bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing Fecal, Saliva and Chicha Microbiomes Between Mothers and Children in an Indigenous Ecuadorian Cohort
Authors: Adams Eric , Oliver Andrew , Gille Alexandria , Alaniz Nadia , Jaime Carolina , Patton John , Whiteson Katrine 
Published: October 2020

ABSTRACTRecent research has elucidated many factors which play a role in the development and composition of human microbiomes. In this study we briefly examine the microbiomes of saliva and fecal samples from 71 indigenous individuals, and chicha samples from 28 single family households in a remote community in the Ecuadorian Amazon. Fecal and saliva samples were collected at two separate time points whereas chicha samples were collected at four time points, once each day of the fermentation process. In total 324 samples were collected: 113 saliva, 108 chicha, and 103 fecal. Microbial composition and diversity were assessed using shotgun metagenome sequence data. Chicha samples were found to be nearly entirely composed of the orderLactobacillales, accounting for 90.1% of the relative abundance. Saliva samples also contained a high relative abundance ofLactobacillales(31.9%) as well as being composed ofNeisseriales(12.8%),Actinomycineae(8.7%),Bacteroidales(7.0%),Clostridiales(6.8%),Micrococcineae(6.5%), andPasteurellales(6.0%). Fecal samples were largely composed of the three ordersClostridiales(33.7%),Bacteroidales(21.9%), andBifidobacteriales(16.5%). Comparison of α-diversity, as calculated by Shannon’s Diversity Index, in mothers and their offspring showed no significant difference between the two groups in either fecal or saliva samples. Comparison of β-diversity in fecal and saliva samples, as calculated by the Bray-Curtis Dissimilarity measure, within household units and between differing households showed that members of the same household were significantly less dissimilar to each other than to members of other households in the community. Average microbiome composition for individuals within fecal and saliva samples was assessed to determine the impact of an individual’s household on the composition of their microbiome. Household was determined to have a significant impact on both fecal and oral microbiome compositions.
South Asian Patient Population Genetics Reveal Strong Founder Effects and High Rates of Homozygosity – New Resources for Precision Medicine
Authors: Wall Jeffrey D. , Sathirapongsasuti J. Fah , Gupta Ravi , Barik Anamitra , Rai Rajesh Kumar , Rasheed Asif , Radha Venkatesan , Belsare Saurabh , Menon Ramesh , Phalke Sameer , Mittal Anuradha , Fang John , Tanneeru Deepak , Robinson Jacqueline , Chaudhary Ruchi , Fuchsberger Christian , Forer Lukas , Schoenherr Sebastian , Bei Qixin , Bhangale Tushar , Tom Jennifer , Krishna Gadde Santosh Gopi , Priya B. V. , Naik Naveen Kumar , Wang Minxian , Kwok Pui-Yan , Khera Amit V. , Lakshmi B. R. , Butterworth Adam , Danesh John , Seshagiri Sekar , Kathiresan Sekar , Ghosh Arkasubhra , Mohan V. , Chowdhury Abhijit , Saleheen Danish , Stawiski Eric , Peterson Andrew S. 
Published: October 2020

AbstractPopulation-scale genetic studies can identify drug targets and allow disease risk to be predicted with resulting benefit for management of individual health risks and system-wide allocation of health care delivery resources. Although population-scale projects are underway in many parts of the world, genetic variation between population groups means that additional projects are warranted. South Asia has a population whose genetics is the least characterized of any of the world’s major populations. Here we describe GenomeAsia studies that characterize population structure in South Asia and that create tools for economical and accurate genotyping at population-scale. Prior work on population structure characterized isolated population groups, the relevance of which to large-scale studies of disease genetics is unclear. For our studies we used whole genome sequence information from 4,807 individuals recruited in the health care delivery systems of Pakistan, India and Bangladesh to ensure relevance to population-scale studies of disease genetics. We combined this with WGS data from 927 individuals from isolated South Asian population groups, and developed a custom SNP array (called SARGAM) that is optimized for future human genetic studies in South Asia. We find evidence for high rates of reproductive isolation, endogamy and consanguinity that vary across the subcontinent and that lead to levels of homozygosity that approach 100 times that seen in outbred populations. We describe founder effects that increase the power to associate functional variants with disease processes and that make South Asia a uniquely powerful place for population-scale genetic studies.
CoffeeProt: An online tool for correlation and functional enrichment of proteome-wide systems genetics
Authors: Molendijk Jeffrey , Seldin Marcus M. , Parker Benjamin L. 
Published: October 2020

ABSTRACTThe integration of genomics, proteomics and phenotypic traits across genetically diverse populations is a powerful approach to discover novel biological regulators. The increasing volume of complex data require new and easy-to-use tools accessible to a variety of scientists for the discovery and visualization of functionally relevant associations. To meet this requirement, we developedCoffeeProt, an open-source tool that analyzes genetic variants associated to protein networks and phenotypic traits.CoffeeProtuses proteomics data to perform correlation network analysis and annotates protein-protein interactions and subcellular localizations. It then integrates genetic and phenotypic associations along with variant effect predictions. We demonstrate its utility with the analysis of mouse and human population data enabling the rapid identification of genetic variants associated with protein complexes and clinical traits. We expectCoffeeProtwill serve the proteomics and systems genetics communities, leading to the discovery of novel biologically relevant associations.CoffeeProtis available atwww.coffeeprot.com.
Amyloidogenic core of a human λ-III immunoglobulin light chain fibril and their germline variants probed by MAS solid state NMR
Authors: Pradhan Tejaswini , Annamalai Karthikeyan , Sarkar Riddhiman , Huhn Stephanie , Hegenbart Ute , Schönland Stefan , Fändrich Marcus , Reif Bernd 
Published: October 2020

AbstractSystemic antibody light chains (AL) amyloidosis is characterized by deposition of amyloid fibrils derived from a particular antibody light chain. Cardiac involvement is a major risk factor for mortality. Using MAS solid-state NMR, we study the fibril structure of a recombinant light chain fragment corresponding to the fibril protein from patient FOR005, together with fibrils formed by protein sequence variants that reflect the closest germline (GL) sequence. Both analyzed fibril structures were seeded withex-vivoamyloid fibrils purified from the explanted heart of this patient. We find that residues 11-42 and 69-102 adopt β-sheet conformation in patient protein fibrils. We identify glycine-49 that is mutated with respect to the germline sequence into arginine-49 as a key residue that forms a salt bridge to aspartate-25 in the patient protein fibril structure. Fibrils from the GL protein and from the patient protein harboring the single point mutation R49G can be both heterologously seeded using patientex-vivofibrils. Seeded R49G fibrils show an increased heterogeneity for the C-terminal residues 80-102 which is reflected by the disappearance of all resonances of these residues. By contrast, residues 11-42 and 69-77, which are visible in the MAS solid-state NMR spectra show13Cα chemical shifts that are highly similar to patient fibrils. The mutation R49G thus induces a conformational heterogeneity at the C-terminus in the fibril state, while the overall fibril topology is retained.
U-Infuse: Democratization of Customizable AI for Object Detection
Authors: Shepley Andrew , Falzon Greg , Lawson Christopher , Meek Paul , Kwan Paul 
Published: October 2020

SummaryImage data is one of the primary sources of ecological data used in biodiversity conservation and management worldwide. However, classifying and interpreting large numbers of images is time and resource expensive, particularly in the context of camera trapping. Deep learning models have been used to achieve this task but are often not suited to specific applications due to their inability to generalise to new environments and inconsistent performance. Models need to be developed for specific species cohorts and environments, but the technical skills required to achieve this are a key barrier to the accessibility of this technology to ecologists. There is a strong need to democratise access to deep learning technologies by providing an easy to use software application allowing non-technical users to custom train custom object detectors.U-Infuse addresses this issue by putting the power of AI into the hands of ecologists. U-Infuse provides ecologists with the ability to train customised models using publicly available images and/or their own camera trap images, without the constraints of annotating and pre-processing large numbers of images, or specific technical expertise. U-Infuse is a free and open-source software solution that supports both multiclass and single class training and inference, allowing ecologists to access state of the art AI on their own device, customised to their application without sharing IP or sensitive data.U-Infuse provides ecological practitioners with the ability to (i) easily achieve camera trap object detection within a user-friendly GUI, generating a species distribution report, and other useful statistics, (ii) custom train deep learning models using publicly available and custom training data, (iii) achieve supervised auto-annotation of images for further training, with the benefit of editing annotations to ensure quality datasets.Broad adoption of U-Infuse by ecological practitioners will improve camera trap image analysis and processing by allowing significantly more image data to be processed with minimal expenditure of time and resources. Ease of training and reliance on transfer learning means domain-specific models can be trained rapidly, and frequently updated without the need for computer science expertise, or data sharing, protecting intellectual property and privacy.
Effects of relocation on Immunological and physiological measures in squirrel monkeys (Saimiri boliviensis boliviensis)
Authors: Nehete Pramod , Nehete Bharti P , Wilkerson Greg K , Schapiro Steve J , Williams Lawrence E 
Published: October 2020

AbstractIn the present study, we have quantified the effects of transport, relocation and acclimate/adapt to their new surroundings on squirrel monkey. These responses are measured in blood samples obtained from squirrel monkeys, at different time points relative to their relocation from their old home to their new home. A variety of immunological assays are performed on the phenotype and function of peripheral blood mononuclear cells (PBMCs) in a group of squirrel monkeys that were transported by road for approximately 10 hours from one facility to another. Using a panel of human antibodies and a set of standardized human immune assays, we evaluated the phenotype of lymphocyte subsets by flow, mitogen-specific immune responses of PBMCs in vitro, and levels of cytokines at various time points including immediately before transport, immediately upon arrival, and after approximately 150 days of acclimation. We observed significant changes in T cells and subsets, NK and B cells (CD4+, CD8+, CD4+/CD8+, CD16+, and CD20+). Mitogen specific (e.g. PHA, PWM and LPS) proliferation responses, IFN-g by ELISPOT assay, and cytokines (IL-2, IL-4 and VEGF) significant changes were observed. Changes seen in the serum chemistry measurements mostly complement those seen in the hematology data. The specific goal was to empirically assess the effects of relocation stress in squirrel monkeys in terms of changes in the numbers and functions of various leukocyte subsets in the blood and the amount of time require for acclimating to their new environment. Such data will help to determine when newly arrived animals become available for use in research studies.
Angulin-1 seals tricellular contacts independently of tricellulin and claudins
Authors: Sugawara Taichi , Furuse Kyoko , Otani Tetsuhisa , Furuse Mikio 
Published: October 2020

AbstractTricellular tight junctions (tTJs) are specialized tight junctions (TJs) that seal the intercellular space at tricellular contacts (TCs), where the vertices of three epithelial cells meet. Tricellulin and angulin family membrane proteins are known constituents of tTJs, but the molecular mechanism of tTJ formation remains elusive. Here, we investigated the roles of angulin-1 and tricellulin in tTJ formation in MDCK II cells by genome editing. Angulin-1-deficient cells lost the plasma membrane contact at TCs with impaired epithelial barrier function. The COOH-terminus of angulin-1 bound to the TJ scaffold protein ZO-1 and disruption of their interaction influenced the localization of claudins at TCs, but not the tricellular sealing. Strikingly, the plasma membrane contact at TCs was formed in tricellulin- or claudin-deficient cells. These findings demonstrate that angulin-1 is responsible for the plasma membrane seal at TCs independently of tricellulin and claudins.
Breeding and hibernation of captive meadow jumping mice (Zapus hudsonius)
Authors: Brem Ethan A. , McNulty Alyssa D. , Israelsen William J. 
Published: October 2020

AbstractHibernating mammals exhibit unique metabolic and physiological phenotypes that have potential applications in medicine or spaceflight, yet our understanding of the genetic basis and molecular mechanisms of hibernation is limited. The meadow jumping mouse, a small North American hibernator, exhibits traits – including a short generation time – that would facilitate genetic approaches to hibernation research. Here we report the collection, captive breeding, and laboratory hibernation of meadow jumping mice. Captive breeders in our colony produced a statistically significant excess of male offspring and a large number of all-male and all-female litters. We confirmed that short photoperiod induced pre-hibernation fattening, and cold ambient temperature facilitated entry into hibernation. During pre-hibernation fattening, food consumption exhibited non-linear dependence on both body mass and temperature, such that food consumption was greatest in the heaviest animals at the coldest temperatures. Meadow jumping mice exhibited a strong circadian rhythm of nightly activity that was disrupted during the hibernation interval. We quantified the length and timing of torpor bouts and arousals obtained from an uninterrupted recording of a hibernating female. Over a 90.6 day hibernation interval, torpor bouts ranged from 2.1 to 12.8 days (mean 7.7 days), and arousal length was relatively constant with a mean length of 9.6 hours. We conclude that it is possible to study hibernation phenotypes using captive-bred meadow jumping mice in a laboratory setting.
The nuclear receptor RORα preserves cardiomyocyte mitochondrial function by regulating mitophagy through caveolin-3
Authors: Beak JY , Kang HS , Huang W , Aghajanian A , Gerrish K , Jetten AM , Jensen BC 
Published: October 2020

AbstractPreserving optimal mitochondrial function is critical in the heart, which is the most ATP-avid organ in the body. Recently, we showed that global deficiency of the nuclear receptor RORα in the “staggerer” (RORαsg/sg) mouse exacerbates angiotensin II-induced cardiac hypertrophy and compromises cardiomyocyte mitochondrial function. The mechanisms underlying these observations have not been defined. Here we present evidence that RORα regulates cardiomyocyte mitophagy using pharmacological and genetic gain- and loss-of-function tools, including a novel cardiomyocyte-specific RORα knockout mouse. Cardiomyocyte RORα is upregulated by hypoxia and the loss of RORα blunts hypoxia-induced mitophagy and broadly compromises mitochondrial function. We show that RORα is a direct transcriptional regulator of the mitophagy mediator caveolin-3 in cardiomyocytes and that increased expression of RORα increases caveolin-3 abundance and enhances mitophagy. Knockdown of RORα impairs cardiomyocyte mitophagy, but this defect can be rescued by caveolin-3 overexpression. Collectively, these findings reveal a novel role for RORα in regulating mitophagy through caveolin-3 and expand our currently limited understanding of the mechanisms underlying RORα-mediated cardioprotection.
ROS-dependent innate immune mechanisms controlStaphylococcus aureusMRSA virulence in theDrosophilalarval model
Authors: Ramond Elodie , Jamet Anne , Ding Xiongqi , Bouvier Clémence , Lallemant Louison , He Xiangyan , Arbibe Laurence , Coureuil Mathieu , Charbit Alain 
Published: October 2020

AbstractAntibiotics multi-resistantStaphylococcus aureusstrains constitute a major public health concern worldwide and are responsible of both healthcare- and community-associated infections. Here we have established a robust and simpleS. aureusoral infection model, usingDrosophila melanogasterlarva, which allowed to followS. aureusfate at the whole organism level as well as the host immune responses. Fluorescence microscopy and Light sheet 3D imaging revealed bacterial clustering at the posterior midgut that displays neutral pH. Our study demonstrates thatS. aureusinfection triggers host H2O2production through Duox enzyme, consequently empowering antimicrobial peptides production through Toll pathway activation. We also show that catalase-mediated quenching of H2O2not only enhancesS. aureussurvival but also minimizes host antimicrobial response, hence reducing bacterial clearancein vivo.Finally, we confirm the versatility of this model by demonstrating the colonization and host stimulation capacities of two other bacterial pathogens:SalmonellaTyphimurium andShigella flexneri.Overall, the drosophila larva may constitute a general model to followin vivohost innate immune responses triggered upon infection with human pathogens.
Neural tube patterning: from a minimal model for rostrocaudal patterning towards an integrated 3D model
Authors: Brambach Max , Ernst Ariane , Nolbrant Sara , Drouin-Ouellet Janelle , Kirkeby Agnete , Parmar Malin , Olariu Victor 
Published: October 2020

AbstractThe rostrocaudal patterning of the neural tube is a key event in early brain development. This process is mainly driven by a gradient of WNT, which defines the fate of the present neural progenitor cells in a dose dependent matter and leads to a subdivision of the tube into forebrain, midbrain and hindbrain. Although this process is extensively studied experimentally bothin vivoandin vitro, an integrated view of the responsible genetic circuitry is currently lacking. In this work, we present a minimal gene regulatory model for rostrocaudal neural tube patterning. The model's nodes and architecture are determined in a data driven way, leading to a tristable configuration of mutually repressing brain regions. Analysis of the parameter sensitivity and simulations of knockdown and overexpression cases show that repression of hindbrain fate is a promising strategy for the improvement of current protocols for the generation of dopaminergic neuronsin vitro. Furthermore, we combine the model with an existing model for dorsoventral neural tube patterning, to test its capabilities in anin vivosetting, by predicting the steady state pattern of a realistic three-dimensional neural tube. This reveals that the rostrocaudal pattern stacks dorsoventrally in the caudal half of the neural tube. Finally, we simulate morphogen secretion overexpression, which highlights the sensitivity of neural tube patterning to the morphogen levels.
Intestinal microbiota modulates adrenomedullary response through Nod1 sensing in chromaffin cells
Authors: Xiang Chen , Chen Peihua , Zhang Qin , Li Yinghui , Pan Ying , Xie Wenchun , Sun Jianyuan , Liu Zhihua 
Published: October 2020

AbstractThe intestinal microbiota closely interacts with the neuroendocrine system and exerts profound effects on host physiology. Many of the molecular mechanisms underlying these interactions await discovery. Here we report that Nod1 ligand derived from intestinal bacteria directly modulates catecholamine storage and secretion in mouse adrenal chromaffin cells. The cytosolic peptidoglycan receptor Nod1 is involved in chromogranin A (CHGA) retention in dense core granules (DCGs) in chromaffin cells in a cell-autonomous manner. Mechanistically, upon recognizing its cognate ligands, Nod1 localizes to DCGs, and recruits Rab2a, which is critical for CHGA retention in DCGs. Loss of Nod1 ligands leads to a profound defect in epinephrine storage in chromaffin cells, and subsequently, less secretion upon stimulation. The intestine-adrenal medulla crosstalk bridged by Nod1 ligands modulates adrenal medullary responses during the immobilization-induced stress response in mice. Thus, our study uncovers a mechanism by which intestinal microbes directly modulate a major pathway in response to stress, which may provide further understanding of the gut-brain axis.
Enhancement of synaptic AMPA receptors depends mutually on Src and PSD-95
Authors: Huang Xiaojie , Krüger Juliane M. , Beroun Anna , Xu Weifeng , Dong Yan , Schlüter Oliver M. 
Published: October 2020

AbstractSynaptic incorporation and removal of AMPA receptors is highly regulated to modulate the strength of synaptic transmission for long-term synaptic plasticity during brain development and associative learning. PSD-93α2 and PSD-95α, two paralogs of the DLG-MAGUK protein family of signaling scaffolds govern the synaptic incorporation and stabilization of AMPA receptors opposingly, with PSD-95α promoting and PSD-93α2 inhibiting it. The associated signaling mechanisms that control the synaptic incorporation and stabilization remain elusive. Here, we used domain swapping between the antagonizing signaling scaffolds to identify the protein motifs responsible for enhancing synaptic AMPA receptors and the associated signaling protein. We narrowed down multiple motifs in the N-terminal domain that are principally responsible for governing the enhancement by Src. Specific activation and inhibiting peptides revealed continuous activity of Src. Together, the results depict a mutual dependence of Src and PSD-95α in enhancing and maintaining synaptic AMPA receptors.
ER-embedded UBE2J1/RNF26 ubiquitylation complex in spatiotemporal control of the endolysosomal pathway
Authors: Cremer Tom , Jongsma Marlieke L.M. , Trulsson Fredrik , Vertegaal Alfred C.O. , Neefjes Jacques J.C. , Berlin Ilana 
Published: October 2020

AbstractThe endolysosomal system fulfills a wide variety of cellular functions, many of which are modulated through interactions with other organelles. In particular, the ER exerts spatiotemporal constraints on the organization and motility of endosomes and lysosomes. We have recently described the ER transmembrane E3 ubiquitin ligase RNF26 to control perinuclear positioning and transport dynamics of the endolysosomal vesicular network. We now report that the ubiquitin conjugating enzyme UBE2J1, also anchored in the ER membrane, collaborates with RNF26 in this context, and that the cellular activity of this E2/E3 pair, localized in a perinuclear ER subdomain, is underpinned by transmembrane interactions. Through modification of its substrate SQSTM1/p62, the ER-embedded UBE2J1/RNF26 ubiquitylation complex recruits endosomal adaptors to immobilize their cognate vesicles in the perinuclear region. The resulting spatiotemporal compartmentalization of the endolysosomal system between the perinuclear vesicle cloud and the cell periphery facilitates timely downregulation of endocytosed cargoes, such as EGFR.