bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can processing of face trustworthiness bypass early visual cortex? A transcranial magnetic stimulation masking study
Authors: Janssens Shanice E. W. , Sack Alexander T. , Jessen Sarah , de Graaf Tom A. 
Published: May 2019

AbstractAs a highly social species, we constantly evaluate human faces to decide whether we can trust someone. Previous studies suggest that face trustworthiness can be processed unconsciously, but the underlying neural pathways remain unclear. Specifically, the question remains whether processing of face trustworthiness relies on early visual cortex (EVC), required for conscious perception. If processing of trustworthiness can bypass EVC, then disrupting EVC should impair conscious trustworthiness perception while leaving forced-choice trustworthiness judgment intact. We applied double-pulse transcranial magnetic stimulation (TMS) to right EVC, at different stimulus onset asynchronies (SOAs) from presentation of a face in either the left or right hemifield. Faces were slightly rotated clockwise or counterclockwise, and were either trustworthy or untrustworthy. On each trial, participants discriminated 1) trustworthiness, 2) stimulus rotation, and 3) subjective visibility of trustworthiness. At early SOAs and specifically in the left hemifield, orientation processing (captured by the rotation task) was impaired by TMS. Crucially, though TMS also impaired subjective visibility of trustworthiness, no effects on trustworthiness discrimination were obtained. Conscious perception of face trustworthiness (captured by visibility ratings) relies on intact EVC, while forced-choice trustworthiness judgments may not. These results are consistent with the hypothesis that trustworthiness processing can bypass EVC. For basic visual features, extrastriate pathways are well-established; but face trustworthiness depends on a complex configuration of features. Its processing without EVC and outside of awareness is therefore of particular interest, further highlighting its ecological relevance.
Exautomate: A user-friendly tool for region-based rare variant association analysis (RVAA)
Authors: Davis Brent D. , Dron Jacqueline S. , Robinson John F. , Hegele Robert A. , Lizotte Dan J. 
Published: May 2019

AbstractRegion-based rare variant association analysis (RVAA) is a popular method to study rare genetic variation in large datasets, especially in the context of complex traits and diseases. Although this method shows great promise in increasing our understanding of the genetic architecture of complex phenotypes, performing a region-based RVAA can be challenging. The sequence kernel association test (SKAT) can be used to perform this analysis, but its inputs and modifiable parameters can be extremely overwhelming and may lead to results that are difficult to reproduce. We have developed a software package called “Exautomate” that contains the tools necessary to run a region-based RVAA using SKAT and is easy-to-use for any researcher, regardless of their previous bioinformatic experiences. In this report, we discuss the utilities of Exautomate and provide detailed examples of implementing our package. Importantly, we demonstrate a proof-of-principle analysis using a previously studied cohort of 313 familial hypercholesterolemia (FH) patients. Our results show an increased burden of rare variants in genes known to cause FH, thereby demonstrating a successful region-based RVAA using Exautomate. With our easy-to-use package, we hope researchers will be able to perform reproducible region-based RVAA to further our collective understanding behind the genetics of complex traits and diseases.
Dynamic colonization of microbes and their functions after fecal microbiota transplantation for inflammatory bowel disease
Authors: Chu Nathaniel D. , Crothers Jessica W. , Nguyen Le T.T. , Kearney Sean M. , Smith Mark B. , Kassam Zain , Collins Cheryl , Xavier Ramnik , Moses Peter L. , Alm Eric J. 
Published: May 2019

AbstractFor fecal microbiota transplantation (FMT) to be successful in complex immune diseases like inflammatory bowel disease (IBD), it is assumed that therapeutic microbes and their beneficial functions and immune interactions must colonize the recipient and persist in sufficient quantity and for a long enough period of time to result in a clinical benefit. But few studies have comprehensively profiled the colonization and persistence of transferred microbes along with the transfer of their microbial and immune functions. Using 16S, metagenomic, and immunoglobulin A (IgA) sequencing, we analyzed hundreds of longitudinal microbiome samples from a randomized controlled trial of 12 patients with ulcerative colitis who received fecal transplant or placebo for 12 weeks. We uncovered a range of competitive dynamics among donor and patient strains, showing that persistence of transferred microbes is far from static. Indeed, one patient experienced dramatic loss of donor bacteria 10 weeks into the trial, coinciding with a bloom of pathogenic bacteria and worsening clinical symptoms. We similarly evaluated transfer of microbial functions, including desired ones like butyrate production and unintended ones like antibiotic resistance. By profiling bacteria coated with IgA, we identified IgA-coated bacteria associated with inflammation, and we found that microbial interactions with the host immune system can be transferred across people. This transfer of immune function is likely critical for gut microbiome therapeutics for immune-related diseases. Our findings elucidate the colonization dynamics of gut microbes as well as their functions in the context of FMT to treat a complex disease—information that may provide a critical foundation for the development of more-targeted therapeutics.
2dSS: a web server for protein secondary structure visualization
Authors: Lotun Diksha Priya , Cochard Charlotte , Vieira Fabio R.J , Bernardes Juliana Silva 
Published: May 2019

2dSS is a web-server for visualising and comparing secondary structure predictions. It provides two main functionalities: 2D-alignment and compare predictions. The “2D-alignment” has been designed to visualise conserved secondary structure elements in a multiple sequence alignment (MSA). From this we can study the secondary structure content of homologous proteins (a protein family) and highlight its structural patterns. The “compare predictions” has been designed to compare the output of several secondary structure prediction tools, and check their accuracy when compared with real secondary structure elements extracted from 3D-structure. 2dSS provides a comprehensive representation of protein secondary structure elements, and it can be used to visualise and compare secondary structures of any prediction tool.Availabilityhttp://genome.lcqb.upmc.fr/2dss/
Malpighamoebainfection compromises fluid secretion and P-glycoprotein detoxification in Malpighian tubules
Authors: Rossi Marta , Ott Swidbert R. , Niven Jeremy E. 
Published: May 2019

AbstractMalpighian tubules, analogous to vertebrate nephrons, play a key role in insect osmoregulation and detoxification. Tubules can become infected with a protozoan,Malpighamoeba,which damages their epithelial cells, potentially compromising their function. Here we used a modified Ramsay assay to quantify the impact ofMalpighamoebainfection on fluid secretion and P-glycoprotein-dependent detoxification by desert locust Malpighian tubules. Infected tubules have a greater surface area and a higher fluid secretion rate than uninfected tubules. Infection also impairs P-glycoprotein-dependent detoxification by reducing the net rhodamine extrusion per surface area. However, due to the increased surface area and fluid secretion rate, infected tubules have similar total net extrusion per tubule to uninfected tubules. Increased fluid secretion rate of infected tubules likely exposes locusts to greater water stress and increased energy costs. Coupled with reduced efficiency of P-glycoprotein detoxification per surface area,Malpighamoebainfection is likely to reduce insect survival in natural environments.
Does variation in glucocorticoid regulation predict fitness? A phylogenetic meta-analysis
Authors: Schoenle Laura A. , Zimmer Cedric , Miller Eliot T. , Vitousek Maren N. 
Published: May 2019

ABSTRACTGlucocorticoid hormones (GCs) are central mediators of metabolism and the response to challenges. Because circulating levels of GCs increase in response to challenges, within-population variation in GCs could reflect individual variation in condition or experience. At the same time, individual variation in the degree to which GCs increase in response to challenges (which is relatively consistent within individuals over time) could have causal effects on stress coping capacity, and the ability to survive and reproduce. Although a number of studies in vertebrates have tested whether within-population variation in GCs predicts components of fitness, it is not clear whether there are consistent patterns across taxa. Here we present the first phylogenetic meta-analysis testing whether within-population variation in GCs is associated with components of fitness across vertebrates. At the same time, we introduce and test predictions about an overlooked but potentially important mediator of GC-fitness relationships: life history context. We suggest that strong context-dependence in the fitness benefit of maintaining elevated GCs could obscure consistent patterns between GCs and fitness across taxa. Meta-analyses revealed that across vertebrates, baseline and stress-induced GCs were consistently negatively correlated with reproductive success. This relationship did not differ depending on life history context. In contrast, the relationships between GCs and survival were highly context dependent, differing according to life history strategy. Both baseline and stress-induced GCs were more strongly negatively associated with survival in longer-lived populations and species. Stress-induced GCs were also more negatively associated with survival in organisms that engage in relatively more valuable reproductive attempts. Fecal GCs did not predict survival or reproductive success. We also used a meta-analytic approach to test whether experimental increases in GCs had consistent causal effects on fitness. Experimental increases in GCs reduced both survival and reproductive success, although the latter relationship was not significant when accounting for phylogeny. Overall, these results support the prediction that GC-fitness relationships can be strongly context dependent, and suggest that incorporating life history may be particularly important for understanding GC-survival relationships. Future studies that explore the role of other aspects of context (e.g., the nature and frequency of stressors, environmental variation) within and across species could provide important insights how and when variation in GC regulation predicts fitness.
Novel mouse model of encephalocele: post-neurulation origin and relationship to open neural tube defects
Authors: Rolo Ana , Galea Gabriel L. , Savery Dawn , Greene Nicholas D. E. , Copp Andrew J. 
Published: May 2019

ABSTRACTEncephalocele is a clinically important birth defect that can lead to severe disability in childhood and beyond. The embryonic pathogenesis of encephalocele is poorly understood and, while usually classified as a ‘neural tube defect’, there is conflicting evidence on whether encephalocele results from defective neural tube closure, or is a post-neurulation defect. It is also unclear whether encephalocele can result from the same causative factors as anencephaly and open spina bifida, or whether it is aetiologically distinct. This lack of information results largely from the scarce availability of animal models of encephalocele, particularly ones that resemble the commonest, non-syndromic human defects. Here we report a novel mouse model of occipito-parietal encephalocele, in which the small GTPase Rac1 is conditionally ablated in the (non-neural) surface ectoderm. Most mutant fetuses have open spina bifida, and some also exhibit exencephaly/anencephaly. However, a large proportion of mutant fetuses exhibit encephalocele affecting the occipito-parietal region. The encephalocele phenotype does not result from a defect in neural tube closure, but rather from a later disruption of the surface ectoderm covering the already closed neural tube, allowing the brain to herniate. The neuroepithelium itself shows no down-regulation of Rac1 and appears morphologically normal until late gestation. A large skull defect develops overlying the region of brain herniation. Our work provides a new genetic model of occipito-parietal encephalocele, particularly resembling non-syndromic human cases. While encephalocele has a different, later-arising pathogenesis than open neural tube defects, both can share the same genetic causation.SUMMARY STATEMENTEncephalocele - a severe brain defect - arises after neural tube closure, but can share a common genetic cause with anencephaly, a defect of neural tube closure.
Leishmaniatargets the macrophage epigenome and dampens the NF-κB/NLRP3-mediated inflammatory response
Authors: Lecoeur Hervé , Prina Eric , Rosazza Thibault , Kokou Kossiwa , N’Diaye Paya , Aulner Nathalie , Varet Hugo , Bussotti Giovanni , Xing Yue , Weil Robert , Meng Guangxun , Späth Gerald F. 
Published: May 2019

SummaryAberrant macrophage activation during intracellular infection generates important immunopathologies that can cause severe human morbidity. A better understanding of microbial immune subversion strategies and macrophage phenotypic and functional responses is a prerequisite for the design of novel, host-directed intervention strategies. Here, we uncover a fine-tuned transcriptional response induced in primary macrophages infected by the human parasiteLeishmania amazonensisthat prevents NF-κB and NLRP3 inflammasome activation. This unusual subversion is characterized by respectively suppression and induction of activating and de-activating components of the NF-κB and NLRP3 pathways. This dichotomic modulation was associated with histone H3 hypoacetylation at promoters of NF-κB-related, pro-inflammatory genes. Our results reveal a novelLeishmaniaimmune subversion strategy targeting host cell epigenetic regulation to modulate the macrophage phenotype. Modulation of the macrophage epigenetic landscape establishes conditions beneficial for intracellular parasite survival, and opens interesting new venues for host-directed, anti-microbial drug discovery.
Prenatal alcohol exposure disrupts Shh pathway and primary cilia genes in the mouse neural tube
Authors: Boschen Karen E. , Fish Eric W. , Parnell Scott E. 
Published: May 2019

AbstractNeurulation-stage alcohol exposure (NAE; embryonic day [E] 8-10) is associated with midline craniofacial and CNS defects that likely arise from disruption of morphogen pathways, such as Sonic hedgehog (Shh). Notably, midline anomalies are also a hallmark of genetic ciliopathies such as Joubert syndrome. We tested whether NAE alters Shh pathway signaling and the number and function of primary cilia, organelles critical for Shh pathway transduction. Female C57BL/6J mice were administered two doses of alcohol (2.9 g/kg/dose) or vehicle on E9. Embryos were collected 6, 12, or 24 hr later, and changes to Shh, cell cycle genes, and primary cilia were measured in the rostroventral neural tube (RVNT). Within the first 24 hours post-NAE, reductions in Shh pathway and cell cycle gene expression and the ratio of Gli3 forms in the full-length activator state were observed. RVNT volume and cell layer width were reduced at 12 hr. In addition, expression of multiple cilia-related genes were observed at 6 hr post-NAE. As a further test of cilia gene-ethanol interaction, mice heterozygous forKif3aexhibited perturbed behavior during adolescence following NAE compared to vehicle-treated mice, andKif3aheterozygosity exacerbated the hyperactive effects of NAE on exploratory activity. These data demonstrate that NAE downregulates the Shh pathway in a region of the neural tube that gives rise to alcohol-sensitive brain structures and identifies disruption of primary cilia function, or a “transient ciliopathy”, as a possible cellular mechanism of prenatal alcohol pathogenesis.
Overexpression of a non-muscle RBFOX2 isoform triggers cardiac conduction defects in myotonic dystrophy
Authors: Misra Chaitali , Bangru Sushant , Lin Feikai , Lam Kin , Koenig Sara N. , Lubbers Ellen R. , Hedhli Jamila , Murphy Nathaniel P. , Parker Darren J. , Dobrucki Lawrence W. , Cooper Thomas A. , Tajkhorshid Emad , Mohler Peter J. , Kalsotra Auinash 
Published: May 2019

SUMMARYMyotonic dystrophy type 1 (DM1) is a multisystemic genetic disorder caused by a CTG trinucleotide repeat expansion in the 3′ untranslated region ofDMPKgene. Heart dysfunctions occur in nearly 80% of DM1 patients and are the second leading cause of DM1-related deaths. Despite these figures, the mechanisms underlying cardiac-based DM1 phenotypes are unknown. Herein, we report that upregulation of a non-muscle splice isoform of RNA binding protein RBFOX2 in DM1 heart tissue—due to altered splicing factor and microRNA activities—induces cardiac conduction defects in DM1 individuals. Mice engineered to express the non-muscle RBFOX2 isoform in heart via tetracycline-inducible transgenesis, or CRISPR/Cas9-mediated genome editing, reproduced DM1-related cardiac-conduction delay and spontaneous episodes of arrhythmia. Further, by integrating RNA binding with cardiac transcriptome datasets from both DM1 patients and mice expressing the non-muscle RBFOX2 isoform, we identified RBFOX2-driven splicing defects in the voltage-gated sodium and potassium channels, which can alter their electrophysiological properties. Thus, our results uncover atrans-dominant role for an aberrantly expressed RBFOX2 isoform in DM1 cardiac pathogenesis.
Fast sequence-based microsatellite genotyping development workflow
Authors: Lepais Olivier , Chancerel Emilie , Boury Christophe , Salin Franck , Manicki Aurélie , Taillebois Laura , Dutech Cyril , Aissi Abdeldjalil , Bacles Cecile F. E. , Daverat Françoise , Launey Sophie , Guichoux Erwan 
Published: May 2019

AbstractApplication of high-throughput sequencing technologies to microsatellite genotyping (SSRseq) has been shown to remove many of the limitations of electrophoresis-based methods and to refine inference of population genetic diversity and structure. We present here a streamlined SSRseq development workflow that includes microsatellite development, multiplexed marker amplification and sequencing, and automated bioinformatics data analysis. We illustrate its application to five groups of species across phyla (fungi, plant, insect and fish) with different levels of genomic resource availability. We found that relying on previously developed microsatellite assay is not optimal and leads to a resulting low number of reliable locus being genotyped. In contrast,de novo ad hocprimer designs gives highly multiplexed microsatellite assays that can be sequenced to produce high quality genotypes for 20 to 40 loci. We highlight critical upfront development factors to consider for effective SSRseq setup in a wide range of situations. Sequence analysis accounting for all linked polymorphisms along the sequence, quickly generates a powerful multi-allelic haplotype-based genotypic dataset, calling to new theoretical and analytical frameworks to extract more information from multi-nucleotide polymorphism marker systems.
Temporal learning of bottom-up connections via spatially nonspecific top-down inputs
Authors: Lee Jung Hoon , Kim Mean-Hwan , Vijayan Sujith 
Published: May 2019

AbstractIn the brain, high-order and low-order areas are connected via bottom-up connections (from low-order to high-order areas) and top-down connections (from high-order to low-order areas). While bottom-up signals are thought to be critical in generating perception, functions of top-down signals have not been clearly delineated. One popular theory is that top-down inputs modify the activity of specific cell assemblies to modulate responses to bottom-up inputs. However, a different line of studies proposes that not all top-down inputs are specifically delivered. As the leading theories cannot account for nonspecific top-down inputs, we seek potential functions of nonspecific top-down signals using network models in our study. Our simulation results suggest that top-down inputs can regulate low-order area responses by providing temporal information even without spatial specificity. Specifically, the temporal information in nonspecific top-down inputs can weaken the undesired bottom-up connections, contributing to bottom-up connections’ learning. Further, we found that cortical rhythms (synchronous oscillatory neural responses) are critical in the proposed learning process of bottom-up connections in our model.
Functional analysis of the UVR8 photoreceptor from the monocot Zea mays
Authors: Belén Fernández María , Lorenzo Lamattina , Raúl Cassia 
Published: May 2019

AbstractLow UV-B fluence is a signaling stimulus that regulates various physiological processes and induces photomorphogenic responses in plants. The specific UV-B receptor UVR8 is a key component in these processes. Although UVR8 sequence is conserved, few homologs have been cloned and reported to be functional. Here we show the cloning and functional analysis of Zea mays UVR8 (ZmUVR8). ZmUVR8 presents 73% of identity with AtUVR8, maintaining the key tryptophan responsible of UV-B perception. ZmUVR8 also contains the VP domain, involved in the interaction with the proteins CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) and REPRESSOR OF UV-B PHOTOMOPHOGENESIS 1 (RUP1). Whereas UVR8 was expressed in non-irradiated Arabidopsis and maize leaves, after 2h of UV-B irradiation, its expression was reduced. The expression of chalcone synthase (CHS), involved in flavonoid biosynthesis and regulated by UVR8, was increased in irradiated Arabidopsis and maize leaves. Arabidopsis uvr8-1 null mutant was complemented with ZmUVR8 driven by the CaMV-35S promoter and fused to eGFP. ZmUVR8-eGFP fusion was mainly localized in nuclei of transgenic lines, irrespective of UV-B treatments. UV-B suppressed hypocotyl elongation in WT Arabidopsis plants, whereas in uvr8-1 hypocotyl growth was observed. However, hypocotyl elongation was reduced in UV-B irradiated transgenic lines complemented with ZmUVR8. Moreover, CHS and transcription factor HY5 (ELONGATED HYPOCOTYL 5) expression were also restored in these plants. These results confirm that ZmUVR8 is similar enough to AtUVR8 to restore UV-B perception and signaling in Arabidopsis mutant uvr8-1, thus being a functional UV-B photoreceptor.
Effector-dependent modulation of working memory maintenance in posterior parietal cortex
Authors: Pilacinski Artur , Höller-Wallscheid Melanie S. , Lindner Axel 
Published: May 2019

ABSTRACTWorking memory (WM) is the key process linking perception to action. Several lines of research have, accordingly, highlighted WM’s engagement in sensori-motor associations between retrospective stimuli and future behavior. Using human fMRI we investigated whether prior information about the effector used to report in a WM task would have an impact on the way the same sensory stimulus is maintained in memory – even if a behavioral response could not be readily planned. Specifically, we focused on WM-related activity in posterior parietal cortex during the maintenance of spatial items for a subsequent match-to-sample comparison, which was reported either with a verbal or with a manual response. We expected WM activity to be higher for manual response trials, because of posterior parietal cortex’s engagement in both spatial WM and hand movement preparation. Increased fMRI activity for manual response trials in bilateral anterior intraparietal sulcus confirmed our expectations. These results imply that the maintenance of sensory material in WM is optimized for motor context of the upcoming behavioral responses.