bluuebunny/crossref_metadata_2025_split huggingface dataset:
Obesity influences composition of salivary and fecal microbiota and impacts the interactions between bacterial taxa
Authors: Bombin Andrei , Mosley Jonathan D. , Yan Shun , Bombin Sergei , Ferguson Jane F. 
Published: October 2021

ABSTRACTObesity is an increasing global health concern and is associated with a broad range of morbidities. The gut microbiota are increasingly recognized as important contributors to obesity and cardiometabolic health. This study aimed to characterize oral and gut microbial communities, and evaluate host:microbiota interactions between clinical obesity classifications. We performed 16S rDNA sequencing on fecal and salivary samples, global metabolomics profiling on plasma and stool samples, and dietary profiling in 135 healthy individuals. We grouped individuals by obesity status, based on body mass index (BMI), including lean (BMI 18-24.9), overweight (BMI 25-29.9), or obese (BMI ≥30). We analyzed differences in microbiome composition, community inter-relationships, and predicted microbial function by obesity status. We found that salivary bacterial communities of lean and obese individuals were compositionally and phylogenetically distinct. An increase in obesity status was positively associated with strong correlations between bacterial taxa, particularly with bacterial groups implicated in metabolic disorders includingFretibacterium, andTannerella. Consumption of sweeteners, especially xylitol, significantly influenced compositional and phylogenetic diversities of salivary and fecal bacterial communities. In addition, obesity groups exhibited differences in predicted bacterial metabolic activity, which was correlated with host’s metabolite concentrations. Overall, obesity was associated with distinct changes in bacterial community dynamics, particularly in saliva. Consideration of microbiome community structure, and inclusion of salivary samples may improve our ability to understand pathways linking microbiota to obesity and cardiometabolic disease.IMPORTANCEObesity is a worldwide epidemic that is associated with a wide range of health issues. Microbiota were shown to influence metabolism and obesity development. Our study aimed to evaluate the interactions between obesity, salivary and fecal microbiota, and metabolite concentrations in healthy individuals. The oral bacterial community was more impacted by the obesity status of the host than fecal microbiota. Consistently for oral and fecal microbiota, the number of strong interactions between bacteria increased with the increase in the obesity status. Several predicted microbial metabolic pathways that were shown to be associated with metabolic health were uniquely enriched between obesity groups. In addition, these metabolic pathways were correlated with plasma and stool metabolites. Our results suggest that oral microbiota might better reflect the obesity status of the host than fecal microbiota, and that correlations between microbial taxa are altered during obesity.
Rates of primary production in groundwater rival those in oligotrophic marine systems
Authors: Overholt Will A. , Trumbore Susan , Xu Xiaomei , Bornemann Till L.V. , Probst Alexander J. , Krüger Markus , Herrmann Martina , Thamdrup Bo , Bristow Laura , Taubert Martin , Schwab Valérie F. , Hölzer Martin , Marz Manja , Küsel Kirsten 
Published: October 2021

AbstractThe terrestrial subsurface contains nearly all of Earth’s freshwater reserves1 and harbors upwards of 60% of our planet’s total prokaryotic biomass2,3. While genetic surveys suggest these organisms rely on in situ carbon fixation, rather than the translocation of photosynthetically derived organic carbon4–6, corroborating measurements of carbon fixation in the subsurface are absent. Using a novel ultra-low level 14C-labeling technique, we show that in situ carbon fixation rates in a carbonate aquifer reached 10% of the median rates measured in oligotrophic marine surface waters, and were up to six-fold greater than those observed in lower euphotic zone waters where deep chlorophyll levels peak. Empirical carbon fixation rates were substantiated by both nitrification and anammox rate data. Metagenomic analyses revealed a remarkable abundance of putative chemolithoautotrophic members of an uncharacterized order of Nitrospiria – the first representatives of this class expected to fix carbon via the Wood-Ljungdahl pathway. Based on these fixation rates, we extrapolate global primary production in carbonate groundwaters to be 0.11 Pg of carbon per year.
The role of cell geometry and cell-cell communication in gradient sensing
Authors: Fiorentino Jonathan , Scialdone Antonio 
Published: October 2021

AbstractCells can measure shallow gradients of external signals to initiate and accomplish a migration or a morphogenetic process. Recently, starting from mathematical models like the local-excitation global-inhibition (LEGI) model and with the support of empirical evidence, it has been proposed that cellular communication improves the measurement of an external gradient. However, the mathematical models that have been used have over-simplified geometries (e.g., they are uni-dimensional) or assumptions about cellular communication, which limit the possibility to analyze the gradient sensing ability of more complex cellular systems. Here, we generalize the existing models to study the effects on gradient sensing of cell number, geometry and of long-versus short-range cellular communication in 2D systems representing epithelial tissues. We find that increasing the cell number can be detrimental for gradient sensing when the communication is weak and limited to nearest neighbour cells, while it is beneficial when there is long-range communication. We also find that, with long-range communication, the gradient sensing ability improves for tissues with more disordered geometries; on the other hand, an ordered structure with mostly hexagonal cells is advantageous with nearest neighbour communication. Our results considerably extend the current models of gradient sensing by epithelial tissues, making a step further toward predicting the mechanism of communication and its putative mediator in many biological processes.Author summaryGroups of cells collectively migrate in many biological processes, ranging from development to cancer metastasis. The migration is often driven by the gradient of a signaling molecule that can be shallow and noisy, raising the question of how cells can measure it reliably. Cellular communication has recently been suggested to play a key role in gradient sensing, and mathematical models with simplified cellular geometries have been developed to help interpret and design experiments. In this work, we generalize the existing mathematical models to investigate how short- and long-range cellular communication can increase gradient sensing in two-dimensional models of epithelial tissues. We analyze various cellular geometries and tissue size, and we identify the optimal setting that corresponds to different types of communication. Our findings will help pinpoint the communication mechanisms at work in a given tissue and the properties of the molecules that mediate the communication.
Guanosine-specific single-stranded ribonuclease effectors of a phytopathogenic fungus potentiate host immune responses
Authors: Kumakura Naoyoshi , Singkaravanit-Ogawa Suthitar , Gan Pamela , Tsushima Ayako , Ishihama Nobuaki , Watanabe Shunsuke , Seo Mitsunori , Iwasaki Shintaro , Narusaka Mari , Narusaka Yoshihiro , Takano Yoshitaka , Shirasu Ken 
Published: October 2021

SummaryPlants activate immunity upon recognition of pathogen-associated molecular patterns. Although phytopathogens have evolved a set of effector proteins to counteract plant immunity, some effectors are perceived by hosts and induce immune responses. Here, we show that two secreted ribonuclease effectors, SRN1 and SRN2, encoded in a phytopathogenic fungus, Colletotrichum orbiculare, induce cell death in a signal peptide- and catalytic residue-dependent manner, when transiently expressed in Nicotiana benthamiana. The pervasive presence of SRN genes across Colletotrichum species suggested the conserved roles. Using a transient gene expression system in cucumber (Cucumis sativus), an original host of C. orbiculare, we show that SRN1 and SRN2 potentiate host pattern-triggered immunity. Consistent with this, C. orbiculare SRN1 and SRN2 deletion mutants exhibited increased virulence on the host. In vitro analysis revealed that SRN1 specifically cleaves single-stranded RNAs at guanosine, leaving a 3′-end phosphate. This activity has not been reported in plants. Importantly, the potentiation of C. sativus responses by SRN1 and SRN2 depends on the signal peptide and ribonuclease catalytic residues, suggesting that secreted SRNs cleave RNAs in apoplast and are detected by the host. We propose that the pathogen-derived apoplastic guanosine-specific single-stranded endoribonucleases lead to immunity potentiation in plants.
Eoulsan 2: an efficient workflow manager for reproducible bulk, long-read and single-cell transcriptomics analyses
Authors: Lehmann Nathalie , Perrin Sandrine , Wallon Claire , Bauquet Xavier , Deshaies Vivien , Firmo Cyril , Du Runxin , Berthelier Charlotte , Hernandez Céline , Michaud Cédric , Thieffry Denis , Le Crom Stéphane , Thomas-Chollier Morgane , Jourdren Laurent 
Published: October 2021

AbstractMotivationCore sequencing facilities produce huge amounts of sequencing data that need to be analysed with automated workflows to ensure reproducibility and traceability. Eoulsan is a versatile open-source workflow engine meeting the needs of core facilities, by automating the analysis of a large number of samples. Its core design separates the description of the workflow from the actual commands to be run. This originality simplifies its usage as the user does not need to handle code, while ensuring reproducibility. Eoulsan was initially developed for bulk RNA-seq data, but the transcriptomics applications have recently widened with the advent of long-read sequencing and single-cell technologies, calling for the development of new workflows.ResultWe present Eoulsan 2, a major update that (i) enhances the workflow manager itself, (ii) facilitates the development of new modules, and (iii) expands its applications to long reads RNA-seq (Oxford Nanopore Technologies) and scRNA-seq (Smart-seq2 and 10x Genomics). The workflow manager has been rewritten, with support for execution on a larger choice of computational infrastructure (workstations, Hadoop clusters, and various job schedulers for cluster usage). Eoulsan now facilitates the development of new modules, by reusing wrappers developed for the Galaxy platform, with support for container images (Docker or Singularity) packaging tools to execute. Finally, Eoulsan natively integrates novel modules for bulk RNA-seq, as well as others specifically designed for processing long read RNA-seq and scRNA-seq. Eoulsan 2 is distributed with ready-to-use workflows and companion tutorials.Availability and implementationEoulsan is implemented in Java, supported on Linux systems and distributed under the LGPL and CeCILL-C licenses at: http://outils.genomique.biologie.ens.fr/eoulsan/. The source code and sample workflows are available on GitHub: https://github.com/GenomicParisCentre/eoulsan. A GitHub repository for modules using the Galaxy tool XML syntax is further provided at: https://github.com/GenomicParisCentre/eoulsan-toolsContacteoulsan@bio.ens.psl.eu
Benchmarking imputation methods for network inference using a novel method of synthetic scRNA-seq data generation
Authors: Lasri Ayoub , Shahrezaei Vahid , Sturrock Marc 
Published: October 2021

AbstractSingle cell RNA-sequencing (scRNA-seq) has very rapidly become the new workhorse of modern biology providing an unprecedented global view on cellular diversity and heterogeneity. In particular, the structure of gene-gene expression correlation contains information on the underlying gene regulatory networks. However, interpretation of scRNA-seq data is challenging due to specific experimental error and biases that are unique to this kind of data including drop-out (or technical zeros). To deal with this problem several methods for imputation of zeros for scRNA-seq have been developed. However, it is not clear how these processing steps affect inference of genetic networks from single cell data. Here, we introduce Biomodelling.jl, a tool for generation of synthetic scRNA-seq data using multiscale modelling of stochastic gene regulatory networks in growing and dividing cells. Our tool produces realistic transcription data with a known ground truth network topology that can be used to benchmark different approaches for gene regulatory network inference. Using this tool we investigate the impact of different imputation methods on the performance of several network inference algorithms. Biomodelling.jl provides a versatile and useful tool for future development and benchmarking of network inference approaches using scRNA-seq data.
Optogenetic control of the Bicoid morphogen reveals fast and slow modes of gap gene regulation
Authors: Singh Anand P. , Wu Ping , Ryabichko Sergey , Raimundo João , Swan Michael , Wieschaus Eric , Gregor Thomas , Toettcher Jared E. 
Published: October 2021

AbstractDevelopmental patterning networks are regulated by multiple inputs and feedback connections that rapidly reshape gene expression, limiting the information that can be gained solely from slow genetic perturbations. Here we show that fast optogenetic stimuli, real-time transcriptional reporters, and a simplified genetic background can be combined to reveal quantitative regulatory dynamics from a complex genetic network in vivo. We engineer light-controlled variants of the Bicoid transcription factor and study their effects on downstream gap genes in embryos. Our results recapitulate known relationships, including rapid Bicoid-dependent expression of giant and hunchback and delayed repression of Krüppel. In contrast, we find that the posterior pattern of knirps exhibits a quick but inverted response to Bicoid perturbation, suggesting a previously unreported role for Bicoid in suppressing knirps expression. Acute modulation of transcription factor concentration while simultaneously recording output gene activity represents a powerful approach for studying how gene circuit elements are coupled to cell identification and complex body pattern formation in vivo.
Cold Atmospheric Plasma Differentially Affects Cell Renewal and Differentiation of Stem Cells and Apc-Deficient-Derived Tumor Cells in Intestinal Organoids
Authors: Hadefi Alia , Leprovots Morgane , Thulliez Max , Bastin Orianne , Lefort Anne , Libert Frédérick , Nonclercq Antoine , Delchambre Alain , Reniers François , Devière Jacques , Garcia Marie-Isabelle 
Published: October 2021

ABSTRACTCold atmospheric plasma (CAP) treatment has been proposed as a potentially innovative therapeutic tool in the biomedical field, notably for cancer due to its proposed toxic selectivity on cancer cells versus healthy cells. In the present study, we addressed the relevance of three-dimensional organoid technology to investigate the biological effects of CAP on normal epithelial stem cells and tumor cells isolated from mouse small intestine. CAP treatment exerted dose-dependent cytotoxicity on normal organoids and induced major transcriptomic changes associated with global response to oxidative stress, fetal-like regeneration reprogramming and apoptosis-mediated cell death. Moreover, we explored the potential selectivity of CAP on tumor-like Apc-deficient versus normal organoids in the same genetic background. Unexpectedly, tumor organoids exhibited higher resistance to CAP treatment, correlating with higher antioxidant activity at baseline as compared to normal organoids. This pilot study suggests that the ex vivo culture system could be a relevant alternative model to further investigate translational medical applications of CAP technology.
DDX17 is required for efficient DSB repair at DNA:RNA hybrid deficient loci
Authors: Bader Aldo S. , Luessing Janna , Hawley Ben R , Skalka George L , Lu Wei-Ting , Lowndes Noel F , Bushell Martin 
Published: October 2021

ABSTRACTProteins with RNA-binding activity are increasingly being implicated in DNA damage responses (DDR). Additionally, DNA:RNA-hybrids are rapidly generated around DNA double-strand breaks (DSBs), and are essential for effective repair. Here, using a meta-analysis of proteomic data, we identify novel DNA repair proteins and characterise a novel role for DDX17 in DNA repair. We found DDX17 to be required for both cell survival and DNA repair in response to numerous agents that induce DSBs. Analysis of DSB repair factor recruitment to damage sites suggested a role for DDX17 early in the DSB ubiquitin cascade. Genome-wide mapping of R-loops revealed that while DDX17 promotes the formation of DNA:RNA-hybrids around DSB sites, this role is specific to loci that are naturally deficient for DNA:RNA-hybrids. We propose that DDX17 facilitates DSB repair at loci that are inefficient at forming DNA:RNA-hybrids by catalysing the formation of DSB-induced hybrids, thereby allowing propagation of the damage response.
The HIV latency reversal agent HODHBt enhances NK Cell effector and memory-like functions by increasing IL-15 mediated-STAT activation
Authors: Macedo Amanda B. , Levinger Callie , Nguyen Bryan , Gupta Mampta , Cruz Conrad Russell Y. , Chiappinelli Katherine B. , Crandall Keith A. , Bosque Alberto 
Published: October 2021

AbstractElimination of latent HIV reservoirs is a critical endpoint to eradicate HIV. One therapeutic intervention against latent HIV is ‘shock and kill’. This strategy is based on the transcriptional activation of latent HIV with a Latency-Reversing Agent (LRA) with the consequent killing of the reactivated cell by either the cytopathic effect of HIV or the immune system. We have previously found that the small molecule 3-Hydroxy-1,2,3-benzotriazin-4(3H)-one (HODHBt) act as an LRA by increasing Signal Transducers and Activators of Transcription (STAT) activation mediated by IL-15 in cells isolated from aviremic participants. The IL-15 superagonist (N-803) is currently under clinical investigation to eliminate latent reservoirs. IL-15 and N-803 share similar mechanism of action by promoting the activation STATs and have shown some promise in pre-clinical models directed towards HIV eradication. In this work, we evaluated the ability of HODHBt to enhance IL-15 signaling in NK cells and the biological consequences associated with increased STAT activation in NK effector and memory-like functions. We showed that HODHBt increased IL-15-mediated STAT phosphorylation in NK cells, resulting in increased secretion of CXCL10 and IFN-γ and expression of cytotoxic proteins including Granzyme B, Granzyme A, Perforin, Granulysin, FASL and TRAIL. This increased cytotoxic profile results in an increase cytotoxicity against different tumor cell lines and HIV-infected cells. HODHBt also improved the generation of cytokine-induced memory-like NK cells. Overall, our data demonstrate that enhancing the magnitude of IL-15 signaling with HODHBt favors NK cell cytotoxicity and memory-like generation, and targeting this pathway could be further explored for HIV cure interventions.Author SummarySeveral clinical trials targeting the HIV latent reservoir with LRAs have been completed. In spite of a lack of clinical benefit of these trials, they have been crucial to elucidate hurdles that ‘shock and kill’ strategies have to overcome to promote an effective reduction of the latent reservoir leading. These hurdles include low reactivation potential mediated by LRAs; the negative influence of some LRAs on the activity of Natural Killer and CD8T effector cells; an increased resistance to apoptosis of latently infected cells; and an exhausted immune system due to chronic inflammation. To that end, finding therapeutic strategies that can overcome some of these challenges could improve the outcome of ‘shock and kill’ strategies aimed towards HIV eradication. In here, we showed that the LRA HODHBt also improves IL-15 mediated NK effector and memory-like functions. As such, pharmacological enhancement of IL-15 mediated STAT activation can open new therapeutic venues towards an HIV cure.
The interaction effect of psychological capital on the relationship between self-driven personality and happiness at work in the present and post-COVID-19 era
Authors: Kawalya Charles , Kasekende Francis , Munene John C. 
Published: October 2021

Purpose
The purpose of this paper is to examine how psychological capital (PsyCap) and self-driven personality fuse to affect happiness at work in the nursing profession in Uganda.

Design/methodology/approach
This paper adopts a cross-sectional descriptive and analytical design. The authors use structural equation modelling to test hypotheses. Using proportionate and simple random sampling procedures, a sample of 900 respondents was drawn from different hospitals in Uganda of which a response rate of 88.9% was obtained.

Findings
The magnitude effect of self-driven personality on happiness at work depends on PsyCap, implying that the assumption of non-additivity is met.

Research limitations/implications
Only a single research methodological approach was used, and future research through interviews could be undertaken to triangulate.

Practical implications
To boost happiness at the workplace, heads of hospitals should always endeavour to find a viable self-driven personality and PsyCap blend that can add value to nurses’ happiness in Uganda.

Social implications
It is essential for health human resource managers to understand, how self-driven personality and PsyCap foster happiness among nurses in Uganda.

Originality/value
This is one of the few studies that focus on testing the interactive effects of PsyCap on the relationship between self-driven personality and happiness at the workplace in Uganda’s health sector.