RESUMEN

Ocean acidification (OA) can affect marine bivalves at various levels of biological organization. Yet, little effort has been devoted to understanding how OA affects the reproductive events of marine bivalves during multiple cycles of maturation. Here, we tested sex-specific reproductive responses of Manila clams (Ruditapes philippinarum) to OA during gonadal rematuration. Under acidified conditions, both male and female clams exhibited delayed gonadal rematuration following spawning and impairments in gonadal tissues, which can be likely ascribed to lowered concentrations of hormones and vitellogenin. The findings indicate that marine bivalves experience significant declines in reproductive capacity as a result of OA during their reproductive cycles, with clear sex-specific differences. Consequently, it is essential to consider sex-specific reproduction responses of marine bivalves to OA when developing conservation strategies and forecasting population sustainability in a rapidly acidifying marine environment.

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Background: Urate concentration and the physiological regulation of urate homeostasis exhibit clear sex differences. DNA methylation has been shown to explain a substantial proportion of serum urate variance, mediate the genetic effect on urate concentration, and co-regulate with cardiometabolic traits. However, whether urate concentration is associated with DNA methylation in a sex-dependent manner is unknown. Additionally, it is worth investigating if urate changes after perturbations, such as vaccination, are associated with DNA methylation in a sex-specific manner. Methods: We investigated the association between DNA methylation and serum urate concentrations in a Dutch cohort of 325 healthy individuals. Urate concentration and DNA methylation were measured before and after Bacillus Calmette-Guérin (BCG) vaccination, used as a perturbation associated with increased gout flares. The association analysis included united, interaction, and sex-stratified analysis. Validation of the identified CpG sites was conducted using three independent cohorts. Results: 215 CpG sites were associated with serum urate in males, while 5 CpG sites were associated with serum urate in females, indicating sex-specific associations. Circulating urate concentrations significantly increased after BCG vaccination, and baseline DNA methylation was associated with differences in urate concentration before and after vaccination in a sex-specific manner. The CpG sites associated with urate concentration in males were enriched in neuro-protection pathways, whereas in females, the urate change-associated CpG sites were related to lipid and glucose metabolism. Conclusion: Our study enhances the understanding of how epigenetic factors contribute to regulating serum urate levels in a sex-specific manner. These insights have significant implications for the diagnosis, prevention, and treatment of various urate-related diseases and highlight the importance of personalized and sex-specific approaches in medicine.

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Bisphenols, parabens, and triclosan (TCS) are common endocrine disrupters used in various consumer products. These chemicals have been shown to cross the placental barrier and affect intrauterine development of fetuses. In this study, we quantified serum levels of six bisphenols, five parabens, and TCS in 483 pregnant women from southern China. Quantile-based g-computation showed that combined exposure to bisphenols, parabens, and TCS was significantly (p < 0.05) and negatively associated with birth weight (ß = -39.9, 95% CI: -73.8, -6.1), birth length (ß = -0.19, 95% CI: -0.34, -0.04), head circumference (ß = -0.13, 95% CI: -0.24, -0.02), and thoracic circumference (ß = -0.16, 95% CI: -0.29, -0.04). An inverse correlation was also identified between mixture exposure and gestational age (ß = -0.12, 95% CI: -0.24, -0.01). Bisphenol A (BPA), bisphenol Z (BPZ), bisphenol AP (BPAP), propylparaben (PrP), and TCS served as the dominant contributors to the overall effect. In subgroup analyses, male newborns were more susceptible to mixture exposure than females, whereas the exposure-outcome link was prominent among pregnant women in the first and second trimesters. More evidence is warranted to elucidate the impacts of exposure to mixtures on birth outcomes, as well as the underlying mechanisms.

Asunto(s)

Peso al Nacer , Edad Gestacional , Parabenos , Fenoles , Triclosán , Humanos , Femenino , Embarazo , Peso al Nacer/efectos de los fármacos , Adulto , Masculino , Recién Nacido , Exposición Materna , Disruptores Endocrinos , Compuestos de Bencidrilo , China , Trimestres del Embarazo

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Caffeine exerts a biphasic effect on zebrafish behavior. High doses of caffeine have been associated with increased stress and anxiety, whereas low doses have been found to enhance performance on tasks requiring focus and attention. However, the sex-specific nature of these biphasic effects on behavior and physiology remains unclear. This study assessed the behavioral responses and hormone levels in male and female zebrafish after acute exposure to caffeine ranging from 0.3 to 600 mg/L. The results showed no significant difference in caffeine intake between males and females after acute exposure at each concentration. Caffeine-induced behavioral and physiological responses indicated a threshold dosage existed between 30 and 300 mg/L. Female fish displayed increased anxiety-like behavioral phenotypes, i.e., latency to upper and freezing, whereas males exhibited more erratic movement following acute exposure to a high-dose treatment. In addition, females exhibited a significant increase in whole-body cortisol levels, while males experienced a testosterone elevation at 300 mg/L of caffeine acute exposure. There was a significant decrease in the duration of erratic movements in males treated with the androgen receptor antagonist flutamide compared to the control group. The transcriptome analysis uncovered 511 and 592 up-regulated and 761 and 922 down-regulated differential expression genes in males and females, respectively, compared to the control. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway analysis revealed that caffeine has the potential to impact various pathways in zebrafish, including phototransduction and steroid hormone biosynthesis. Our findings demonstrate that testosterone and cortisol play a combined role in regulating stress responses in both behavior and physiology. Furthermore, our study highlights the significance of encompassing both male and female zebrafish as a model system.

Asunto(s)

Ansiedad , Conducta Animal , Cafeína , Hidrocortisona , Caracteres Sexuales , Testosterona , Pez Cebra , Animales , Cafeína/farmacología , Cafeína/administración & dosificación , Femenino , Masculino , Ansiedad/inducido químicamente , Ansiedad/metabolismo , Hidrocortisona/metabolismo , Hidrocortisona/sangre , Testosterona/metabolismo , Testosterona/sangre , Conducta Animal/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/farmacología , Estimulantes del Sistema Nervioso Central/administración & dosificación , Flutamida/farmacología , Factores Sexuales , Relación Dosis-Respuesta a Droga

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We present a systematic analysis of epigenetic age acceleration based on by far the largest collection of publicly available DNA methylation data for healthy samples (93 datasets, 23 K samples), focusing on the geographic (25 countries) and ethnic (31 ethnicities) aspects around the world. We employed the most popular epigenetic tools for assessing age acceleration and examined their quality metrics and ability to extrapolate to epigenetic data from different tissue types and age ranges different from the training data of these models. In most cases, the models proved to be inconsistent with each other and showed different signs of age acceleration, with the PhenoAge model tending to systematically underestimate and different versions of the GrimAge model tending to systematically overestimate the age prediction of healthy subjects. Referring to data availability and consistency, most countries and populations are still not represented in GEO, moreover, different datasets use different criteria for determining healthy controls. Because of this, it is difficult to fully isolate the contribution of "geography/environment", "ethnicity" and "healthiness" to epigenetic age acceleration. Among the explored metrics, only the DunedinPACE, which measures aging rate, appears to adequately reflect the standard of living and socioeconomic indicators in countries, although it has a limited application to blood methylation data only. Invariably, by epigenetic age acceleration, males age faster than females in most of the studied countries and populations.

Asunto(s)

Envejecimiento , Metilación de ADN , Epigénesis Genética , Humanos , Envejecimiento/genética , Epigénesis Genética/genética

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Mammals have evolved sex-specific adaptations to reduce energy usage in times of food scarcity. These adaptations are well described for peripheral tissue, though much less is known about how the energy-expensive brain adapts to food restriction, and how such adaptations differ across the sexes. Here, we examined how food restriction impacts energy usage and function in the primary visual cortex (V1) of adult male and female mice. Molecular analysis and RNA sequencing in V1 revealed that in males, but not in females, food restriction significantly modulated canonical, energy-regulating pathways, including pathways associated waith AMP-activated protein kinase, peroxisome proliferator-activated receptor alpha, mammalian target of rapamycin, and oxidative phosphorylation. Moreover, we found that in contrast to males, food restriction in females did not significantly affect V1 ATP usage or visual coding precision (assessed by orientation selectivity). Decreased serum leptin is known to be necessary for triggering energy-saving changes in V1 during food restriction. Consistent with this, we found significantly decreased serum leptin in food-restricted males but no significant change in food-restricted females. Collectively, our findings demonstrate that cortical function and energy usage in female mice are more resilient to food restriction than in males. The neocortex, therefore, contributes to sex-specific, energy-saving adaptations in response to food restriction.

Asunto(s)

Metabolismo Energético , Neocórtex , Animales , Femenino , Masculino , Neocórtex/fisiología , Neocórtex/metabolismo , Ratones , Corteza Visual/fisiología , Corteza Visual/metabolismo , Factores Sexuales , Privación de Alimentos/fisiología , Ratones Endogámicos C57BL , Caracteres Sexuales , Leptina/metabolismo , Leptina/sangre , Adaptación Fisiológica , Restricción Calórica

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OBJECTIVE: Osteoarthritis is a common and complex joint disorder that shows higher prevalence and greater disease severity in women. Here, we investigate genome-wide methylation profiles of primary chondrocytes from osteoarthritis patients. DESIGN: We compare genome-wide methylation profiles of macroscopically intact (low-grade) and degraded (high-grade) osteoarthritis cartilage samples matched from osteoarthritis patients undergoing knee replacement surgery. We perform an epigenome-wide association study for cartilage degeneration across 170 patients and separately in 96 women and 74 men. RESULTS: We reveal widespread epigenetic differences with enrichments of nervous system and apoptosis-related processes. We further identify substantial similarities between sexes, but also sex-specific markers and pathways. CONCLUSIONS: Together, we provide the largest genome-wide methylation profiles of primary cartilage to date with enhanced and sex-specific insights into epigenetic processes underlying osteoarthritis progression.

Asunto(s)

Cartílago Articular , Condrocitos , Metilación de ADN , Epigénesis Genética , Estudio de Asociación del Genoma Completo , Osteoartritis de la Rodilla , Humanos , Femenino , Masculino , Cartílago Articular/metabolismo , Cartílago Articular/patología , Osteoartritis de la Rodilla/genética , Osteoartritis de la Rodilla/metabolismo , Osteoartritis de la Rodilla/patología , Persona de Mediana Edad , Anciano , Condrocitos/metabolismo , Condrocitos/patología , Epigenómica , Factores Sexuales , Índice de Severidad de la Enfermedad

RESUMEN

Background: Previous epidemiological research has linked posttraumatic stress disorder (PTSD) with specific physical health problems, but the comprehensive landscape of medical conditions associated with PTSD remains uncharacterized. Electronic health records provide an opportunity to overcome clinical knowledge gaps and uncover associations with biological relevance that potentially vary by sex. Methods: PTSD was defined among biobank participants (N = 145,959) in 3 major healthcare systems using 2 ICD code-based definitions: broad (≥1 PTSD or acute stress codes vs. 0; n cases = 16,706) and narrow (≥2 PTSD codes vs. 0; n cases = 3325). Using a phenome-wide association study design, we tested associations between each PTSD definition and all prevalent disease umbrella categories, i.e., phecodes. We also conducted sex-stratified phenome-wide association study analyses including a sex × diagnosis interaction term in each logistic regression. Results: A substantial number of phecodes were significantly associated with PTSDNarrow (61%) and PTSDBroad (83%). While the strongest associations were shared between the 2 definitions, PTSDBroad captured 334 additional phecodes not significantly associated with PTSDNarrow and exhibited a wider range of significantly associated phecodes across various categories, including respiratory, genitourinary, and circulatory conditions. Sex differences were observed in that PTSDBroad was more strongly associated with osteoporosis, respiratory failure, hemorrhage, and pulmonary heart disease among male patients and with urinary tract infection, acute pharyngitis, respiratory infections, and overweight among female patients. Conclusions: This study provides valuable insights into a diverse range of comorbidities associated with PTSD, including both known and novel associations, while highlighting the influence of sex differences and the impact of defining PTSD using electronic health records.

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Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder that some people develop following a traumatic event. In addition to mental symptoms, PTSD can impact human health in ways other ways; for example, there are many known conditions that co-occur with PTSD, such as cardiovascular conditions. In this study, we set out to understand the breadth and degree to which PTSD co-occurs with medical outcomes in a sample of over 146,000 patients across 3 large medical systems. We found that both narrowly and broadly defined PTSD diagnosis co-occurred with hundreds of medical conditions, and the strongest associations were with other psychiatric disorders, respiratory conditions (asthma, GERD), sleep-related conditions, and pain. These results provide insights into future genetic studies of PTSD in large-scale biobanks and deepen our understanding of the complex needs of patients with PTSD.

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BACKGROUND: The vasoconstrictor effects of angiotensin II via type 1 angiotensin II receptors in vascular smooth muscle cells are well established, but the direct effects of angiotensin II on vascular endothelial cells (VECs) in vivo and the mechanisms how VECs may mitigate angiotensin II-mediated vasoconstriction are not fully understood. The present study aimed to explore the molecular mechanisms and pathophysiological relevance of the direct actions of angiotensin II on VECs in kidney and brain microvessels in vivo. METHODS AND RESULTS: Changes in VEC intracellular calcium ([Ca2+]i) and nitric oxide (NO) production were visualized by intravital multiphoton microscopy of cadherin 5-Salsa6f mice or the endothelial uptake of NO-sensitive dye 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate, respectively. Kidney fibrosis by unilateral ureteral obstruction and Ready-to-use adeno-associated virus expressing Mouse Renin 1 gene (Ren1-AAV) hypertension were used as disease models. Acute systemic angiotensin II injections triggered >4-fold increases in VEC [Ca2+]i in brain and kidney resistance arterioles and capillaries that were blocked by pretreatment with the type 1 angiotensin II receptor inhibitor losartan, but not by the type 2 angiotensin II receptor inhibitor PD123319. VEC responded to acute angiotensin II by increased NO production as indicated by >1.5-fold increase in 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate fluorescence intensity. In mice with kidney fibrosis or hypertension, the angiotensin II-induced VEC [Ca2+]i and NO responses were significantly reduced, which was associated with more robust vasoconstrictions, VEC shedding, and microthrombi formation. CONCLUSIONS: The present study directly visualized angiotensin II-induced increases in VEC [Ca2+]i and NO production that serve to counterbalance agonist-induced vasoconstriction and maintain residual organ blood flow. These direct and endothelium-specific angiotensin II effects were blunted in disease conditions and linked to endothelial dysfunction and the development of vascular pathologies.

Asunto(s)

Angiotensina II , Encéfalo , Calcio , Hipertensión , Riñón , Microvasos , Óxido Nítrico , Vasoconstricción , Animales , Ratones , Angiotensina II/farmacología , Encéfalo/metabolismo , Encéfalo/irrigación sanguínea , Calcio/metabolismo , Señalización del Calcio/efectos de los fármacos , Modelos Animales de Enfermedad , Células Endoteliales/metabolismo , Células Endoteliales/efectos de los fármacos , Hipertensión/metabolismo , Hipertensión/fisiopatología , Hipertensión/tratamiento farmacológico , Riñón/irrigación sanguínea , Riñón/metabolismo , Ratones Endogámicos C57BL , Microvasos/metabolismo , Microvasos/efectos de los fármacos , Microvasos/patología , Óxido Nítrico/metabolismo , Vasoconstricción/efectos de los fármacos

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Sex and gender disparities in biomedical research have been emphasized to improve scientific knowledge applied for the health of both men and women. Despite sex differences in cancer incidence, prognosis, and responses to therapeutic agents, mechanistic explanations at molecular levels are far from enough. Recent studies suggested that cell sex is an important biological variable due to differences in sex chromosome gene expression and differences in events associated with developmental biology. The objective of this study was to analyze the reporting of sex of cells used in cancer research using articles published in Cancer Cell, Molecular Cancer, Journal of Hematology & Oncology, Journal for ImmunoTherapy of Cancer, and Cancer Research in 2020, and to examine whether there exists any sex bias. We found that the percentage of cells with sex notation in the article was 36.5%. Primary cells exhibited higher sex notation compared to cell lines. A higher percentage of female cells were used in cell cultures with sex notation. Also, sex-common cells omitted sex description more often compared to sex-specific cells. None of the cells isolated from embryo and esophagus reported the cell sex in the article. Our results indicate cell sex report in cancer research is limited to a small proportion of cells used in the study. These results call for acknowledging the sex of cells to increase the applicability of biomedical research discoveries.

Asunto(s)

Investigación Biomédica , Células Cultivadas , Neoplasias , Femenino , Humanos , Masculino , Publicaciones , Factores Sexuales , Sexismo

RESUMEN

Introduction: Dilatation of the optic nerve sheath diameter and swelling of the optic disc are known phenomena associated with intracranial pressure elevation. Research question: Do sex and disease etiology have an impact on the development of optic disc elevation and optic nerve sheath extension in children in the setting of ICP elevation? Fundoscopic papilledema and point-of-care-ultrasound techniques-optic nerve sheath diameter (US-ONSD) and optic disc elevation (US-ODE) - were compared in this regard. Material and methods: 72 children were included in this prospective study; 50 with proven pathology (e.g. pseudotumor cerebri, tumor), 22 with pathology excluded. Bilateral US-ONSD and US-ODE were quantified by US using a 12-MHz-linear-array-transducer. This was compared with fundoscopic optic disc findings and in 28 patients with invasive ICP values, stratified for sex and etiology. Results: In patients with proven disease, significant more girls (69%) had fundoscopic papilledema compared with boys (37%, p < 0.05). Girls had also larger US-ODE values (0.86 ± 0.36 mm vs. 0.65 ± 0.40 mm in boys). 80% of tumor patients had initial papilledema (100% girls, 79% boys), compared with 50% in pseudotumor cerebri (PTC) (83% girls, 30% boys). US-ONSD had no sex- and no etiology-specificity. Discussion and conclusion: Presence of papilledema appears to be influenced by sex and etiology, whereas US-ONSD is not. Girls seem more likely to develop papilledema under similar conditions. Male sex and PTC appear as risk factors for being undetected by fundoscopic findings. US-ONSD and US-ODE seem useful tools to identify pathologies with potentially increased ICP requiring treatment in children regardless of sex and etiology.

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BACKGROUND: While prenatal exposure to alkylphenols (APs) has been demonstrated to be associated with neurodevelopmental impairments in animals, the evidence from epidemiological studies remains limited and inconclusive. This study aimed to explore the link between AP exposure during pregnancy and the intelligence quotient (IQ) of preschool children. METHODS: A total of 221 mother-child pairs from the Guangxi Zhuang Birth Cohort were recruited. Nonylphenol (NP), 4-tert-octylphenol (4-T-OP), 4-n-nonylphenol (4-N-NP), and 4-n-octylphenol were measured in maternal serum in early pregnancy. Childhood IQ was evaluated by the Fourth Edition of Wechsler Preschool and Primary Scale of the Intelligence at 3 to 6 years of age. The impact of APs on childhood IQ were evaluated by generalized linear models (GLMs), restricted cubic spline (RCS), and Bayesian kernel machine regression (BKMR). RESULTS: In GLMs, prenatal exposure to NP and the second tertile of 4-T-OP exhibited an inverse association with full-scale IQ (FSIQ) (ß = -2.38; 95% CI: -4.59, -0.16) and working memory index (WMI) (ß = -5.24; 95% CI: -9.58, -0.89), respectively. Prenatal exposure to the third tertile of 4-N-NP showed a positive association with the fluid reasoning index (ß = 4.95; 95% CI: 1.14, 8.77) in total children, as well as in girls when stratified by sex. A U-shaped relationship between maternal 4-T-OP and WMI was noted in total children and girls by RCS (all P nonlinear < 0.05). The combined effect primarily driven by NP, of maternal AP mixtures at concentrations above the 50th percentile exhibited an inverse trend on FSIQ in total children and girls in BKMR. CONCLUSIONS: Prenatal exposure to various APs affects IQ in preschool children, and there may be nonmonotonic and sex-specific effects. Further investigation across the population is required to elucidate the potential neurotoxic effects of APs.

Asunto(s)

Fenoles , Efectos Tardíos de la Exposición Prenatal , Masculino , Embarazo , Femenino , Humanos , Preescolar , Niño , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/epidemiología , Teorema de Bayes , China , Pruebas de Inteligencia , Inteligencia

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The exposure to sublethally high temperature reduces reproductive performance in diverse organisms. Although this effect has been particularly emphasized for males or male reproductive functioning, it remains largely unknown whether the effect of heat on fertility is sex-specific. Here we examined the impact of sublethally high temperature on male and female functions in a simultaneously hermaphroditic snail species, Lymnaea stagnalis. Examining hermaphrodites is useful to evaluate the sex-specific impacts of heat exposure, since they possess male and female functions within a single individual, sharing genetic and environmental factors. Moreover, previously developed sex allocation theory allows us to compare the differential performance of sex functions. In this study, we exposed snails to 20°C (control), 24°C and 28°C for 14 days and assessed their egg and sperm production, sperm transfer, mating behaviour and growth. Both types of gamete production were significantly reduced by higher temperature, leading to an overall reduction of reproductive investment. By quantifying sex allocation, we furthermore revealed that the heat-stressed snails reduced the relative investment in their male function. This study illustrates that examining simultaneous hermaphrodites can provide significant insights for the impact of heat, and the proximate mechanism, on reproduction in diverse organisms.

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Today's challenge for precision medicine involves the integration of the impact of molecular clocks on drug pharmacokinetics, toxicity, and efficacy toward personalized chronotherapy. Meaningful improvements of tolerability and/or efficacy of medications through proper administration timing have been confirmed over the past decade for immunotherapy and chemotherapy against cancer, as well as for commonly used pharmacological agents in cardiovascular, metabolic, inflammatory, and neurological conditions. Experimental and human studies have recently revealed sexually dimorphic circadian drug responses. Dedicated randomized clinical trials should now aim to issue personalized circadian timing recommendations for daily medical practice, integrating innovative technologies for remote longitudinal monitoring of circadian metrics, statistical prediction of molecular clock function from single-timepoint biopsies, and multiscale biorhythmic mathematical modelling. Importantly, chronofit patients with a robust circadian function, who would benefit most from personalized chronotherapy, need to be identified. Conversely, nonchronofit patients could benefit from the emerging pharmacological class of chronobiotics targeting the circadian clock.

Asunto(s)

Relojes Circadianos , Neoplasias , Masculino , Femenino , Humanos , Ritmo Circadiano , Cronoterapia , Neoplasias/tratamiento farmacológico , Preparaciones Farmacéuticas

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BACKGROUND: Yakuts are one of the indigenous populations of the subarctic and arctic territories of Siberia characterized by a continental subarctic climate with severe winters, with the regular January average temperature in the regional capital city of Yakutsk dipping below - 40 °C. The epigenetic mechanisms of adaptation to such ecologies and environments and, in particular, epigenetic age acceleration in the local population have not been studied before. RESULTS: This work reports the first epigenetic study of the Yakutian population using whole-blood DNA methylation data, supplemented with the comparison to the residents of Central Russia. Gene set enrichment analysis revealed, among others, geographic region-specific differentially methylated regions associated with adaptation to climatic conditions (water consumption, digestive system regulation), aging processes (actin filament activity, cell fate), and both of them (channel activity, regulation of steroid and corticosteroid hormone secretion). Further, it is demonstrated that the epigenetic age acceleration of the Yakutian representatives is significantly higher than that of Central Russia counterparts. For both geographic regions, we showed that epigenetically males age faster than females, whereas no significant sex differences were found between the regions. CONCLUSIONS: We performed the first study of the epigenetic data of the Yakutia cohort, paying special attention to region-specific features, aging processes, age acceleration, and sex specificity.

Asunto(s)

Metilación de ADN , Epigénesis Genética , Humanos , Masculino , Femenino , Siberia , Regiones Árticas

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Ocean acidification (OA) can seriously affect marine bivalves at different levels of biological organization, generating widespread consequences on progeny recruitment and population maintenance. Yet, few effort has been devoted to elucidating whether female and male bivalves respond differentially to OA in their reproductive seasons. Here, we estimated differences in physiological responses of female and male Manila clams (Ruditapes philippinarum) to OA during gonadal maturation. In comparison to OA-stressed male clams, females significantly depressed activities in enzymes related to energy metabolism (NKA, T-ATP), antioxidant defence (SOD and MDA), and non-specific immune function (ACP), and downregulated expression of AMPK that plays a key role in cellular metabolism, indicating that sex did significantly affect responses of R. philippinarum to OA. Such sex-based differences can be likely couched in energetic terms, given the much more energetically expensive cost of egg production than that of sperms. These results indicate that sex-specific responses to OA during reproductive seasons do exist in marine bivalves, and therefore accounting for such sex specificity is of paramount importance when projecting population sustainability and formulating conservation strategies in an acidifying ocean.

Asunto(s)

Bivalvos , Acidificación de los Océanos , Animales , Femenino , Masculino , Concentración de Iones de Hidrógeno , Agua de Mar , Bivalvos/fisiología , Antioxidantes

RESUMEN

Myristoylated alanine-rich C-kinase substrate (MARCKS) is a critical member of a signaling cascade that influences disease-relevant neural functions such as neural growth and plasticity. The effector domain (ED) of MARCKS interacts with the extracellular glycan polysialic acid (PSA) through the cell membrane to stimulate neurite outgrowth in cell culture. We have shown that a synthetic ED peptide improves functional recovery after spinal cord injury in female but not male mice. However, peptides themselves are unstable in therapeutic applications, so we investigated more pharmacologically relevant small organic compounds that mimic the ED peptide to maximize therapeutic potential. Using competition ELISAs, we screened small organic compound libraries to identify molecules that structurally and functionally mimic the ED peptide of MARCKS. Since we had shown sex-specific effects of MARCKS on spinal cord injury recovery, we assayed neuronal viability as well as neurite outgrowth from cultured cerebellar granule cells of female and male mice separately. We found that epigallocatechin, amiodarone, sertraline, tegaserod, and nonyloxytryptamine bind to a monoclonal antibody against the ED peptide, and compounds stimulate neurite outgrowth in cultured cerebellar granule cells of female mice only. Therefore, a search for compounds that act in males appears warranted.

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Purpose: To identify practice and social contextual factors that associate with physical activity (PA) levels of children during their participation in a youth soccer program. Methods: Twenty-seven youth soccer teams serving children ages 6-11 years participated. Research staff directly observed and recorded PA intensity and practice and social contextual factors using momentary time-sampling procedures. Each team was observed for 1 practice, during which approximately 6 children were each observed for twenty 30-s observation blocks (10-s observation, 20-s recording). In total, children were observed for 3,102 intervals. Multilevel logistic regression analyses were conducted to describe associations between PA intensity and practice and social contexts. Interaction terms were introduced into the models to determine if the associations differed across girls-only, boys-only, and coed teams. Results: A total of 158 children were observed across the 27 teams. Children were more likely to engage in moderate or vigorous PA while performing fitness (Odds Ratio [OR], 9.9, 95% CI = 5.34-18.04), game (OR, 4.0, 95% CI = 2.88-5.66), warm-up (OR, 2.8, 95% CI = 1.85-4.11), and drill (OR, 1.9, 95% CI = 1.41-2.67) activities compared to tactic/instructional activities. The associations between PA intensity levels and practice and social contexts did not differ across girls-only, boys-only, and coed teams. Conclusions: Fitness activities and full-team game play were associated with higher PA intensity levels during children's participation in youth soccer practices. Youth sport practice protocols can be modified to increase children's physical activity.

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Microglia have been shown to sculpt postnatal circuitry from birth up to adulthood due to their role in both synapse formation, synaptic pruning, and the elimination of weak, redundant synapses. Microglia are differentiated in a sex-dependent manner. In this study, we tested whether sexual differentiation of microglia results in sex-dependent postnatal reorganization of CA1 synaptic connectivity in the hippocampus. The stereological counting of synapses in mice using electron microscopy showed a continuous rise in synapse density until the fourth week, followed by a plateau phase and loss of synapses from the eighth week onwards, with no difference between sexes. This course of alteration in synapse numbers did not differ between sexes. However, selectively, on postnatal day (P) 14 the density of synapses was significantly higher in the female than in the male hippocampus. Higher synapse density in females was paralleled by higher activity of microglia, as indicated by morphological changes, CD68 expression, and proximity of microglia to synaptic sites. In Thy1-GFP mice, consistent with increased synapse numbers, bouton density was also clearly increased in females at P14. At this time point, CD47 expression, the "don't eat me" signal of neurons, was similar in males and females. The decrease in bouton density thereafter in conjunction with increased synapse numbers argues for a role of microglia in the formation of multispine boutons (MSB). Our data in females at P14 support the regulatory role of microglia in synapse density. Sexual differentiation of microglia, however, does not substantially affect long-term synaptic reorganization in the hippocampus.

Asunto(s)

Hipocampo , Microglía , Ratones , Masculino , Femenino , Animales , Microglía/metabolismo , Neuronas , Sinapsis/metabolismo , Terminales Presinápticos

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OBJECTIVES: To examine hip muscle strength deficits in patients with femoroacetabular impingent syndrome (FAIS), with special emphasis on potential sex- and comparison-related (between-subject vs within-subject) differences. DESIGN: Cross-sectional comparative study. PARTICIPANTS: Forty FAIS patients (20 women), 40 healthy controls (20 women) and 40 athletes (20 women). MAIN OUTCOME MEASURES: Hip abduction, adduction and flexion isometric strength was tested using a commercially-available dynamometer. Two between-subject comparisons (FAIS patients vs controls and FAIS patients vs athletes) and one within-subject comparison (inter-limb asymmetry) of strength deficits were conducted, based on the calculation of respective percent differences. RESULTS: For all hip muscle groups, women were 14-18% weaker than men (p < 0.001), but no sex-related interactions were observed. For all hip muscle groups, FAIS patients were 16-19% weaker than controls (p = 0.001) and 24-30% weaker than athletes (p < 0.001). For FAIS patients, the involved hip abductors were 8.5% weaker than the uninvolved ones (p = 0.015), while no inter-limb asymmetry was observed for the other hip muscles. CONCLUSION: Sex had no influence on hip muscle strength deficits in FAIS patients while a major impact of comparison method/group was observed. Hip abductors showed consistent deficits for all comparison methods, suggestive of a possible greater impairment compared to hip flexors and adductors.

Asunto(s)

Pinzamiento Femoroacetabular , Humanos , Masculino , Femenino , Estudios Transversales , Cadera , Articulación de la Cadera , Fuerza Muscular/fisiología , Atletas , Artroscopía/métodos