bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alignment free identification of clones in B cell receptor repertoires
Authors: Lindenbaum Ofir , Nouri Nima , Kluger Yuval , Kleinstein Steven H. 
Published: April 2020

AbstractFollowing pathogenic challenge, activated B cells rapidly expand and undergo somatic hypermutation, yielding groups of clonally related B-cells with diversified immunoglobulin receptors. Inference of clonal relationships based on the receptor sequence is an essential step in many adaptive immune receptor repertoire sequencing studies. These relationships are typically identified by a multi-step process that involves: (1) grouping sequences based on shared V and J gene assignments, and junction lengths, and (2) clustering these sequences using a junction-based distance. However, this approach is sensitive to the initial V(D)J gene assignments, which are error-prone, and fails to identify clonal relatives whose junction length has changed through accumulation of indels. Through defining a translation-invariant feature space in which we cluster the sequences, we develop an alignment-free clonal identification method that does not require gene assignments and is not restricted to a fixed junction length. This alignment-free approach has higher sensitivity compared to a typical junction-based distance method without loss of specificity and PPV. While the alignment-free procedure identifies clones that are broadly consistent with the junction-based distance method, it also identifies clones with characteristics (multiple V or J gene assignments or junction lengths) that are not detectable with thejunction based distancemethod.
The Institutional and Cultural Context of Cross-National Variation in COVID-19 Outbreaks
Authors: Messner Wolfgang 
Published: April 2020

BackgroundThe COVID-19 pandemic poses an unprecedented and cascading threat to the health and economic prosperity of the world’s population.ObjectivesTo understand whether the institutional and cultural context influences the COVID-19 outbreak.MethodsAt the ecological level, regression coefficients are examined to figure out contextual variables influencing the pandemic’s exponential growth rate across 96 countries.ResultsWhile a strong institutional context is negatively associated with the outbreak (B = −0.55 … −0.64, p < 0.001), the pandemic’s growth rate is steeper in countries with a quality education system (B = 0.33, p < 0.001). Countries with an older population are more affected (B = 0.46, p < 0.001). Societies with individualistic (rather than collectivistic) values experience a flatter rate of pathogen proliferation (B = −0.31, p < 0.001), similarly for higher levels of power distance (B = −0.32, p < 0.001). Hedonistic values, that is seeking indulgence and not enduring restraints, are positively related to the outbreak (B = 0.23, p = 0.001).ConclusionsThe results emphasize the need for public policy makers to pay close attention to the institutional and cultural context in their respective countries when instigating measures aimed at constricting the pandemic’s growth.
Modeling social distancing strategies to prevent SARS-CoV2 spread in Israel- A Cost-effectiveness analysis
Authors: Shlomai Amir , Leshno Ari , Sklan Ella H. , Leshno Moshe 
Published: April 2020

AbstractObjectivesWhile highly effective in preventing SARS-CoV-2 spread, national lockdowns come with an enormous economic price. Few countries have adopted an alternative “testing, tracing, and isolation” approach to selectively isolate people at high exposure risk, thereby minimizing the economic impact. To assist policy makers, we performed a cost-effectiveness analysis of these two strategies.MethodsA modified Susceptible, Exposed, Infectious, Recovered and Deceased (SEIRD) model was employed to assess the situation in Israel, a small country with ~9 million people. The incremental cost-effectiveness ratio (ICER) of these strategies, as well as the expected number of infected individuals and deaths were calculated.ResultsA nationwide lockdown is expected to save on average 274 (median 124, interquartile range (IQR): 71-221) lives compared to the “testing, tracing, and isolation” approach. However, the ICER will be on average $45,104,156 (median $ 49.6 million, IQR: 22.7-220.1) to prevent one case of death.ConclusionsA national lockdown has a moderate advantage in saving lives with tremendous costs and possible overwhelming economic effects. These findings should assist decision-makers dealing with additional waves of this pandemic.HighlightsDrastic measures of national lockdowns are taken by many countries to slow-down SARS-CoV-2 spread. However, these measures have detrimental economic effects.Here we compare two strategies to control the epidemic using a modified SEIRD model: 1. Global national lockdown 2. Focused isolation of people at high exposure risk, following detailed epidemiological investigations.We show that strategy 1 is modestly superior in saving lives compared to strategy 2, but with tremendous costs to prevent one case of death. This might result in overwhelming economic effects that are expected to increase future death toll.
Forecasting the CoViD–19 Diffusion in Italy and the Related Occupancy of Intensive Care Units
Authors: Fenga Livio 
Published: April 2020

AbstractThis paper provides a model–based method for the forecast of the total number of currently CoVoD-19 positive individuals and of the occupancy of the available Intensive Care Units in Italy. The predictions obtained – for a time horizon of 10 days starting from March 29th – will be provided at a national as well as at a more disaggregate levels, following a criterion based on the magnitude of the phenomenon. While the Regions which have been hit the most by the pandemic have been kept separated, the less affected ones have been aggregated into homogeneous macro-areas. Results show that – within the forecast period considered (March 29th - April 7th) – all of the Italian regions will show a decreasing number of CoViD-19 positive people. Same for the number of people who will need to be hospitalized in a Intensive Care Unit (ICU). These estimates are valid under constancy of the Government’s current containment policies. In this scenario, Northern Regions will remain the most affected ones and no significant outbreak are foreseen in the southern regions.
Deep analysis of the USP18-dependent ISGylome and proteome unveils important roles for USP18 in tumour cell antigenicity and radiosensitivity
Authors: Pinto-Fernandez Adan , Salio Mariolina , Partridge Tom , Chen Jianzhou , Vere George , Greenwood Helene , Olie Cyriel Sebastiaan , Damianou Andreas , Scott Hannah Claire , Pegg Henry Jack , Chiarenza Alessandra , Díaz-Saez Laura , Smith Paul , Gonzalez-Lopez Claudia , Patel Bhavisha , Anderton Emma , Jones Neil , Hammonds Tim R. , Huber Kilian , Muschel Ruth , Borrow Persephone , Cerundolo Vincenzo , Kessler Benedikt M. 
Published: April 2020

AbstractThe deubiquitylating enzyme USP18 is a major negative regulator of the interferon (IFN) signalling cascade. IFN pathways contribute to resistance to conventional chemotherapy, radiotherapy, and immunotherapy and are often deregulated in cancer. USP18 is the predominant human protease that cleaves interferon-stimulated gene ISG15, a ubiquitin-like protein tightly regulated in the context of innate immunity, from its modified substrate proteinsin vivo. In this study, using advanced proteomic techniques, we have expanded the USP18-dependent ISGylome and proteome in a chronic myeloid leukaemia (CML)-derived cell line (HAP1) treated with type I IFN. Novel ISGylation targets were characterised that modulate the sensing of innate ligands, antigen presentation and secretion of cytokines. Consequently, CML USP18-deficient cells are more antigenic, driving increased activation of cytotoxic T lymphocytes (CTLs) and are more susceptible to irradiation. Our results suggest USP18 as a pharmacological target in cancer immunotherapy and radiotherapy.
Computational tools for serial block EM reveal differences in plasmodesmata distributions and wall environments
Authors: Paterlini Andrea , Belevich Ilya , Jokitalo Eija , Helariutta Ykä 
Published: April 2020

AbstractPlasmodesmata are small channels that connect plant cells. While recent technological advances have facilitated the analysis of the ultrastructure of these channels, there are limitations to efficiently addressing their presence over an entire cellular interface. Here, we highlight the value of serial block electron microscopy for this purpose. We developed a computational pipeline to study plasmodesmata distributions and we detect presence/absence of plasmodesmata clusters, pit fields, at the phloem unloading interfaces ofArabidopsis thalianaroots. Pit fields can be visualised and quantified. As the wall environment of plasmodesmata is highly specialised we also designed a tool to extract the thickness of the extracellular matrix at and outside plasmodesmata positions. We show and quantify clear wall thinning around plasmodesmata with differences between genotypes, namely in the recently publishedplm-2sphingolipid mutant. Our tools open new avenues for quantitative approaches in the analysis of symplastic trafficking.Sentence summaryWe developed computational tools for serial block electron microscopy datasets to extract information on the spatial distribution of plasmodesmata over an entire cellular interface and on the wall environment the plasmodesmata are in.
Periprotein lipidomes ofSaccharomyces cerevisiaeprovide a flexible environment for conformational changes of membrane proteins
Authors: van ’t Klooster Joury S , Cheng Tan-Yun , Sikkema Hendrik R , Jeucken Aike , Moody D. Branch , Poolman Bert 
Published: April 2020

AbstractYeast tolerates a low pH and high solvent concentrations. The permeability of the plasma membrane (PM) for small molecules is low and lateral diffusion of proteins is slow. These findings suggest a high degree of lipid order, which raises the question of how membrane proteins function in such an environment. The yeast PM is segregated into the Micro-Compartment-of-Can1 (MCC) and Pma1 (MCP), which have different lipid compositions. We extracted proteins from these microdomains via stoichiometric capture of lipids and proteins in styrene-maleic-acid-lipid-particles (SMALPs). We purified SMALP-lipid-protein complexes by chromatography and quantitatively analyzed periprotein lipids located within the diameter defined by one SMALP. Phospholipid and sterol concentrations are similar for MCC and MCP, but sphingolipids are enriched in MCP. Ergosterol is depleted from this periprotein lipidome, whereas phosphatidylserine is enriched relative to the bulk of the plasma membrane. Direct detection of PM lipids in the ‘periprotein space’ supports the conclusion that proteins function in the presence of a locally disordered lipid state.
Automated Feature Extraction from Population Wearable Device Data Identified Novel Loci Associated with Sleep and Circadian Rhythms
Authors: Li Xinyue , Zhao Hongyu 
Published: April 2020

AbstractWearable devices have been increasingly used in research to provide continuous physical activity monitoring, but how to effectively extract features remains challenging for researchers. To analyze the generated actigraphy data in large-scale population studies, we developed computationally efficient methods to derive sleep and activity features through a Hidden Markov Model-based sleep/wake identification algorithm, and circadian rhythm features through a Penalized Multi-band Learning approach adapted from machine learning. Unsupervised feature extraction is useful when labeled data are unavailable, especially in large-scale population studies. We applied these two methods to the UK Biobank wearable device data and used the derived sleep and circadian features as phenotypes in genome-wide association studies. We identified 53 genetic loci with p<5×10-8including genes known to be associated with sleep disorders and circadian rhythms as well as novel loci associated with Body Mass Index, mental diseases and neurological disorders, which suggest shared genetic factors of sleep and circadian rhythms with physical and mental health. Further cross-tissue enrichment analysis highlights the important role of the central nervous system and the shared genetic architecture with metabolism-related traits and the metabolic system. Our study demonstrates the effectiveness of our unsupervised methods for wearable device data when additional training data cannot be easily acquired, and our study further expands the application of wearable devices in population studies and genetic studies to provide novel biological insights.
Convergence and novelty in adaptation to whole genome duplication in three independent polyploids
Authors: Bray Sian M. , Wolf Eva M. , Zhou Min , Busoms Silvia , Bohutínská Magdalena , Paajanen Pirita , Monnahan Patrick , Koch Jordan , Fischer Sina , Koch Marcus A. , Yant Levi 
Published: April 2020

AbstractConvergent evolution is observed broadly across the web of life, but the degree of evolutionary constraint during adaptation of core intracellular processes is not known. High constraint has been assumed for conserved processes, such as cell division and DNA repair, but reports of nimble evolutionary shifts in these processes have confounded this expectation. Whole genome duplication (WGD) necessitates the concerted adjustment of a wide range of fundamental intracellular functions but nevertheless has been repeatedly survived in all kingdoms. Given this repeated adaptation to WGD despite obvious intracellular challenges to core processes such as meiosis, we asked: how do lineages not only survive WGD, but sometimes ultimately thrive? Are the solutions employed constrained or diverse? Here we detect genes and processes under selection following WGD in theCochleariaspecies complex by performing a scan for selective sweeps following WGD in a large-scale survey of 73 resequenced individuals from 23 populations across Europe. We then contrast our results from two independent WGDs inArabidopsis arenosaandCardamine amara.We find that while WGD does require the adaptation of particular functional processes in all three cases, the specific genes recruited to respond are highly flexible. We also observe evidence of varying degrees of convergence between different cases. Our results point to a polygenic basis for the distributed adaptive systems that control meiotic crossover number, ionomic rewiring, cell cycle control, and nuclear regulation. Given the sheer number of loci under selection post-WGD, we surmise that this polygenicity may explain the general lack of convergence between these species that are ~30 million years diverged. Based on our results, we speculate that adaptive processes themselves – such as the rate of generation of structural genomic variants—may be altered by WGD in nascent autopolyploids, contributing to the occasionally spectacular adaptability of autopolyploids observed across kingdoms.
Laser capture microdissection in combination with mass spectrometry: Approach to characterization of tissue-specific proteomes ofEudiplozoon nipponicum(Monogenea, Polyopisthocotylea)
Authors: Roudnický Pavel , Potěšil David , Zdráhal Zbyněk , Gelnar Milan , Kašný Martin 
Published: April 2020

AbstractEudiplozoon nipponicum(Goto, 1891) is a hematophagous monogenean ectoparasite which inhabits the gills of the common carp (Cyprinus carpio). Heavy infestation can lead to anemia and in conjunction with secondary bacterial infections cause poor health and eventual death of the host.This study is based on an innovative approach to protein localization which has never been used in parasitology before. Using laser capture microdissection, we dissected particular areas of the parasite body without contaminating the samples by surrounding tissue, and in combination with analysis by mass spectrometry obtained tissue-specific proteomes of tegument, intestine, and parenchyma of our model organism,E. nipponicum. We successfully verified the presence of certain functional proteins (e.g. cathepsin L) in tissues where their presence was expected (intestine) and confirmed that there were no traces of these proteins in other tissues (tegument and parenchyma). Additionally, we identified a total of 2,059 proteins, including 72 peptidases and 33 peptidase inhibitors. As expected, the greatest variety was found in the intestine and the lowest variety in the parenchyma.Our results are significant on two levels. Firstly, we demonstrated how one can localize all proteins in one analysis and without using laboratory animals (antibodies for immunolocalization of single proteins). Secondly, this study offers the first complex proteomic data on not only theE. nipponicumbut within the whole class of Monogenea, which was from this point of view until recently neglected.
Multiscale Co-Expression in the Brain
Authors: Harris Benjamin D. , Crow Megan , Fischer Stephan , Gillis Jesse 
Published: April 2020

ABSTRACTSingle-cell RNA-sequencing (scRNAseq) data can reveal co-regulatory relationships between genes that may be hidden in bulk RNAseq due to cell type confounding. Using the primary motor cortex data from the Brain Initiative Cell Census Network (BICCN), we study cell type specific co-expression across 500,000 cells. Surprisingly, we find that the same gene-gene relationships that differentiate cell types are evident at finer and broader scales, suggesting a consistent multiscale regulatory landscape.
The ModelSEED Database for the integration of metabolic annotations and the reconstruction, comparison, and analysis of metabolic models for plants, fungi, and microbes
Authors: Seaver Samuel M. D. , Liu Filipe , Zhang Qizhi , Jeffryes James , Faria José P. , Edirisinghe Janaka N. , Mundy Michael , Chia Nicholas , Noor Elad , Beber Moritz E. , Best Aaron A. , DeJongh Matthew , Kimbrel Jeffrey A. , D’haeseleer Patrik , Pearson Erik , Canon Shane , Wood-Charlson Elisha M. , Cottingham Robert W. , Arkin Adam P. , Henry Christopher S. 
Published: April 2020

ABSTRACTFor over ten years, ModelSEED has been a primary resource for the construction of draft genome-scale metabolic models based on annotated microbial or plant genomes. Now being released, the biochemistry database serves as the foundation of biochemical data underlying ModelSEED and KBase. The biochemistry database embodies several properties that, taken together, distinguish it from other published biochemistry resources by: (i) including compartmentalization, transport reactions, charged molecules and proton balancing on reactions;; (ii) being extensible by the user community, with all data stored in GitHub; and (iii) design as a biochemical “Rosetta Stone” to facilitate comparison and integration of annotations from many different tools and databases. The database was constructed by combining chemical data from many resources, applying standard transformations, identifying redundancies, and computing thermodynamic properties. The ModelSEED biochemistry is continually tested using flux balance analysis to ensure the biochemical network is modeling-ready and capable of simulating diverse phenotypes. Ontologies can be designed to aid in comparing and reconciling metabolic reconstructions that differ in how they represent various metabolic pathways. ModelSEED now includes 33,978 compounds and 36,645 reactions, available as a set of extensible files on GitHub, and available to search athttps://modelseed.organd KBase.
Brain Network Organization During Mindful Acceptance of Emotions
Authors: Dixon Matthew Luke , Girn Manesh , Christoff Kalina 
Published: April 2020

AbstractIndividuals use various strategies to cope with challenging emotions such as anxiety. Mindful acceptance involves broadening attentional scope and fully experiencing present moment sensory feelings (whether pleasant or unpleasant) without judgment or elaboration. In contrast, narrative-evaluation involves focusing on a narrow band of sensory experience and generating an elaborate narrative about the meaning and desirability of one’s emotional feelings. The current study examined brain network organization during these strategies using graph theoretic analyses. We used a naturalistic task paradigm in which participants reflected on an anxiety-provoking issue from their personal lives and adopted each strategy in different blocks. Compared to narrative-evaluation, mindful acceptance was associated with: (i) increased global network connectivity; (ii) greater integration of interoceptive regions (mid and posterior insula) into large-scale networks; (iii) reorganization of motivational circuits including a shift in the striatum’s network assignment from the default network to the salience network; and (iv) a shift from default network to frontoparietal control network (FPCN) regions as central hubs that coordinate information flow. Functional connectivity patterns within the left FPCN were associated with acceptance reports. Thus, broadening attentional scope during mindful acceptance is supported by a more globally interconnected neural landscape, as well as greater information flow through FPCN regions that underlie metacognitive awareness and cognitive control.
The quorum-sensing systems ofVibrio campbelliiDS40M4 and BB120 are genetically and functionally distinct
Authors: Simpson Chelsea A. , Petersen Blake D. , Haas Nicholas W. , Geyman Logan J. , Lee Aimee H. , Podicheti Ram , Pepin Robert , Brown Laura C. , Rusch Douglas B. , Manzella Michael P. , Papenfort Kai , van Kessel Julia C. 
Published: April 2020

SummaryVibrio campbelliiBB120 (previously classified asVibrio harveyi) is a fundamental model strain for studying quorum sensing in vibrios. A phylogenetic evaluation of sequencedVibriostrains in Genbank revealed that BB120 is closely related to the environmental isolateV. campbelliiDS40M4. We exploited DS40M4’s competence for exogenous DNA uptake to rapidly generate >30 isogenic strains with deletions of genes encoding BB120 quorum-sensing system homologs. Our results show that the quorum-sensing circuit of DS40M4 is distinct from BB120 in three ways: 1) DS40M4 does not produce an acyl homoserine lactone autoinducer but encodes an active orphan LuxN receptor, 2) the quorum regulatory small RNAs (Qrrs) are not solely regulated by autoinducer signaling through the response regulator LuxO, and 3) the DS40M4 quorum-sensing regulon is much smaller than BB120 (~100 genes vs ~400 genes, respectively). Using comparative genomics to expand our understanding of quorum-sensing circuit diversity, we observe that conservation of LuxM/LuxN proteins differs widely both between and withinVibriospecies. These strains are also phenotypically distinct: DS40M4 exhibits stronger interbacterial cell killing, whereas BB120 forms more robust biofilms and is bioluminescent. These results underscore the need to examine wild isolates for a broader view of bacterial diversity in the marine ecosystem.Originality-Significance StatementWild bacterial isolates yield important information about traits that vary within species. Here, we compare environmental isolateVibrio campbelliiDS40M4 to its close relative, the model strain BB120 that has been a fundamental strain for studying quorum sensing for >30 years. We examine several phenotypes that define this species, including quorum sensing, bioluminescence, and biofilm formation. Importantly, DS40M4 is naturally transformable with exogenous DNA, which allows for the rapid generation of mutants in a laboratory setting. By exploiting natural transformation, we genetically dissected the functions of BB120 quorum-sensing system homologs in the DS40M4 strain, including two-component signaling systems, transcriptional regulators, and small RNAs.