Systems Biology
NCoR1 controls Mycobacterium tuberculosis growth in myeloid cells by regulating the AMPK-mTOR-TFEB axis
PLoS Biol. 2023 Aug 17;21(8):e3002231. doi: 10.1371/journal.pbio.3002231. Online ahead of print.
ABSTRACT
Mycobacterium tuberculosis (Mtb) defends host-mediated killing by repressing the autophagolysosome machinery. For the first time, we report NCoR1 co-repressor as a crucial host factor, controlling Mtb growth in myeloid cells by regulating both autophagosome maturation and lysosome biogenesis. We found that the dynamic expression of NCoR1 is compromised in human peripheral blood mononuclear cells (PBMCs) during active Mtb infection, which is rescued upon prolonged anti-mycobacterial therapy. In addition, a loss of function in myeloid-specific NCoR1 considerably exacerbates the growth of M. tuberculosis in vitro in THP1 differentiated macrophages, ex vivo in bone marrow-derived macrophages (BMDMs), and in vivo in NCoR1MyeKO mice. We showed that NCoR1 depletion controls the AMPK-mTOR-TFEB signalling axis by fine-tuning cellular adenosine triphosphate (ATP) homeostasis, which in turn changes the expression of proteins involved in autophagy and lysosomal biogenesis. Moreover, we also showed that the treatment of NCoR1 depleted cells by Rapamycin, Antimycin-A, or Metformin rescued the TFEB activity and LC3 levels, resulting in enhanced Mtb clearance. Similarly, expressing NCoR1 exogenously rescued the AMPK-mTOR-TFEB signalling axis and Mtb killing. Overall, our data revealed a central role of NCoR1 in Mtb pathogenesis in myeloid cells.
PMID:37590294 | DOI:10.1371/journal.pbio.3002231
The Influence of Protein Secretomes of Enterococcus durans on ex vivo Human Gut Microbiome
Probiotics Antimicrob Proteins. 2023 Aug 17. doi: 10.1007/s12602-023-10136-9. Online ahead of print.
ABSTRACT
The gut microbiome plays a critical role to all animals and humans health. Methods based on ex vivo cultures are time and cost-effective solutions for rapid evaluation of probiotic effects on microbiomes. In this study, we assessed whether the protein secretome from the potential probiotic Enterococcus durans LAB18S grown on fructoligosaccharides (FOS) and galactoligosaccharides (GOS) had specific effects on ex vivo cultured intestinal microbiome obtained from a healthy individual. Metaproteomics was used to evaluate changes in microbial communities of the human intestinal microbiome. Hierarchical clustering analysis revealed 654 differentially abundant proteins from the metaproteome samples, showing that gut microbial protein expression varied on the presence of different E. durans secretomes. Increased amount of Bacteroidetes phylum was observed in treatments with secretomes from E. durans cultures on FOS, GOS and albumin, resulting in a decrease of the Firmicutes to Bacteroidetes (F/B) ratio. The most functionally abundant bacterial taxa were Roseburia, Bacteroides, Alistipes and Faecalibacterium. The results suggest that the secretome of E. durans may have favorable effects on the intestinal microbial composition, stimulating growth and different protein expression of beneficial bacteria. These findings suggest that proteins secreted by E. durans growing on FOS and GOS have different effects on the modulation of gut microbiota functional activities during cultivation.
PMID:37589783 | DOI:10.1007/s12602-023-10136-9
Predicted structural proteome of Sphagnum divinum and proteome-scale annotation
Bioinformatics. 2023 Aug 17:btad511. doi: 10.1093/bioinformatics/btad511. Online ahead of print.
ABSTRACT
MOTIVATION: Sphagnum-dominated peatlands store a substantial amount of terrestrial carbon. The genus is undersampled and under-studied. No experimental crystal structure from any Sphagnum species exists in the Protein Data Bank and fewer than 200 Sphagnum-related genes have structural models available in the AlphaFold Protein Structure Database. Tools and resources are needed to help bridge these gaps, and to enable the analysis of other structural proteomes now made possible by accurate structure prediction.
RESULTS: We present the predicted structural proteome (25,134 primary transcripts) of S. divinum computed using AlphaFold, structural alignment results of all high-confidence models against an annotated non-redundant crystallographic database of over 90,000 structures, a structure-based classification of putative Enzyme Commission (EC) numbers across this proteome, and the computational method to perform this proteome-scale structure-based annotation.
AVAILABILITY: All data and code are available in public repositories, detailed at https://github.com/BSDExabio/SAFA. The structural models of the S. divinum proteome have been deposited in the ModelArchive repository at https://modelarchive.org/doi/10.5452/ma-ornl-sphdiv.
SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
PMID:37589594 | DOI:10.1093/bioinformatics/btad511
Weight gain, gender and antipsychotics: a disproportionality analysis of the FDA Adverse event reporting System database (FAERS)
Expert Opin Drug Saf. 2023 Aug 17. doi: 10.1080/14740338.2023.2248873. Online ahead of print.
ABSTRACT
INTRODUCTION: Side effects are a very important aspect of antipsychotic treatments. Weight gain is an important side effect that jeopardizes the uninterrupted therapy administration, especially in patients with psychiatric conditions. This case-non case pharmacovigilance study aims at investigating in a real-world adverse event reporting system whether several antipsychotics increase the risk of weight gain reporting, and the differences among men and women as far as weight gain as a reported adverse event is concerned.
AREAS COVERED: Adverse event reports submitted to FDA Adverse Event Reporting System of the Food and Drug Administration of the United States (FAERS) of 24 major antipsychotics were extracted, cleaned and analyzed to determine which of these drugs were correlated with weight gain. The Reported Odds Ratio (ROR) and the adjusted Reported Odds Ratio (aROR) were calculated for each antipsychotic using logistic regression models. Demographics like age, the gender and the concomitant insulin use were taken into consideration for each drug.
EXPERT OPINION: Women had a statistically significant increase in weight gain reporting compared to men, while the men group was associated with a reduced weight gain reporting in every antipsychotic in the logistic regression analyses. Out of the 24 antipsychotics included in our analysis Aripiprazole, Brexpiprazole, Olanzapine and Haloperidol had statistically significant more weight increase reporting compared to the others.
PMID:37589503 | DOI:10.1080/14740338.2023.2248873
A stochastic model of hippocampal synaptic plasticity with geometrical readout of enzyme dynamics
Elife. 2023 Aug 17;12:e80152. doi: 10.7554/eLife.80152.
ABSTRACT
Discovering the rules of synaptic plasticity is an important step for understanding brain learning. Existing plasticity models are either (1) top-down and interpretable, but not flexible enough to account for experimental data, or (2) bottom-up and biologically realistic, but too intricate to interpret and hard to fit to data. To avoid the shortcomings of these approaches, we present a new plasticity rule based on a geometrical readout mechanism that flexibly maps synaptic enzyme dynamics to predict plasticity outcomes. We apply this readout to a multi-timescale model of hippocampal synaptic plasticity induction that includes electrical dynamics, calcium, CaMKII and calcineurin, and accurate representation of intrinsic noise sources. Using a single set of model parameters, we demonstrate the robustness of this plasticity rule by reproducing nine published ex vivo experiments covering various spike-timing and frequency-dependent plasticity induction protocols, animal ages, and experimental conditions. Our model also predicts that in vivo-like spike timing irregularity strongly shapes plasticity outcome. This geometrical readout modelling approach can be readily applied to other excitatory or inhibitory synapses to discover their synaptic plasticity rules.
PMID:37589251 | DOI:10.7554/eLife.80152
Deciphering gastric inflammation-induced tumorigenesis through multi-omics data and AI methods
Cancer Biol Med. 2023 Aug 17:j.issn.2095-3941.2023.0129. doi: 10.20892/j.issn.2095-3941.2023.0129. Online ahead of print.
ABSTRACT
Gastric cancer (GC), the fifth most common cancer globally, remains the leading cause of cancer deaths worldwide. Inflammation-induced tumorigenesis is the predominant process in GC development; therefore, systematic research in this area should improve understanding of the biological mechanisms that initiate GC development and promote cancer hallmarks. Here, we summarize biological knowledge regarding gastric inflammation-induced tumorigenesis, and characterize the multi-omics data and systems biology methods for investigating GC development. Of note, we highlight pioneering studies in multi-omics data and state-of-the-art network-based algorithms used for dissecting the features of gastric inflammation-induced tumorigenesis, and we propose translational applications in early GC warning biomarkers and precise treatment strategies. This review offers integrative insights for GC research, with the goal of paving the way to novel paradigms for GC precision oncology and prevention.
PMID:37589244 | DOI:10.20892/j.issn.2095-3941.2023.0129
Gene-exercise interaction on brain health in children with overweight/obesity: The ActiveBrains randomized controlled trial
J Appl Physiol (1985). 2023 Aug 17. doi: 10.1152/japplphysiol.00435.2023. Online ahead of print.
ABSTRACT
We investigated the interaction between a genetic score and an exercise intervention on brain health in children with overweight/obesity. One hundred one children with overweight/obesity (10.0 ± 1.5 years, 59% girls) were randomized into a 20-week combined exercise intervention or a control group. Several cognitive and academic outcomes were measured with validated tests. Hippocampal volume was quantified using magnetic resonance imaging. Six brain health-related polymorphisms (rs6265 [BDNF], rs2253206 [CREB1], rs2289656 [NTRK2], rs4680 [COMT], rs429358, and rs7412 [APOE]) were genotyped. Cognitive flexibility and academic skills improved significantly more in the exercise than in the control group only in the children with a "favorable" genetic profile (mean z score, 0.41-0.67 [95% CI 0.11 to 1.18], yet not in those with "less favorable" genetic profile. An individual response analysis showed that children responded to exercise in cognitive flexibility only in the "genetically favorable" group (i.e. 62% of them had a meaningful [≥0.2 Cohen d] increase in the exercise group compared with only 25% in the control group). This finding was consistent in per-protocol and intention-to-treat analyses (P=0.01 and P=0.03, respectively). The results were not significant or not consistent for the rest of outcomes studied. Our findings suggest that having a more favorable genetic profile makes children with overweight-obesity more responsive to exercise, particularly for cognitive flexibility.
PMID:37589055 | DOI:10.1152/japplphysiol.00435.2023
Elemental composition and material properties of radular teeth in the heterobranch snail <em>Gastropteron rubrum</em> (Mollusca, Gastropoda, Cephalaspidea) foraging on hard organisms
Ecol Evol. 2023 Aug 14;13(8):e10332. doi: 10.1002/ece3.10332. eCollection 2023 Aug.
ABSTRACT
The molluscan feeding structure is the radula, a chitinous membrane with teeth, which are highly adapted to the food and the substrate to which the food is attached. In Polyplacophora and Patellogastropoda, the handling of hard ingesta can be facilitated by high content of chemical compounds containing Fe or Si in the tooth cusps. Other taxa, however, possess teeth that are less mineralized, even though animals have to avoid structural failure or high wear during feeding as well. Here, we investigated the gastropod Gastropteron rubrum, feeding on hard Foraminifera, diatoms and Porifera. Tooth morphologies and wear were documented by scanning electron microscopy and their mechanical properties were tested by nanoindentation. We determined that gradients of hard- and stiffness run along each tooth, decreasing from cusp to basis. We also found that inner lateral teeth were harder and stiffer than the outer ones. These findings allowed us to propose hypotheses about the radula-ingesta interaction. In search for the origins of the gradients, teeth were visualized using confocal laser scanning microscopy, to determine the degree of tanning, and analyzed with energy-dispersive X-ray spectroscopy, to test the elemental composition. We found that the mechanical gradients did not have their origins in the elemental content, as the teeth did not contain high proportions of metals or other minerals. This indicates that their origin might be the degree of tanning. However, in the tooth surfaces that interact with the ingesta high Si and Ca contents were determined, which is likely an adaptation to reduce wear.
PMID:37589038 | PMC:PMC10425275 | DOI:10.1002/ece3.10332
RNA m<sup>6</sup>A reader YTHDF2 facilitates precursor miR-126 maturation to promote acute myeloid leukemia progression
Genes Dis. 2023 Mar 28;11(1):382-396. doi: 10.1016/j.gendis.2023.01.016. eCollection 2024 Jan.
ABSTRACT
As the most common internal modification of mRNA, N6-methyladenosine (m6A) and its regulators modulate gene expression and play critical roles in various biological and pathological processes including tumorigenesis. It was reported previously that m6A methyltransferase (writer), methyltransferase-like 3 (METTL3) adds m6A in primary microRNAs (pri-miRNAs) and facilitates its processing into precursor miRNAs (pre-miRNAs). However, it is unknown whether m6A modification also plays a role in the maturation process of pre-miRNAs and (if so) whether such a function contributes to tumorigenesis. Here, we found that YTHDF2 is aberrantly overexpressed in acute myeloid leukemia (AML) patients, especially in relapsed patients, and plays an oncogenic role in AML. Moreover, YTHDF2 promotes expression of miR-126-3p (also known as miR-126, as it is the main product of precursor miR-126 (pre-miR-126)), a miRNA that was reported as an oncomiRNA in AML, through facilitating the processing of pre-miR-126 into mature miR-126. Mechanistically, YTHDF2 recognizes m6A modification in pre-miR-126 and recruits AGO2, a regulator of pre-miRNA processing, to promote the maturation of pre-miR-126. YTHDF2 positively and negatively correlates with miR-126 and miR-126's downstream target genes, respectively, in AML patients, and forced expression of miR-126 could largely rescue YTHDF2/Ythdf2 depletion-mediated suppression on AML cell growth/proliferation and leukemogenesis, indicating that miR-126 is a functionally important target of YTHDF2 in AML. Overall, our studies not only reveal a previously unappreciated YTHDF2/miR-126 axis in AML and highlight the therapeutic potential of targeting this axis for AML treatment, but also suggest that m6A plays a role in pre-miRNA processing that contributes to tumorigenesis.
PMID:37588203 | PMC:PMC10425806 | DOI:10.1016/j.gendis.2023.01.016
Using Single Molecule Imaging to Explore Intracellular Heterogeneity
Int J Biochem Cell Biol. 2023 Aug 14:106455. doi: 10.1016/j.biocel.2023.106455. Online ahead of print.
ABSTRACT
Despite more than 100 years of study, it is unclear if the movement of proteins inside the cell is best described as a mosh pit or an exquisitely choreographed dance. Recent studies suggest the latter. Local interactions induce molecular condensates such as liquid-liquid phase separations (LLPSs) or non-liquid, functionally significant molecular aggregates, including synaptic densities, nucleoli, and Amyloid fibrils. Molecular condensates trigger intracellular signaling and drive processes ranging from gene expression to cell division. However, the descriptions of condensates tend to be qualitative and correlative. Here, we indicate how single-molecule imaging and analyses can be applied to quantify condensates. We discuss the pros and cons of different techniques for measuring differences between transient molecular behaviors inside and outside condensates. Finally, we offer suggestions for how imaging and analyses from different time and space regimes can be combined to identify molecular behaviors indicative of condensates within the dynamic high-density intracellular environment.
PMID:37586643 | DOI:10.1016/j.biocel.2023.106455
Boosting NAD preferentially blunts Th17 inflammation via arginine biosynthesis and redox control in healthy and psoriasis subjects
Cell Rep Med. 2023 Aug 9:101157. doi: 10.1016/j.xcrm.2023.101157. Online ahead of print.
ABSTRACT
To evaluate whether nicotinamide adenine dinucleotide-positive (NAD+) boosting modulates adaptive immunity, primary CD4+ T cells from healthy control and psoriasis subjects were exposed to vehicle or nicotinamide riboside (NR) supplementation. NR blunts interferon γ (IFNγ) and interleukin (IL)-17 secretion with greater effects on T helper (Th) 17 polarization. RNA sequencing (RNA-seq) analysis implicates NR blunting of sequestosome 1 (sqstm1/p62)-coupled oxidative stress. NR administration increases sqstm1 and reduces reactive oxygen species (ROS) levels. Furthermore, NR activates nuclear factor erythroid 2-related factor 2 (Nrf2), and genetic knockdown of nrf2 and the Nrf2-dependent gene, sqstm1, diminishes NR amelioratory effects. Metabolomics analysis identifies that NAD+ boosting increases arginine and fumarate biosynthesis, and genetic knockdown of argininosuccinate lyase ameliorates NR effects on IL-17 production. Hence NR via amino acid metabolites orchestrates Nrf2 activation, augments CD4+ T cell antioxidant defenses, and attenuates Th17 responsiveness. Oral NR supplementation in healthy volunteers similarly increases serum arginine, sqstm1, and antioxidant enzyme gene expression and blunts Th17 immune responsiveness, supporting evaluation of NAD+ boosting in CD4+ T cell-linked inflammation.
PMID:37586364 | DOI:10.1016/j.xcrm.2023.101157
Archival single-cell genomics reveals persistent subclones during DCIS progression
Cell. 2023 Aug 10:S0092-8674(23)00802-4. doi: 10.1016/j.cell.2023.07.024. Online ahead of print.
ABSTRACT
Ductal carcinoma in situ (DCIS) is a common precursor of invasive breast cancer. Our understanding of its genomic progression to recurrent disease remains poor, partly due to challenges associated with the genomic profiling of formalin-fixed paraffin-embedded (FFPE) materials. Here, we developed Arc-well, a high-throughput single-cell DNA-sequencing method that is compatible with FFPE materials. We validated our method by profiling 40,330 single cells from cell lines, a frozen tissue, and 27 FFPE samples from breast, lung, and prostate tumors stored for 3-31 years. Analysis of 10 patients with matched DCIS and cancers that recurred 2-16 years later show that many primary DCIS had already undergone whole-genome doubling and clonal diversification and that they shared genomic lineages with persistent subclones in the recurrences. Evolutionary analysis suggests that most DCIS cases in our cohort underwent an evolutionary bottleneck, and further identified chromosome aberrations in the persistent subclones that were associated with recurrence.
PMID:37586362 | DOI:10.1016/j.cell.2023.07.024
Maize and heat stress: Physiological, genetic, and molecular insights
Plant Genome. 2023 Aug 16:e20378. doi: 10.1002/tpg2.20378. Online ahead of print.
ABSTRACT
Global mean temperature is increasing at a rapid pace due to the rapid emission of greenhouse gases majorly from anthropogenic practices and predicted to rise up to 1.5°C above the pre-industrial level by the year 2050. The warming climate is affecting global crop production by altering biochemical, physiological, and metabolic processes resulting in poor growth, development, and reduced yield. Maize is susceptible to heat stress, particularly at the reproductive and early grain filling stages. Interestingly, heat stress impact on crops is closely regulated by associated environmental covariables such as humidity, vapor pressure deficit, soil moisture content, and solar radiation. Therefore, heat stress tolerance is considered as a complex trait, which requires multiple levels of regulations in plants. Exploring genetic diversity from landraces and wild accessions of maize is a promising approach to identify novel donors, traits, quantitative trait loci (QTLs), and genes, which can be introgressed into the elite cultivars. Indeed, genome wide association studies (GWAS) for mining of potential QTL(s) and dominant gene(s) is a major route of crop improvement. Conversely, mutation breeding is being utilized for generating variation in existing populations with narrow genetic background. Besides breeding approaches, augmented production of heat shock factors (HSFs) and heat shock proteins (HSPs) have been reported in transgenic maize to provide heat stress tolerance. Recent advancements in molecular techniques including clustered regularly interspaced short palindromic repeats (CRISPR) would expedite the process for developing thermotolerant maize genotypes.
PMID:37587553 | DOI:10.1002/tpg2.20378
Nuclear genetic control of mtDNA copy number and heteroplasmy in humans
Nature. 2023 Aug 16. doi: 10.1038/s41586-023-06426-5. Online ahead of print.
ABSTRACT
Mitochondrial DNA (mtDNA) is a maternally inherited, high-copy-number genome required for oxidative phosphorylation1. Heteroplasmy refers to the presence of a mixture of mtDNA alleles in an individual and has been associated with disease and ageing. Mechanisms underlying common variation in human heteroplasmy, and the influence of the nuclear genome on this variation, remain insufficiently explored. Here we quantify mtDNA copy number (mtCN) and heteroplasmy using blood-derived whole-genome sequences from 274,832 individuals and perform genome-wide association studies to identify associated nuclear loci. Following blood cell composition correction, we find that mtCN declines linearly with age and is associated with variants at 92 nuclear loci. We observe that nearly everyone harbours heteroplasmic mtDNA variants obeying two principles: (1) heteroplasmic single nucleotide variants tend to arise somatically and accumulate sharply after the age of 70 years, whereas (2) heteroplasmic indels are maternally inherited as mixtures with relative levels associated with 42 nuclear loci involved in mtDNA replication, maintenance and novel pathways. These loci may act by conferring a replicative advantage to certain mtDNA alleles. As an illustrative example, we identify a length variant carried by more than 50% of humans at position chrM:302 within a G-quadruplex previously proposed to mediate mtDNA transcription/replication switching2,3. We find that this variant exerts cis-acting genetic control over mtDNA abundance and is itself associated in-trans with nuclear loci encoding machinery for this regulatory switch. Our study suggests that common variation in the nuclear genome can shape variation in mtCN and heteroplasmy dynamics across the human population.
PMID:37587338 | DOI:10.1038/s41586-023-06426-5
Cell fate determinant Llgl1 is required for propagation of acute myeloid leukemia
Leukemia. 2023 Aug 16. doi: 10.1038/s41375-023-02005-9. Online ahead of print.
ABSTRACT
Scribble complex proteins can influence cell fate decisions and self-renewal capacity of hematopoietic cells. While specific cellular functions of Scribble complex members are conserved in mammalian hematopoiesis, they appear to be highly context dependent. Using CRISPR/Cas9-based genetic screening, we have identified Scribble complex-related liabilities in AML including LLGL1. Despite its reported suppressive function in HSC self-renewal, inactivation of LLGL1 in AML confirms its relevant role for proliferative capacity and development of AML. Its function was conserved in human and murine models of AML and across various genetic backgrounds. Inactivation of LLGL1 results in loss of stemness-associated gene-expression including HoxA-genes and induces a GMP-like phenotype in the leukemia stem cell compartment. Re-expression of HoxA9 facilitates functional and phenotypic rescue. Collectively, these data establish LLGL1 as a specific dependency and putative target in AML and emphasizes its cell-type specific functions.
PMID:37587260 | DOI:10.1038/s41375-023-02005-9
Association of the human gut microbiota with vascular stiffness
Sci Rep. 2023 Aug 16;13(1):13348. doi: 10.1038/s41598-023-40178-6.
ABSTRACT
Gut microbiota metabolites have been mechanistically linked to inflammatory pathway activation and atherosclerosis, which are major causes of vascular stiffness (VS). Aiming to investigate if the gut microbiome might be involved in VS development, we performed a cross-sectional study (n = 3,087), nested within the population-based European Prospective Investigations into Cancer and Nutrition (EPIC) Potsdam. We investigated the correlation of the gut microbiota (alpha diversity and taxa abundance) with 3 vascular stiffness measures: carotid-femoral (PWV), aortic augmentation index (AIX) and ankle-brachial index (ABI). Shannon index was not significantly associated with VS but the number of observed Amplicon Sequence Variants (ASV) was positively associated with PWV and AIX. We found a total of 19 ASVs significantly associated with at least one VS measure in multivariable-adjusted models. One ASV (classified as Sutterella wadsworthensis) was associated with 2 VS measures, AIX (- 0.11 ± 0.04) and PWV (-0.14 ± 0.03). Other examples of ASVs associated with VS were Collinsella aerofaciens, previously reported to be affected by diet and Bacteroides uniformis, commercially available as probiotics. In conclusion, our study suggests a potential role of individual components of the gut microbiota in the aetiology of VS.
PMID:37587126 | DOI:10.1038/s41598-023-40178-6
Effects of astaxanthin on expression of apoptosis and oxidative stress related genes in H<sub>2</sub>O<sub>2</sub> induced oxidative stress BE(2)-C human neuroblastoma cell line
Prep Biochem Biotechnol. 2023 Aug 10:1-8. doi: 10.1080/10826068.2023.2243506. Online ahead of print.
ABSTRACT
Antioxidants may affect the apoptosis induced by oxidative stress experimental models. The present study was conducted to investigate the effects of astaxanthin on expression of apoptosis and oxidative stress-related genes in H2O2 induced oxidative stress BE(2)-C human neuroblastoma cell line. This experimental study consisted of six groups including control, H2O2 induced oxidative stress control, 100 mM vitamin C intervention, 25 μM astaxanthin intervention (Ax1), 50 μM astaxanthin intervention (Ax2) and 100 μM astaxanthin intervention (Ax3). Real-time PCR was used to study the expression of BAX, BCL2, Caspase3 (CAS3), P53, peroxisome proliferator-activated receptor γ (PPARγ), superoxide dismutase (SOD), glutathione peroxidase 1 (GPX), catalase (CAT) and nuclear factor erythroid 2-related factor 2 (NRF2). According to the results, among the apoptosis-related genes, CAS3 was down-regulated in groups vitamin C, Ax1 and Ax2 compared with H2O2 group, while P53 was down-regulated only in group vitamin C (P < 0.05). Among the oxidative stress-related genes, GPX was up-regulated in groups Ax1, Ax2 and Ax3 compared with H2O2 group, while all the experimental groups showed up-regulation for CAT and NRF2 (P < 0.05). In conclusion, astaxanthin as a powerful antioxidant could inhibit apoptosis via amelioration of CAS3 gene which might be through amelioration of some antioxidant-related genes.
PMID:37585718 | DOI:10.1080/10826068.2023.2243506
Neighborhood Watch: Genomic epidemiology of SARS-CoV-2 variants circulating in a German federal state, Mecklenburg-Western Pomerania, in 2020-2022
Emerg Microbes Infect. 2023 Aug 10:2245916. doi: 10.1080/22221751.2023.2245916. Online ahead of print.
ABSTRACT
Global and even national genome surveillance approaches do not provide the resolution necessary for rapid and accurate direct response by local public health authorities. Hence, a regional network of microbiological laboratories in collaboration with the health departments of all districts of the German federal state of Mecklenburg-Western Pomerania (M-V) was formed to investigate the regional molecular epidemiology of circulating SARS-CoV-2 lineages between 11/2020 and 03/2022. More than 4750 samples from all M-V counties were sequenced using Illumina and Nanopore technologies. Overall, 3493 (73.5%) sequences fulfilled quality criteria for time-resolved and/or spatially-resolved maximum likelihood phylogenic analyses and k-mean/ median clustering (KMC). We identified 116 different Pangolin virus lineages that can be assigned to 16 Nextstrain clades. The ten most frequently detected virus lineages belonged to B.1.1.7, AY.122, AY.43, BA.1, B.1.617.2, BA.1.1, AY.9.2, AY.4, P.1 and AY.126. Time-resolved phylogenetic analyses showed the occurrence of virus clades as determined worldwide, but with a substantial delay of one to two months. Further spatio-temporal phylogenetic analyses revealed a regional outbreak of a Gamma variant limited to western M-V counties. Finally, KMC elucidated a successive introduction of the various virus lineages into M-V, possibly triggered by vacation periods with increased (inter-) national travel activities. The COVID-19 pandemic in M-V was shaped by a combination of several SARS-CoV-2 introductions, lockdown measures, restrictive quarantine of patients and the lineage specific replication rate. Complementing global and national surveillance, regional surveillance adds value by providing a higher level of surveillance resolution tailored to local health authorities.
PMID:37585712 | DOI:10.1080/22221751.2023.2245916
cyjShiny: A cytoscape.js R Shiny Widget for network visualization and analysis
PLoS One. 2023 Aug 16;18(8):e0285339. doi: 10.1371/journal.pone.0285339. eCollection 2023.
ABSTRACT
cyjShiny is an open-source R package that allows users to embed network visualization into Shiny apps and R Markdown documents. cyjShiny (https://github.com/cytoscape/cyjShiny) builds on the cytoscape.js Javascript graph library. Additionally, the package provides helper functions to convert common R data representations (e.g., data.frame) into forms compatible with cytoscape.js.
PMID:37585474 | DOI:10.1371/journal.pone.0285339
Don't show us your instrument park: Give us your students/give us to your students!
Microb Biotechnol. 2023 Aug 16. doi: 10.1111/1751-7915.14326. Online ahead of print.
NO ABSTRACT
PMID:37585211 | DOI:10.1111/1751-7915.14326