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.
197 results found. For more information, click each entry to expand.
28 tweets bioRxiv neuroscience
Visual systems can exploit spatial correlations in the visual scene by using retinotopy, the organizing principle by which neighboring cells encode neighboring spatial locations. However, retinotopy is often lost, such as when visual pathways are integrated with other sensory modalities. How is spatial information processed in the absence of retinotopy? Here, we focused on visual looming responsive LC6 cells in Drosophila, a population whose dendrites collectively tile the visual field, but whose axons form a single glomerulus--a structure lacking retinotopic organization--in the central brain. We identified multiple glomerulus neurons and found that they respond to looming in different portions of the visual field, unexpectedly preserving spatial information. Through EM reconstruction of all LC6 synaptic inputs to the glomerulus, we found that LC6 and downstream cell types form circuits within the glomerulus that establish spatial readout of visual features and contralateral suppression--mechanisms that transform visual information for behavioral control. ### Competing Interest Statement The authors have declared no competing interest.
18 tweets bioRxiv developmental biology
Karin D. Prummel, Helena L Crowell, Susan Nieuwenhuize, Eline C. Brombacher, Stephan Daetwyler, Charlotte Soneson, Jelena Kresoja-Rakic, Manuel Ronner, Agnese Kocere, Alexander Ernst, Zahra Labbaf, David E. Clouthier, Anthony B. Firulli, Hector Sanchez-Iranzo, Rebecca O'Rourke, Erez Raz, Nadia Mercader, Alexa Burger, Emanuela Felley-Bosco, Jan Huisken, Mark D Robinson, Christian Mosimann
The mesothelium forms epithelial membranes that line the bodies cavities and surround the internal organs. Mesothelia widely contribute to organ homeostasis and regeneration, and their dysregulation can result in congenital anomalies of the viscera, ventral wall defects, and mesothelioma tumors. Nonetheless, the embryonic ontogeny and developmental regulation of mesothelium formation has remained uncharted. Here, we combine genetic lineage tracing, in toto live imaging, and single-cell transcriptomics in zebrafish to track mesothelial progenitor origins from the lateral plate mesoderm (LPM). Our single-cell analysis uncovers a post-gastrulation gene expression signature centered on hand2 that delineates distinct progenitor populations within the forming LPM. Combining gene expression analysis and imaging of transgenic reporter zebrafish embryos, we chart the origin of mesothelial progenitors to the lateral-most, hand2-expressing LPM and confirm evolutionary conservation in mouse. Our time-lapse imaging of transgenic hand2 reporter embryos captures zebrafish mesothelium formation, documenting the coordinated cell movements that form pericardium and visceral and parietal peritoneum. We establish that the primordial germ cells migrate associated with the forming mesothelium as ventral migration boundary. Functionally, hand2 mutants fail to close the ventral mesothelium due to perturbed migration of mesothelium progenitors. Analyzing mouse and human mesothelioma tumors hypothesized to emerge from transformed mesothelium, we find de novo expression of LPM-associated transcription factors, and in particular of Hand2, indicating the re-initiation of a developmental transcriptional program in mesothelioma. Taken together, our work outlines a genetic and developmental signature of mesothelial origins centered around Hand2, contributing to our understanding of mesothelial pathologies and mesothelioma.
16 tweets bioRxiv animal behavior and cognition
Fabiana Heredia, Yanel Volonté, Joana Pereirinha, Magdalena Fernandez-Acosta, Andreia P. Casimiro, Cláudia G. Belém, Filipe Viegas, Kohtaro Tanaka, Maite Arana, Gisele A. Cardoso, André Macedo, Malwina Kotowicz, Facundo H. Prado Spalm, Marcos J. Dibo, Raquel D. Monfardini, Tatiana T. Torres, César S. Mendes, Andres Garelli, Alisson M. Gontijo
Innate behaviors consist of a succession of genetically-hardwired motor and physiological subprograms that can be coupled to drastic morphogenetic changes. How these integrative responses are orchestrated is not completely understood. Here, we provide insight into these mechanisms by studying pupariation, a multi-step innate behavior of fly larvae that is critical for survival during metamorphosis. We find that the steroid-hormone ecdysone triggers parallel pupariation neuromotor and morphogenetic subprograms, which include the induction of the relaxin-peptide hormone, Dilp8, in the epidermis. Dilp8 acts on six Lgr3-positive thoracic interneurons to couple both subprograms in time and to instruct neuromotor subprogram switching during behavior. Our work reveals that interorgan feedback gates progression between subunits of an innate behavior and points to an ancestral neuromodulatory function of relaxin signaling. ### Competing Interest Statement The authors have declared no competing interest.
12 tweets bioRxiv microbiology
The Human Immunodeficiency Virus (HIV) enters the nucleus to establish infection. The nuclear envelope is a physical barrier for HIV. The role of nuclear pore components in promoting HIV infection is well established. In contrast, the role of other proteins of the nuclear envelope is much less understood. SUN1 and SUN2 are inner nuclear membrane proteins that connect the nuclear Lamin proteins to the cytoskeleton. Increased levels of SUN1 or SUN2 proteins potently restrict HIV infection through an unresolved mechanism. Here, we identify a strain-specific antiviral activity of SUN1 and SUN2 against HIV-1 and HIV-2 that we leverage to investigate the cellular basis of the antiviral effect. SUN1 preferentially restricts HIV-1 in macrophages and HeLa cells. This specificity maps to the nucleoplasmic domain of SUN proteins, which associates with Lamin A/C and participates to the DNA damage response. We find that etoposide, a DNA-damaging drug, stimulates infection. Inhibition of ATR, which induces a DNA damage response, also enhances HIV-1 infection. The proviral effect of ATR inhibition on infection requires the Vpr gene in HIV-1. Depletion of endogenous Lamin A/C, which sensitize cells to DNA damage, also enhances HIV-1 infection in HeLa cells. SUN1 over-expression neutralizes these proviral effects, while the antiviral effect of SUN2 is rescued by etoposide treatment. Finally, we show that inhibition of HIV-1 infection by over-expressed SUN proteins and endogenous Lamin A/C is associated with reduced internal movements of chromatin and reduced rotations of the nucleus. Altogether, the results highlight distinct antiviral activities of SUN1 and SUN2 and they reveal an emerging role of nuclear movements and the DNA damage response in the control of HIV infection by structural components of the nuclear envelope.
10 tweets bioRxiv genomics
Methylation of viral DNA in a CpG context (5mCpG) can alter the expression patterns of viral genes related to infection and cellular transformation. Moreover, it may also provide clues to why certain infections are cleared, or persist with or without progression to cancer. The detection 5mCpG often requires techniques that damage DNA or introduce bias through a myriad of limitations. Therefore, we developed a method for the detection of 5mCpG on the HBV genome that does not rely on bisulfite conversion or PCR. We used cas9 guided RNPs to specifically target and enrich in HBV DNA from infected PHH, prior to sequencing with nanopores. This method is a novel approach that enables the enrichment of viral DNA in a mixture of nucleic acid material from different species. Moreover, using the developed technique, we have provided the first de novo assembly of naive HBV DNA, as well as the first landscape of 5mCpG from naive HBV sequences.
10 tweets bioRxiv evolutionary biology
Human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is most closely related, by average genetic distance, to two coronaviruses isolated from bats, RaTG13 and RmYN02. However, there is a segment of high amino acid similarity between human SARS-CoV-2 and a pangolin isolated strain, GD410721, in the receptor binding domain (RBD) of the spike protein, a pattern that can be caused by either recombination or by convergent amino acid evolution driven by natural selection. We perform a detailed analysis of the synonymous divergence, which is less likely to be affected by selection than amino acid divergence, between human SARS-CoV-2 and related strains. We show that the synonymous divergence between the bat derived viruses and SARS-CoV-2 is larger than between GD410721 and SARS-CoV-2 in the RBD, providing strong additional support for the recombination hypothesis. However, the synonymous divergence between pangolin strain and SARS-CoV-2 is also relatively high, which is not consistent with a recent recombination between them, instead it suggests a recombination into RaTG13. We also find a 14-fold increase in the dN/dS ratio from the lineage leading to SARS-CoV-2 to the strains of the current pandemic, suggesting that the vast majority of non-synonymous mutations currently segregating within the human strains have a negative impact on viral fitness. Finally, we estimate that the time to the most recent common ancestor of SARS-CoV-2 and RaTG13 or RmYN02 based on synonymous divergence, is 51.71 years (95% C.I., 28.11-75.31) and 37.02 years (95% C.I., 18.19-55.85), respectively. ### Competing Interest Statement The authors have declared no competing interest.
8 tweets bioRxiv biophysics
Motile cells migrate directionally in the electric field in a process known as galvanotaxis. Galvanotaxis is important in wound healing, development, cell division, and nerve growth. Different cell types migrate in opposite directions in electric fields, to either cathode, or anode, and the same cell can switch the directionality depending on chemical conditions. We previously reported that individual fish keratocyte cells sense electric fields and migrate to the cathode, while inhibition of PI3K reverses single cells to the anode. Many physiological processes rely on collective, not individual, cell migration, so here we report on directional migration of cohesive cell groups in electric fields. Uninhibited cell groups of any size move to the cathode, with speed decreasing and directionality increasing with the group size. Surprisingly, large groups of PI3K-inhibited cells move to the cathode, in the direction opposite to that of individual cells, which move to the anode, while such small groups are not persistently directional. In the large groups, cells' velocities are distributed unevenly: the fastest cells are at the front of the uninhibited groups, but at the middle and rear of the PI3K-inhibited groups. Our results are most consistent with the hypothesis, supported by the computational model, that cells inside and at the edge of the groups interpret directional signals differently. Namely, cells in the group interior are directed to the cathode independently of their chemical state. Meanwhile, edge cells behave like the individual cells: they are directed to the cathode/anode in uninhibited/PI3K-inhibited groups, respectively. As a result, all cells drive uninhibited groups to the cathode, but a mechanical tug-of-war between the inner and edge cells directs large PI3K-inhibited groups with cell majority in the interior to the cathode, while rendering small groups non-directional.
7 tweets bioRxiv developmental biology
Fluorescent proteins and epitope tags can reveal protein localization in cells and animals. However, the large size of many tags hinders efficient genome targeting. Accordingly, many studies have relied on characterizing overexpressed proteins, which might not recapitulate endogenous protein activities. We present two approaches for higher throughput production of endogenous protein reporters. Our first approach makes use of a split fluorescent protein mNeonGreen2 (mNG2). Knock-in of a small portion of the mNG2 gene, in frame with gene coding regions of interest was highly efficient in embryos, eliminating the need to establish mouse lines. When complemented by the larger portion of the mNG2 gene, fluorescence was reconstituted and endogenous protein localization faithfully reported in living embryos. However, we report a threshold of detection using this approach. By contrast, the V5 epitope enabled high efficiency and higher sensitivity protein reporting. We describe complementary advantages and prospective applications of these two approaches. ### Competing Interest Statement The authors have declared no competing interest.
7 tweets bioRxiv microbiology
Dylan H Morris, Kwe Claude Yinda, Amandine Gamble, Fernando W. Rossine, Qishen Huang, Trenton Bushmaker, Robert J. Fischer, M. Jeremiah Matson, Neeltje van Doremalen, Peter J. Vikesland, Linsey C. Marr, Vincent J. Munster, James O Lloyd-Smith
Understanding the impact of environmental conditions on virus viability and transmission potential is crucial to anticipating epidemic dynamics and designing mitigation strategies. Ambient temperature and humidity are known to have strong effects on the environmental stability of viruses, but a general quantitative understanding of how temperature and humidity affect virus stability has remained elusive. We characterize the stability of SARS-CoV-2 on an inert surface at a variety of temperature and humidity conditions, and introduce a mechanistic model that enables accurate prediction of virus stability in unobserved conditions. We find that SARS-CoV-2 survives better at low temperatures and extreme relative humidities; median estimated virus half-life was more than 24 hours at 10 °C and 40 % RH, but approximately an hour and a half at 27 °C and 65 % RH. Moreover, our model predicts observations from other human coronaviruses and other studies of SARS-CoV-2, suggesting the existence of shared mechanisms that determine environmental stability across a number of enveloped viruses. Our results highlight scenarios of particular transmission risk and point to broad strategies for pandemic mitigation, while opening new frontiers for the mechanistic study of viral transmission. ### Competing Interest Statement The authors have declared no competing interest.
7 tweets bioRxiv neuroscience
The hippocampus is essential for human memory. Thus, memory deficiencies in infants are often attributed to hippocampal immaturity. However, the functionality of the infant hippocampus has never been tested directly. Here we report that the human hippocampus is indeed active in infancy. We recorded hippocampal activity using fMRI while awake infants aged 3-24 months viewed sequences of objects. Greater activity was observed when the order of the sequence contained regularities that could be learned compared to when the order was random. The involvement of the hippocampus in such statistical learning, with additional recruitment of the medial prefrontal cortex, is consistent with findings from adults. These results suggest that the hippocampus supports the important ability of infants to extract the structure of their environment through experience. ### Competing Interest Statement The authors have declared no competing interest.
7 tweets bioRxiv biochemistry
In mammals HP1-mediated heterochromatin forms positionally and mechanically stable genomic domains even though the component HP1 paralogs, HP1α, HP1β, and HP1γ, display rapid on-off dynamics. Here we investigate whether phase-separation by HP1 proteins can explain these biological observations. Using bulk and single-molecule methods, we show that, within phase-separated HP1α-DNA condensates, HP1α acts as a dynamic liquid, while compacted DNA molecules are constrained in local territories. These condensates are resistant to large forces yet can be readily dissolved by HP1β. Finally, we find that differences in each HP1 paralog's DNA compaction and phase-separation properties arise from their respective disordered regions. Our findings suggest a generalizable model for genome organization in which a pool of weakly bound proteins collectively capitalize on the polymer properties of DNA to produce self-organizing domains that are simultaneously resistant to large forces at the mesoscale and susceptible to competition at the molecular scale. ### Competing Interest Statement The authors have declared no competing interest.
7 tweets bioRxiv neuroscience
Young infants learn about the world by overtly shifting their attention to perceptually salient events. In adults, attention recruits several brain regions spanning the frontal and parietal lobes. However, these regions are thought to have a protracted maturation and so it is unclear whether they are recruited in infancy and, more generally, how infant attention is supported by the brain. We used event-related fMRI with 24 awake behaving infants 3-12 months old while they performed a child-friendly attentional cuing task. A target was presented to either the left or right of the infant's fixation and eye-tracking was used to measure the latency with which they saccaded to the target. To manipulate attention, a brief cue was presented before the target in three conditions: on the same side as the upcoming target (valid), on the other side (invalid), or on both sides (neutral). All infants were faster to look at the target on valid versus invalid trials, with valid faster than neutral and invalid slower than neutral, indicating that the cues effectively captured attention. We then compared the fMRI activity evoked by these trial types. Regions of adult attention networks activated more strongly for invalid than valid trials, particularly frontal regions such as anterior cingulate cortex. Neither behavioral nor neural effects varied by infant age within the first year, suggesting that these regions may function early in development to support the reorienting of attention. Together, this furthers our mechanistic understanding of how the infant brain controls the allocation of attention. ### Competing Interest Statement The authors have declared no competing interest.
7 tweets bioRxiv bioinformatics
Experimental single-cell approaches are becoming widely used for many purposes, including investigation of the dynamic behaviour of developing biological systems. Consequently, a large number of computational methods for extracting dynamic information from such data have been developed. One example is RNA velocity analysis, in which spliced and unspliced RNA abundances are jointly modeled in order to infer a 'direction of change' and thereby a future state for each cell in the gene expression space. Naturally, the accuracy and interpretability of the inferred RNA velocities depend crucially on the correctness of the estimated abundances. Here, we systematically compare four widely used quantification tools, in total yielding twelve different quantification approaches, in terms of their estimates of spliced and unspliced RNA abundances in four experimental droplet scRNA-seq data sets. We show that there are substantial differences between the quantifications obtained from different tools, and identify typical genes for which such discrepancies are observed. We further show that these abundance differences propagate to the downstream analysis, and can have a large effect on estimated velocities as well as the biological interpretation. Our results highlight that abundance quantification is a crucial aspect of the RNA velocity analysis workflow, and that both the definition of the genomic features of interest and the quantification algorithm itself require careful consideration.
7 tweets bioRxiv immunology
Alexander A Cohen, Priyanthi N.P. Gnanapragasam, Yu E. Lee, Susan Ou, Leesa M. Kakutani, Jennifer R Keeffe, Christopher O. Barnes, Hung-Jen Wu, Mark Howarth, Anthony P. West, Michel C. Nussenzweig, Pamela J Bjorkman
Protection against SARS-CoV-2 and SARS-related zoonotic coronaviruses with pandemic potential is urgently needed. To evaluate immunization strategies, we made nanoparticles displaying the receptor-binding domain (RBD) of only SARS-CoV-2 (homotypic nanoparticles) or co-displaying the SARS-CoV-2 RBD along with RBDs from animal betacoronaviruses that represent threats to humans (mosaic nanoparticles; 4-8 distinct RBDs). Mice immunized with RBD-nanoparticles, but not soluble antigen, elicited cross-reactive antibody binding and neutralization responses, confirming increased immunogenicity from multimerization. Mosaic-RBD-nanoparticles elicited antibodies with superior cross-reactive recognition of heterologous RBDs compared to sera from immunizations with homotypic SARS-CoV-2-RBD-nanoparticles or antibodies from COVID-19 convalescent human plasmas. Moreover, sera from mosaic-RBD-immunized mice neutralized heterologous pseudotyped coronaviruses equivalently or better after priming than sera from homotypic SARS-CoV-2-RBD-nanoparticle immunizations, demonstrating no loss of immunogenicity against any particular RBD resulting from co-display. Thus, a single immunization with mosaic-RBD-nanoparticles provides a potential strategy to simultaneously protect against SARS-CoV-2 and emerging zoonotic coronaviruses.
6 tweets bioRxiv cell biology
Fluorescence microscopy relies on dyes that absorb short-wavelength photons and emit longer-wavelength light. In addition to this fluorescence process, dyes can undergo other photochemical reactions that result in spectral shifts and irreversible photobleaching. Increases in brightness, 'chromostability', and photostability of fluorescent dyes are therefore crucial for advancing the frontier of bioimaging. Here, we describe a general approach to improve small-molecule fluorophores using deuteration. Incorporating deuterium into the alkylamino substituents of rhodamines and other dyes improves fluorescence quantum yield, inhibits photochemically induced spectral shifts, and slows irreparable photobleaching. These compounds are easily synthesized and show improved performance in cellular imaging experiments. ### Competing Interest Statement The authors declare the following competing financial interest: Patents and patent applications describing azetidine- and deuterium-containing fluorophores (with inventors J.B.G. and L.D.L.) are assigned to HHMI.
6 tweets bioRxiv biophysics
SARS-CoV-2 recently emerged as a human pathogen and is the causative agent of the COVID-19 pandemic. A molecular framework of how the virus manipulates host cellular machinery to facilitate infection remains unclear. Here, we focus on SARS-CoV-2 NSP1, which is proposed to be a virulence factor that inhibits protein synthesis by directly binding the human ribosome. Using extract-based and reconstitution experiments, we demonstrate that NSP1 inhibits translation initiation on model human and SARS-CoV-2 mRNAs. NSP1 also specifically binds to the small (40S) ribosomal subunit, which is required for translation inhibition. Using single-molecule fluorescence assays to monitor NSP1-40S subunit binding in real time, we demonstrate that eukaryotic translation initiation factors (eIFs) modulate the interaction: NSP1 rapidly and stably associates with most ribosomal pre-initiation complexes in the absence of mRNA, with particular enhancement and inhibition by eIF1 and eIF3j, respectively. Using model mRNAs and an inter-ribosomal-subunit FRET signal, we elucidate that NSP1 competes with RNA segments downstream of the start codon to bind the 40S subunit and that the protein is unable to associate rapidly with 80S ribosomes assembled on an mRNA. Collectively, our findings support a model where NSP1 associates with the open head conformation of the 40S subunit to inhibit an early step of translation, by preventing accommodation of mRNA within the entry channel. ### Competing Interest Statement The authors have declared no competing interest.
6 tweets bioRxiv neuroscience
Understanding spoken language requires transforming ambiguous stimulus streams into a hierarchy of increasingly abstract representations, ranging from speech sounds to meaning. It has been suggested that the brain uses predictive computations to guide the interpretation of incoming information. However, the exact role of prediction in language understanding remains unclear, with widespread disagreement about both the ubiquity of prediction, and the level of representation at which predictions unfold. Here, we address both issues by analysing brain recordings of participants listening to audiobooks, and using a state-of-the-art deep neural network (GPT-2) to quantify predictions in a fine-grained, contextual fashion. First, we establish clear evidence for predictive processing, confirming that brain responses to words are modulated by probabilistic predictions. Next, we factorised the model-based predictions into distinct linguistic dimensions, revealing dissociable neural signatures of syntactic, phonemic and semantic predictions. Finally, we show that high-level (word) predictions inform low-level (phoneme) predictions, supporting theories of hierarchical predictive processing. Together, these results underscore the ubiquity of prediction in language processing, and demonstrate that linguistic prediction is not implemented by a single system but occurs throughout the language network, forming a hierarchy of linguistic predictions across all levels of analysis.
6 tweets bioRxiv neuroscience
Being confronted with social-evaluative stress elicits a physiological and a psychological stress response. This calls for regulatory processes to manage negative affect and maintain self-related optimistic beliefs. The aim of the current study was to investigate the affect-regulating potential of self-related belief updating after exposure to social-evaluative stress, in comparison to non-social physical stress or no stress. We assessed self-related belief updating using trial-by-trial performance feedback and described the updating behavior in a mechanistic way using computational modeling. We found that social-evaluative stress was accompanied by an increase in cortisol and negative affect which was related to a shift in self-related belief updating towards the positive direction. This self-beneficial belief updating, which was absent after physical stress or control, was associated with a better recovery from stress-induced negative affect. This indicates that enhanced integration of positive self-related feedback can act as a coping strategy to deal with social-evaluative stress.
6 tweets bioRxiv bioinformatics
Precision medicine, regarded as the future of healthcare, is gaining increasing attention these years. As an essential part of precision medicine, clinical omics have been successfully applied in disease diagnosis and prognosis using machine learning techniques. However, existing methods mainly make predictions based on gene-level individual features or their random combinations, none of the previous work has considered the activation of signaling pathways. Therefore, the model interpretability and accuracy are limited, and reasonable signaling pathways are yet to be discovered. In this paper, we propose a novel multi-level attention graph neural network (MLA-GNN), which applies weighted correlation network analysis (WGCNA) to format the omic data of each patient into graph-structured data, and then constructs multi-level graph features, and fuses them through a well-designed multi-level graph feature fully fusion (MGFFF) module to conduct multi-task prediction. Moreover, a novel full-gradient graph saliency mechanism is developed to make the MLA-GNN interpretable. MLA-GNN achieves state-of-the-art performance on transcriptomic data from TCGA-LGG/TCGA-GBM and proteomic data from COVID-19/non-COVID-19 patient sera. More importantly, the proposed model's decision can be interpreted in the signaling pathway level and is consistent with the clinical understanding.
6 tweets bioRxiv ecology
Dissolved Organic Matter (DOM) represents a mixture of organic molecules that vary due to different source materials and degree of processing. Characterizing how DOM composition evolves along the aquatic continuum can be difficult. Using a size-exclusion chromatography technique (LC-OCD), we assessed the variability in DOM composition from both surface and groundwaters across a number of Canadian ecozones (mean annual temperature spanning -10 to +6 C). A wide range in DOM concentration was found from 0.2 to 120 mg C/L. Proportions of different size-based groupings across ecozones were variable, yet similarities between specific water-body types, regardless of location, suggest commonality in the processes dictating DOM composition. A PCA identified 70% of the variation in LC-OCD derived DOM compositions could be explained by the water-body type. We find that DOM composition within a specific water-body type is similar regardless of the differences in climate or surrounding vegetation where the sample originated from.
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- 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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- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
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