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Cell Stress & Chaperones Jun 2024Epigenetic variations result from long-term adaptation to environmental factors. The Bos indicus (zebu) adapted to tropical conditions whereas Bos taurus to temperate...
Epigenetic variations result from long-term adaptation to environmental factors. The Bos indicus (zebu) adapted to tropical conditions whereas Bos taurus to temperate conditions, hence the native zebu cattle and its crossbred (B indicus X B taurus) show differences in responses to heat stress. The present study evaluated genome-wide DNA methylation profiles of these two breeds of cattle that may explain distinct heat stress responses. Physiological responses to heat stress and estimated values of Iberia heat tolerance coefficient (HTC) and Benezra's coefficient of adaptability (BCA) revealed better relative thermo-tolerance of Hariana compared to the Vrindavani cattle. Genome-wide DNA methylation patterns were different for Hariana and Vrindavani cattle. The comparison between breeds indicated presence of 4599 significant differentially methylated CpGs (DMC) with 756 hyper-methylated and 3845 hypo-methylated in Hariana compared to the Vrindavani cattle. Further, we found 79 genes that showed both differential methylation and differential expression that are involved cellular stress response functions. Differential methylations in the microRNA coding sequences also revealed their functions in heat stress responses. Taken together, epigenetic differences represent potential regulation of long-germ adaptation of Hariana (B indicus) cattle to the tropical environment and relative thermotolerance.
PubMed: 38936463
DOI: 10.1016/j.cstres.2024.06.005 -
Redox Biology Jun 2024Hydrogen peroxide is a key element in redox signaling and in setting cellular redox tone. DUOX1 and DUOX2, that directly synthesize hydrogen peroxide, are the most...
Hydrogen peroxide is a key element in redox signaling and in setting cellular redox tone. DUOX1 and DUOX2, that directly synthesize hydrogen peroxide, are the most abundant NADPH oxidase transcripts in most epithelia. DUOX1 and DUOX2 hydrogen peroxide synthesis is regulated by intracellular calcium transients and thus cells can respond to signals and initiate responses by increasing cellular hydrogen peroxide synthesis. Nevertheless, many details of their enzymatic regulation are still unexplored. DUOX1 and DUOXA1 were expressed in HEK293T cells and activity was studied in homogenates and membrane fractions. When DUOX1 homogenates or membranes were pre-incubated in NADPH and started with addition of Ca, to mimic intracellular activation, progress curves were distinctly different from those pre-incubated in Ca and started with NADPH. The Ca EC for DUOX1's initial rate when pre-incubated in Ca, was three orders of magnitude lower (EC ∼ 10 M) than with preincubation in NADPH (EC ∼ 10 M). In addition, activity was several fold lower with Ca start. Identical results were obtained using homogenates and membrane fractions. The data suggested that DUOX1 Ca binding in expected physiological signaling conditions only slowly leads to maximal hydrogen peroxide synthesis and that full hydrogen peroxide synthesis activity in vivo only can occur when encountering extremely high concentration Ca signals. Thus, a complex interplay of intracellular NADPH and Ca concentrations regulate DUOX1 over a wide extent and may limit DUOX1 activity to a restricted range and spatial distribution.
PubMed: 38936256
DOI: 10.1016/j.redox.2024.103251 -
Redox Biology Jun 2024GPCR-G protein signaling from endosomes plays a crucial role in various physiological and pathological processes. However, the mechanism by which endosomal G protein...
GPCR-G protein signaling from endosomes plays a crucial role in various physiological and pathological processes. However, the mechanism by which endosomal G protein signaling is terminated remains largely unknown. In this study, we aimed to investigate the regulatory mechanisms involved in terminating the signaling of Gα subunits from endosomes. Through structural analysis and cell-based assays, we have discovered that SNX25, a protein that targets endosomes via its PXA or PXC domain, interacts with regulator of G protein signaling (RGS) proteins (including RGS2, RGS4, RGS8, and RGS17) in a redox-regulated manner. The interaction between SNX25 and these RGS proteins enhances their GTPase-accelerating activity towards Gα and their ability to bind GDP-bound (inactive form) Gα. As a result, SNX25 recruits these RGS proteins to endosomes, leading to the termination of endosomal Gα signaling. Furthermore, we have found that the SNX25/RGS complex also exerts a negative regulatory effect on Gα signaling from the plasma membrane. This is achieved by recruiting Gα to endosomes and preventing its activation on the plasma membrane. Our findings shed light on the previously unknown role of redox-modulated SNX25 in inhibiting Gα signaling, thereby uncovering a novel mechanism for terminating Gα signaling from endosomes. Importantly, this study expands our understanding of the regulation of GPCR-Gα signaling beyond the plasma membrane.
PubMed: 38936254
DOI: 10.1016/j.redox.2024.103253 -
JMIR Research Protocols Jun 2024Sound therapy methods have seen a surge in popularity, with a predominant focus on music among all types of sound stimulation. There is substantial evidence documenting... (Review)
Review
BACKGROUND
Sound therapy methods have seen a surge in popularity, with a predominant focus on music among all types of sound stimulation. There is substantial evidence documenting the integrative impact of music therapy on psycho-emotional and physiological outcomes, rendering it beneficial for addressing stress-related conditions such as pain syndromes, depression, and anxiety. Despite these advancements, the therapeutic aspects of sound, as well as the mechanisms underlying its efficacy, remain incompletely understood. Existing research on music as a holistic cultural phenomenon often overlooks crucial aspects of sound therapy mechanisms, particularly those related to speech acoustics or the so-called "music of speech."
OBJECTIVE
This study aims to provide an overview of empirical research on sound interventions to elucidate the mechanism underlying their positive effects. Specifically, we will focus on identifying therapeutic factors and mechanisms of change associated with sound interventions. Our analysis will compare the most prevalent types of sound interventions reported in clinical studies and experiments. Moreover, we will explore the therapeutic effects of sound beyond music, encompassing natural human speech and intermediate forms such as traditional poetry performances.
METHODS
This review adheres to the methodological guidance of the Joanna Briggs Institute and follows the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) checklist for reporting review studies, which is adapted from the Arksey and O'Malley framework. Our search strategy encompasses PubMed, Web of Science, Scopus, and PsycINFO or EBSCOhost, covering literature from 1990 to the present. Among the different study types, randomized controlled trials, clinical trials, laboratory experiments, and field experiments were included.
RESULTS
Data collection began in October 2022. We found a total of 2027 items. Our initial search uncovered an asymmetry in the distribution of studies, with a larger number focused on music therapy compared with those exploring prosody in spoken interventions such as guided meditation or hypnosis. We extracted and selected papers using Rayyan software (Rayyan) and identified 41 eligible papers after title and abstract screening. The completion of the scoping review is anticipated by October 2024, with key steps comprising the analysis of findings by May 2024, drafting and revising the study by July 2024, and submitting the paper for publication in October 2024.
CONCLUSIONS
In the next step, we will conduct a quality evaluation of the papers and then chart and group the therapeutic factors extracted from them. This process aims to unveil conceptual gaps in existing studies. Gray literature sources, such as Google Scholar, ClinicalTrials.gov, nonindexed conferences, and reference list searches of retrieved studies, will be added to our search strategy to increase the number of relevant papers that we cover.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
DERR1-10.2196/54030.
Topics: Humans; Stress, Psychological; Music Therapy; Adult
PubMed: 38935945
DOI: 10.2196/54030 -
PloS One 2024We investigated the interactions of unopsonized and opsonized Mycoplasma mycoides subsp. mycoides (Mmm) with bovine macrophages in vitro. Mmm survived and proliferated...
We investigated the interactions of unopsonized and opsonized Mycoplasma mycoides subsp. mycoides (Mmm) with bovine macrophages in vitro. Mmm survived and proliferated extracellularly on bovine macrophage cell layers in the absence of Mmm-specific antisera. Bovine complement used at non-bactericidal concentrations did neither have opsonizing effect nor promoted intracellular survival, whereas Mmm-specific antisera substantially increased phagocytosis and Mmm killing. A phagocytosis-independent uptake of Mmm by macrophages occurred at a high multiplicity of infection, also found to induce the production of TNF, and both responses were unaffected by non-bactericidal doses of bovine complement. Bovine complement used at higher doses killed Mmm in cell-free cultures and completely abrogated TNF responses by macrophages. These results provide a framework to identify Mmm antigens involved in interactions with macrophages and targeted by potentially protective antibodies and point towards a pivotal role of complement in the control of inflammatory responses in contagious bovine pleuropneumonia.
Topics: Animals; Cattle; Macrophages; Phagocytosis; Complement System Proteins; Mycoplasma; Tumor Necrosis Factor-alpha; Pleuropneumonia, Contagious; Mycoplasma mycoides
PubMed: 38935768
DOI: 10.1371/journal.pone.0305851 -
PloS One 2024High blood pressure, also known as hypertension (HTN), is a complicated disorder that is controlled by a complex network of physiological processes. Untreated...
BACKGROUND
High blood pressure, also known as hypertension (HTN), is a complicated disorder that is controlled by a complex network of physiological processes. Untreated hypertension is associated with increased death incidence, rise the need for understanding the genetic basis affecting hypertension susceptibility and development. The current study sought to identify the genetic association between twelve single nucleotide polymorphisms (SNPs) within seven candidate genes (NOS3, NOS1AP, REN, PLA2G4A, TCF7L, ADRB1, and PTPRD).
METHODS
The current study included 200 Jordanian individuals diagnosed with hypertension, compared to 224 healthy controls. Whole blood samples were drawn from each individual for DNA isolation and genotyping. The SNPStats tool was used to assess haplotype, genotype, and allele frequencies by the mean of chi-square (χ2).
RESULTS
Except for rs10739150 of PTPRD (P = 0.0003), the genotypic and allelic distribution of the SNP was identical between patients and controls. The prevalence of the G/G genotype in healthy controls (45.5%) was lower than in hypertension patients (64.3%), suggesting that it might be a risk factor for the disease. PTPRD TTC genetic haplotypes were strongly linked with hypertension (P = 0.003, OR = 4.03).
CONCLUSION
This study provides a comprehensive understanding of the involvement of rs10739150 within the PTPRD gene in hypertension. This new knowledge could potentially transform the way we approach hypertension diagnosis, providing an accurate diagnostic tool for classifying individuals who are at a higher risk of developing this condition.
Topics: Humans; Polymorphism, Single Nucleotide; Hypertension; Female; Male; Middle Aged; Genetic Predisposition to Disease; Adult; Gene Frequency; Haplotypes; Case-Control Studies; Receptor-Like Protein Tyrosine Phosphatases, Class 2; Genotype; Jordan; Alleles
PubMed: 38935682
DOI: 10.1371/journal.pone.0304950 -
PloS One 2024Monitoring and improving the quality of sleep are crucial from a public health perspective. In this study, we propose a change-point detection method using diffusion...
Monitoring and improving the quality of sleep are crucial from a public health perspective. In this study, we propose a change-point detection method using diffusion maps for a more accurate detection of respiratory arrest points. Conventional change-point detection methods are limited when dealing with complex nonlinear data structures, and the proposed method overcomes these limitations. The proposed method embeds subsequence data in a low-dimensional space while considering the global and local structures of the data and uses the distance between the data as the score of the change point. Experiments using synthetic and real-world contact-free sensor data confirmed the superiority of the proposed method when dealing with noise, and it detected apnea events with greater accuracy than conventional methods. In addition to improving sleep monitoring, the proposed method can be applied in other fields, such as healthcare, manufacturing, and finance. This study will contribute to the development of advanced monitoring systems that adapt to diverse conditions while protecting privacy.
Topics: Humans; Sleep Apnea Syndromes; Polysomnography; Algorithms; Monitoring, Physiologic
PubMed: 38935677
DOI: 10.1371/journal.pone.0306139 -
PloS One 2024Aluminum (Al) toxicity is an important factor restricting the normal growth of plants in acidic soil. Rhododendron (Ericaceae) can grow relatively well in acidic soil....
Aluminum (Al) toxicity is an important factor restricting the normal growth of plants in acidic soil. Rhododendron (Ericaceae) can grow relatively well in acidic soil. To uncover the adaptive mechanisms of photosynthesis under Al stress, the influence of Al stress on the photosynthetic activities of Al-sensitive (Baijinpao) and Al-resistant (Kangnaixin) rhododendron cultivars was examined by measuring gas exchange, chlorophyll fluorescence, and the modulated reflection of light at 820 nm. Under Al stress conditions, the net photosynthetic rate and stomatal conductance of the rhododendron leaves decreased, whereas the intercellular CO2 concentration increased. The Al stress treatment damaged the oxygen-evolving complex of the rhododendron seedlings, while also inhibiting electron transport on the photosystem II (PSII) donor side. In addition, the exposure to Al stress restricted the oxidation of plastocyanin (PC) and the photosystem I (PSI) reaction center (P700) and led to the re-reduction of PC+ and P700+. The comparison with Kangnaixin revealed an increase in the PSII connectivity in Baijinpao. Additionally, the donor-side electron transport efficiency was more inhibited and the overall activity of PSII, PSI, and the intersystem electron transport chain decreased more extensively in Baijinpao than in Kangnaixin. On the basis of the study findings, we concluded that Al stress adversely affects photosynthesis in rhododendron seedlings by significantly decreasing the activity of PSII and PSI. Under Al stress, Kangnaixin showed stronger tolerance compared with Baijinpao.
Topics: Rhododendron; Aluminum; Chlorophyll; Photosynthesis; Fluorescence; Photosystem II Protein Complex; Stress, Physiological; Plant Leaves; Electron Transport; Light; Photosystem I Protein Complex
PubMed: 38935623
DOI: 10.1371/journal.pone.0305133 -
PloS One 2024Mucosal-delivered drugs have to pass through the mucus layer before absorption through the epithelial cell membrane. Although there has been increasing interest in...
Mucosal-delivered drugs have to pass through the mucus layer before absorption through the epithelial cell membrane. Although there has been increasing interest in polymeric mucins, a major structural component of mucus, potentially acting as important physiological regulators of mucosal drug absorption, there are no reports that have systematically evaluated the interaction between mucins and drugs. In this study, we assessed the potential interaction between human polymeric mucins (MUC2, MUC5B, and MUC5AC) and various drugs with different chemical profiles by simple centrifugal method and fluorescence analysis. We found that paclitaxel, rifampicin, and theophylline likely induce the aggregation of MUC5B and/or MUC2. In addition, we showed that the binding affinity of drugs for polymeric mucins varied, not only between individual drugs but also among mucin subtypes. Furthermore, we demonstrated that deletion of MUC5AC and MUC5B in A549 cells increased the cytotoxic effects of cyclosporin A and paclitaxel, likely due to loss of mucin-drug interaction. In conclusion, our results indicate the necessity to determine the binding of drugs to mucins and their potential impact on the mucin network property.
Topics: Humans; Paclitaxel; Mucin 5AC; A549 Cells; Drug Interactions; Mucin-5B; Mucins; Mucin-2; Rifampin; Cyclosporine; Protein Binding
PubMed: 38935605
DOI: 10.1371/journal.pone.0306058 -
Cell Reports Jun 2024Kisspeptin signaling through its G protein-coupled receptor, KISS1R, plays an indispensable role in regulating reproduction via the hypothalamic-pituitary-gonadal axis....
Kisspeptin signaling through its G protein-coupled receptor, KISS1R, plays an indispensable role in regulating reproduction via the hypothalamic-pituitary-gonadal axis. Dysregulation of this pathway underlies severe disorders like infertility and precocious puberty. Here, we present cryo-EM structures of KISS1R bound to the endogenous agonist kisspeptin-10 and a synthetic analog TAK-448. These structures reveal pivotal interactions between peptide ligands and KISS1R extracellular loops for receptor activation. Both peptides exhibit a conserved binding mode, unveiling their common activation mechanism. Intriguingly, KISS1R displays a distinct 40° angular deviation in its intracellular TM6 region compared to other G-coupled receptors, enabling distinct interactions with G. This study reveals the molecular intricacies governing ligand binding and activation of KISS1R, while highlighting its exceptional ability to couple with G. Our findings pave the way for structure-guided design of therapeutics targeting this physiologically indispensable receptor.
PubMed: 38935498
DOI: 10.1016/j.celrep.2024.114389