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840356
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Smoking may explain why more men than women die of COVID-19 in Spain
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Whether or not you are a smoker could condition how the coronavirus affects you. At least that is what numerous researchers are saying, insisting that tobacco use is to blame for the weakened cardiovascular systems which are at greatest risk from COVID-19. Among these researchers are Javier C. Vázquez, from the Bordeaux Neurocampus, and Diego Redolar, from the Universitat Oberta de Catalunya (UOC), who confirm that the data indicates that "tobacco use is one of the reasons that more men die from the virus than women in Spain". Over 30% of those who have died from the disease suffered from some form of cardiovascular disease - the leading cause of death in Spain (28% in 2018) - and approximately 10% of cardiovascular disease is attributed to smoking. COVID-19 is an infectious disease provoked by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As explained repeatedly in the news on the virus, it is transmitted mainly person to person via small respiratory droplets through sneezing or coughing, and the most common symptoms are fever, cough and difficulty breathing. Regarding its impact on the population in Spain, over 90% of deaths have occurred in people over 60 and over 45% had some pre-existing condition.
Men versus women
Although the number of COVID-19 infections among men and women is fairly similar in Spain, the mortality rate after 5 April stood at 8% for men and 4% for women. This is what the analysis by Redolar, associate dean for research at the UOC's Faculty of Health Sciences and researcher with the Cognitive NeuroLab research group, and Vázquez, researcher in the University of Bordeaux's Neuroscience Department, has shown. In Redolar's opinion, "it is evidence that gender plays a role in patterns such as the prevalence of tobacco use", since according to data for 2017, in Spain over 25% of men smoke while only 18% of women do.
The biological effects of tobacco use
The researchers, who have published an article on this topic in the scientific journal Tobacco Induced Diseases, state that it is important that biological data be taken into account. For instance, smoking tobacco can upregulate the angiotensin-converting enzyme 2 (ACE2), which, among other things, lowers blood pressure. Some coronaviruses use this enzyme as a cellular entry receptor. SARS-CoV-2 is one such virus, joining itself to ACE2 receptors in the lower respiratory tract of infected individuals to again access to the lungs. The researchers confirm that "existing data suggests that patients with COPD, or chronic obstructive pulmonary disease, or who smoke have a higher risk of becoming more seriously ill from COVID-19, since it increases ACE2 expression in weaker airways, which this type of patient has". These conclusions have already been confirmed in lab mice.
More data and measures against tobacco use
Given tobacco's apparent interaction with the coronavirus, the two researchers are alarmed at the lack of data that would allow us to better study how smoking and the pandemic are related. The researchers point out that in Spain there is currently no data on smoking in patients with COVID-19 and that this is something to be remedied by registering and sharing data on the issue.
They also state that we should launch campaigns to reduce tobacco use adapted to the current context and adopt interventions that have proven effective in curbing the habit, like increased taxes on tobacco, prohibiting its sale during the pandemic or improving programmes to help people quit smoking.
Researchers demand data on tobacco use among those infected and advise that its sale should be prohibited during the pandemic
Cardiovascular diseases aggravated by smoking are present in over 30% of coronavirus mortalities
Whether or not you are a smoker could condition how the coronavirus affects you. At least that is what numerous researchers are saying, insisting that tobacco use is to blame for the weakened cardiovascular systems which are at greatest risk from COVID-19. Among these researchers are Javier C. Vázquez, from the Bordeaux Neurocampus, and Diego Redolar, from the Universitat Oberta de Catalunya (UOC), who confirm that the data indicates that "tobacco use is one of the reasons that more men die from the virus than women in Spain". Over 30% of those who have died from the disease suffered from some form of cardiovascular disease - the leading cause of death in Spain (28% in 2018) - and approximately 10% of cardiovascular disease is attributed to smoking.
COVID-19 is an infectious disease provoked by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As explained repeatedly in the news on the virus, it is transmitted mainly person to person via small respiratory droplets through sneezing or coughing, and the most common symptoms are fever, cough and difficulty breathing. Regarding its impact on the population in Spain, over 90% of deaths have occurred in people over 60 and over 45% had some pre-existing condition.
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10.18332/tid/120005
| 2,020 |
Tobacco Induced Diseases
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COVID-19 outbreak impact in Spain: A role for tobacco smoking?
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1. Smoking, Vaping, and Tobacco Industry During COVID-19 Pandemic: Twitter Data Analysis Mikołaj Kamiński, Agnieszka Muth, Paweł Bogdański Cyberpsychology, Behavior, and Social Networking CrossRef
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911955
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Catalysts for heavy oil extraction developed at Kazan University
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The catalysts speed up heavy oil extraction under the conditions of in-situ combustion.
Projected heavy oil and viscous oil reserves in Russia are up to 40 - 50 billion barrels and a significant portion of that volume lies within Tatarstan. Heavy oil extraction warrants special technological processes, and research in that direction is currently becoming the center of attention in heavy oil-rich countries (USA, Canada, Venezuela, Russia).
Researchers at Kazan University cooperate with their peers from Stanford University. Their latest results were published in Energy and Fuels.
Senior Researcher at the Interbedding Combustion Lab Andrey Galukhin speaks about the research:
"Calorimetric experiments show that crude oil with higher saturate content and low resin fraction has higher heating value. Additionally, the crude oils undergo two major transitions when subjected to an oxidizing and constant rate environment known as low- and high-temperature oxidations at each heating rate studied. There are ways to pump extremely hot steam into a reservoir to liquefy viscous oil, what facilitates the extraction. However, there are limitations - if the reservoir more than 1 km deep, steam loses most of its heat energy. That is why in-situ combustion is interesting for us - the heat for liquefying is generated in the reservoir. Our group works on catalysts that provide combustion during this process. The catalysts help to oxidize oil deposits in reservoirs that are relatively resistant to burning".
Dr. Galukhin won a grant for this particular work from the Russian Foundation for Basic Research in 2015.
The catalysts developed by the group have already shown promising results in lab tests, and the work continues.
###
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10.1007/s10973-015-4892-6
| 2,015 |
Journal of Thermal Analysis and Calorimetry
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Contribution of thermal analysis and kinetics of Siberian and Tatarstan regions crude oils for in situ combustion process
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© 2015 Akadémiai Kiadó, Budapest, Hungary. This research focused on the characterization and kinetics of Siberian and Tatarstan crude oils by gas chromatography, combustion calorimetry, and thermogravimetry (TG-DTG) techniques. Calorimetric experiments show that crude oil with higher saturate content and low resin fraction has higher heating value. TG-DTG curves indicates that the crude oils undergoes two major transitions when subjected to an oxidizing and constant rate environment known as low- and high-temperature oxidations at each heating rate studied. Kinetic analysis in the low- and high-temperature oxidation regions was performed using model-free methods knows as Ozawa-Flynn-Wall and Kissinger-Akahira-Sunose. Throughout the study, it was observed that the activation energy values of the crude oil samples are varied between 41-72 and 145-198 kJ mol-1 in low- and high-temperature oxidation regions, respectively.
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927659
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Researchers find immune cells that guard frequent site of cancer spread
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LEBANON, NH – In the progressing field of immunotherapy, surprisingly little is known about immunity to metastatic tumors in locations such as lymph nodes, a frequent place where cancers first spread. Not only do lymph nodes act as a gateway for cancer cells to travel throughout the body, but they are also home to infection-fighting white blood cells called T cells. In some cases, T cells in lymph nodes activate to kill invading cancer cells. In other cases, that process clearly fails.
To address the need to understand why, researchers in the laboratory of Mary Jo Turk, PhD, Co-Director of the Immunology and Cancer Immunotherapy Research Program at Dartmouth’s and Dartmouth-Hitchcock’s Norris Cotton Cancer Center (NCCC) have spent the past year studying immunity to metastatic cancer within lymph nodes.
While T cells can freely travel from lymph nodes into the bloodstream and back to the lymph nodes, researchers in Turk’s lab have discovered a novel population of tumor-fighting T cells that do not circulate, but rather stay in lymph nodes where they provide protection against melanoma. “These T cells, for whatever reason, have changed their program and stay in the lymph nodes where they persist and kill tumor cells for many months while never entering circulation,” says Turk.
These long-lived T cells, called “lymph node resident memory T cells,” were shown to counteract melanoma spreading in mice. Turk’s team found that when melanoma cells were put back into mice that had been cured of cancer with immunotherapy a month earlier, the lymph nodes were still resistant to the cancer—the melanoma would not grow.
“We also identified T cells with similar characteristics in melanoma-invaded patient lymph nodes, showing that similar populations exist in humans,” reveals Turk.
Computational analysis of melanoma specimen data from The Cancer Genome Atlas revealed that the presence of T cells with this gene signature predicted better outcomes and improved survival for human melanoma patients with lymph node metastases. “These studies reveal a new population of T cells that is vital for counteracting the earliest stages of cancer metastasis,” says Turk.
Although the concept of T cells taking up residence in lymph nodes is not entirely new, it has never been shown in cancer. The team’s findings, “Resident memory T cells in regional lymph nodes mediate immunity to metastatic melanoma,” are newly published in Immunity.
The team, including clinicians at Dartmouth-Hitchcock Medical Center, as well as researchers at Baylor College of Medicine led by computational biologist, Chao Cheng, PhD, employed innovative sequencing techniques to identify the unique transcriptional profile that makes these resident T cells specific to lymph nodes and to cancer. “We found that these cells have a unique gene expression profile that differentiates them from cells in circulation, and from memory T cells that reside in and protect other tissues such as the skin,” says Cheng.
Other collaborators on this work include the University of Michigan and University of Texas, San Antonio.
In the coming year, the Turk research team hopes to better understand how these memory T cells are most effectively generated and activated within lymph nodes. The ultimate goal is to understand how memory T cells can be positioned throughout tissues to efficiently block cancer from spreading.
* * *
Mary Jo Turk, PhD, is the O. Ross McIntyre, MD, Endowed Professor and Professor of Microbiology and Immunology at the Geisel School of Medicine at Dartmouth, and the Co-Director of the Immunology and Cancer Immunotherapy Research Program at Dartmouth’s and Dartmouth-Hitchcock’s Norris-Cotton Cancer Center. Her laboratory's research focuses on generating memory T cell responses for long-lived immunity to cancer.
Chao Cheng, PhD, is an associate professor of the Dan L. Duncan Comprehensive Cancer Center, the Institute for Clinical and Translational Research, and Department of Medicine at Baylor College of Medicine. His laboratory focuses on computational method development and application to cancer systems biology and cancer immunology.
* * *
About Norris Cotton Cancer Center
Norris Cotton Cancer Center, located on the campus of Dartmouth-Hitchcock Medical Center (DHMC) in Lebanon, NH, combines advanced cancer research at Dartmouth College’s Geisel School of Medicine in Hanover, NH with the highest level of high-quality, innovative, personalized, and compassionate patient-centered cancer care at DHMC, as well as at regional, multi-disciplinary locations and partner hospitals throughout NH and VT. NCCC is one of only 51 centers nationwide to earn the National Cancer Institute’s prestigious “Comprehensive Cancer Center” designation, the result of an outstanding collaboration between DHMC, New Hampshire’s only academic medical center, and Dartmouth College. Now entering its fifth decade, NCCC remains committed to excellence, outreach and education, and strives to prevent and cure cancer, enhance survivorship and to promote cancer health equity through its pioneering interdisciplinary research. Each year the NCCC schedules 61,000 appointments seeing nearly 4,000 newly diagnosed patients, and currently offers its patients more than 100 active clinical trials.
About the Geisel School of Medicine
Founded in 1797, the Geisel School of Medicine at Dartmouth strives to improve the lives of the communities it serves through excellence in learning, discovery, and healing. The Geisel School of Medicine is renowned for its leadership in medical education, healthcare policy and delivery science, biomedical research, global health, and in creating innovations that improve lives worldwide. As one of America’s leading medical schools, Dartmouth’s Geisel School of Medicine is committed to training new generations of diverse leaders who will help solve our most vexing challenges in healthcare.
About Dartmouth-Hitchcock Health
Dartmouth-Hitchcock Health (D-HH), New Hampshire’s only academic health system and the state’s largest private employer, serves a population of 1.9 million across northern New England. D-H provides access to more than 2,000 providers in almost every area of medicine, delivering care at its flagship hospital, Dartmouth-Hitchcock Medical Center (DHMC) in Lebanon, NH. DHMC was named again in 2020 as the #1 hospital in New Hampshire by U.S. News & World Report, and recognized for high performance in 9 clinical specialties and procedures. Dartmouth-Hitchcock also includes the Norris Cotton Cancer Center, one of only 51 NCI-designated Comprehensive Cancer Centers in the nation; the Children's Hospital at Dartmouth-Hitchcock, the state’s only children’s hospital; affiliated member hospitals in Lebanon, Keene, and New London, NH, and Windsor, VT, and Visiting Nurse and Hospice for Vermont and New Hampshire; and 24 Dartmouth-Hitchcock clinics that provide ambulatory services across New Hampshire and Vermont. The D-H system trains nearly 400 residents and fellows annually, and performs world-class research, in partnership with the Geisel School of Medicine at Dartmouth and the White River Junction VA Medical Center in White River Junction, VT.
Immunity
10.1016/j.immuni.2021.08.019
Computational simulation/modeling
Resident memory T cells in regional lymph nodes mediate immunity to metastatic melanoma
14-Sep-2021
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10.1016/j.immuni.2021.08.019
| 2,021 |
Immunity
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Resident memory CD8+ T cells in regional lymph nodes mediate immunity to metastatic melanoma
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The nature of the anti-tumor immune response changes as primary tumors progress and metastasize. We investigated the role of resident memory (Trm) and circulating memory (Tcirm) cells in anti-tumor responses at metastatic locations using a mouse model of melanoma-associated vitiligo. We found that the transcriptional characteristics of tumor-specific CD8+ T cells were defined by the tissue of occupancy. Parabiosis revealed that tumor-specific Trm and Tcirm compartments persisted throughout visceral organs, but Trm cells dominated lymph nodes (LNs). Single-cell RNA-sequencing profiles of Trm cells in LN and skin were distinct, and T cell clonotypes that occupied both tissues were overwhelmingly maintained as Trm in LNs. Whereas Tcirm cells prevented melanoma growth in the lungs, Trm afforded long-lived protection against melanoma seeding in LNs. Expanded Trm populations were also present in melanoma-involved LNs from patients, and their transcriptional signature predicted better survival. Thus, tumor-specific Trm cells persist in LNs, restricting metastatic cancer.
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681981
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Early maternal anemia tied to intellectual disability, ADHD and autism
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10.1001/jamapsychiatry.2019.2309
| 2,019 |
JAMA Psychiatry
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Association of Prenatal Maternal Anemia With Neurodevelopmental Disorders
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<h3>Importance</h3> Given the critical role that iron plays in neurodevelopment, an association between prenatal iron deficiency and later risk of neurodevelopmental disorders, such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and intellectual disability (ID), is plausible. <h3>Objective</h3> To test the a priori hypothesis that anemia diagnosed in mothers during pregnancy is associated with an increased risk of ASD, ADHD, and ID in offspring and that the magnitude of the risk varies with regard to the timing of anemia in pregnancy. <h3>Design, Setting, and Participants</h3> This cohort study used health and population register data from the Stockholm Youth Cohort to evaluate 532 232 nonadoptive children born from January 1, 1987, to December 31, 2010, in Sweden, with follow-up in health registers until December 31, 2016. Data analysis was performed from January 15, 2018, to June 20, 2018. <h3>Exposures</h3> Registered diagnoses of anemia during pregnancy. Gestational timing of the first recorded anemia diagnosis (≤30 weeks or >30 weeks) was considered to assess potential critical windows of development. <h3>Main Outcomes and Measures</h3> Registered diagnoses of ASD, ADHD, or ID or co-occurring combinations of these disorders. <h3>Results</h3> The cohort included 532 232 individuals (272 884 [51.3%] male) between 6 and 29 years of age at the end of follow-up (mean [SD] age, 17.6 [7.1] years) and their 299 768 mothers. The prevalence of ASD, ADHD, and ID was higher among children born to mothers diagnosed with anemia within the first 30 weeks of pregnancy (4.9% ASD, 9.3% ADHD, and 3.1% ID) compared with mothers with anemia diagnosed later in pregnancy (3.8% ASD, 7.2% ADHD, and 1.1% ID) or mothers not diagnosed with anemia (3.5% ASD, 7.1% ADHD, and 1.3% ID). Anemia diagnosed during the first 30 weeks of pregnancy but not later was associated with increased risk of diagnosis of ASD (odds ratio [OR], 1.44; 95% CI, 1.13-1.84), ADHD (OR, 1.37; 95% CI, 1.14-1.64), and ID (OR, 2.20; 95% CI, 1.61-3.01) in offspring in models that included socioeconomic, maternal, and pregnancy-related factors. Early anemia diagnosis was similarly associated with risk of ASD (OR, 2.25; 95% CI, 1.24-4.11) and ID (OR, 2.59; 95% CI, 1.08-6.22) in a matched sibling comparison. Considering mutually exclusive diagnostic groups, we observed the strongest association between anemia and ID without co-occurring ASD (OR, 2.72; 95% CI, 1.84-4.01). Associations of these disorders with anemia diagnosed later in pregnancy were greatly diminished. <h3>Conclusions and Relevance</h3> In contrast to maternal anemia diagnosed toward the end of pregnancy, anemia diagnosed earlier in pregnancy was associated with increased risk of the development of ASD, ADHD, and particularly ID in offspring. Given that iron deficiency and anemia are common among women of childbearing age, our findings emphasize the importance of early screening for iron status and nutritional counseling in antenatal care.
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954687
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Advanced liquid crystal devices for AR/VR displays: Principles and Applications
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Augmented reality (AR) and virtual reality (VR) have potential to revolutionize the ways we perceive and interact with digital information. Since the 1990s, AR and VR experienced their first boom ushering in the dawn of evolution in display and information platforms. At one end of the spectrum is VR display, which effectively extends the field of view (FoV), blocks the entire ambient, and offers a completely immersive virtual environment. At the other end of the spectrum is AR display, which enables see-through capability while overlaying digital content to the real world. With the refreshing visual experiences, AR/VR displays have opened a new gateway for many attractive applications, including healthcare, education, engineering, manufacturing, and entertainment, just to name a few. These new display platforms are mutually reinforcing with emerging functional LC-based optics, resulting in many impressive, AR/VR-ready LC devices. Due to the unique requirements, diverse capabilities, and rapid development of LC devices in near-eye systems, it is increasingly important to discuss advanced LC-based devices in AR/VR from a comprehensive perspective to provide valuable reference for future development.
In a new paper published in Light Science & Application, a team of scientists, led by Professor Shin-Tson Wu from College of Optics and Photonics, University of Central Florida, USA, have conducted a systematic and comprehensive analysis to bridge various functional LC devices with their corresponding applications in near-eye displays. In this paper, three major LC devices, including transmissive active matrix microdisplays, reflective Liquid-Crystal-on-Silicon (LCoS), and LC planar optics, are described in detail. Figure 1 shows the classification of LC photonic devices and their structures and working principles, which have been widely used in AR/VR systems as emerging technologies to support various functionalities.
More specifically, high-dynamic-range (HDR) LCDs for VR headsets suffer from low transmittance issues caused by small aperture ratios and disclination lines blocking the backlight, achieving a high-performing VR that is compatible with directional backlight and spatial patterned beam steerer represents a promising solution. Meanwhile, LCoS spatial light modulators offer an unrivaled phase modulation to realize holographic views beyond conventional displays for near-eye system. Emerging LC planar optics provide excellent optical properties with an ultrathin formfactor and high efficiency. These advanced LC devices cover the entire AR/VR systems from light engines, imaging optics, optical combiner, to various functional elements, and play pivotal roles for systematically improving the image quality and formfactor of the AR/VR displays.
With the presented work, Wu and co-workers provided an overview of LC devices in the rapidly growing field of AR/VR systems. Taking advanced LC as the cornerstone, a variety of devices, such as HDR and high-resolution density microdisplays for VR, high-brightness and high-resolution LCoS light engines for AR, and polarization selective beam deflector and lens are discussed. Based on the specific AR/VR requirements, such as light efficiency, resolution density, ambient contrast ratio, form factor, imaging performance, FoV, and vergence-accommodation conflict, Wu’s team demonstrated several promising photonic solutions to address these challenges and provide useful guidelines for future LC device development.
Light Science & Applications
10.1038/s41377-022-00851-3
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10.1038/s41377-022-00851-3
| 2,022 |
Light Science & Applications
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Advanced liquid crystal devices for augmented reality and virtual reality displays: principles and applications
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Liquid crystal displays (LCDs) and photonic devices play a pivotal role to augmented reality (AR) and virtual reality (VR). The recently emerging high-dynamic-range (HDR) mini-LED backlit LCDs significantly boost the image quality and brightness and reduce the power consumption for VR displays. Such a light engine is particularly attractive for compensating the optical loss of pancake structure to achieve compact and lightweight VR headsets. On the other hand, high-resolution-density, and high-brightness liquid-crystal-on-silicon (LCoS) is a promising image source for the see-through AR displays, especially under high ambient lighting conditions. Meanwhile, the high-speed LCoS spatial light modulators open a new door for holographic displays and focal surface displays. Finally, the ultrathin planar diffractive LC optical elements, such as geometric phase LC grating and lens, have found useful applications in AR and VR for enhancing resolution, widening field-of-view, suppressing chromatic aberrations, creating multiplanes to overcome the vergence-accommodation conflict, and dynamic pupil steering to achieve gaze-matched Maxwellian displays, just to name a few. The operation principles, potential applications, and future challenges of these advanced LC devices will be discussed.
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623510
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Advanced prostate cancer has an unexpected weakness that can be targeted by drugs
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Kanazawa, Japan - The compound thymoquinone (TQ) selectively kills prostate cancer cells at advanced stages, according to a new study published in Oncogene. Led by researchers at Kanazawa University, the study reports that prostate cancer cells with a deletion of the SUCLA2 gene can be therapeutically targeted. SUCLA2-deficient prostate cancers represent a significant fraction of those resistant to hormone therapy or metastatic, and a new therapeutic option for this disease would have immense benefits for patients.
Hormone therapy is often chosen for the treatment of metastatic prostate cancer but nearly half of patients develop resistance to the treatment in as little as 2 years. A mutation in RB1, a tumor suppressor gene that keeps cell growth under control, has been pegged as a particularly strong driver of treatment resistance and predicts poor outcome in patients.
"Mutations in tumor suppressor genes are enough to induce initiation and malignant progression of prostate cancer, but so far we haven't been able to directly target these mutations with drugs to treat prostate cancer," says the lead author Susumu Kohno. "We wanted to find a genetic aberration associated with that of a tumor suppressor gene which we could target therapeutically."
In the genome, SUCLA2 neighbors RB1. An analysis of prostate cancer cells showed that cells with a RB1 deletion were also missing SUCLA2, pairing up the SUCLA2 deletion with the RB1 deletion present in advanced stage prostate cancer. Kohno and colleagues analyzed prostate cancer tissue and found that 11% of cases were missing both SUCLA2 and RB1.
The researchers screened compounds to identify drugs that would selectively kill cells with a SUCLA2 deletion. Out of around 2,000 compounds, TQ emerged as a hit compound. TQ already has known anti-cancer effects and was shown to be safe in a phase I clinical trial. Kohno and colleagues applied the TQ treatment to a mouse model of SUCLA2-deficient prostate cancer and TQ selectively suppressed tumor growth.
"These findings show that TQ treatment could be an effective therapy for treating prostate cancer cells that harbor SUCLA2 deficiency" says the senior author Chiaki Takahashi.
In a search of genetic databases from patients with prostate cancer, the researchers found that the frequency of SUCLA2 loss was almost perfectly aligned with RB1 loss at every disease stage--meaning the SUCLA2 deletion could identify people with prostate cancer needing advanced therapy.
Finding this drug-targetable vulnerability opens a crack in the barrier of treatment resistance for prostate cancer. More work needs to be done to improve efficacy of TQ and identify patients that would benefit from this type of treatment, but the compound provides a promising route for new treatment options for advanced prostate cancer.
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10.1038/s41388-020-1381-6
| 2,020 |
Oncogene
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Pharmacologically targetable vulnerability in prostate cancer carrying RB1-SUCLA2 deletion
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RB1 gene is often homozygously deleted or mutated in prostate adenocarcinomas following acquirement of castration resistance and/or metastatic ability. We found that SUCLA2 gene is frequently involved in the deletion of the RB1 gene region in advanced prostate cancer. SUCLA2 constitutes the β-subunit of succinate CoA ligase heterodimer that reversibly converts succinyl CoA into succinate. We sought the possibility that deletion of SUCLA2 gives rise to a metabolic vulnerability that could be targeted therapeutically. We found a significant metabolic shift in SUCLA2-deleted prostate cancer cells, including lower mitochondrial respiratory activity. By screening a number of libraries for compounds that induce cell death selectively in SUCLA2-deficient prostate cancer cells, we identified thymoquinone (2-isopropyl-5-methylbenzo-1,4-quinone) and PMA (phorbol-12-myristate-13-acetate) from a natural compound library. These findings indicate that the metabolic vulnerability in SUCLA2-deficient prostate cancer cells is pharmacologically targetable.
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766095
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Pediatric endocrinologist gives iconic 'Mona Lisa' a second medical opinion
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Leonardo da Vinci's world-renowned "Mona Lisa" painting of Lisa Gherardini has captivated millions since it was created in the early 1500s, including experts in the medical community. For years, scientists and physicians have studied the discoloration of Gherardini's skin, the thickness of her neck, and her enigmatic smile to hypothesize about her health during the Renaissance time period.
The most recent published theory suggests she suffered from severe hypothyroidism, or underactive thyroid. The cardiologist cites her yellow skin, the enlarged appearance of her thyroid gland, and lack of eyebrows as symptoms to support his theory. He also writes that her mysterious smile may represent a hint of resulting psychomotor retardation and muscle weakness.
Not so fast, said Michael Yafi, MD, a pediatric endocrinologist at The University of Texas Health Science Center at Houston (UTHealth).
"I felt a personal responsibility to defend the "Mona Lisa" and the fascinating lady the painting portrays," said Yafi, the director of the Division of Pediatric Endocrinology at McGovern Medical School and a specialist with UT Physicians, the clinical practice of UTHealth. "She has inspired thousands of people over the past few centuries. I couldn't have the public thinking she had hypothyroidism, when it seems to me she was euthyroid, meaning her thyroid was normal. So, I decided to give her a fresh 21st-century medical opinion."
Yafi's opinion was recently published in Hormones-International Journal of Endocrinology and Metabolism. In it, he explains that the documentation of thyroid disease is well known in art history, and this painting doesn't match the countless other depictions of goiters, or enlargements of the thyroid gland.
"Artists often depicted what they saw in society. Sculptures from the ancient Andean and Egyptian civilizations recorded endemic goiters in areas of environmental iodine deficiency, like the Tuscany region where Gherardini lived. Ancient Greek art represents this symptom as well, as do several poetic works and even Shakespearean literature. If Gherardini had a goiter from iodine deficiency, it would have been severe and more clearly demarcated in the painting like the other historical representations; a talented painter like da Vinci would have had no problem expressing it," Yafi said.
Yafi also points out that many of da Vinci's paintings depict women without eyebrows, so it's not conclusive to attribute that feature to underactive thyroid.
Additionally, he says the yellowing of the skin only develops after a long duration of the disease. Typically, having long-term hypothyroidism would have severely affected fertility, but Gherardini is known to have given birth to five children, including one only months before sitting for the painting.
"The discoloration could simply be attributed to the age of the artwork, as well as the varnish applied by the artist. Furthermore, the painting was stolen and then hidden away for almost three years, and someone also once vandalized it with acid in an act of sabotage," Yafi said.
And as for the mysterious smile and the proposal that it's caused by muscle weakness:
"Making a diagnosis of hypothyroidism on the basis of subtle and vague features in an old painting is, needless to say, risky," Yafi said. "Hypothyroid myopathy, or muscle tissue disease, manifests in muscles that are closer to the body's midline. It is usually severe, which means that it would have prevented Gherardini from posing with a straight back. Moreover, there are plenty of people who have an asymmetric smile, but this does not necessarily mean that they are hypothyroid."
Yafi, an avid art lover and active member of Houston's art community, enjoys studying the intersection between art and medicine. His second medical diagnosis of a famous piece of art, this time focused on Edward Munch's "The Scream," was just published in Hektoen International, A Journal of Medical Humanities.
"Artists and art interpreters throughout history were able to detect many diagnoses and conditions, even before doctors. However, they weren't always correct," he said. "The artwork or person in the artwork may need a second opinion, or even third or fourth, based on current medical or scientific discoveries. It's always best to keep an open mind."
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10.1007/s42000-019-00103-x
| 2,019 |
HORMONES
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Mona Lisa is euthyroid: a modern-day diagnosis
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Making any medical diagnosis of an individual appearing in an old painting is risky. Throughout history, the famous painting of the Mona Lisa by Leonardo da Vinci has challenged many scientists and physicians to scrutinize this striking and enigmatic female image for the purpose of potentially explaining the woman "behind the smile" and offering a medical diagnosis of her state of health. A recent proposal was that she suffered from severe hypothyroidism and that her asymmetric smile was due to psychomotor retardation. Today, in the twenty-first century, can Mona Lisa get "a second opinion?"
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946851
|
Urinary proteomics identified alternation of an enzyme that consumes itaconate in the TCA cycle and implicated a role of itaconite as an immune modulating metabolite in COVID-19
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In the very beginning of the COVID-19 outbreak (February, 2020), a proteomics expert, Dr. Jun Qin (State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics) and a clinical doctor, Dr. Zhongde Zhang (The Second Affiliated Hospital of Guangzhou University of Chinese Medicine), who worked in the forefront line of compacting COVID-19 disease, wondered whether they could find clues for what happened to the living COVID-19 patients at the molecular level. As urine can be readily obtained from living people, they teamed up to look at all kinds of proteins in the urine.
By applying LC/MS-MS-based proteomics, scientists analyzed 317 urine proteomes from 86 COVID-19 and 55 pneumonia patients and 176 healthy controls, they identified 4,255 proteins from the urine, in which proteins with functions of immune and metabolism were among the most significantly altered after SARS-CoV-2 infection.
It was exciting and reassuring to find proteins in the anti-virus response pathway from the urinary proteome, including the up-regulated dsRNA detector DDX58/RIG-I, the virus response specific transcription factor STAT1, and a collection of ISG proteins. This suggests that urine may provide a window for us to see what is happening inside the human body. Trawling through the data, scientists came across an under-studied protein, CLYBL, which was not included in the commonly used database for annotation in bioinformatics. CLYBL, a citramalyl-CoA lyase, catalyzes the transition of itaconate to acetyl-CoA in the TCA cycle. Thus, increased CLYBL indeed led to the consumption of anti-inflammatory metabolite itaconate in COVID-19 patients. As Itaconate was shown to play an important role in antioxidation, cellular protection, and anti-inflammation, these observations led to the speculation that supplement of itaconate along or with inhibition of CLYBL might be possible therapeutic options for treating COVID-19 patients.
By comparing the proteomes of the early-disease-stage patients who later turned into severity with those of the patients who remained moderate across disease progression, the team identified a number of proteins, which may predict the transition from moderate to severe disease in COVID-19 progression. Increased levels of CD14, RBP4, SPON2, GMFG, SERPINA1, SERPINB6 and SERPINC1 in severe COVID-19 patients and their known biological functions suggested that macrophage-induced inflammation and thrombolysis may play a critical role in worsening the disease.
The current study showed that the urine proteome contained clues to what is happening inside the human body. It is a convenient source of biological samples that can be obtained from living people under physiological and pathological conditions. Peeking through the urine proteome, one can find signaling pathways as well as potential drug targets. In this specific COVID-19 case, the finding that the endogenous immune-modulating metabolite itaconate as a potential therapy option for treating the disease is particular timely, as an immune modulating therapy is independent of mutating virus, say it is Delta or Omicron.
Science China Life Sciences
10.1007/s11427-021-2070-y
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10.1007/s11427-021-2070-y
| 2,022 |
Science China Life Sciences
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A urinary proteomic landscape of COVID-19 progression identifies signaling pathways and therapeutic options
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Signaling pathway alterations in COVID-19 of living humans as well as therapeutic targets of the host proteins are not clear. We analyzed 317 urine proteomes, including 86 COVID-19, 55 pneumonia and 176 healthy controls, and identified specific RNA virus detector protein DDX58/RIG-I only in COVID-19 samples. Comparison of the COVID-19 urinary proteomes with controls revealed major pathway alterations in immunity, metabolism and protein localization. Biomarkers that may stratify severe symptoms from moderate ones suggested that macrophage induced inflammation and thrombolysis may play a critical role in worsening the disease. Hyper activation of the TCA cycle is evident and a macrophage enriched enzyme CLYBL is up regulated in COVID-19 patients. As CLYBL converts the immune modulatory TCA cycle metabolite itaconate through the citramalyl-CoA intermediate to acetyl-CoA, an increase in CLYBL may lead to the depletion of itaconate, limiting its anti-inflammatory function. These observations suggest that supplementation of itaconate and inhibition of CLYBL are possible therapeutic options for treating COVID-19, opening an avenue of modulating host defense as a means of combating SARS-CoV-2 viruses.
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981579
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UC Davis study uncovers age-related brain differences in autistic individuals
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A new study led by UC Davis MIND Institute researchers confirms that brain development in people with autism differs from those with typical neurodevelopment. According to the study published in PNAS, these differences are linked to genes involved in inflammation, immunity response and neural transmissions. They begin in childhood and evolve across the lifespan.
About one in 44 children in the U.S. has autism. Autistic individuals may behave, communicate and learn in ways that are different from neurotypical people. As they age, they often have challenges with social communication and interaction.
The researchers aimed to understand how neurons in the brain communicate and the interaction between age and autism. They studied the genetic differences in brain neurons in people with autism at different ages and compared them to those with neurotypical development.
Earlier studies have shown that certain brain regions mark early excess, followed by reductions in volume, connectivity, and cell densities of neurons as people with autism age through adulthood.
“Initial excess and overconnectivity of neurons may make the brain more vulnerable to early aging and inflammation, which may lead to further changes in the brain structure and function,” said co-senior author Cynthia Schumann. Schumann is a professor of neuroscience in the Department of Psychiatry and Behavioral Sciences. She is affiliated with the UC Davis MIND Institute. “Understanding how the brain in a person with autism changes throughout life will provide opportunities for early intervention.”
Method
The researchers analyzed brain tissues from 27 deceased individuals with autism and 32 without autism. The age of these individuals ranged between 2 and 73 years.
The tissues were taken from the superior temporal gyrus (STG) region — an area in the brain responsible for sound and language processing and social perception.
“The STG plays a critical role in integrating information. It helps provide meaning about our surroundings. Despite its importance, it remains relatively unexplored,” Schumann commented. “We wanted to understand how the molecular changes in this critical part of the brain are happening in autism.”
The team analyzed brain tissues as well as isolated neurons using laser capture microdissection techniques. They studied mRNA expression on a molecular level in the STG tissue and the isolated neurons. The mRNA translates the DNA code into instructions the cell machinery can recognize and use to make proteins for different body functions.
Main findings
The study identified 194 significantly different genes in the brains of people with autism. Of those genes, 143 produced more mRNA (upregulated) and 51 produced less (downregulated) in autistic brains than in typical ones.
The downregulated genes were mainly linked to brain connectivity. This may indicate that the neurons may not communicate as efficiently. Too much activity in the neurons may cause the brain to age faster in autistic individuals.
The study also found more mRNA for heat-shock proteins in autistic brains. These proteins respond to stress and activate immune response and inflammation.
Age-related brain differences between neurotypical and autistic people
The study identified 14 genes in bulk STG tissue that showed age-dependent differences between autistic and neurotypical individuals and three genes in isolated neurons. These genes were connected to synaptic as well as immunity and inflammation pathways.
For example, in typical brains, the expression of the HTRA2 gene is much higher before age 30 and decreases with age. In the STG neurons of people with autism, the expression levels of this gene begin lower and increase with age.
“Changes in HTRA2 have been implicated in neuronal cell loss and cell functions - such as proper protein folding, and reusing and recycling cell components,” explained co-senior author Boryana Stamova, associate professor in the Department of Neurology. She is also affiliated with the MIND Institute. “HTRA2’s role is vital for normal brain function.”
The researchers also uncovered different inflammation patterns in autistic brain tissues. Several immune and inflammation-related genes were strongly upregulated, indicating immune dysfunction that may get worse with age.
The study pointed to an age-related decrease in the gene expression involved in Gamma-aminobutyric acid (GABA) synthesis. GABA is a chemical messenger that helps slow down the brain. It works as an inhibitory neurotransmitter.
“GABA is known for producing a dampening effect in controlling neuronal hyperactivity in anxiety and stress. Our study showed age-dependent alterations in genes involved in GABA signaling in brains of people with autism,” Stamova said.
The study found direct molecular-level evidence that insulin signaling was altered in the neurons of people with autism. It also noted significant similarities of mRNA expressions in the STG region between people with autism and those with Alzheimer’s disease. These expressions may be linked to increased likelihood of neurodegenerative and cognitive decline.
“The findings from our study are really important in understanding what is happening in the brains of people with autism. Identifying these changes over time gives us an opportunity to think about some interventions that might be more useful in certain periods,” Schumann said.
Credits
The study’s co-authors are Bradley Ander of the UC Davis MIND Institute and the Department of Neurology; Alicja Omanska of the UC Davis MIND Institute and the Department of Psychiatry and Behavioral Sciences; and Michael Gandal and Pan Zhang of UCLA.
The researchers are grateful to the families of the brain donors for their invaluable gift to autism research. Brain tissues were provided by the University of Maryland Brain and Tissue Bank, Autism Tissue Program (now Autism BrainNet), Brain Endowment for Autism Research Sciences (BEARS) at the UC Davis MIND Institute, and the Harvard Brain Tissue Resource Center.
This work is supported by National Institutes of Health (NIH) grants MH108909 and the Intellectual and Developmental Disabilities Research Center at UC Davis (1U54HD079125). The study also benefited from NIH instrumentation funding (S10RR-023555, S10OD-018174) for the laser capture microdissection and RNA sequencing.
Proceedings of the National Academy of Sciences
10.1073/pnas.2206758120
Human tissue samples
Neuron-specific transcriptomic signatures indicate neuroinflammation and altered neuronal activity in ASD temporal cortex
2-Mar-2023
No conflict of interest
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10.1073/pnas.2206758120
| 2,023 |
Proceedings of the National Academy of Sciences
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Neuron-specific transcriptomic signatures indicate neuroinflammation and altered neuronal activity in ASD temporal cortex
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Autism spectrum disorder (ASD) is a highly heterogeneous disorder, yet transcriptomic profiling of bulk brain tissue has identified substantial convergence among dysregulated genes and pathways in ASD. However, this approach lacks cell-specific resolution. We performed comprehensive transcriptomic analyses on bulk tissue and laser-capture microdissected (LCM) neurons from 59 postmortem human brains (27 ASD and 32 controls) in the superior temporal gyrus (STG) of individuals ranging from 2 to 73 years of age. In bulk tissue, synaptic signaling, heat shock protein-related pathways, and RNA splicing were significantly altered in ASD. There was age-dependent dysregulation of genes involved in gamma aminobutyric acid (GABA) (
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970770
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A second chance for the Sumatran rhino
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Malaysia’s last male Sumatran rhino, Kertam, died in 2019. Now, a team from the Max Delbrück Center has successfully grown stem cells and mini-brains from his skin cells. As they report in iScience, their goal is to create sperm cells that may help to save the endangered species from extinction.
The Sumatran rhinoceros was once found across large parts of East and Southeast Asia. Today, poaching and habitat destruction have decimated the population of the world’s smallest and most ancient rhino species, leaving only a few dozen individuals living in the rainforests of Sumatra and the Indonesian part of Borneo. As a result, mating encounters between males and females are increasingly rare.
The last of their kind in Malaysia
The Sumatran rhinoceros, which is the only surviving rhino species with hair, has been considered extinct in Malaysia since 2019 following the death of male Kertam and, just a few months later, female Iman. But a team of Berlin scientists led by Dr Vera Zywitza and Dr Sebastian Diecke, head of the Pluripotent Stem Cells Platform at the Max Delbrück Center in Berlin, are not content with this. They and their international partners have an ambitious goal: to turn skin cells taken from now deceased Sumatran rhinos into stem cells, from which they can then derive egg and sperm cells to be used in assisted reproduction – in this case, fertilization in the laboratory. The embryos bred in the petri dish, which will be the offspring of Kertam and other already deceased or infertile individuals, will be carried to term by surrogate rhino mothers.
In the scientific journal iScience, the team led by first author Zywitza and last author Diecke has now reported an initial success: they have generated induced pluripotent stem cells, or iPS cells for short, from Kertam’s skin samples. These cells have two key advantages. First, they are able to divide infinitely and therefore never die; and second, they are able to transform into any cell type in the body. For their recently published study, the group has already grown brain organoids, also called “mini-brains,” from Kertam’s iPS cells.
Learning from the white rhino
The technology platform developed its stem cell technologies as part of the BioRescue research project for the even more critically endangered northern white rhinoceros – of which only two females now remain, living in a Kenyan wildlife reserve. “Our current study has benefited a lot from the knowledge gained through this large-scale project, which is funded by the German Federal Ministry of Education and Research,” says Zywitza. Professor Thomas Hildebrandt, head of the Reproduction Management Department at the Leibniz Institute for Zoo and Wildlife Research (IZW) in Berlin, and his research group were also significantly involved in the project.
Zywitza recounts how all those involved in the current study were surprised and pleased to discover that the methods used to turn the skin cells of northern white rhinos into stem cells also worked well with the cells of Sumatran rhinos. Under the microscope, the stem cells of both rhino species were barely distinguishable from human iPS cells. Nevertheless, there were species-specific differences: “In contrast to northern white rhino iPS cells, Kertam’s iPSCs could not be cultivated without feeder cells, which release growth factors that help to keep stem cells in a pluripotent state,” explains Zywitza.
A deeper look into evolution
In addition to preserving the species, the stem cells obtained from Kertam’s skin could serve another purpose: “iPS cells from exotic animals provide a unique tool to gain insights into the evolution of organ development,” says Zywitza. To demonstrate this, Dr Silke Frahm-Barske, who is also a scientist in Diecke’s research group, grew brain organoids from the cells.
“To the best of our knowledge, mini-brains like these have only been obtained from mouse, human, and non-human primates so far,” says Frahm-Barske. “So we were very pleased to see that the stem cells we generated from the Sumatran rhino formed organoids quite similar to those of humans.” However, she added that the team had to treat the human and rhino iPS cells slightly differently in order to generate the brain organoids.
The next step is sperm cells
The team’s next goal is to use Kertam’s iPS cells to grow sperm suitable for artificial insemination. “This step is more difficult,” says Zywitza. “To obtain sperm cells, we first need to use the iPS cells to cultivate primordial germ cells – the precursors of eggs and sperm.” This is the tricky task the scientists are now going to tackle. They also plan to obtain iPS cells from other Sumatran rhinos.
Reproduction expert Thomas Hildebrandt explains why efforts like these are necessary: “Measures are indeed being taken in Indonesia to preserve the Sumatran rhino population by bringing together the remaining individuals in wildlife reserves,” he says. “But females that have not been pregnant for a long time often become infertile, for example due to cysts that develop on their reproductive organs, or they may just be too old to bear young.”
“Even though our work is attempting to make the seemingly impossible possible – i.e., to ensure the survival of animals that would otherwise probably disappear from our planet – it must remain an exception and not become the rule,” emphasizes Zywitza. “Despite all the buzz around what we are doing in the lab, this can at best make a small contribution to saving these rhinos from extinction. The protection and conservation of the animals’ few remaining habitats is at least equally important.”
Further information
Pluripotent Stem Cells Platform at Max Delbrück Center
Rhinos from skin cells
BioRescue consortium
Literature
Vera Zywitza et al. (2022): “Induced pluripotent stem cells and cerebral organoids from the critically endangered Sumatran rhinoceros.” iScience, DOI: 10.1016/j.isci.2022.105414
The Max Delbrück Center
The Max Delbrück Center for Molecular Medicine in the Helmholtz Association (Max Delbrück Center) is one of the world’s leading biomedical research institutions. Max Delbrück, a Berlin native, was a Nobel laureate and one of the founders of molecular biology. At the locations in Berlin-Buch and Mitte, researchers from some 70 countries study human biology – investigating the foundations of life from its most elementary building blocks to systems-wide mechanisms. By understanding what regulates or disrupts the dynamic equilibrium of a cell, an organ, or the entire body, we can prevent diseases, diagnose them earlier, and stop their progression with tailored therapies. Patients should benefit as soon as possible from basic research discoveries. The Max Delbrück Center therefore supports spin-off creation and participates in collaborative networks. It works in close partnership with Charité – Universitätsmedizin Berlin in the jointly run Experimental and Clinical Research Center (ECRC), the Berlin Institute of Health (BIH) at Charité, and the German Center for Cardiovascular Research (DZHK). Founded in 1992, the Max Delbrück Center today employs 1,800 people and is funded 90 percent by the German federal government and 10 percent by the State of Berlin. www.mdc-berlin.de
iScience
10.1016/j.isci.2022.105414
Experimental study
Cells
Induced pluripotent stem cells and cerebral organoids from the critically endangered Sumatran rhinoceros
18-Nov-2022
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10.1016/j.isci.2022.105414
| 2,022 |
iScience
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Induced pluripotent stem cells and cerebral organoids from the critically endangered Sumatran rhinoceros
|
<jats:title>SUMMARY</jats:title><jats:p>Less than 80 Sumatran rhinos (SR, <jats:italic>Dicerorhinus sumatrensis)</jats:italic> are left on earth. Habitat loss and limited breeding possibilities are the greatest threats for the species and lead to a continuous population decline. To stop erosion of genetic diversity, reintroduction of genetic material is indispensable. However, as the propagation rate of captive breeding is far too low, innovative technologies have to be developed. Induced pluripotent stem cells (iPSCs) are a powerful tool to fight extinction. They give rise to each cell within the body including gametes, and provide a unique modality to preserve genetic material across time. Additionally, they enable studying species-specific developmental processes.</jats:p><jats:p>Here, we generate iPSCs from the last male Malaysian SR Kertam, who died in 2019, and characterize them comprehensively. Differentiation in cells of the three germ layers and cerebral organoids demonstrate their high quality and great potential for supporting rescue of this critically endangered species.</jats:p><jats:sec><jats:title>HIGHLIGHTS</jats:title><jats:list list-type="simple"><jats:list-item><jats:label>-</jats:label><jats:p>Characterization of Sumatran Rhino (SR) fibroblasts</jats:p></jats:list-item><jats:list-item><jats:label>-</jats:label><jats:p>Generation of SR induced pluripotent stem cells (SR-iPSCs)</jats:p></jats:list-item><jats:list-item><jats:label>-</jats:label><jats:p>SR-iPSCs generate cells of the three germ layers</jats:p></jats:list-item><jats:list-item><jats:label>-</jats:label><jats:p>SR-iPSCs give rise to cerebral organoids</jats:p></jats:list-item></jats:list></jats:sec>
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935418
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Gout drug colchicine doesn’t lessen COVID-19 severity or stave off risk of death
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Gout drug colchicine doesn’t lessen COVID-19 severity or stave off risk of death
Nor does it cut hospital stay and is associated with high side effect risk
Colchicine, a cheap anti-inflammatory drug normally used to treat gout, doesn’t lessen COVID-19 severity or stave off the risk of death from the infection in hospital patients, finds a pooled analysis of the available evidence, published in the open access journal RMD Open.
What’s more, it’s associated with a high risk of side effects, particularly diarrhoea, the analysis shows.
Early observational studies suggested that colchicine might be a useful addition to the treatments available for COVID-19 infection, and it has already found its way into clinical practice in some places.
In a bid to clarify its safety and effectiveness, the researchers trawled research databases looking for relevant comparative clinical trial data on the use of the drug for the treatment of COVID-19 infection, published up to July 2021.
The researchers wanted to find out if colchicine reduced the risk of death, the need for ventilatory support, intensive care admission and length of hospital stay; and if its use was associated with any particular side effects.
They applied the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach to assess the quality of the evidence for each of these outcomes.
Observational studies, laboratory studies, animal studies, and studies with fewer than 10 participants were all excluded.
Out of 69 full texts assessed, 6 randomised controlled trials involving 16,148 patients with varying degrees of severity of COVID-19 were included in the pooled data analysis.
This showed that there was no significant reduction in the risk of death (6 studies), the need for ventilatory support (5 studies), admission to intensive care (3 studies), length of hospital stay (4 studies) or serious side effects (3 studies) between those patients treated with colchicine and those given usual supportive care only.
Patients taking colchicine also had 58% higher rates of side effects and almost double the risk of diarrhoea than those given supportive care.
The GRADE quality of the evidence was moderate for most of the outcomes studied.
The researchers caution: “Our findings on colchicine should be interpreted cautiously due to the inclusion of open labelled randomised clinical trials. The analysis of efficacy and safety outcomes are based on a small number of [randomised controlled trials] in control interventions.”
But they conclude: “Colchicine does not reduce the risk of mortality, need for ventilatory support, intensive care unit admission or length of hospital stay among patients with COVID-19. There is no additional benefit of adding colchicine to supportive care in the management of patients with COVID-19.”
RMD Open
10.1136/rmdopen-2021-001746
Meta-analysis
People
Efficacy and safety of colchicine in COVID-19: a meta-analysis of randomised controlled trials
22-Nov-2021
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10.1136/rmdopen-2021-001746
| 2,021 |
RMD Open
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Efficacy and safety of colchicine in COVID-19: a meta-analysis of randomised controlled trials
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Background Colchicine, an anti-inflammatory drug is prescribed nowadays for COVID-19. In this meta-analysis, we evaluated efficacy and safety of colchicine in patients with COVID-19. Methods We searched databases for randomised controlled studies evaluating efficacy and/or safety of colchicine as compared with supportive care in patients with COVID-19. The efficacy outcomes were mortality, ventilatory support, intensive care unit (ICU) admission and length of hospital stay. The safety outcomes were adverse events, serious adverse events and diarrhoea. A meta-analytical summary was estimated using random effects model through Mantle-Hanzle method. An I 2 test was used to assess heterogeneity. The Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach was used to assess quality of evidence for each outcome. Results Out of 69 full texts assessed, 6 studies (16148 patients with COVID-19) were included in meta-analysis. Patients receiving colchicine did not show significant reduction in mortality (risk difference, RD −0.00 (95% CI −0.01 to 0.01), I 2 =15%), ventilatory support (risk ratio, RR 0.67 (95% CI 0.38 to 1.21), I 2 =47%), ICU admission (RR 0.49 (95% CI 0.19 to 1.25), I 2 =34%), length of hospital stay (mean difference: −1.17 (95% CI −3.02 to 0.67), I 2 =77%) and serious adverse events (RD −0.01 (95% CI −0.02 to 0.00), I 2 =28%) than those who received supportive care only. Patients receiving colchicine had higher rates of adverse events (RR 1.58 (95% CI 1.07 to 2.33), I 2 =81%) and diarrhoea (RR 1.93 (95% CI 1.62 to 2.29), I 2 =0%) than supportive care treated patients. The GRADE quality of evidence was moderate for most outcomes. Conclusion The moderate quality evidence suggests no benefit of addition of colchicine to the standard care regimen in patients with COVID-19.
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906197
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Study shows promising new web approach to prevent firearm suicide
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Access to firearms and other lethal methods of suicide during periods of risk can make it more likely that a suicide attempt will end in death. Yet many patients with suicidal thoughts or behaviors receive no counseling about this from healthcare providers, and many have questions about options for firearm or medication storage.
To address the issue, clinicians and researchers at the University of Colorado School of Medicine at the Anschutz Medical Campus partnered with Grit Digital Health. The team created Lock to Live, a web resource to help suicidal adults - and family, friends or providers - make decisions about reducing access to firearms, medications, and other potential suicide methods.
The self-administered online tool guides a person through detailed questions on storage factors and personal preferences. It then displays storage or disposal options for firearms and medications, including logistical considerations like cost and legal issues.
A pilot trial for Lock to Live was completed at three large emergency departments in Colorado to test the feasibility and acceptability of the tool for adults with suicidal thoughts or behavior. The results were published today in the Journal of Medical Internet Research.
"Efforts in healthcare settings, like providing this tool to change how dangerous items are stored, can make a big difference for people in crisis," said Emmy Betz, MD, MPH, associate professor of emergency medicine at the University of Colorado School of Medicine and director of the project. "This isn't about gun control. It's about helping people take action to keep themselves and their loved ones safe during tough times."
Over ten months, 49 adult patients were enrolled in the trial, with 33 randomized to the Lock to Live intervention group and 16 to the control group. The results include:
Interest in the Lock to Live resource was very high among adults with acute suicide risk. Almost all reported they would recommend it to someone in the same situation.
Participants overwhelmingly found the tool to be useful, informative, and respectful of their values with regard to firearm ownership.
Seventy three percent wanted a print-out of the storage recommendations.
Additionally, the tool proved to be feasible for use in a clinical setting. There were no issues accessing the content via tablet in the emergency department and it didn't interrupt the patient experience, taking only six minutes to complete.
"Lock to Live is an exciting new tool. We don't know yet if it changes behavior or home storage, but other ongoing studies should help answer that question. Its web format has the potential for rapid and widespread dissemination and integration into suicide prevention efforts," said Deborah Azrael, PhD, Director of Research, Harvard Injury Control Research Center, Harvard School of Public Health and co-investigator on the study. ###
About the University of Colorado Anschutz Medical Campus
The University of Colorado Anschutz Medical Campus is a world-class medical destination at the forefront of transformative science, medicine, education, and patient care. The campus encompasses the University of Colorado health professional schools, more than 60 centers and institutes, and two nationally ranked hospitals that treat more than 2 million adult and pediatric patients each year. Innovative, interconnected and highly collaborative, together we deliver life-changing treatments, patient care, professional training, and conduct world-renowned research powered by more than $550 million in research awards. For more information, visit https://www.cuanschutz.edu/
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10.2196/16253
| 2,019 |
Journal of Medical Internet Research
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Lock to Live—An Interactive Web-Based Lethal Means Safety Decision Aid for Suicidal Adults: Pilot Randomized Controlled Trial
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Counseling to reduce access to lethal means such as firearms and medications is recommended for suicidal adults but does not routinely occur. We developed the Web-based Lock to Live (L2L) decision aid to help suicidal adults and their families choose options for safer home storage.
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681066
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THC and CBD content on labels of medicinal cannabis products may not be accurate
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BOSTON - Medical cannabis products are not always what they seem, according to a new study led by researchers at the Massachusetts General Hospital (MGH).
In fact, the contents of these products can vary considerably from distributors' claims, according to the study, published in JAMA Network Open. This is particularly important when THC, the metabolite responsible for the "high" cannabis provides, is present in medical cannabis products labeled to be CBD only.
As more states legalize cannabis sales, demand has increased. However, there is little consistency in product regulation or labeling, unlike the strict regulation of medicines purchased through a pharmacy. As a result, labeling is often not accurately informing patients of the content of the cannabis-derived products they buy.
The psychoactive metabolite in cannabis is Δ9-tetrahydrocannabinol (THC). Cannabis products containing THC are federally banned, but states have been passing laws legalizing these products. This has in turn led to a patchwork of laws that have varied impact on guaranteeing that consumers get what they expect. Cannabidiol (CBD) does not come under FDA regulation.
In this study, researchers analyzed urine samples from nearly 100 patients enrolled in a clinical trial of the effect of medical cannabis for anxiety, depression, pain or insomnia. The purpose of the study was to see if these products were delivering the ingredients patients expected.
The results showed no CBD in about a third of the urine samples from patients who said they were using cannabis products that were CBD-dominant or had roughly equal parts CBD and THC. THC was detected in almost 80% of those samples, including among patients who thought they were only receiving CBD.
"People are buying products they think are THC-free but in fact contain a significant amount of THC," says Jodi M. Gilman, PhD, the paper's lead author and an investigator in the Center for Addiction Medicine in MGH's Department of Psychiatry. "One patient reported that she took a product she thought only contained CBD, and then when driving home that day she felt intoxicated, disoriented and very scared."
Exactly how the cannabis was consumed mattered, too. About 20% of patients who reported that they were vaping their medical cannabis had no detectable levels of THC or CBD metabolites in their urine samples. This suggests that some vaping devices may not heat cannabis products sufficiently for patients to even inhale the active ingredients.
"A lot of questions about the content of the products and their effects remain," says Gilman. "Patients need more information about what's in these products and what effects they can expect."
###
About the Massachusetts General Hospital
Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In August 2020, Mass General was named #6 in the U.S. News & World Report list of "America's Best Hospitals."
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10.1001/jamanetworkopen.2021.5490
| 2,021 |
JAMA Network Open
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Variation in Cannabinoid Metabolites Present in the Urine of Adults Using Medical Cannabis Products in Massachusetts
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Among adults using medical cannabis frequently and recently, THC and CBD metabolite concentrations in urine often differed from expected exposure. Approximately one-third of samples from people reporting using CBD-dominant products contained no measurable CBD metabolite. Nearly 1 in 5 samples from those using vaped cannabis contained no detectable cannabinoids....
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965481
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International study: Improved air quality accelerates global warming in recent decades
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Global warming is caused by the emission of greenhouse gases. According to the Intergovernmental Panel on Climate Change (IPCC), by 2019 the temperature had risen by 1.1 degrees Celsius compared to pre-industrial levels. However, at the same time, the combustion of fossil fuels emits aerosols, in the form of pollutant particles such as soot or sulfuric acid, which cool our climate. They reflect sunlight and also increase the reflectivity of clouds. According to the IPCC, the presence of aerosols in the atmosphere caused the climate to be 0.5 degrees Celsius cooler in 2019 than without them. Other effects such as land use change also play a role.
In a new international analysis, Professor Johannes Quaas, a meteorologist at Leipzig University, and colleagues from across Europe, China, and the US have now documented robust evidence of this effect on the climate of improved air quality. “We analysed data from NASA’s Terra and Aqua satellites. They have been providing comprehensive satellite observations of the Earth since the year 2000, measuring incoming and outgoing radiation, but also clouds and aerosol pollution. The latter has decreased significantly across North America, Europe and East Asia since 2000,” says Professor Johannes Quaas, lead author of the study, which was initiated in a meeting by the two European research projects CONSTRAIN and FORCES.
This has also reduced the cooling effect of aerosols. Compared to the year 2000, it has led to an increase in the warming effect that is up to 50 per cent of the one by CO2 increases in the same period. This means an acceleration of the drivers of global warming compared to the previous period. “Our study should not be interpreted to mean that we should now be emitting more aerosols to cool the climate. On the contrary: aerosols are harmful to human health and the environment, which is why we need to keep reducing emissions,” Quaas concludes. And it is why air quality legislation has become increasingly stringent since the 1970s and is being implemented by more and more countries. Professor Quaas and his colleagues on the new study stress the ever more urgent need for rapid and strong reductions in greenhouse gas emissions.
Atmospheric Chemistry and Physics
10.5194/acp-22-12221-2022
Observational study
Robust evidence for reversal of the trend in aerosol effective climate forcing
21-Sep-2022
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10.5194/acp-22-12221-2022
| 2,022 |
Atmospheric chemistry and physics
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Robust evidence for reversal of the trend in aerosol effective climate forcing
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Abstract. Anthropogenic aerosols exert a cooling influence that offsets part of the greenhouse gas warming. Due to their short tropospheric lifetime of only several days, the aerosol forcing responds quickly to emissions. Here, we present and discuss the evolution of the aerosol forcing since 2000. There are multiple lines of evidence that allow us to robustly conclude that the anthropogenic aerosol effective radiative forcing (ERF) – both aerosol–radiation interactions (ERFari) and aerosol–cloud interactions (ERFaci) – has become less negative globally, i.e. the trend in aerosol effective radiative forcing changed sign from negative to positive. Bottom-up inventories show that anthropogenic primary aerosol and aerosol precursor emissions declined in most regions of the world; observations related to aerosol burden show declining trends, in particular of the fine-mode particles that make up most of the anthropogenic aerosols; satellite retrievals of cloud droplet numbers show trends in regions with aerosol declines that are consistent with these in sign, as do observations of top-of-atmosphere radiation. Climate model results, including a revised set that is constrained by observations of the ocean heat content evolution show a consistent sign and magnitude for a positive forcing relative to the year 2000 due to reduced aerosol effects. This reduction leads to an acceleration of the forcing of climate change, i.e. an increase in forcing by 0.1 to 0.3 W m−2, up to 12 % of the total climate forcing in 2019 compared to 1750 according to the Intergovernmental Panel on Climate Change (IPCC).
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777617
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How to track and trace a protein: Nanosensors monitor intracellular deliveries
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Researchers at the University of Basel's Biozentrum have developed a method for tracing the movement of proteins within the cell. They tagged proteins with tiny nanosensors, so-called nanobodies, which enable the scientists to live track and trace the proteins' pathway through the cell. The method described in the current issue of PNAS is suitable for a wide range of research purposes.
Membrane proteins are a basic component of each individual cell of the human body and play a vital role in the cell's structure, metabolism and transport. They ensure that many substances, such as hormones and other proteins, are transported from the cell surface into the cell or carried out again.
It is quite easy to determine the distribution of membrane proteins in the cell. Tracking the paths that they take within the cell and identifying their intended destination is considerably more difficult. The new nanobody tool, developed by the Spiess research group at the Biozentrum, University of Basel, makes it possible to observe the movement of proteins into and out of the cell. In the future, this quantitative method can also be applied to elucidate the molecular transport mechanisms inside the cells.
Tiny antibodies as nanosensors
The researchers used so-called nanobodies, tiny antibody fragments. These consist solely of a single protein chain and so, in contrast to antibodies that are composed of four proteins, they have the advantage to be only about one-tenth of the size, very compact and stable. "Nanobodies were originally obtained from camels and llamas. We altered the nanobodies, so that we could produce them with the help of bacteria and use them as nanosensors," says Professor Martin Spiess.
Nano tags enable live tracking
The nanobodies can be genetically altered to fluoresce. "We attach them like a tag to the targeted protein, where they remain fastened no matter which path the protein takes to enter the cell," explains Dominik Buser, a postdoc in Martin Spiess's lab and the first author of the study. Using a microscope, the path of entry and distribution of surface proteins can be observed in living cells.
"The nanosensor with its fluorescent dye makes the exact movements of the proteins visible. This enables us to follow the natural pathways taken by the proteins into the cell, as well as the speed of transport within the cell." Furthermore, the researchers altered the nanobodies, in a way that the proteins could be localized in the cell by the electron microscope.
In the future, the research team plans to apply this new method to track and trace various proteins and to more closely study their transport pathways.
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10.1073/pnas.1801865115
| 2,018 |
Proceedings of the National Academy of Sciences
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A versatile nanobody-based toolkit to analyze retrograde transport from the cell surface
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Retrograde transport of membranes and proteins from the cell surface to the Golgi and beyond is essential to maintain homeostasis, compartment identity, and physiological functions. To study retrograde traffic biochemically, by live-cell imaging or by electron microscopy, we engineered functionalized anti-GFP nanobodies (camelid VHH antibody domains) to be bacterially expressed and purified. Tyrosine sulfation consensus sequences were fused to the nanobody for biochemical detection of trans-Golgi arrival, fluorophores for fluorescence microscopy and live imaging, and APEX2 (ascorbate peroxidase 2) for electron microscopy and compartment ablation. These functionalized nanobodies are specifically captured by GFP-modified reporter proteins at the cell surface and transported piggyback to the reporters' homing compartments. As an application of this tool, we have used it to determine the contribution of adaptor protein-1/clathrin in retrograde transport kinetics of the mannose-6-phosphate receptors from endosomes back to the trans-Golgi network. Our experiments establish functionalized nanobodies as a powerful tool to demonstrate and quantify retrograde transport pathways.
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795302
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Simulations show fundamental interactions inside the cell
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Actin filaments have several important functions inside cells. For one, they support the cell membrane by binding to it. However, scientists did not know exactly how the actin interacts with the membrane lipids. Simulations performed at the University of Groningen, supported by experiments, provide a molecular view on this very fundamental process. The results were published in the journal Proceedings of the National Academy of Sciences on 2 March.
Actin filaments are involved in many important processes in eukaryotic cells, from motility to division to the contraction of muscle fibers. Actin can also form a network underneath the lipid bilayer. Here, it provides additional support for this structure, while curved filaments also play a role in cell division, when the membrane needs to constrict. Despite its importance, the molecular processes underlying the binding of actin to cell membranes is still not clear.
Simulations
'The literature provides conflicting results,' says University of Groningen Professor of Molecular Dynamics Siewert-Jan Marrink. 'All agree that actin, which is negatively charged, could bind to positively charged lipids and some say that they can even bind to membranes with no positive or even a negative charge.' The latter is relevant for the biological situation as normal cell membranes carry a negative charge on the inside.
Marrink and his colleagues, therefore, performed molecular dynamics simulations of the interaction between lipids and actin. They used the Martini coarse-grained forcefield, which was developed by Marrink and is now used worldwide.
Molecular glue
By varying the components in the simulation, the scientists discovered that the ions that are present define the binding process. Marrink: 'Actin could only bind to negatively charged lipids in the presence of calcium ions. The two positive charges of calcium act as a kind of molecular glue.' In contrast, in the presence of positively charged lipids, calcium ions inhibited the binding of actin. The results of this simulation were confirmed by experiments performed in Professor Gijsje Koenderink's lab at Delft University of Technology.
'The concentrations of calcium that were required in the simulations are higher than you would find inside cells,' says Marrink. 'However, calcium ions tend to bind to membrane lipids, so the local concentration could be high enough.'
Synthetic cell
The results provide the first clear picture of actin-binding to membrane lipids. 'We want to use this in a national effort to build an artificial cell,' Marrink explains. The Dutch BaSyC (Building a Synthetic Cell) project involves many different steps and one of them is constructing membranes. 'These need to be reinforced with actin, so we have to understand how to control the interaction between the filaments and the lipid membrane. And we need to guide division of the artificial cell, where actin is needed for constriction.'
###
Reference: Carsten F. E. Schroer, Lucia Baldauf, Lennard van Buren, Tsjerk A. Wassenaar, Manuel N. Melo, Gijsje H. Koenderink, and Siewert J. Marrink: Charge-dependent interactions of monomeric and filamentous actin with lipid bilayers. PNAS, 2 March 2020
Simple Science Summary
Actin fibers are important for the shape, strength, and movement of cells. They can bind to the cell membrane, providing it with support. However, exactly how they bind is unknown. University of Groningen scientists used computer simulations to investigate the interaction of actin with the cell membrane. They discovered that positively charged calcium ions are important: these act as a kind of glue between the negatively charged actin and negatively charged lipids. These results are important for the construction of a synthetic cell.
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10.1073/pnas.1914884117
| 2,020 |
Proceedings of the National Academy of Sciences
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Charge-dependent interactions of monomeric and filamentous actin with lipid bilayers
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The cytoskeletal protein actin polymerizes into filaments that are essential for the mechanical stability of mammalian cells. In vitro experiments showed that direct interactions between actin filaments and lipid bilayers are possible and that the net charge of the bilayer as well as the presence of divalent ions in the buffer play an important role. In vivo, colocalization of actin filaments and divalent ions are suppressed, and cells rely on linker proteins to connect the plasma membrane to the actin network. Little is known, however, about why this is the case and what microscopic interactions are important. A deeper understanding is highly beneficial, first, to obtain understanding in the biological design of cells and, second, as a possible basis for the building of artificial cortices for the stabilization of synthetic cells. Here, we report the results of coarse-grained molecular dynamics simulations of monomeric and filamentous actin in the vicinity of differently charged lipid bilayers. We observe that charges on the lipid head groups strongly determine the ability of actin to adsorb to the bilayer. The inclusion of divalent ions leads to a reversal of the binding affinity. Our in silico results are validated experimentally by reconstitution assays with actin on lipid bilayer membranes and provide a molecular-level understanding of the actin–membrane interaction.
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958973
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Robot dog learns to walk in one hour
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Embargo Monday July 18, 2022 at 4 pm London time / 11 am US eastern time
Stuttgart – A newborn giraffe or foal must learn to walk on its legs as fast as possible to avoid predators. Animals are born with muscle coordination networks located in their spinal cord. However, learning the precise coordination of leg muscles and tendons takes some time. Initially, baby animals rely heavily on hard-wired spinal cord reflexes. While somewhat more basic, motor control reflexes help the animal to avoid falling and hurting themselves during their first walking attempts. The following, more advanced and precise muscle control must be practiced, until eventually the nervous system is well adapted to the young animal’s leg muscles and tendons. No more uncontrolled stumbling – the young animal can now keep up with the adults.
Researchers at the Max Planck Institute for Intelligent Systems (MPI-IS) in Stuttgart conducted a research study to find out how animals learn to walk and learn from stumbling. They built a four-legged, dog-sized robot, that helped them figure out the details.
"As engineers and roboticists, we sought the answer by building a robot that features reflexes just like an animal and learns from mistakes," says Felix Ruppert, a former doctoral student in the Dynamic Locomotion research group at MPI-IS. "If an animal stumbles, is that a mistake? Not if it happens once. But if it stumbles frequently, it gives us a measure of how well the robot walks."
Felix Ruppert is first author of "Learning Plastic Matching of Robot Dynamics in Closed-loop Central Pattern Generators", which will be published July 18, 2022 in the prestigious journal Nature Machine Intelligence.
Learning algorithm optimizes virtual spinal cord
After learning to walk in just one hour, Ruppert's robot makes good use of its complex leg mechanics. A Bayesian optimization algorithm guides the learning: the measured foot sensor information is matched with target data from the modeled virtual spinal cord running as a program in the robot’s computer. The robot learns to walk by continuously comparing sent and expected sensor information, running reflex loops, and adapting its motor control patterns.
The learning algorithm adapts control parameters of a Central Pattern Generator (CPG). In humans and animals, these central pattern generators are networks of neurons in the spinal cord that produce periodic muscle contractions without input from the brain. Central pattern generator networks aid the generation of rhythmic tasks such as walking, blinking or digestion. Furthermore, reflexes are involuntary motor control actions triggered by hard-coded neural pathways that connect sensors in the leg with the spinal cord.
As long as the young animal walks over a perfectly flat surface, CPGs can be sufficient to control the movement signals from the spinal cord. A small bump on the ground, however, changes the walk. Reflexes kick in and adjust the movement patterns to keep the animal from falling. These momentary changes in the movement signals are reversible, or 'elastic', and the movement patterns return to their original configuration after the disturbance. But if the animal does not stop stumbling over many cycles of movement – despite active reflexes – then the movement patterns must be relearned and made 'plastic', i.e., irreversible. In the newborn animal, CPGs are initially not yet adjusted well enough and the animal stumbles around, both on even or uneven terrain. But the animal rapidly learns how its CPGs and reflexes control leg muscles and tendons.
The same holds true for the Labrador-sized robot-dog named "Morti". Even more, the robot optimizes its movement patterns faster than an animal, in about one hour. Morti’s CPG is simulated on a small and lightweight computer that controls the motion of the robot’s legs. This virtual spinal cord is placed on the quadruped robot’s back where the head would be. During the hour it takes for the robot to walk smoothly, sensor data from the robot’s feet are continuously compared with the expected touch-down predicted by the robot’s CPG. If the robot stumbles, the learning algorithm changes how far the legs swing back and forth, how fast the legs swing, and how long a leg is on the ground. The adjusted motion also affects how well the robot can utilize its compliant leg mechanics. During the learning process, the CPG sends adapted motor signals so that the robot henceforth stumbles less and optimizes its walking. In this framework, the virtual spinal cord has no explicit knowledge about the robot’s leg design, its motors and springs. Knowing nothing about the physics of the machine, it lacks a robot ‘model’.
"Our robot is practically ‘born’ knowing nothing about its leg anatomy or how they work," Ruppert explains. "The CPG resembles a built-in automatic walking intelligence that nature provides and that we have transferred to the robot. The computer produces signals that control the legs’ motors, and the robot initially walks and stumbles. Data flows back from the sensors to the virtual spinal cord where sensor and CPG data are compared. If the sensor data does not match the expected data, the learning algorithm changes the walking behavior until the robot walks well, and without stumbling. Changing the CPG output while keeping reflexes active and monitoring the robot stumbling is a core part of the learning process."
Energy efficient robot dog control
Morti’s computer draws only five watts of power in the process of walking. Industrial quadruped robots from prominent manufacturers, which have learned to run with the help of complex controllers, are much more power hungry. Their controllers are coded with the knowledge of the robot’s exact mass and body geometry – using a model of the robot. They typically draw several tens, up to several hundred watts of power. Both robot types run dynamically and efficiently, but the computational energy consumption is far lower in the Stuttgart model. It also provides important insights into animal anatomy.
"We can't easily research the spinal cord of a living animal. But we can model one in the robot," says Alexander Badri-Spröwitz, who co-authored the publication with Ruppert and heads the Dynamic Locomotion Research Group. "We know that these CPGs exist in many animals. We know that reflexes are embedded; but how can we combine both so that animals learn movements with reflexes and CPGs? This is fundamental research at the intersection between robotics and biology. The robotic model gives us answers to questions that biology alone can't answer."
Nature Machine Intelligence
10.1038/s42256-022-00505-4
Experimental study
Learning plastic matching of robot dynamics in closed-loop central pattern generators
18-Jul-2022
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10.1038/s42256-022-00505-4
| 2,022 |
Nature Machine Intelligence
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Learning plastic matching of robot dynamics in closed-loop central pattern generators
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Abstract Animals achieve agile locomotion performance with reduced control effort and energy efficiency by leveraging compliance in their muscles and tendons. However, it is not known how biological locomotion controllers learn to leverage the intelligence embodied in their leg mechanics. Here we present a framework to match control patterns and mechanics based on the concept of short-term elasticity and long-term plasticity. Inspired by animals, we design a robot, Morti, with passive elastic legs. The quadruped robot Morti is controlled by a bioinspired closed-loop central pattern generator that is designed to elastically mitigate short-term perturbations using sparse contact feedback. By minimizing the amount of corrective feedback on the long term, Morti learns to match the controller to its mechanics and learns to walk within 1 h. By leveraging the advantages of its mechanics, Morti improves its energy efficiency by 42% without explicit minimization in the cost function.
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