nonuniform archaeal response to pH could reflect variation in the archaeal community composition along the gradient, with some archaea adapted to acidic conditions and others to neutral to slightly alkaline conditions. This suggestion is reinforced by observations of contrasting outcomes of the (competitive) interactions between archaea, bacteria, and fungi toward the lower and higher ends of the examined pH gradient.
Archaea, Bacteria, Fungi, Genes, rRNA, Hydrogen-Ion Concentration, RNA, Archaeal, RNA, Ribosomal, 16S, Real-Time Polymerase Chain Reaction, Soil, Soil Microbiology
null
22,706,048
2012-12-11
2021-10-21
1098-5336
Applied and environmental microbiology
Comparative survey of rumen microbial communities and metabolites across one caprine and three bovine groups, using bar-coded pyrosequencing and ¹H nuclear magnetic resonance spectroscopy.
Lee Hyo Jung, Jung Ji Young, Oh Young Kyoon, Lee Sang-Suk, Madsen Eugene L, Jeon Che Ok
eng
null
Journal Article, Research Support, Non-U.S. Gov't
DNA, Bacterial, DNA, Ribosomal, RNA, Ribosomal, 16S
IM
22706048, AEM.00104-12, 10.1128/AEM.00104-12, PMC3416611, 15570040, 3452303, 17117998, 16820449, 15630514, 16820507, 13057, 19587773, 17916733, 11375193, 15539930, 16699105, 20668490, 16731699, 20729286, 7016031, 19411407, 21273488, 1608980, 3427163, 12147459, 19801464, 7618894, 21951902, 21906219, 16549033, 21044097, 21223325, 16756332, 18785930, 18378594, 15006742, 18264105, 16880384, 18424540, 21346791, 21546353, 19717632, 17299583, 18509054, 17317231, 19181843, 22443874, 16056220, 18797866, 7024344, 4968010, 16332807, 19004872, 21317261, 20370919, 19668203, 16845035, 11055964, 18043639
Pyrosequencing of 16S rRNA genes (targeting Bacteria and Archaea) and (1)H nuclear magnetic resonance were applied to investigate the rumen microbiota and metabolites of Hanwoo steers in the growth stage (HGS), Hanwoo steers in the late fattening stage (HFS), Holstein-Friesian dairy cattle (HDC), and Korean native goats (KNG) in the late fattening stage. This was a two-part investigation. We began by comparing metabolites and microbiota of Hanwoo steers at two stages of husbandry. Statistical comparisons of metabolites and microbial communities showed no significant differences between HFS and HGS (differing by a dietary shift at 24 months and age [67 months versus 12 months]). We then augmented the study by extending the investigation to HDC and KNG. Overall, pyrosequencing of 16S rRNA genes showed that the rumens had highly diverse microbial communities containing many previously undescribed microorganisms. Bioinformatic analysis revealed that the bacterial sequences were predominantly affiliated with four phyla-Bacteroidetes, Firmicutes, Fibrobacteres, and Proteobacteria-in all ruminants. However, interestingly, the bacterial reads belonging to Fibrobacteres were present at a very low abundance (<0.1%) in KNG. Archaeal community analysis showed that almost all of these reads fell into a clade related to, but distinct from, known cultivated methanogens. Statistical analyses showed that the microbial communities and metabolites of KNG were clearly distinct from those of other ruminants. In addition, bacterial communities and metabolite profiles of HGS and HDC, fed similar diets, were distinctive. Our data indicate that bovine host breeds override diet as the key factor that determines bacterial community and metabolite profiles in the rumen.
Animals, Archaea, Bacteria, Biota, Cattle, DNA Barcoding, Taxonomic, DNA, Bacterial, DNA, Ribosomal, Goats, Korea, Magnetic Resonance Spectroscopy, Metabolome, Metagenome, RNA, Ribosomal, 16S, Rumen, Sequence Analysis, DNA
null
22,706,050
2012-11-28
2021-10-21
1098-5336
Applied and environmental microbiology
Expression of the laccase gene from a white rot fungus in Pichia pastoris can enhance the resistance of this yeast to H2O2-mediated oxidative stress by stimulating the glutathione-based antioxidative system.
Yang Yang, Fan Fangfang, Zhuo Rui, Ma Fuying, Gong Yangmin, Wan Xia, Jiang Mulan, Zhang Xiaoyu
eng
null
Journal Article, Research Support, Non-U.S. Gov't
Hydrogen Peroxide, Laccase, Glutathione
IM
22706050, AEM.00218-12, 10.1128/AEM.00218-12, PMC3406150, 10499781, 16502330, 21533903, 11319086, 11164314, 6134525, 19502720, 3178190, 20154118, 7887613, 18943218, 12962915, 8951820, 9797454, 9130715, 942051, 16716556, 12949171, 21287231, 16568314, 1535523, 10543802, 14602606, 18451056, 14757236, 17205039, 6216890, 16535685, 19341391, 21754936, 10919791, 9177046, 16472305, 10036768, 4831804, 4823943, 11693920, 7915005, 12480904, 21809327, 19252120, 16358757, 655387, 21125266, 10347154
Laccase is a copper-containing polyphenol oxidase that has great potential in industrial and biotechnological applications. Previous research has suggested that fungal laccase may be involved in the defense against oxidative stress, but there is little direct evidence supporting this hypothesis, and the mechanism by which laccase protects cells from oxidative stress also remains unclear. Here, we report that the expression of the laccase gene from white rot fungus in Pichia pastoris can significantly enhance the resistance of yeast to H(2)O(2)-mediated oxidative stress. The expression of laccase in yeast was found to confer a strong ability to scavenge intracellular H(2)O(2) and to protect cells from lipid oxidative damage. The mechanism by which laccase gene expression increases resistance to oxidative stress was then investigated further. We found that laccase gene expression in Pichia pastoris could increase the level of glutathione-based antioxidative activity, including the intracellular glutathione levels and the enzymatic activity of glutathione peroxidase, glutathione reductase, and γ-glutamylcysteine synthetase. The transcription of the laccase gene in Pichia pastoris was found to be enhanced by the oxidative stress caused by exogenous H(2)O(2). The stimulation of laccase gene expression in response to exogenous H(2)O(2) stress further contributed to the transcriptional induction of the genes involved in the glutathione-dependent antioxidative system, including PpYAP1, PpGPX1, PpPMP20, PpGLR1, and PpGSH1. Taken together, these results suggest that the expression of the laccase gene in Pichia pastoris can enhance the resistance of yeast to H(2)O(2)-mediated oxidative stress by stimulating the glutathione-based antioxidative system to protect the cell from oxidative damage.
Gene Expression Regulation, Fungal, Glutathione, Hydrogen Peroxide, Laccase, Lipid Metabolism, Lipid Peroxidation, Oxidative Stress, Pichia, Transcription, Genetic
null
22,706,047
2012-11-28
2021-10-21
1098-5336
Applied and environmental microbiology
Quorum sensing in the context of food microbiology.
Skandamis Panagiotis N, Nychas George-John E
eng
null
Journal Article, Research Support, Non-U.S. Gov't, Review
null
IM
22706047, AEM.00468-12, 10.1128/AEM.00468-12, PMC3406170, 9535661, 12878381, 12624209, 8561477, 11131069, 18680957, 11524130, 12142477, 15270501, 15240313, 10427034, 18834641, 16943048, 9286976, 16459080, 18045400, 1502599, 15214641, 8750675, 11282475, 12448722, 18034729, 12200329, 16156705, 19508295, 9351226, 22356617, 14597754, 11489131, 11160117, 18093756, 17032221, 21936639, 22062098, 18387117, 12694909, 9343359, 17258895, 19028314, 16352847, 14696323, 21182299, 8508772, 18787455, 17304251, 18048907, 21569946, 15812045, 18703250, 9562874, 17133818, 2764574, 15660994, 15716452, 14732326, 10510239, 15968046, 11953406, 12000619, 15184178, 8157581, 17351095, 11297357, 21477479, 16411920, 16740963, 9973347, 12562806, 21794942, 11240047, 10500159, 8188582, 21192848, 15933035, 19827025, 18236673, 14507367, 5473898, 15251193, 11104821, 10844645, 16174357, 18387116, 15151251, 19350992, 15292148, 20003745, 8278364, 3293613, 14597753, 21511146, 19465248, 11544237, 15374643, 20097823, 16501584, 17897197, 19627477, 11450110, 12222639, 12847292, 11966822, 15466044, 8508773, 19683678, 8861211, 19040778, 12160634, 14678172, 15870357, 15175293, 17220220, 17047948, 16706905, 16797762, 11934035, 17338438, 19767476
Food spoilage may be defined as a process that renders a product undesirable or unacceptable for consumption and is the outcome of the biochemical activity of a microbial community that eventually dominates according to the prevailing ecological determinants. Although limited information are reported, this activity has been attributed to quorum sensing (QS). Consequently, the potential role of cell-to-cell communication in food spoilage and food safety should be more extensively elucidated. Such information would be helpful in designing approaches for manipulating these communication systems, thereby reducing or preventing, for instance, spoilage reactions or even controlling the expression of virulence factors. Due to the many reports in the literature on the fundamental features of QS, e.g., chemistry and definitions of QS compounds, in this minireview, we only allude to the types and chemistry of QS signaling molecules per se and to the (bioassay-based) methods of their detection and quantification, avoiding extensive documentation. Conversely, we attempt to provide insights into (i) the role of QS in food spoilage, (ii) the factors that may quench the activity of QS in foods and review the potential QS inhibitors that might "mislead" the bacterial coordination of spoilage activities and thus may be used as biopreservatives, and (iii) the future experimental approaches that need to be undertaken in order to explore the "gray" or "black" areas of QS, increase our understanding of how QS affects microbial behavior in foods, and assist in finding answers as to how we can exploit QS for the benefit of food preservation and food safety.
Bacteria, Bacterial Physiological Phenomena, Food Microbiology, Quorum Sensing
null
22,706,049
2012-11-28
2021-10-21
1098-5336
Applied and environmental microbiology
Fluid flow induces biofilm formation in Staphylococcus epidermidis polysaccharide intracellular adhesin-positive clinical isolates.
Weaver Westbrook M, Milisavljevic Vladana, Miller Jeff F, Di Carlo Dino
eng
null
Journal Article, Research Support, Non-U.S. Gov't
Adhesins, Bacterial, Polysaccharides, Bacterial
IM
22706049, AEM.01139-12, 10.1128/AEM.01139-12, PMC3406141, 10225932, 18926307, 20521936, 20356880, 21402020, 2735435, 10225938, 21249255, 14996815, 11177147, 18720093, 15752207, 8809760, 709740, 19267282, 22290986, 11827198, 11274123, 8550413, 12499208, 12142410, 17172522, 11909845, 18834725
Staphylococcus epidermidis is a common cause of catheter-related bloodstream infections, resulting in significant morbidity and mortality and increased hospital costs. The ability to form biofilms plays a crucial role in pathogenesis; however, not all clinical isolates form biofilms under normal in vitro conditions. Strains containing the ica operon can display significant phenotypic variation with respect to polysaccharide intracellular adhesin (PIA)-based biofilm formation, including the induction of biofilms upon environmental stress. Using a parallel microfluidic approach to investigate flow as an environmental signal for S. epidermidis biofilm formation, we demonstrate that fluid shear alone induces PIA-positive biofilms of certain clinical isolates and influences biofilm structure. These findings suggest an important role of the catheter microenvironment, particularly fluid flow, in the establishment of S. epidermidis infections by PIA-dependent biofilm formation.
Adhesins, Bacterial, Biofilms, Hydrodynamics, Polysaccharides, Bacterial, Staphylococcal Infections, Staphylococcus epidermidis
null
22,706,052
2012-11-28
2021-10-21
1098-5336
Applied and environmental microbiology
Electrical conductivity in a mixed-species biofilm.
Malvankar Nikhil S, Lau Joanne, Nevin Kelly P, Franks Ashley E, Tuominen Mark T, Lovley Derek R
eng
null
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.
Sewage
IM
22706052, AEM.01803-12, 10.1128/AEM.01803-12, PMC3406156, 15726203, 16778836, 21441020, 18769460, 23761228, 21862629, 21822253, 16936064, 22253215, 19895647, 17392190, 20000550, 21897384, 17570714, 18564184, 21127257, 22614997, 17995953, 18294928, 18800535, 18330564, 18646217
Geobacter sulfurreducens can form electrically conductive biofilms, but the potential for conductivity through mixed-species biofilms has not been examined. A current-producing biofilm grown from a wastewater sludge inoculum was highly conductive with low charge transfer resistance even though microorganisms other than Geobacteraceae accounted for nearly half the microbial community.
Biofilms, Electric Conductivity, Microbial Consortia, Sewage
null
22,706,051
2012-11-28
2021-10-21
1098-5336
Applied and environmental microbiology
Genotypic and phenotypic traits that distinguish neonatal meningitis-associated Escherichia coli from fecal E. coli isolates of healthy human hosts.
Logue Catherine M, Doetkott Curt, Mangiamele Paul, Wannemuehler Yvonne M, Johnson Timothy J, Tivendale Kelly A, Li Ganwu, Sherwood Julie S, Nolan Lisa K
eng
null
Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
Anti-Bacterial Agents, Virulence Factors
IM
22706051, AEM.07869-11, 10.1128/AEM.07869-11, PMC3406136, 17277222, 19946140, 17374506, 6995336, 2580792, 16385064, 20160015, 9843981, 11010916, 20515929, 16940062, 16885466, 20610687, 21988401, 15942016, 11920295, 17293413, 19553581, 15040260, 18820066, 10678971, 19966814, 1943778, 20439758, 19307211
Neonatal meningitis Escherichia coli (NMEC) is one of the top causes of neonatal meningitis worldwide. Here, 85 NMEC and 204 fecal E. coli isolates from healthy humans (HFEC) were compared for possession of traits related to virulence, antimicrobial resistance, and plasmid content. This comparison was done to identify traits that typify NMEC and distinguish it from commensal strains to refine the definition of the NMEC subpathotype, identify traits that might contribute to NMEC pathogenesis, and facilitate choices of NMEC strains for future study. A large number of E. coli strains from both groups were untypeable, with the most common serogroups occurring among NMEC being O18, followed by O83, O7, O12, and O1. NMEC strains were more likely than HFEC strains to be assigned to the B2 phylogenetic group. Few NMEC or HFEC strains were resistant to antimicrobials. Genes that best discriminated between NMEC and HFEC strains and that were present in more than 50% of NMEC isolates were mainly from extraintestinal pathogenic E. coli genomic and plasmid pathogenicity islands. Several of these defining traits had not previously been associated with NMEC pathogenesis, are of unknown function, and are plasmid located. Several genes that had been previously associated with NMEC virulence did not dominate among the NMEC isolates. These data suggest that there is much about NMEC virulence that is unknown and that there are pitfalls to studying single NMEC isolates to represent the entire subpathotype.
Anti-Bacterial Agents, Drug Resistance, Bacterial, Escherichia coli, Feces, Humans, Meningitis, Escherichia coli, Plasmids, Serotyping, Virulence Factors
null
22,706,053
2012-11-28
2021-10-21
1098-5336
Applied and environmental microbiology
Fratricide is essential for efficient gene transfer between pneumococci in biofilms.
Wei Hua, Håvarstein Leiv Sigve
eng
null
Journal Article, Research Support, Non-U.S. Gov't
Bacterial Proteins, Amidohydrolases, CbpD protein, Streptococcus pneumoniae, LytC protein, Streptococcus, N-Acetylmuramoyl-L-alanine Amidase
IM
22706053, AEM.01343-12, 10.1128/AEM.01343-12, PMC3406168, 8065267, 19389766, 22407687, 12032343, 16430701, 10447890, 10438773, 20676145, 18628950, 8878046, 14763981, 20384696, 18656532, 6619096, 17459765, 22123253, 12765834, 1973677, 7479953, 9466264, 14413322, 11021916, 1987129, 17555432, 8878047, 17277796, 15039376, 14763980, 20514044, 16936041, 15928084, 11679344, 12765833, 18485065, 7256084, 12598132, 15968042, 21933920, 17725562
Streptococcus pneumoniae and a number of commensal streptococcal species are competent for natural genetic transformation. The natural habitat of these bacteria is multispecies biofilms in the human oral cavity and nasopharynx. Studies investigating lateral transfer of virulence and antibiotic resistance determinants among streptococci have shown that interspecies as well as intraspecies gene exchange takes place in these environments. We have previously shown that the action of a competence-specific murein hydrolase termed CbpD strongly increases the rate of gene transfer between pneumococci grown in liquid cultures. CbpD is the key component of a bacteriolytic mechanism termed the fratricide mechanism. It is secreted by competent pneumococci and mediates the release of donor DNA from sensitive streptococci present in the same environment. However, in nature, gene exchange between streptococci takes place in biofilms and not in liquid cultures. In the present study, we therefore investigated whether CbpD affects the rate of gene transfer in laboratory-grown biofilms. Our results show that the fratricide mechanism has a strong positive impact on intrabiofilm gene exchange, indicating that it is important for active acquisition of homologous donor DNA under natural conditions. Furthermore, we found that competent biofilm cells of S. pneumoniae acquire a Nov(r) marker much more efficiently from neighboring cells than from the growth medium. Efficient lysis of target cells requires that CbpD act in conjunction with the murein hydrolase LytC. In contrast, the major autolysin LytA does not seem to be important for fratricide-mediated gene exchange in a biofilm environment.
Amidohydrolases, Bacterial Proteins, Bacteriolysis, Biofilms, DNA Transformation Competence, Gene Transfer, Horizontal, N-Acetylmuramoyl-L-alanine Amidase, Streptococcus pneumoniae
null
22,706,055
2012-11-28
2021-10-21
1098-5336
Applied and environmental microbiology
Impact of processing method on recovery of bacteria from wipes used in biological surface sampling.
Downey Autumn S, Da Silva Sandra M, Olson Nathan D, Filliben James J, Morrow Jayne B
eng
null
Evaluation Study, Journal Article, Research Support, U.S. Gov't, Non-P.H.S.
null
IM
22706055, AEM.00873-12, 10.1128/AEM.00873-12, PMC3406133, 12381029, 730629, 17973307, 14706265, 18997021, 19435214, 17122390, 6619285, 18779342, 394682, 18034727, 7130703, 17897212, 21610120, 19644689, 21296945, 21965403, 4594405, 21458684, 13403633, 21818321, 21821742, 18637873, 20799932, 20453913, 17897214, 15574898, 19429546, 20017946, 22121364, 20654658, 16336651, 19903773, 6520602, 5807156, 15508632, 21764960, 16914034, 20184669, 15294810, 16725056, 21864762, 20023101, 2023362, 14723697, 17416685, 16346141, 11165341, 12775670, 15207053, 18492049, 17140698, 16751562, 20193714
Environmental sampling for microbiological contaminants is a key component of hygiene monitoring and risk characterization practices utilized across diverse fields of application. However, confidence in surface sampling results, both in the field and in controlled laboratory studies, has been undermined by large variation in sampling performance results. Sources of variation include controlled parameters, such as sampling materials and processing methods, which often differ among studies, as well as random and systematic errors; however, the relative contributions of these factors remain unclear. The objective of this study was to determine the relative impacts of sample processing methods, including extraction solution and physical dissociation method (vortexing and sonication), on recovery of Gram-positive (Bacillus cereus) and Gram-negative (Burkholderia thailandensis and Escherichia coli) bacteria from directly inoculated wipes. This work showed that target organism had the largest impact on extraction efficiency and recovery precision, as measured by traditional colony counts. The physical dissociation method (PDM) had negligible impact, while the effect of the extraction solution was organism dependent. Overall, however, extraction of organisms from wipes using phosphate-buffered saline with 0.04% Tween 80 (PBST) resulted in the highest mean recovery across all three organisms. The results from this study contribute to a better understanding of the factors that influence sampling performance, which is critical to the development of efficient and reliable sampling methodologies relevant to public health and biodefense.
Bacillus cereus, Bacteriological Techniques, Burkholderia, Environmental Microbiology, Escherichia coli, Sensitivity and Specificity, Specimen Handling
null
22,706,054
2012-11-28
2021-10-21
1098-5336
Applied and environmental microbiology
Surface display of N-terminally anchored invasin by Lactobacillus plantarum activates NF-κB in monocytes.
Fredriksen Lasse, Kleiveland Charlotte R, Hult Lene T Olsen, Lea Tor, Nygaard Cathrine S, Eijsink Vincent G H, Mathiesen Geir
eng
null
Journal Article, Research Support, Non-U.S. Gov't
Adhesins, Bacterial, NF-kappa B, invasin, Yersinia
IM
22706054, AEM.01227-12, 10.1128/AEM.01227-12, PMC3406107, 18024129, 18632920, 17081660, 19246373, 21085599, 10768935, 16929299, 9488419, 16051192, 2727147, 15823960, 21181148, 9234806, 17935691, 15617524, 16790806, 18430080, 16581299, 21995317, 10928981, 19447955, 17476345, 15141160, 14641180, 11438703, 19149590, 19920124, 11179325, 18303997, 8809553, 19744343, 14659551, 21995674, 9632584, 16170763, 21959131, 12566566, 16285893, 19029990, 10514372, 17446874, 2311122, 18324887, 15071180, 11801687, 16000734, 20851975, 18539799, 18512940, 19681907, 18345021, 11418555, 21784918, 16796731, 10064587, 19923575, 21092245, 17076597, 22101918, 18298538, 15096553, 16301635, 22129390, 19059780
The probiotic lactic acid bacterium Lactobacillus plantarum is a potential delivery vehicle for mucosal vaccines because of its generally regarded as safe (GRAS) status and ability to persist at the mucosal surfaces of the human intestine. However, the inherent immunogenicity of vaccine antigens is in many cases insufficient to elicit an efficient immune response, implying that additional adjuvants are needed to enhance the antigen immunogenicity. The goal of the present study was to increase the proinflammatory properties of L. plantarum by expressing a long (D1 to D5 [D1-D5]) and a short (D4-D5) version of the extracellular domain of invasin from the human pathogen Yersinia pseudotuberculosis. To display these proteins on the bacterial surface, four different N-terminal anchoring motifs from L. plantarum were used, comprising two different lipoprotein anchors, a transmembrane signal peptide anchor, and a LysM-type anchor. All these anchors mediated surface display of invasin, and several of the engineered strains were potent activators of NF-κB when interacting with monocytes in cell culture. The most distinct NF-κB responses were obtained with constructs in which the complete invasin extracellular domain was fused to a lipoanchor. The proinflammatory L. plantarum strains constructed here represent promising mucosal delivery vehicles for vaccine antigens.
Adhesins, Bacterial, Cell Line, Cell Surface Display Techniques, Humans, Lactobacillus plantarum, Monocytes, NF-kappa B, Yersinia pseudotuberculosis
null
22,706,056
2012-12-11
2021-10-21
1098-5336
Applied and environmental microbiology
Dual-serotype biofilm formation by shiga toxin-producing Escherichia coli O157:H7 and O26:H11 strains.
Wang Rong, Kalchayanand Norasak, Bono James L, Schmidt John W, Bosilevac Joseph M
eng
null
Journal Article, Research Support, Non-U.S. Gov't
null
IM
22706056, AEM.01137-12, 10.1128/AEM.01137-12, PMC3416587, 17331254, 17715820, 17292501, 9381722, 16170761, 9041412, 20453142, 10966439, 20367070, 19446903, 12134240, 22856565
Escherichia coli O26:H11 strains were able to outgrow O157:H7 companion strains in planktonic and biofilm phases and also to effectively compete with precolonized O157:H7 cells to establish themselves in mixed biofilms. E. coli O157:H7 strains were unable to displace preformed O26:H11 biofilms. Therefore, E. coli O26:H11 remains a potential risk in food safety.
Biofilms, Food Microbiology, Serotyping, Shiga-Toxigenic Escherichia coli
null
22,706,057
2012-12-11
2021-10-21
1098-5336
Applied and environmental microbiology
The TetR-type transcriptional repressor RolR from Corynebacterium glutamicum regulates resorcinol catabolism by binding to a unique operator, rolO.
Li Tang, Zhao Kexin, Huang Yan, Li Defeng, Jiang Cheng-Ying, Zhou Nan, Fan Zheng, Liu Shuang-Jiang
eng
null
Journal Article, Research Support, Non-U.S. Gov't
DNA, Bacterial, Hydroquinones, Repressor Proteins, Resorcinols, hydroxyhydroquinone, resorcinol
IM
22706057, AEM.01304-12, 10.1128/AEM.01304-12, PMC3416628, 20081038, 7584402, 942589, 11160798, 14651620, 21559286, 11846609, 12384340, 12232668, 10700280, 11251828, 9150211, 17158677, 8626295, 1429435, 942051, 11418577, 10941016, 12460754, 15944459, 9660841, 7217008, 8631713, 16610745, 17928374, 17555841, 18485072, 11717268, 11867549, 10972815, 16963551, 7826010, 15353566
The rol (designated for resorcinol) gene cluster rolRHMD is involved in resorcinol catabolism in Corynebacterium glutamicum, and RolR is the TetR-type regulator. In this study, we investigated how RolR regulated the transcription of the rol genes in C. glutamicum. The transcription start sites and promoters of rolR and rolHMD were identified. Quantitative reverse transcription-PCR and promoter activity analysis indicated that RolR negatively regulated the transcription of rolHMD and of its own gene. Further, a 29-bp operator rolO was located at the intergenic region of rolR and rolHMD and was identified as the sole binding site for RolR. It contained two overlapping inverted repeats and they were essential for RolR-binding. The binding of RolR to rolO was affected by resorcinol and hydroxyquinol, which are the starting compounds of resorcinol catabolic pathway. These two compounds were able to dissociate RolR-rolO complex, thus releasing RolR from the complex and derepressing the transcription of rol genes in C. glutamicum. It is proposed that the binding of RolR to its operator rolO blocks the transcription of rolHMD and of its own gene, thus negatively regulated resorcinol degradation in C. glutamicum.
Biotransformation, Corynebacterium glutamicum, DNA, Bacterial, Gene Expression Profiling, Gene Expression Regulation, Bacterial, Hydroquinones, Operator Regions, Genetic, Operon, Protein Binding, Real-Time Polymerase Chain Reaction, Repressor Proteins, Resorcinols, Transcription, Genetic
null
22,706,059
2012-12-11
2021-10-21
1098-5336
Applied and environmental microbiology
Chromosomal complementation using Tn7 transposon vectors in Enterobacteriaceae.
Crépin Sébastien, Harel Josée, Dozois Charles M
eng
null
Journal Article, Research Support, Non-U.S. Gov't
DNA Transposable Elements, DNA, Bacterial, Transposases
IM
22706059, AEM.00986-12, 10.1128/AEM.00986-12, PMC3416591, 7009570, 17406228, 2182540, 17709421, 22665376, 2542960, 21700403, 10536150, 18458066, 18248418, 9092630, 16646962, 20171928, 20920882, 1100846, 14672541, 10858231, 18599831, 12065485, 11715047, 9209066, 599885, 17406229, 3316027, 18043230, 6338386, 21306443, 6343344, 19038054, 10829079, 2055470, 2836362, 12506201, 17406227, 20019794, 15908923, 11987295, 19349746, 15972503, 22318320, 3055197, 1398960, 19332817, 12471157
Genetic complementation in many bacteria is commonly achieved by reintroducing functional copies of the mutated or deleted genes on a recombinant plasmid. Chromosomal integration systems using the Tn7 transposon have the advantage of providing a stable single-copy integration that does not require selective pressure. Previous Tn7 systems have been developed, although none have been shown to work effectively in a variety of enterobacteria. We have developed several mini-Tn7 and transposase vectors to provide a more versatile system. Transposition of Tn7 at the chromosomal attTn7 site was achieved by a classical conjugation approach, wherein the donor strain harbored the mini-Tn7 vector and the recipient strain possessed the transposase vector. This approach was efficient for five different pathogenic enterobacterial species. Thus, this system provides a useful tool for single-copy complementation at an episomal site for research in bacterial genetics and microbial pathogenesis. Furthermore, these vectors could also be used for the introduction of foreign genes for use in biotechnology applications, vaccine development, or gene expression and gene fusion constructs.
Conjugation, Genetic, DNA Transposable Elements, DNA, Bacterial, Enterobacteriaceae, Genetic Complementation Test, Genetic Vectors, Genetics, Microbial, Molecular Sequence Data, Sequence Analysis, DNA, Transposases
null
22,706,058
2012-12-11
2021-10-21
1098-5336
Applied and environmental microbiology
Transport of Cryptosporidium parvum oocysts in soil columns following applications of raw and separated liquid slurries.
Petersen Heidi H, Enemark Heidi L, Olsen Annette, Amin M G Mostofa, Dalsgaard Anders
eng
null
Journal Article, Research Support, Non-U.S. Gov't
Sewage, Soil, Water
IM
22706058, AEM.07829-11, 10.1128/AEM.07829-11, PMC3416631, 9327547, 6178277, 12772956, 3294122, 7818640, 16159658, 2339894, 9554076, 21948848, 19875795, 20097810, 16159697, 10877794, 9920307, 18178902, 8702272, 15691968, 7870140, 16797848, 17076923, 12044087, 19329684, 1482174, 16204565, 18304807, 8595856
The potential for the transport of viable Cryptosporidium parvum oocysts through soil to land drains and groundwater was studied using simulated rainfall and intact soil columns which were applied raw slurry or separated liquid slurry. Following irrigation and weekly samplings over a 4-week period, C. parvum oocysts were detected from all soil columns regardless of slurry type and application method, although recovery rates were low (<1%). Soil columns with injected liquid slurry leached 73 and 90% more oocysts compared to columns with injected and surface-applied raw slurries, respectively. Among leachate samples containing oocysts, 44/72 samples yielded viable oocysts as determined by a dye permeability assay (DAPI [4',6'-diamidino-2-phenylindole]/propidium iodide) with the majority (41%) of viable oocysts found in leachate from soil columns with added liquid slurry. The number of viable oocysts was positively correlated (r = 0.63) with the total number of oocysts found. Destructively sampling of the soil columns showed that type of slurry and irrigation played a role in the vertical distribution of oocysts, with more oocysts recovered from soil columns added liquid slurry irrespective of the irrigation status. Further studies are needed to determine the effectiveness of different slurry separation technologies to remove oocysts and other pathogens, as well as whether the application of separated liquid slurry to agricultural land may represent higher risks for groundwater contamination compared to application of raw slurry.
Cell Survival, Cryptosporidium parvum, Oocysts, Sewage, Soil, Water, Water Purification
null
22,706,060
2012-12-11
2021-10-21
1098-5336
Applied and environmental microbiology
Determination of whether quorum quenching is a common activity in marine bacteria by analysis of cultivable bacteria and metagenomic sequences.
Romero Manuel, Martin-Cuadrado Ana-Belen, Otero Ana
eng
null
Journal Article, Research Support, Non-U.S. Gov't
Bacterial Proteins, DNA, Bacterial, Enzymes
IM
22706060, AEM.01266-12, 10.1128/AEM.01266-12, PMC3416589, 17355176, 17360274, 16439655, 12147515, 15870355, 15845853, 12228292, 19542347, 19072824, 17107561, 21155853, 15001713, 23761357, 11097877, 18211268, 19661506, 18194337, 15746331, 17105187, 22003839
The abundance of quorum quenching (QQ) activity was evaluated in cultivable bacteria obtained from oceanic and estuarine seawater and compared with the frequency of QQ enzyme sequences in the available marine metagenomic collections. The possible role of the high QQ activity found among marine bacteria is discussed.
Bacteria, Bacterial Physiological Phenomena, Bacterial Proteins, DNA, Bacterial, Enzymes, Metagenome, Molecular Sequence Data, Quorum Sensing, Seawater, Sequence Analysis, DNA, Signal Transduction
null
22,706,063
2012-12-11
2021-10-21
1098-5336
Applied and environmental microbiology
Quantification of diatom gene expression in the sea by selecting uniformly transcribed mRNA as the basis for normalization.
Kang Lee-Kuo, Tsui Feng-Hsiu, Chang Jeng
eng
null
Journal Article, Research Support, Non-U.S. Gov't
RNA, Messenger
IM
22706063, AEM.00935-12, 10.1128/AEM.00935-12, PMC3416636, 16840529, 10373629, 15705200, 27034216, 17521426, 10527427, 21075880, 9660741, 15815687, 18474036, 19120456, 18458344, 15248161, 21219943, 19200351, 16332870, 16054107, 17694413, 17658702, 17553708, 15492217, 12200227, 7984417, 15331581, 16166256
To quantify gene expressions by quantitative reverse transcription-PCR (Q-RT-PCR) in natural diatom assemblages, it is necessary to seek a biomass reference specific to the target species. Two housekeeping genes, TBP (encoding the TATA box-binding protein) and EFL (encoding the translation elongation factor-like protein), were evaluated as candidates for reference genes in Q-RT-PCR assays. Transcript levels of TBP and EFL were relatively stable under various test conditions including growth stages, light-dark cycle phases, and nutrient stresses in Skeletonema costatum and Chaetoceros affinis, and TBP expression was more stable than that of EFL. Next, the sequence diversity of diatom assemblages was evaluated by obtaining 32 EFL and 29 TBP homologous gene fragments from the East China Sea (ECS). Based on sequence alignments, EFL and TBP primer sets were designed for Chaetoceros and Skeletonema groups in the ECS. An evaluation of primer specificity and PCR efficiency indicated that the EFL primer sets performed better. To demonstrate the applicability of EFL primer sets in the ECS, they were employed to measure mRNA levels of the FcpB (fucoxanthin-chlorophyll protein) gene in diatoms. The results correctly revealed prominent diel variations in FcpB expression and confirmed EFL as a good reference gene.
China, Diatoms, Gene Expression, Molecular Sequence Data, RNA, Messenger, Real-Time Polymerase Chain Reaction, Reference Standards, Seawater, Sequence Analysis, DNA
null
22,706,061
2012-12-11
2024-03-18
1098-5336
Applied and environmental microbiology
Relationship between enterococcal levels and sediment biofilms at recreational beaches in South Florida.
Piggot Alan M, Klaus James S, Johnson Sara, Phillips Matthew C, Solo-Gabriele Helena M
eng
P50 ES012736 (NIEHS NIH HHS, United States); P50 ES12736 (NIEHS NIH HHS, United States)
Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.
DNA, Bacterial, Polysaccharides, Bacterial
IM
22706061, AEM.00603-12, 10.1128/AEM.00603-12, PMC3416616, 788634, 12513993, 16108802, 16463160, 20220231, 17610908, 19659700, 17472641, 10427056, 12571013, 19151188, 12656230, 18033823, 7646026, 10618229, 19302327, 20629750, 22296573, 1637157, 17695890, 19541858, 15078507, 10098779, 21945015, 12957945, 19464704, 20818058, 16478456, 15644913, 16793111, 9797307, 21447014, 10971769, 16382928, 16391098, 10948147, 7934344, 20390555, 15933000, 8979355, 15240275, 18453412, 11104821, 11872464, 10097157, 7224629, 22157306, 7162524, 10401868, 19966020, 16393653, 20231463
Enterococci, recommended at the U.S. federal level for monitoring water quality at marine recreational beaches, have been found to reside and grow within beach sands. However, the environmental and ecological factors affecting enterococcal persistence remain poorly understood, making it difficult to determine levels of fecal pollution and assess human health risks. Here we document the presence of enterococci associated with beach sediment biofilms at eight south Florida recreational beaches. Enterococcal levels were highest in supratidal sands, where they displayed a nonlinear, unimodal relationship with extracellular polymeric secretions (EPS), the primary component of biofilms. Enterococcal levels peaked at intermediate levels of EPS, suggesting that biofilms may promote the survival of enterococci but also inhibit enterococci as the biofilm develops within beach sands. Analysis of bacterial community profiles determined by terminal restriction fragment length polymorphisms showed the bacterial communities of supratidal sediments to be significantly different from intertidal and subtidal communities; however, no differences were observed in bacterial community compositions associated with different EPS concentrations. Our results suggest that supratidal sands are a microbiologically unique environment favorable for the incorporation and persistence of enterococci within beach sediment biofilms.
Bathing Beaches, Biofilms, Biota, DNA, Bacterial, Enterococcus, Florida, Geologic Sediments, Humans, Molecular Sequence Data, Molecular Typing, Polymorphism, Restriction Fragment Length, Polysaccharides, Bacterial, Sequence Analysis, DNA
null
22,706,064
2012-12-11
2021-10-21
1098-5336
Applied and environmental microbiology
Identification and characterization of Cronobacter iron acquisition systems.
Grim C J, Kothary M H, Gopinath G, Jarvis K G, Beaubrun J Jean-Gilles, McClelland M, Tall B D, Franco A A
eng
null
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.
Membrane Transport Proteins, Siderophores, Iron
IM
22706064, AEM.01457-12, 10.1128/AEM.01457-12, PMC3416605, 15998312, 16193283, 11222606, 12068807, 21037008, 16039742, 2279379, 3308853, 1444386, 16214803, 12057967, 2139473, 11553558, 3032906, 9575233, 14638784, 15329720, 2982793, 9039558, 10515908, 17804665, 19130265, 18523192, 1500158, 1592838, 20221447, 9157252, 21421789, 14723994, 3447015, 16484199, 10103258, 21097627, 22661070, 19748571, 1838574, 14756576, 17600077, 19467725, 19229321, 15563736, 17627767, 8384682, 22182729, 21546353, 15059207, 6315685, 2794464, 18687498, 9393841, 16076215, 18261238, 8576065, 11872840, 8083157, 21245266, 12563288, 15501767, 10735886, 11987295, 7287892, 1640832, 11136786, 22150228, 19564607, 17331606, 6226306, 28561359, 8407793, 11553538, 16718600, 7768795, 12655062, 8021177, 15633700, 12732308, 2254301, 2114609, 12654809
Cronobacter spp. are emerging pathogens that cause severe infantile meningitis, septicemia, or necrotizing enterocolitis. Contaminated powdered infant formula has been implicated as the source of Cronobacter spp. in most cases, but questions still remain regarding the natural habitat and virulence potential for each strain. The iron acquisition systems in 231 Cronobacter strains isolated from different sources were identified and characterized. All Cronobacter spp. have both the Feo and Efe systems for acquisition of ferrous iron, and all plasmid-harboring strains (98%) have the aerobactin-like siderophore, cronobactin, for transport of ferric iron. All Cronobacter spp. have the genes encoding an enterobactin-like siderophore, although it was not functional under the conditions tested. Furthermore, all Cronobacter spp. have genes encoding five receptors for heterologous siderophores. A ferric dicitrate transport system (fec system) is encoded specifically by a subset of Cronobacter sakazakii and C. malonaticus strains, of which a high percentage were isolated from clinical samples. Phylogenetic analysis confirmed that the fec system is most closely related to orthologous genes present in human-pathogenic bacterial strains. Moreover, all strains of C. dublinensis and C. muytjensii encode two receptors, FcuA and Fct, for heterologous siderophores produced by plant pathogens. Identification of putative Fur boxes and expression of the genes under iron-depleted conditions revealed which genes and operons are components of the Fur regulon. Taken together, these results support the proposition that C. sakazakii and C. malonaticus may be more associated with the human host and C. dublinensis and C. muytjensii with plants.
Cluster Analysis, Cronobacter, Food Microbiology, Gene Order, Genes, Bacterial, Humans, Infant Formula, Iron, Membrane Transport Proteins, Phylogeny, Plasmids, Sequence Homology, Siderophores
null
22,706,062
2012-12-11
2021-10-21
1098-5336
Applied and environmental microbiology
Prophage carriage and diversity within clinically relevant strains of Clostridium difficile.
Shan Jinyu, Patel Krusha V, Hickenbotham Peter T, Nale Janet Y, Hargreaves Katherine R, Clokie Martha R J
eng
G0700855 (Medical Research Council, United Kingdom)
Journal Article, Research Support, Non-U.S. Gov't
Anti-Bacterial Agents, DNA Primers, DNA, Bacterial, DNA, Viral, Viral Proteins
IM
22706062, AEM.01311-12, 10.1128/AEM.01311-12, PMC3416593, 20565959, 12902252, 18708505, 15673505, 16182895, 9603813, 20438817, 19941785, 19781061, 21441508, 1406491, 21266997, 8702280, 19168661, 15691969, 2529136, 16980415, 21631945, 16965399, 22919598, 11018145, 16547044, 16804543, 17322187, 22624004, 8623526, 22066608, 6586860, 18326836, 16828113, 9929388, 10094706, 19776116, 18927415, 17015669, 10368133, 14060656, 17133077, 17488738, 19761828, 6874905, 22096150, 16141157, 8043060, 20667135, 20368420, 18417537, 17890338, 15640224, 7510324, 15659686
Prophages are encoded in most genomes of sequenced Clostridium difficile strains. They are key components of the mobile genetic elements and, as such, are likely to influence the biology of their host strains. The majority of these phages are not amenable to propagation, and therefore the development of a molecular marker is a useful tool with which to establish the extent and diversity of C. difficile prophage carriage within clinical strains. To design markers, several candidate genes were analyzed including structural and holin genes. The holin gene is the only gene present in all sequenced phage genomes, conserved at both terminals, with a variable mid-section. This allowed us to design two sets of degenerate PCR primers specific to C. difficile myoviruses and siphoviruses. Subsequent PCR analysis of 16 clinical C. difficile ribotypes showed that 15 of them are myovirus positive, and 2 of them are also siphovirus positive. Antibiotic induction and transmission electron microscope analysis confirmed the molecular prediction of myoviruses and/or siphovirus presence. Phylogenetic analysis of the holin sequences identified three groups of C. difficile phages, two within the myoviruses and a divergent siphovirus group. The marker also produced tight groups within temperate phages that infect other taxa, including Clostridium perfringens, Clostridium botulinum, and Bacillus spp., which suggests the potential application of the holin gene to study prophage carriage in other bacteria. This study reveals the high incidence of prophage carriage in clinically relevant strains of C. difficile and correlates the molecular data to the morphological observation.
Anti-Bacterial Agents, Clostridioides difficile, Clostridium Infections, DNA Primers, DNA, Bacterial, DNA, Viral, Genetic Variation, Microscopy, Electron, Transmission, Molecular Sequence Data, Myoviridae, Polymerase Chain Reaction, Prophages, Ribotyping, Sequence Analysis, DNA, Siphoviridae, United States, Viral Proteins, Virus Activation
null
22,706,065
2012-12-11
2022-03-31
1098-5336
Applied and environmental microbiology
Reduction of photoautotrophic productivity in the cyanobacterium Synechocystis sp. strain PCC 6803 by phycobilisome antenna truncation.
Page Lawrence E, Liberton Michelle, Pakrasi Himadri B
eng
null
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.
Phycobilisomes, Carbon Dioxide
IM
22706065, AEM.00499-12, 10.1128/AEM.00499-12, PMC3416626, 18383143, 1901865, 17116880, 7681841, 22331410, 15583167, 5966919, 9617824, 19480949, 27067764, 21078863
Truncation of the algal light-harvesting antenna is expected to enhance photosynthetic productivity. The wild type and three mutant strains of Synechocystis sp. strain 6803 with a progressively smaller phycobilisome antenna were examined under different light and CO(2) conditions. Surprisingly, such antenna truncation resulted in decreased whole-culture productivity for this cyanobacterium.
Autotrophic Processes, Carbon Dioxide, Light, Phototrophic Processes, Phycobilisomes, Sequence Deletion, Synechocystis
null
22,706,068
2012-12-18
2012-08-02
1473-6586
Current opinion in urology
Growth kinetics and active surveillance for small renal masses.
Lane Brian R, Tobert Conrad M, Riedinger Christopher B
eng
null
Journal Article, Review
null
IM
22706068, 10.1097/MOU.0b013e328355ecdf
Management options for small renal masses (SRMs) include excision, ablation, and active surveillance. Increasing interest in active surveillance, particularly for tumors of limited oncologic potential, in patients with other significant health concerns continues to rise, but precise protocols are still lacking.
Cell Proliferation, Disease Management, Disease Progression, Follow-Up Studies, Humans, Kidney Diseases, Kidney Neoplasms, Life Expectancy, Retrospective Studies, Risk Factors, Watchful Waiting
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