bluuebunny/crossref_metadata_2025_split huggingface dataset:
DILS: Demographic Inferences with Linked Selection by using ABC
Authors: Fraïsse Christelle , Popovic Iva , Mazoyer Clément , Spataro Bruno , Delmotte Stéphane , Romiguier Jonathan , Loire Étienne , Simon Alexis , Galtier Nicolas , Duret Laurent , Bierne Nicolas , Vekemans Xavier , Roux Camille 
Published: June 2020

ABSTRACTWe present DILS, a deployable statistical analysis platform for conducting demographic inferences with linked selection from population genomic data using an Approximate Bayesian Computation framework. DILS takes as input single-population or two-population datasets (multilocus fasta sequences) and performs three types of analyses in a hierarchical manner, identifying: 1) the best demographic model to study the importance of gene flow and population size change on the genetic patterns of polymorphism and divergence, 2) the best genomic model to determine whether the effective sizeNeand migration rateN.mare heterogeneously distributed along the genome (implying linked selection) and 3) loci in genomic regions most associated with barriers to gene flow. Also availableviaa web interface, an objective of DILS is to facilitate collaborative research in speciation genomics. Here, we show the performance and limitations of DILS by using simulations, and finally apply the method to published data on a divergence continuum composed by 28 pairs ofMytilusmussel populations/species.
The Effect of Between-Probe Variability in Haptic Feedback on Stiffness Perception and Grip Force Adjustment
Authors: Kossowsky Hanna , Farajian Mor , Milstein Amit , Nisky Ilana 
Published: June 2020

AbstractWhen interacting with objects, haptic information is used to create perception of the object stiffness and to regulate grip force. Studies have shown that introducing noise into sensory inputs can create uncertainty in those sensory channels, yet a method of creating haptic uncertainty without distorting the haptic information has yet to be discovered. Toward this end, we investigated the effect of between-probe haptic variability on stiffness perception and grip force control. In a stiffness discrimination task, we added different levels of between-probe haptic variability by changing the stiffness of the force fields between consecutive probes. Unlike the low and high variability levels, the medium level created perceptual haptic uncertainty. Additionally, we ascertained that participants calculated a weighted average of the different stiffness levels applied by a given force field. Examining participants’ grip force showed that the modulation of the grip force with the load force decreased with repeated exposure to the force field, whereas no change in the baseline was observed. These results were observed in all the variability levels and suggest that between-probe variability created haptic uncertainty that affected the grip force control. Overall, the medium variability level can be effective in inducing uncertainty in both perception and action.
Mapping RNA dependent RNA polymerase activity and immune gene expression using PRO-seq
Authors: Mahajan Lakshmi S. , Kim Grace Eunyoo , Kwak Hojoong 
Published: June 2020

SummaryPositive strand, single strand RNA viruses ((+)ssRNA viruses) are viruses with an RNA genome that have broad impacts on a wide range of hosts, including SARS-CoV-2 human respiratory infections. Their replication and gene expression are driven by RNA dependent RNA polymerases (RdRp). Detecting active RNA synthesis by RdRp is critical for assessing the infectivity and pathogenicity of (+)ssRNA viruses. Current approaches rely on viral RNA detection, which cannot distinguish viral titer from RdRp activity. Precision Run-On sequencing (PRO-seq) is a nuclear run-on based nascent RNA sequencing method, widely used to map eukaryotic RNA polymerases by using labeled nucleotide analogues. Here we provide evidence that PRO-seq also detects RdRp activity and can serve as a highly sensitive RdRp mapping method. Coupled to PRO-seq in human blood samples, we propose to use PRO-seq as a single package method to detect (+)ssRNA virus RdRp activity and its interaction with host immune response through transcriptome-wide profiling of leukocyte gene expressions at once.
Exposure to artemisinin at the trophozoite stage increases sexual conversion rates in the malaria parasite Plasmodium falciparum
Authors: Portugaliza Harvie P. , Miyazaki Shinya , Geurten Fiona J.A. , Pell Christopher , Rosanas-Urgell Anna , Janse Chris J. , Cortés Alfred 
Published: June 2020

ABSTRACTMalaria transmission is dependent on formation of gametocytes in the human blood. The sexual conversion rate, the proportion of asexual parasites that convert into gametocytes at each multiplication cycle, is variable and reflects the relative parasite investment between transmission and maintaining the infection. The impact of environmental factors such as drugs on sexual conversion rates is not well understood. We developed a robust assay using gametocyte-reporter parasite lines to accurately measure the impact of drugs on conversion rates, independently from their gametocytocidal activity. We found that exposure to subcurative doses of the frontline antimalarial drug dihydroartemisinin (DHA) at the trophozoite stage resulted in a ~4-fold increase in sexual conversion. In contrast, no increase was observed when ring stages were exposed or in cultures in which sexual conversion was stimulated by choline depletion. Our results reveal a complex relationship between antimalarial drugs and sexual conversion, with potential public health implications.
Cumulative effect of aging and SARS-CoV2 infection on poor prognosis in the elderly: Insights from transcriptomic analysis of lung and blood
Authors: Bhattacharyya Upasana , Thelma B K 
Published: June 2020

AbstractIntroductionThe ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) has affected millions of people worldwide and with notable heterogeneity in its clinical presentation. Probability of contracting this highly contagious infection is similar across age groups but disease severity and fatality among aged patients with or without comorbidities are higher. We hypothesized that SARS-CoV-2 infection may augment aging-related gene expression alterations resulting in severe outcomes in elderly patients.MethodologyWe performed a comparative analysis of publicly available transcriptome data from Broncho Alveolar Lavage Fluid (BALF)/lung/blood of healthy aging group with i) COVID-19 patients; and ii) data of host genes interacting with SARS-CoV-2 proteins.ResultsWe observed i) a significant overlap of gene expression profiles of patients’ BALF and blood with lung and blood of the healthy group respectively; ii) a more pronounced overlap in blood compared to lung; and iii) a similar overlap between host genes interacting with SARS-CoV-2 and aging blood transcriptome.ConclusionsPathway enrichment analysis of overlapping gene sets suggests that infection alters expression of genes already dysregulated in the elderly, which together may lead to poor prognosis. eQTLs in these genes may also confer poor outcome in young patients worsening with age and co-morbidities. Furthermore, the pronounced overlap observed in blood may explain clinical symptoms including blood clots, strokes, heart attack, multi-organ failure etc. in severe cases. This model based on a limited patient dataset seems robust and holds promise for testing larger tissue specific datasets from patients with varied severity and across populations.
Visually-evoked choice behavior driven by distinct population computations with non-sensory neurons in visual cortical areas
Authors: Osako Yuma , Ohnuki Tomoya , Tanisumi Yuta , Shiotani Kazuki , Manabe Hiroyuki , Sakurai Yoshio , Hirokawa Junya 
Published: June 2020

AbstractIt is widely assumed that variability in visual detection performance is attributed to the fidelity of the visual responses in visual cortical areas, which could be modulated by fluctuations of internal states such as vigilance and behavioral history. However, it is not clear what neural ensembles represent such different internal states. Here, we utilized a visual detection task, which distinguishes perceptual states to identical stimuli, while recording neurons simultaneously from the primary visual cortex (V1) and the posterior parietal cortex (PPC). We found distinct population dynamics segregating hit responses from misses despite no clear differences in visual responses. The population-level computation was significantly contributed by heterogenous non-sensory neurons in V1, whereas the contribution from non-neurons with the previous outcome selectivity was prominent in PPC. These results indicate different contributions of non-sensory neurons in V1 and PPC for the population-level computation that enables behavioral responses from visual information.
μSPIM: A Software Platform for Selective Plane Illumination Microscopy
Authors: Saska Daniel , Pichler Paul , Qian Chen , Pegasiou Chrysia , Buckley Christopher L. , Lagnado Leon 
Published: June 2020

AbstractSelective Plane Illumination Microscopy (SPIM) is a fluorescence imaging technique that allows volumetric imaging at high spatio-temporal resolution to monitor neural activity in live organisms such as larval zebrafish. A major challenge in the construction of a custom SPIM microscope is the control and synchronization of the various hardware components. Here we present a control toolset, μSPIM, built around the open-source MicroManager platform that has already been widely adopted for the control of microscopy hardware. Installation of μSPIM is relatively straightforward, involving a single C++ executable and a Java-based extension to Micro-Manager. Imaging protocols are defined through the μSPIM extension to Micro-Manager. The extension then synchronizes the camera shutter with the galvanometer mirrors to create a light-sheet that is scanned in the z-dimension, in synchrony with the imaging objective, to produce volumetric recordings. A key advantage of μSPIM is that a series of calibration procedures optimizes acquisition for a given set-up making it relatively independent of the optical design of the microscope, or the hardware used to build it. Two laser illumination arms can be used while also allowing for the introduction of illumination masks. μSPIM allows imaging of calcium activity throughout the brain of larval zebrafish at rates of 100 planes per second with single cell resolution as well as slower imaging to reconstruct cell populations, for example, in the cleared brains of mice.
Dynamics of Tpm1.8 domains on actin filaments with single molecule resolution
Authors: Bareja Ilina , Wioland Hugo , Janco Miro , Nicovich Philip R. , Jégou Antoine , Romet-Lemonne Guillaume , Walsh James , Böcking Till 
Published: June 2020

ABSTRACTTropomyosins regulate dynamics and functions of the actin cytoskeleton by forming long chains along the two strands of actin filaments that act as gatekeepers for the binding of other actin-binding proteins. The fundamental molecular interactions underlying the binding of tropomyosin to actin are still poorly understood. Using microfluidics and fluorescence microscopy, we observed the binding of fluorescently labelled tropomyosin isoform Tpm1.8 to unlabelled actin filaments in real time. This approach in conjunction with mathematical modeling enabled us to quantify the nucleation, assembly and disassembly kinetics of Tpm1.8 on single filaments and at the single molecule level. Our analysis suggests that Tpm1.8 decorates the two strands of the actin filament independently. Nucleation of a growing tropomyosin domain proceeds with high probability as soon as the first Tpm1.8 molecule is stabilised by the addition of a second molecule, ultimately leading to full decoration of the actin filament. In addition, Tpm1.8 domains are asymmetrical, with enhanced dynamics at the edge oriented towards the barbed end of the actin filament. The complete description of Tpm1.8 kinetics on actin filaments presented here provides molecular insight into actin-tropomyosin filament formation and the role of tropomyosins in regulating actin filament dynamics.
Phase dynamics of cerebral blood flow in subarachnoid haemorrhage in response to sodium nitrite infusion
Authors: Ezra Martyn , Garry Payashi , Rowland Matthew J , Mitsis Georgios D , Pattinson Kyle TS 
Published: June 2020

AbstractAneurysmal subarachnoid haemorrhage (SAH) is a devastating subset of stroke. One of the major determinates of morbidity is the development of delayed cerebral ischemia (DCI). Disruption of the nitric oxide (NO) pathway and consequently the control of cerebral blood flow (CBF), known as cerebral autoregulation, is believed to play a role in its pathophysiology. Through the pharmacological manipulation ofin vivoNO levels using an exogenous NO donor we sought to explore this relationship.Phase synchronisation index (PSI), an expression of the interdependence between CBF and arterial blood pressure (ABP) and thus cerebral autoregulation, was calculated before and during sodium nitrite administration in 10 high-grade SAH patients acutely postrupture. In patients that did not develop DCI, there was a significant increase in PSI around 0.1 Hz during the administration of sodium nitrite (33%; p-value 0.006). In patients that developed DCI, PSI did not change significantly.Synchronisation between ABP and CBF at 0.1 Hz has been proposed as a mechanism by which organ perfusion is maintained, during periods of physiological stress. These findings suggest that functional NO depletion plays a role in impaired cerebral autoregulation following SAH, but the development of DCI may have a distinct pathophysiological aetiology.
Demonstration of re-epithelialization in a bioprinted human skin equivalent wound model
Authors: Jara Carlos Poblete , Catarino Carolina Motter , Lei Yuguo , Velloso Lício Augusto , Karande Pankaj , Velander William H. , de Araujo Eliana Pereira 
Published: June 2020

AbstractObjectiveThe development of an in vitro platform for modeling human skin injury and the re-epithelization process.ApproachA fibrin provisional matrix (FPM) was installed into a wound facsimile of a bioprinted human skin equivalent (HSE). A mixture of plasma-derived fibrinogen-containing factor XIII, fibronectin, thrombin, and macrophages (an FPM “bioink”) was extruded into the wound site. The surroundingin vitrotissue culture became a source of keratinocytes to achieve wound closure by a re-epithelialization process signaled by the FPM.ResultsAnin vitroanalog of wound closure and re-epithelialization by keratinocytes occurred over the FPM after a normal migration initiation at 3 days.InnovationA physiologic mixture of macrophage/fibrinogen/fibronectin that supports macrophage differentiation was applied to a mechanically wounded, bioprinted dermal tissue. We developed a transitional culture medium to mimic the changing microenvironment during the initial phases of wound healing. As a reference, we temporally compared ourin vitromodel with a murine skin wound healing.ConclusionThis co-culture model was shown to temporally synchronize a re-epithelization process for initiation of keratinocyte migration from a surrounding tissue and the migration process over the top of an FPM. A future study of the analogous subepithelial healing pathway is envisioned using the samein vitrobioprinted tissue study platform for co-culture of keratinocytes, melanocytes, fibroblasts, endothelial cells, and macrophages using more specialized FPMs.
Categorical judgments do not modify sensory information in working memory
Authors: Luu Long , Stocker Alan A. 
Published: June 2020

AbstractCategorical judgments can systematically bias the perceptual interpretation of stimulus features. However, it remained unclear whether categorical judgments directly modify working memory representations or, alternatively, generate these biases via an inference process down-stream from working memory. To address this question we ran two novel psychophysical experiments in which human subjects had to revert their categorical judgments about a stimulus feature, if incorrect based on feedback, before providing an estimate of the feature. If categorical judgments indeed directly altered sensory representations in working memory, subjects’ estimates should reflect some aspects of their initial (incorrect) categorical judgment in those trials.We found no traces of the initial categorical judgment. Rather, subjects seem to be able to flexibly switch their categorical judgment if needed and use the correct corresponding categorical prior to properly perform feature inference. A cross-validated model comparison also revealed that feedback may lead to selective memory recall such that only memory samples that are consistent with the categorical judgment are accepted for the inference process. Our results suggest that categorical judgments do not modify sensory information in working memory but rather act as top-down expectation in the subsequent sensory recall and inference process down-stream from working memory.
Genetic Variation Regulates Opioid-Induced Respiratory Depression in Mice
Authors: Bubier Jason A. , He Hao , Philip Vivek M. , Roy Tyler , Hernandez Christian Monroy , Donohue Kevin D. , O’Hara Bruce F. , Chesler Elissa J. 
Published: June 2020

AbstractIn the U.S., opioid prescription for treatment of pain nearly quadrupled from 1999 to 2014, leading to an epidemic in addiction and overdose deaths. The most common cause of opioid overdose and death is opioid-induced respiratory depression (OIRD), a life-threatening depression in respiratory rate thought to be caused by stimulation of opioid receptors in the inspiratory-generating regions of the brain. Studies in mice have revealed that variation in opiate lethality is associated with strain differences, suggesting that sensitivity to OIRD is genetically determined. We first tested the hypothesis that genetic variation in inbred strains of mice influences the innate variability in opioid-induced responses in respiratory depression, recovery time and survival time. Using the founders of the advanced, high-diversity mouse populations, the Collaborative Cross (CC) and Diversity Outbred (DO), we found substantial sex and genetic effects on respiratory sensitivity and opiate lethality. To define genetic modifiers of OIRD, we then used the high precision DO population treated with morphine to map and identify quantitative trait loci (QTL) for respiratory depression, recovery time and survival time. Trait mapping and integrative functional genomic analysis in GeneWeaver has allowed us to implicateGalnt11, an N-acetylgalactosaminyltransferase, as a candidate gene that regulates OIRD.
STACAS: Sub-Type Anchor Correction for Alignment in Seurat to integrate single-cell RNA-seq data
Authors: Andreatta Massimo , Carmona Santiago J. 
Published: June 2020

AbstractComputational tools for the integration of single-cell transcriptomics data are designed to correct batch effects between technical replicates or different technologies applied to the same population of cells. However, they have inherent limitations when applied to heterogeneous sets of data with moderate overlap in cell states or sub-types. STACAS is a package for the identification of integration anchors in the Seurat environment, optimized for the integration of datasets that share only a subset of cell types. We demonstrate that byi)correcting batch effects while preserving relevant biological variability across datasets,ii)filtering aberrant integration anchors with a quantitative distance measure, andiii)constructing optimal guide trees for integration, STACAS can accurately align scRNA-seq datasets composed of only partially overlapping cell populations. We anticipate that the algorithm will be a useful tool for the construction of comprehensive single-cell atlases by integration of the growing amount of single-cell data becoming available in public repositories.Code availabilityR package:https://github.com/carmonalab/STACASDocker image:https://hub.docker.com/repository/docker/mandrea1/stacas_demo
Identification of new insect Host Defense Peptides (HDP) from Dung Beetles (Coleoptera: Scarabaeidae) transcriptomes
Authors: Ramirez Germán Alberto Téllez , Osorio-Méndez Juan Felipe , Arias Diana Carolina Henao , Toro S Lily Johanna , Castrillón Juliana Franco , Rojas-Montoya Maribel , Osorio Jhon Carlos Castaño 
Published: June 2020

AbstractIntroductionThe Coleoptera Scarabaeidae family is one of the most diverse groups of insects on the planet, living in complex microbiological environments. Their immune systems have evolved with the generation of host defense peptides but only a small number of these peptides have been characterized.MethodsIn this work two sources of information were retrieved: 1)De novotranscriptomic data from two species of neotropical Scarabidae (Dichotomius satanasandOntophagus curvicornis); 2) Sequence data deposited in available databases. A BLAST-based search against the transcriptomes with a subset of sequences representative of the Host Defense Peptides (HDP). The HDP were described with the cecropin, defensin, attacin, and coleoptericin families; their physical/chemical and structural properties were described.ResultsThis work reports 155 novel sequences of HDP identified in 9 transcriptomes from seven species from the Coleoptera order:D. satanas(n= 76; 49.03%),O. curvicornis(n= 23; 14.83%),T. dichotomus(n= 18; 11.61%),O. nigriventris(n= 10; 6.45%),Heterochelus sp(n= 6; 3.87%),O. conspicillatum(n= 18; 11.61%) andP. japonica(n= 4; 2.58%). These sequences were identified based on similarity to known HDP insect families. New members of defensins (n= 58; 37.42%), cecropins (n= 18; 11.61%), attancins (n= 41; 26.45%) and coleoptericins (n= 38; 24.52%), with their physicochemical, structural characteristics, and sequence relationship to other insect HDP were analyzed.Conclusions155 new HDP could be identified, based on similarity to known HDP insect families on nine transcriptome sequences of seven beetle species.HighlightsThis work identified 155 novel sequences of HDP found in nine transcriptomes from seven Coleoptera species.De novotranscriptomic data from two species of neotropical Scarabaeidae (Dichotomius satanasandOntophagus curvicornis).In silicoprediction of physicochemical properties, structural features, sequence similarity, and antimicrobial activity of Scarabaeidae HDP.
Coronatine is More Potent than Jasmonates in Regulating Arabidopsis Circadian Clock
Authors: Gao Min , Zhang Chong , Lu Hua 
Published: June 2020

AbstractRecent studies establish a crucial role of the circadian clock in regulating plant defense against pathogens. Whether pathogens modulate host circadian clock as a potential strategy to suppress host innate immunity is not well understood. Coronatine is a toxin produced by the bacterial pathogenPseudomonas syringaethat is known to counteract Arabidopsis defense through mimicking defense signaling molecules, jasmonates (JAs). We report here that COR preferentially suppresses expression of clock-related genes in high throughput gene expression studies, compared with the plant-derived JA molecule methyl jasmonate (MJ). COR treatment dampens the amplitude and lengthens the period of all four reporters tested while MJ and another JA agonist JA-isoleucine (JA-Ile) only affect some reporters. COR, MJ, and JA-Ile act through the canonical JA receptor COI1 in clock regulation. These data support a stronger role of the pathogen-derived molecule COR than plant-derived JA molecules in regulating Arabidopsis clock. Further study shall reveal mechanisms underlying COR regulation of host circadian clock.