Most tweeted biology preprints, last 24 hours
*There are gaps in historical Twitter data, most notably in spring 2020. This may result in some preprints appearing with less tweets than they should.
265 results found. For more information, click each entry to expand.
58 tweets bioRxiv immunology
Mark M. Painter, Timothy S. Johnston, Kendall A Lundgreen, Jefferson J.S. Santos, Juliana S Qin, Rishi R. Goel, Sokratis A. Apostolidis, Divij Mathew, Bria Fulmer, Justine C Williams, Michelle L. McKeague, Ajinkya Pattekar, Ahmad Goode, Sean Nasta, Amy E. Baxter, Josephine R. Giles, Ashwin N Skelly, Laura E. Felley, Maura McLaughlin, Joellen Weaver, Penn Medicine BioBank, Oliva Kuthuru, Jeanette Dougherty, Sharon Adamski, Sherea Long, Macy Kee, Cynthia Clendenin, Ricardo da Silva Antunes, Alba Grifoni, Daniela Weiskopf, Alessandro Sette, Alexander C Huang, Daniel J Rader, Scott E. Hensley, Paul Bates, Allison R. Greenplate, E. John Wherry
SARS-CoV-2 infection of vaccinated individuals is increasingly common but rarely results in severe disease, likely due to the enhanced potency and accelerated kinetics of memory immune responses. However, there have been few opportunities to rigorously study early recall responses during human viral infection. To better understand human immune memory and identify potential mediators of lasting vaccine efficacy, we used high-dimensional flow cytometry and SARS-CoV-2 antigen probes to examine immune responses in longitudinal samples from vaccinated individuals infected during the Omicron wave. These studies revealed heightened Spike-specific responses during infection of vaccinated compared to unvaccinated individuals. Spike-specific CD4 T cells and plasmablasts expanded and CD8 T cells were robustly activated during the first week. In contrast, memory B cell activation, neutralizing antibody production, and primary responses to non-Spike antigens occurred during the second week. Collectively, these data demonstrate the functionality of vaccine-primed immune memory and highlight memory T cells as rapid responders during SARS-CoV-2 infection.
54 tweets bioRxiv neuroscience
Anthony W. Azevedo, Ellen Lesser, Brandon Mark, Jasper S. Phelps, Leila Elabbady, Sumiya Kuroda, Anne E Sustar, Anthony J Moussa, Avinash Kandelwal, Chris J. Dallmann, Sweta Agrawal, Su-Yee J. Lee, Brandon G. Pratt, Andrew Cook, Kyobi Skutt-Kakari, Stephan Gerhard, Ran Lu, Nico Kemnitz, Kisuk Lee, Akhilesh Halageri, Manuel Castro, Dodam Ih, Jay Gager, Marwan Tammam, Sven Dorkenwald, Forrest C Collman, Casey M Schneider-Mizell, Derrick Brittain, Chris S. Jordan, Michael H Dickinson, Alexandra Pacureanu, H. Sebastian Seung, Thomas Macrina, Wei-Chung Allen Lee, John C. Tuthill
Like the vertebrate spinal cord, the insect ventral nerve cord (VNC) mediates limb sensation and motor control. Here, we applied automated tools for electron microscopy (EM) volume alignment, neuron reconstruction, and synapse prediction to create a draft connectome of the Drosophila VNC. To interpret the VNC connectome, it is crucial to know its relationship with the rest of the body. We therefore mapped the muscle targets of leg and wing motor neurons in the connectome by comparing their morphology to genetic driver lines, dye fills, and x-ray holographic nano-tomography volumes of the fly leg and wing. Knowing the outputs of the connectome allowed us to identify neural circuits that coordinate the wings with the middle and front legs during escape takeoff. We provide the draft VNC connectome and motor neuron atlas, along with tools for programmatic and interactive access, as community resources.
27 tweets bioRxiv microbiology
Pablo Sánchez, Marta Sebastián, Massimo Ciro Pernice, Raquel Rodríguez-Martínez, Stéphane Pesant, Susana Agustí, Takashi Gojobori, Ramiro Logares, Maria Montserrat Sala, Dolors Vaqué, Ramon Massana, Carlos M Duarte, Silvia G Acinas, Josep M Gasol
The Ocean microbiome has a crucial role on Earth's biogeochemical cycles, but also represents a tremendous potential for biological applications as part of the blue-biotechnology. During the last decade, global cruises such as Tara Oceans or the Malaspina Expedition have expanded our knowledge on the diversity and genetic repertoire of marine microbes. Nevertheless, there is still a gap of knowledge on broad scale patterns between photic and bathypelagic dark ocean microbes derived by the lack of detailed vertical profiles covering contrasting oceans regions. Here we present 76 microbial metagenomes of the picoplankton size fraction (0.2-3.0 microns) from 11 stations along the Malaspina Expedition circumnavigation that cover vertical profiles sampling at 7 depths, from surface to the 4000m deep (or the sea floor in shallower waters). The Malaspina Microbial Vertical Profiles metagenomes (MProfile) dataset produced 1.66 Tbp of raw DNA sequences and assembled them into a total 25.3 Gbp. After gene prediction and annotation, we built a 46.3 million non-redundant gene compendium with their corresponding annotations (M-GeneDB-VP), clustered at 95% sequence similarity. This dataset will be a valuable resource for exploring the functional and taxonomic connectivity between the photic and bathypelagic ocean at a global scale, while increasing our general knowledge on the Ocean microbiome.
20 tweets medRxiv epidemiology
Noah A. Haber, Sarah E. Wieten, Julia M. Rohrer, Onyebuchi A. Arah, Peter W.G. Tennant, Elizabeth A. Stuart, Eleanor J Murray, Sophie Pilleron, Sze Tung Lam, Emily Riederer, Sarah Jane Howcutt, Alison E. Simmons, Clemence Leyrat, Philipp Schoenegger, Anna Booman, Mi-suk Kang Dufour, Ashley L. O'Donoghue, Rebekah Baglini, Stefanie Do, Mari De La Rosa Takashima, Thomas Rhys Evans, Daloha Rodriguez-Molina, Taym M. Alsalti, Daniel J. Dunleavy, Gideon Meyerowitz-Katz, Alberto Antonietti, Jose Andres Calvache, Mark J. Kelson, Meg G. Salvia, Camila Olarte Parra, Saman Khalatbari-Soltani, Taylor McLinden, Arthur Chatton, Jessie Seiler, Andreea Steriu, Talal S. Alshihayb, Sarah E. Twardowski, Julia Dabravolskaj, Eric Au, Rachel A. Hoopsick, Shashank Suresh, Nicholas Judd, Sebastian Pena, Cathrine Axfors, Palwasha Khan, Ariadne E. Rivera Aguirre, Nnaemeka U. Odo, Ian Schmid, Matthew P. Fox
Background: Avoiding "causal" language with observational study designs is common publication practice, often justified as being a more cautious approach to interpretation. We aimed to i) estimate the degree to which causality was implied by both the language linking exposures to outcomes and by action recommendations in the high-profile health literature, ii) examine disconnects between language and recommendations, iii) identify which linking phrases were most common, and iv) generate estimates by which these phrases imply causality. Methods: We identified 18 of the most prominent general medical/public health/epidemiology journals, and searched and screened for articles published from 2010 to 2019 that investigated exposure/outcome pairs until we reached 65 non-RCT articles per journal (n=1,170). Two independent reviewers and an arbitrating reviewer rated the degree to which they believed causality had been implied by the language in abstracts based on written guidance. Reviewers then rated causal implications of linking words in isolation. For comparison, additional review was performed for full texts and for a secondary sample of RCTs. Results: Reviewers rated the causal implication of the sentence and phrase linking the exposure and outcome as None (i.e., makes no causal implication) in 13.8%, Weak in 34.2%, Moderate in 33.2%, and Strong in 18.7% of abstracts. Reviewers identified an action recommendation in 34.2% of abstracts. Of these action recommendations, reviewers rated the causal implications as None in 5.3%, Weak in 19.0%, Moderate in 42.8% and Strong in 33.0% of cases. The implied causality of action recommendations was often higher than the implied causality of linking sentences (44.5%) or commensurate (40.3%), with 15.3% being weaker. The most common linking word root identified in abstracts was "associate" (n=535/1,170; 45.7%) (e.g. "association," "associated," etc). There were only 16 (1.4%) abstracts using "cause" in the linking or modifying phrases. Reviewer ratings for causal implications of word roots were highly heterogeneous, including those commonly considered non-causal. Discussion: We found substantial disconnects between causal implications used to link an exposure to an outcome and the action implications made. This undercuts common assumptions about what words are often considered non-causal and that policing them eliminates causal implications. We recommend that instead of policing words, editors, researchers, and communicators should increase efforts at making research questions, as well as the potential of studies to answer them, more transparent.
16 tweets bioRxiv neuroscience
Functional magnetic resonance imaging (fMRI) has proven to be a powerful tool for noninvasively measuring human brain activity; yet, thus far, fMRI has been relatively limited in its temporal resolution. A key challenge is understanding the relationship between neural activity and the blood-oxygenation-level-dependent (BOLD) signal obtained from fMRI, generally modeled by the hemodynamic response function (HRF). The timing of the HRF varies across the brain and individuals, confounding our ability to make inferences about the timing of the underlying neural processes. Here we show that resting-state fMRI signals contain information about HRF temporal dynamics that can be leveraged to understand and characterize variations in HRF timing across both cortical and subcortical regions. We found that the frequency spectrum of resting-state fMRI signals significantly differs between voxels with fast versus slow HRFs in human visual cortex. These spectral differences extended to subcortex as well, revealing significantly faster hemodynamic timing in the lateral geniculate nucleus of the thalamus. Ultimately, our results demonstrate that the temporal properties of the HRF impact the spectral content of resting-state fMRI signals and enable voxel-wise characterization of relative hemodynamic response timing. Furthermore, our results show that caution should be used in studies of resting-state fMRI spectral properties, as differences can arise from purely vascular origins. This finding provides new insight into the temporal properties of fMRI signals across voxels, which is crucial for accurate fMRI analyses, and enhances the ability of fast fMRI to identify and track fast neural dynamics.
15 tweets bioRxiv ecology
The tendency for animals in warmer climates to be longer-limbed (Allen's Rule) is widely attributed to the demands of thermoregulation. However, it remains unclear whether this pattern is driven by selection for efficient heat retention at low temperatures or increased demand for heat dissipation at high temperatures. Using comparative phylogenetic models, we find that occurrence in warmer climates is associated with longer wing bones for 1,520 species of passerine birds. The highly vascularized musculature along these bones functions in heat exchange during flight when the overwhelming thermoregulatory challenge is dissipating heat, suggesting longer wing-bone length is driven by heat dissipation demands. Our findings reveal the pervasive impacts of thermoregulation on even the most critical features of vertebrate anatomy, and establish a clear mechanism linking spatial and temporal trends in appendage length.
15 tweets bioRxiv neuroscience
Eric M. Trautmann, Janis K. Hesse, Gabrial Stine, Ruobing Xia, Shude Shude Zhu, Daniel J. O'Shea, Bill Karsh, Jennifer Colonell, Frank Lanfranchi, Saurabh Vyas, Andrew Zimnik, Natalie A. Steinemann, Daniel A. Wagenaar, Alexandru Andrei, Carolina Mora Lopez, John M. OCallaghan, Jan Putzeys, Bogdan C. Raducanu, Marleen Welkenhuysen, Mark Churchland, Tirin Moore, Michael N. Shadlen, Krishna V Shenoy, Doris Tsao, Baruneb Dutta, Tim Harris
High-density, integrated silicon electrodes have begun to transform systems neuroscience, by enabling large-scale neural population recordings with single cell resolution. Existing technologies, however, have provided limited functionality in nonhuman primate species such as macaques, which offer close models of human cognition and behavior. Here, we report the design, fabrication, and performance of Neuropixels 1.0-NHP, a high channel count linear electrode array designed to enable large-scale simultaneous recording in superficial and deep structures within the macaque or other large animal brain. These devices were fabricated in two versions: 4416 electrodes along a 45 mm shank, and 2496 along a 25 mm shank. For both versions, users can programmably select 384 channels, enabling simultaneous multi-area recording with a single probe. We demonstrate recording from over 3000 single neurons within a session, and simultaneous recordings from over 1000 neurons using multiple probes. This technology represents a significant increase in recording access and scalability relative to existing technologies, and enables new classes of experiments involving fine-grained electrophysiological characterization of brain areas, functional connectivity between cells, and simultaneous brain-wide recording at scale.
14 tweets bioRxiv systems biology
Aleš Holfeld, Dina Schuster, Fabian Sesterhenn, Patrick Stalder, Walther Haenseler, Inigo Barrio-Hernandez, Dhiman Ghosh, Jane Vowles, Sally A. Cowley, Luise Nagel, Basavraj Khanppnavar, Pedro Beltrao, Volodymyr M. Korkhov, Roland Riek, Natalie de Souza, Paola Picotti
Protein-protein interactions (PPIs) mediate numerous essential functions and regulatory events in living organisms. The physical interactome of a protein can be abnormally altered in response to external and internal cues, thus modulating cell physiology and contributing to human disease. In particular, neurodegenerative diseases due to the accumulation of aberrantly folded and aggregated proteins may lead to alterations in protein interactomes. Identifying changes in the interactomes of normal and disease states of proteins could help to understand molecular disease mechanisms, but current interactomics methods are limited in the ability to pinpoint structure-specific PPIs and their interaction interfaces on a proteome-wide scale. Here, we adapted limited proteolysis-mass spectrometry (LiP-MS) to systematically identify putative structure-specific PPIs by probing protein structural alterations within cellular extracts upon treatment with specific structural states of a given protein. We demonstrate the feasibility of our method to detect well-characterized PPIs, including antibody-target protein interactions and interactions with membrane proteins, and show that it pinpoints PPI interfaces. We then applied the LiP-MS approach to study the structure-specific interactors of the Parkinson's disease hallmark protein alpha-synuclein (aSyn). We identified several previously known interactors of both aSyn monomer and fibrils and provide a resource of novel putative structure-specific interactors for further studies. This approach is applicable to identify structure-specific interactomes of any protein, including posttranslationally modified and unmodified, or metabolite-bound and unbound structural states of proteins.
12 tweets bioRxiv neuroscience
Sangderk Lee, Holden C. Williams, Amy A Gorman, Nicholas A. Devanney, Douglas A. Harrison, Adeline E. Walsh, Danielle S Goulding, Tony Tuck, James L Schwartz, Diana J Zajac, Shannon L. Macauley, Steve Estus, Julia TCW, Lance Johnson, Josh Morganti
Apolipoprotein E4 (APOE4) is the strongest risk allele associated with the development of late onset Alzheimers disease (AD). Across the CNS, astrocytes are the predominant expressor of ApoE while also being critical mediators of neuroinflammation and cerebral metabolism. APOE4 has been consistently linked with dysfunctional inflammation and metabolic processes, yet insights into the molecular constituents driving these responses remain unclear. Utilizing complementary approaches across humanized APOE mice and isogenic human iPSC astrocytes, we demonstrate that ApoE4 alters the astrocyte immunometabolic response to pro-inflammatory stimuli. Our findings demonstrate that ApoE4-expressing astrocytes acquire distinct transcriptional repertoires at single-cell and spatially-resolved domains, which are driven in-part by preferential utilization of the cRel transcription factor. Further, inhibiting cRel translocation in ApoE4 astrocytes abrogates inflammatory-induced glycolytic shift and in tandem mitigates production of multiple pro-inflammatory cytokines. Altogether, our findings elucidate novel cellular underpinnings by which ApoE4 drives maladaptive immunometabolic responses of astrocytes.
11 tweets bioRxiv systems biology
The theory of autopoiesis has been influential in many areas of theoretical biology, especially in the fields of artificial life and origins of life. However, it has not managed to productively connect with mainstream biology, partly for theoretical reasons, but arguably mainly because deriving specific working hypotheses has been challenging. The theory has recently undergone significant conceptual development in the enactive approach to life and mind. Hidden complexity in the original conception of autopoiesis has been explicated in the service of other operationalizable concepts related to self-individuation: precariousness, adaptivity, and agency. Here we advance these developments by highlighting the interplay of these concepts with considerations from thermodynamics: reversibility, irreversibility, and path-dependence. We interpret this interplay in terms of the self-optimization model, and present modeling results that illustrate how these minimal conditions enable a system to re-organize itself such that it tends toward coordinated constraint satisfaction at the system level. Although the model is still very abstract, these results point in a direction where the enactive approach could productively connect with cell biology.
11 tweets bioRxiv animal behavior and cognition
Decision scientists have grown increasingly interested in how people adaptively control their decision making. Researchers have demonstrated that parameters governing the accumulation of evidence towards a choice, such as the decision threshold, are shaped by information available prior to or in parallel with one's evaluation of an option set (e.g., recent outcomes or choice conflict). A recent account has taken a bold leap forward in this approach, suggesting that adjustments in decision parameters can be motivated by the value of the options under consideration. This motivated control account predicts that when faced with difficult choices (similarly valued options) under time pressure, people will adaptively lower their decision threshold to ensure that they make a choice in time. This account was supported by drift diffusion modeling of a deadlined choice task, demonstrating that decision thresholds decrease for difficult relative to easy choices. Here, we reanalyze the data from this experiment, and show that evidence for this novel account does not hold up to further scrutiny. Using a more systematic and comprehensive modeling approach, we show that this previously observed threshold adjustment disappears (or even reverses) under a more complete model of the data. Importantly, we further show how this and other apparent evidence for motivated control arises as an artifact of model (mis)specification, where one model's putatively controlled decision process (e.g., value-driven threshold adjustments) can mimic another model's stimulus-driven decision processes (e.g., accumulator competition or collapsing bounds). Collectively, this work reveals crucial insights and constraints in the pursuit of understanding how control guides decision-making, and when it doesn't.
11 tweets bioRxiv microbiology
The vaginal microbiome has been linked to numerous negative health outcomes including preterm birth. Specific taxa, including Gardnerella spp., have been identified as risk factors for these conditions. Historically, microbiome analysis methods have treated all Gardnerella spp. as one species, but the broad diversity of Gardnerella has recently become more apparent. In the present study, we explore the diversity of Gardnerella clades and genomic species in the vaginal microbiome of pregnant women and their impacts on microbiome composition and associations with preterm birth. Shotgun metagenomic sequencing data collected longitudinally from three distinct cohorts of pregnant women were assessed. Relative abundance of Gardnerella clades and genomic species and other taxa was quantified, and associations between Gardnerella clades and signatures of the vaginal microbiome were measured. We also assessed the diversity and abundance of Gardnerella variants in 16S rRNA gene amplicon sequencing data from seven previously conducted studies in differing populations on the vaginal microbiome and preterm birth. Individual microbiomes often contained multiple Gardnerella variants, and the number of clades was associated with increased microbial load. The genus Gardnerella was also associated with increased microbial load, or the ratio of non-human reads to human reads. Taxon co-occurrence patterns matched previously described community structures, and were largely consistent across Gardnerella clades and among cohorts. Some variants previously described as rare were prevalent in other cohorts, highlighting the importance of surveying a diverse set of populations to fully capture the diversity of Gardnerella. The diversity of Gardnerella both across populations and within individual vaginal microbiomes has long been unappreciated, as has been the intra-species diversity of many other members of the vaginal microbiome.1 The broad genomic diversity of Gardnerella has led to its reclassification as multiple species; here we demonstrate the diversity of Gardnerella found within and between vaginal microbiomes. Further studies should investigate the phenotypes of Gardnerella variants that may underlie the mechanisms by which Gardnerella species may differentially shape the vaginal microbiome.
10 tweets bioRxiv microbiology
Background: The gastrointestinal microbiome plays a significant role in numerous host processes and has an especially large impact on modulating the host metabolism. Prior studies have shown that when mice receive fecal transplants from obese donors that were fed high-fat diets (HFD) (even when recipient mice are fed normal diets after transplantation), they develop obese phenotypes. These studies demonstrate the prominent role that the gut microbiota play in determining lean and obese phenotypes. While much of the credit has been given to gut bacteria, studies have not measured the impact of gut viruses on these phenotypes. To address this shortcoming, we gavaged mice with viromes isolated from donors fed HFD or normal chow. By characterizing the mice gut bacterial biota and weight-gain phenotypes over time, we demonstrate that viruses can shape the gut bacterial community and affect weight gain or loss. Results: We gavaged mice longitudinally over 4 weeks while measuring their body weights and collecting fecal samples for 16S rRNA amplicon sequencing. We evaluated mice that were fed normal chow or high-fat diets, and gavaged each group with either chow-derived fecal viromes, HFD-derived fecal viromes, or phosphate buffered saline controls. We found a significant effect of gavage type, where mice fed chow but gavaged with HFD-derived viromes gained significantly more weight than their counterparts receiving chow-derived viromes. The converse was also true: mice fed HFD but gavaged with chow-derived viromes gained significantly less weight than their counterparts receiving HFD-derived viromes. These results were replicated in two separate experiments and the phenotypic changes were accompanied by significant and identifiable differences in the fecal bacterial biota. Notably, there were differences in Lachnospirales and Clostridia in mice fed chow but gavaged with HFD-derived fecal viromes, and in Peptostreptococcales, Oscillospirales, and Lachnospirales in mice fed HFD but gavaged with chow-derived fecal viromes. Due to methodological limitations, we were unable to identify specific bacterial species or strains that were responsible for respective phenotypic changes. Conclusions: This study confirms that virome-mediated perturbations can alter the fecal microbiome in an in vivo model and indicates that such perturbations are sufficient to drive lean and obese phenotypes in mice.
9 tweets bioRxiv bioengineering
Jinhai Wang, Baofeng Su, De Xing, Timothy J. Bruce, Shangjia Li, Logan Bern, Mei Shang, Andrew Johnson, Rhoda Mae C. Simora, Michael Coogan, Darshika U. Hettiarachchi, Wenwen Wang, Tasnuba Hasin, Jacob Al-Armanazi, Cuiyu Lu, Rex A. Dunham
The CRISPR/Cas9 platform holds promise for modifying fish traits of interest as a precise and versatile tool for genome manipulation. To reduce introgression of transgene and control reproduction, catfish species have been studied for upscaled disease resistance and intervening of reproduction to lower the potential environmental risks of introgression of escapees' as transgenic animals. Taking advantage of the CRISPR/Cas9-mediated system, we succeeded in integrating the cathelicidin gene from an alligator (Alligator sinensis; As-Cath) into the target luteinizing hormone (LH) locus of channel catfish (Ictalurus punctatus) using two delivery systems assisted by double-stranded DNA (dsDNA) and single-stranded oligodeoxynucleotides (ssODNs), respectively. In this study, high knock-in (KI) efficiency (22.38%, 64/286) but low on-target was achieved using the ssODN strategy, whereas adopting a dsDNA as the donor template led to an efficient on-target KI (10.80%, 23/213). On-target KI of As-Cath was instrumental in establishing the LH knockout (LH--As-Cath+) catfish line, which displayed heightened disease resistance and reduced fecundity compared to the wild-type sibling fish. Furthermore, implanting with HCG and LHRHa can restore the fecundity, spawnability and hatchability of the new transgenic fish line. Overall, we replaced the LH gene with an alligator cathelicidin transgene and then administered hormone therapy to gain complete reproductive control of disease-resistant transgenic catfish in an environmentally sound manner. This strategy not only effectively improves the consumer-valued traits, but also guards against genetic contamination. This is a breakthrough in aquaculture genetics to confine fish reproduction and prevent the establishment of transgenic or domestic genotypes in the natural environment.
9 tweets bioRxiv developmental biology
Despite their barrier function, epithelial layers can locally lose their integrity to create physiological openings during morphogenesis. The cellular and molecular mechanisms driving the formation of these epithelial breaks are only starting to be investigated. Here, we studied the formation of the zebrafish nostril (the olfactory orifice), which opens in the skin epithelium to expose the olfactory neurons to external odorant cues. Combining live imaging, drug treatments, laser ablation and tissue-specific functional perturbations, we demonstrate that the formation of the orifice is driven by a mechanical interplay between the olfactory placode neurons and the skin: the neurons pull on the overlying skin cells in an actomyosin-dependent manner, thus triggering the opening of the orifice. This work unravels an original mechanism to break an epithelial sheet, in which an adjacent group of cells instructs and mechanically assists the epithelium to induce its local rupture.
9 tweets medRxiv epidemiology
The infection fatality rate (IFR) of COVID-19 among non-elderly people in the absence of vaccination or prior infection is important to estimate accurately, since 94% of the global population is younger than 70 years and 86% is younger than 60 years. In systematic searches in SeroTracker and PubMed (protocol: https://osf.io/xvupr), we identified 40 eligible national seroprevalence studies covering 38 countries with pre-vaccination seroprevalence data. For 29 countries (24 high-income, 5 others), publicly available age-stratified COVID-19 death data and age-stratified seroprevalence information were available and were included in the primary analysis. The IFRs had a median of 0.035% (interquartile range (IQR) 0.013 - 0.056%) for the 0-59 years old population, and 0.095% (IQR 0.036 - 0.125%,) for the 0-69 years old. The median IFR was 0.0003% at 0-19 years, 0.003% at 20-29 years, 0.011% at 30-39 years, 0.035% at 40-49 years, 0.129% at 50-59 years, and 0.501% at 60-69 years. Including data from another 9 countries with imputed age distribution of COVID-19 deaths yielded median IFR of 0.025-0.032% for 0-59 years and 0.063-0.082% for 0-69 years. Meta-regression analyses also suggested global IFR of 0.03% and 0.07%, respectively in these age groups. The current analysis suggests a much lower pre-vaccination IFR in non-elderly populations than previously suggested. Large differences did exist between countries and may reflect differences in comorbidities and other factors. These estimates provide a baseline from which to fathom further IFR declines with the widespread use of vaccination, prior infections, and evolution of new variants.
9 tweets bioRxiv cancer biology
Joann Chongsaritsinsuk, Alexandra D. Steigmeyer, Keira E. Mahoney, Mia A. Rosenfeld, Taryn M Lucas, Deniz Ince, Fiona L. Kearns, Alexandria S. Battison, Marie A. Hollenhorst, Judy Shon, Katherine H. Tiemeyer, Victor Attah, Catherine Kwon, Carolyn R. Bertozzi, Michael J Ferracane, Rommie E. Amaro, Stacy A Malaker
Mucin-domain glycoproteins are densely O-glycosylated and play critical roles in a host of biological functions. In particular, the T cell immunoglobulin and mucin-domain containing family of proteins (TIM-1, -3, -4) decorate immune cells and act as key checkpoint inhibitors in cancer. However, their dense O-glycosylation remains enigmatic both in terms of glycoproteomic landscape and structural dynamics, primarily due to the challenges associated with studying mucin domains. Here, we present a mucinase (SmE) and demonstrate its ability to selectively cleave along the mucin glycoprotein backbone, similar to others of its kind. Unlike other mucinases, though, SmE harbors the unique ability to cleave at residues bearing extremely complex glycans which enabled improved mass spectrometric analysis of several mucins, including the entire TIM family. With this information in-hand, we performed molecular dynamics (MD) simulations of TIM-3 and -4 to demonstrate how glycosylation affects structural features of these proteins. Overall, we present a powerful workflow to better understand the detailed molecular structures of the mucinome.
8 tweets bioRxiv biophysics
Liquid-liquid phase separation is the process in which two immiscible liquids demix. This spontaneous phenomenon yields spherical droplets that eventually coarsen to one large, stable droplet governed by the principle of minimal free energy. In chemically fueled phase separation, the formation of phase-separating molecules is coupled to a fuel-driven, non-equilibrium reaction cycle. Chemically fueled phase separation yields dissipative structures sustained by a continuous fuel conversion. Such dissipative structures are ubiquitous in biology but poorly understood as they are governed by non-equilibrium thermodynamics. Here, we bridge the gap between passive, close-to-equilibrium, and active, dissipative structures with chemically fueled phase separation. We observe that spherical, active droplets can transition into a new morphology, i.e., a liquid, spherical shell of droplet material. A spherical shell would be highly unstable at equilibrium. Only by continuously converting chemical energy, this dissipative structure can be sustained. We demonstrate the transition mechanism, which is related to the activation of a product outside of the droplet, and the deactivation within the droplets leading to gradients of droplet material. We characterize how far out of equilibrium the spherical shell state is and the chemical power necessary to sustain it. Our work suggests new avenues for assembling complex stable morphologies, which might already be exploited to form membraneless organelles by cells.
8 tweets bioRxiv genomics
Kazumasa Kanemaru, James Cranley, Daniele Muraro, Antonio M.A. Miranda, Jan Patrick Pett, Monika Litvinukova, Natsuhiko Kumasaka, Siew Yen Ho, Krzysztof Polanski, Laura Richardson, Lukas Mach, Monika Dabrowska, Nathan Richoz, Sam N. Barnett, Shani Perera, Anna L Wilbrey-Clark, Carlos Talavera-López, Ilaria Mulas, Krishnaa T Mahbubani, Liam Bolt, Lira Mamanova, Liz Tuck, Lu Wang, Margaret M. Huang, Martin Prete, Sophie Pritchard, John Dark, Kourosh Saeb-Parsy, Minal Patel, Menna R. Clatworthy, Norbert Hübner, Rasheda A Chowdhury, Michela Noseda, Sarah A. Teichmann
A cells function is defined by its intrinsic characteristics and its niche: the tissue microenvironment in which it dwells. Here, we combine single-cell and spatial transcriptomic data to discover cellular niches within eight regions of the human heart. We map cells to micro-anatomic locations and integrate knowledge-based and unsupervised structural annotations. For the first time, we profile the cells of the human cardiac conduction system, revealing their distinctive repertoire of ion channels, G-protein coupled receptors, and cell interactions using a custom CellPhoneDB.org module. We show that the sinoatrial node is compartmentalised, with a core of pacemaker cells, fibroblasts and glial cells supporting paracrine glutamatergic signalling. We introduce a druggable target prediction tool, drug2cell, which leverages single-cell profiles and drug-target interactions, providing unexpected mechanistic insights into the chronotropic effects of drugs, including GLP-1 analogues. In the epicardium, we show enrichment of both IgG+ and IgA+ plasma cells forming immune niches which may contribute to infection defence. We define a ventricular myocardial-stress niche enriched for activated fibroblasts and stressed cardiomyocytes, cell states that are expanded in cardiomyopathies. Overall, we provide new clarity to cardiac electro-anatomy and immunology, and our suite of computational approaches can be deployed to other tissues and organs.
8 tweets bioRxiv genomics
Mariateresa de Cesare, Mulenga Mwenda, Anna E. Jeffreys, Jacob Chirwa, Chris Drakeley, Kammerle Schneider, Isaac Ghinai, George B. Busby, Busiku Hamainza, Moonga Hawela, Daniel J Bridges, Jason A. Hendry
Genomic surveillance of Plasmodium falciparum malaria can provide policy-relevant information about antimalarial drug resistance, rapid diagnostic test failure, and the evolution of vaccine targets. Yet the large and low complexity genome of P. falciparum limits the scope of genomic surveillance, as whole-genome sequencing approaches are costly and targeted approaches are challenging to develop. Moreover, the majority of the morbidity and mortality caused by P. falciparum occurs in sub-Saharan Africa, where resource constraints can make implementing genomic surveillance difficult. Here, we demonstrate a flexible and cost-effective approach for targeted nanopore sequencing of P. falciparum to enable genomic surveillance of malaria in low-resource settings. We release open-source software that facilitates rapid and flexible design of amplicon sequencing panels for P. falciparum, coupled with a simple and cost-effective protocol that uses dried blood spots as input. We use this software to design two amplicon panels. The first, called NOMADS8, targets seven major antimalarial drug-resistance associated genes as well as the highly polymorphic gene msp2. The second, NOMAD16, incorporates an additional eight genes including the vaccine target csp and genes coding for the antigens detected in rapid diagnostic tests, hrp2 and hrp3. The panels generate reads between 3 to 4kbp that span the entire coding sequence of most target genes. We validate the panels and protocol on mock and field samples, demonstrating robust sequencing coverage across targets, high single-nucleotide polymorphism calling accuracy within coding sequences, and the ability to explore the within-sample diversity of mixed P. falciparum infections.
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
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