bluuebunny/crossref_metadata_2025_split huggingface dataset:
Designing and studying a mutant form of the ice-binding protein fromChoristoneura fumiferana
Authors: Glukhova Ksenia A. , Okulova Julia D. , Melnik Bogdan S. 
Published: September 2020

AbstractIce-binding proteins are expressed in the cells of some organisms, helping them to survive extremely low temperatures. One of the problems in study of such proteins is the difficulty of isolation and purification. For example, eight cysteine residues in cfAFP fromChoristoneura fumiferana(the eastern spruce budworm) form intermolecular bridges during the overexpression of this protein. This impedes the process of the protein purification dramatically.In this work we designed a mutant form of ice-binding protein cfAFP, which is much more easy to isolate that the wild-type protein. The mutant form named mIBP83 did not lose the ability to bind to ice surface. Besides, observation of the processes of freezing and melting of ice in presence of mIBP83 showed that this protein affects the process of ice melting, increasing its melting temperature, and at least does not decrease the freezing temperature.
Date palm virus A: first plant virus found in date palm trees
Authors: Maachi Ayoub , Nagata Tatsuya , Silva João Marcos Fagundes 
Published: September 2020

AbstractIn this work, a novel ssRNA (+) viral genomic sequence with gene organization typical of members of the subfamilyQuinvirinae(familyBetaflexiviridae) was identified using high throughput sequencing data of date palm obtained from the Sequence Read Archive database. The viral genome sequence consists of 7860 nucleotides and contains five ORFs encoding for the replication protein (Rep), triple gene block proteins 1, 2, 3 (TGB 1, 2 and 3) and coat protein (CP). Phylogenetic analysis based on the Rep and the CP amino acid sequences showed the closest relationship to garlic yellow mosaic-associated virus (GYMaV). Based on the demarcation criteria of the familyBetaflexiviridae, this new virus, provisionally named date palm virus A (DPVA), could constitute a member of a novel genus. However, considering that DPVA and GYMaV share the same genomic organization and that they cluster together on the Rep phylogenetic analysis, they could also constitute a novel genus together, highlighting the necessity of a revision of the taxonomic criteria of the familyBetaflexiviridae.
IL-4-induced hysteresis in naïve T cell activation
Authors: Meli Alexandre P. , Wang Yaqiu , de Kouchkovsky Dimitri A. , Kong Yong , Basu Malay K. , Ghosh Sourav , Rothlin Carla V. 
Published: September 2020

AbstractNaïve T cells are generally considered to be a homogeneous population, but for their unique T cell receptors (TCRs). Naïve T cells are activated within a specific cytokine milieu upon interaction with antigen-presenting cells through cognate TCR::MHC-peptide interaction and co-stimulation. Here we demonstrate that naïve T cells are transcriptionally heterogeneous, and that the relative proportions of transcriptionally distinct naïve T cell subpopulations are modified by immune responses, such as during helminth infection. Not only are cognate naïve T cells activated during an immune response, but the cytokine produced - such as IL-4 during helminth infection - changes the transcriptome of bystander naïve T cells. Such changes in gene expression and population level heterogeneity in bystander naïve T cells result in altered responses to a concurrent immune challenge, for instance, hypo-responsiveness to vaccination. Thus, naïve T cell activation is not the result of a singular temporal event, but is characterized by hysteresis. Our studies suggest that antigen-agnostic, cytokine-dependent naïve T cell conditioning and resulting hysteresis is a mechanism that integrates input signals from concurrent infections for the regulation of the overall magnitude of the immune response.
SLEAP: Multi-animal pose tracking
Authors: Pereira Talmo D. , Tabris Nathaniel , Li Junyu , Ravindranath Shruthi , Papadoyannis Eleni S. , Wang Z. Yan , Turner David M. , McKenzie-Smith Grace , Kocher Sarah D. , Falkner Annegret L. , Shaevitz Joshua W. , Murthy Mala 
Published: September 2020

AbstractThe desire to understand how the brain generates and patterns behavior has driven rapid methodological innovation to quantify and model natural animal behavior. This has led to important advances in deep learning-based markerless pose estimation that have been enabled in part by the success of deep learning for computer vision applications. Here we present SLEAP (Social LEAP Estimates Animal Poses), a framework for multi-animal pose tracking via deep learning. This system is capable of simultaneously tracking any number of animals during social interactions and across a variety of experimental conditions. SLEAP implements several complementary approaches for dealing with the problems inherent in moving from single-to multi-animal pose tracking, including configurable neural network architectures, inference techniques, and tracking algorithms, enabling easy specialization and tuning for particular experimental conditions or performance requirements. We report results on multiple datasets of socially interacting animals (flies, bees, and mice) and describe how dataset-specific properties can be leveraged to determine the best configuration of SLEAP models. Using a high accuracy model (<2.8 px error on 95% of points), we were able to track two animals from full size 1024 × 1024 pixel frames at up to 320 FPS. The SLEAP framework comes with a sophisticated graphical user interface, multi-platform support, Colab-based GPU-free training and inference, and complete tutorials available, in addition to the datasets, atsleap.ai.
Ciliary signaling-patterned smooth muscle drives tubular elongation
Authors: Yang Ying , Paivinen Pekka , Xie Chang , Krup Alexis Leigh , Makela Tomi P. , Mostov Keith E. , Reiter Jeremy F. 
Published: September 2020

SummaryDuring development, many tubular organs undergo extensive longitudinal growth to reach their defined length, essential for their function, but how they lengthen is poorly understood. Here, we found that primary cilia are critical for the elongation of the small intestine and esophagus during murine embryonic development. More specifically, HH ligands produced by the epithelium signaled via cilia in the surrounding mesenchyme to pattern the smooth muscle. Like attenuated ciliary HH signaling, partial ablation of the smooth muscle reduced elongation, revealing an essential role for smooth muscle in longitudinal growth. Disruption of cilia, HH signaling or the smooth muscle reduced residual stress within the gut wall, indicating that smooth muscle contributes to the mechanical properties of the developing gut. Reducing residual stress decreased nuclear YAP, an effector of the mechanotransductive Hippo pathway. Removing YAP in the mesenchyme did not affect smooth muscle formation, but attenuated proliferation and elongation, demonstrating that YAP interprets smooth muscle-generated force to promote proliferation. Together, our results reveal that ciliary signaling directs the formation of the smooth muscle layer which, in turn, generates mechanical forces that activate YAP-mediated proliferation. As this interplay of biochemical and mechanical signals drives elongation of both the esophagus and small intestine, we propose that this mechanism may underlie tubular organ elongation generally.HighlightsPrimary cilia are essential for the elongation of the small intestine and esophagus during embryonic developmentCiliary signaling patterns the smooth muscle in the developing intestine and esophagusThe smooth muscle contributes to tissue mechanicsSmooth muscle-generated strain activates YAP to drive longitudinal growth of the tubular organs
SOCS1/SOCS3 Immune Axis Modulates Synthetic Perturbations in IL6 Biological Circuit for Dynamical Cellular Response
Authors: Soni Bhavnita , Singh Shailza 
Published: September 2020

AbstractMacrophage phenotype plays a crucial role in the pathogenesis of Leishmanial infection. Pro-inflammatory cytokines are the key regulators that eliminate the infection induced by Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Suppressor of cytokine signaling (SOCS) is a well-known negative feedback regulator of JAK/STAT pathway. However, change in expression levels of SOCS in correlation with the establishment of infection is not well understood. Mathematical modeling of IL6 signaling pathway have helped identified the role of SOCS1 in establishment of infection. Furthermore, the ratio of SOCS1 and SOCS3 has been quantified bothin silicoas well asin vitro, indicating an immune axis which governs the macrophage phenotype duringL. majorinfection. The ability of SOCS1 protein to inhibit the JAK/STAT1 signaling pathway and thereby decreasing pro-inflammatory cytokine expression makes it a strong candidate for therapeutic intervention. Using synthetic biology approaches, peptide based immuno-regulatory circuit have been designed to target the activity of SOCS1 which can restore pro-inflammatory cytokine expression during infection.
Crucial role of ppGpp in the resilience ofEscherichia colito growth disruption
Authors: Patacq Clément , Chaudet Nicolas , Letisse Fabien 
Published: September 2020

ABSTRACTBacteria grow in constantly changing environments that can suddenly become completely deleted in essential nutrients. The stringent response, a rewiring of the cellular metabolism mediated by the alarmone (p)ppGpp, plays a crucial role in adjusting bacterial growth to the severity of the nutritional insult. The ability of (p)ppGpp to trigger a slowdown of cell growth or induce bacterial dormancy has been widely investigated. However, little is known about the role of (p)ppGpp in promoting growth recovery after severe growth inhibition. In this study, we performed a time-resolved analysis of (p)ppGpp metabolism inEscherichia colias it recovered from a sudden slowdown in growth. Results show thatE. colirecovers by itself from the growth disruption provoked by the addition of serine hydroxamate, the serine analogue that we used to induce the stringent response. Growth inhibition was accompanied by a severe disturbance of metabolic activity and more surprisingly, by a transient overflow of valine and alanine. Our data also show that ppGpp is crucial for growth recovery since in the absence of ppGpp,E. coli’s growth recovery was slower. In contrast, an increased concentration of pppGpp was found to have no significant effect on growth recovery. Interestingly, the observed decrease in intracellular ppGpp levels in the recovery phase correlated with bacterial growth and the main effect involved was identified as growth dilution rather than active degradative process. This report thus significantly expands our knowledge of (p)ppGpp metabolism inE. coliphysiology.IMPORTANCEThe capacity of microbes to resist and overcome environmental insults, know as resilience, allows them to survive in changing environments but also to resist antibiotic and biocide treatments, immune system responses. Although the role of the stringent response in bacterial resilience to nutritional insults has been well studied, little is known about its importance in the ability of the bacteria to not just resist but also recover from these disturbances. To address this important question, we investigated growth disruption resilience in the model bacteriumEscherichia coliand its dependency on the stringent response alarmone (p)ppGpp by quantifying ppGpp and pppGpp levels as growth was disrupted and then recovered. Our findings may thus contribute to understanding how ppGpp improvesE. coli’s resilience to nutritional stress and other environmental insults.
Community pharmacists’ knowledge and preparedness to participate in the fight against Coronavirus disease 2019 (COVID-19) in Zambia
Authors: Hangoma Jimmy Mapenzi , Mudenda Steward , Mwenechanya Mpande Mukumbwa , Kalungia Aubrey Chichoni 
Published: September 2020

AbstractBackgroundCoronavirus disease (COVID-19) pandemic has severely strained healthcare systems globally. Community pharmacists remain vital health professionals with unique roles in responding to symptoms, supplying medicines, and providing health promotion in the communities where they serve. The purpose of this study was to assess the level of knowledge and preparedness of community pharmacists in Zambia as frontline workers in curbing COVID-19.MethodThis descriptive cross-sectional survey was conducted among 300 registered community pharmacists in Zambia. A self-administered online questionnaire was used to collect the data. Descriptive statistics were used to analyse the data using the Statistical Package for Social Sciences version 23.ResultsFrom a total of 393 community pharmacists, 300 participated in the study indicating a response rate of 76.3%. 97% of the pharmacists knew the common signs and symptoms of COVID-19, 83% knew the national guidelines for screening criteria, and 93% were aware that a suspected case of COVID-19 presenting to the community pharmacy needed to be alerted to the national response team. Only 59% knew they needed to self-isolate and self-report should they experience symptoms of COVID-19. 85% stated that personal protective equipment was inadequate in the pharmacies they operated from. 60% of the pharmacists were prepared to participate in the frontline fight against COVID-19.ConclusionCommunity pharmacists in Zambia are knowledgeable about COVID-19 signs and symptoms, including the technical guidelines on the screening and detection of suspected cases. Community pharmacists are prepared to participate in the frontline fight against the COVID-19 pandemic in Zambia.
Social multipliers and the Covid-19 epidemic: Analysis through constrained maximum entropy modeling
Authors: Foley Duncan K. 
Published: September 2020

AbstractSocial multipliers occur when individual actions influence other individual actions so as to lead to amplified aggregate effects. Epidemic infections offer a dramatic example of this phenomenon since individual actions such as social distancing and masking that have small effects on individuals’ risk can have very large effects in reducing risk when they are widely adopted. This paper uses the info-metric method of constrained maximum entropy modeling to estimate the impact of social multiplier effects in the Covid-19 epidemic with a model that infers the length of infection, the rate of mortality, the base infection factor, and reductions in the infection factor due to changes in social behavior from data on daily infections and deaths. When the model takes account of the rate of reporting of infections, it can produce three rather different scenarios of epidemic dynamics, which have marginally different posterior probabilities: one in which reporting is very low, under 10% and the estimated infection is correspondingly large, and immunity effects play a significant role in stabilizing the epidemic; a second in which reporting is on the order of 25% and the model estimates a significant portion of the population as having inherent immunity to the infection; and a third where reporting rates are close to 100%, and the epidemic is controlled mostly by changes in social behavior. These qualitatively different scenarios reflect the limited data the method can extract information from in this case.
Rats strategically manage learning during perceptual decision making
Authors: Masís Javier , Chapman Travis , Rhee Juliana Y. , Cox David D. , Saxe Andrew M. 
Published: September 2020

AbstractBalancing the speed and accuracy of decisions is crucial for survival, but how organisms manage this trade-off during learning is largely unknown. Here, we track this trade-off during perceptual learning in rats and simulated agents. At the start of learning, rats chose long reaction times that did not optimize instantaneous reward rate, but by the end of learning chose near-optimal reaction times. To understand this behavior, we analyzed learning dynamics in a recurrent neural network model of the task. The model reveals a fundamental trade-off between instantaneous reward rate and perceptual learning speed, putting the goals of learning quickly and accruing immediate reward in tension. We find that the rats’ strategy of long initial responses can dramatically expedite learning, yielding higher total reward over task engagement. Our results demonstrate that prioritizing learning can be advantageous from a total reward perspective, and suggest that rats engage in cognitive control of learning.
Efficient Spline Regression for Neural Spiking Data
Authors: Sarmashghi Mehrad , Jadhav Shantanu P , Eden Uri 
Published: September 2020

AbstractPoint process generalized linear models (GLMs) provide a powerful tool for characterizing the coding properties of neural populations. Spline basis functions are often used in point process GLMs, when the relationship between the spiking and driving signals are nonlinear, but common choices for the structure of these spline bases often lead to loss of statistical power and numerical instability when the signals that influence spiking are bounded above or below. In particular, history dependent spike train models often suffer these issues at times immediately following a previous spike. This can make inferences related to refractoriness and bursting activity more challenging. Here, we propose a modified set of spline basis functions that assumes a flat derivative at the endpoints and show that this limits the uncertainty and numerical issues associated with cardinal splines. We illustrate the application of this modified basis to the problem of simultaneously estimating the place field and history dependent properties of a set of neurons from the CA1 region of rat hippocampus, and compare it with the other commonly used basis functions. We have made code available in MATLAB to implement spike train regression using these modified basis functions.
SuperPlotsOfData – a web app for the transparent display and quantitative comparison of continuous data from discrete conditions
Authors: Goedhart Joachim 
Published: September 2020

AbstractPlots and charts are graphical tools that make data intelligible and digestible by humans. But the oversimplification of data by only plotting the statistical summaries conflicts with the transparent communication of results. Therefore, plotting of all data is generally encouraged and this can be achieved by using a dotplot for discrete conditions. Dotplots, however, often fail to communicate whether the data are from different technical or biological replicates. The superplot has been proposed to improve the communication of experimental design and results. To simplify the plotting of data from discrete conditions as a superplot, the SuperPlotsOfData web app was generated. The tool offers easy and open access to state-of-the-art data visualization. In addition, it incorporates recent innovations in data visualization and analysis, including raindcloud plots and estimation statistics. The free, open-source webtool can be accessed at:https://huygens.science.uva.nl/SuperPlotsOfData/Abstract Figure
Drought tolerance ofHakeaspecies (Proteaceae) from a range of biomes and life-histories predicted by climatic niche
Authors: Oyanoghafo Osazee O. , O’ Brien Corey , Choat Brendan , Tissue David , Rymer Paul D. 
Published: September 2020

AbstractExtreme drought conditions across the globe are impacting biodiversity with serious implications for the persistence of native species. However, quantitative data on drought tolerance is not available for diverse flora to inform conservation management. We quantified physiological drought tolerance in the diverse Hakea genus (Proteaceae) to test predictions based on climatic-origin, life history and functional traits. We sampled terminal branches of replicate plants of 16 species in a common garden. Xylem cavitation was induced in branches under varying water potential (tension) in a centrifuge and the tension generating 50% loss of conductivity (stem P50) was characterized as a metric for drought tolerance. The same branches were used to estimate plant functional traits, including wood density, specific leaf area, and Huber value (sap flow area to leaf area ratio). There was significant variation in stem P50 among species, which was negatively associated with the species climate-origin (rainfall and aridity). Drought tolerance did not differ among life histories; however, a drought avoidance strategy with terete leaf form and greater Huber value may be important for species to colonize and persist in the arid biome. Our findings will contribute to future prediction of species vulnerability to drought and adaptive management under climate change.
Phenotypic and clonal stability of antigen-inexperienced memory-like T cells across the genetic background, hygienic status, and aging
Authors: Moudra Alena , Niederlova Veronika , Novotny Jiri , Schmiedova Lucie , Kubovciak Jan , Matejkova Tereza , Drobek Ales , Pribikova Michaela , Stopkova Romana , Cizkova Dagmar , Neuwirth Ales , Michalik Juraj , Krizova Katerina , Hudcovic Tomas , Kolar Michal , Kozakova Hana , Kreisinger Jakub , Stopka Pavel , Stepanek Ondrej 
Published: September 2020

AbstractAntigen-inexperienced memory-like T (AIMT) cells are functionally unique T cells representing one of the two largest subsets of murine CD8+T cells. However, differences between laboratory inbred strains, insufficient data from germ-free mice, a complete lack of data from feral mice, and unclear relationship between AIMT cells formation during aging represent major barriers for better understanding of their biology. We performed a thorough characterization of AIMT cells from mice of different genetic background, age, and hygienic status by flow cytometry and multi-omics approaches including analyses of gene expression, TCR repertoire, and microbial colonization. Our data showed that AIMT cells are steadily present in mice independently of their genetic background and hygienic status. Despite differences in their gene expression profiles, young and aged AIMT cells originate from identical clones. We identified that CD122 discriminates two major subsets of AIMT cells in a strain-independent manner. Whereas thymic CD122LOWAIMT cells (innate memory) prevail only in young animals with high thymic IL-4 production, peripheral CD122HIGHAIMT cells (virtual memory) dominate in aged mice. Co-housing with feral mice changed the bacterial colonization of laboratory strains, but had only minimal effects on the CD8+T-cell compartment including AIMT cells.
CENP-A chromatin prevents replication stress at centromeres to avoid structural aneuploidy
Authors: Giunta Simona , Hervé Solène , White Ryan R. , Wilhelm Therese , Dumont Marie , Scelfo Andrea , Gamba Riccardo , Wong Cheng Kit , Rancati Giulia , Smogorzewska Agata , Funabiki Hironori , Fachinetti Daniele 
Published: September 2020

AbstractChromosome segregation relies on centromeres, yet their repetitive DNA is often prone to aberrant rearrangements under pathological conditions. Factors that maintain centromere integrity to prevent centromere-associated chromosome translocations are unknown. Here, we demonstrate the importance of the centromere-specific histone H3 variant CENP-A in safeguarding DNA replication of alpha-satellite repeats to prevent structural aneuploidy. Rapid removal of CENP-A in S-phase, but not other cell cycle stages, caused accumulation of R-loops with increased centromeric transcripts, and interfered with replication fork progression. Replication without CENP-A causes recombination at alpha-satellites in an R-loop-dependent manner, unfinished replication and anaphase bridges. In turn, chromosome breakage and translocations arise specifically at centromeric regions. Our findings provide insights into how specialized centromeric chromatin maintains the integrity of transcribed noncoding repetitive DNA during S-phase.Abstract Figure