bluuebunny/crossref_metadata_2025_split huggingface dataset:
In-VitroEfficacy of Targeted FODMAP Enzymatic Digestion (FODZYME®) in a High-Fidelity Simulated Gastrointestinal Environment
Authors: Ochoa Kenny Castro , Samant Shalaka , Liu Anjie , Duysburgh Cindy , Marzorati Massimo , Singh Prashant , Hachuel David , Chey William , Wallach Thomas 
Published: May 2022

AbstractIntroductionIrritable bowel syndrome (IBS) is characterized by abdominal pain and changes in bowel habits. FODMAPs are poorly absorbed short-chain carbohydrates that may drive commensal microbial gas production, promoting abdominal pain in IBS. Low-FODMAP diet can result in symptomatic improvement in 50-80% of IBS patients. However, this diet is not meant to be sustained long term, with concern for downstream nutrition and microbial issues. In this study, we evaluate the function of a targeted FODMAP enzymatic digestion food supplement FODZYME® containing an fructan hydrolase enzyme in a simulated gastrointestinal environment.MethodsUsing SHIME®, a multi-compartment simulator of the human gut, FODZYME® dose finding assay in modeled gastrointestinal conditions assessed enzymatic ability to hydrolyze 3 g of inulin. Full intestinal modeling assessing digestion of inulin, absorption of fructose, gas production and other measures of commensal microbial behavior was completed using 1.125 g of FODZYME®.ResultsAfter 30 minutes, 90% of the inulin was converted to fructose by 1.125 g of FODZYME®.Doubling dosage showed no significant improvement in conversion, whereas a half dose decreased performance to 77.2%. 70% of released fructose was absorbed during simulated small intestinal transit, with a corresponding decrease in microbial gas production, and a small decrease in butyrate and short chain fatty acid (SCFA) production.DiscussionFODZYME® specifically breaks down inulin in representative gastrointestinal conditions, resulting in decreased gas production while substantially preserving SCFA and butyrate production in the model colon. Our results suggest dietary supplementation with FODZYME® would decrease intestinal FODMAP burden and gas production.
Unsupervised outlier detection applied to SARS-CoV-2 nucleotide sequences can identify sequences of common variants and other variants of interest
Authors: Hahn Georg , Lee Sanghun , Prokopenko Dmitry , Abraham Jonathan , Novak Tanya , Hecker Julian , Cho Michael , Khurana Surender , Baden Lindsey R. , Randolph Adrienne G. , Weiss Scott T. , Lange Christoph 
Published: May 2022

AbstractAs of June 2022, the GISAID database contains more than one million SARS-CoV-2 genomes, including several thousand nucleotide sequences for the most common variants such as delta or omicron. These SARS-CoV-2 strains have been collected from patients around the world since the beginning of the pandemic. We start by assessing the similarity of all pairs of nucleotide sequences using the Jaccard index and principal component analysis. As shown previously in the literature, an unsupervised cluster analysis applied to the SARS-CoV-2 genomes results in clusters of sequences according to certain characteristics such as their strain or their clade. Importantly, we observe that nucleotide sequences of common variants are often outliers in clusters of sequences stemming from variants identified earlier on during the pandemic. Motivated by this finding, we are interested in applying outlier detection to nucleotide sequences. We demonstrate that nucleotide sequences of common variants (such as alpha, delta, or omicron) can be identified solely based on a statistical outlier criterion. We argue that outlier detection might be a useful surveillance tool to identify emerging variants in real time as the pandemic progresses.
Primary cilia regulate Meibomian glands development and dimensions without impairing lipid composition of the meibum
Authors: Portal Céline , Lin Yvonne , Rastogi Varuni , Peterson Cornelia , Foster James , Wilkerson Amber , Butovich Igor , Iomini Carlo 
Published: May 2022

ABSTRACTPurposePrimary cilia regulate the development of various ectoderm-derived tissues, including the corneal epithelium, skin, hair follicle and sebaceous glands. We aimed to investigate their role in meibomian gland (MG) development.MethodsPrimary cilium ablation in MGs was achieved by crossing a floxed Ift88 mouse (Ift88fl/fl) with a mouse expressing the Cre recombinase under the keratin 14 (K14) promoter, to generateK14-Cre;Ift88fl/flmice. MG morphology was evaluated by histology and immunostaining, as well as lipid staining and 2-photon microscopy on whole mount tarsal plates. MG lipid profiles were assessed by chromatography.ResultsWe showed that most of MG cells are ciliated during early stages of MG development and that MG ciliated rate decreases throughout morphogenesis. In morphologically mature glands, only the MG central duct and ductules are ciliated, and meibocytes lose their cilia as they differentiate and become filled with lipids. Primary cilium ablation induces enlargement of MGs, dilation of the MG central duct, and an increased production of lipids, without dramatically changing the lipid profiles. In addition, primary cilia regulate MG elongation and the spatial distribution of proliferating and dying cells within MGs, without changing the total cell proliferation and death rates.ConclusionsThese findings indicate that primary cilia are not necessary for normal MG development. However, they promote MG enlargement and lipid production, suggesting that primary cilia could be an interesting target for treatments of ocular surface diseases involving MGs, like dry eye disease.
Activity of Tricyclic Pyrrolopyrimidine Gyrase B Inhibitor against Mycobacterium abscessus
Authors: Madani Abdeldjalil , Negatu Dereje A. , El Marrouni Abdellatif , Miller Randy R. , Boyce Christopher , Murgolo Nicholas , Bungard Christopher J. , Zimmerman Matthew D. , Dartois Véronique , Gengenbacher Martin , Olsen David B. , Dick Thomas 
Published: May 2022

ABSTRACTTricyclic pyrrolopyrimidines (TPPs) are a new class of antibacterials inhibiting the ATPase of DNA gyrase. TPP8, a representative of this class, is active against Mycobacterium abscessus in vitro. Spontaneous TPP8 resistance mutations mapped to the ATPase domain of M. abscessus DNA gyrase and the compound inhibited DNA supercoiling activity of recombinant M. abscessus enzyme. Further profiling of TPP8 in macrophage and mouse infection studies demonstrated proof-of-concept activity against M. abscessus ex vivo and in vivo.
Enhancement of Cell Adhesion by Anaplasma phagocytophilum Nucleolin-interacting Protein AFAP
Authors: Tang Hongcheng , Zhu Jiafeng , Wu Shuyan , Niu Hua 
Published: May 2022

AbstractAnaplasma phagocytophilum, the aetiologic agent of human granulocytic anaplasmosis (HGA) is an obligate intracellular Gram-negative bacterium. During infection, A. phagocytophilum enhances the adhesion of neutrophils to infected endothelial cells. However the bacterial factors contributing to this phenomenon remain unknown. In this study, we characterized a type IV secretion system substrate of A. phagocytophilum, AFAP (an actin filament-associated Anaplasma phagocytophilumprotein), and found it enhanced cell adhesion. Tandem affinity purification combined with mass spectrometry identified host nucleolin as an AFAP-binding protein. Further study showed disruption of nucleolin by RNA interference and treatment of a nucleolin-binding DNA aptamer AS1411 attenuated AFAP-mediated cell adhesion. The characterization of AFAP with enhancement effect on cell adhesion and identification of its interaction partner may help understand the mechanism underlying A. phagocytophilum-promoting cell adhesion, facilitating elucidation of HGA pathogenesis.HighlightsAnaplasma phagocytophilum AFAP localized to cell periphery.AFAP enhanced cell adhesion.AFAP interacted with host nucleolin.Disruption of nucleolin attenuated AFAP-mediated cell adhesion.
Genome dynamics in mosses: Extensive synteny coexists with a highly dynamic gene space
Authors: Kirbis Alexander , Rahmatpour Nasim , Dong Shanshan , Yu Jin , van Gessel Nico , Waller Manuel , Reski Ralf , Lang Daniel , Rensing Stefan A. , Temsch Eva M. , Wegrzyn Jill L. , Goffinet Bernard , Liu Yang , Szövényi Péter 
Published: May 2022

ABSTRACTBackgroundWhile genome evolutionary processes of seed plants are intensively investigated, very little is known about seed-free plants in this respect. Here, we use one of the largest groups of seed-free plants, the mosses, and newly generated chromosome-scale genome assemblies to investigate three poorly known aspects of genome dynamics and their underlying processes in seed-free plants: (i) genome size variation, (ii) genomic collinearity/synteny, and (iii) gene set differentiation.ResultsComparative genomic analyses on the model moss Physcomitrium (Physcomitrella) patens and two genomes of Funaria hygrometrica reveal that, like in seed plants, genome size change (approx. 140 Mbp) is primarily due to transposable element expansion/contraction. Despite 60 million years of divergence, the genomes of P. patens and F. hygrometrica show remarkable chromosomal stability with the majority of homologous genes located in conserved collinear blocks. In addition, both genomes contain a relatively large set of lineage-specific genes with no detectible homologs in the other species’ genome, suggesting a highly dynamic gene space fueled by the process of de novo gene birth and loss rather than by gene family diversification/duplication.ConclusionsThese, combined with previous observations suggest that genome dynamics in mosses involves the coexistence of a collinear homologous and a highly dynamic species-specific gene sets. Besides its significance for understanding genome evolution, the presented chromosome-scale genome assemblies will provide a foundation for comparative genomic and functional studies in the Funariaceae, a family holding historical and contemporary model taxa in the evolutionary biology of mosses.
Radiation-Induced Metabolic Reprogramming of Fibroblasts Regulates the Breast Cancer Microenvironment
Authors: Corn Kevin C. , Britto Lucy S. , Mohamed Youssef K. , Ivanova Yoanna I. , Zhu Tian , Rafat Marjan 
Published: May 2022

AbstractPatients with triple negative breast cancer (TNBC) continue to have high recurrence rates despite current interventions, including radiation therapy (RT). Radiation-resistant TNBC cells and circulating tumor cells thought to be involved in recurrence survive due to changes in their metabolic profiles, which may be influenced by their interactions with radiation-damaged stromal cells, such as fibroblasts, following treatment. How fibroblasts metabolically respond to RT and influence the metabolism of TNBC cells is poorly understood. In this study, we identify that radiation-damaged fibroblasts accumulate lipids due to increased autophagic flux. The radiation damage response allows fibroblasts to maintain increased fatty acid oxidation, overall mitochondrial respiration, and aerobic glycolysis rates, leading to increased lactate secretion. TNBC cells respond to these metabolic changes by increasing migration rates and tumor spheroid growth. Our work reveals how metabolic crosstalk between irradiated fibroblasts and TNBC cells leads to a microenvironment conducive to recurrence.SummaryAlthough radioresistant and circulating tumor cell survival has been attributed to altered metabolism, the metabolic impact of radiation therapy on stromal cells is unknown. The authors provide a burgeoning mechanism for radiation-induced metabolic crosstalk between fibroblasts and breast cancer cells that may influence recurrence.Graphical Abstract
Substrate adhesion determines migration during mesenchymal cell condensation in chondrogenesis
Authors: Casanellas Ignasi , Jiang Hongkai , David Carolyn M. , Vida Yolanda , Pérez-Inestrosa Ezequiel , Samitier Josep , Lagunas Anna 
Published: May 2022

AbstractEffective cartilage development relies on the successful formation of mesenchymal cell condensates. Mesenchymal condensation is a prevalent morphogenetic transition, which involves the upregulation of the adhesive extracellular glycoprotein fibronectin (FN). During condensation, there is an active directional migration of cells from the surrounding loose mesenchyme towards regions of increasing matrix adherence (the condensation centers). In this study, we live imaged the first 40 h of mesenchymal condensation during chondrogenesis on nanopatterns of the cell-adhesive peptide arginine-glycine-aspartic acid (RGD), present in FN. Results show cell-substrate adhesions modulate both single-cell and collective cell migration during mesenchymal condensation. Single cell tracking analysis showed that substrate adhesion determines the migration mode, protrusion formation and the directionality of the cell movement. Cells on the more adhesive nanopatterns presented traits among amoeboid and mesenchymal modes of migration facilitating a more directional movement and reducing contact inhibition of locomotion (CIL), which allows merging and condensation. Inhibition experiments demonstrated that neural cadherin (N-Cad) is required in cell-cell interactions, enabling cells to coordinate their movement and directionality in a multicellular environment and to maintain the group cohesiveness during migration. Altogether, this contributes to create a sufficiently dynamic scenario, in which there is a balance between cell-substrate and cell-cell adhesions for condensates to grow. Our results provide a framework for the regulation of single and collective cell migration during mesenchymal condensation, through nanoscale cell-substrate adherence.Summary statementThe fine tuning of substrate adherence through nanopatterning allows control of mesenchymal cell migration and determines condensation during chondrogenesis in vitro.
Pervasive tandem duplications and convergent evolution shape coral genomes
Authors: Noel Benjamin , Denoeud France , Rouan Alice , Buitrago-López Carol , Capasso Laura , Poulain Julie , Boissin Emilie , Pousse Mélanie , Da Silva Corinne , Couloux Arnaud , Armstrong Eric , Carradec Quentin , Cruaud Corinne , Labadie Karine , Lê-Hoang Julie , Tambutté Sylvie , Barbe Valérie , Moulin Clémentine , Bourdin Guillaume , Iwankow Guillaume , Romac Sarah ,   Tara Pacific Consortium Coordinators, Allemand Denis , Planes Serge , Gilson Eric , Zoccola Didier , Wincker Patrick , Voolstra Christian R , Aury Jean-Marc 
Published: May 2022

AbstractOver the last decade, several coral genomes have been sequenced allowing a better understanding of these symbiotic organisms threatened by climate change. Scleractinian corals are reef builders and are central to these ecosystems, providing habitat and food to a great diversity of species. In the frame of the Tara Pacific expedition, we generated two coral genomes,Porites lobataandPocillopora meandrinawith vastly improved contiguity that allowed us to study the functional organisation of these genomes. We annotated their gene catalog and report a relatively higher gene number (43,000 and 32,000 genes respectively) than that found in other public coral genome sequences. This finding is explained by a high number of tandemly duplicated genes (almost a third of the predicted genes). We show that these duplicated genes originate from multiple and distinct duplication events throughout the coral lineage. They contribute to the amplification of gene families, mostly related to immune system and disease-resistance, which we suggest to be functionally linked to coral host resilience. At large, we show the importance of duplicated genes to inform the biology of reef-building corals and provide novel avenues to understand and screen for differences in stress resilience.
Single cell kinetic modeling of redox-based drug metabolism in head and neck squamous cell carcinoma
Authors: Raddatz Andrew D. , Furdui Cristina , Bey Erik , Kemp Melissa L. 
Published: May 2022

AbstractHead and neck squamous cell carcinoma (HNSCC) cells are highly heterogeneous in their metabolism and typically experience elevated reactive oxygen species (ROS) levels in the tumor microenvironment. The tumor cells survive under these chronic oxidative conditions by upregulating antioxidant systems compared to healthy cells. Radiation and the majority of chemotherapies used clinically for treatment of HNSCC rely directly or indirectly upon the generation of short-lived ROS to induce cancer cell death. To investigate the heterogeneity of cellular responses to chemotherapeutic ROS generation in tumor and healthy tissue, we leveraged single cell RNA-sequencing (scRNA-seq) data to perform redox systems-level simulations of quinone-cycling β-lapachone treatment as a source of NQO1-dependent rapid superoxide and hydrogen peroxide (H2O2) production. Transcriptomic data from 10 HNSCC patient tumors was used to populate over 4000 single cell antioxidant enzymatic models. The simulations reflected significant systems-level differences between the redox states of healthy and cancer cells, demonstrating in some patient samples a targetable cancer cell population or in others statistically indistinguishable effects between non-malignant and malignant cells. Subsequent multivariate analyses between healthy and malignant cellular models point to distinct contributors of redox responses between these phenotypes. This model framework provides a mechanistic basis for explaining mixed outcomes of NQO1-bioactivatable therapeutics despite the tumor specificity of these drugs as defined by NQO1/catalase expression.
A conserved enzyme of smut fungi facilitates cell-to-cell movement in the plant bundle sheath
Authors: Ökmen Bilal , Jaeger Elaine , Schilling Lena , Finke Natalie , Lee Yoon Joo , Wemhöner Raphael , Pauly Markus , Neumann Ulla , Doehlemann Gunther 
Published: May 2022

SummaryThe smut fungi are one of the largest groups of fungal plant pathogens, causing disease in all cereal crops. They directly penetrate their hosts and establish a biotrophic interaction. During colonization of the plant, smut fungi secrete a wide range of effector proteins, which suppress plant immunity and modulate cellular functions as well as development of the host, thereby determining the pathogen’s life-style and virulence potential.The conserved effector Erc1 (enzyme required for cell-to-cell movement) contributes to virulence of the corn smut Ustilago maydis in maize leaves, but not on the tassel. Erc1 binds to host cell wall components and has a 1,3-β-glucanase activity, which is required to attenuate β-glucan-induced defense responses in host leaves. Confocal microscopy revealed that Erc1 has a cell type-specific virulence function, being necessary for fungal cell-to-cell movement in the plant bundle sheath. This cell type-specific virulence function of Erc1 is fully conserved in the barley pathogen Ustilago hordei, which has a functionally conserved Erc1 orthologue.Thus, Erc1 is an enzymatically active core virulence factor with a cell type-specific virulence function in different hosts, which is important for cell-to-cell movement during host colonization of pathogenic smut fungi.
Extraintestinal roles of intestinal vitamin D receptor in protecting against dysbiosis and tumorigenesis in breast cancer
Authors: Zhang Yong-Guo , Zhang Jilei , Deb Shreya , Garrett Shari , Xia Yinglin , Sun Jun 
Published: May 2022

AbstractThe microbiota play critical roles in regulating the function and health of intestine and extraintestinal organs. A fundamental question is whether there is an intestinal-microbiome-breast axis during the development of breast cancer. If yes, what are the roles of host factors? Vitamin D receptor (VDR) involves host factors and the human microbiome. Vdr gene variation shapes the human microbiome and VDR deficiency leads to dysbiosis. We hypothesized that intestinal VDR protects hosts against tumorigenesis in breast. Reduced VDR mRNA expression was observed in patients with breast cancer. We used a 7,12-dimethylbenzanthracene (DMBA)-induced breast cancer model in intestinal epithelial VDR knockout (VDRΔIEC) mice. We reported that VDRΔIEC mice with dysbiosis are more susceptible to breast cancer induced by DMBA. Intestinal and breast microbiota analysis showed that lacking VDR leads to bacterial profile shift from normal to susceptible carcinogenesis. We found enhanced bacterial staining within breast tumors. At the molecular and cellular levels, we identified the mechanisms by which intestinal epithelial VDR deficiency led to increased gut permeability, disrupted tight junctions, microbial translocation, and enhanced inflammation, thus increasing the tumor size and number in breast. Furthermore, treatment with beneficial bacterial metabolite butyrate or probiotic Lactobacillus plantarum reduced the breast tumors, enhanced the tight junctions, and inhibited inflammation in the VDRΔIEC mice. Gut microbiome contribute to the pathogenesis of diseases, not only in the intestine, but also in the breast. Our study provides new insights into the mechanism by which intestinal VDR dysfunction and gut dysbiosis led to high risk of extraintestinal tumorigenesis. Gut-tumor-microbiome interactions indicate a new target in the prevention and treatment of breast cancer.Abstract Figure
HARIBOSS: a curated database of RNA-small molecules structures to aid rational drug design
Authors: Panei F. P. , Torchet R. , Menager H. , Gkeka P. , Bonomi M. 
Published: May 2022

AbstractRNA molecules are implicated in numerous fundamental biological processes and many human pathologies, such as cancer, neurodegenerative disorders, muscular diseases, and bacterial infections. Modulating the mode of action of disease-implicated RNA molecules can lead to the discovery of new therapeutical agents and even address pathologies linked to 8undruggable9 protein targets. This modulation can be achieved by direct targeting of RNA with small molecules. As of today, only a few RNA-targeting small molecules are used clinically. One of the main obstacles that has hampered the development of a rational drug design protocol to target RNA with small molecules is the lack of a comprehensive understanding of the molecular mechanisms at the basis of RNA-small molecule recognition. Here, we present HARIBOSS, a curated collection of RNA-small molecule structures determined by X-ray crystallography, Nuclear Magnetic Resonance spectroscopy and cryo-electron microscopy. HARIBOSS facilitates the exploration of drug-like compounds known to bind RNA, the analysis of ligands and pockets properties, and ultimately the development of in silico strategies to identify RNA-targeting small molecules. HARIBOSS can be explored via a web interface available at http://hariboss.pasteur.cloud.