bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prolactin and the shared regulation of parental care and cooperative helping in white-browed sparrow weaver societies
Authors: Walker Lindsay A. , Tschirren Linda , York Jennifer E. , Sharp Peter J. , Meddle Simone L. , Young Andrew J. 
Published: September 2021

ABSTRACTIn many cooperatively breeding species non-breeding individuals help to rear the offspring of breeders. The physiological mechanisms that regulate such cooperative helping behavior are poorly understood, but may have been co-opted, during the evolution of cooperative breeding, from pre-existing mechanisms that regulated parental care. Key among these may be a role for prolactin. Here we investigate whether natural variation in circulating prolactin levels predicts both parental and helper contributions to nestling provisioning in cooperatively breeding white-browed sparrow weavers,Plocepasser mahali. In sparrow weaver groups, a single dominant pair monopolize reproduction and non-breeding subordinates help with nestling feeding. We show that: (i) among parents, dominant females feed nestlings at higher rates, make longer provisioning visits, and have higher prolactin levels than dominant males; and (ii) among subordinates, engaged in cooperative helping behavior, those within their natal groups feed nestlings at higher rates and have higher prolactin levels than immigrants. Accordingly, continuous variation in prolactin levels positively predicts nestling-provisioning rates and mean provisioning visit durations when all bird classes are combined. These relationships are principally driven by differences among bird classes in both circulating prolactin levels and provisioning traits. The more limited within-class variation in prolactin and provisioning traits were not evidently correlated, highlighting a likely role for additional mechanisms in the fine-scale regulation of care. Our findings broadly support the hypothesis that parental care and cooperative helping behavior are regulated by a common underlying mechanism and highlight the need for experimentation to now establish the causality of any role for prolactin.
A multiplex serological assay for the characterization of IgG immune response to SARS-CoV-2
Authors: Brochot Etienne , Souplet Vianney , Follet Pauline , Ponthieu Pauline , Olivier Christophe , Even Gaël , Audebert Christophe , Malbec Rémi 
Published: September 2021

AbstractBackgroundIn the fight against SARS-COV-2, the development of serological assays based on different antigenic domains represent a versatile tool to get a comprehensive picture of the immune response or differentiate infection from vaccination beyond simple diagnosis.ObjectivesHere we use a combination of the Nucleoprotein (NP), the Spike 1 (S1) and Spike 2 (S2) subunits, and the receptor binding domain (RBD) and N-terminal domain (NTD) of the Spike antigens from the Syrius-CoViDiag® multiplex IgG assay, to follow the immune response to SARS-CoV-2 infection over a long time period and depending on disease severity.ResultsUsing a panel of 209 sera collected from 61 patients up to eight months after infection, we observed that most patients develop an immune response against multiple viral epitope, but anti-S2 antibodies seemed to last longer. For all the tested IgGs, we have found higher titers for hospitalized patients than for non-hospitalized ones. Moreover the combination of the five different IgG titers increased the correlation to the neutralizing antibody titers than if considered individually.ConclusionMultiplex immunoassays have the potential to improve diagnostic performances, especially for ancient infection or mild form of the disease presenting weaker antibody titers. Also the combined detection of anti-NP and anti-Spike-derived domains can be useful to differentiate vaccination from viral infection and accurately assess the antibody potential to neutralize the virus.
Mechanism of the CBM35 domain in assisting catalysis by Ape1, a Campylobacter jejuni O-acetyl esterase
Authors: Lin Chang Sheng-Huei , Yen Ian Y. , Chan Anson C. K. , Murphy Michael E. P. 
Published: September 2021

AbstractPeptidoglycan (PG) is O-acetylated by bacteria to resist killing by host lysozyme. During PG turnover, however, deacetylation is a prerequisite for glycan strand hydrolysis by lytic transglycosylases. Ape1, a de-O-acetylase from Campylobacter jejuni, is a bi-modular protein composed of an SGNH hydrolase domain and a CBM35 domain. The conserved Asp-His-Ser catalytic triad in the SGNH hydrolase domain confers enzymatic activity. The PG binding mode and function of the CBM35 domain in de-O-acetylation remained unclear. In this paper, we present a 1.8 Å resolution crystal structure of a complex between acetate and Ape1. An active site cleft is formed at the interface of the two domains and two large loops from the CBM35 domain form part of the active site. Site-directed mutagenesis of residues in these loops coupled with activity assays using p-nitrophenol acetate indicate the CBM35 loops are required for full catalytic efficiency. Molecular docking of a model O-acetylated hexasaccharide PG substrate to Ape1 using HADDOCK suggests the interaction is formed by the active cleft and the saccharide motif of PG. Together, we propose that the active cleft of Ape1 diverges from other SGNH hydrolase members by using the CBM35 loops to assist catalysis. The concave Ape1 active cleft may accommodate the long glycan strands for selecting PG substrates to regulate subsequent biological events.
Oligomerization of the FliF domains suggests a coordinated assembly of the bacterial flagellum MS ring
Authors: Mariano Giuseppina , Faba-Rodriguez Raquel , Bui Soi , Zhao Weilong , Ross James , Tsokov Svetomir , Bergeron Julien 
Published: September 2021

AbstractThe bacterial flagellum is a complex, self-assembling macromolecular machine that powers bacterial motility. It plays diverse roles in bacterial virulence, including aiding in colonization and dissemination during infection. The flagellum consists of a filamentous structure protruding from the cell, and the basal body, a large assembly that spans the cell envelope. The basal body is comprised of over 10 different proteins, forming several concentric ring structures, termed the M- S- L- P- and C-rings, respectively. In particular, the MS rings are formed by a single protein FliF, which consists of two trans-membrane helices anchoring it to the inner membrane and surrounding a large periplasmic domain. Assembly of the MS ring, through oligomerization of FliF, is one of the first steps of basal body assembly.Previous computational analysis had shown that the periplasmic region of FliF consists of three structurally similar domains, termed Ring-Building Motif (RBM)1, RBM2 and RBM3. The structure of the MS-ring has been reported recently, and unexpectedly shown that these three domains adopt different symmetries, with RBM3 having a 34-mer stoichiometry, while RBM2 adopts two distinct positions in the complex, including a 23-mer ring. This observation raises some important question on the assembly of the MS ring, and the formation of this symmetry mis-match within a single protein. In this study, we analyze the oligomerization of the individual RBM domains in isolation, in the Salmonella typhimurium FliF orthologue. We demonstrate that the periplasmic domain of FliF assembles into the MS ring, in the absence of the trans-membrane helices. We also report that the RBM2 and RBM3 domains oligomerize into ring structures, but not RBM1. Intriguingly, we observe that a construct encompassing RBM1 and RBM2 is monomeric, suggesting that RBM1 interacts with RBM2, and inhibits its oligomerization. However, this inhibition is lifted by the addition of RBM3. Collectively, this data suggests a mechanism for the controlled assembly of the MS ring.
A Discrete Formulation of Two Alternative Forced Choice Decision Dynamics Derived from a Double-Well Quantum Landscape
Authors: Rosendahl Morgan , Cohen Jonathan 
Published: September 2021

AbstractTools from quantum theory have been effectively leveraged in modeling otherwise poorly understood effects in decision-making such as apparent fallacies in probability judgments and context effects. This approach has described the dynamics of two alternative forced choice (2AFC) decisions in terms of the path of a single quantum particle evolving in a single potential well. Here, we present a variant on that approach, which we name the Multi-Particle and Multi-Well (MPMW) quantum cognitive framework, in which decisions among N alternatives are treated by the sum of positional measurements of many independent quantum particles representing stimulus information, acted on by an N-well landscape that defines the decision alternatives. In this article, we apply the MPMW model to the simplest and most common case of N-alternative decision making, 2AFC dynamics. This application calls for a multi-particle double-well implementation, which allows us to construct a simple, analytically tractable discrete drift diffusion model (DDM), in the form of a Markov chain, wherein the parameters of the attractor wells reflect bottom-up (automatic) and top-down (control-dependent) influences on the integration of external information. We first analyze this Markov chain in its simplest form, as a single integrator with a generative process arising from a static quantum landscape and fixed thresholds, and then consider the case of multi-integrator processing under the same conditions. Within this system, stochasticity arises directly from the double-well quantum attractor landscape as a function of the dimensions of its wells, rather than as an external parameter requiring independent fitting. The simplicity of the Markov chain component of this model allows for easy analytical computation of closed forms for response time distributions and response probabilities that match qualitative properties of the accuracies and reaction times of humans performing 2AFC tasks. The MPMW framework produces response time distributions following inverse gaussian curves familiar from previous DDM models and empirical data, including the common observation that mean response times are faster for incorrect than for correct responses. The work presented in this paper serves as a proof of concept, based on which the MPMW framework can be extended to address more complex decision-making processes, (e.g., N-alternative forced choice, dynamic control allocation, and nesting quantum landscapes to allow for modeling at both the task and stimulus levels of processing) that we discuss as future directions.
BionetBF: A Novel Bloom Filter for Faster Membership Identification of Large Biological Graph
Authors: Nayak Sabuzima , Patgiri Ripon 
Published: September 2021

ABSTRACTBig Graph is a graph having thousands of vertices and hundreds of thousands of edges. The study of graphs is crucial because the interlinkage among the vertices provides various insights and uncovers the hidden truth developed due to their relationship. The graph processing has non-linear time complexity. The overwhelming number of vertices and edges of Big Graph further enhances the processing complexity by many folds. One of the significant challenges is searching for an edge in Big Graph. This article proposes a novel Bloom Filter to determine the existence of a relationship in Big Graph, specifically biological networks. In this article, we propose a novel Bloom Filter called Biological network Bloom Filter (BionetBF) for fast membership identification of the biological network edges or paired biological data. BionetBF is capable of executing millions of operations within a second while occupying a tiny main memory footprint. We have conducted rigorous experiments to prove the performance of BionetBF with large datasets. The experiment is performed using 12 synthetic datasets and three biological network datasets. It takes less than 8 sec for insertion and query of 40 million biological edges. It demonstrates higher performance while maintaining a 0.001 false positive probability. BionetBF is compared with other filters: Cuckoo Filter and Libbloom, where small-sized BionetBF proves its supremacy by exhibiting higher performance compared with large-sized Cuckoo Filter and Libbloom. The source code is available at https://github.com/patgiri/BionetBF. The code is written in the C programming language. All data are available at the given link.HighlightsProposed a novel Bloom Filter, BionetBF, for faster boolean query on Big Graph.BionetBF has a low memory footprint and the lowest false positive probability.It has high performance with constant searching time complexity.BionetBF has the potential to application in Big Graph, de-Bruijn Graph, and Drug Discovery.
Vertex-wise characterization of Non-Human Primate cortical development with prenatal insights
Authors: Ramirez Julian S.B. , Hermosillo Robert , Thomas Elina , Zhu Jennifer Y. , Sturgeon Darrick , Schifsky Emma , Galassi Anthony , Thompson Jacqueline R. , Bagley Jennifer L. , Milham Michael P. , Miranda-Dominguez Oscar , Papadakis Samantha , Bah Muhammed , Mitchell AJ , Xu Ting , Graham Alice M. , Feczko Eric , Sullivan Elinor L. , Fair Damien A. 
Published: September 2021

AbstractCharacterization of the interwoven complexities of early cortical thickness development has been an ongoing undertaking in neuroscience research. Longitudinal studies of Non-Human Primates (NHP) offer unique advantages to categorizing the diverse patterns of cortical growth trajectories. Here, we used latent growth models to characterize the trajectories of typical cortical thickness development in Japanese macaques at each cortical surface vertex (i.e. grayordinate). Cortical thickness from 4 to 36 months showed regional specific linear and non-linear trajectories and distinct maturation timing across the cortex. Intriguingly, we revealed a “accumulation/ablation phenomenon” of cortical maturation where the most profound development changes in cortical thickness occur in the accumulation or ablation zones surrounding the focal points (i.e., a center of a delineated regions where cortical thickness is thickest or thinnest) throughout the brain. We further examined maternal diet and inflammation in the context of these typical brain trajectories and known network architecture. A well-controlled NHP model of a maternal “Western-style” diet was used alongside measures of inflammatory cytokine interleukin-6 (IL-6) in the mothers during gestation. We observed that these accumulation and ablation zones of variable change might be most susceptible to environmental effects. The maternal factors, diet and inflammation during pregnancy were distinctively associated with different aspects of offspring cortical development reflected in regions related to distinctive functional networks. Our findings characterize the versatile intricacies of typical cortical thickness development and highlight how the maternal environment plays a role in offspring cortical development.
Developmental dynamics of sex reprogramming by high incubation temperatures in a dragon lizard
Authors: Whiteley Sarah L. , Holleley Clare E. , Georges Arthur 
Published: September 2021

AbstractIn some vertebrate species, gene-environment interactions can determine sex, driving bipotential gonads to differentiate into either ovaries or testes. In the central bearded dragon (Pogona vitticeps), the genetic influence of sex chromosomes (ZZ/ZW) can be overridden by high incubation temperatures, causing ZZ male to female sex reversal. Previous research showed ovotestes, a rare gonadal phenotype with traits of both sexes, develop during sex reversal, leading to the hypothesis that sex reversal relies on high temperature feminisation to outcompete the male genetic cue. To test this, we conducted temperature switching experiments at key developmental stages, and analysed the effect on gonadal phenotypes using histology and transcriptomics. We found sexual fate is more strongly influenced by the ZZ genotype than temperature. Any exposure to low temperatures (28°C) caused testes differentiation, whereas sex reversal required longer exposure to high temperatures. We revealed ovotestes exist along a spectrum of female-ness to male-ness at the transcriptional level. We found inter-individual variation in gene expression changes following temperature switches, suggesting both genetic sensitivity to, and the timing and duration of the temperature cue influences sex reversal. These findings bring new insights to the mechanisms underlying sex reversal, improving our understanding of thermosensitive sex systems in vertebrates.
Functional Communication between IP3R and STIM2 at sub-threshold stimuli is a critical checkpoint for initiation of SOCE
Authors: Ahmad Moaz , Ong Hwei Ling , Saadi Hassan , Son Ga Yeon , Shokatian Zahra , Terry Lara E. , Trebak Mohamed , Yule David I. , Ambudkar Indu 
Published: September 2021

AbstractStromal interaction molecules, STIM1 and STIM2, sense decreases in the endoplasmic reticulum (ER) [Ca2+] ([Ca2+]ER) and cluster in ER-plasma membrane (ER-PM) junctions where they recruit and activate Orai1. While STIM1 responds when [Ca2+]ER is relatively low, STIM2 displays constitutive clustering in the junctions and is suggested to regulate basal Ca2+ entry. The cellular cues that determine STIM2 clustering under basal conditions is not known. By using gene editing to fluorescently tag endogenous STIM2, we report that endogenous STIM2 is constitutively localized in mobile and immobile clusters. The latter associate with ER-PM junctions and recruit Orai1 under basal conditions. Agonist stimulation increases immobile STIM2 clusters which co- ordinate recruitment of Orai1 and STIM1 to the junctions. Extended synaptotagmin (E-Syt)2/3 are required for forming the ER-PM junctions, but are not sufficient for STIM2 clustering. Importantly, inositol 1,4,5-triphosphate receptor (IP3R) function and local [Ca2+]ER are the main drivers of immobile STIM2 clusters. Enhancing, or decreasing, IP3R function at ambient [IP3] causes corresponding increase, or attenuation, of immobile STIM2 clusters. We show that immobile STIM2 clusters denote decreases in local [Ca2+]ER mediated by IP3R that is sensed by the STIM2-N terminus. Finally, under basal conditions, ambient PIP2-PLC activity of the cell determines IP3R function, immobilization of STIM2, and basal Ca2+ entry while agonist stimulation augments these processes. Together, our findings reveal that immobilization of STIM2 clusters within ER-PM junctions, a first response to ER-Ca2+ store depletion, is facilitated by the juxtaposition of IP3R and marks a checkpoint for initiation of Ca2+ entry.SignificanceSTIM proteins sense decreases in [Ca2+]ER and cluster in endoplasmic reticulum (ER)-plasma membrane (PM) junctions where they recruit and activate Orai1. While STIM1 clustering requires substantial [Ca2+]ER decrease, STIM2 displays pre-clustering under resting conditions and regulates basal Ca2+ entry. The mechanism(s) underlying constitutive clustering of STIM2 is not known. We show herein that endogenous STIM2 assembles as mobile and immobile clusters and that Orai1 is recruited to the latter. Anchoring of STIM2 clusters is triggered by decreases in local [Ca2+]ER that is mediated by ambient activity of IP3R and sensed by the STIM2 N-terminus. This functional link between IP3R and STIM2 governs constitutive STIM2 clustering and ensures coupling of [Ca2+]ER decrease at sub-threshold stimuli with activation of Ca2+ entry.
The mosquito microbiome includes habitat-specific but rare symbionts
Authors: Schrieke Hans , Maignien Loïs , Constancias Florentin , Trigodet Florian , Chakloute Sarah , Rakotoarivony Ignace , Marie Albane , L’Ambert Gregory , Makoundou Patrick , Pages Nonito , Eren A. Murat , Weill Mylène , Sicard Mathieu , Reveillaud Julie 
Published: September 2021

AbstractMicrobial communities are known to influence mosquito lifestyles by modifying essential metabolic and behavioral processes that affect reproduction, development, immunity, digestion, egg survival, and ability to transmit pathogens. Many studies have used 16S rRNA gene amplicons to characterize mosquito microbiota and investigate factors that influence host-microbiota dynamics. However, a relatively low taxonomic resolution due to clustering methods based on arbitrary threshold and the overall dominance of Wolbachia or Asaia populations obscured the investigation of rare members of mosquito microbiota in previous studies. Here, we used high resolution Shannon entropy-based oligotyping approaches to analyze the microbiota of Culex pipiens, Culex quinquefasciatus and Aedes individuals from continental and overseas regions in Southern France and Guadeloupe as well as from laboratories with or without antibiotics treatment. Our experimental design that resulted in a series of mosquito samples with a gradient of Wolbachia density and relative abundance along with high-resolution analyses of amplicon sequences enabled the recovery of a robust signal from typically less accessible bacterial taxa. Our data confirm species-specific mosquito-bacteria associations with geography as a primary factor that influences bacterial community structure. But interestingly, they also reveal co-occurring symbiotic bacterial variants within single individuals for both Elizabethkingia and Erwinia genera, distinct and specific Asaia and Chryseobacterium in continental and overseas territories and a putative rare Wolbachia variant. Overall, our study reveals the presence of previously-overlooked microdiversity and multiple closely related symbiotic strains within mosquito individuals with a remarkable habitat-specificity.
Towards a combined therapy for spinal muscular atrophy based on opposing effects of an antisense oligonucleotide on chromatin and splicing
Authors: Marasco Luciano E. , Dujardin Gwendal , Sousa-Luís Rui , Liu Ying Hsiu , Stigliano José , Nomakuchi Tomoki , Proudfoot Nick J. , Krainer Adrian R. , Kornblihtt Alberto R. 
Published: September 2021

SummarySpinal Muscular Atrophy (SMA) is a motor-neuron disease caused by loss-of-function mutations of the SMN1 gene. Humans have a paralog, SMN2, whose exon 7 is predominantly skipped, and so it cannot fully compensate for the lack of SMN1. Nusinersen (Spinraza) is a splicing-correcting antisense oligonucleotide drug (ASO) approved for clinical use. Nusinersen targets a splicing silencer located in SMN2 intron 7 pre-mRNA and, by blocking the binding of the splicing repressors hnRNPA1 and A2, it promotes higher E7 inclusion, increasing SMN protein levels. We show here that, by promoting transcriptional elongation, histone deacetylase (HDAC) inhibitors cooperate with a nusinersen-like ASO to upregulate E7 inclusion. Surprisingly, the ASO also elicits the deployment of the silencing histone mark H3K9me2 on the SMN2 gene, creating a roadblock to RNA polymerase II elongation that acts negatively on E7 inclusion. By removing the roadblock, HDAC inhibition counteracts the undesired chromatin effects of the ASO, resulting in higher E7 inclusion. Combined systemic administration of the nusinersen-like ASO and HDAC inhibitors in neonate SMA mice had strong synergistic effects on SMN expression, growth, survival, and neuromuscular function. Thus, we suggest that HDAC inhibitors have the potential to increase the clinical efficacy of nusinersen, and perhaps other splicing-modulatory ASO drugs, without large pleiotropic effects, as assessed by genome-wide analyses.