Energy Analysis and Heat Integration in the Joint Process of Biomass Fast Pyrolysis and In Line Sorption Enhanced Steam Reforming.

Biomass Fast Pyrolysis and in line Steam Reforming (PY-SR) is promising alternative for H2 production. However, there are potential strategies for intensifying the process, such as capturing the CO2 in situ in the reforming step, which is so-called Sorption Enhanced Steam Reforming (SESR). Both PY-SR and PY-SESR were simulated using a thermodynamic approach and empirical correlations, and they were compared based on the energy requirements, H2 production, and H2 purity at different temperatures (500-800 °C) and steam to biomass (S/B) ratios (0-4). Then, the energy requirements for the PY-SESR were analyzed in detail for a reforming temperature of 600 °C and several S/B ratios, and a heat integration scheme was proposed, aiming at making the process thermally autosustained. Although the energy requirement of PY-SESR is always higher than that of PY-SR at the same reforming conditions, it allows the use of milder operating conditions, with the process performance being even better. Thus, PY-SESR outshines PY-SR, as it allows obtaining a higher H2 production (0.124 kgH2 kg-1 biomass vs 0.118 kgH2 kg-1 biomass) and H2 purity (98 mol % vs 67 mol %), with a lower energy requirement, and capturing the CO2 generated, thereby attaining negative emissions. The main energy demands of this process account for water evaporation and sorbent calcination. Nevertheless, a thermally autosustained PY-SESR process may be attained by recovering heat from the product streams, transferring heat from the reforming reactor to the pyrolysis reactor, and burning the char generated in the pyrolysis step.

Evaluation of four chatbots in autoimmune liver disease: A comparative analysis.

INTRODUCTION AND OBJECTIVES: Autoimmune liver diseases (AILDs) are rare and require precise evaluation, which is often challenging for medical providers. Chatbots are innovative solutions to assist healthcare professionals in clinical management. In our study, ten liver specialists systematically evaluated four chatbots to determine their utility as clinical decision support tools in the field of AILDs. MATERIALS AND METHODS: We constructed a 56-question questionnaire focusing on AILD evaluation, diagnosis, and management of Autoimmune Hepatitis (AIH), Primary Biliary Cholangitis (PBC), and Primary Sclerosing Cholangitis (PSC). Four chatbots -ChatGPT 3.5, Claude, Microsoft Copilot, and Google Bard- were presented with the questions in their free tiers in December 2023. Responses underwent critical evaluation by ten liver specialists using a standardized 1 to 10 Likert scale. The analysis included mean scores, the number of highest-rated replies, and the identification of common shortcomings in chatbots performance. RESULTS: Among the assessed chatbots, specialists rated Claude highest with a mean score of 7.37 (SD = 1.91), followed by ChatGPT (7.17, SD = 1.89), Microsoft Copilot (6.63, SD = 2.10), and Google Bard (6.52, SD = 2.27). Claude also excelled with 27 best-rated replies, outperforming ChatGPT (20), while Microsoft Copilot and Google Bard lagged with only 6 and 9, respectively. Common deficiencies included listing details over specific advice, limited dosing options, inaccuracies for pregnant patients, insufficient recent data, over-reliance on CT and MRI imaging, and inadequate discussion regarding off-label use and fibrates in PBC treatment. Notably, internet access for Microsoft Copilot and Google Bard did not enhance precision compared to pre-trained models. CONCLUSIONS: Chatbots hold promise in AILD support, but our study underscores key areas for improvement. Refinement is needed in providing specific advice, accuracy, and focused up-to-date information. Addressing these shortcomings is essential for enhancing the utility of chatbots in AILD management, guiding future development, and ensuring their effectiveness as clinical decision-support tools.

Bhlhe40 Regulates Proliferation and Angiogenesis in Mouse Embryoid Bodies under Hypoxia.

Knowledge of the molecular mechanisms that underlie the regulation of major adaptive responses to an unbalanced oxygen tension is central to understanding tissue homeostasis and disease. Hypoxia-inducible transcription factors (HIFs) coordinate changes in the transcriptome that control these adaptive responses. Here, we focused on the functional role of the transcriptional repressor basic-helix-loop-helix family member e40 (Bhlhe40), which we previously identified in a meta-analysis as one of the most consistently upregulated genes in response to hypoxia across various cell types. We investigated the role of Bhlhe40 in controlling proliferation and angiogenesis using a gene editing strategy in mouse embryonic stem cells (mESCs) that we differentiated in embryoid bodies (EBs). We observed that hypoxia-induced Bhlhe40 expression was compatible with the rapid proliferation of pluripotent mESCs under low oxygen tension. However, in EBs, hypoxia triggered a Bhlhe40-dependent cell cycle arrest in most progenitor cells and endothelial cells within vascular structures. Furthermore, Bhlhe40 knockout increased the basal vascularization of the EBs in normoxia and exacerbated the hypoxia-induced vascularization, supporting a novel role for Bhlhe40 as a negative regulator of blood vessel formation. Our findings implicate Bhlhe40 in mediating key functional adaptive responses to hypoxia, such as proliferation arrest and angiogenesis.

SinglePointRNA, an user-friendly application implementing single cell RNA-seq analysis software.

Single-cell transcriptomics techniques, such as scRNA-seq, attempt to characterize gene expression profiles in each cell of a heterogeneous sample individually. Due to growing amounts of data generated and the increasing complexity of the computational protocols needed to process the resulting datasets, the demand for dedicated training in mathematical and programming skills may preclude the use of these powerful techniques by many teams. In order to help close that gap between wet-lab and dry-lab capabilities we have developed SinglePointRNA, a shiny-based R application that provides a graphic interface for different publicly available tools to analyze single cell RNA-seq data. The aim of SinglePointRNA is to provide an accessible and transparent tool set to researchers that allows them to perform detailed and custom analysis of their data autonomously. SinglePointRNA is structured in a context-driven framework that prioritizes providing the user with solid qualitative guidance at each step of the analysis process and interpretation of the results. Additionally, the rich user guides accompanying the software are intended to serve as a point of entry for users to learn more about computational techniques applied to single cell data analysis. The SinglePointRNA app, as well as case datasets for the different tutorials are available at www.github.com/ScienceParkMadrid/SinglePointRNA.

Biomass Source Influence on Hydrogen Production through Pyrolysis and in Line Oxidative Steam Reforming.

This study evaluates the potential of several biomasses differing in nature and composition for their valorization by pyrolysis and in line oxidative steam reforming. The first task involved the fast pyrolysis of the biomasses in a conical spouted bed reactor (CSBR) at 500 °C, in which product yields were analyzed in detail. Then, the oxidative steam reforming (OSR) of pyrolysis volatiles (gases and bio-oil) was approached in a fluidized bed reactor (FBR). The reforming experiments were performed at 600 °C, with a steam/biomass (S/B) ratio of 3 and catalyst (Ni/Al2O3) space times of 7.5 and 20 gcat min gvol -1. Concerning equivalence ratio (ER), a value of 0.12 was selected to ensure autothermal operation. Remarkable differences were observed in H2 production depending on the type of biomass. Thus, pine wood led to a H2 production of 9.3 wt %. The lower productions obtained with rice husk (7.7 wt %) and orange peel (5.5 wt %) are associated with their higher ash and fixed carbon content, respectively, which limit the efficiency of biomass conversion to bio-oil. However, in the case of the microalgae, the poor performance observed is because of the lower conversion in the reforming step toward gases due to the composition of its pyrolysis volatile stream.

Food phenolics and Lactiplantibacillus plantarum.

Phenolic compounds are important constituents of plant food products. These compounds play a key role in food characteristics such as flavor, astringency and color. Lactic acid bacteria are naturally found in raw vegetables, being Lactiplantibacillus plantarum the most commonly used commercial starter for the fermentation of plant foods. Hence, the metabolism of phenolic compounds of L. plantarum has been a subject of study in recent decades. Such studies confirm that L. plantarum, in addition to presenting catalytic capacity to transform aromatic alcohols and phenolic glycosides, exhibits two main differentiated metabolic routes that allow the biotransformation of dietary hydroxybenzoic and hydroxycinnamic acid-derived compounds. These metabolic pathways lead to the production of new compounds with new biological and organoleptic properties. The described metabolic pathways involve the action of specialized esterases, decarboxylases and reductases that have been identified through genetic analysis and biochemically characterized. The purpose of this review is to provide a comprehensive and up-to-date summary of the current knowledge of the metabolism of food phenolics in L. plantarum.

Appraisal of agroforestry biomass wastes for hydrogen production by an integrated process of fast pyrolysis and in line steam reforming.

The pyrolysis and in line steam reforming of different types of representative agroforestry biomass wastes (pine wood, citrus wastes and rice husk) was performed in a two-reactor system made up of a conical spouted bed and a fluidized bed. The pyrolysis step was carried out at 500 °C, and the steam reforming at 600 °C with a space time of 20 gcatalyst min gvolatiles-1 and a steam/biomass ratio (S/B) of 4. A study was conducted on the effect that the pyrolysis volatiles composition obtained with several biomasses has on the reforming conversion, product yields and H2 production. The different composition of the pyrolysis volatiles obtained with the three biomasses studied led to differences in the initial activity and, especially, in the catalyst deactivation rate. Initial conversions higher than 99% were obtained in all cases and the H2 production obtained varied in the 6.7-11.2 wt% range, depending on the feedstock used. The stability of the catalysts decreased depending on the feedstock as follows: pine wood â‰« citrus waste > rice husk. A detailed assessment of the mechanisms of catalyst deactivation revealed that coke deposition is the main cause of catalyst decay in all the runs. However, the volatile composition derived from the pyrolysis of citrus waste and rice husk involved the formation of an encapsulating coke, which severely blocked the catalyst pores, leading to catalyst deactivation during the first minutes of reaction.

Formal Meta-Analysis of Hypoxic Gene Expression Profiles Reveals a Universal Gene Signature.

Integrating transcriptional profiles results in identifying gene expression signatures that are more robust than those obtained for individual datasets. However, a direct comparison of datasets derived from heterogeneous experimental conditions is problematic, hence their integration requires applying of specific meta-analysis techniques. The transcriptional response to hypoxia has been the focus of intense research due to its central role in tissue homeostasis and prevalent diseases. Accordingly, many studies have determined the gene expression profile of hypoxic cells. Yet, despite this wealth of information, little effort has been made to integrate these datasets to produce a robust hypoxic signature. We applied a formal meta-analysis procedure to datasets comprising 430 RNA-seq samples from 43 individual studies including 34 different cell types, to derive a pooled estimate of the effect of hypoxia on gene expression in human cell lines grown ingin vitro. This approach revealed that a large proportion of the transcriptome is significantly regulated by hypoxia (8556 out of 20,888 genes identified across studies). However, only a small fraction of the differentially expressed genes (1265 genes, 15%) show an effect size that, according to comparisons to gene pathways known to be regulated by hypoxia, is likely to be biologically relevant. By focusing on genes ubiquitously expressed, we identified a signature of 291 genes robustly and consistently regulated by hypoxia. Overall, we have developed a robust gene signature that characterizes the transcriptomic response of human cell lines exposed to hypoxia in vitro by applying a formal meta-analysis to gene expression profiles.

p73 is required for vessel integrity controlling endothelial junctional dynamics through Angiomotin.

Preservation of blood vessel integrity, which is critical for normal physiology and organ function, is controlled at multiple levels, including endothelial junctions. However, the mechanism that controls the adequate assembly of endothelial cell junctions is not fully defined. Here, we uncover TAp73 transcription factor as a vascular architect that orchestrates transcriptional programs involved in cell junction establishment and developmental blood vessel morphogenesis and identify Angiomotin (AMOT) as a TAp73 direct transcriptional target. Knockdown of p73 in endothelial cells not only results in decreased Angiomotin expression and localization at intercellular junctions, but also affects its downstream function regarding Yes-associated protein (YAP) cytoplasmic sequestration upon cell-cell contact. Analysis of adherens junctional morphology after p73-knockdown in human endothelial cells revealed striking alterations, particularly a sharp increase in serrated junctions and actin bundles appearing as stress fibers, both features associated with enhanced barrier permeability. In turn, stabilization of Angiomotin levels rescued those junctional defects, confirming that TAp73 controls endothelial junction dynamics, at least in part, through the regulation of Angiomotin. The observed defects in monolayer integrity were linked to hyperpermeability and reduced transendothelial electric resistance. Moreover, p73-knockout retinas showed a defective sprout morphology coupled with hemorrhages, highlighting the physiological relevance of p73 regulation in the maintenance of vessel integrity in vivo. We propose a new model in which TAp73 acts as a vascular architect integrating transcriptional programs that will impinge with Angiomotin/YAP signaling to maintain junctional dynamics and integrity, while balancing endothelial cell rearrangements in angiogenic vessels.

Hypoxia classifier for transcriptome datasets.

Molecular gene signatures are useful tools to characterize the physiological state of cell populations, but most have developed under a narrow range of conditions and cell types and are often restricted to a set of gene identities. Focusing on the transcriptional response to hypoxia, we aimed to generate widely applicable classifiers sourced from the results of a meta-analysis of 69 differential expression datasets which included 425 individual RNA-seq experiments from 33 different human cell types exposed to different degrees of hypoxia (0.1-5%[Formula: see text]) for 2-48 h. The resulting decision trees include both gene identities and quantitative boundaries, allowing for easy classification of individual samples without control or normoxic reference. Each tree is composed of 3-5 genes mostly drawn from a small set of just 8 genes (EGLN1, MIR210HG, NDRG1, ANKRD37, TCAF2, PFKFB3, BHLHE40, and MAFF). In spite of their simplicity, these classifiers achieve over 95% accuracy in cross validation and over 80% accuracy when applied to additional challenging datasets. Our results indicate that the classifiers are able to identify hypoxic tumor samples from bulk RNAseq and hypoxic regions within tumor from spatially resolved transcriptomics datasets. Moreover, application of the classifiers to histological sections from normal tissues suggest the presence of a hypoxic gene expression pattern in the kidney cortex not observed in other normoxic organs. Finally, tree classifiers described herein outperform traditional hypoxic gene signatures when compared against a wide range of datasets. This work describes a set of hypoxic gene signatures, structured as simple decision tress, that identify hypoxic samples and regions with high accuracy and can be applied to a broad variety of gene expression datasets and formats.

Seroprevalence against Diphtheria in Pregnant Women and Newborns in Colombia: New Arguments to Promote Maternal Immunization.

The tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine is recommended during pregnancy for neonatal protection against pertussis, although little is known of the protection it provides against diphtheria. The work used a cross-sectional design to estimate seroprevalence against diphtheria in 805 pregnant women with ≥37 gestation weeks and their newborns whose deliveries were attended in eight hospitals randomly chosen from a subregion of Antioquia, Colombia and to explore factors related with maternal protection. Levels of IgG antibodies were determined by using a commercial enzyme-linked immunosorbent assay test. Placental transfer of antibodies and crude and adjusted prevalence ratio (aPR) were analyzed to describe factors related with maternal protection against diphtheria. Protection against diphtheria was observed in 91.7% (95% CI 90.3-93.0) of the pregnant women and 93.1% (95% CI 91.7-94.4) of newborns, whose antibody levels were positively correlated (Spearman's r = 0.769; p = 0.000). Maternal protection could be influenced by having been vaccinated during the current pregnancy (aPR 0.85, 95% CI: 0.82-0.93). The protective effect of vaccination during pregnancy and the efficiency of maternal antibody transfers were detected. Public health efforts should focus on increasing Tdap vaccination during each pregnancy to protect mothers and newborns against diphtheria.

Progress on Catalyst Development for the Steam Reforming of Biomass and Waste Plastics Pyrolysis Volatiles: A Review.

In recent decades, the production of H2 from biomass, waste plastics, and their mixtures has attracted increasing attention in the literature in order to overcome the environmental problems associated with global warming and CO2 emissions caused by conventional H2 production processes. In this regard, the strategy based on pyrolysis and in-line catalytic reforming allows for obtaining high H2 production from a wide variety of feedstocks. In addition, it provides several advantages compared to other thermochemical routes such as steam gasification, making it suitable for its further industrial implementation. This review analyzes the fundamental aspects involving the process of pyrolysis-reforming of biomass and waste plastics. However, the optimum design of transition metal based reforming catalysts is the bottleneck in the development of the process and final H2 production. Accordingly, this review focuses especially on the influence the catalytic materials (support, promoters, and active phase), synthesis methods, and pyrolysis-reforming conditions have on the process performance. The results reported in the literature for the steam reforming of the volatiles derived from biomass, plastic wastes, and biomass/plastics mixtures on different metal based catalysts have been compared and analyzed in terms of H2 production.

The use of Lactobacillus plantarum esterase genes: a biotechnological strategy to increase the bioavailability of dietary phenolic compounds in lactic acid bacteria.

In Lactobacillus plantarum the metabolism of hydroxybenzoic and hydroxycinnamic acid derivatives follows a similar two-step pathway, an esterase action followed by a decarboxylation. The L. plantarum esterase genes involved in these reactions have been cloned into pNZ8048 or pT1NX plasmids and transformed into technologically relevant lactic acid bacteria. None of the strains assayed can hydrolyse methyl gallate, a hydroxybenzoic ester. The presence of the L. plantarum tannase encoding genes (tanALp or tanBLp) on these bacteria conferred their detectable esterase (tannase) activity. Similarly, on hydroxycinnamic compounds, esterase activity for the hydrolysis of ferulic acid was acquired by lactic acid bacteria when L. plantarum esterase (JDM1_1092) was present. This study showed that the heterologous expression of L. plantarum esterase genes involved in the metabolism of phenolic acids allowed the production of healthy compounds which increase the bioavailability of these dietary compounds in food relevant lactic acid bacteria.

Transcriptomic Evidence of Molecular Mechanisms Underlying the Response of Lactobacillus Plantarum WCFS1 to Hydroxytyrosol.

Abstract: This study was aimed to gain new insights into the molecular mechanisms used by Lactobacillus plantarum WCFS1 to respond to hydroxytyrosol (HXT), one of the main and health-relevant plant phenolics present in olive oil. To this goal, whole genome transcriptomic profiling was used to better understand the contribution of differential gene expression in the adaptation to HXT by this microorganism. The transcriptomic profile reveals an HXT-triggered antioxidant response involving genes from the ROS (reactive oxygen species) resistome of L. plantarum, genes coding for H2S-producing enzymes and genes involved in the response to thiol-specific oxidative stress. The expression of a set of genes involved in cell wall biogenesis was also upregulated, indicating that this subcellular compartment was a target of HXT. The expression of several MFS (major facilitator superfamily) efflux systems and ABC-transporters was differentially affected by HXT, probably to control its transport across the membrane. L. plantarum transcriptionally reprogrammed nitrogen metabolism and involved the stringent response (SR) to adapt to HXT, as indicated by the reduced expression of genes involved in cell proliferation or related to the metabolism of (p)ppGpp, the molecule that triggers the SR. Our data have identified, at genome scale, the antimicrobial mechanisms of HXT action as well as molecular mechanisms that potentially enable L. plantarum to cope with the effects of this phenolic compound.

Hypoxia compensates cell cycle arrest with progenitor differentiation during angiogenesis.

Angiogenesis, the main mechanism that allows vascular expansion for tissue regeneration or disease progression, is often triggered by an imbalance between oxygen consumption and demand. Here, by analyzing changes in the transcriptomic profile of endothelial cells (ECs) under hypoxia we uncovered that the repression of cell cycle entry and DNA replication stand as central responses in the early adaptation of ECs to low oxygen tension. Accordingly, hypoxia imposed a restriction in S-phase in ECs that is mediated by Hypoxia-Inducible Factors. Our results indicate that the induction of angiogenesis by hypoxia in Embryoid Bodies generated from murine Stem Cells is accomplished by the compensation of decreased S-phase entry in mature ECs and differentiation of progenitor cells. This conditioning most likely allows an optimum remodeling of the vascular network. Identification of the molecular underpinnings of cell cycle arrest by hypoxia would be relevant for the design of improved strategies aimed to suppress angiogenesis in pathological contexts where hypoxia is a driver of neovascularization.

Oleuropein Transcriptionally Primes Lactobacillus plantarum to Interact With Plant Hosts.

Oleuropein (OLE) is a secoiridoid unique to Oleaceae known to play a role in the plant-herbivore interaction. However, it is not clear how this molecule is induced to mediate plant responses to microbes and how microbes, in turn, withstand with OLE. To better understand how OLE affects the plant-microbe interaction, the contribution of differential gene expression in the adaptation to OLE was characterized by whole genome transcriptional profiling in Lactobacillus plantarum, a bacterium associated to the olive. OLE downregulated functions associated to rapid growth, remodeled membrane phospholipid biosynthesis pathways and markedly repressed the expression of several ABC transporters from L. plantarum. Genes encoding the plantaricin and lamABDCA quorum-sensing (QS) systems were down-regulated indicating the potential of OLE as a QS-antagonist. Notably, OLE diminished the expression of a set of genes encoding inmunomodulatory components and reoriented metabolic pathways to increase protein acetylation, probably to attenuate plant immunity. Responses were also triggered to repress the transport of acetoin and to buffer reactive oxygen species accumulation, two signals involved in plant development. The results suggest that OLE could act as a signaling molecule in the plant-microbe interaction and facilitate the accommodation of beneficial microbes such as L. plantarum by the plant host, via controlled expression of bacterial molecular players involved in this reciprocal interplay.

TFEA.ChIP: a tool kit for transcription factor binding site enrichment analysis capitalizing on ChIP-seq datasets.

SUMMARY: The computational identification of the transcription factors (TFs) [more generally, transcription regulators, (TR)] responsible for the co-regulation of a specific set of genes is a common problem found in genomic analysis. Herein, we describe TFEA.ChIP, a tool that makes use of ChIP-seq datasets to estimate and visualize TR enrichment in gene lists representing transcriptional profiles. We validated TFEA.ChIP using a wide variety of gene sets representing signatures of genetic and chemical perturbations as input and found that the relevant TR was correctly identified in 126 of a total of 174 analyzed. Comparison with other TR enrichment tools demonstrates that TFEA.ChIP is an highly customizable package with an outstanding performance. AVAILABILITY AND IMPLEMENTATION: TFEA.ChIP is implemented as an R package available at Bioconductor https://www.bioconductor.org/packages/devel/bioc/html/TFEA.ChIP.html and github https://github.com/LauraPS1/TFEA.ChIP_downloads. A web-based GUI to the package is also available at https://www.iib.uam.es/TFEA.ChIP/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Improving bio-oil properties through the fast co-pyrolysis of lignocellulosic biomass and waste tyres.

Pinewood sawdust and the waste rubber from truck tyres have been co-pyrolysed in order to improve the properties of bio-oil for its integration in oil refineries. In addition, an analysis has been conducted of the effect the interactions between these two materials' pyrolysis reactions have on product yields and properties. Biomass/tyre mixing ratios of 100/0, 75/25, 50/50, 25/75 and 0/100 by weight percentage have been pyrolysed in continuous mode at 500 °C in a conical spouted bed reactor, obtaining oil yields in the 55.2-71.6 wt% range. Gaseous, oil and solid fractions have been characterised for the 50/50 biomass/tyre mixture, paying special attention to the oil fraction by determining its detailed composition, elemental analysis and calorific value. Co-processing enables the stabilization of the liquid, as the co-pyrolysis oil has a stable single phase, being composed mainly of water, aromatic hydrocarbons and phenols in concentrations of 14.5, 11.1 and 9.7 wt%, respectively. Adding tyre rubber to the biomass in the pyrolysis feed improves the oil's properties, as a liquid with higher carbon content and lower oxygen and water is obtained, even if sulphur content is also increased.

Effects of the Inhibition of Late Sodium Current by GS967 on Stretch-Induced Changes in Cardiac Electrophysiology.

PURPOSE: Mechanical stretch increases sodium and calcium entry into myocytes and activates the late sodium current. GS967, a triazolopyridine derivative, is a sodium channel blocker with preferential effects on the late sodium current. The present study evaluates whether GS967 inhibits or modulates the arrhythmogenic electrophysiological effects of myocardial stretch. METHODS: Atrial and ventricular refractoriness and ventricular fibrillation modifications induced by acute stretch were studied in Langendorff-perfused rabbit hearts (n = 28) using epicardial multiple electrodes and high-resolution mapping techniques under control conditions and during the perfusion of GS967 at different concentrations (0.03, 0.1, and 0.3 µM). RESULTS: On comparing ventricular refractoriness, conduction velocity and wavelength obtained before stretch had no significant changes under each GS967 concentration while atrial refractoriness increased under GS967 0.3 µM. Under GS967, the stretch-induced changes were attenuated, and no significant differences were observed between before and during stretch. GS967 0.3 µM diminished the normal stretch-induced changes resulting in longer (less shortened) atrial refractoriness (138 ± 26 ms vs 95 ± 9 ms; p < 0.01), ventricular refractoriness (155 ± 18 ms vs 124 ± 16 ms; p < 0.01) and increments in spectral concentration (23 ± 5% vs 17 ± 2%; p < 0.01), the fifth percentile of ventricular activation intervals (46 ± 8 ms vs 31 ± 3 ms; p < 0.05), and wavelength of ventricular fibrillation (2.5 ±0.5 cm vs 1.7 ± 0.3 cm; p < 0.05) during stretch. The stretch-induced increments in dominant frequency during ventricular fibrillation (control = 38%, 0.03 µM = 33%, 0.1 µM = 33%, 0.3 µM = 14%; p < 0.01) and the stretch-induced increments in arrhythmia complexity index (control = 62%, 0.03µM = 41%, 0.1 µM = 32%, 0.3 µM = 16%; p < 0.05) progressively decreased on increasing the GS967 concentration. CONCLUSIONS: GS967 attenuates stretch-induced changes in cardiac electrophysiology.

A Diverse Range of Human Gut Bacteria Have the Potential To Metabolize the Dietary Component Gallic Acid.

The human gut microbiota contains a broad variety of bacteria that possess functional genes, with resultant metabolites that affect human physiology and therefore health. Dietary gallates are phenolic components that are present in many foods and beverages and are regarded as having health-promoting attributes. However, the potential for metabolism of these phenolic compounds by the human microbiota remains largely unknown. The emergence of high-throughput sequencing (HTS) technologies allows this issue to be addressed. In this study, HTS was used to assess the incidence of gallate-decarboxylating bacteria within the gut microbiota of healthy individuals for whom bacterial diversity was previously determined to be high. This process was facilitated by the design and application of degenerate PCR primers to amplify a region encoding the catalytic C subunit of gallate decarboxylase (LpdC) from total metagenomic DNA extracted from human fecal samples. HTS resulted in the generation of a total of 3,261,967 sequence reads and revealed that the primary gallate-decarboxylating microbial phyla in the intestinal microbiota were Firmicutes (74.6%), Proteobacteria (17.6%), and Actinobacteria (7.8%). These reads corresponded to 53 genera, i.e., 47% of the bacterial genera detected previously in these samples. Among these genera, Anaerostipes and Klebsiella accounted for the majority of reads (40%). The usefulness of the HTS-lpdC method was demonstrated by the production of pyrogallol from gallic acid, as expected for functional gallate decarboxylases, among representative strains belonging to species identified in the human gut microbiota by this method.IMPORTANCE Despite the increasing wealth of sequencing data, the health contributions of many bacteria found in the human gut microbiota have yet to be elucidated. This study applies a novel experimental approach to predict the ability of gut microbes to carry out a specific metabolic activity, i.e., gallate metabolism. The study showed that, while gallate-decarboxylating bacteria represented 47% of the bacterial genera detected previously in the same human fecal samples, no gallate decarboxylase homologs were identified from representatives of Bacteroidetes The presence of functional gallate decarboxylases was demonstrated in representative Proteobacteria and Firmicutes strains from the human microbiota, an observation that could be of considerable relevance to the in vivo production of pyrogallol, a physiologically important bioactive compound.