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An orally bioavailable SARS-CoV-2 main protease inhibitor exhibits improved affinity and reduced sensitivity to mutations Sci. Transl. Med. (IF 17.1) Pub Date : 2024-03-13 Michael Westberg, Yichi Su, Xinzhi Zou, Pinghan Huang, Arjun Rustagi, Jaishree Garhyan, Puja Bhavesh Patel, Daniel Fernandez, Yan Wu, Chenzhou Hao, Chieh-Wen Lo, Marwah Karim, Lin Ning, Aimee Beck, Panatda Saenkham-Huntsinger, Vivian Tat, Aleksandra Drelich, Bi-Hung Peng, Shirit Einav, Chien-Te K. Tseng, Catherine Blish, Michael Z. Lin
Inhibitors of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) such as nirmatrelvir (NTV) and ensitrelvir (ETV) have proven effective in reducing the severity of COVID-19, but the presence of resistance-conferring mutations in sequenced viral genomes raises concerns about future drug resistance. Second-generation oral drugs that retain function against these mutants
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A day in the life of a medical student from Ukraine BMJ (IF 105.7) Pub Date : 2024-03-18 Éabha Lynn
In our series taking you to meet medical students from across the globe from the comfort of your own home, BMJ student spoke to a medical student who has made a truly international curriculum for herself and her peers in the wake of war and destruction in her home country You have just set off from home to attend your placement or to meet your friends for a cocktail or a cup of coffee. Life goes on
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Switching from disposable to reusable PPE BMJ (IF 105.7) Pub Date : 2024-03-18 Rebecca Bromley-Dulfano, Joshua Chan, Navami Jain, James Marvel
### What you need to know Sustainable sourcing, use, and disposal of personal protective equipment (PPE) can help healthcare providers reduce the environmental impacts of their work. In this article we review supporting evidence and provide guidance for healthcare institutions to adopt reusable forms of PPE as safe, cost saving, and sustainable alternatives to single use disposables. The first step
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Peter McGuffin: psychiatrist and researcher who set out to find better ways of defining severe mental illness BMJ (IF 105.7) Pub Date : 2024-03-18 John Illman
Photo credit: King’s College London There was always something different about Peter McGuffin, professor of psychiatric genetics at the Institute of Psychiatry, Psychology, and Neuroscience Centre, London (IOPPNC). In 1963, when many 15 year olds discovered the Beatles, he found psychoanalysis. After locating Freud’s introductory lectures in his local library on the Isle of Wight, he decided to become
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Evidence based exercise prescriptions in primary care BMJ (IF 105.7) Pub Date : 2024-03-18 Ediriweera Desapriya, Shaluka Manchanayake, Hasara Illuppelle, Peter Tiu, Crystal Ma
Noetel and colleagues’ study provides compelling evidence supporting the effectiveness of various exercise modalities in alleviating symptoms of depression.1 This empowers primary care doctors to make recommendations grounded in solid evidence, tailored to the unique preferences, abilities, and needs of individual patients. Many types of exercise—for example, walking, jogging, strength training, yoga
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Long covid and myalgic encephalomyelitis/chronic fatigue syndrome are overlapping conditions BMJ (IF 105.7) Pub Date : 2024-03-18 Vikki McKeever
Ladds and colleagues’ practice pointer explores the complexities of post-viral cognitive symptoms and provides guidance on management strategies.1 But there is no mention of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Given that debilitating fatigue, post-exertional malaise, and cognitive issues are the core symptoms of ME/CFS it would be prudent to describe the clear overlaps between
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ONS refines method to estimate excess deaths BMJ (IF 105.7) Pub Date : 2024-03-18 Veena Raleigh
This upgrade should improve our understanding of short term changes in mortality As the UK emerges from the ravages of the pandemic, the Office for National Statistics (ONS) has announced a new method for estimating excess deaths in the UK.1 Measurement of excess deaths became widely used in 2020 when timely data on the effect of covid-19 on mortality was vital for monitoring the spread of the virus
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Use of nitrous oxide for execution is a concerning development in ongoing medicalisation of the death penalty BMJ (IF 105.7) Pub Date : 2024-03-18 British Medical Journal Publishing Group
This article ( BMJ 2024;384:q593, doi:10.1136/bmj.q593 …
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Can I share my political views online? BMJ (IF 105.7) Pub Date : 2024-03-18 Abi Rimmer
While social media may seem like a place for sharing personal feelings rather than professional opinions, doctors must remain aware of how they could be perceived, Abi Rimmer hears Emma Davies, medicolegal consultant at the Medical Protection Society, says, “Given the conflicts around the world and the pressures on the NHS, it’s expected that we’ll have our own opinions on these emotive matters. Social
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Statins, risk, and personalised care BMJ (IF 105.7) Pub Date : 2024-03-18 Sam Finnikin, Brian Finney, Rani Khatib, James McCormack
Sam Finnikin and colleagues argue that guidelines should focus less on population level risk thresholds and more on shared decision making conversations based on individualised risk and patient preferences Statins are the most prescribed medications in England with over 82 million prescriptions issued in the 12 months to July 2023.1 However, the 2023 update of guidelines from the UK National Institute
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UK Public Health Science 2024: a call for abstracts Lancet (IF 168.9) Pub Date : 2024-03-18 Daniel R R Bradford, Francesco Aletta, UK Public Health Science conference organising committee
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Music and medicine: quickening the tempo of progress Lancet (IF 168.9) Pub Date : 2024-03-18 Wen G Chen, Emmeline Edwards, Sunil Iyengar, Robert Finkelstein, Deborah F Rutter, Renée Fleming, Francis S Collins
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A timeline of biomarker changes before Alzheimer’s disease Nat. Med. (IF 82.9) Pub Date : 2024-03-15
Longitudinal data from the China Cognition and Aging Study map the sequential biomarker changes that begin almost two decades before clinical onset of Alzheimer’s disease.
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Verbose robots, and why some people love Bach: Books in Brief Nature (IF 64.8) Pub Date : 2024-03-15
Andrew Robinson reviews five of the best science picks.
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A year in the life: what I learnt from using a time-tracking spreadsheet Nature (IF 64.8) Pub Date : 2024-03-15
A low-tech solution helped Megan Rogers to increase her productivity and maintain a good work–life balance.
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Building a heart atlas: researchers map organ in stunning detail Nature (IF 64.8) Pub Date : 2024-03-13
Cutting edge imaging techniques reveal how cells organise as the heart develops.
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Mobile delivery of COVID-19 vaccines improved uptake in rural Sierra Leone Nature (IF 64.8) Pub Date : 2024-03-13 Alison Buttenheim, Harsha Thirumurthy
Vaccination rates in rural areas improve when vaccines are delivered.
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What I Do Not Tell the Medical Student N. Engl. J. Med. (IF 158.5) Pub Date : 2024-03-16 Erica Andrist
What do we tell medical students who are wowed by senior physicians’ power and control over patients’ conditions and outcomes when we know this power and control are largely illusory?
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Rhino-orbital-cerebral Mucormycosis N. Engl. J. Med. (IF 158.5) Pub Date : 2024-03-16 Cristian-Mihail Niculae, Laura Craciun
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Bird-flu threat disrupts Antarctic penguin studies Nature (IF 64.8) Pub Date : 2024-03-15
Projects have been cancelled in an effort to curb the virus’s spread.
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Inside China’s giant underground neutrino lab Nature (IF 64.8) Pub Date : 2024-03-15
Due to come online this year, the JUNO facility will help to determine which type of neutrino has the highest mass — one of the biggest mysteries in physics.
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People, passion, publishable: an early-career researcher’s checklist for prioritizing projects Nature (IF 64.8) Pub Date : 2024-03-15
Stuck between several lines of research? Here’s how we decide which ones to pursue, say Elizabeth Tenney, Jacqueline Chen and McKenzie Preston.
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First US drug approved for a liver disease surging around the world Nature (IF 64.8) Pub Date : 2024-03-15
A therapy called resmetirom improves hallmarks of an obesity-linked condition that can lead to liver failure.
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A fundamental constant in physics gets an update Nature (IF 64.8) Pub Date : 2024-03-14
Scientists controlled a hydrogen atom with electric fields to derive a highly precise estimate of the Rydberg constant.
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Ditching ‘Anthropocene’: why ecologists say the term still matters Nature (IF 64.8) Pub Date : 2024-03-14
Beyond stratigraphic definitions, the name has broader significance for understanding humans’ place on Earth.
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Neural and behavioural state switching during hippocampal dentate spikes Nature (IF 64.8) Pub Date : 2024-03-13 Jordan S. Farrell, Ernie Hwaun, Barna Dudok, Ivan Soltesz
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AIRE relies on Z-DNA to flag gene targets for thymic T cell tolerization Nature (IF 64.8) Pub Date : 2024-03-13 Yuan Fang, Kushagra Bansal, Sara Mostafavi, Christophe Benoist, Diane Mathis
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Blueprinting extendable nanomaterials with standardized protein blocks Nature (IF 64.8) Pub Date : 2024-03-13 Timothy F. Huddy, Yang Hsia, Ryan D. Kibler, Jinwei Xu, Neville Bethel, Deepesh Nagarajan, Rachel Redler, Philip J. Y. Leung, Connor Weidle, Alexis Courbet, Erin C. Yang, Asim K. Bera, Nicolas Coudray, S. John Calise, Fatima A. Davila-Hernandez, Hannah L. Han, Kenneth D. Carr, Zhe Li, Ryan McHugh, Gabriella Reggiano, Alex Kang, Banumathi Sankaran, Miles S. Dickinson, Brian Coventry, T. J. Brunette
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Drought triggers and sustains overnight fires in North America Nature (IF 64.8) Pub Date : 2024-03-13 Kaiwei Luo, Xianli Wang, Mark de Jong, Mike Flannigan
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Fork coupling directs DNA replication elongation and termination Science (IF 56.9) Pub Date : 2024-03-15 Yang Liu, Zhengrong Zhangding, Xuhao Liu, Tingting Gan, Chen Ai, Jinchun Wu, Haoxin Liang, Mohan Chen, Yuefeng Guo, Rusen Lu, Yongpeng Jiang, Xiong Ji, Ning Gao, Daochun Kong, Qing Li, Jiazhi Hu
DNA replication is initiated at multiple loci to ensure timely duplication of eukaryotic genomes. Sister replication forks progress bidirectionally, and replication terminates when two convergent forks encounter one another. To investigate the coordination of replication forks, we developed a replication-associated in situ HiC method to capture chromatin interactions involving nascent DNA. We identify
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Penning micro-trap for quantum computing Nature (IF 64.8) Pub Date : 2024-03-13 Shreyans Jain, Tobias Sägesser, Pavel Hrmo, Celeste Torkzaban, Martin Stadler, Robin Oswald, Chris Axline, Amado Bautista-Salvador, Christian Ospelkaus, Daniel Kienzler, Jonathan Home
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Chatbot AI makes racist judgements on the basis of dialect Nature (IF 64.8) Pub Date : 2024-03-13
Some large language models harbour hidden biases that cannot be removed using standard methods.
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Did ‘alien’ debris hit Earth? Startling claim sparks row at scientific meeting Nature (IF 64.8) Pub Date : 2024-03-13
Astrophysicist Avi Loeb says that an interstellar meteor showered Earth with particles. At a planetary-science conference this week, researchers begged to differ.
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Daily briefing: In most mammal species, males and females are the same size — or females are bigger Nature (IF 64.8) Pub Date : 2024-03-13
Charles Darwin’s claim about male mammals usually being bigger than females is proved wrong. Plus, OpenAI’s Sora can create amazing video from text prompts, and what’s wrong with how we treat the menopause.
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Continuous evolution of compact protein degradation tags regulated by selective molecular glues Science (IF 56.9) Pub Date : 2024-03-15 Jaron A. M. Mercer, Stephan J. DeCarlo, Shourya S. Roy Burman, Vedagopuram Sreekanth, Andrew T. Nelson, Moritz Hunkeler, Peter J. Chen, Katherine A. Donovan, Praveen Kokkonda, Praveen K. Tiwari, Veronika M. Shoba, Arghya Deb, Amit Choudhary, Eric S. Fischer, David R. Liu
Conditional protein degradation tags (degrons) are usually >100 amino acids long or are triggered by small molecules with substantial off-target effects, thwarting their use as specific modulators of endogenous protein levels. We developed a phage-assisted continuous evolution platform for molecular glue complexes (MG-PACE) and evolved a 36–amino acid zinc finger (ZF) degron (SD40) that binds the ubiquitin
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Generalized fear after acute stress is caused by change in neuronal cotransmitter identity Science (IF 56.9) Pub Date : 2024-03-15 Hui-quan Li, Wuji Jiang, Li Ling, Marta Pratelli, Cong Chen, Vaidehi Gupta, Swetha K. Godavarthi, Nicholas C. Spitzer
Overgeneralization of fear to harmless situations is a core feature of anxiety disorders resulting from acute stress, yet the mechanisms by which fear becomes generalized are poorly understood. In this study, we show that generalized fear in mice results from a transmitter switch from glutamate to γ-aminobutyric acid (GABA) in serotonergic neurons of the lateral wings of the dorsal raphe. Similar change
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David Oliver: Senior medical leaders have mishandled doctors’ concerns over physician and anaesthesia associates BMJ (IF 105.7) Pub Date : 2024-03-15 David Oliver
On 13 March the Royal College of Physicians (RCP) held an extraordinary general meeting of fellows to discuss the role of physician associates (PAs) in the NHS.1 Such meetings have been rare events in the college’s history. Its members and fellows aren’t known for being radical firebrands, and medical royal colleges are not trade unions or single issue campaigning charities. We seem to have reached
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When I use a word . . . Medicines regulation—penicillin BMJ (IF 105.7) Pub Date : 2024-03-15 Jeffrey K Aronson
Penicillin has a history that antedates its discovery by Alexander Fleming in London and its isolation and purification by Howard Florey, Ernst Chain, and Norman Heatley in Oxford. Before that it had been used as a raw broth of Penicillium organisms in local treatment of infections such as furuncles and conjunctivitis. After its introduction for parenteral administration and its manufacture in the
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Telehealth enables safe medication abortion in shifting health and legal contexts Nat. Med. (IF 82.9) Pub Date : 2024-03-15 Dana M. Johnson, Abigail R. A. Aiken, Terri-Ann Thompson
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Prolonged benefits of bariatric surgery for patients with Type 2 Diabetes Nat. Med. (IF 82.9) Pub Date : 2024-03-15
People with type 2 diabetes who underwent bariatric surgery compared to medical or lifestyle interventions had better long-term outcomes, such as greater diabetes remission and less reliance on medication.
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The DTC microbiome testing industry needs more regulation Science (IF 56.9) Pub Date : 2024-03-15 Diane E. Hoffmann, Erik C. von Rosenvinge, Mary-Claire Roghmann, Francis B. Palumbo, Daniel McDonald, Jacques Ravel
A growing body of research has suggested the potential for improving human health by better understanding the human microbiome. This research has led to the emergence of a global industry selling direct-to-consumer (DTC) microbiome testing services. Regulation of this industry has been generally ignored despite its having made a mark on the lifestyle health and wellness market. Yet companies’ claims
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Divas, captains, ghosts, ants and bumble-bees: collaborator attitudes explained Nature (IF 64.8) Pub Date : 2024-03-15
Olga Lehmann made sense of challenges she faced in teamwork by analysing how she and her colleagues behaved and what she could have done differently.
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A Black mathematical history Nature (IF 64.8) Pub Date : 2024-03-14
Documentary reveals how Black US scholars shaped today’s mathematics community and provides hope for the future.
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More than 4,000 plastic chemicals are hazardous, report finds Nature (IF 64.8) Pub Date : 2024-03-14
Year-long effort compiles comprehensive database of chemicals in plastics.
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The neuroscientist formerly known as Prince’s audio engineer Nature (IF 64.8) Pub Date : 2024-03-14
Susan Rogers worked with the legendary singer-songwriter before earning a PhD in her 50s on auditory memory and how we listen to music throughout life.
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Do black holes explode? The 50-year-old puzzle that challenges quantum physics Nature (IF 64.8) Pub Date : 2024-03-14
Stephen Hawking’s paradoxical finding that black holes don’t live forever has profound, unresolved implications for the quest for unifying theories of reality.
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Fungal diseases are spreading undetected Nature (IF 64.8) Pub Date : 2024-03-14
Low- and middle-income countries are grappling with widespread shortages of diagnostic tests for infections that kill millions.
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Daily briefing: How Hawking’s paradox still puzzles physicists Nature (IF 64.8) Pub Date : 2024-03-14
On the sixth anniversary of Stephen Hawking’s death, we revisit his landmark paper. Plus, a stunning 3D atlas of the heart and the mysterious rise of cancer in young people.
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These cyborg jellyfish could monitor the changing seas Nature (IF 64.8) Pub Date : 2024-03-13
A hat-like prosthesis helps the invertebrates to swim more efficiently and can be used to carry ocean sensors.
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Couple-close construction of polycyclic rings from diradicals Nature (IF 64.8) Pub Date : 2024-03-13 Alice Long, Christian J. Oswood, Christopher B. Kelly, Marian C. Bryan, David W. C. MacMillan
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US oil and gas system emissions from nearly one million aerial site measurements Nature (IF 64.8) Pub Date : 2024-03-13 Evan D. Sherwin, Jeffrey S. Rutherford, Zhan Zhang, Yuanlei Chen, Erin B. Wetherley, Petr V. Yakovlev, Elena S. F. Berman, Brian B. Jones, Daniel H. Cusworth, Andrew K. Thorpe, Alana K. Ayasse, Riley M. Duren, Adam R. Brandt
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Spatially organized cellular communities form the developing human heart Nature (IF 64.8) Pub Date : 2024-03-13 Elie N. Farah, Robert K. Hu, Colin Kern, Qingquan Zhang, Ting-Yu Lu, Qixuan Ma, Shaina Tran, Bo Zhang, Daniel Carlin, Alexander Monell, Andrew P. Blair, Zilu Wang, Jacqueline Eschbach, Bin Li, Eugin Destici, Bing Ren, Sylvia M. Evans, Shaochen Chen, Quan Zhu, Neil C. Chi
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High-speed and large-scale intrinsically stretchable integrated circuits Nature (IF 64.8) Pub Date : 2024-03-13 Donglai Zhong, Can Wu, Yuanwen Jiang, Yujia Yuan, Min-gu Kim, Yuya Nishio, Chien-Chung Shih, Weichen Wang, Jian-Cheng Lai, Xiaozhou Ji, Theodore Z. Gao, Yi-Xuan Wang, Chengyi Xu, Yu Zheng, Zhiao Yu, Huaxin Gong, Naoji Matsuhisa, Chuanzhen Zhao, Yusheng Lei, Deyu Liu, Song Zhang, Yuto Ochiai, Shuhan Liu, Shiyuan Wei, Jeffrey B.-H. Tok, Zhenan Bao
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Substrate-induced condensation activates plant TIR domain proteins Nature (IF 64.8) Pub Date : 2024-03-13 Wen Song, Li Liu, Dongli Yu, Hanna Bernardy, Jan Jirschitzka, Shijia Huang, Aolin Jia, Wictoria Jemielniak, Julia Acker, Henriette Laessle, Junli Wang, Qiaochu Shen, Weijie Chen, Pilong Li, Jane E. Parker, Zhifu Han, Paul Schulze-Lefert, Jijie Chai
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Dopamine receptor D2 confers colonization resistance via microbial metabolites Nature (IF 64.8) Pub Date : 2024-03-13 Samantha A. Scott, Jingjing Fu, Pamela V. Chang
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Time-resolved cryo-EM of G-protein activation by a GPCR Nature (IF 64.8) Pub Date : 2024-03-13 Makaía M. Papasergi-Scott, Guillermo Pérez-Hernández, Hossein Batebi, Yang Gao, Gözde Eskici, Alpay B. Seven, Ouliana Panova, Daniel Hilger, Marina Casiraghi, Feng He, Luis Maul, Peter Gmeiner, Brian K. Kobilka, Peter W. Hildebrand, Georgios Skiniotis
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Mitochondrial complex I activity in microglia sustains neuroinflammation Nature (IF 64.8) Pub Date : 2024-03-13 L. Peruzzotti-Jametti, C. M. Willis, G. Krzak, R. Hamel, L. Pirvan, R.-B. Ionescu, J. A. Reisz, H. A. Prag, M. E. Garcia-Segura, V. Wu, Y. Xiang, B. Barlas, A. M. Casey, A. M. R. van den Bosch, A. M. Nicaise, L. Roth, G. R. Bates, H. Huang, P. Prasad, A. E. Vincent, C. Frezza, C. Viscomi, G. Balmus, Z. Takats, J. C. Marioni, A. D’Alessandro, M. P. Murphy, I. Mohorianu, S. Pluchino
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Last-mile delivery increases vaccine uptake in Sierra Leone Nature (IF 64.8) Pub Date : 2024-03-13 Niccolò F. Meriggi, Maarten Voors, Madison Levine, Vasudha Ramakrishna, Desmond Maada Kangbai, Michael Rozelle, Ella Tyler, Sellu Kallon, Junisa Nabieu, Sarah Cundy, Ahmed Mushfiq Mobarak