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MSystems Jun 2024Relationships between bacterial taxa are traditionally defined using 16S rRNA nucleotide similarity or average nucleotide identity. Improvements in sequencing technology...
UNLABELLED
Relationships between bacterial taxa are traditionally defined using 16S rRNA nucleotide similarity or average nucleotide identity. Improvements in sequencing technology provide additional pairwise information on genome sequences, which may provide valuable information on genomic relationships. Mapping orthologous gene locations between genome pairs, known as synteny, is typically implemented in the discovery of new species and has not been systematically applied to bacterial genomes. Using a data set of 378 bacterial genomes, we developed and tested a new measure of synteny similarity between a pair of genomes, which was scaled onto 16S rRNA distance using covariance matrices. Based on the input gene functions used (i.e., core, antibiotic resistance, and virulence), we observed varying topological arrangements of bacterial relationship networks by applying (i) complete linkage hierarchical clustering and (ii) K-nearest neighbor graph structures to synteny-scaled 16S data. Our metric improved clustering quality comparatively to state-of-the-art average nucleotide identity metrics while preserving clustering assignments for the highest similarity relationships. Our findings indicate that syntenic relationships provide more granular and interpretable relationships for within-genera taxa compared to pairwise similarity measures, particularly in functional contexts.
IMPORTANCE
Given the prevalence and necessity of the 16S rRNA measure in bacterial identification and analysis, this additional analysis adds a functional and synteny-based layer to the identification of relatives and clustering of bacteria genomes. It is also of computational interest to model the bacterial genome as a graph structure, which presents new avenues of genomic analysis for bacteria and their closely related strains and species.
PubMed: 38940518
DOI: 10.1128/msystems.00497-24 -
MSphere Jun 2024The gut microbiome has the potential to buffer temporal variations in resource availability and consumption, which may play a key role in the ability of animals to adapt...
UNLABELLED
The gut microbiome has the potential to buffer temporal variations in resource availability and consumption, which may play a key role in the ability of animals to adapt to a broad range of habitats. We investigated the temporal composition and function of the gut microbiomes of wild common marmosets () exploiting a hot, dry environment-Caatinga-in northeastern Brazil. We collected fecal samples during two time periods (July-August and February-March) for 2 years from marmosets belonging to eight social groups. We used 16S rRNA gene amplicon sequencing, metagenomic sequencing, and butyrate RT-qPCR to assess changes in the composition and potential function of their gut microbiomes. Additionally, we identified the plant, invertebrate, and vertebrate components of the marmosets' diet via DNA metabarcoding. Invertebrate, but not plant or vertebrate, consumption varied across the year. However, gut microbiome composition and potential function did not markedly vary across study periods or as a function of diet composition. Instead, the gut microbiome differed markedly in both composition and potential function across marmosets residing in different social groups. We highlight the likely role of factors, such as behavior, residence, and environmental heterogeneity, in modulating the structure of the gut microbiome.
IMPORTANCE
In a highly socially cohesive and cooperative primate, group membership more strongly predicts gut microbiome composition and function than diet.
PubMed: 38940510
DOI: 10.1128/msphere.00233-24 -
Frontiers in Bioscience (Landmark... Jun 2024Transcription factors (TFs) are essential proteins regulating gene expression by binding to specific nucleotide sequences upstream of genes. Among TF families, the... (Review)
Review
Transcription factors (TFs) are essential proteins regulating gene expression by binding to specific nucleotide sequences upstream of genes. Among TF families, the forkhead box (FOX) proteins, characterized by a conserved DNA-binding domain, play vital roles in various cellular processes, including cancer. The FOXA subfamily, encompassing FOXA1, FOXA2, and FOXA3, stands out for its pivotal role in mammalian development. FOXA1, initially identified in the liver, exhibits diverse expression across multiple organ tissues and plays a critical role in cell proliferation, differentiation, and tumor development. Its structural composition includes transactivation domains and a DNA-binding domain, facilitating its function as a pioneer factor, which is crucial for chromatin interaction and the recruitment of other transcriptional regulators. The involvement of FOXA1 in sex hormone-related tumors underscores its significance in cancer biology. This review provides an overview of multifaceted roles of FOXA1 in normal development and its implications in the pathogenesis of hormone-related cancers, particularly breast cancer and prostate cancer.
Topics: Humans; Hepatocyte Nuclear Factor 3-alpha; Male; Female; Breast Neoplasms; Prostatic Neoplasms; Gonadal Steroid Hormones; Neoplasms; Animals; Gene Expression Regulation, Neoplastic
PubMed: 38940052
DOI: 10.31083/j.fbl2906225 -
Frontiers in Bioscience (Landmark... Jun 2024Hormone receptors exert their function through binding with their ligands, which results in cellular signaling activation mediated by genomic or non-genomic mechanisms....
BACKGROUND
Hormone receptors exert their function through binding with their ligands, which results in cellular signaling activation mediated by genomic or non-genomic mechanisms. The intrinsic molecular communication of tick and its host comprises an endocrine regulation involving hormones. In the present study, we performed a molecular and analysis of a Membrane Associated Progesterone Receptor in (RmMAPRC).
METHODS
The RmMAPRC protein sequence was analyzed with bioinformatics tools, and its structure was characterized by three-dimensional (3D) modeling and molecular docking. A semi-quantitative reverse transcription and polymerase chain reaction (sqRT-PCR) assessed the gene presence and relative expression in tick organs and embryonic cells.
RESULTS
relative expression in salivary glands, ovaries, and embryonic cells showed overexpression of 3%, 13%, and 24%, respectively. Bioinformatic analysis revealed that RmMAPRC corresponded to a Progesterone Receptor Membrane Component 1 (RmPGRMC1) of ~23.7 kDa, with an N-terminal transmembrane domain and a C-terminal Cytochrome b5-like heme/steroid binding domain. The docking results suggest that RmPGRMC1 could bind to progesterone (P4), some progestins, and P4 antagonists. The phylogenetic reconstruction showed that spp. MAPRC receptors were clustered in a clade that includes , , and (RmMAPRC), and mammals and helminths MAPRC receptors clustered in two separated clades away from ticks.
CONCLUSIONS
The presence of RmPGRMC1 highlights the importance of transregulation as a conserved adaptive mechanism that has succeeded for arthropod parasites, making it a target for tick control.
Topics: Animals; Rhipicephalus; Receptors, Progesterone; Progesterone; Cattle; Molecular Docking Simulation; Host-Parasite Interactions; Female; Amino Acid Sequence; Protein Binding; Phylogeny
PubMed: 38940045
DOI: 10.31083/j.fbl2906238 -
Frontiers in Bioscience (Landmark... Jun 2024The endoplasmic reticulum (ER) played an important role in the folding, assembly and post-translational modification of proteins. ER homeostasis could be disrupted by... (Review)
Review
The endoplasmic reticulum (ER) played an important role in the folding, assembly and post-translational modification of proteins. ER homeostasis could be disrupted by the accumulation of misfolded proteins, elevated reactive oxygen species (ROS) levels, and abnormal Ca2+ signaling, which was referred to ER stress (ERS). Ferroptosis was a unique programmed cell death model mediated by iron-dependent phospholipid peroxidation and multiple signaling pathways. The changes of mitochondrial structure, the damage of glutathione peroxidase 4 (GPX4) and excess accumulation of iron were the main characteristics of ferroptosis. ROS produced by ferroptosis can interfere with the activity of protein-folding enzymes, leading to the accumulation of large amounts of unfolded proteins, thus causing ERS. On the contrary, the increase of ERS level could promote ferroptosis by the accumulation of iron ion and lipid peroxide, the up-regulation of ferroptosis related genes. At present, the studies on the relationship between ferroptosis and ERS were one-sided and lack of in-depth studies on the interaction mechanism. This review aimed to explore the molecular mechanism of cross-talk between ferroptosis and ERS, and provide new strategies and targets for the treatment of liver diseases.
Topics: Ferroptosis; Humans; Endoplasmic Reticulum Stress; Liver Diseases; Reactive Oxygen Species; Animals; Signal Transduction; Iron; Lipid Peroxidation; Endoplasmic Reticulum
PubMed: 38940044
DOI: 10.31083/j.fbl2906221 -
Frontiers in Bioscience (Landmark... Jun 2024Existing animal models for testing therapeutics in the skin are limited. Mouse and rat models lack similarity to human skin in structure and wound healing mechanism....
BACKGROUND
Existing animal models for testing therapeutics in the skin are limited. Mouse and rat models lack similarity to human skin in structure and wound healing mechanism. Pigs are regarded as the best model with regards to similarity to human skin; however, these studies are expensive, time-consuming, and only small numbers of biologic replicates can be obtained. In addition, local-regional effects of treating wounds that are closely adjacent to one-another with different treatments make assessment of treatment effectiveness difficult in pig models. Therefore, here, a novel nude mouse model of xenografted porcine hypertrophic scar (HTS) cells was developed. This model system was developed to test if supplying hypo-pigmented cells with exogenous alpha melanocyte stimulating hormone (α-MSH) will reverse pigment loss .
METHODS
Dyschromic HTSs were created in red Duroc pigs. Epidermal scar cells (keratinocytes and melanocytes) were derived from regions of hyper-, hypo-, or normally pigmented scar or skin and were cryopreserved. Dermal fibroblasts (DFs) were isolated separately. Excisional wounds were created on nude mice and a grafting dome was placed. DFs were seeded on day 0 and formed a dermis. On day 3, epidermal cells were seeded onto the dermis. The grafting dome was removed on day 7 and hypo-pigmented xenografts were treated with synthetic α-MSH delivered with microneedling. On day 10, the xenografts were excised and saved. Sections were stained using hematoxylin and eosin hematoxylin and eosin (H&E) to assess xenograft structure. RNA was isolated and quantitative real-time polymerase chain reaction (qRT-PCR) was performed for melanogenesis-related genes , , and .
RESULTS
The seeding of HTSDFs formed a dermis that is similar in structure and cellularity to HTS dermis from the porcine model. When hyper-, hypo-, and normally-pigmented epidermal cells were seeded, a fully stratified epithelium was formed by day 14. H&E staining and measurement of the epidermis showed the average thickness to be 0.11 ± 0.07 µm 0.06 ± 0.03 µm in normal pig skin. Hypo-pigmented xenografts that were treated with synthetic α-MSH showed increases in pigmentation and had increased gene expression of , , and compared to untreated controls (TYR: 2.7 ± 1.1 0.3 ± 1.1; TYRP1: 2.6 ± 0.6 0.3 ± 0.7; DCT 0.7 ± 0.9 0.3 ± 1-fold change from control; n = 3).
CONCLUSIONS
The developed nude mouse skin xenograft model can be used to study treatments for the skin. The cells that can be xenografted can be derived from patient samples or from pig samples and form a robust dual-skin layer containing epidermis and dermis that is responsive to treatment. Specifically, we found that hypo-pigmented regions of scar can be stimulated to make melanin by synthetic α-MSH .
Topics: Animals; Mice, Nude; Cicatrix, Hypertrophic; Mice; Disease Models, Animal; Swine; alpha-MSH; Humans; Skin; Fibroblasts; Melanocytes; Keratinocytes; Transplantation, Heterologous; Wound Healing; Skin Pigmentation
PubMed: 38940034
DOI: 10.31083/j.fbl2906230 -
Frontiers in Bioscience (Landmark... May 2024Epigenetics refers to heritable changes in gene expression and function that impact nuclear processes associated with chromatin, all without altering DNA sequences.... (Review)
Review
Epigenetics refers to heritable changes in gene expression and function that impact nuclear processes associated with chromatin, all without altering DNA sequences. These epigenetic patterns, being heritable traits, are vital biological mechanisms that intricately regulate gene expression and heredity. The application of chemical labeling and single-cell resolution mapping strategies has significantly facilitated large-scale epigenetic modifications in nucleic acids over recent years. Notably, epigenetic modifications can induce heritable phenotypic changes, regulate cell differentiation, influence cell-specific gene expression, parentally imprint genes, activate the X chromosome, and stabilize genome structure. Given their reversibility and susceptibility to environmental factors, epigenetic modifications have gained prominence in disease diagnosis, significantly impacting clinical medicine research. Recent studies have uncovered strong links between epigenetic modifications and the pathogenesis of metabolic cardiovascular diseases, including congenital heart disease, heart failure, cardiomyopathy, hypertension, and atherosclerosis. In this review, we provide an overview of the progress in epigenetic research within the context of cardiovascular diseases, encompassing their pathogenesis, prevention, diagnosis, and treatment. Furthermore, we shed light on the potential prospects of nucleic acid epigenetic modifications as a promising avenue in clinical medicine and biomedical applications.
Topics: Humans; Epigenesis, Genetic; Cardiovascular Diseases; DNA Methylation; Animals
PubMed: 38940023
DOI: 10.31083/j.fbl2906205 -
Frontiers in Pharmacology 2024Mesaconitine (MA), a diester-diterpenoid alkaloid extracted from the medicinal herb , is commonly used to treat various diseases. Previous studies have indicated the...
Mesaconitine (MA), a diester-diterpenoid alkaloid extracted from the medicinal herb , is commonly used to treat various diseases. Previous studies have indicated the potent toxicity of aconitum despite its pharmacological activities, with limited understanding of its effects on the nervous system and the underlying mechanisms. HT22 cells and zebrafish were used to investigate the neurotoxic effects of MA both and , employing multi-omics techniques to explore the potential mechanisms of toxicity. Our results demonstrated that treatment with MA induces neurotoxicity in zebrafish and HT22 cells. Subsequent analysis revealed that MA induced oxidative stress, as well as structural and functional damage to mitochondria in HT22 cells, accompanied by an upregulation of mRNA and protein expression related to autophagic and lysosomal pathways. Furthermore, methylated RNA immunoprecipitation sequencing (MeRIP-seq) showed a correlation between the expression of autophagy-related genes and N6-methyladenosine (m6A) modification following MA treatment. In addition, we identified METTL14 as a potential regulator of m6A methylation in HT22 cells after exposure to MA. Our study has contributed to a thorough mechanistic elucidation of the neurotoxic effects caused by MA, and has provided valuable insights for optimizing the rational utilization of traditional Chinese medicine formulations containing aconitum in clinical practice.
PubMed: 38939838
DOI: 10.3389/fphar.2024.1393717 -
ISME Communications Jan 2024The majority of bacteriophage diversity remains uncharacterized, and new intriguing mechanisms of their biology are being continually described. Members of some phage...
The majority of bacteriophage diversity remains uncharacterized, and new intriguing mechanisms of their biology are being continually described. Members of some phage lineages, such as the , repurpose stop codons to encode an amino acid by using alternate genetic codes. Here, we investigated the prevalence of stop codon reassignment in phage genomes and its subsequent impacts on functional annotation. We predicted 76 genomes within INPHARED and 712 vOTUs from the Unified Human Gut Virome Catalogue (UHGV) that repurpose a stop codon to encode an amino acid. We re-annotated these sequences with modified versions of Pharokka and Prokka, called Pharokka-gv and Prokka-gv, to automatically predict stop codon reassignment prior to annotation. Both tools significantly improved the quality of annotations, with Pharokka-gv performing best. For sequences predicted to repurpose TAG to glutamine (translation table 15), Pharokka-gv increased the median gene length (median of per genome median) from 287 to 481 bp for UHGV sequences (67.8% increase) and from 318 to 550 bp for INPHARED sequences (72.9% increase). The re-annotation increased median coding capacity from 66.8% to 90.0% and from 69.0% to 89.8% for UHGV and INPHARED sequences predicted to use translation table 15. Furthermore, the proportion of genes that could be assigned functional annotation increased, including an increase in the number of major capsid proteins that could be identified. We propose that automatic prediction of stop codon reassignment before annotation is beneficial to downstream viral genomic and metagenomic analyses.
PubMed: 38939532
DOI: 10.1093/ismeco/ycae079 -
Frontiers in Microbiology 2024Sodium pheophorbide a (SPA) is a natural plant-derived photosensitizer, with high photoactivated antifungal activity against some phytopathogenic fungi. However, its...
INTRODUCTION
Sodium pheophorbide a (SPA) is a natural plant-derived photosensitizer, with high photoactivated antifungal activity against some phytopathogenic fungi. However, its fungicidal effect on , a novel pathogen that causes leaf spot blight, is unclear.
METHODS
In the present study, we explored its inhibitory effects on spore germination and mycelial growth of . Then we determined its effects on the cell membrane, mycelial morphology, redox homeostasis, and cell death through bioassay. Finally, RNA-seq was used further to elucidate its mode of action at the transcriptional level.
RESULTS
We found that SPA effectively inhibited the growth of , with half-maximal effective concentrations to inhibit mycelial growth and spore germination of 1.059 and 2.287 mg/mL, respectively. After 1.0 mg/mL SPA treatment, the conductivity and malondialdehyde content of were significantly increased. Scanning electron microscopy and transmission electron microscopy indicated that SPA significantly affected the morphology and ultrastructure of hyphae, revealing that SPA can destroy the mycelial morphology and cell structure, especially the cell membrane of . Furthermore, transcriptome analysis revealed that SPA significantly suppressed the expression of genes involved in morphology, cell membrane permeability, and oxidative stress. Then, we also found that SPA significantly promoted the accumulation of reactive oxygen species (ROS) in of , while it decreased the content of reduced glutathione, inhibited the enzyme activities of superoxide dismutase and catalase, and exacerbated DNA damage. Annexin V-FITC/PI staining also confirmed that 1.0 mg/mL SPA could significantly induce apoptosis and necrosis.
DISCUSSION
Generally, SPA can induce ROS-mediated oxidative stress and cell death, thus destroying the cell membrane and hyphal morphology, and ultimately inhibiting mycelial growth, which indicates that SPA has multiple modes of action, providing a scientific basis for the use of SPA as an alternative plant-derived photoactivated fungicide against leaf spot blight.
PubMed: 38939192
DOI: 10.3389/fmicb.2024.1403478