bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Mean Unfulfilled Lifespan (MUL): A new indicator of the impact of mortality shocks on the individual lifespan, with application to global 2020 quarterly mortality from COVID-19
Authors: Heuveline Patrick 
Published: August 2020

AbstractDeclines in period life expectancy at birth (PLEB) provide intuitive indicators of the impact of a cause of death on the individual lifespan. Derived under the assumption that future mortality conditions will remain indefinitely those observed during a reference period, however, the intuitive interpretation of a PLEB becomes problematic when that period conditions reflect a temporary mortality “shock”, resulting from a natural disaster or the diffusion of a new epidemic in the population for instance.Rather than to make assumptions about future mortality, I propose measuring the difference between a period average age at death and the average expected age at death of the same individuals (death cohort): the Mean Unfulfilled Lifespan (MUL). For fine-grained tracking of the mortality impact of an epidemic, I also provide an empirical shortcut to MUL estimation for small areas or short periods.For illustration, quarterly MUL values in 2020 are derived from estimates of COVID-19 deaths in 159 national populations and 122 sub-national populations in Italy, Mexico, Spain and the US. The highest quarterly values in national populations are obtained for Ecuador (5.12 years, second quarter) and Peru (4.56 years, third quarter) and, in sub-national populations, for New York (5.52 years), New Jersey (5.56 years, second quarter) and Baja California (5.19 years, fourth quarter). Using a seven-day rolling window, the empirical shortcut suggests the MUL peaked at 9.12 years in Madrid, 9.20 years in New York, and 9.15 years in Baja California, and in Guayas (Ecuador) it even reached 12.6 years for the entire month of April.Based on reported COVID-19 deaths that might substantially underestimate overall mortality change in affected populations, these results nonetheless illustrate how the MUL tracks the mortality impact of the pandemic, or any mortality shock, retaining the intuitive metric of differences in PLEB, without their problematic underlying assumptions.
Cumulative survival profiling: a new PAP-based method for detecting heteroresistance in staphylococcal clinical isolates
Authors: Alsallaq Ramzi A. , Dao Tina H. , Rosch Jason W. , Margolis Elisa 
Published: August 2020

AbstractThe area under the population analysis profile (PAP) is used in the gold standard method for detecting heteroresistance in staphylococci. We tested the hypothesis that the initial inoculum strongly influences the area under the population analysis profile. We sought to interpret this dependence and develop a new metric that lacks this dependence to retrospectively detect heteroresistance to vancomycin in coagulase-negative staphylococcal (CoNS) isolates.We tested our hypothesis on 20 PAPs from the heteroresistant positive control isolate (Mu3) and 7 PAPs from one CoNS isolate which is associated with poor clinical response. The area under the PAP depended linearly (p<0.001) on the initial inoculum. We interpreted the slope to be the cumulative survival under vancomycine concentration gradient. The statistical distribution of the cumulative survival for Mu3 and the CoNS isolate constituted the cumulative survival profiles for each. The profiles reflect ed spectrum of response under vancomycine gradient with the left-tail of CoNS isolate profile located near the median of Mu3 profile indicating the heteroresistance of the CoNS isolate and that the most resistant in the spectrum are likely to be associated with poor clinical response. We estimated that about two-third of the CoNS from unique participants are heteroresistant with 80% of heteroresistant isolates may be associated with a poor clinical response.
Fine-tuned Forecasting Techniques for COVID-19 Prediction in India
Authors: Gola Abhinav , Arya Ravi Kumar , Animesh  , Dugh Ravi , Khan Zuber 
Published: August 2020

AbstractEstimation of statistical quantities plays a cardinal role in handling of convoluted situations such as COVID-19 pandemic and forecasting the number of affected people and fatalities is a major component for such estimations. Past researches have shown that simplistic numerical models fare much better than the complex stochastic and regression-based models when predicting for countries such as India, United States and Brazil where there is no indication of a peak anytime soon. In this research work, we present two models which give most accurate results when compared with other forecasting techniques. We performed both short-term and long-term forecasting based on these models and present the results for two discrete durations.
Bias and precision of parameter estimates from models using polygenic scores to estimate environmental and genetic parental influences
Authors: Kim Yongkang , Balbona Jared V. , Keller Matthew C. 
Published: August 2020

AbstractIn a companion paper (Balbona et al. (2020)), we introduced a series of causal models that use polygenic scores from transmitted and nontransmitted alleles, the offspring trait, and parental traits to estimate the variation due to the environmental influences the parental trait has on the offspring trait (vertical transmission) as well as additive genetic effects. These models also estimate and account for the gene-gene and gene-environment covariation that arises from assortative mating and vertical transmission respectively. In the current study, we simulated polygenic scores and phenotypes of parents and offspring under genetic and vertical transmission scenarios, assuming two types of assortative mating. We instantiated the models from our companion paper in the OpenMx software, and compared the true values of parameters to maximum likelihood estimates from models fitted on the simulated data to quantify the bias and precision of estimates. We show that parameter estimates from these models are unbiased when assumptions are met, but as expected, they are biased to the degree that assumptions are unmet. Standard errors of the estimated variances due to vertical transmission and to genetic effects decrease with increasing sample sizes and with increasingr2values of the polygenic score. Even when the polygenic score explains a modest amount of trait variation (r2= .05), standard errors of these standardized estimates were reasonable (< .05) forn= 16Ktrios, and smaller sample sizes (e.g., down to 4K) when the polygenic score is more predictive. These causal models offer a novel approach for understanding how parents influence their offspring, but their use requires polygenic scores on relevant traits that are modestly predictive (e.g.,r2> .025) as well as datasets with genomic and phenotypic information on parents and offspring. The utility of polygenic scores for elucidating parental influences should thus serve as additional motivation for large genomic biobanks to perform GWAS’s on traits that may be relevant to parenting and to oversample close relatives, particularly parents and offspring.
Understanding transformation tolerant visual object representations in the human brain and convolutional neural networks
Authors: Xu Yaoda , Vaziri-Pashkam Maryam 
Published: August 2020

AbstractForming transformation-tolerant object representations is critical to high-level primate vision. Despite its significance, many details of tolerance in the human brain remain unknown. Likewise, despite the ability of convolutional neural networks (CNNs) to exhibit human-like object categorization performance, whether CNNs form tolerance similar to that of the human brain is unknown. Here we provide the first comprehensive documentation and comparison of three tolerance measures in the human brain and CNNs. We measured fMRI responses from human ventral visual areas to real-world objects across both Euclidean and non-Euclidean feature changes. In single fMRI voxels in higher visual areas, we observed robust object response rank-order preservation across feature changes. This is indicative of functional smoothness in tolerance at the fMRI meso-scale level that has never been reported before. At the voxel population level, we found highly consistent object representational structure across feature changes towards the end of ventral processing. Rank-order preservation, consistency, and a third tolerance measure, cross-decoding success (i.e., a linear classifier’s ability to generalize performance across feature changes) showed an overall tight coupling. These tolerance measures were lower for Euclidean than non-Euclidean feature changes in lower visual areas, but increased over the course of ventral processing in most cases. These characteristics of tolerance, however, were absent in eight CNNs pretrained with ImageNet images with varying network architecture, depth, the presence/absence of recurrent processing, or whether a network was pretrained with the original or stylized ImageNet images that encouraged shape processing. Most notably, CNNs do not show increased representational consistency across feature changes at the higher layers. CNNs thus do not appear to develop the same kind of tolerance as the human brain over the course of visual processing.Significant StatementPerceiving object identity among changes in non-identity features and forming transformation-tolerant object representations is essential to high-level primate vision. Here we provide a comprehensive documentation and comparison of three tolerance measures between the human brain and CNNs pretrained for object classification. While all three measures show increased tolerance in the human brain across four types of feature changes towards the end of ventral visual processing, CNNs fail to develop the same kind of tolerance with visual processing.
PCNA monoubiquitination is regulated by diffusion of Rad6/Rad18 complexes along RPA filaments
Authors: Li Mingjie , Sengupta Bhaswati , Benkovic Stephen J. , Lee Tae Hee , Hedglin Mark 
Published: August 2020

ABSTRACTTranslesion DNA synthesis (TLS) enables DNA replication through damaging modifications to template DNA and requires monoubiquitination of the PCNA sliding clamp by the Rad6/Rad18 complex. This posttranslational modification is critical to cell survival following exposure to DNA damaging agents and is tightly regulated to restrict TLS to damaged DNA. RPA, the major single strand DNA (ssDNA) binding protein, forms filaments on ssDNA exposed at TLS sites and plays critical yet undefined roles in regulating PCNA monoubiquitination. Here, we utilize kinetic assays and single molecule FRET microscopy to monitor PCNA monoubiquitination and Rad6/Rad18 complex dynamics on RPA filaments, respectively. Results reveal that a Rad6/Rad18 complex is recruited to an RPA filament via Rad18•RPA interactions and randomly translocates along the filament. These translocations promote productive interactions between the Rad6/Rad18 complex and the resident PCNA, significantly enhancing monoubiquitination. These results illuminate critical roles of RPA in the specificity and efficiency of PCNA monoubiquitination.
Development and application of aerobic, chemically defined media forDysgonomonas
Authors: Bridges Charles M. , Gage Daniel J. 
Published: August 2020

AbstractMembers ofDysgonomonasare Gram-negative, non-motile, facultatively anaerobic coccobacilli originally described in relation to their isolation stool and wounds of human patients (CDC group DF-3). More recentlyDysgonomonashave been found to be widely distributed in terrestrial environments and are particularly enriched in insect systems. Their prevalence in xylophagous insects such as termites and wood-feeding cockroaches, as well as in soil-fed microbial fuel cells, elicit interest in lignocellulose degradation and biofuel production, respectively. Their prevalence in mosquito and fruit fly have implications relating to symbiosis, host immunology and developmental biology. Additionally, their prevalence in termite, mosquito and nematode present novel opportunities for pest and vector control. Currently, the absolute growth requirements ofDysgonomonasare unknown, and they are cultured solely under anaerobic conditions on complex media containing blood, peptones, tryptones, and yeast, plant or meat extracts. Restrictive & undefined culturing conditions preclude physiological and genetic studies, and thus further understanding of metabolic potential. Here we describe the requirements for growth of termite-derivedDysgonomonasisolates and create parallel defined, minimal and complex media that permit vigorous and reliable aerobic growth. Furthermore, we show that these media can be used to easily enrich forDysgonomonasisolates from complex and microbially-diverse environmental samples.Impact StatementMembers of the genusDysgonomonasare increasingly prevalent in ecological, medical and biotechnological contexts. To the best of our knowledge, there are currently no formulations for chemically defined or minimal media forDysgonomonas, and limited complex formulations that allow aerobic growth, particularly on solid media. We have created three parallel media formulations (complex, defined & minimal) that permit robust aerobic and anaerobic growth in liquid and agar-solidified media. These formulations remove the necessity for animal blood and expensive equipment such as anaerobic chambers, which can inhibit basic research by groups with biosafety and resource limitations.
MultiPaths: a Python framework for analyzing multi-layer biological networks using diffusion algorithms
Authors: Marín-Llaó Josep , Mubeen Sarah , Perera-Lluna Alexandre , Hofmann-Apitius Martin , Picart-Armada Sergio , Domingo-Fernández Daniel 
Published: August 2020

AbstractSummaryHigh-throughput screening yields vast amounts of biological data which can be highly challenging to interpret. In response, knowledge-driven approaches emerged as possible solutions to analyze large datasets by leveraging prior knowledge of biomolecular interactions represented in the form of biological networks. Nonetheless, given their size and complexity, their manual investigation quickly becomes impractical. Thus, computational approaches, such as diffusion algorithms, are often employed to interpret and contextualize the results of high-throughput experiments. Here, we present MultiPaths, a framework consisting of two independent Python packages for network analysis. While the first package, DiffuPy, comprises numerous state-of-the-art diffusion algorithms applicable to any generic network, the second, DiffuPath, enables the application of these algorithms on multi-layer biological networks. To facilitate its usability, the framework includes a command line interface, reproducible examples, and documentation. To demonstrate the framework, we conducted several diffusion experiments on three independent multi-omicsdatasets over disparate networks generated from pathway databases, thus, highlighting the ability of multi-layer networks to integrate multiple modalities. Finally, the results of these experiments demonstrate how the generation of harmonized networks from disparate databases can improve predictive performance with respect to individual resources.AvailabilityDiffuPy and DiffuPath are publicly available under the Apache License 2.0 athttps://github.com/multipaths.Contactsergi.picart@upc.eduanddaniel.domingo.fernandez@scai.fraunhofer.de
Characterization of a newLeishmania majorisolate for use in a controlled human infection model
Authors: Ashwin Helen , Sadlova Jovana , Vojtkova Barbora , Becvar Tomas , Lypaczewski Patrick , Schwartz Eli , Greensted Elizabeth , Van Bocxlaer Katrien , Pasin Marion , Lipinski Kai S. , Parkash Vivak , Matlashewski Greg , Layton Alison M. , Lacey Charles J. , Jaffe Charles L. , Volf Petr , Kaye Paul M. 
Published: August 2020

AbstractLeishmaniasis is widely regarded as a vaccine-preventable disease, but the costs required to reach pivotal Phase 3 studies and uncertainty about which candidate vaccines should be progressed into human studies significantly limits progress in vaccine development for this neglected tropical disease. Controlled human infection models (CHIM) provide a pathway for accelerating vaccine development and to more fully understand disease pathogenesis and correlates of protection. Here, we describe the isolation, characterization and GMP manufacture of a new clinical isolate ofLeishmania major. Two fresh isolates ofL. majorfrom Israel were initially compared by genome sequencing,in vivoinfectivity and drug sensitivity in mice, and development and transmission competence in sand flies, allowing one (L. major_MRC-02) to be selected for GMP production. This study addresses a major roadblock in the development of vaccines for leishmaniasis, providing a key resource for CHIM studies of sand fly transmitted cutaneous leishmaniasis.
Wine terroir and the soil microbiome: an amplicon sequencing–based assessment of the Barossa Valley and its sub-regions
Authors: Zhou Jia , Cavagnaro Timothy R. , De Bei Roberta , Nelson Tiffanie M. , Stephen John R. , Metcalfe Andrew , Gilliham Matthew , Breen James , Collins Cassandra , Rodríguez López Carlos M. 
Published: August 2020

AbstractSoil is an important factor that contributes to the uniqueness of a wine produced by vines grown in specific conditions. Recent data shows that the composition, diversity and function of soil microbial communities may play important roles in determining wine quality and indirectly affect its economic value. Here, we evaluated the impact of environmental variables on the soil microbiomes of 22 Barossa Valley vineyard sites based on the 16S rRNA gene hypervariable region 4. In this study, we report that environmental heterogeneity (soil plant-available P content, elevation, rainfall, temperature, spacing between row and spacing between vine) caused more microbial dissimilarity than geographic distance. Vineyards located in cooler and wetter regions showed lower beta diversity and a higher ratio of dominant taxa. Differences in microbial community composition were significantly associated with differences in fruit traits and in wine chemical and metabolomic profiles, highlighting the potential influence of microbial communities on the phenotype of grapevines. Our results suggest that environmental factors affect wine terroir, and this may be mediated by changes in microbial structure, thus providing a basic understanding of how growing conditions affect interactions between plants and their soil microbiomes.
Reference genes for gene expression analysis in the fungal pathogenNeonectria ditissimaand their use demonstrating expression up-regulation of candidate virulence genes
Authors: Florez Liz M. , Scheper Reiny W. A. , Fisher Brent M. , Sutherland Paul W. , Templeton Matthew D. , Bowen Joanna K. 
Published: August 2020

AbstractEuropean canker, caused by the necrotrophic fungal phytopathogenNeonectria ditissima, is one of the most damaging apple diseases worldwide. An understanding of the molecular basis ofN. ditissimavirulence is currently lacking. Identification of genes with an up-regulation of expression during infection, which are therefore probably involved in virulence, is a first step towards this understanding. Real-time quantitative reverse transcription PCR (qRT-PCR) can be used to identify these candidate virulence genes, but relies on the use of reference genes for relative gene expression data normalisation. However, no report that addresses selecting appropriate fungal reference genes for use in theN. ditissima-apple pathosystem has been published to date. In this study, eightN. ditissimagenes were selected as candidate qRT-PCR reference genes for gene expression analysis. A subset of the primers (six) designed to amplify regions from these genes were specific forN. ditissima, failing to amplify PCR products with template from other fungal pathogens present in the apple orchard. The efficiency of amplification of these six primer sets was satisfactory, ranging from 81.8 to 107.53%. Analysis of expression stability when a highly pathogenicN. ditissimaisolate was cultured under 10 regimes, using the statistical algorithms geNorm, NormFinder and BestKeeper, indicated thatactinandmyo-inositol-1-phosphate synthase(mips), or their combination, could be utilised as the most suitable reference genes for normalisation ofN. ditissimagene expression. As a test case, these reference genes were used to study expression of three candidate virulence genes during a time course of infection. All three, which shared traits with fungal effector genes, had up-regulated expressionin plantacompared toin vitrowith expression peaking between five and six weeks post inoculation (wpi). Thus, these three genes may well be involved inN. ditissimapathogenicity and are priority candidates for further functional characterization.
CAP1 and cofilin1 cooperate in neuronal actin dynamics, growth cone function and neuron connectivity
Authors: Schneider Felix , Duong Thuy-An , Metz Isabell , Winkelmeier Jannik , Hübner Christian A. , Endesfelder Ulrike , Rust Marco B. 
Published: August 2020

AbstractNeuron connectivity depends on growth cones that navigate axons through the developing brain. Growth cones protrude and retract actin-rich structures to sense guidance cues. These cues control local actin dynamics and steer growth cones towards attractants and away from repellents, thereby directing axon outgrowth. Hence, actin binding proteins (ABPs) moved into the focus as critical regulators of neuron connectivity. We found cyclase-associated protein 1 (CAP1), an ABP with unknown brain function, abundant in growth cones. Super-resolution microscopy and live cell imaging combined with pharmacological approaches on hippocampal neurons from gene-targeted mice revealed a crucial role for CAP1 in actin dynamics that is critical for growth cone morphology and function. Growth cone defects in mutant neurons compromised neuron differentiation and was associated with impaired neuron connectivity in CAP1 mutant brains. Mechanistically, we found that CAP1 and cofilin1 synergistically control growth cone actin dynamic and morphology. Together, we identified CAP1 as a novel actin regulator in growth cone that is relevant for neuron connectivity.