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Frontiers in Psychiatry 2024Ectodomain shedding (ES) is a fundamental process involving the proteolytic cleavage of membrane-bound proteins, leading to the release of soluble extracellular...
Ectodomain shedding (ES) is a fundamental process involving the proteolytic cleavage of membrane-bound proteins, leading to the release of soluble extracellular fragments (shed ectodomains) with potential paracrine and autocrine signaling functions. In the central nervous system (CNS), ES plays pivotal roles in brain development, axonal regulation, synapse formation, and disease pathogenesis, spanning from cancer to Alzheimer's disease. Recent evidence also suggests its potential involvement in neurodevelopmental conditions like autism and schizophrenia. Past investigations of ES in the CNS have primarily relied on cell culture supernatants or cerebrospinal fluid (CSF) samples, but these methods have limitations, offering limited insights into how ES is modulated in the intact brain parenchyma. In this study, we introduce a methodology for analyzing shed ectodomains globally within rodent brain samples. Through biochemical tissue subcellular separation, mass spectrometry, and bioinformatic analysis, we show that the brain's soluble fraction sheddome shares significant molecular and functional similarities with neuronal and CSF sheddomes. This approach provides a promising means of exploring ES dynamics in the CNS, allowing for the evaluation of ES at different developmental stages and pathophysiological states. This methodology has the potential to help us deepen our understanding of ES and its role in CNS function and pathology, offering new insights and opportunities for research in this field.
PubMed: 38962061
DOI: 10.3389/fpsyt.2024.1367526 -
Heliyon Jun 2024The mutualistic symbiotic relationship between insects and bacteria greatly influences the growth and development of host insects. (Thunberg) (Hemiptera:...
The mutualistic symbiotic relationship between insects and bacteria greatly influences the growth and development of host insects. (Thunberg) (Hemiptera: Tessaratomidae), also referred to as the litchi stink bug, has recently been established as an important insect pest of Sonn. and causes substantial yield loss in India. To design effective and environmentally safe management strategies, an understanding of the diversity and functions of microbiota harbored across the development stages is very important. The assessment of the diversity of development-associated bacteria in and their predicted functions was conducted using 16S rRNA gene sequences obtained by the Illumina MiSeq technology. The result showed that taxonomic analysis of associated bacteria in different developmental stages includes a total of 46 phyla, encompassing 139 classes, 271 orders, 474 families, and 893 genera of bacteria. All developmental stages of shared a total of 42.82 percent of operational taxonomic units (OTUs), with a 97 % similarity threshold. Alpha diversity indices showed maximum species richness in the egg and adult stages. The phyla Proteobacteria followed by Firmicutes, Bacteriodetes, and Actinobacteria, exhibited the highest levels of abundance across all the developmental stages of . Microbiota were most different between the egg and the 4th nymphal stage (χ2 = 711.67) and least different between the 2nd and 4th nymphal instars (χ2 = 44.45). The predicted functions of the microbiota associated with . are mainly involved in amino acid metabolism, cell motility, cellular processes and signaling, glycan biosynthesis and metabolism, lipid metabolism, and membrane transport. The present study documentation and information on symbiotic bacteria across life stages will prompt the development of novel biological management strategies.
PubMed: 38961890
DOI: 10.1016/j.heliyon.2024.e32384 -
Insect Science Jul 2024Wing dimorphism in Nilaparvata lugens is controlled by the insulin-like growth factor 1 (IGF-1) signaling - Forkhead transcription factors (IIS-FoxO) pathway. However,...
Wing dimorphism in Nilaparvata lugens is controlled by the insulin-like growth factor 1 (IGF-1) signaling - Forkhead transcription factors (IIS-FoxO) pathway. However, the role of this signal in the wing development program remains largely unclear. Here, we identified 2 R-SMAD proteins, NlMAD1 and NlMAD2, in the brown planthopper (BPH) transcriptome, derived from the intrinsic transforming growth factor-β pathway of insect wing development. Both proteins share high sequence similarity and conserved domains. Phylogenetic analysis placed them in the R-SMAD group and revealed related insect orthologs. The expression of Nlmad1 was elevated in the late instar stages of the macropterous BPH strain. Nlmad1 knockdown in nymphs results in malformed wings and reduced wing size in adults, which affects the forewing membrane. By contrast, Nlmad2 expression was relatively consistent across BPH strains and different developmental stages. Nlmad2 knockdown had a milder effect on wing morphology and mainly affected forewing veins and cuticle thickness in the brachypterous strain. NlMAD1 functions downstream of the IIS-FoxO pathway by mediating the FoxO-regulated vestigial transcription and wing morph switching. Inhibiting Nlmad1 partially reversed the long-winged phenotype caused by NlFoxO knockdown. These findings indicate that NlMAD1 and NlMAD2 play distinct roles in regulating wing development and morph differentiation in BPH. Generally, NlMAD1 is a key mediator of the IIS-FoxO pathway in wing morph switching.
PubMed: 38961475
DOI: 10.1111/1744-7917.13409 -
Nature Communications Jul 2024Hybrid mapping is a powerful approach to efficiently identify and characterize genes regulated through mechanisms in cis. In this study, using reciprocal crosses of the...
Hybrid mapping is a powerful approach to efficiently identify and characterize genes regulated through mechanisms in cis. In this study, using reciprocal crosses of the phenotypically divergent Duroc and Lulai pig breeds, we perform a comprehensive multi-omic characterization of regulatory variation across the brain, liver, muscle, and placenta through four developmental stages. We produce one of the largest multi-omic datasets in pigs to date, including 16 whole genome sequenced individuals, as well as 48 whole genome bisulfite sequencing, 168 ATAC-Seq and 168 RNA-Seq samples. We develop a read count-based method to reliably assess allele-specific methylation, chromatin accessibility, and RNA expression. We show that tissue specificity was much stronger than developmental stage specificity in all of DNA methylation, chromatin accessibility, and gene expression. We identify 573 genes showing allele specific expression, including those influenced by parent-of-origin as well as allele genotype effects. We integrate methylation, chromatin accessibility, and gene expression data to show that allele specific expression can be explained in great part by allele specific methylation and/or chromatin accessibility. This study provides a comprehensive characterization of regulatory variation across multiple tissues and developmental stages in pigs.
Topics: Animals; DNA Methylation; Alleles; Swine; Female; Chromatin; Organ Specificity; Liver; Placenta; Male; Brain; Sus scrofa; Whole Genome Sequencing; Pregnancy; Multiomics
PubMed: 38961076
DOI: 10.1038/s41467-024-49923-5 -
Trends in Cell Biology Jul 2024Mutations in the p53 gene compromise its role as guardian of genomic integrity, yielding predominantly missense p53 mutant proteins. The gain-of-function hypothesis has... (Review)
Review
Mutations in the p53 gene compromise its role as guardian of genomic integrity, yielding predominantly missense p53 mutant proteins. The gain-of-function hypothesis has long suggested that these mutant proteins acquire new oncogenic properties; however, recent studies challenge this notion, indicating that targeting these mutants may not impact the fitness of cancer cells. Mounting evidence indicates that tumorigenesis involves a cooperative interplay between driver mutations and cellular state, influenced by developmental stage, external insults, and tissue damage. Consistently, the behavior and properties of p53 mutants are altered by the context. This article aims to provide a balanced summary of the evolving evidence regarding the contribution of p53 mutants in the biology of cancer while contemplating alternative frameworks to decipher the complexity of p53 mutants within their physiological contexts.
PubMed: 38960851
DOI: 10.1016/j.tcb.2024.06.003 -
Life Science Alliance Sep 2024A pleiotropic immunoregulatory cytokine, TGF-β, signals via the receptor-regulated SMADs: SMAD2 and SMAD3, which are constitutively expressed in normal cells. Here, we...
A pleiotropic immunoregulatory cytokine, TGF-β, signals via the receptor-regulated SMADs: SMAD2 and SMAD3, which are constitutively expressed in normal cells. Here, we show that selective repression of SMAD3 induces cDC differentiation from the CD115 common DC progenitor (CDP). SMAD3 was expressed in haematopoietic cells including the macrophage DC progenitor. However, SMAD3 was specifically down-regulated in CD115 CDPs, SiglecH pre-DCs, and cDCs, whereas SMAD2 remained constitutive. SMAD3-deficient mice showed a significant increase in cDCs, SiglecH pre-DCs, and CD115 CDPs compared with the littermate control. SMAD3 repressed the mRNA expression of FLT3 and the cDC-related genes: IRF4 and ID2. We found that one of the SMAD transcriptional corepressors, c-SKI, cooperated with phosphorylated STAT3 at Y705 and S727 to repress the transcription of SMAD3 to induce cDC differentiation. These data indicate that STAT3 and c-Ski induce cDC differentiation by repressing SMAD3: the repressor of the cDC-related genes during the developmental stage between the macrophage DC progenitor and CD115 CDP.
Topics: Animals; Cell Differentiation; Dendritic Cells; Smad3 Protein; STAT3 Transcription Factor; Mice; Interferon Regulatory Factors; Inhibitor of Differentiation Protein 2; Mice, Knockout; Mice, Inbred C57BL; fms-Like Tyrosine Kinase 3; Proto-Oncogene Proteins; Smad2 Protein; Phosphorylation; Signal Transduction
PubMed: 38960622
DOI: 10.26508/lsa.201900581 -
Journal of Affective Disorders Jul 2024Depression is a leading cause of disability and poor health worldwide and is expected to rank first worldwide by 2030. The aim of this study is to analyze the transition...
BACKGROUND
Depression is a leading cause of disability and poor health worldwide and is expected to rank first worldwide by 2030. The aim of this study is to analyze the transition and trend of depression burden in China and various income-level countries by utilizing the Global Burden of Disease (GBD) database and the Joinpoint regression model. This analysis seeks to comprehend the variations in the burden of depression across different income regions and evaluate their developmental patterns.
METHODS
Based on the GBD 2019 open dataset, this study extracted data on YLD (Years Lived with Disability), DALY (Disability-Adjusted Life Years), and incidence related to depression. The analysis focused on the period between 1990 and 2019, covering global data and distinguishing between high-income, upper-middle-income, lower-middle-income, low-income countries, and China. We utilized the Joinpoint regression model to fit the spatiotemporal trend changes among different income-level countries. Pairwise comparisons were conducted to examine the parallelism and to determine if the differences in trend changes among various regions were statistically significant.
RESULTS
From 1990 to 2019, the age-standardized YLD and DALY for depression female were higher than that in male. The YLD total change rate of depression men was higher than that of women. China exhibited the largest disparity in total YLD change rates between genders, reaching 0.08. During 1990 to 2019, the incidence of depression in 2005-2019 increased among females in middle to high-income countries, low-income countries, and China as compare to that of 1990-2005. Notably, China shown the most increase the incidence rate of females (from -0.4 % to 0.84 %). China experienced the most significant change in the YLD of depression during this period (AAPC = 0.45, 95 % CI = 0.41, 0.48, P < 0.01). China's YLD/Incidence rate was higher compared to the global, HICs, UMCs, LMCs, and LICs. In China, the YLD/incidence rate of depression began to rise in 1994, peaking around 2010, and then gradually declining. Since 2010, the growth rate of depression DALYs in China has been higher than the global average, high-income countries, upper-middle-income countries, lower-middle-income countries, and low-income countries. The DALY's AAPC value for the HLCs was the highest (AAPC = 0.24, 95 % CI = 0.22, 0.25, P < 0.01). The UMCs, in comparison to other regions, incidence rate had the highest AAPC value (AAPC = 0.48, 95 % CI = 0.46, 0.50, P < 0.01).
CONCLUSIONS
Given the significant variations in the burden of depression across countries with different income levels, future strategies aimed at reducing the burden of depression should adopt tailored and differentiated approaches according to each country's specific needs and developmental stages.
PubMed: 38960335
DOI: 10.1016/j.jad.2024.06.067 -
Clinica Chimica Acta; International... Jul 2024The SEPHS1 (Selenophosphate Synthetase 1) gene encodes a critical enzyme for synthesizing selenophosphate, the active donor of selenium (Se) necessary for selenoprotein... (Review)
Review
The SEPHS1 (Selenophosphate Synthetase 1) gene encodes a critical enzyme for synthesizing selenophosphate, the active donor of selenium (Se) necessary for selenoprotein biosynthesis. Selenoproteins are vital for antioxidant defense, thyroid hormone metabolism, and cellular homeostasis. Mutations in SEPHS1 gene, are associated with neurodevelopmental disorders with developmental delay, poor growth, hypotonia, and dysmorphic features. Due to Se's critical role in brain development and function, SEPHS1 gene has taken center stage in neurodevelopmental research. This review explores the structure and function of the SEPHS1 gene, its role in neurodevelopment, and the implications of its dysregulation for neurodevelopmental disorders. Therapeutic strategies, including Se supplementation, gene therapy, and targeted therapies, are discussed as potential interventions to address SEPHS1 associated neurodevelopmental dysfunction. The study's findings reveal how SEPHS1 mutations disrupt neurodevelopment, emphasizing the gene's intolerance to loss of function. Future research should focus on functional characterization of SEPHS1 variants, broader genetic screenings, and therapeutic developments.
PubMed: 38960024
DOI: 10.1016/j.cca.2024.119844 -
PloS One 2024Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse birth and developmental outcomes in children. We aimed to describe prenatal PAH...
OBJECTIVE
Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse birth and developmental outcomes in children. We aimed to describe prenatal PAH exposures in a large, multisite U.S. consortium.
METHODS
We measured 12 mono-hydroxylated metabolites (OH-PAHs) of 7 PAHs (naphthalene, fluorene, phenanthrene, pyrene, benzo(c)phenanthrene, chrysene, benz(a)anthracene) in mid-pregnancy urine of 1,892 pregnant individuals from the ECHO PATHWAYS consortium cohorts: CANDLE (n = 988; Memphis), TIDES (n = 664; Minneapolis, Rochester, San Francisco, Seattle) and GAPPS (n = 240; Seattle and Yakima, WA). We described concentrations of 8 OH-PAHs of non-smoking participants (n = 1,695) by site, socioeconomic characteristics, and pregnancy stage (we report intraclass correlation coefficients (ICC) for n = 677 TIDES participants).
RESULTS
Exposure to the selected PAHs was ubiquitous at all sites. 2-hydroxynaphthalene had the highest average concentrations at all sites. CANDLE had the highest average concentrations of most metabolites. Among non-smoking participants, we observed some patterns by income, education, and race but these were not consistent and varied by site and metabolite. ICCs of repeated OH-PAH measures from TIDES participants were ≤ 0.51.
CONCLUSION
In this geographically-diverse descriptive analysis of U.S. pregnancies, we observed ubiquitous exposure to low molecular weight PAHs, highlighting the importance of better understanding PAH sources and their pediatric health outcomes attributed to early life PAH exposure.
Topics: Humans; Female; Pregnancy; Polycyclic Aromatic Hydrocarbons; United States; Adult; Cohort Studies; Maternal Exposure; Young Adult
PubMed: 38959439
DOI: 10.1371/journal.pone.0305004 -
Proceedings of the National Academy of... Jul 2024Phoresy is an interspecies interaction that facilitates spatial dispersal by attaching to a more mobile species. Hitchhiking species have evolved specific traits for...
Phoresy is an interspecies interaction that facilitates spatial dispersal by attaching to a more mobile species. Hitchhiking species have evolved specific traits for physical contact and successful phoresy, but the regulatory mechanisms involved in such traits and their evolution are largely unexplored. The nematode displays a hitchhiking behavior known as nictation during its stress-induced developmental stage. Dauer-specific nictation behavior has an important role in natural populations, which experience boom-and-bust population dynamics. In this study, we investigated the nictation behavior of 137 wild strains sampled throughout the world. We identified species-wide natural variation in nictation and performed a genome-wide association mapping. We show that the variants in the promoter of , encoding a putative steroidogenic enzyme, underlie differences in nictation. This difference is due to the changes in expression in glial cells, which implies that glial steroid metabolism regulates phoretic behavior. Population genetic analysis and geographic distribution patterns suggest that balancing selection maintained two haplotypes that existed in ancestral populations. Our findings contribute to further understanding of the molecular mechanism of species interaction and the maintenance of genetic diversity within natural populations.
Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Neuroglia; Genome-Wide Association Study; Behavior, Animal; Genetic Variation; Promoter Regions, Genetic; Steroids
PubMed: 38959036
DOI: 10.1073/pnas.2320796121