bluuebunny/crossref_metadata_2025_split huggingface dataset:
Jumper enables discontinuous transcript assembly in coronaviruses
Authors: Sashittal Palash , Zhang Chuanyi , Peng Jian , El-Kebir Mohammed 
Published: November 2021

AbstractGenes in SARS-CoV-2 and other viruses in the order of Nidovirales are expressed by a process of discontinuous transcription which is distinct from alternative splicing in eukaryotes and is mediated by the viral RNA-dependent RNA polymerase. Here, we introduce the DISCONTINUOUS TRANSCRIPT ASSEMBLYproblem of finding transcripts and their abundances given an alignment of paired-end short reads under a maximum likelihood model that accounts for varying transcript lengths. We show, using simulations, that our method, JUMPER, outperforms existing methods for classical transcript assembly. On short-read data of SARS-CoV-1, SARS-CoV-2 and MERS-CoV samples, we find that JUMPER not only identifies canonical transcripts that are part of the reference transcriptome, but also predicts expression of non-canonical transcripts that are supported by subsequent orthogonal analyses. Moreover, application of JUMPER on samples with and without treatment reveals viral drug response at the transcript level. As such, JUMPER enables detailed analyses of Nidovirales transcriptomes under varying conditions.
30-year record of Himalaya mass-wasting reveals landscape perturbations by extreme events
Authors: Jones Joshua N. , Boulton Sarah J. , Stokes Martin , Bennett Georgina L. , Whitworth Michael R. Z. 
Published: November 2021

AbstractIn mountainous environments, quantifying the drivers of mass-wasting is fundamental for understanding landscape evolution and improving hazard management. Here, we quantify the magnitudes of mass-wasting caused by the Asia Summer Monsoon, extreme rainfall, and earthquakes in the Nepal Himalaya. Using a newly compiled 30-year mass-wasting inventory, we establish empirical relationships between monsoon-triggered mass-wasting and monsoon precipitation, before quantifying how other mass-wasting drivers perturb this relationship. We find that perturbations up to 5 times greater than that expected from the monsoon alone are caused by rainfall events with 5-to-30-year return periods and short-term (< 2 year) earthquake-induced landscape preconditioning. In 2015, the landscape preconditioning is strongly controlled by the topographic signature of the Gorkha earthquake, whereby high Peak Ground Accelerations coincident with high excess topography (rock volume above a landscape threshold angle) amplifies landscape damage. Furthermore, earlier earthquakes in 1934, 1988 and 2011 are not found to influence 2015 mass-wasting.
DeepPhospho accelerates DIA phosphoproteome profiling through in silico library generation
Authors: Lou Ronghui , Liu Weizhen , Li Rongjie , Li Shanshan , He Xuming , Shui Wenqing 
Published: November 2021

AbstractPhosphoproteomics integrating data-independent acquisition (DIA) enables deep phosphoproteome profiling with improved quantification reproducibility and accuracy compared to data-dependent acquisition (DDA)-based phosphoproteomics. DIA data mining heavily relies on a spectral library that in most cases is built on DDA analysis of the same sample. Construction of this project-specific DDA library impairs the analytical throughput, limits the proteome coverage, and increases the sample size for DIA phosphoproteomics. Herein we introduce a deep neural network, DeepPhospho, which conceptually differs from previous deep learning models to achieve accurate predictions of LC-MS/MS data for phosphopeptides. By leveraging in silico libraries generated by DeepPhospho, we establish a DIA workflow for phosphoproteome profiling which involves DIA data acquisition and data mining with DeepPhospho predicted libraries, thus circumventing the need of DDA library construction. Our DeepPhospho-empowered workflow substantially expands the phosphoproteome coverage while maintaining high quantification performance, which leads to the discovery of more signaling pathways and regulated kinases in an EGF signaling study than the DDA library-based approach. DeepPhospho is provided as a web server as well as an offline app to facilitate user access to model training, predictions and library generation.
Mapping protein carboxymethylation sites provides insights into their role in proteostasis and cell proliferation
Authors: Di Sanzo Simone , Spengler Katrin , Leheis Anja , Kirkpatrick Joanna M. , Rändler Theresa L. , Baldensperger Tim , Dau Therese , Henning Christian , Parca Luca , Marx Christian , Wang Zhao-Qi , Glomb Marcus A. , Ori Alessandro , Heller Regine 
Published: November 2021

AbstractPosttranslational mechanisms play a key role in modifying the abundance and function of cellular proteins. Among these, modification by advanced glycation end products has been shown to accumulate during aging and age-associated diseases but specific protein targets and functional consequences remain largely unexplored. Here, we devise a proteomic strategy to identify sites of carboxymethyllysine modification, one of the most abundant advanced glycation end products. We identify over 1000 sites of protein carboxymethylation in mouse and primary human cells treated with the glycating agent glyoxal. By using quantitative proteomics, we find that protein glycation triggers a proteotoxic response and indirectly affects the protein degradation machinery. In primary endothelial cells, we show that glyoxal induces cell cycle perturbation and that carboxymethyllysine modification reduces acetylation of tubulins and impairs microtubule dynamics. Our data demonstrate the relevance of carboxymethyllysine modification for cellular function and pinpoint specific protein networks that might become compromised during aging.
A cerebellar internal model calibrates a feedback controller involved in sensorimotor control
Authors: Markov Daniil A. , Petrucco Luigi , Kist Andreas M. , Portugues Ruben 
Published: November 2021

AbstractAnimals must adapt their behavior to survive in a changing environment. Behavioral adaptations can be evoked by two mechanisms: feedback control and internal-model-based control. Feedback controllers can maintain the sensory state of the animal at a desired level under different environmental conditions. In contrast, internal models learn the relationship between the motor output and its sensory consequences and can be used to recalibrate behaviors. Here, we present multiple unpredictable perturbations in visual feedback to larval zebrafish performing the optomotor response and show that they react to these perturbations through a feedback control mechanism. In contrast, if a perturbation is long-lasting, fish adapt their behavior by updating a cerebellum-dependent internal model. We use modelling and functional imaging to show that the neuronal requirements for these mechanisms are met in the larval zebrafish brain. Our results illustrate the role of the cerebellum in encoding internal models and how these can calibrate neuronal circuits involved in reactive behaviors depending on the interactions between animal and environment.
Soft elasticity optimises dissipation in 3D-printed liquid crystal elastomers
Authors: Mistry D. , Traugutt N. A. , Sanborn B. , Volpe R. H. , Chatham L. S. , Zhou R. , Song B. , Yu K. , Long K. N. , Yakacki C. M. 
Published: November 2021

AbstractSoft-elasticity in monodomain liquid crystal elastomers (LCEs) is promising for impact-absorbing applications where strain energy is ideally absorbed at constant stress. Conventionally, compressive and impact studies on LCEs have not been performed given the notorious difficulty synthesizing sufficiently large monodomain devices. Here, we use direct-ink writing 3D printing to fabricate bulk (>cm3) monodomain LCE devices and study their compressive soft-elasticity over 8 decades of strain rate. At quasi-static rates, the monodomain soft-elastic LCE dissipated 45% of strain energy while comparator materials dissipated less than 20%. At strain rates up to 3000 s−1, our soft-elastic monodomain LCE consistently performed closest to an ideal-impact absorber. Drop testing reveals soft-elasticity as a likely mechanism for effectively reducing the severity of impacts – with soft elastic LCEs offering a Gadd Severity Index 40% lower than a comparable isotropic elastomer. Lastly, we demonstrate tailoring deformation and buckling behavior in monodomain LCEs via the printed director orientation.
Follicular T cells are clonally and transcriptionally distinct in B cell-driven mouse autoimmune disease
Authors: Akama-Garren Elliot H. , van den Broek Theo , Simoni Lea , Castrillon Carlos , van der Poel Cees E. , Carroll Michael C. 
Published: November 2021

AbstractPathogenic autoantibodies contribute to tissue damage and clinical decline in autoimmune disease. Follicular T cells are central regulators of germinal centers, although their contribution to autoantibody-mediated disease remains unclear. Here we perform single cell RNA and T cell receptor (TCR) sequencing of follicular T cells in a mouse model of autoantibody-mediated disease, allowing for analyses of paired transcriptomes and unbiased TCRαβ repertoires at single cell resolution. A minority of clonotypes are preferentially shared amongst autoimmune follicular T cells and clonotypic expansion is associated with differential gene signatures in autoimmune disease. Antigen prediction using algorithmic and machine learning approaches indicates convergence towards shared specificities between non-autoimmune and autoimmune follicular T cells. However, differential autoimmune transcriptional signatures are preserved even amongst follicular T cells with shared predicted specificities. These results demonstrate that follicular T cells are phenotypically distinct in B cell-driven autoimmune disease, providing potential therapeutic targets to modulate autoantibody development.
Multifactorial seroprofiling dissects the contribution of pre-existing human coronaviruses responses to SARS-CoV-2 immunity
Authors: Abela Irene A. , Pasin Chloé , Schwarzmüller Magdalena , Epp Selina , Sickmann Michèle E. , Schanz Merle M. , Rusert Peter , Weber Jacqueline , Schmutz Stefan , Audigé Annette , Maliqi Liridona , Hunziker Annika , Hesselman Maria C. , Niklaus Cyrille R. , Gottschalk Jochen , Schindler Eméry , Wepf Alexander , Karrer Urs , Wolfensberger Aline , Rampini Silvana K. , Meyer Sauteur Patrick M. , Berger Christoph , Huber Michael , Böni Jürg , Braun Dominique L. , Marconato Maddalena , Manz Markus G. , Frey Beat M. , Günthard Huldrych F. , Kouyos Roger D. , Trkola Alexandra 
Published: November 2021

AbstractDetermination of SARS-CoV-2 antibody responses in the context of pre-existing immunity to circulating human coronavirus (HCoV) is critical for understanding protective immunity. Here we perform a multifactorial analysis of SARS-CoV-2 and HCoV antibody responses in pre-pandemic (N = 825) and SARS-CoV-2-infected donors (N = 389) using a custom-designed multiplex ABCORA assay. ABCORA seroprofiling, when combined with computational modeling, enables accurate definition of SARS-CoV-2 seroconversion and prediction of neutralization activity, and reveals intriguing interrelations with HCoV immunity. Specifically, higher HCoV antibody levels in SARS-CoV-2-negative donors suggest that pre-existing HCoV immunity may provide protection against SARS-CoV-2 acquisition. In those infected, higher HCoV activity is associated with elevated SARS-CoV-2 responses, indicating cross-stimulation. Most importantly, HCoV immunity may impact disease severity, as patients with high HCoV reactivity are less likely to require hospitalization. Collectively, our results suggest that HCoV immunity may promote rapid development of SARS-CoV-2-specific immunity, thereby underscoring the importance of exploring cross-protective responses for comprehensive coronavirus prevention.
Decadal-scale onset and termination of Antarctic ice-mass loss during the last deglaciation
Authors: Weber Michael E. , Golledge Nicholas R. , Fogwill Chris J. , Turney Chris S. M. , Thomas Zoë A. 
Published: November 2021

AbstractEmerging ice-sheet modeling suggests once initiated, retreat of the Antarctic Ice Sheet (AIS) can continue for centuries. Unfortunately, the short observational record cannot resolve the tipping points, rate of change, and timescale of responses. Iceberg-rafted debris data from Iceberg Alley identify eight retreat phases after the Last Glacial Maximum that each destabilized the AIS within a decade, contributing to global sea-level rise for centuries to a millennium, which subsequently re-stabilized equally rapidly. This dynamic response of the AIS is supported by (i) a West Antarctic blue ice record of ice-elevation drawdown >600 m during three such retreat events related to globally recognized deglacial meltwater pulses, (ii) step-wise retreat up to 400 km across the Ross Sea shelf, (iii) independent ice sheet modeling, and (iv) tipping point analysis. Our findings are consistent with a growing body of evidence suggesting the recent acceleration of AIS mass loss may mark the beginning of a prolonged period of ice sheet retreat and substantial global sea level rise.
Sand spikes pinpoint powerful palaeoseismicity
Authors: Buchner Elmar , Sach Volker J. , Schmieder Martin 
Published: November 2021

AbstractSand spikes, pin-shaped, carbonate-cemented sandstone bodies of variable size widely interpreted as sedimentary concretions, have been enigmatic for nearly two centuries. We here present a high-energy mechanism for their formation. Two classic sand spike occurrences are found in the North Alpine Foreland Basin of Central Europe and at Mount Signal in southern California, USA. A distinct seismite horizon in Mid-Miocene Molasse sediments of southern Germany, genetically linked with the Ries impact event, exhibits dewatering structures and contains numerous sand spikes with tails systematically orientated away from the Ries crater. Sand spikes at Mount Signal, strikingly similar in shape to those found in Germany, have tails that point away from the nearby San Andreas Fault. Based on their structural and stratigraphic context, we interpret sand spikes as a new type of seismite and a promising tool to identify strong impact-induced or tectonic palaeo-earthquakes and their source regions in the geologic record.
MDA5 disease variant M854K prevents ATP-dependent structural discrimination of viral and cellular RNA
Authors: Yu Qin , Herrero del Valle Alba , Singh Rahul , Modis Yorgo 
Published: November 2021

AbstractOur innate immune responses to viral RNA are vital defenses. Long cytosolic double-stranded RNA (dsRNA) is recognized by MDA5. The ATPase activity of MDA5 contributes to its dsRNA binding selectivity. Mutations that reduce RNA selectivity can cause autoinflammatory disease. Here, we show how the disease-associated MDA5 variant M854K perturbs MDA5-dsRNA recognition. M854K MDA5 constitutively activates interferon signaling in the absence of exogenous RNA. M854K MDA5 lacks ATPase activity and binds more stably to synthetic Alu:Alu dsRNA. CryoEM structures of MDA5-dsRNA filaments at different stages of ATP hydrolysis show that the K854 sidechain forms polar bonds that constrain the conformation of MDA5 subdomains, disrupting key steps in the ATPase cycle- RNA footprint expansion and helical twist modulation. The M854K mutation inhibits ATP-dependent RNA proofreading via an allosteric mechanism, allowing MDA5 to form signaling complexes on endogenous RNAs. This work provides insights on how MDA5 recognizes dsRNA in health and disease.
Distinct conformations of the HIV-1 V3 loop crown are targetable for broad neutralization
Authors: Friedrich Nikolas , Stiegeler Emanuel , Glögl Matthias , Lemmin Thomas , Hansen Simon , Kadelka Claus , Wu Yufan , Ernst Patrick , Maliqi Liridona , Foulkes Caio , Morin Mylène , Eroglu Mustafa , Liechti Thomas , Ivan Branislav , Reinberg Thomas , Schaefer Jonas V. , Karakus Umut , Ursprung Stephan , Mann Axel , Rusert Peter , Kouyos Roger D. , Robinson John A. , Günthard Huldrych F. , Plückthun Andreas , Trkola Alexandra 
Published: November 2021

AbstractThe V3 loop of the HIV-1 envelope (Env) protein elicits a vigorous, but largely non-neutralizing antibody response directed to the V3-crown, whereas rare broadly neutralizing antibodies (bnAbs) target the V3-base. Challenging this view, we present V3-crown directed broadly neutralizing Designed Ankyrin Repeat Proteins (bnDs) matching the breadth of V3-base bnAbs. While most bnAbs target prefusion Env, V3-crown bnDs bind open Env conformations triggered by CD4 engagement. BnDs achieve breadth by focusing on highly conserved residues that are accessible in two distinct V3 conformations, one of which resembles CCR5-bound V3. We further show that these V3-crown conformations can, in principle, be attacked by antibodies. Supporting this conclusion, analysis of antibody binding activity in the Swiss 4.5 K HIV-1 cohort (n = 4,281) revealed a co-evolution of V3-crown reactivities and neutralization breadth. Our results indicate a role of V3-crown responses and its conformational preferences in bnAb development to be considered in preventive and therapeutic approaches.
Acyl carrier protein promotes MukBEF action in Escherichia coli chromosome organization-segregation
Authors: Prince Josh P. , Bolla Jani R. , Fisher Gemma L. M. , Mäkelä Jarno , Fournier Marjorie , Robinson Carol V. , Arciszewska Lidia K. , Sherratt David J. 
Published: November 2021

AbstractStructural Maintenance of Chromosomes (SMC) complexes act ubiquitously to compact DNA linearly, thereby facilitating chromosome organization-segregation. SMC proteins have a conserved architecture, with a dimerization hinge and an ATPase head domain separated by a long antiparallel intramolecular coiled-coil. Dimeric SMC proteins interact with essential accessory proteins, kleisins that bridge the two subunits of an SMC dimer, and HAWK/KITE proteins that interact with kleisins. The ATPase activity of the Escherichia coli SMC protein, MukB, which is essential for its in vivo function, requires its interaction with the dimeric kleisin, MukF that in turn interacts with the KITE protein, MukE. Here we demonstrate that, in addition, MukB interacts specifically with Acyl Carrier Protein (AcpP) that has essential functions in fatty acid synthesis. We characterize the AcpP interaction at the joint of the MukB coiled-coil and show that the interaction is necessary for MukB ATPase and for MukBEF function in vivo.
The role of cyclonic activity in tropical temperature-rainfall scaling
Authors: Traxl Dominik , Boers Niklas , Rheinwalt Aljoscha , Bookhagen Bodo 
Published: November 2021

AbstractThe attribution of changing intensity of rainfall extremes to global warming is a key challenge of climate research. From a thermodynamic perspective, via the Clausius-Clapeyron relationship, rainfall events are expected to become stronger due to the increased water-holding capacity of a warmer atmosphere. Here, we employ global, 1-hourly temperature and 3-hourly rainfall data to investigate the scaling between temperature and extreme rainfall. Although the Clausius-Clapeyron scaling of +7% rainfall intensity increase per degree warming roughly holds on a global average, we find very heterogeneous spatial patterns. Over tropical oceans, we reveal areas with consistently strong negative scaling (below −40%∘C−1). We show that the negative scaling is due to a robust linear correlation between pre-rainfall cooling of near-surface air temperature and extreme rainfall intensity. We explain this correlation by atmospheric and oceanic dynamics associated with cyclonic activity. Our results emphasize that thermodynamic arguments alone are not enough to attribute changing rainfall extremes to global warming. Circulation dynamics must also be thoroughly considered.
Assessing saliva microbiome collection and processing methods
Authors: Armstrong Abigail J. S. , Parmar Veenat , Blaser Martin J. 
Published: November 2021

AbstractThe oral microbiome has been connected with lung health and may be of significance in the progression of SARS-CoV-2 infection. Saliva-based SARS-CoV-2 tests provide the opportunity to leverage stored samples for assessing the oral microbiome. However, these collection kits have not been tested for their accuracy in measuring the oral microbiome. Saliva is highly enriched with human DNA and reducing it prior to shotgun sequencing may increase the depth of bacterial reads. We examined both the effect of saliva collection method and sequence processing on measurement of microbiome depth and diversity by 16S rRNA gene amplicon and shotgun metagenomics. We collected 56 samples from 22 subjects. Each subject provided saliva samples with and without preservative, and a subset provided a second set of samples the following day. 16S rRNA gene (V4) sequencing was performed on all samples, and shotgun metagenomics was performed on a subset of samples collected with preservative with and without human DNA depletion before sequencing. We observed that the beta diversity distances within subjects over time was smaller than between unrelated subjects, and distances within subjects were smaller in samples collected with preservative. Samples collected with preservative had higher alpha diversity measuring both richness and evenness. Human DNA depletion before extraction and shotgun sequencing yielded higher total and relative reads mapping to bacterial sequences. We conclude that collecting saliva with preservative may provide more consistent measures of the oral microbiome and depleting human DNA increases yield of bacterial sequences.
Penultimate deglaciation Asian monsoon response to North Atlantic circulation collapse
Authors: Wassenburg Jasper A. , Vonhof Hubert B. , Cheng Hai , Martínez-García Alfredo , Ebner Pia-Rebecca , Li Xianglei , Zhang Haiwei , Sha Lijuan , Tian Ye , Edwards R. Lawrence , Fiebig Jens , Haug Gerald H. 
Published: November 2021

AbstractDuring glacial terminations, massive iceberg discharges and meltwater pulses in the North Atlantic triggered a shutdown of the Atlantic Meridional Overturning Circulation (AMOC). Speleothem calcium carbonate oxygen isotope records (δ18OCc) indicate that the collapse of the AMOC caused dramatic changes in the distribution and variability of the East Asian and Indian monsoon rainfall. However, the mechanisms linking changes in the intensity of the AMOC and Asian monsoon δ18OCc are not fully understood. Part of the challenge arises from the fact that speleothem δ18OCc depends on not only the δ18O of precipitation but also temperature and kinetic isotope effects. Here we quantitatively deconvolve these parameters affecting δ18OCc by applying three geochemical techniques in speleothems covering the penultimate glacial termination. Our data suggest that the weakening of the AMOC during meltwater pulse 2A caused substantial cooling in East Asia and a shortening of the summer monsoon season, whereas the collapse of the AMOC during meltwater pulse 2B (133,000 years ago) also caused a dramatic decrease in the intensity of the Indian summer monsoon. These results reveal that the different modes of the AMOC produced distinct impacts on the monsoon system.