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Sample records for sex-specific differential survival

  1. Sex-specific differential survival of extra-pair and within-pair offspring in song sparrows, Melospiza melodia.

    Science.gov (United States)

    Sardell, Rebecca J; Arcese, Peter; Keller, Lukas F; Reid, Jane M

    2011-11-07

    It is widely hypothesized that the evolution of female extra-pair reproduction in socially monogamous species reflects indirect genetic benefits to females. However, a critical prediction of this hypothesis, that extra-pair young (EPY) are fitter than within-pair young (WPY), has rarely been rigorously tested. We used 18 years of data from free-living song sparrows, Melospiza melodia, to test whether survival through major life-history stages differed between EPY and WPY maternal half-siblings. On average, survival of hatched chicks to independence from parental care and recruitment, and their total lifespan, did not differ significantly between EPY and WPY. However, EPY consistently tended to be less likely to survive, and recruited EPY survived for significantly fewer years than recruited WPY. Furthermore, the survival difference between EPY and WPY was sex-specific; female EPY were less likely to survive to independence and recruitment and lived fewer years than female WPY, whereas male EPY were similarly or slightly more likely to survive and to live more years than male WPY. These data indicate that extra-pair paternity may impose an indirect cost on females via their female offspring and that sex-specific genetic, environmental or maternal effects may shape extra-pair reproduction.

  2. Sex-specific effects of yolk testosterone on survival, begging and growth of zebra finches

    NARCIS (Netherlands)

    von Engelhardt, N; Carere, C; Dijkstra, C; Groothuis, TGG

    2006-01-01

    Yolk androgens affect offspring hatching, begging, growth and survival in many bird species. If these effects are sex-specific, yolk androgen deposition may constitute a mechanism for differential investment in male and female offspring. We tested this hypothesis in zebra finches. In this species,

  3. Differential sex-specific effects of oxygen toxicity in human umbilical vein endothelial cells

    International Nuclear Information System (INIS)

    Zhang, Yuhao; Lingappan, Krithika

    2017-01-01

    Despite the well-established sex-specific differences in the incidence of bronchopulmonary dysplasia (BPD), the molecular mechanism(s) behind these are not completely understood. Pulmonary angiogenesis is critical for alveolarization and arrest in vascular development adversely affects lung development. Human neonatal umbilical vein endothelial cells (HUVECs) provide a robust in vitro model for the study of endothelial cell physiology and function. Male and Female HUVECs were exposed to room air (21% O 2 , 5% CO 2 ) or hyperoxia (95% O 2 , 5% CO 2 ) for up to 72 h. Cell viability, proliferation, H 2 O 2 production and angiogenesis were analyzed. Sex-specific differences in the expression of VEGFR2 and modulation of NF-kappa B pathway were measured. Male HUVECs have decreased survival, greater oxidative stress and impairment in angiogenesis compared to similarly exposed female cells. There is differential expression of VEGFR2 between male and female HUVECs and greater activation of the NF-kappa B pathway in female HUVECs under hyperoxic conditions. The results indicate that sex differences exist between male and female HUVECs in vitro after hyperoxia exposure. Since endothelial dysfunction has a major role in the pathogenesis of BPD, these differences could explain in part the mechanisms behind sex-specific differences in the incidence of this disease. - Highlights: • Cellular sex effects viability and oxidative stress in HUVECs exposed to hyperoxia. • Male HUVECs show greater impairment in angiogenesis compared to female cells. • Sex-specific modulation of VEGFR2 and the NF-kappaB pathway was noted.

  4. Do sex-specific densities affect local survival of free-ranging great tits?

    NARCIS (Netherlands)

    Michler, Stephanie P. M.; Nicolaus, Marion; Ubels, Richard; van der Velde, Marco; Both, Christiaan; Tinbergen, Joost M.; Komdeur, Jan

    2011-01-01

    Competition within sexes is expected when resources are sex specific, whereas competition between sexes can occur when similar resources are exploited. Local population density and sex ratio will determine the amount of sex-specific interactions and thus the potential degree of sex-specific

  5. Sex-specific effects of altered competition on nestling growth and survival: an experimental manipulation of brood size and sex ratio.

    Science.gov (United States)

    Nicolaus, Marion; Michler, Stephanie P M; Ubels, Richard; van der Velde, Marco; Komdeur, Jan; Both, Christiaan; Tinbergen, Joost M

    2009-03-01

    1. An increase of competition among adults or nestlings usually negatively affects breeding output. Yet little is known about the differential effects that competition has on the offspring sexes. This could be important because it may influence parental reproductive decisions. 2. In sexual size dimorphic species, two main contradictory mechanisms are proposed regarding sex-specific effects of competition on nestling performance assuming that parents do not feed their chicks differentially: (i) the larger sex requires more resources to grow and is more sensitive to a deterioration of the rearing conditions ('costly sex hypothesis'); (ii) the larger sex has a competitive advantage in intra-brood competition and performs better under adverse conditions ('competitive advantage hypothesis'). 3. In the present study, we manipulated the level of sex-specific sibling competition in a great tit population (Parus major) by altering simultaneously the brood size and the brood sex ratio on two levels: the nest (competition for food among nestlings) and the woodlot where the parents breed (competition for food among adults). We investigated whether altered competition during the nestling phase affected nestling growth traits and survival in the nest and whether the effects differed between males, the larger sex, and females. 4. We found a strong negative and sex-specific effect of experimental brood size on all the nestling traits. In enlarged broods, sexual size dimorphism was smaller which may have resulted from biased mortality towards the less competitive individuals i.e. females of low condition. No effect of brood sex ratio on nestling growth traits was found. 5. Negative brood size effects on nestling traits were stronger in natural high-density areas but we could not confirm this experimentally. 6. Our results did not support the 'costly sex hypothesis' because males did not suffer from higher mortality under harsh conditions. The 'competitive advantage hypothesis' was

  6. Highly dynamic and sex-specific expression of microRNAs during early ES cell differentiation.

    Directory of Open Access Journals (Sweden)

    Constance Ciaudo

    2009-08-01

    Full Text Available Embryonic stem (ES cells are pluripotent cells derived from the inner cell mass of the mammalian blastocyst. Cellular differentiation entails loss of pluripotency and gain of lineage-specific characteristics. However, the molecular controls that govern the differentiation process remain poorly understood. We have characterized small RNA expression profiles in differentiating ES cells as a model for early mammalian development. High-throughput 454 pyro-sequencing was performed on 19-30 nt RNAs isolated from undifferentiated male and female ES cells, as well as day 2 and 5 differentiating derivatives. A discrete subset of microRNAs (miRNAs largely dominated the small RNA repertoire, and the dynamics of their accumulation could be readily used to discriminate pluripotency from early differentiation events. Unsupervised partitioning around meloids (PAM analysis revealed that differentiating ES cell miRNAs can be divided into three expression clusters with highly contrasted accumulation patterns. PAM analysis afforded an unprecedented level of definition in the temporal fluctuations of individual members of several miRNA genomic clusters. Notably, this unravelled highly complex post-transcriptional regulations of the key pluripotency miR-290 locus, and helped identify miR-293 as a clear outlier within this cluster. Accordingly, the miR-293 seed sequence and its predicted cellular targets differed drastically from those of the other abundant cluster members, suggesting that previous conclusions drawn from whole miR-290 over-expression need to be reconsidered. Our analysis in ES cells also uncovered a striking male-specific enrichment of the miR-302 family, which share the same seed sequence with most miR-290 family members. Accordingly, a miR-302 representative was strongly enriched in embryonic germ cells derived from primordial germ cells of male but not female mouse embryos. Identifying the chromatin remodelling and E2F-dependent transcription

  7. Sex-Specific Habitat Utilization and Differential Breeding Investments in Christmas Island Frigatebirds throughout the Breeding Cycle.

    Directory of Open Access Journals (Sweden)

    Janos C Hennicke

    Full Text Available In seabirds, equal bi-parental care is the rule, as it is considered crucial for raising chicks successfully because seabirds forage in an environment with unpredictable and highly variable food supply. Frigatebirds forage in poor tropical waters, yet males reduce and even stop parental care soon after chick brooding, leaving the female to provision the chick alone for an extended fledging period. Using bird-borne tracking devices, male and female Christmas Island Frigatebirds (Fregata andrewsi were investigated during the brooding, late chick rearing and post-fledging period to examine whether sexes exhibit foraging strategies that may be linked to differential breeding investments. During brooding, males and females showed similar foraging behaviour under average marine productivity of oceanic waters close to the colony, but males shifted to more distant and more productive habitats when conditions deteriorated to continue with reduced chick provisioning. During the late chick rearing period, females progressively increased their foraging range to the more distant but productive marine areas that only males had visited during brooding. Birds spent the non-breeding period roosting in highly productive waters of the Sunda Shelf. The sex-specific utilisation of three different foraging habitats with different primary productivity (oceanic, coastal, and shelf areas allowed for temporal and spatial segregation in the exploitation of favourable habitats which seems to enable each sex to optimise its foraging profitability. In addition, post-fledging foraging movements of females suggest a biennial breeding cycle, while limited information on males suggests the possibility of an annual breeding cycle.

  8. Sex-specific patterns in abundance, temporary emigration and survival of Indo-Pacific bottlenose dolphins (Tursiops aduncus in coastal and estuarine waters

    Directory of Open Access Journals (Sweden)

    Kate R Sprogis

    2016-02-01

    Full Text Available Inherent difficulties in determining the sex of free-ranging sexually monomorphic species often prevents a sex-specific focus on estimating abundance, movement patterns and survival rates. This study provides insights into sex-specific population parameters of Indo-Pacific bottlenose dolphins (Tursiops aduncus. Systematic, boat-based photo-identification surveys (n = 417 were conducted year-round from 2007-2013 in coastal and estuarine waters off Bunbury, Western Australia. Pollock’s Robust Design was used to quantify population parameters for three datasets: i adults and juveniles combined, ii adult females and iii adult males. For all datasets, abundance estimates varied seasonally, with general highs during summer and/or autumn, and lows during winter. Dolphins had seasonally structured temporary emigration rates with similar trends between sexes. The derived return rate (1-γ’ of temporary emigrants into the study area was highest from winter to spring, indicating that dolphins had a high probability of return into the study area during spring. We suggest that the return of dolphins into the study area and increase in abundance is influenced by the breeding season (summer/autumn. Prey availability is likely a main driver responsible for the movement of dolphins out of the study area during winter. Seasonal apparent survival rates were constant and high (0.98-0.99 for all datasets. High apparent survival rates suggest there is no permanent emigration from the study area. Our sex-specific modeling approach offers a comprehensive interpretation of the population dynamics of a top predator in a coastal and estuarine environment and acts as a model for future sex-based population studies on sexually monomorphic species.

  9. Sex-specific hormone receptors in urothelial carcinomas of the human urinary bladder: a comparative analysis of clinicopathological features and survival outcomes according to receptor expression.

    Science.gov (United States)

    Tuygun, Can; Kankaya, Duygu; Imamoglu, Abdurrahim; Sertcelik, Ayse; Zengin, Kursad; Oktay, Murat; Sertcelik, Nurettin

    2011-01-01

    To investigate the expression of sex-specific hormone receptors in normal bladder urothelium and urothelial carcinomas (UCs) of the bladder, and to analyze clinicopathological features and survival outcomes according to receptor expression. We evaluated the clinical data and tumor specimens of 139 patients with bladder cancer (BC). In addition, 72 samples of normal urothelium were included. Immunohistochemistry was performed using streptavidin-biotin peroxidase method, a monoclonal androgen receptor (AR), and an estrogen receptor-β (ERβ) antibody on paraffin-embedded tissue sections. Expression levels of each receptor were assessed by evaluating 500 tumor cells for each case and the percentage of positively-stained nuclei was recorded. None of the 58 male control cases showed any AR and ERβ expression. Five (35, 71%) of the 14 female control cases expressed ERβ. Of the 139 patients with UCs, 71 (51, 07%) expressed AR (62 male vs. 9 female; P = 0.413) and 44 (31, 65%) (39 male vs. 5 female; P = 0.402) showed ERβ expression (P receptors alone cannot be responsible for gender differences in BC rates because they were expressed in similar rates in both sexes. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Sex-specific effects of altered competition on nestling growth and survival : an experimental manipulation of brood size and sex ratio

    NARCIS (Netherlands)

    Nicolaus, Marion; Michler, Stephanie P. M.; Ubels, Richard; van der Velde, Marco; Komdeur, Jan; Both, Christiaan; Tinbergen, Joost M.; Wright, Jonathan

    An increase of competition among adults or nestlings usually negatively affects breeding output. Yet little is known about the differential effects that competition has on the offspring sexes. This could be important because it may influence parental reproductive decisions. In sexual size dimorphic

  11. Eicosapentaenoic Acid and Docosahexaenoic Acid in Whole Blood Are Differentially and Sex-Specifically Associated with Cardiometabolic Risk Markers in 8–11-Year-Old Danish Children

    Science.gov (United States)

    Damsgaard, Camilla T.; Eidner, Maj B.; Stark, Ken D.; Hjorth, Mads F.; Sjödin, Anders; Andersen, Malene R.; Andersen, Rikke; Tetens, Inge; Astrup, Arne; Michaelsen, Kim F.; Lauritzen, Lotte

    2014-01-01

    insulin resistance, and both were inversely associated with heart rate in children. The sex-specific associations with blood pressure confirm our previous findings and warrant further investigation. PMID:25330302

  12. Seasonal Variation in Parental Care Drives Sex-Specific Foraging by a Monomorphic Seabird.

    Science.gov (United States)

    Burke, Chantelle M; Montevecchi, William A; Regular, Paul M

    2015-01-01

    Evidence of sex-specific foraging in monomorphic seabirds is increasing though the underlying mechanisms remain poorly understood. We investigate differential parental care as a mechanism for sex-specific foraging in monomorphic Common Murres (Uria aalge), where the male parent alone provisions the chick after colony departure. Using a combination of geolocation-immersion loggers and stable isotopes, we assess two hypotheses: the reproductive role specialization hypothesis and the energetic constraint hypothesis. We compare the foraging behavior of females (n = 15) and males (n = 9) during bi-parental at the colony, post-fledging male-only parental care and winter when parental care is absent. As predicted by the reproductive role specialization hypothesis, we found evidence of sex-specific foraging during post-fledging only, the stage with the greatest divergence in parental care roles. Single-parenting males spent almost twice as much time diving per day and foraged at lower quality prey patches relative to independent females. This implies a potential energetic constraint for males during the estimated 62.8 ± 8.9 days of offspring dependence at sea. Contrary to the predictions of the energetic constraint hypothesis, we found no evidence of sex-specific foraging during biparental care, suggesting that male parents did not forage for their own benefit before colony departure in anticipation of post-fledging energy constraints. We hypothesize that unpredictable prey conditions at Newfoundland colonies in recent years may limit male parental ability to allocate additional time and energy to self-feeding during biparental care, without compromising chick survival. Our findings support differential parental care as a mechanism for sex-specific foraging in monomorphic murres, and highlight the need to consider ecological context in the interpretation of sex-specific foraging behavior.

  13. Seasonal Variation in Parental Care Drives Sex-Specific Foraging by a Monomorphic Seabird.

    Directory of Open Access Journals (Sweden)

    Chantelle M Burke

    Full Text Available Evidence of sex-specific foraging in monomorphic seabirds is increasing though the underlying mechanisms remain poorly understood. We investigate differential parental care as a mechanism for sex-specific foraging in monomorphic Common Murres (Uria aalge, where the male parent alone provisions the chick after colony departure. Using a combination of geolocation-immersion loggers and stable isotopes, we assess two hypotheses: the reproductive role specialization hypothesis and the energetic constraint hypothesis. We compare the foraging behavior of females (n = 15 and males (n = 9 during bi-parental at the colony, post-fledging male-only parental care and winter when parental care is absent. As predicted by the reproductive role specialization hypothesis, we found evidence of sex-specific foraging during post-fledging only, the stage with the greatest divergence in parental care roles. Single-parenting males spent almost twice as much time diving per day and foraged at lower quality prey patches relative to independent females. This implies a potential energetic constraint for males during the estimated 62.8 ± 8.9 days of offspring dependence at sea. Contrary to the predictions of the energetic constraint hypothesis, we found no evidence of sex-specific foraging during biparental care, suggesting that male parents did not forage for their own benefit before colony departure in anticipation of post-fledging energy constraints. We hypothesize that unpredictable prey conditions at Newfoundland colonies in recent years may limit male parental ability to allocate additional time and energy to self-feeding during biparental care, without compromising chick survival. Our findings support differential parental care as a mechanism for sex-specific foraging in monomorphic murres, and highlight the need to consider ecological context in the interpretation of sex-specific foraging behavior.

  14. Tracking plasma cell differentiation and survival.

    Science.gov (United States)

    Roth, Katrin; Oehme, Laura; Zehentmeier, Sandra; Zhang, Yang; Niesner, Raluca; Hauser, Anja E

    2014-01-01

    Plasma cells play a crucial role for the humoral immune response as they represent the body's factories for antibody production. The differentiation from a B cell into a plasma cell is controlled by a complex transcriptional network and happens within secondary lymphoid organs. Based on their lifetime, two types of antibody secreting cells can be distinguished: Short-lived plasma cells are located in extrafollicular sites of secondary lymphoid organs such as lymph node medullary cords and the splenic red pulp. A fraction of plasmablasts migrate from secondary lymphoid organs to the bone marrow where they can become long-lived plasma cells. Bone marrow plasma cells reside in special microanatomical environments termed survival niches, which provide factors promoting their longevity. Reticular stromal cells producing the chemokine CXCL12, which is known to attract plasmablasts to the bone marrow but also to promote plasma cell survival, play a crucial role in the maintenance of these niches. In addition, hematopoietic cells are contributing to the niches by providing other soluble survival factors. Here, we review the current knowledge on the factors involved in plasma cell differentiation, their localization and migration. We also give an overview on what is known regarding the maintenance of long lived plasma cells in survival niches of the bone marrow. © 2013 International Society for Advancement of Cytometry.

  15. Infant sex-specific placental cadmium and DNA methylation associations

    Energy Technology Data Exchange (ETDEWEB)

    Mohanty, April F., E-mail: april.mohanty@va.gov [Cardiovascular Health Research Unit, University of Washington, 1730 Minor Ave, Seattle, WA 98101 (United States); Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA (United States); Farin, Fred M., E-mail: freddy@u.washington.edu [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, 4225 Roosevelt Way N.E., Suite #100, Seattle, WA 98105 (United States); Bammler, Theo K., E-mail: tbammler@u.washington.edu [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, 4225 Roosevelt Way N.E., Suite #100, Seattle, WA 98105 (United States); MacDonald, James W., E-mail: jmacdon@uw.edu [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, 4225 Roosevelt Way N.E., Suite #100, Seattle, WA 98105 (United States); Afsharinejad, Zahra, E-mail: zafshari@u.washington.edu [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, 4225 Roosevelt Way N.E., Suite #100, Seattle, WA 98105 (United States); Burbacher, Thomas M., E-mail: tmb@uw.edu [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Box: 357234, 1705 N.E. Pacific Street, Seattle, WA 98195 (United States); Siscovick, David S., E-mail: dsiscovick@nyam.org [Cardiovascular Health Research Unit, University of Washington, 1730 Minor Ave, Seattle, WA 98101 (United States); Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA (United States); Department of Medicine, University of Washington, Seattle, WA (United States); and others

    2015-04-15

    Background: Recent evidence suggests that maternal cadmium (Cd) burden and fetal growth associations may vary by fetal sex. However, mechanisms contributing to these differences are unknown. Objectives: Among 24 maternal-infant pairs, we investigated infant sex-specific associations between placental Cd and placental genome-wide DNA methylation. Methods: We used ANOVA models to examine sex-stratified associations of placental Cd (dichotomized into high/low Cd using sex-specific Cd median cutoffs) with DNA methylation at each cytosine-phosphate-guanine site or region. Statistical significance was defined using a false discovery rate cutoff (<0.10). Results: Medians of placental Cd among females and males were 5 and 2 ng/g, respectively. Among females, three sites (near ADP-ribosylation factor-like 9 (ARL9), siah E3 ubiquitin protein ligase family member 3 (SIAH3), and heparin sulfate (glucosamine) 3-O-sulfotransferase 4 (HS3ST4) and one region on chromosome 7 (including carnitine O-octanoyltransferase (CROT) and TP5S target 1 (TP53TG1)) were hypomethylated in high Cd placentas. Among males, high placental Cd was associated with methylation of three sites, two (hypomethylated) near MDS1 and EVI1 complex locus (MECOM) and one (hypermethylated) near spalt-like transcription factor 1 (SALL1), and two regions (both hypomethylated, one on chromosome 3 including MECOM and another on chromosome 8 including rho guanine nucleotide exchange factor (GEF) 10 (ARHGEF10). Differentially methylated sites were at or close to transcription start sites of genes involved in cell damage response (SIAH3, HS3ST4, TP53TG1) in females and cell differentiation, angiogenesis and organ development (MECOM, SALL1) in males. Conclusions: Our preliminary study supports infant sex-specific placental Cd-DNA methylation associations, possibly accounting for previously reported differences in Cd-fetal growth associations across fetal sex. Larger studies are needed to replicate and extend these

  16. Infant sex-specific placental cadmium and DNA methylation associations

    International Nuclear Information System (INIS)

    Mohanty, April F.; Farin, Fred M.; Bammler, Theo K.; MacDonald, James W.; Afsharinejad, Zahra; Burbacher, Thomas M.; Siscovick, David S.

    2015-01-01

    Background: Recent evidence suggests that maternal cadmium (Cd) burden and fetal growth associations may vary by fetal sex. However, mechanisms contributing to these differences are unknown. Objectives: Among 24 maternal-infant pairs, we investigated infant sex-specific associations between placental Cd and placental genome-wide DNA methylation. Methods: We used ANOVA models to examine sex-stratified associations of placental Cd (dichotomized into high/low Cd using sex-specific Cd median cutoffs) with DNA methylation at each cytosine-phosphate-guanine site or region. Statistical significance was defined using a false discovery rate cutoff (<0.10). Results: Medians of placental Cd among females and males were 5 and 2 ng/g, respectively. Among females, three sites (near ADP-ribosylation factor-like 9 (ARL9), siah E3 ubiquitin protein ligase family member 3 (SIAH3), and heparin sulfate (glucosamine) 3-O-sulfotransferase 4 (HS3ST4) and one region on chromosome 7 (including carnitine O-octanoyltransferase (CROT) and TP5S target 1 (TP53TG1)) were hypomethylated in high Cd placentas. Among males, high placental Cd was associated with methylation of three sites, two (hypomethylated) near MDS1 and EVI1 complex locus (MECOM) and one (hypermethylated) near spalt-like transcription factor 1 (SALL1), and two regions (both hypomethylated, one on chromosome 3 including MECOM and another on chromosome 8 including rho guanine nucleotide exchange factor (GEF) 10 (ARHGEF10). Differentially methylated sites were at or close to transcription start sites of genes involved in cell damage response (SIAH3, HS3ST4, TP53TG1) in females and cell differentiation, angiogenesis and organ development (MECOM, SALL1) in males. Conclusions: Our preliminary study supports infant sex-specific placental Cd-DNA methylation associations, possibly accounting for previously reported differences in Cd-fetal growth associations across fetal sex. Larger studies are needed to replicate and extend these

  17. Survival and death causes in differentiated thyroid carcinoma

    NARCIS (Netherlands)

    Eustatia-Rutten, Carmen F. A.; Corssmit, Eleonora P. M.; Biermasz, Nienke R.; Pereira, Alberto M.; Romijn, Johannes A.; Smit, Johannes W.

    2006-01-01

    Survival studies in differentiated thyroid carcinoma (DTC) may be biased because they have been performed in heterogeneous populations. In addition, specific death causes in DTC have not been documented well in the literature. The aim of our study was to investigate survival and specific death

  18. Anthropogenic impacts on Costa Rican bat parasitism are sex specific.

    Science.gov (United States)

    Frank, Hannah K; Mendenhall, Chase D; Judson, Seth D; Daily, Gretchen C; Hadly, Elizabeth A

    2016-07-01

    While anthropogenic impacts on parasitism of wildlife are receiving growing attention, whether these impacts vary in a sex-specific manner remains little explored. Differences between the sexes in the effect of parasites, linked to anthropogenic activity, could lead to uneven sex ratios and higher population endangerment. We sampled 1108 individual bats in 18 different sites across an agricultural mosaic landscape in southern Costa Rica to investigate the relationships between anthropogenic impacts (deforestation and reductions in host species richness) and bat fly ectoparasitism of 35 species of Neotropical bats. Although female and male bat assemblages were similar across the deforestation gradient, bat fly assemblages tracked their hosts closely only on female bats. We found that in female hosts, parasite abundance per bat decreased with increasing bat species richness, while in male hosts, parasite abundance increased. We hypothesize the differences in the parasite-disturbance relationship are due to differences in roosting behavior between the sexes. We report a sex-specific parasite-disturbance relationship and argue that sex differences in anthropogenic impacts on wildlife parasitism could impact long-term population health and survival.

  19. Stage- and sex-specific heat tolerance in the yellow dung fly Scathophaga stercoraria.

    Science.gov (United States)

    Blanckenhorn, Wolf U; Gautier, Roland; Nick, Marcel; Puniamoorthy, Nalini; Schäfer, Martin A

    2014-12-01

    Thermal tolerance varies at all hierarchical levels of biological organization: among species, populations, individuals, and even within individuals. Age- or developmental stage- and sex-specific thermal effects have received relatively little attention in the literature, despite being crucial for understanding thermal adaptation in nature and responses to global warming. We document stage- and sex- specific heat tolerance in the yellow dung fly Scathophaga stercoraria (Diptera: Scathophagidae), a species common throughout the northern hemisphere that generally favours cool climates. Exposure of eggs to temperatures up to 32°C did not affect larval hatching rate, but subsequent egg-to-adult survival at a benign temperature was reduced. Permanent transfer from benign (18°C) to hot temperatures (up to 31°C) at different larval and pupal stages strongly decreased egg-to-adult survival, though survival continuously improved the later the transfer occurred. Temporary transfer for only two days increased mortality more weakly, survival being lowest when temperature stress was imposed early during the larval or pupal stages. Adult flies provided with sugar and water tolerated 31°C longer than previously thought (5 days in males to 9 days in females). Eggs were thus less susceptible to thermal stress than larvae, pupae or adults, in agreement with the hypothesis that more mobile stages require less physiological protection against heat because they can behaviourally thermoregulate. The probability of mating, of laying a clutch, and hatching success were generally independently reduced by exposure of females or males to warm temperatures (24°C) during the juvenile or adult stages, with some interactions evident. High temperature stress thus affects survival differentially depending on when it occurs during the juvenile or the pre-reproductive adult life stage, and affects reproductive success via the mating behaviour of both sexes, female physiology in terms of

  20. Sex-specific selection under environmental stress in seed beetles.

    Science.gov (United States)

    Martinossi-Allibert, I; Arnqvist, G; Berger, D

    2017-01-01

    Sexual selection can increase rates of adaptation by imposing strong selection in males, thereby allowing efficient purging of the mutation load on population fitness at a low demographic cost. Indeed, sexual selection tends to be male-biased throughout the animal kingdom, but little empirical work has explored the ecological sensitivity of this sex difference. In this study, we generated theoretical predictions of sex-specific strengths of selection, environmental sensitivities and genotype-by-environment interactions and tested them in seed beetles by manipulating either larval host plant or rearing temperature. Using fourteen isofemale lines, we measured sex-specific reductions in fitness components, genotype-by-environment interactions and the strength of selection (variance in fitness) in the juvenile and adult stage. As predicted, variance in fitness increased with stress, was consistently greater in males than females for adult reproductive success (implying strong sexual selection), but was similar in the sexes in terms of juvenile survival across all levels of stress. Although genetic variance in fitness increased in magnitude under severe stress, heritability decreased and particularly so in males. Moreover, genotype-by-environment interactions for fitness were common but specific to the type of stress, sex and life stage, suggesting that new environments may change the relative alignment and strength of selection in males and females. Our study thus exemplifies how environmental stress can influence the relative forces of natural and sexual selection, as well as concomitant changes in genetic variance in fitness, which are predicted to have consequences for rates of adaptation in sexual populations. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

  1. Sex-specific gonadal and gene expression changes throughout development in fathead minnow

    Science.gov (United States)

    Although fathead minnows (Pimephales promelas) are commonly used as a model fish in endocrine disruption studies, none have characterized sex-specific baseline expression of genes involved in sex differentiation during development in this species. Using a sex-linked DNA marker t...

  2. Conservation and sex-specific splicing of the doublesex gene

    Indian Academy of Sciences (India)

    Genetic control of sex determination in insects has been best characterized in Drosophila melanogaster, where the master gene Sxl codes for RNA that is sex specifically spliced to produce a functional protein only in females. SXL regulates the sex-specific splicing of transformer (tra) RNA which, in turn, regulates the ...

  3. A sex-specific metabolite identified in a marine invertebrate utilizing phosphorus-31 nuclear magnetic resonance.

    Directory of Open Access Journals (Sweden)

    Robert A Kleps

    Full Text Available Hormone level differences are generally accepted as the primary cause for sexual dimorphism in animal and human development. Levels of low molecular weight metabolites also differ between men and women in circulating amino acids, lipids and carbohydrates and within brain tissue. While investigating the metabolism of blue crab tissues using Phosphorus-31 Nuclear Magnetic Resonance, we discovered that only the male blue crab (Callinectes sapidus contained a phosphorus compound with a chemical shift well separated from the expected phosphate compounds. Spectra obtained from male gills were readily differentiated from female gill spectra. Analysis from six years of data from male and female crabs documented that the sex-specificity of this metabolite was normal for this species. Microscopic analysis of male and female gills found no differences in their gill anatomy or the presence of parasites or bacteria that might produce this phosphorus compound. Analysis of a rare gynandromorph blue crab (laterally, half male and half female proved that this sex-specificity was an intrinsic biochemical process and was not caused by any variations in the diet or habitat of male versus female crabs. The existence of a sex-specific metabolite is a previously unrecognized, but potentially significant biochemical phenomenon. An entire enzyme system has been synthesized and activated only in one sex. Unless blue crabs are a unique species, sex-specific metabolites are likely to be present in other animals. Would the presence or absence of a sex-specific metabolite affect an animal's development, anatomy and biochemistry?

  4. HDAC inhibitors: modulating leukocyte differentiation, survival, proliferation and inflammation.

    Science.gov (United States)

    Sweet, Matthew J; Shakespear, Melanie R; Kamal, Nabilah A; Fairlie, David P

    2012-01-01

    Therapeutic effects of histone deacetylase (HDAC) inhibitors in cancer models were first linked to their ability to cause growth arrest and apoptosis of tumor cells. It is now clear that these agents also have pleiotropic effects on angiogenesis and the immune system, and some of these properties are likely to contribute to their anti-cancer activities. It is also emerging that inhibitors of specific HDACs affect the differentiation, survival and/or proliferation of distinct immune cell populations. This is true for innate immune cells such as macrophages, as well as cells of the acquired immune system, for example, T-regulatory cells. These effects may contribute to therapeutic profiles in some autoimmune and chronic inflammatory disease models. Here, we review our current understanding of how classical HDACs (HDACs 1-11) and their inhibitors impact on differentiation, survival and proliferation of distinct leukocyte populations, as well as the likely relevance of these effects to autoimmune and inflammatory disease processes. The ability of HDAC inhibitors to modulate leukocyte survival may have implications for the rationale of developing selective inhibitors as anti-inflammatory drugs.

  5. Sex-Specific Neurotoxic Effects of Organophosphate Pesticides Across the Life Course.

    Science.gov (United States)

    Comfort, Nicole; Re, Diane B

    2017-12-01

    This review discusses the sex-specific effects of exposure to various organophosphate (OP) pesticides throughout the life course and potential reasons for the differential vulnerabilities observed across sexes. Sex is a crucial factor in the response to toxicants, yet the sex-specific effects of OP exposure, particularly in juveniles and adults, remain unresolved. This is largely due to study design and inconsistencies in exposure and outcome assessments. Exposure to OPs results in multiple adverse outcomes influenced by many factors including sex. Reported sex-specific effects suggest that males are more susceptible to OPs, which reflects the sex-dependent prevalence of various neurodevelopmental and neurodegenerative disorders such as autism and amyotrophic lateral sclerosis (ALS), in which males are at greater risk. Thus, this review proposes that the biological sex-specific effects elicited by OP exposure may in part underlie the dimorphic susceptibilities observed in neurological disorders. Understanding the immediate and long-term effects of OP exposure across sexes will be critical in advancing our understanding of OP-induced neurotoxicity and disease.

  6. Sex-specific differences in transcriptome profiles of brain and muscle tissue of the tropical gar.

    Science.gov (United States)

    Cribbin, Kayla M; Quackenbush, Corey R; Taylor, Kyle; Arias-Rodriguez, Lenin; Kelley, Joanna L

    2017-04-07

    The tropical gar (Atractosteus tropicus) is the southernmost species of the seven extant species of gar fishes in the world. In Mexico and Central America, the species is an important food source due to its nutritional quality and low price. Despite its regional importance and increasing concerns about overexploitation and habitat degradation, basic genetic information on the tropical gar is lacking. Determining genetic information on the tropical gar is important for the sustainable management of wild populations, implementation of best practices in aquaculture settings, evolutionary studies of ancient lineages, and an understanding of sex-specific gene expression. In this study, the transcriptome of the tropical gar was sequenced and assembled de novo using tissues from three males and three females using Illumina sequencing technology. Sex-specific and highly differentially expressed transcripts in brain and muscle tissues between adult males and females were subsequently identified. The transcriptome was assembled de novo resulting in 80,611 transcripts with a contig N50 of 3,355 base pairs and over 168 kilobases in total length. Male muscle, brain, and gonad as well as female muscle and brain were included in the assembly. The assembled transcriptome was annotated to identify the putative function of expressed transcripts using Trinotate and SwissProt, a database of well-annotated proteins. The brain and muscle datasets were then aligned to the assembled transcriptome to identify transcripts that were differentially expressed between males and females. The contrast between male and female brain identified 109 transcripts from 106 genes that were significantly differentially expressed. In the muscle comparison, 82 transcripts from 80 genes were identified with evidence for significant differential expression. Almost all genes identified as differentially expressed were sex-specific. The differentially expressed transcripts were enriched for genes involved in

  7. Sex-specific hippocampal 5-hydroxymethylcytosine is disrupted in response to acute stress.

    Science.gov (United States)

    Papale, Ligia A; Li, Sisi; Madrid, Andy; Zhang, Qi; Chen, Li; Chopra, Pankaj; Jin, Peng; Keleş, Sündüz; Alisch, Reid S

    2016-12-01

    Environmental stress is among the most important contributors to increased susceptibility to develop psychiatric disorders. While it is well known that acute environmental stress alters gene expression, the molecular mechanisms underlying these changes remain largely unknown. 5-hydroxymethylcytosine (5hmC) is a novel environmentally sensitive epigenetic modification that is highly enriched in neurons and is associated with active neuronal transcription. Recently, we reported a genome-wide disruption of hippocampal 5hmC in male mice following acute stress that was correlated to altered transcript levels of genes in known stress related pathways. Since sex-specific endocrine mechanisms respond to environmental stimulus by altering the neuronal epigenome, we examined the genome-wide profile of hippocampal 5hmC in female mice following exposure to acute stress and identified 363 differentially hydroxymethylated regions (DhMRs) linked to known (e.g., Nr3c1 and Ntrk2) and potentially novel genes associated with stress response and psychiatric disorders. Integration of hippocampal expression data from the same female mice found stress-related hydroxymethylation correlated to altered transcript levels. Finally, characterization of stress-induced sex-specific 5hmC profiles in the hippocampus revealed 778 sex-specific acute stress-induced DhMRs some of which were correlated to altered transcript levels that produce sex-specific isoforms in response to stress. Together, the alterations in 5hmC presented here provide a possible molecular mechanism for the adaptive sex-specific response to stress that may augment the design of novel therapeutic agents that will have optimal effectiveness in each sex. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Sex-specific asymmetry in eye development in interspecific hybrids ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 94; Issue 3. Sex-specific asymmetry in eye development in interspecific hybrids in the Drosophila bipectinata species complex. Bashisth N. Singh Parul Banerjee. Research Note Volume 94 Issue 3 September 2015 pp 493-495 ...

  9. Sex-specific inhibition and stimulation of worker-reproductive transition in a termite

    Science.gov (United States)

    Sun, Qian; Haynes, Kenneth F.; Hampton, Jordan D.; Zhou, Xuguo

    2017-10-01

    In social insects, the postembryonic development of individuals exhibits strong phenotypic plasticity in response to the environment, thus generating the caste system. Different from eusocial Hymenoptera, in which queens dominate reproduction and inhibit worker fertility, the primary reproductive caste in termites (kings and queens) can be replaced by neotenic reproductives derived from functionally sterile individuals. Feedback regulation of nestmate differentiation into reproductives has been suggested, but the sex specificity remains inconclusive. In the eastern subterranean termite, Reticulitermes flavipes, we tested the hypothesis that neotenic reproductives regulate worker-reproductive transition in a sex-specific manner. With this R. flavipes system, we demonstrate a sex-specific regulatory mechanism with both inhibitory and stimulatory functions. Neotenics inhibit workers of the same sex from differentiating into additional reproductives but stimulate workers of the opposite sex to undergo this transition. Furthermore, this process is not affected by the presence of soldiers. Our results highlight the reproductive plasticity of termites in response to social cues and provide insights into the regulation of reproductive division of labor in a hemimetabolous social insect.

  10. Sex-Specific Associations Between Thyrotropin and Serum Lipid Profiles

    DEFF Research Database (Denmark)

    Meisinger, Christa; Ittermann, Till; Tiller, Daniel

    2014-01-01

    BACKGROUND: Population-based studies investigating the sex-specific association between thyrotropin (TSH) levels and serum lipid concentrations are scarce. We examined the association between TSH and total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL......) cholesterol, and triglycerides in men and women from the general population. Furthermore, the association with TSH outside and within the reference range and lipid levels was studied. METHODS: Individual data of 13,571 men and women without lipid medication of four population-based studies conducted...... in Western European adults were pooled for cross-sectional analyses. The association between TSH levels and lipid concentrations were analyzed by calculating sex-specific multivariable median regression models. RESULTS: In the pooled population, serum TSH levels were significantly positively associated...

  11. Sex-specific differences in injury types among basketball players

    OpenAIRE

    Ito E; Iwamoto J; Azuma K; Matsumoto H

    2014-01-01

    Eri Ito, Jun Iwamoto, Koichiro Azuma, Hideo MatsumotoInstitute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, JapanAbstract: The purpose of the present study was to investigate sex-specific differences in injury types among basketball players. According to our database, during the 20-year period between October 1991 and June 2011, 1,219 basketball players (640 males and 579 females) consulted our sports medicine clinic; in total, 1,414 injuries in basketball player...

  12. Sex-specific mechanism of social hierarchy in mice.

    Science.gov (United States)

    van den Berg, Wouter E; Lamballais, Sander; Kushner, Steven A

    2015-05-01

    The establishment of social hierarchies is a naturally occurring, evolutionarily conserved phenomenon with a well-established impact on fitness and health. Investigations of complex social group dynamics may offer novel opportunities for translational studies of autism spectrum disorder. Here we describe a robust behavioral paradigm using an automated version of the tube test. Isogenic groups of male and female mice establish linear social hierarchies that remain highly stable for at least 14 days, the longest interval tested. Remarkably, however, their social strategy is sex-specific: females primarily utilize intrinsic attributes, whereas males are strongly influenced by prior social experience. Using both genetic and pharmacological manipulations, we identify testosterone as a critical sex-specific factor for determining which social strategy is used. Males inheriting a null mutation of the sex-determining region Y (Sry) gene used a similar social cognitive strategy as females. In contrast, females with transgenic expression of Sry utilized a typically male social strategy. Analogously, castration of males and testosterone supplementation of females yielded similar outcomes, with a reversal of their social cognitive strategy. Together, our results demonstrate a sex-specific mechanism underlying social hierarchy, in which both males and females retain the functional capacity to adapt their social strategy. More generally, we expect the automated tube test to provide an important complementary approach for both fundamental and translational studies of social behavior.

  13. Food stress causes sex-specific maternal effects in mites.

    Science.gov (United States)

    Walzer, Andreas; Schausberger, Peter

    2015-08-01

    Life history theory predicts that females should produce few large eggs under food stress and many small eggs when food is abundant. We tested this prediction in three female-biased size-dimorphic predatory mites feeding on herbivorous spider mite prey: Phytoseiulus persimilis, a specialized spider mite predator; Neoseiulus californicus, a generalist preferring spider mites; Amblyseius andersoni, a broad diet generalist. Irrespective of predator species and offspring sex, most females laid only one small egg under severe food stress. Irrespective of predator species, the number of female but not male eggs decreased with increasing maternal food stress. This sex-specific effect was probably due to the higher production costs of large female than small male eggs. The complexity of the response to the varying availability of spider mite prey correlated with the predators' degree of adaptation to this prey. Most A. andersoni females did not oviposit under severe food stress, whereas N. californicus and P. persimilis did oviposit. Under moderate food stress, only P. persimilis increased its investment per offspring, at the expense of egg number, and produced few large female eggs. When prey was abundant, P. persimilis decreased the female egg sizes at the expense of increased egg numbers, resulting in a sex-specific egg size/number trade-off. Maternal effects manifested only in N. californicus and P. persimilis. Small egg size correlated with the body size of daughters but not sons. Overall, our study provides a key example of sex-specific maternal effects, i.e. food stress during egg production more strongly affects the sex of the large than the small offspring. © 2015. Published by The Company of Biologists Ltd.

  14. Sex-Specificity in the Reward Value of Facial Attractiveness.

    Science.gov (United States)

    Hahn, Amanda C; Fisher, Claire I; DeBruine, Lisa M; Jones, Benedict C

    2016-05-01

    Studies of the sex-specificity of sexual arousal in adults (i.e., the tendency to respond more strongly to preferred-sex individuals than non-preferred sex individuals) have suggested that heterosexual men, homosexual men, and homosexual women show stronger sex-specific responses than do heterosexual women. Evidence for a similar pattern of results in studies investigating the reward value of faces is equivocal. Consequently, we investigated the effects of (1) sexual orientation (homosexual vs. heterosexual), (2) sex (male vs. female), (3) image sex (preferred-sex vs. non-preferred-sex), and (4) the physical attractiveness of the individual shown in the image on the reward value of faces. Participants were 130 heterosexual men, 130 homosexual men, 130 heterosexual women, and 130 homosexual women. The reward value of faces was assessed using a standard key-press task. Multilevel modeling of responses indicated that images of preferred-sex individuals were more rewarding than images of non-preferred-sex individuals and that this preferred-sex bias was particularly pronounced when more physically attractive faces were presented. These effects were not qualified by interactions involving either the sexual orientation or the sex of our participants, however, suggesting that the preferred-sex bias in the reward value of faces is similar in heterosexual men, homosexual men, heterosexual women, and homosexual women.

  15. Sex-specific mechanisms for responding to stress.

    Science.gov (United States)

    Bangasser, Debra A; Wicks, Brittany

    2017-01-02

    Posttraumatic stress disorder and major depression share stress as an etiological contributor and are more common in women than in men. Traditionally, preclinical studies investigating the neurobiological underpinnings of stress vulnerability have used only male rodents; however, recent studies that include females are finding sex-specific mechanisms for responding to stress. This Mini-Review examines recent literature using a framework developed by McCarthy and colleagues (2012; J Neurosci 32:2241-2247) that highlights different types of sex differences. First, we detail how learned fear responses in rats are sexually dimorphic. Then, we contrast this finding with fear extinction, which is similar in males and females at the behavioral level but at the circuitry level is associated with sex-specific cellular changes and, thus, exemplifies a sex convergence. Next, sex differences in stress hormones are detailed. Finally, the effects of stress on learning, attention, and arousal are used to highlight the concept of a sex divergence in which the behavior of males and females is similar at baseline but diverges following stressor exposure. We argue that appreciating and investigating the diversity of sex differences in stress response systems will improve our understanding of vulnerability and resilience to stress-related psychiatric disorders and likely lead to the development of novel therapeutics for better treatment of these disorders in both men and women. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Sex-specific lifespan and its evolution in nematodes.

    Science.gov (United States)

    Ancell, Henry; Pires-daSilva, Andre

    2017-10-01

    Differences between sexes of the same species in lifespan and aging rate are widespread. While the proximal and evolutionary causes of aging are well researched, the factors that contribute to sex differences in these traits have been less studied. The striking diversity of nematodes provides ample opportunity to study variation in sex-specific lifespan patterns associated with shifts in life history and mating strategy. Although the plasticity of these sex differences will make it challenging to generalize from invertebrate to vertebrate systems, studies in nematodes have enabled empirical evaluation of predictions regarding the evolution of lifespan. These studies have highlighted how natural and sexual selection can generate divergent patterns of lifespan if the sexes are subject to different rates or sources of mortality, or if trade-offs between complex traits and longevity are resolved differently in each sex. Here, we integrate evidence derived mainly from nematodes that addresses the molecular and evolutionary basis of sex-specific aging and lifespan. Ultimately, we hope to generate a clearer picture of current knowledge in this area, and also highlight the limitations of our understanding. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Sex-specific determinants of fitness in a social mammal.

    Science.gov (United States)

    Lardy, Sophie; Allainé, Dominique; Bonenfant, Christophe; Cohas, Aurélie

    2015-11-01

    Sociality should evolve when the fitness benefits of group living outweigh the costs. Theoretical models predict an optimal group size maximizing individual fitness. However, beyond the number of individuals present in a group, the characteristics of these individuals, like their sex, are likely to affect the fitness payoffs of group living. Using 20 years of individually based data on a social mammal, the Alpine marmot (Marmota marmota), we tested for the occurrence of an optimal group size and composition, and for sex-specific effects of group characteristics on fitness. Based on lifetime data of 52 males and 39 females, our findings support the existence of an optimal group size maximizing male fitness and an optimal group composition maximizing fitness of males and females. Additionally, although group characteristics (i.e., size, composition and instability) affecting male and female fitness differed, fitness depended strongly on the number of same-sex subordinates within the social group in the two sexes. By comparing multiple measures of social group characteristics and of fitness in both sexes, we highlighted the sex-specific determinants of fitness in the two sexes and revealed the crucial role of intrasexual competition in shaping social group composition.

  18. Survival at the Center - The Stability of Minimum Differentiation

    OpenAIRE

    Hehenkamp , Burkhard; Wambach , Achim

    2010-01-01

    International audience; We model a Hotelling market with multidimensional product differentiation in an evolutionary framework. Both evolutionary stability (in the sense of Schaffer, 1989) and stochastic stability (following Kandori et al., 1993, and Young, 1993) are analysed. It is shown that firms move towards the center in product space, i.e. a "principle of minimum differentiation" on all dimensions of the product space applies.

  19. The role of metallothionein II in neuronal differentiation and survival

    DEFF Research Database (Denmark)

    Køhler, Lene B; Berezin, Vladimir; Bock, Elisabeth

    2003-01-01

    -I+II can affect neurons directly. It is likely that MT isoforms could be beneficial also during neurodegenerative disorders. In this study, we have examined if MT-II affects survival and neurite extension of dopaminergic and hippocampal neurons. We show for the first time that MT-II treatment can....... Accordingly, treatment with MT-II may be of therapeutic value in neurodegenerative disorders....

  20. Sex-specific genetic diversity is shaped by cultural factors in Inner Asian human populations.

    Science.gov (United States)

    Marchi, Nina; Hegay, Tatyana; Mennecier, Philippe; Georges, Myriam; Laurent, Romain; Whitten, Mark; Endicott, Philipp; Aldashev, Almaz; Dorzhu, Choduraa; Nasyrova, Firuza; Chichlo, Boris; Ségurel, Laure; Heyer, Evelyne

    2017-04-01

    Sex-specific genetic structures have been previously documented worldwide in humans, even though causal factors have not always clearly been identified. In this study, we investigated the impact of ethnicity, geography and social organization on the sex-specific genetic structure in Inner Asia. Furthermore, we explored the process of ethnogenesis in multiple ethnic groups. We sampled DNA in Central and Northern Asia from 39 populations of Indo-Iranian and Turkic-Mongolic native speakers. We focused on genetic data of the Y chromosome and mitochondrial DNA. First, we compared the frequencies of haplogroups to South European and East Asian populations. Then, we investigated the genetic differentiation for eight Y-STRs and the HVS1 region, and tested for the effect of geography and ethnicity on such patterns. Finally, we reconstructed the male demographic history, inferred split times and effective population sizes of different ethnic groups. Based on the haplogroup data, we observed that the Indo-Iranian- and Turkic-Mongolic-speaking populations have distinct genetic backgrounds. However, each population showed consistent mtDNA and Y chromosome haplogroups patterns. As expected in patrilocal populations, we found that the Y-STRs were more structured than the HVS1. While ethnicity strongly influenced the genetic diversity on the Y chromosome, geography better explained that of the mtDNA. Furthermore, when looking at various ethnic groups, we systematically found a genetic split time older than historical records, suggesting a cultural rather than biological process of ethnogenesis. This study highlights that, in Inner Asia, specific cultural behaviors, especially patrilineality and patrilocality, leave a detectable signature on the sex-specific genetic structure. © 2017 Wiley Periodicals, Inc.

  1. Developmental trajectories of paediatric headache - sex-specific analyses and predictors.

    Science.gov (United States)

    Isensee, Corinna; Fernandez Castelao, Carolin; Kröner-Herwig, Birgit

    2016-01-01

    Headache is the most common pain disorder in children and adolescents and is associated with diverse dysfunctions and psychological symptoms. Several studies evidenced sex-specific differences in headache frequency. Until now no study exists that examined sex-specific patterns of change in paediatric headache across time and included pain-related somatic and (socio-)psychological predictors. Latent Class Growth Analysis (LCGA) was used in order to identify different trajectory classes of headache across four annual time points in a population-based sample (n = 3 227; mean age 11.34 years; 51.2 % girls). In multinomial logistic regression analyses the influence of several predictors on the class membership was examined. For girls, a four-class model was identified as the best fitting model. While the majority of girls reported no (30.5 %) or moderate headache frequencies (32.5 %) across time, one class with a high level of headache days (20.8 %) and a class with an increasing headache frequency across time (16.2 %) were identified. For boys a two class model with a 'no headache class' (48.6 %) and 'moderate headache class' (51.4 %) showed the best model fit. Regarding logistic regression analyses, migraine and parental headache proved to be stable predictors across sexes. Depression/anxiety was a significant predictor for all pain classes in girls. Life events, dysfunctional stress coping and school burden were also able to differentiate at least between some classes in both sexes. The identified trajectories reflect sex-specific differences in paediatric headache, as seen in the number and type of classes extracted. The documented risk factors can deliver ideas for preventive actions and considerations for treatment programmes.

  2. Sex-Specific Response to Stress in Populus

    Directory of Open Access Journals (Sweden)

    Nataliya V. Melnikova

    2017-10-01

    Full Text Available Populus is an effective model for genetic studies in trees. The genus Populus includes dioecious species, and the differences exhibited in males and females have been intensively studied. This review focused on the distinctions between male and female poplar and aspen plants under stress conditions, such as drought, salinity, heavy metals, and nutrient deficiency on morphological, physiological, proteome, and gene expression levels. In most studies, males of Populus species were more adaptive to the majority of the stress conditions and showed less damage, better growth, and higher photosynthetic capacity and antioxidant activity than that of the females. However, in two recent studies, no differences in non-reproductive traits were revealed for male and female trees. This discrepancy of the results could be associated with experimental design: different species and genotypes, stress conditions, types of plant materials, sampling sizes. Knowledge of sex-specific differences is crucial for basic and applied research in Populus species.

  3. Sex-specific differences in injury types among basketball players.

    Science.gov (United States)

    Ito, Eri; Iwamoto, Jun; Azuma, Koichiro; Matsumoto, Hideo

    2015-01-01

    The purpose of the present study was to investigate sex-specific differences in injury types among basketball players. According to our database, during the 20-year period between October 1991 and June 2011, 1,219 basketball players (640 males and 579 females) consulted our sports medicine clinic; in total, 1,414 injuries in basketball players (729 injuries in males and 685 injuries in females) were recorded. The mean age of patients was 19.6 years. The most common injury site was the knee, followed by the foot and ankle, lower back, and upper extremities. There was a higher proportion of female players presenting with a knee injury, compared with male players (50.4% vs 41.7%), and a lower proportion of female players presenting with an upper extremity injury (5.1% vs 9.7%). The proportion of anterior cruciate ligament injury in the 10-19-year-old age group was higher among female players than among male players (45.9% vs 22.1%), while the proportions of Osgood-Schlatter disease in the 10-19-year-old age group and jumper's knee (patellar and femoral tendinopathy) in the 20-29-year-old age group were higher among male players than among female players (12.5% vs 1.8% and 14.6% vs 3.7%, respectively). However, the proportions of other injuries did not differ significantly between male and female players. The present observational study, which was performed using a retrospective case-series design, showed the existence of sex-specific differences in knee injuries sustained while participating in basketball.

  4. Passive limb movement: evidence of mechanoreflex sex specificity.

    Science.gov (United States)

    Ives, Stephen J; McDaniel, John; Witman, Melissa A H; Richardson, Russell S

    2013-01-01

    Previous studies have determined that premenopausal women exhibit an attenuated metaboreflex; however, little is known about sex specificity of the mechanoreflex. Thus, we sought to determine if sex differences exist in the central and peripheral hemodynamic responses to passive limb movement. Second-by-second measurements of heart rate, stroke volume, cardiac output (CO), mean arterial pressure, and femoral artery blood flow (FBF) were recorded during 3 min of supine passive knee extension in 24 young healthy subjects (12 women and 12 men). Normalization of CO and stroke volume to body surface area, expressed as cardiac index and stroke index, eliminated differences in baseline central hemodynamics, whereas, peripherally, basal FBF and femoral vascular conductance were similar between the sexes. In response to passive limb movement, women displayed significantly attenuated peak central hemodynamic responses compared with men (heart rate: 9.0 ± 1 vs. 14.8 ± 2% change, stroke index: 4.5 ± 0.6 vs. 7.8 ± 1.2% change, cardiac index: 9.6 ± 1 vs. 17.2 ± 2% change, all P movement induced similar increases in peak FBF (167 ± 32 vs. 193 ± 17% change) and femoral vascular conductance (172 ± 31 vs. 203 ± 16% change) in both sexes (women vs. men, respectively). Additionally, there was a significant positive relationship between individual peak FBF and peak CO response to passive movement in men but not in women. Thus, although both sexes exhibited similar movement-induced hyperemia and peripheral vasodilatory function, the central hemodynamic response was blunted in women, implying an attenuated mechanoreflex. Therefore, this study reveals that, as already recognized with the metaboreflex, there is likely a sex-specific attenuation of the mechanoreflex in women.

  5. Sex-specific differences in injury types among basketball players

    Directory of Open Access Journals (Sweden)

    Ito E

    2014-12-01

    Full Text Available Eri Ito, Jun Iwamoto, Koichiro Azuma, Hideo MatsumotoInstitute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, JapanAbstract: The purpose of the present study was to investigate sex-specific differences in injury types among basketball players. According to our database, during the 20-year period between October 1991 and June 2011, 1,219 basketball players (640 males and 579 females consulted our sports medicine clinic; in total, 1,414 injuries in basketball players (729 injuries in males and 685 injuries in females were recorded. The mean age of patients was 19.6 years. The most common injury site was the knee, followed by the foot and ankle, lower back, and upper extremities. There was a higher proportion of female players presenting with a knee injury, compared with male players (50.4% vs 41.7%, and a lower proportion of female players presenting with an upper extremity injury (5.1% vs 9.7%. The proportion of anterior cruciate ligament injury in the 10–19-year-old age group was higher among female players than among male players (45.9% vs 22.1%, while the proportions of Osgood–Schlatter disease in the 10–19-year-old age group and jumper's knee (patellar and femoral tendinopathy in the 20–29-year-old age group were higher among male players than among female players (12.5% vs 1.8% and 14.6% vs 3.7%, respectively. However, the proportions of other injuries did not differ significantly between male and female players. The present observational study, which was performed using a retrospective case-series design, showed the existence of sex-specific differences in knee injuries sustained while participating in basketball.Keywords: sports injury, sex, anterior cruciate ligament injury, Osgood–Schlatter disease, basketball

  6. Temporal and sex-specific variability in Rhinoceros Auklet diet in the central California Current system

    Science.gov (United States)

    Carle, Ryan D.; Beck, Jessie N.; Calleri, David M.; Hester, Michelle M.

    2015-06-01

    We used stable isotopes (δ15N and δ13C) and compared prey provided to chicks by each sex to evaluate seasonal and sex-specific diets in Rhinoceros Auklets (Cerorhinca monocerata) in the central California Current system during 2012-2013. Mixing models indicated northern anchovy (Engraulis mordax) were important prey for adults during fall/winter and juvenile rockfishes (Sebastes spp.) were important prey during incubation both years. Adult trophic level increased between incubation and chick-rearing periods in both years. During 2012, δ15N and δ13C of chick-rearing males and females differed significantly; mixing models indicated that females ate more Pacific saury (Cololabis saira) and less market squid (Doryteuthis opalescens) than males. Likewise, females delivered significantly more Pacific saury and less market squid to chicks than males during 2012. Chick growth (g d- 1) and chick survival to fledging were significantly lower during 2012 than 2013, likely because chicks were fed lesser quality prey or fed less frequently in 2012. Lesser body mass of females during incubation in 2012 indicated sex-specific diet differences may have been related to female energetic constraints. The observed variability in Rhinoceros Auklet diet underscores the importance of managing multiple prey populations in this system so that generalist predators have sufficient resources through changing conditions.

  7. STAT signaling in mammary gland differentiation, cell survival and tumorigenesis

    OpenAIRE

    Haricharan, S; Li, Y

    2013-01-01

    The mammary gland is a unique organ that undergoes extensive and profound changes during puberty, menstruation, pregnancy, lactation and involution. The changes that take place during puberty involve large-scale proliferation and invasion of the fat-pad. During pregnancy and lactation, the mammary cells are exposed to signaling pathways that inhibit apoptosis, induce proliferation and invoke terminal differentiation. Finally, during involution the mammary gland is exposed to milk stasis, prog...

  8. Sex linkage, sex-specific selection, and the role of recombination in the evolution of sexually dimorphic gene expression.

    Science.gov (United States)

    Connallon, Tim; Clark, Andrew G

    2010-12-01

    Sex-biased genes--genes that are differentially expressed within males and females--are nonrandomly distributed across animal genomes, with sex chromosomes and autosomes often carrying markedly different concentrations of male- and female-biased genes. These linkage patterns are often gene- and lineage-dependent, differing between functional genetic categories and between species. Although sex-specific selection is often hypothesized to shape the evolution of sex-linked and autosomal gene content, population genetics theory has yet to account for many of the gene- and lineage-specific idiosyncrasies emerging from the empirical literature. With the goal of improving the connection between evolutionary theory and a rapidly growing body of genome-wide empirical studies, we extend previous population genetics theory of sex-specific selection by developing and analyzing a biologically informed model that incorporates sex linkage, pleiotropy, recombination, and epistasis, factors that are likely to vary between genes and between species. Our results demonstrate that sex-specific selection and sex-specific recombination rates can generate, and are compatible with, the gene- and species-specific linkage patterns reported in the genomics literature. The theory suggests that sexual selection may strongly influence the architectures of animal genomes, as well as the chromosomal distribution of fixed substitutions underlying sexually dimorphic traits. © 2010 The Author(s). Evolution© 2010 The Society for the Study of Evolution.

  9. STAT signaling in mammary gland differentiation, cell survival and tumorigenesis.

    Science.gov (United States)

    Haricharan, S; Li, Y

    2014-01-25

    The mammary gland is a unique organ that undergoes extensive and profound changes during puberty, menstruation, pregnancy, lactation and involution. The changes that take place during puberty involve large-scale proliferation and invasion of the fat-pad. During pregnancy and lactation, the mammary cells are exposed to signaling pathways that inhibit apoptosis, induce proliferation and invoke terminal differentiation. Finally, during involution the mammary gland is exposed to milk stasis, programmed cell death and stromal reorganization to clear the differentiated milk-producing cells. Not surprisingly, the signaling pathways responsible for bringing about these changes in breast cells are often subverted during the process of tumorigenesis. The STAT family of proteins is involved in every stage of mammary gland development, and is also frequently implicated in breast tumorigenesis. While the roles of STAT3 and STAT5 during mammary gland development and tumorigenesis are well studied, others members, e.g. STAT1 and STAT6, have only recently been observed to play a role in mammary gland biology. Continued investigation into the STAT protein network in the mammary gland will likely yield new biomarkers and risk factors for breast cancer, and may also lead to novel prophylactic or therapeutic strategies against breast cancer. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  10. Radiation-induced bystander effects in vivo are sex specific

    International Nuclear Information System (INIS)

    Koturbash, Igor; Kutanzi, Kristy; Hendrickson, Karl; Rodriguez-Juarez, Rocio; Kogosov, Dmitry; Kovalchuk, Olga

    2008-01-01

    Ionizing radiation (IR) effects span beyond the area of direct exposure and can be observed in neighboring and distant naive cells and organs. This phenomenon is termed a 'bystander effect'. IR effects in directly exposed tissue in vivo are epigenetically mediated and distinct in males and females. Yet, IR-induced bystander effects have never been explored in a sex-specificity domain. We used an in vivo mouse model, whereby the bystander effects are studied in spleen of male and female animals subjected to head exposure when the rest of the body is protected by a medical-grade lead shield. We analyzed the induction of DNA damage and alterations in global DNA methylation. Molecular parameters were correlated with cellular proliferation and apoptosis levels. The changes observed in bystander organs are compared to the changes in unexposed animals and animals exposed to predicted and measured scatter doses. We have found the selective induction of DNA damage levels, global DNA methylation, cell proliferation and apoptosis in exposed and bystander spleen tissue of male and female mice. Sex differences were significantly diminished in animals subjected to a surgical removal of gonads. These data constitute the first evidence of sex differences in radiation-induced bystander effects in mouse spleen in vivo. We show the role of sex hormones in spleen bystander responses and discuss implications of the observed changes

  11. Radiation-induced bystander effects in vivo are sex specific

    Energy Technology Data Exchange (ETDEWEB)

    Koturbash, Igor; Kutanzi, Kristy; Hendrickson, Karl; Rodriguez-Juarez, Rocio; Kogosov, Dmitry [Department of Biological Sciences, University of Lethbridge, Alberta T1K 3M4 (Canada); Kovalchuk, Olga [Department of Biological Sciences, University of Lethbridge, Alberta T1K 3M4 (Canada)], E-mail: olga.kovalchuk@uleth.ca

    2008-07-03

    Ionizing radiation (IR) effects span beyond the area of direct exposure and can be observed in neighboring and distant naive cells and organs. This phenomenon is termed a 'bystander effect'. IR effects in directly exposed tissue in vivo are epigenetically mediated and distinct in males and females. Yet, IR-induced bystander effects have never been explored in a sex-specificity domain. We used an in vivo mouse model, whereby the bystander effects are studied in spleen of male and female animals subjected to head exposure when the rest of the body is protected by a medical-grade lead shield. We analyzed the induction of DNA damage and alterations in global DNA methylation. Molecular parameters were correlated with cellular proliferation and apoptosis levels. The changes observed in bystander organs are compared to the changes in unexposed animals and animals exposed to predicted and measured scatter doses. We have found the selective induction of DNA damage levels, global DNA methylation, cell proliferation and apoptosis in exposed and bystander spleen tissue of male and female mice. Sex differences were significantly diminished in animals subjected to a surgical removal of gonads. These data constitute the first evidence of sex differences in radiation-induced bystander effects in mouse spleen in vivo. We show the role of sex hormones in spleen bystander responses and discuss implications of the observed changes.

  12. Aging obviates sex-specific physiological responses to exercise.

    Science.gov (United States)

    Deschenes, Michael R; Taylor, Jessica L; Mangis, Katherine A

    2013-01-01

    Both sex and aging have been shown to affect physiological responses to exercise. The aim of the present investigation was to determine whether aging impacted the sex-specific nature of physiological responses to exercise commonly noted among young adults. Ten aged men (69.0 ± 1.7 years; mean ± SE) and 10 aged women (71.6 ± 1.3 years) reporting similar levels of habitual physical activity performed a 30-min exercise session at 60-65% of their predetermined peak oxygen uptake. Cardiovascular, thermoregulatory, and metabolic variables were assessed before exercise, at the 15th and 30th min of exercise, and at 5 and 15 min into a passive postexercise recovery period. Variables of interest were statistically analyzed via two-way analysis of variance with repeated measures; significance was set at P physiological variable of interest were identified, but not once was a significant effect of group (i.e., sex) detected. Exercise-induced physiological responses to prolonged, moderate intensity exercise were similar among aged men and aged women. This evidence that the sexually dimorphic nature of physiological responses to exercise is obviated with age should be taken into account when prescribing health-related exercise training programs for older individuals. Copyright © 2013 Wiley Periodicals, Inc.

  13. Radiation-induced bystander effects in vivo are sex specific.

    Science.gov (United States)

    Koturbash, Igor; Kutanzi, Kristy; Hendrickson, Karl; Rodriguez-Juarez, Rocio; Kogosov, Dmitry; Kovalchuk, Olga

    2008-07-03

    Ionizing radiation (IR) effects span beyond the area of direct exposure and can be observed in neighboring and distant naïve cells and organs. This phenomenon is termed a 'bystander effect'. IR effects in directly exposed tissue in vivo are epigenetically mediated and distinct in males and females. Yet, IR-induced bystander effects have never been explored in a sex-specificity domain. We used an in vivo mouse model, whereby the bystander effects are studied in spleen of male and female animals subjected to head exposure when the rest of the body is protected by a medical-grade lead shield. We analyzed the induction of DNA damage and alterations in global DNA methylation. Molecular parameters were correlated with cellular proliferation and apoptosis levels. The changes observed in bystander organs are compared to the changes in unexposed animals and animals exposed to predicted and measured scatter doses. We have found the selective induction of DNA damage levels, global DNA methylation, cell proliferation and apoptosis in exposed and bystander spleen tissue of male and female mice. Sex differences were significantly diminished in animals subjected to a surgical removal of gonads. These data constitute the first evidence of sex differences in radiation-induced bystander effects in mouse spleen in vivo. We show the role of sex hormones in spleen bystander responses and discuss implications of the observed changes.

  14. Differential sexual survival of Drosophila melanogaster on copper sulfate.

    Science.gov (United States)

    Balinski, Michael A; Woodruff, Ronny C

    2017-04-01

    Based on studies of the influence of X-chromosomes on the viability of Drosophila melanogaster exposed to cadmium, and on the role of X-linked genes on copper homeostasis, we examined the effect of copper sulfate (CuSO 4 ) on offspring viability using three independent, inbred D. melanogaster crosses (ensuring identical autosomes for males and females within each cross). Each cross was performed with attached X-chromosome females and males with a single X-chromosome. As female D. melanogaster have less metallothionein RNA expression than males, we predicted fewer female offspring than male offspring in crosses exposed to CuSO 4 , even though females have two copies of X-chromosome genes, possibly resulting in overdominant heterozygosity. In two of three crosses, CuSO 4 caused significantly higher numbers of male offspring compared to female offspring. We hypothesized that these gender-based viability differences to copper exposure are caused by X-chromosome ploidy and X-linked genetic variation affecting metallothionein expression. Observed differential offspring viability responses among crosses to copper exposure also showed that different genetic backgrounds (autosomal and/or X-chromosome) can result in significant differences in heavy metal and metallothionein regulation. These results suggest that the effect of copper on offspring viability depends on both genetic background and gender, as both factors can affect the regulation of metallothionein proteins as well as homeostasis of biologically necessary heavy metals.

  15. Acceleration of astrocytic differentiation in neural stem cells surviving X-irradiation.

    Science.gov (United States)

    Ozeki, Ayumi; Suzuki, Keiji; Suzuki, Masatoshi; Ozawa, Hiroki; Yamashita, Shunichi

    2012-03-28

    Neural stem cells (NSCs) are highly susceptible to DNA double-strand breaks; however, little is known about the effects of radiation in cells surviving radiation. Although the nestin-positive NSCs predominantly became glial fibrillary acidic protein (GFAP)-positive in differentiation-permissive medium, little or no cells were GFAP positive in proliferation-permissive medium. We found that more than half of the cells surviving X-rays became GFAP positive in proliferation-permissive medium. Moreover, localized irradiation stimulated differentiation of cells outside the irradiated area. These results indicate for the first time that ionizing radiation is able to stimulate astrocyte-specific differentiation of surviving NSCs, whose process is mediated both by the direct activation of nuclear factor-κB and by the indirect bystander effect induced by X-irradiation.

  16. Surviving endoplasmic reticulum stress is coupled to altered chondrocyte differentiation and function.

    Directory of Open Access Journals (Sweden)

    Kwok Yeung Tsang

    2007-03-01

    Full Text Available In protein folding and secretion disorders, activation of endoplasmic reticulum (ER stress signaling (ERSS protects cells, alleviating stress that would otherwise trigger apoptosis. Whether the stress-surviving cells resume normal function is not known. We studied the in vivo impact of ER stress in terminally differentiating hypertrophic chondrocytes (HCs during endochondral bone formation. In transgenic mice expressing mutant collagen X as a consequence of a 13-base pair deletion in Col10a1 (13del, misfolded alpha1(X chains accumulate in HCs and elicit ERSS. Histological and gene expression analyses showed that these chondrocytes survived ER stress, but terminal differentiation is interrupted, and endochondral bone formation is delayed, producing a chondrodysplasia phenotype. This altered differentiation involves cell-cycle re-entry, the re-expression of genes characteristic of a prehypertrophic-like state, and is cell-autonomous. Concomitantly, expression of Col10a1 and 13del mRNAs are reduced, and ER stress is alleviated. ERSS, abnormal chondrocyte differentiation, and altered growth plate architecture also occur in mice expressing mutant collagen II and aggrecan. Alteration of the differentiation program in chondrocytes expressing unfolded or misfolded proteins may be part of an adaptive response that facilitates survival and recovery from the ensuing ER stress. However, the altered differentiation disrupts the highly coordinated events of endochondral ossification culminating in chondrodysplasia.

  17. Sex-specific selection for MHC variability in Alpine chamois

    Directory of Open Access Journals (Sweden)

    Schaschl Helmut

    2012-02-01

    Full Text Available Abstract Background In mammals, males typically have shorter lives than females. This difference is thought to be due to behavioural traits which enhance competitive abilities, and hence male reproductive success, but impair survival. Furthermore, in many species males usually show higher parasite burden than females. Consequently, the intensity of selection for genetic factors which reduce susceptibility to pathogens may differ between sexes. High variability at the major histocompatibility complex (MHC genes is believed to be advantageous for detecting and combating the range of infectious agents present in the environment. Increased heterozygosity at these immune genes is expected to be important for individual longevity. However, whether males in natural populations benefit more from MHC heterozygosity than females has rarely been investigated. We investigated this question in a long-term study of free-living Alpine chamois (Rupicapra rupicapra, a polygynous mountain ungulate. Results Here we show that male chamois survive significantly (P = 0.022 longer if heterozygous at the MHC class II DRB locus, whereas females do not. Improved survival of males was not a result of heterozygote advantage per se, as background heterozygosity (estimated across twelve microsatellite loci did not change significantly with age. Furthermore, reproductively active males depleted their body fat reserves earlier than females leading to significantly impaired survival rates in this sex (P Conclusions Increased MHC class II DRB heterozygosity with age in males, suggests that MHC heterozygous males survive longer than homozygotes. Reproductively active males appear to be less likely to survive than females most likely because of the energetic challenge of the winter rut, accompanied by earlier depletion of their body fat stores, and a generally higher parasite burden. This scenario renders the MHC-mediated immune response more important for males than for females

  18. Arctigenin protects against neuronal hearing loss by promoting neural stem cell survival and differentiation.

    Science.gov (United States)

    Huang, Xinghua; Chen, Mo; Ding, Yan; Wang, Qin

    2017-03-01

    Neuronal hearing loss has become a prevalent health problem. This study focused on the function of arctigenin (ARC) in promoting survival and neuronal differentiation of mouse cochlear neural stem cells (NSCs), and its protection against gentamicin (GMC) induced neuronal hearing loss. Mouse cochlea was used to isolate NSCs, which were subsequently cultured in vitro. The effects of ARC on NSC survival, neurosphere formation, differentiation of NSCs, neurite outgrowth, and neural excitability in neuronal network in vitro were examined. Mechanotransduction ability demonstrated by intact cochlea, auditory brainstem response (ABR), and distortion product optoacoustic emissions (DPOAE) amplitude in mice were measured to evaluate effects of ARC on GMC-induced neuronal hearing loss. ARC increased survival, neurosphere formation, neuron differentiation of NSCs in mouse cochlear in vitro. ARC also promoted the outgrowth of neurites, as well as neural excitability of the NSC-differentiated neuron culture. Additionally, ARC rescued mechanotransduction capacity, restored the threshold shifts of ABR and DPOAE in our GMC ototoxicity murine model. This study supports the potential therapeutic role of ARC in promoting both NSCs proliferation and differentiation in vitro to functional neurons, thus supporting its protective function in the therapeutic treatment of neuropathic hearing loss in vivo. © 2017 Wiley Periodicals, Inc.

  19. Sex-Specificity of Mineralocorticoid Target Gene Expression during Renal Development, and Long-Term Consequences

    Science.gov (United States)

    Dumeige, Laurence; Storey, Caroline; Decourtye, Lyvianne; Nehlich, Melanie; Lhadj, Christophe; Viengchareun, Say; Kappeler, Laurent; Lombès, Marc; Martinerie, Laetitia

    2017-01-01

    Sex differences have been identified in various biological processes, including hypertension. The mineralocorticoid signaling pathway is an important contributor to early arterial hypertension, however its sex-specific expression has been scarcely studied, particularly with respect to the kidney. Basal systolic blood pressure (SBP) and heart rate (HR) were measured in adult male and female mice. Renal gene expression studies of major players of mineralocorticoid signaling were performed at different developmental stages in male and female mice using reverse transcription quantitative PCR (RT-qPCR), and were compared to those of the same genes in the lung, another mineralocorticoid epithelial target tissue that regulates ion exchange and electrolyte balance. The role of sex hormones in the regulation of these genes was also investigated in differentiated KC3AC1 renal cells. Additionally, renal expression of the 11 β-hydroxysteroid dehydrogenase type 2 (11βHSD2) protein, a regulator of mineralocorticoid specificity, was measured by immunoblotting and its activity was indirectly assessed in the plasma using liquid-chromatography coupled to mass spectrometry in tandem (LC-MSMS) method. SBP and HR were found to be significantly lower in females compared to males. This was accompanied by a sex- and tissue-specific expression profile throughout renal development of the mineralocorticoid target genes serum and glucocorticoid-regulated kinase 1 (Sgk1) and glucocorticoid-induced leucine zipper protein (Gilz), together with Hsd11b2, Finally, the implication of sex hormones in this sex-specific expression profile was demonstrated in vitro, most notably for Gilz mRNA expression. We demonstrate a tissue-specific, sex-dependent and developmentally-regulated pattern of expression of the mineralocorticoid pathway that could have important implications in physiology and pathology. PMID:28230786

  20. Competitive interactions are mediated in a sex-specific manner by arbuscular mycorrhiza in Antennaria dioica.

    Science.gov (United States)

    Varga, S; Vega-Frutis, R; Kytöviita, M-M

    2017-03-01

    Plants usually interact with other plants, and the outcome of such interaction ranges from facilitation to competition depending on the identity of the plants, including their sexual expression. Arbuscular mycorrhizal (AM) fungi have been shown to modify competitive interactions in plants. However, few studies have evaluated how AM fungi influence plant intraspecific and interspecific interactions in dioecious species. The competitive abilities of female and male plants of Antennaria dioica were examined in a greenhouse experiment. Females and males were grown in the following competitive settings: (i) without competition, (ii) with intrasexual competition, (iii) with intersexual competition, and (iv) with interspecific competition by Hieracium pilosella - a plant with similar characteristics to A. dioica. Half of the pots were grown with Claroideoglomus claroideum, an AM fungus isolated from the same habitat as the plant material. We evaluated plant survival, growth, flowering phenology, and production of AM fungal structures. Plant survival was unaffected by competition or AM fungi. Competition and the presence of AM fungi reduced plant biomass. However, the sexes responded differently to the interaction between fungal and competition treatments. Both intra- and interspecific competition results were sex-specific, and in general, female performance was reduced by AM colonization. Plant competition or sex did not affect the intraradical structures, extraradical hyphae, or spore production of the AM fungus. These findings suggest that plant sexual differences affect fundamental processes such as competitive ability and symbiotic relationships with AM fungi. © 2016 German Botanical Society and The Royal Botanical Society of the Netherlands.

  1. p62 modulates Akt activity via association with PKCζ in neuronal survival and differentiation

    International Nuclear Information System (INIS)

    Joung, Insil; Kim, Hak Jae; Kwon, Yunhee Kim

    2005-01-01

    p62 is a ubiquitously expressed phosphoprotein that interacts with a number of signaling molecules and a major component of neurofibrillary tangles in the brain of Alzheimer's disease patients. It has been implicated in important cellular functions such as cell proliferation and anti-apoptotic pathways. In this study, we have addressed the potential role of p62 during neuronal differentiation and survival using HiB5, a rat neuronal progenitor cell. We generated a recombinant adenovirus encoding T7-epitope tagged p62 to reliably transfer p62 cDNA into the neuronal cells. The results show that an overexpression of p62 led not only to neuronal differentiation, but also to decreased cell death induced by serum withdrawal in HiB5 cells. In this process p62-dependent Akt phosphorylation occurred via the release of Akt from PKCζ by association of p62 and PKCζ, which is known as a negative regulator of Akt activation. These findings indicate that p62 facilitates cell survival through novel signaling cascades that result in Akt activation. Furthermore, we found that p62 expression was induced during neuronal differentiation. Taken together, the data suggest p62 is a regulator of neuronal cell survival and differentiation

  2. The Role of Lipid Metabolism in T Lymphocyte Differentiation and Survival

    Directory of Open Access Journals (Sweden)

    Duncan Howie

    2018-01-01

    Full Text Available The differentiation and effector functions of both the innate and adaptive immune system are inextricably linked to cellular metabolism. The features of metabolism which affect both arms of the immune system include metabolic substrate availability, expression of enzymes, transport proteins, and transcription factors which control catabolism of these substrates, and the ability to perform anabolic metabolism. The control of lipid metabolism is central to the appropriate differentiation and functions of T lymphocytes, and ultimately to the maintenance of immune tolerance. This review will focus on the role of fatty acid (FA metabolism in T cell differentiation, effector function, and survival. FAs are important sources of cellular energy, stored as triglycerides. They are also used as precursors to produce complex lipids such as cholesterol and membrane phospholipids. FA residues also become incorporated into hormones and signaling moieties. FAs signal via nuclear receptors and their channeling, between storage as triacyl glycerides or oxidation as fuel, may play a role in survival or death of the cell. In recent years, progress in the field of immunometabolism has highlighted diverse roles for FA metabolism in CD4 and CD8 T cell differentiation and function. This review will firstly describe the sensing and modulation of the environmental FAs and lipid intracellular signaling and will then explore the key role of lipid metabolism in regulating the balance between potentially damaging pro-inflammatory and anti-inflammatory regulatory responses. Finally the complex role of extracellular FAs in determining cell survival will be discussed.

  3. 3D porous chitosan scaffolds suit survival and neural differentiation of dental pulp stem cells.

    Science.gov (United States)

    Feng, Xingmei; Lu, Xiaohui; Huang, Dan; Xing, Jing; Feng, Guijuan; Jin, Guohua; Yi, Xin; Li, Liren; Lu, Yuanzhou; Nie, Dekang; Chen, Xiang; Zhang, Lei; Gu, Zhifeng; Zhang, Xinhua

    2014-08-01

    A key aspect of cell replacement therapy in brain injury treatment is construction of a suitable biomaterial scaffold that can effectively carry and transport the therapeutic cells to the target area. In the present study, we created small 3D porous chitosan scaffolds through freeze-drying, and showed that these can support and enhance the differentiation of dental pulp stem cells (DPSCs) to nerve cells in vitro. The DPSCs were collected from the dental pulp of adult human third molars. At a swelling rate of ~84.33 ± 10.92 %, the scaffold displayed high porosity and interconnectivity of pores, as revealed by SEM. Cell counting kit-8 assay established the biocompatibility of the chitosan scaffold, supporting the growth and survival of DPSCs. The successful neural differentiation of DPSCs was assayed by RT-PCR, western blotting, and immunofluorescence. We found that the scaffold-attached DPSCs showed high expression of Nestin that decreased sharply following induction of differentiation. Exposure to the differentiation media also increased the expression of neural molecular markers Microtubule-associated protein 2, glial fibrillary acidic protein, and 2',3'-cyclic nucleotide phosphodiesterase. This study demonstrates that the granular 3D chitosan scaffolds are non-cytotoxic, biocompatible, and provide a conducive and favorable micro-environment for attachment, survival, and neural differentiation of DPSCs. These scaffolds have enormous potential to facilitate future advances in treatment of brain injury.

  4. The influence of fractionation on cell survival and premature differentiation after carbon ion irradiation

    International Nuclear Information System (INIS)

    Wang Jufang; Li Renming; Guo Chuanling; Fournier, C.; K-Weyrather, W.

    2008-01-01

    To investigate the influence of fractionation on cell survival and radiation induced premature differentiation as markers for early and late effects after X-rays and carbon irradiation. Normal human fibroblasts NHDF, AG1522B and WI-38 were irradiated with 250 kV X-rays, or 266 MeV/u, 195 MeV/u and 11 MeV/u carbon ions. Cytotoxicity was measured by a clonogenic survival assay or by determination of the differentiation pattern. Experiments with high-energy carbon ions show that fractionation induced repair effects are similar to photon irradiation. The relative biological effective (RBE) 10 values for clonogenic survival are 1.3 and 1.6 for irradiation in one or two fractions for NHDF cells and around 1.2 for AG1522B cells regardless of the fractionation scheme. The RBE for a doubling of post mitotic fibroblasts (PMF) in the population is 1 for both single and two fractionated irradiation of NHDF cells. Using 11 MeV/u carbon ions, no repair effect can be seen in WI-38 cells. The RBE 10 for clonogenic survival is 3.2 for single irradiation and 4.9 for two fractionated irradiations. The RBE for a doubling of PMF is 3.1 and 5.0 for single and two fractionated irradiations, respectively. For both cell lines the effects of high-energy carbon ions representing the irradiation of the skin and the normal tissue in the entrance channel are similar to the effects of X-rays. The fractionation effects are maintained. For the lower energy, which is representative for the irradiation of the tumor region, RBE is enhanced for clonogenic survival as well as for premature terminal differentiation. Fractionation effects are not detectable. Consequently, the therapeutic ratio is significantly enhanced by fractionated irradiation with carbon ions. (author)

  5. Somatic sex-specific transcriptome differences in Drosophila revealed by whole transcriptome sequencing

    Directory of Open Access Journals (Sweden)

    Arbeitman Michelle N

    2011-07-01

    Full Text Available Abstract Background Understanding animal development and physiology at a molecular-biological level has been advanced by the ability to determine at high resolution the repertoire of mRNA molecules by whole transcriptome resequencing. This includes the ability to detect and quantify rare abundance transcripts and isoform-specific mRNA variants produced from a gene. The sex hierarchy consists of a pre-mRNA splicing cascade that directs the production of sex-specific transcription factors that specify nearly all sexual dimorphism. We have used deep RNA sequencing to gain insight into how the Drosophila sex hierarchy generates somatic sex differences, by examining gene and transcript isoform expression differences between the sexes in adult head tissues. Results Here we find 1,381 genes that differ in overall expression levels and 1,370 isoform-specific transcripts that differ between males and females. Additionally, we find 512 genes not regulated downstream of transformer that are significantly more highly expressed in males than females. These 512 genes are enriched on the × chromosome and reside adjacent to dosage compensation complex entry sites, which taken together suggests that their residence on the × chromosome might be sufficient to confer male-biased expression. There are no transcription unit structural features, from a set of features, that are robustly significantly different in the genes with significant sex differences in the ratio of isoform-specific transcripts, as compared to random isoform-specific transcripts, suggesting that there is no single molecular mechanism that generates isoform-specific transcript differences between the sexes, even though the sex hierarchy is known to include three pre-mRNA splicing factors. Conclusions We identify thousands of genes that show sex-specific differences in overall gene expression levels, and identify hundreds of additional genes that have differences in the abundance of isoform

  6. Activated Fps/Fes tyrosine kinase regulates erythroid differentiation and survival.

    Science.gov (United States)

    Sangrar, Waheed; Gao, Yan; Bates, Barbara; Zirngibl, Ralph; Greer, Peter A

    2004-10-01

    A substantial body of evidence implicates the cytoplasmic protein tyrosine kinase Fps/Fes in regulation of myeloid differentiation and survival. In this study we wished to determine if Fps/Fes also plays a role in the regulation of erythropoiesis. Mice tissue-specifically expressing a "gain-of-function" mutant fps/fes transgene (fps(MF)) encoding an activated variant of Fps/Fes (MFps), were used to explore the in vivo biological role of Fps/Fes. Erythropoiesis in these mice was assessed by hematological analysis, lineage marker analysis, bone-marrow colony assays, and biochemical approaches. fps(MF) mice displayed reductions in peripheral red cell counts. However, there was an accumulation of immature erythroid precursors, which displayed increased survival. Fps/Fes and the related Fer kinase were both detected in early erythroid progenitors/blasts and in mature red cells. Fps/Fes was also activated in response to erythropoietin (EPO) and stem cell factor (SCF), two critical factors in erythroid development. In addition, increased Stat5A/B activation and reduced Erk1/2 phosphorylation was observed in fps(MF) primary erythroid cells in response to EPO or SCF, respectively. These data support a role for Fps/Fes in regulating the survival and differentiation of erythroid cells through modulation of Stat5A/B and Erk kinase pathways induced by EPO and SCF. The increased numbers and survival of erythroid progenitors from fps(MF) mice, and their differential responsiveness to SCF and EPO, implicates Fps/Fes in the commitment of multilineage progenitors to the erythroid lineage. The anemic phenotype in fps(MF) mice suggests that downregulation of Fps/Fes activity might be required for terminal erythroid differentiation.

  7. Sex-specific effects of dehydroepiandrosterone (DHEA) on glucose metabolism in the CNS.

    Science.gov (United States)

    Vieira-Marques, Claudia; Arbo, Bruno Dutra; Cozer, Aline Gonçalves; Hoefel, Ana Lúcia; Cecconello, Ana Lúcia; Zanini, Priscila; Niches, Gabriela; Kucharski, Luiz Carlos; Ribeiro, Maria Flávia M

    2017-07-01

    DHEA is a neuroactive steroid, due to its modulatory actions on the central nervous system (CNS). DHEA is able to regulate neurogenesis, neurotransmitter receptors and neuronal excitability, function, survival and metabolism. The levels of DHEA decrease gradually with advancing age, and this decline has been associated with age related neuronal dysfunction and degeneration, suggesting a neuroprotective effect of endogenous DHEA. There are significant sex differences in the pathophysiology, epidemiology and clinical manifestations of many neurological diseases. The aim of this study was to determine whether DHEA can alter glucose metabolism in different structures of the CNS from male and female rats, and if this effect is sex-specific. The results showed that DHEA decreased glucose uptake in some structures (cerebral cortex and olfactory bulb) in males, but did not affect glucose uptake in females. When compared, glucose uptake in males was higher than females. DHEA enhanced the glucose oxidation in both males (cerebral cortex, olfactory bulb, hippocampus and hypothalamus) and females (cerebral cortex and olfactory bulb), in a sex-dependent manner. In males, DHEA did not affect synthesis of glycogen, however, glycogen content was increased in the cerebral cortex and olfactory bulb. DHEA modulates glucose metabolism in a tissue-, dose- and sex-dependent manner to increase glucose oxidation, which could explain the previously described neuroprotective role of this hormone in some neurodegenerative diseases. Copyright © 2016. Published by Elsevier Ltd.

  8. Pathological and immunological responses associated with differential survival of Chinook salmon following Renibacterium salmoninarum challenge

    Science.gov (United States)

    Metzger, David C.; Elliott, Diane G.; Wargo, Andrew; Park, Linda K.; Purcell, Maureen K.

    2010-01-01

    Chinook salmon Oncorhynchus tshawytscha are highly susceptible to Renibacterium salmoninarum, the causative agent of bacterial kidney disease (BKD). Previously we demonstrated that introduced Chinook salmon from Lake Michigan, Wisconsin (WI), USA, have higher survival following R. salmoninarum challenge relative to the progenitor stock from Green River, Washington, USA. In the present study, we investigated the pathological and immunological responses that are associated with differential survival in the 2 Chinook salmon stocks following intra-peritoneal R. salmoninarum challenge of 2 different cohort years (2003 and 2005). Histological evaluation revealed delayed appearance of severe granulomatous lesions in the kidney and lower overall prevalence of membranous glomerulopathy in the higher surviving WI stock. The higher survival WI stock had a lower bacterial load at 28 d post-infection, as measured by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR). However, at all other time points, bacterial load levels were similar despite higher mortality in the more susceptible Green River stock, suggesting the possibility that the stocks may differ in their tolerance to infection by the bacterium. Interferon-γ, inducible nitric oxide synthase (iNOS), Mx-1, and transferrin gene expression were up-regulated in both stocks following challenge. A trend of higher iNOS gene expression at later time points (≥28 d post-infection) was observed in the lower surviving Green River stock, suggesting the possibility that higher iNOS expression may contribute to greater pathology in that stock.

  9. Survival rate of patients with differentiated thyroid cancer without early postoperative external radiation of the neck

    International Nuclear Information System (INIS)

    Saur, H.B.; Lerch, H.; Schober, O.

    1996-01-01

    Results of survival rates in differentiated thyroid carcinoma and comparison with a review of literature are given. Four hundred and sixty-four patients with differentiated cancer of the thyroid (354 female, 110 male, range: 6 to 84 years, median: 46.8 years; 275 patients with papillary and 190 with follicular cancer) were analyzed retrospectively. All patients were treated with ablative doses of radioiodine after thyroidectomy including compartment oriented lymphadenectomy in 27 patients. All patients passed an individual systematic follow-up according to risk: 'Low risk' pT≤3NxM0 vs. 'high risk' pT4 and/or M1. Early postoperative radiation was not included even in patients with local invasion (pT4). The corrected 5- and 10-year survival rates for papillary cancer are 0.91 and 0.91, for follicular cancer 0.94 resp. 0.78 (p=0.55), age (≤40 years 0.96 and 0.96, >40 years 0.90 and 0.80; p=0.008), gender (female 0.93 and 0.92, male 0.90 and 0.70; p=0.06) and invasion/distant metastases (pT4 and/or M1 0.83 and 0.71, other 0.97 and 0.97; p=0.0001). A systematic follow-up with an individually adapted standardized scheme is associated with high survival rates in patients with differentiated cancer of the thyroid. Early diagnosis of recurrences, locoregional lymph node and distant metastases with early surgical treatment including compartment oriented lymphadenectomy and radioiodine therapy yield high survival even without external radiation. (orig./MG) [de

  10. Evaluation of Sex-Specific Gene Expression in Archived Dried Blood Spots (DBS

    Directory of Open Access Journals (Sweden)

    Scott Jewell

    2012-08-01

    Full Text Available Screening newborns for treatable serious conditions is mandated in all US states and many other countries. After screening, Guthrie cards with residual blood (whole spots or portions of spots are typically stored at ambient temperature in many facilities. The potential of archived dried blood spots (DBS for at-birth molecular studies in epidemiological and clinical research is substantial. However, it is also challenging as analytes from DBS may be degraded due to preparation and storage conditions. We previously reported an improved assay for obtaining global RNA gene expression from blood spots. Here, we evaluated sex-specific gene expression and its preservation in DBS using oligonucleotide microarray technology. We found X inactivation-specific transcript (XIST, lysine-specific demethylase 5D (KDM5D (also known as selected cDNA on Y, homolog of mouse (SMCY, uncharacterized LOC729444 (LOC729444, and testis-specific transcript, Y-linked 21 (TTTY21 to be differentially-expressed by sex of the newborn. Our finding that trait-specific RNA gene expression is preserved in unfrozen DBS, demonstrates the technical feasibility of performing molecular genetic profiling using such samples. With millions of DBS potentially available for research, we see new opportunities in using newborn molecular gene expression to better understand molecular pathogenesis of perinatal diseases.

  11. Influence of depth on sex-specific energy allocation patterns in a tropical reef fish

    Science.gov (United States)

    Hoey, J.; McCormick, M. I.; Hoey, A. S.

    2007-09-01

    The effect of depth on the distribution and sex-specific energy allocation patterns of a common coral reef fish, Chrysiptera rollandi (Pomacentridae), was investigated using depth-stratified collections over a broad depth range (5-39 m) and a translocation experiment. C. rollandi consistently selected rubble habitats at each depth, however abundance patterns did not reflect the availability of the preferred microhabitat suggesting a preference for depth as well as microhabitat. Reproductive investment (gonado-somatic index), energy stores (liver cell density and hepatocyte vacuolation), and overall body condition (hepato-somatic index and Fulton’s K) of female fish varied significantly among depths and among the three reefs sampled. Male conspecifics displayed no variation between depth or reef. Depth influenced growth dynamics, with faster initial growth rates and smaller mean asymptotic lengths with decreasing depth. In female fish, relative gonad weight and overall body condition (Fulton’s K and hepato-somatic index) were generally higher in shallower depths (≤10 m). Hepatic lipid storage was highest at the deepest sites sampled on each reef, whereas hepatic glycogen stores tended to decrease with depth. Depth was found to influence energy allocation dynamics in C. rollandi. While it is unclear what processes directly influenced the depth-related patterns in energy allocation, this study shows that individuals across a broad depth gradient are not all in the same physiological state and may contribute differentially to the population reproductive output.

  12. The geography of sex-specific selection, local adaptation, and sexual dimorphism.

    Science.gov (United States)

    Connallon, Tim

    2015-09-01

    Local adaptation and sexual dimorphism are iconic evolutionary scenarios of intraspecific adaptive differentiation in the face of gene flow. Although theory has traditionally considered local adaptation and sexual dimorphism as conceptually distinct processes, emerging data suggest that they often act concurrently during evolutionary diversification. Here, I merge theories of local adaptation in space and sex-specific adaptation over time, and show that their confluence yields several new predictions about the roles of context-specific selection, migration, and genetic correlations, in adaptive diversification. I specifically revisit two influential predictions from classical studies of clinal adaptation and sexual dimorphism: (1) that local adaptation should decrease with distance from the species' range center and (2) that opposing directional selection between the sexes (sexual antagonism) should inevitably accompany the evolution of sexual dimorphism. I show that both predictions can break down under clinally varying selection. First, the geography of local adaptation can be sexually dimorphic, with locations of relatively high local adaptation differing profoundly between the sexes. Second, the intensity of sexual antagonism varies across the species' range, with subpopulations near the range center representing hotspots for antagonistic selection. The results highlight the context-dependent roles of migration versus sexual conflict as primary constraints to adaptive diversification. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  13. Integrative Analysis of Sex-Specific microRNA Networks Following Stress in Mouse Nucleus Accumbens.

    Science.gov (United States)

    Pfau, Madeline L; Purushothaman, Immanuel; Feng, Jian; Golden, Sam A; Aleyasin, Hossein; Lorsch, Zachary S; Cates, Hannah M; Flanigan, Meghan E; Menard, Caroline; Heshmati, Mitra; Wang, Zichen; Ma'ayan, Avi; Shen, Li; Hodes, Georgia E; Russo, Scott J

    2016-01-01

    Adult women are twice as likely as men to suffer from affective and anxiety disorders, although the mechanisms underlying heightened female stress susceptibility are incompletely understood. Recent findings in mouse Nucleus Accumbens (NAc) suggest a role for DNA methylation-driven sex differences in genome-wide transcriptional profiles. However, the role of another epigenetic process-microRNA (miR) regulation-has yet to be explored. We exposed male and female mice to Subchronic Variable Stress (SCVS), a stress paradigm that produces depression-like behavior in female, but not male, mice, and performed next generation mRNA and miR sequencing on NAc tissue. We applied a combination of differential expression, miR-mRNA network and functional enrichment analyses to characterize the transcriptional and post-transcriptional landscape of sex differences in NAc stress response. We find that male and female mice exhibit largely non-overlapping miR and mRNA profiles following SCVS. The two sexes also show enrichment of different molecular pathways and functions. Collectively, our results suggest that males and females mount fundamentally different transcriptional and post-transcriptional responses to SCVS and engage sex-specific molecular processes following stress. These findings have implications for the pathophysiology and treatment of stress-related disorders in women.

  14. Sex-specific responses of Populus deltoides to defoliation

    Directory of Open Access Journals (Sweden)

    Li Shuxin

    2017-12-01

    Full Text Available There has been an increasing interest in understanding the differential effects of sexual dimorphism on plant stress responses. However, there is no clear pattern in the responses of the sexes to defoliation. In this study, the effects of different severity of artificial defoliation on biomass production, total nonstructural carbohydrate (NSC concentration, and photosynthetic rate (PN of male and female Populus deltoides were examined. We used half and full defoliation to observe the differences between the sexes in three harvest dates (1 week, 4 weeks, and 8 weeks after treatments. We hypothesized that female and male P. deltoides compared with an undefoliated control would have compensatory growth in response to defoliation treatments. Results showed that half and full defoliation reduced the growth of both sexes. Following half defoliation, root growth was reduced, especially in males, at T2 (4 weeks after defoliation and T3 (8 weeks after defoliation, while males showed an increase in height increment under the half defoliation compared with the nondefoliation treatments. By contrast, females were more negatively affected by defoliation than males in terms of biomass after 8 weeks. One week after defoliation, PN increased significantly in females and males under half defoliation (+30%, +32%, respectively and full defoliation (+58%, +56%, respectively. However, 8 weeks after defoliation, there was little difference in PN between defoliated and undefoliated female cuttings. Increases in stomatal conductance (gs and leaf nitrogen were observed under fully defoliated female and male cuttings. Moreover, males had less NSC concentrations following half defoliation compared with females. Our results indicate that leaf compensatory growth in male cuttings of P. deltoides was maintained by obtaining greater photosynthetic capacity, higher leaf nitrogen, and lower NSC concentration following half and full defoliation. Our results highlight that

  15. Gender differentials and old age survival in the Nairobi slums, Kenya.

    Science.gov (United States)

    Bennett, Rachel; Chepngeno-Langat, Gloria; Evandrou, Maria; Falkingham, Jane

    2016-08-01

    This paper examines gender differentials in survival amongst older people (50+ years) in the Nairobi slums and to the best of our knowledge is the first study of its kind in an urban African setting. The results provide evidence contrary to the expected paradox of poorer self-rated health yet better survival amongst older women. Older women in the Nairobi slums have poorer self-rated health and poorer circumstances across other factors, including disability and socio-economic status. Further, older women in the slums do not have better survival. The conventional female advantage in mortality only becomes apparent after accounting for the cumulative influence of individual characteristics, social networks, health and socio-economic status, suggesting the female advantage in unadjusted old-age mortality does not apply to contexts where women experience significant disadvantage across multiple life domains. This highlights the urgent need to redress the support, status and opportunities available for women across the life course in contexts such as the Nairobi slums. In addition, a greater number of factors differentiate mortality risk amongst men than amongst women, suggesting inequality amongst slum dwelling older men and highlighting the need for gender sensitive interventions which account for the particular needs of both genders in old age. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Youth's perceptions of HIV infection risk: a sex-specific test of two ...

    African Journals Online (AJOL)

    Youth's perceptions of HIV infection risk: a sex-specific test of two risk models. ... The analysis is based on data from the 2003 Demographic and Health survey ... multiple partners, Nigeria, risk perception, sexual behaviour, vulnerability to HIV ...

  17. TAM receptors support neural stem cell survival, proliferation and neuronal differentiation.

    Science.gov (United States)

    Ji, Rui; Meng, Lingbin; Jiang, Xin; Cvm, Naresh Kumar; Ding, Jixiang; Li, Qiutang; Lu, Qingxian

    2014-01-01

    Tyro3, Axl and Mertk (TAM) receptor tyrosine kinases play multiple functional roles by either providing intrinsic trophic support for cell growth or regulating the expression of target genes that are important in the homeostatic regulation of immune responses. TAM receptors have been shown to regulate adult hippocampal neurogenesis by negatively regulation of glial cell activation in central nervous system (CNS). In the present study, we further demonstrated that all three TAM receptors were expressed by cultured primary neural stem cells (NSCs) and played a direct growth trophic role in NSCs proliferation, neuronal differentiation and survival. The cultured primary NSCs lacking TAM receptors exhibited slower growth, reduced proliferation and increased apoptosis as shown by decreased BrdU incorporation and increased TUNEL labeling, than those from the WT NSCs. In addition, the neuronal differentiation and maturation of the mutant NSCs were impeded, as characterized by less neuronal differentiation (β-tubulin III+) and neurite outgrowth than their WT counterparts. To elucidate the underlying mechanism that the TAM receptors play on the differentiating NSCs, we examined the expression profile of neurotrophins and their receptors by real-time qPCR on the total RNAs from hippocampus and primary NSCs; and found that the TKO NSC showed a significant reduction in the expression of both nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), but accompanied by compensational increases in the expression of the TrkA, TrkB, TrkC and p75 receptors. These results suggest that TAM receptors support NSCs survival, proliferation and differentiation by regulating expression of neurotrophins, especially the NGF.

  18. Mitochondrial DNA paradox: sex-specific genetic structure in a marine mussel – despite maternal inheritance and passive dispersal

    Directory of Open Access Journals (Sweden)

    Teske Peter R

    2012-06-01

    Full Text Available Abstract Background When genetic structure is identified using mitochondrial DNA (mtDNA, but no structure is identified using biparentally-inherited nuclear DNA, the discordance is often attributed to differences in dispersal potential between the sexes. Results We sampled the intertidal rocky shore mussel Perna perna in a South African bay and along the nearby open coast, and sequenced maternally-inherited mtDNA (there is no evidence for paternally-inherited mtDNA in this species and a biparentally-inherited marker. By treating males and females as different populations, we identified significant genetic structure on the basis of mtDNA data in the females only. Conclusions This is the first study to report sex-specific differences in genetic structure based on matrilineally-inherited mtDNA in a passively dispersing species that lacks social structure or sexual dimorphism. The observed pattern most likely stems from females being more vulnerable to selection in habitats from which they did not originate, which also manifests itself in a male-biased sex ratio. Our results have three important implications for the interpretation of population genetic data. First, even when mtDNA is inherited exclusively in the female line, it also contains information about males. For that reason, using it to identify sex-specific differences in genetic structure by contrasting it with biparentally-inherited markers is problematic. Second, the fact that sex-specific differences were found in a passively dispersing species in which sex-biased dispersal is unlikely highlights the fact that significant genetic structure is not necessarily a function of low dispersal potential or physical barriers. Third, even though mtDNA is typically used to study historical demographic processes, it also contains information about contemporary processes. Higher survival rates of males in non-native habitats can erase the genetic structure present in their mothers within a single

  19. Stage- and sex-specific heat tolerance in the yellow dung fly Scathophaga stercoraria

    OpenAIRE

    Blanckenhorn Wolf U.; Gautier Roland; Nick Marcel; Puniamoorthy Nalini; Schäfer Martin A.

    2014-01-01

    Thermal tolerance varies at all hierarchical levels of biological organization: among species populations individuals and even within individuals. Age or developmental stage and sex specific thermal effects have received relatively little attention in the literature despite being crucial for understanding thermal adaptation in nature and responses to global warming. We document stage and sex specific heat tolerance in the yellow dung fly Scathophaga stercoraria (Diptera: Scathophagidae) a...

  20. Habitat Fragmentation Differentially Affects Genetic Variation, Phenotypic Plasticity and Survival in Populations of a Gypsum Endemic

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    Silvia Matesanz

    2017-05-01

    Full Text Available Habitat fragmentation, i.e., fragment size and isolation, can differentially alter patterns of neutral and quantitative genetic variation, fitness and phenotypic plasticity of plant populations, but their effects have rarely been tested simultaneously. We assessed the combined effects of size and connectivity on these aspects of genetic and phenotypic variation in populations of Centaurea hyssopifolia, a narrow endemic gypsophile that previously showed performance differences associated with fragmentation. We grew 111 maternal families sampled from 10 populations that differed in their fragment size and connectivity in a common garden, and characterized quantitative genetic variation, phenotypic plasticity to drought for key functional traits, and plant survival, as a measure of population fitness. We also assessed neutral genetic variation within and among populations using eight microsatellite markers. Although C. hyssopifolia is a narrow endemic gypsophile, we found substantial neutral genetic variation and quantitative variation for key functional traits. The partition of genetic variance indicated that a higher proportion of variation was found within populations, which is also consistent with low population differentiation in molecular markers, functional traits and their plasticity. This, combined with the generally small effect of habitat fragmentation suggests that gene flow among populations is not restricted, despite large differences in fragment size and isolation. Importantly, population’s similarities in genetic variation and plasticity did not reflect the lower survival observed in isolated populations. Overall, our results indicate that, although the species consists of genetically variable populations able to express functional plasticity, such aspects of adaptive potential may not always reflect populations’ survival. Given the differential effects of habitat connectivity on functional traits, genetic variation and fitness

  1. Differential survival among sSOD-1* genotypes in Chinook Salmon

    Science.gov (United States)

    Hayes, Michael C.; Reisenbichler, Reginald R.; Rubin, Stephen P.; Wetzel, Lisa A.; Marshall , Anne R.

    2011-01-01

    Differential survival and growth were tested in Chinook salmon Oncorhynchus tshawytscha expressing two common alleles, *–100 and *–260, at the superoxide dismutase locus (sSOD-1*). These tests were necessary to support separate studies in which the two alleles were used as genetic marks under the assumption of mark neutrality. Heterozygous adults were used to produce progeny with –100/–100, –100/–260, and –260/–260 genotypes that were reared in two natural streams and two hatcheries in the states of Washington and Oregon. The latter also were evaluated as returning adults. In general, the genotype ratios of juveniles reared at hatcheries were consistent with high survival and little or no differential survival in the hatchery. Adult returns at one hatchery were significantly different from the expected proportions, and the survival of the –260/–260 genotype was 0.56–0.89 times that of the –100/–100 genotype over four year-classes. Adult returns at a second hatchery (one year-class) were similar but not statistically significant: survival of the –260/–260genotype relative to the –100/–100 genotype was 0.76. The performance of the heterozygote group was intermediate at both hatcheries. Significant differences in growth were rarely observed among hatchery fish (one year-class of juveniles and one age-class of adult males) but were consistent with greater performance for the –100/–100 genotype. Results from two groups of juveniles reared in streams (one year-class from each stream) suggested few differences in growth, but the observed genotype ratios were significantly different from the expected ratios in one stream. Those differences were consistent with the adult data; survival for the –260/–260 genotype was 76% of that of the –100/–100 genotype. These results, which indicate nonneutrality among sSOD-1* genotypes, caused us to modify our related studies and suggest caution in the interpretation of results and analyses in

  2. Differential Survival for Men and Women with HIV/AIDS-Related Neurologic Diagnoses.

    Directory of Open Access Journals (Sweden)

    Martha L Carvour

    Full Text Available Neurologic complications of human immunodeficiency virus (HIV infection and acquired immune deficiency syndrome (AIDS frequently lead to disability or death in affected patients. The aim of this study was to determine whether survival patterns differ between men and women with HIV/AIDS-related neurologic disease (neuro-AIDS.Retrospective cohort data from a statewide surveillance database for HIV/AIDS were used to characterize survival following an HIV/AIDS-related neurologic diagnosis for men and women with one or more of the following conditions: cryptococcosis, toxoplasmosis, primary central nervous system lymphoma, progressive multifocal leukoencephalopathy, and HIV-associated dementia. A second, non-independent cohort was formed using university-based cases to confirm and extend the findings from the statewide data. Kaplan-Meier analysis was used to compare the survival experiences for men and women in the cohorts. Cox regression was employed to characterize survival while controlling for potential confounders in the study population.Women (n=27 had significantly poorer outcomes than men (n=198 in the statewide cohort (adjusted hazard ratio=2.31, 95% CI: 1.22 to 4.35, and a similar, non-significant trend was observed among university-based cases (n=17 women, 154 men. Secondary analyses suggested that this difference persisted over the course of the AIDS epidemic and was not attributable to differential antiretroviral therapy responses among men and women.The survival disadvantage of women compared to men should be confirmed and the mechanisms underlying this disparity elucidated. If this relationship is confirmed, targeted clinical and public health efforts might be directed towards screening, treatment, and support for women affected by neuro-AIDS.

  3. REST/NRSF Knockdown Alters Survival, Lineage Differentiation and Signaling in Human Embryonic Stem Cells.

    Directory of Open Access Journals (Sweden)

    Kaushali Thakore-Shah

    Full Text Available REST (RE1 silencing transcription factor, also known as NRSF (neuron-restrictive silencer factor, is a well-known transcriptional repressor of neural genes in non-neural tissues and stem cells. Dysregulation of REST activity is thought to play a role in diverse diseases including epilepsy, cancer, Down's syndrome and Huntington's disease. The role of REST/NRSF in control of human embryonic stem cell (hESC fate has never been examined. To evaluate the role of REST in hESCs we developed an inducible REST knockdown system and examined both growth and differentiation over short and long term culture. Interestingly, we have found that altering REST levels in multiple hESC lines does not result in loss of self-renewal but instead leads to increased survival. During differentiation, REST knockdown resulted in increased MAPK/ERK and WNT signaling and increased expression of mesendoderm differentiation markers. Therefore we have uncovered a new role for REST in regulation of growth and early differentiation decisions in human embryonic stem cells.

  4. Evaluation of the Physiological Challenges in Extreme Environments: Implications for Enhanced Training, Operational Performance and Sex-Specific Responses

    Science.gov (United States)

    2017-10-01

    Operational Performance and Sex -Specific Responses PRINCIPAL INVESTIGATOR: Brent C. Ruby CONTRACTING ORGANIZATION: The University of Montana Missoula...Implications for Enhanced Training, Operational Performance and Sex -Specific Responses 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...Evaluation of the physiological challenges in extreme environments: Implications for enhanced training, operational performance and sex -specific

  5. HCMV Reprogramming of Infected Monocyte Survival and Differentiation: A Goldilocks Phenomenon

    Directory of Open Access Journals (Sweden)

    Emily V. Stevenson

    2014-02-01

    Full Text Available The wide range of disease pathologies seen in multiple organ sites associated with human cytomegalovirus (HCMV infection results from the systemic hematogenous dissemination of the virus, which is mediated predominately by infected monocytes. In addition to their role in viral spread, infected monocytes are also known to play a key role in viral latency and life-long persistence. However, in order to utilize infected monocytes for viral spread and persistence, HCMV must overcome a number of monocyte biological hurdles, including their naturally short lifespan and their inability to support viral gene expression and replication. Our laboratory has shown that HCMV is able to manipulate the biology of infected monocytes in order to overcome these biological hurdles by inducing the survival and differentiation of infected monocytes into long-lived macrophages capable of supporting viral gene expression and replication. In this current review, we describe the unique aspects of how HCMV promotes monocyte survival and differentiation by inducing a “finely-tuned” macrophage cell type following infection. Specifically, we describe the induction of a uniquely polarized macrophage subset from infected monocytes, which we argue is the ideal cellular environment for the initiation of viral gene expression and replication and, ultimately, viral spread and persistence within the infected host.

  6. Cellular Glycolysis and The Differential Survival of Lung Fibroblast and Lung Carcinoma Cell Lines.

    Science.gov (United States)

    Farah, Ibrahim O

    2016-04-01

    Tumor growth and abnormal cell survival were shown to be associated with a number of cellular metabolic abnormalities revealed by impaired oral glucose tolerance, depressed lipoprotein lipase activity leading to hypertriglyceridemia, and changes in amino acid profile as evidenced by increased plasma free tryptophan levels in patients with breast, lung, colon, stomach, and other cancers from various origins. The above findings seem to relate to or indicate a shift to non-oxidative metabolic pathways in cancer. In contrast to normal cells, cancer cells may lose the ability to utilize aerobic respiration due to either defective mitochondria or hypoxia within the tumor microenvironments. Glucose was shown to be the major energy source in cancer cells where it utilizes aerobic /anaerobic glycolysis with the resultant lactic acid formation. The role of energetic modulations and use of glycolytic inhibitors on cancer/normal cell survival is not clearly established in the literature. We hypothesize that natural intermediates of glycolysis and the citric acid cycle will differentially and negatively impact the cancer phenotype in contrast to their no effects on the normal cell phenotype. Therefore, the purpose of this study was to evaluate six potential glycolytic modulators namely, Pyruvic acid, oxalic acid, Zn acetate, sodium citrate, fructose diphosphate (FDP) and sodium bicarbonate at μM concentrations on growing A549 (lung cancer) and MRC-5 (normal; human lung fibroblast) cell lines with the objective of determining their influence on visual impact, cell metabolic activity, cell viability and end-point cell survival. Exposed and non-exposed cells were tested with phase-contrast micro-scanning, survival/death and metabolic activity trends through MTT-assays, as well as death end-point determinations by testing re-growth on complete media and T4 cellometer counts. Results showed that oxalic acid and Zn acetate both influenced the pH of the medium and resulted in

  7. Association of Glioblastoma Multiforme Stem Cell Characteristics, Differentiation, and Microglia Marker Genes with Patient Survival

    Directory of Open Access Journals (Sweden)

    Sandra Bien-Möller

    2018-01-01

    Full Text Available Patients with glioblastoma multiforme (GBM are at high risk to develop a relapse despite multimodal therapy. Assumedly, glioma stem cells (GSCs are responsible for treatment resistance of GBM. Identification of specific GSC markers may help to develop targeted therapies. Here, we performed expression analyses of stem cell (ABCG2, CD44, CD95, CD133, ELF4, Nanog, and Nestin as well as differentiation and microglia markers (GFAP, Iba1, and Sparc in GBM compared to nonmalignant brain. Furthermore, the role of these proteins for patient survival and their expression in LN18 stem-like neurospheres was analyzed. At mRNA level, ABCG2 and CD95 were reduced, GFAP was unchanged; all other investigated markers were increased in GBM. At protein level, CD44, ELF4, Nanog, Nestin, and Sparc were elevated in GBM, but only CD133 and Nestin were strongly associated with survival time. In addition, ABCG2 and GFAP expression was decreased in LN18 neurospheres whereas CD44, CD95, CD133, ELF4, Nanog, Nestin, and Sparc were upregulated. Altogether only CD133 and Nestin were associated with survival rates. This raises concerns regarding the suitability of the other target structures as prognostic markers, but makes both CD133 and Nestin candidates for GBM therapy. Nevertheless, a search for more specific marker proteins is urgently needed.

  8. Association of Glioblastoma Multiforme Stem Cell Characteristics, Differentiation, and Microglia Marker Genes with Patient Survival

    Science.gov (United States)

    Balz, Ellen; Herzog, Susann; Plantera, Laura; Vogelgesang, Silke; Seifert, Carolin; Bialke, Angela; Venugopal, Chitra; Singh, Sheila K.; Hoffmann, Wolfgang; Schroeder, Henry W. S.

    2018-01-01

    Patients with glioblastoma multiforme (GBM) are at high risk to develop a relapse despite multimodal therapy. Assumedly, glioma stem cells (GSCs) are responsible for treatment resistance of GBM. Identification of specific GSC markers may help to develop targeted therapies. Here, we performed expression analyses of stem cell (ABCG2, CD44, CD95, CD133, ELF4, Nanog, and Nestin) as well as differentiation and microglia markers (GFAP, Iba1, and Sparc) in GBM compared to nonmalignant brain. Furthermore, the role of these proteins for patient survival and their expression in LN18 stem-like neurospheres was analyzed. At mRNA level, ABCG2 and CD95 were reduced, GFAP was unchanged; all other investigated markers were increased in GBM. At protein level, CD44, ELF4, Nanog, Nestin, and Sparc were elevated in GBM, but only CD133 and Nestin were strongly associated with survival time. In addition, ABCG2 and GFAP expression was decreased in LN18 neurospheres whereas CD44, CD95, CD133, ELF4, Nanog, Nestin, and Sparc were upregulated. Altogether only CD133 and Nestin were associated with survival rates. This raises concerns regarding the suitability of the other target structures as prognostic markers, but makes both CD133 and Nestin candidates for GBM therapy. Nevertheless, a search for more specific marker proteins is urgently needed. PMID:29535786

  9. Developmental and sex-specific differences in expression of neuropeptides derived from allatotropin gene in the silkmoth Bombyx mori.

    Science.gov (United States)

    Bednár, Branislav; Roller, Ladislav; Čižmár, Daniel; Mitrová, Diana; Žitňan, Dušan

    2017-05-01

    Allatotropin (AT) and related neuropeptides are widespread bioactive molecules that regulate development, food intake and muscle contractions in insects and other invertebrates. In moths, alternative splicing of the at gene generates three mRNA precursors encoding AT with different combinations of three structurally similar AT-like peptides (ATLI-III). We used in situ hybridization and immunohistochemistry to map the differential expression of these transcripts during the postembryonic development of Bombyx mori. Transcript encoding AT alone was expressed in numerous neurons of the central nervous system and frontal ganglion, whereas transcripts encoding AT with ATLs were produced by smaller specific subgroups of neurons in larval stages. Metamorphosis was associated with considerable developmental changes and sex-specific differences in the expression of all transcripts. The most notable was the appearance of AT/ATL transcripts (1) in the brain lateral neurosecretory cells producing prothoracicotropic hormone; (2) in the male-specific cluster of about 20 neurons in the posterior region of the terminal abdominal ganglion; (3) in the female-specific medial neurons in the abdominal ganglia AG2-7. Immunohistochemical staining showed that these neurons produced a mixture of various neuropeptides and innervated diverse peripheral organs. Our data suggest that AT/ATL neuropeptides are involved in multiple stage- and sex-specific functions during the development of B. mori.

  10. Sex-specific sleep patterns among university students in Lebanon: impact on depression and academic performance.

    Science.gov (United States)

    Kabrita, Colette S; Hajjar-Muça, Theresa A

    2016-01-01

    Good sleep quality and quantity are fundamental to the maintenance of normal physiological processes. Changes in sleep patterns are commonly observed among young adults and are shown to impact neurocognitive, academic, and psychological well-being. Given the scarcity of sleep information about Lebanon and acknowledging the sex differences in various sleep dimensions, we conducted a study that aimed at assessing sex differences in sleep habits among university students in Lebanon in relation to psychoacademic status. A total of 540 students (50.6% females) completed a questionnaire that inquired about sociodemographics and evaluated sleep quality and depression using the Pittsburg Sleep Quality Index (PSQI) and Center for Epidemiological Studies Depression Scale (CES-D), respectively. The mean PSQI global score (6.57±3.49) indicated poor sleep, with no significant differences between men and women. The sleep/wake rhythm was delayed on weekends for both sexes. Females exhibited earlier bedtimes and rise times and longer sleep durations on both weekdays and weekends. However, unlike males females showed a greater phase delay in wake times than bedtimes on weekends (149 minutes vs 74 minutes, respectively). In all, 70.9% of females suffered from depressive symptoms, which was a significantly higher proportion compared with 58.5% of males (Pacademic performance of females was significantly better than that of males (2.8±0.61 vs 2.65±0.61, Psleep duration (r=-0.221, Psleep timing, such as bedtime/rise time and nocturnal sleep duration, rather than sleep quality exist among Lebanese university students. Sex-specific sleep patterns have differential impact on psychological and academic well-being.

  11. The importance of sex-specific quantitative criteria in thallium-201 myocardial scintigraphy

    International Nuclear Information System (INIS)

    Rabinovitch, M.A.; Suissa, S.; Elstein, J.; Turek, M.; Addas, A.; Burgess, J.H.; Rosenthall, L.

    1984-01-01

    Breast attenuation is an important cause of artifactual cold spots on visually interpreted TL-201 myocardial images. This study was undertaken to determine the need for sex-specific criteria in the quantitative analysis of exercise-redistribution TL-201 myocardial scintigraphy (SCINT). The studies of 13 normal females (F) and 12 normal males (M) were processed according to the method of a previous study. Significant sexual differences were found in 7/12 regional uptake (U) proportions, 9/11 regional washout (WO) percentages, 0/3 image redistribution indices, and 0/1 lung to heart ratio. The differences primarily reflected a proportionately decreased anterior and septal uptake in F, a proportionately decreased inferior and inferoapical U in M, and faster WO in F. Sex-specific and total population normal boundaries were set a +- 3SD of the mean for each parameter. Sex-specific boundaries were narrower, and, for 5 parameters (4U and 1WO), contained within the total population boundaries. It was estimated that these differences in boundaries would result in a 6 to 25% discrepancy in patient classification. These results predict that a subset of M and F with coronary artery stenoses could be misclassified as normal by total population criteria, while properly classified as abnormal by sex-specific criteria. The authors conclude that since important differences exist between M and F in the detected pattern of TL-201 myocardial U and WO, sex-specific cr4iteria may enhance the predictive accuracy of SCINT

  12. Emerging role of LRRK2 in human neural progenitor cell cycle progression, survival and differentiation

    Directory of Open Access Journals (Sweden)

    Meyer Anne K

    2009-06-01

    Full Text Available Abstract Despite a comprehensive mapping of the Parkinson's disease (PD-related mRNA and protein leucine-rich repeat kinase 2 (LRRK2 in the mammalian brain, its physiological function in healthy individuals remains enigmatic. Based on its structural features and kinase properties, LRRK2 may interact with other proteins involved in signalling pathways. Here, we show a widespread LRRK2 mRNA and/or protein expression in expanded or differentiated human mesencephalic neural progenitor cells (hmNPCs and in post-mortem substantia nigra PD patients. Using small interfering RNA duplexes targeting LRRK2 in hmNPCs following their differentiation into glia and neurons, we observed a reduced number of dopaminergic neurons due to apoptosis in LRRK2 knockdown samples. LRRK2-deficient hmNPCs exhibited elevated cell cycle- and cell death-related markers. In conclusion, a reduction of LRRK2 expression in hmNPCs severely impaired dopaminergic differentiation and/or survival of dopaminergic neurons most likely via preserving or reactivating the cell cycle.

  13. Effect of 3D-scaffold formation on differentiation and survival in human neural progenitor cells.

    Science.gov (United States)

    Ortinau, Stefanie; Schmich, Jürgen; Block, Stephan; Liedmann, Andrea; Jonas, Ludwig; Weiss, Dieter G; Helm, Christiane A; Rolfs, Arndt; Frech, Moritz J

    2010-11-11

    3D-scaffolds have been shown to direct cell growth and differentiation in many different cell types, with the formation and functionalisation of the 3D-microenviroment being important in determining the fate of the embedded cells. Here we used a hydrogel-based scaffold to investigate the influences of matrix concentration and functionalisation with laminin on the formation of the scaffolds, and the effect of these scaffolds on human neural progenitor cells cultured within them. In this study we used different concentrations of the hydrogel-based matrix PuraMatrix. In some experiments we functionalised the matrix with laminin I. The impact of concentration and treatment with laminin on the formation of the scaffold was examined with atomic force microscopy. Cells from a human fetal neural progenitor cell line were cultured in the different matrices, as well as in a 2D culture system, and were subsequently analysed with antibody stainings against neuronal markers. In parallel, the survival rate of the cells was determined by a live/dead assay. Atomic force microscopy measurements demonstrated that the matrices are formed by networks of isolated PuraMatrix fibres and aggregates of fibres. An increase of the hydrogel concentration led to a decrease in the mesh size of the scaffolds and functionalisation with laminin promoted aggregation of the fibres (bundle formation), which further reduces the density of isolated fibres. We showed that laminin-functionalisation is essential for human neural progenitor cells to build up 3D-growth patterns, and that proliferation of the cells is also affected by the concentration of matrix. In addition we found that 3D-cultures enhanced neuronal differentiation and the survival rate of the cells compared to 2D-cultures. Taken together, we have demonstrated a direct influence of the 3D-scaffold formation on the survival and neuronal differentiation of human neural progenitor cells. These findings emphasize the importance of optimizing 3

  14. Survival and differentiation defects contribute to neutropenia in glucose-6-phosphatase-β (G6PC3) deficiency in a model of mouse neutrophil granulocyte differentiation.

    Science.gov (United States)

    Gautam, S; Kirschnek, S; Gentle, I E; Kopiniok, C; Henneke, P; Häcker, H; Malleret, L; Belaaouaj, A; Häcker, G

    2013-08-01

    Differentiation of neutrophil granulocytes (neutrophils) occurs through several steps in the bone marrow and requires a coordinate regulation of factors determining survival and lineage-specific development. A number of genes are known whose deficiency disrupts neutrophil generation in humans and in mice. One of the proteins encoded by these genes, glucose-6-phosphatase-β (G6PC3), is involved in glucose metabolism. G6PC3 deficiency causes neutropenia in humans and in mice, linked to enhanced apoptosis and ER stress. We used a model of conditional Hoxb8 expression to test molecular and functional differentiation as well as survival defects in neutrophils from G6PC3(-/-) mice. Progenitor lines were established and differentiated into neutrophils when Hoxb8 was turned off. G6PC3(-/-) progenitor cells underwent substantial apoptosis when differentiation was started. Transgenic expression of Bcl-XL rescued survival; however, Bcl-XL-protected differentiated cells showed reduced proliferation, immaturity and functional deficiency such as altered MAP kinase signaling and reduced cytokine secretion. Impaired glucose utilization was found and was associated with ER stress and apoptosis, associated with the upregulation of Bim and Bax; downregulation of Bim protected against apoptosis during differentiation. ER-stress further caused a profound loss of expression and secretion of the main neutrophil product neutrophil elastase during differentiation. Transplantation of wild-type Hoxb8-progenitor cells into irradiated mice allowed differentiation into neutrophils in the bone marrow in vivo. Transplantation of G6PC3(-/-) cells yielded few mature neutrophils in bone marrow and peripheral blood. Transgenic Bcl-XL permitted differentiation of G6PC3(-/-) cells in vivo. However, functional deficiencies and differentiation abnormalities remained. Differentiation of macrophages from Hoxb8-dependent progenitors was only slightly disturbed. A combination of defects in differentiation

  15. Sex-specific mouse liver gene expression: genome-wide analysis of developmental changes from pre-pubertal period to young adulthood

    Directory of Open Access Journals (Sweden)

    Conforto Tara L

    2012-04-01

    Full Text Available Abstract Background Early liver development and the transcriptional transitions during hepatogenesis are well characterized. However, gene expression changes during the late postnatal/pre-pubertal to young adulthood period are less well understood, especially with regards to sex-specific gene expression. Methods Microarray analysis of male and female mouse liver was carried out at 3, 4, and 8 wk of age to elucidate developmental changes in gene expression from the late postnatal/pre-pubertal period to young adulthood. Results A large number of sex-biased and sex-independent genes showed significant changes during this developmental period. Notably, sex-independent genes involved in cell cycle, chromosome condensation, and DNA replication were down regulated from 3 wk to 8 wk, while genes associated with metal ion binding, ion transport and kinase activity were up regulated. A majority of genes showing sex differential expression in adult liver did not display sex differences prior to puberty, at which time extensive changes in sex-specific gene expression were seen, primarily in males. Thus, in male liver, 76% of male-specific genes were up regulated and 47% of female-specific genes were down regulated from 3 to 8 wk of age, whereas in female liver 67% of sex-specific genes showed no significant change in expression. In both sexes, genes up regulated from 3 to 8 wk were significantly enriched (p p Ihh; female-specific Cdx4, Cux2, Tox, and Trim24 and may contribute to the developmental changes that lead to global acquisition of liver sex-specificity by 8 wk of age. Conclusions Overall, the observed changes in gene expression during postnatal liver development reflect the deceleration of liver growth and the induction of specialized liver functions, with widespread changes in sex-specific gene expression primarily occurring in male liver.

  16. Professional Niche Differentiation: Understanding Dai (Traditional Midwife Survival in Rural Rajasthan

    Directory of Open Access Journals (Sweden)

    Sharmeen Azher

    2017-04-01

    Full Text Available Prescribing medicine, providing contraception, delivering babies – although we may turn to physicians, rural Rajasthani women turn to Barefoot Doctors out of necessity. Such care is available courtesy of the Barefoot College, a pioneering NGO that transforms the skills of the illiterate poor into local infrastructure. Barefoot Doctors are innovative because of their origins as dais (traditional midwives; once abundant across South Asia, dais are mostly extinct due to government/NGO interventions emphasizing “modernity”, like the Accredited Social Health Activist program. Why, then, have dais survived as Barefoot Doctors when they are extinct elsewhere? Ecological niche differentiation refers to when competing species successfully coexist; one species adapts to fulfill another role. Using over fifty interviews with stakeholders, I explain the persistence of Barefoot Doctors as health resources using “professional niche differentiation”. Barefoot Doctors exemplify how health infrastructure can be sustainable in resource-poor settings when created according to local needs and ideologies.

  17. The effect of interferon-{beta} on mouse neural progenitor cell survival and differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Hirsch, Marek [Neurology Department, University of Vermont College of Medicine, Burlington, VT (United States); Knight, Julia [Neuroscience Department, University of Vermont College of Medicine, Burlington, VT (United States); Tobita, Mari; Soltys, John; Panitch, Hillel [Neurology Department, University of Vermont College of Medicine, Burlington, VT (United States); Mao-Draayer, Yang, E-mail: yang.mao-draayer@vtmednet.org [Neurology Department, University of Vermont College of Medicine, Burlington, VT (United States)

    2009-10-16

    Interferon-{beta} (IFN-{beta}) is a mainstay therapy for relapse-remitting multiple sclerosis (MS). However, the direct effects of IFN-{beta} on the central nervous system (CNS) are not well understood. To determine whether IFN-{beta} has direct neuroprotective effects on CNS cells, we treated adult mouse neural progenitor cells (NPCs) in vitro with IFN-{beta} and examined the effects on proliferation, apoptosis, and differentiation. We found that mouse NPCs express high levels of IFN{alpha}/{beta} receptor (IFNAR). In response to IFN-{beta} treatment, no effect was observed on differentiation or proliferation. However, IFN-{beta} treated mouse NPCs demonstrated decreased apoptosis upon growth factor withdrawal. Pathway-specific polymerase chain reaction (PCR) arrays demonstrated that IFN-{beta} treatment upregulated the STAT 1 and 2 signaling pathway, as well as GFRA2, NOD1, Caspases 1 and 12, and TNFSF10. These results suggest that IFN-{beta} can directly affect NPC survival, possibly playing a neuroprotective role in the CNS by modulating neurotrophic factors.

  18. The effect of interferon-β on mouse neural progenitor cell survival and differentiation

    International Nuclear Information System (INIS)

    Hirsch, Marek; Knight, Julia; Tobita, Mari; Soltys, John; Panitch, Hillel; Mao-Draayer, Yang

    2009-01-01

    Interferon-β (IFN-β) is a mainstay therapy for relapse-remitting multiple sclerosis (MS). However, the direct effects of IFN-β on the central nervous system (CNS) are not well understood. To determine whether IFN-β has direct neuroprotective effects on CNS cells, we treated adult mouse neural progenitor cells (NPCs) in vitro with IFN-β and examined the effects on proliferation, apoptosis, and differentiation. We found that mouse NPCs express high levels of IFNα/β receptor (IFNAR). In response to IFN-β treatment, no effect was observed on differentiation or proliferation. However, IFN-β treated mouse NPCs demonstrated decreased apoptosis upon growth factor withdrawal. Pathway-specific polymerase chain reaction (PCR) arrays demonstrated that IFN-β treatment upregulated the STAT 1 and 2 signaling pathway, as well as GFRA2, NOD1, Caspases 1 and 12, and TNFSF10. These results suggest that IFN-β can directly affect NPC survival, possibly playing a neuroprotective role in the CNS by modulating neurotrophic factors.

  19. Differentially expressed and survival-related proteins of lung adenocarcinoma with bone metastasis.

    Science.gov (United States)

    Yang, Mengdi; Sun, Yi; Sun, Jing; Wang, Zhiyu; Zhou, Yiyi; Yao, Guangyu; Gu, Yifeng; Zhang, Huizhen; Zhao, Hui

    2018-04-01

    Despite recent advances in targeted and immune-based therapies, the poor prognosis of lung adenocarcinoma (LUAD) with bone metastasis (BM) remains a challenge. First, two-dimensional gel electrophoresis (2-DE) was used to identify proteins that were differentially expressed in LUAD with BM, and then matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) was used to identify these proteins. Second, the Cancer Genome Atlas (TCGA) was used to identify mutations in these differentially expressed proteins and Kaplan-Meier plotter (KM Plotter) was used to generate survival curves for the analyzed cases. Immunohistochemistry (IHC) was used to check the expression of proteins in 28 patients with BM and nine patients with LUAD. Lastly, the results were analyzed with respect to clinical features and patient's follow-up. We identified a number of matched proteins from 2-DE. High expression of enolase 1 (ENO1) (HR = 1.67, logrank P = 1.9E-05), ribosomal protein lateral stalk subunit P2 (RPLP2) (HR = 1.77, logrank P = 2.9e-06), and NME/NM23 nucleoside diphosphate kinase 2 (NME1-NME2) (HR = 2.65, logrank P = 3.9E-15) was all significantly associated with poor survival (P < 0.05). Further, ENO1 was upregulated (P = 0.0004) and calcyphosine (CAPS1) was downregulated (P = 5.34E-07) in TCGA LUAD RNA-seq expression data. IHC revealed that prominent ENO1 staining (OR = 7.5, P = 0.034) and low levels of CAPS1 (OR = 0.01, P < 0.0001) staining were associated with BM incidence. Finally, we found that LUAD patients with high expression of ENO1 and RPLP2 had worse overall survival. This is the first instance where the genes ENO1, RPLP2, NME1-NME2 and CAPS1 were associated with disease severity and progression in LUAD patients with BM. Thus, with this study, we have identified potential biomarkers and therapeutic targets for this disease. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  20. ALS/FTLD-linked TDP-43 regulates neurite morphology and cell survival in differentiated neurons

    Energy Technology Data Exchange (ETDEWEB)

    Han, Jeong-Ho; Yu, Tae-Hoon; Ryu, Hyun-Hee; Jun, Mi-Hee; Ban, Byung-Kwan [Department of Biotechnology, College of Life Science and Nanotechnology, Hannam University, Dajeon 305-811 (Korea, Republic of); Jang, Deok-Jin [Department of Applied Biology, College of Ecology and Environment, Kyungpook National University, 386, Gajang-dong, Sangju-si, Kyungbuk 742-711 (Korea, Republic of); Lee, Jin-A, E-mail: leeja@hnu.kr [Department of Biotechnology, College of Life Science and Nanotechnology, Hannam University, Dajeon 305-811 (Korea, Republic of)

    2013-08-01

    Tar-DNA binding protein of 43 kDa (TDP-43) has been characterized as a major component of protein aggregates in brains with neurodegenerative diseases such as frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). However, physiological roles of TDP-43 and early cellular pathogenic effects caused by disease associated mutations in differentiated neurons are still largely unknown. Here, we investigated the physiological roles of TDP-43 and the effects of missense mutations associated with diseases in differentiated cortical neurons. The reduction of TDP-43 by siRNA increased abnormal neurites and decreased cell viability. ALS/FTLD-associated missense mutant proteins (A315T, Q331K, and M337V) were partially mislocalized to the cytosol and neurites when compared to wild-type and showed abnormal neurites similar to those observed in cases of loss of TDP-43. Interestingly, cytosolic expression of wild-type TDP-43 with mutated nuclear localization signals also induced abnormal neurtie morphology and reduction of cell viability. However, there was no significant difference in the effects of cytosolic expression in neuronal morphology and cell toxicity between wild-type and missense mutant proteins. Thus, our results suggest that mislocalization of missense mutant TDP-43 may contribute to loss of TDP-43 function and affect neuronal morphology, probably via dominant negative action before severe neurodegeneration in differentiated cortical neurons. Highlights: • The function of nuclear TDP-43 in neurite morphology in mature neurons. • Partial mislocalization of TDP-43 missense mutants into cytosol from nucleus. • Abnormal neurite morphology caused by missense mutants of TDP-43. • The effect of cytosolic expression of TDP-43 in neurite morphology and in cell survival.

  1. ALS/FTLD-linked TDP-43 regulates neurite morphology and cell survival in differentiated neurons

    International Nuclear Information System (INIS)

    Han, Jeong-Ho; Yu, Tae-Hoon; Ryu, Hyun-Hee; Jun, Mi-Hee; Ban, Byung-Kwan; Jang, Deok-Jin; Lee, Jin-A

    2013-01-01

    Tar-DNA binding protein of 43 kDa (TDP-43) has been characterized as a major component of protein aggregates in brains with neurodegenerative diseases such as frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). However, physiological roles of TDP-43 and early cellular pathogenic effects caused by disease associated mutations in differentiated neurons are still largely unknown. Here, we investigated the physiological roles of TDP-43 and the effects of missense mutations associated with diseases in differentiated cortical neurons. The reduction of TDP-43 by siRNA increased abnormal neurites and decreased cell viability. ALS/FTLD-associated missense mutant proteins (A315T, Q331K, and M337V) were partially mislocalized to the cytosol and neurites when compared to wild-type and showed abnormal neurites similar to those observed in cases of loss of TDP-43. Interestingly, cytosolic expression of wild-type TDP-43 with mutated nuclear localization signals also induced abnormal neurtie morphology and reduction of cell viability. However, there was no significant difference in the effects of cytosolic expression in neuronal morphology and cell toxicity between wild-type and missense mutant proteins. Thus, our results suggest that mislocalization of missense mutant TDP-43 may contribute to loss of TDP-43 function and affect neuronal morphology, probably via dominant negative action before severe neurodegeneration in differentiated cortical neurons. Highlights: • The function of nuclear TDP-43 in neurite morphology in mature neurons. • Partial mislocalization of TDP-43 missense mutants into cytosol from nucleus. • Abnormal neurite morphology caused by missense mutants of TDP-43. • The effect of cytosolic expression of TDP-43 in neurite morphology and in cell survival

  2. Association Between CNDP1 Genotype and Diabetic Nephropathy Is Sex Specific

    NARCIS (Netherlands)

    Mooyaart, Antien L.; Zutinic, Ana; Bakker, Stephan J. L.; Grootendorst, Diana C.; Kleefstra, Nanne; van Valkengoed, Irene G. M.; Bohringer, Stefan; Bilo, Henk J. G.; Dekker, Friedo W.; Bruijn, Jan Anthonie; Navis, Gerjan; Janssen, Bart; Baelde, Hans J.; De Heer, Emile

    OBJECTIVE-The 5-5 homozygous CNDP1 (carnosinase) genotype is associated with a reduced risk of diabetic nephropathy. We investigated whether this association is sex specific and independent of susceptibility for type 2 diabetes. RESEARCH DESIGN AND METHODS-Three separate groups of 114, 90, and 66

  3. Facial Resemblance Exaggerates Sex-Specific Jealousy-Based Decisions1

    Directory of Open Access Journals (Sweden)

    Steven M. Platek

    2007-01-01

    Full Text Available Sex differences in reaction to a romantic partner's infidelity are well documented and are hypothesized to be attributable to sex-specific jealousy mechanisms which are utilized to solve adaptive problems associated with risk of extra-pair copulation. Males, because of the risk of cuckoldry become more upset by sexual infidelity, while females, because of loss of resources and biparental investment tend to become more distressed by emotional infidelity. However, the degree to which these sex-specific reactions to jealousy interact with cues to kin are completely unknown. Here we investigated the interaction of facial resemblance with decisions about sex-specific jealousy scenarios. Fifty nine volunteers were asked to imagine that two different people (represented by facial composites informed them about their romantic partner's sexual or emotional infidelity. Consistent with previous research, males ranked sexual infidelity scenarios as most upsetting and females ranked emotional infidelity scenarios most upsetting. However, when information about the infidelity was provided by a face that resembled the subject, sex-specific reactions to jealousy were exaggerated. This finding highlights the use of facial resemblance as a putative self-referent phenotypic matching cue that impacts trusting behavior in sexual contexts.

  4. Sex-specific evolution during the diversification of live-bearing fishes.

    Science.gov (United States)

    Culumber, Zachary W; Tobler, Michael

    2017-08-01

    Natural selection is often assumed to drive parallel functional diversification of the sexes. But males and females exhibit fundamental differences in their biology, and it remains largely unknown how sex differences affect macroevolutionary patterns. On microevolutionary scales, we understand how natural and sexual selection interact to give rise to sex-specific evolution during phenotypic diversification and speciation. Here we show that ignoring sex-specific patterns of functional trait evolution misrepresents the macroevolutionary adaptive landscape and evolutionary rates for 112 species of live-bearing fishes (Poeciliidae). Males and females of the same species evolve in different adaptive landscapes. Major axes of female morphology were correlated with environmental variables but not reproductive investment, while male morphological variation was primarily associated with sexual selection. Despite the importance of both natural and sexual selection in shaping sex-specific phenotypic diversification, species diversification was overwhelmingly associated with ecological divergence. Hence, the inter-predictability of mechanisms of phenotypic and species diversification may be limited in many systems. These results underscore the importance of explicitly addressing sex-specific diversification in empirical and theoretical frameworks of evolutionary radiations to elucidate the roles of different sources of selection and constraint.

  5. Sex-specific genetic effects in physical activity: results from a quantitative genetic analysis.

    Science.gov (United States)

    Diego, Vincent P; de Chaves, Raquel Nichele; Blangero, John; de Souza, Michele Caroline; Santos, Daniel; Gomes, Thayse Natacha; dos Santos, Fernanda Karina; Garganta, Rui; Katzmarzyk, Peter T; Maia, José A R

    2015-08-01

    The objective of this study is to present a model to estimate sex-specific genetic effects on physical activity (PA) levels and sedentary behaviour (SB) using three generation families. The sample consisted of 100 families covering three generations from Portugal. PA and SB were assessed via the International Physical Activity Questionnaire short form (IPAQ-SF). Sex-specific effects were assessed by genotype-by-sex interaction (GSI) models and sex-specific heritabilities. GSI effects and heterogeneity were tested in the residual environmental variance. SPSS 17 and SOLAR v. 4.1 were used in all computations. The genetic component for PA and SB domains varied from low to moderate (11% to 46%), when analyzing both genders combined. We found GSI effects for vigorous PA (p = 0.02) and time spent watching television (WT) (p < 0.001) that showed significantly higher additive genetic variance estimates in males. The heterogeneity in the residual environmental variance was significant for moderate PA (p = 0.02), vigorous PA (p = 0.006) and total PA (p = 0.001). Sex-specific heritability estimates were significantly higher in males only for WT, with a male-to-female difference in heritability of 42.5 (95% confidence interval: 6.4, 70.4). Low to moderate genetic effects on PA and SB traits were found. Results from the GSI model show that there are sex-specific effects in two phenotypes, VPA and WT with a stronger genetic influence in males.

  6. Using RAD-seq to recognize sex-specific markers and sex chromosome systems.

    Science.gov (United States)

    Gamble, Tony

    2016-05-01

    Next-generation sequencing methods have initiated a revolution in molecular ecology and evolution (Tautz et al. ). Among the most impressive of these sequencing innovations is restriction site-associated DNA sequencing or RAD-seq (Baird et al. ; Andrews et al. ). RAD-seq uses the Illumina sequencing platform to sequence fragments of DNA cut by a specific restriction enzyme and can generate tens of thousands of molecular genetic markers for analysis. One of the many uses of RAD-seq data has been to identify sex-specific genetic markers, markers found in one sex but not the other (Baxter et al. ; Gamble & Zarkower ). Sex-specific markers are a powerful tool for biologists. At their most basic, they can be used to identify the sex of an individual via PCR. This is useful in cases where a species lacks obvious sexual dimorphism at some or all life history stages. For example, such tests have been important for studying sex differences in life history (Sheldon ; Mossman & Waser ), the management and breeding of endangered species (Taberlet et al. ; Griffiths & Tiwari ; Robertson et al. ) and sexing embryonic material (Hacker et al. ; Smith et al. ). Furthermore, sex-specific markers allow recognition of the sex chromosome system in cases where standard cytogenetic methods fail (Charlesworth & Mank ; Gamble & Zarkower ). Thus, species with male-specific markers have male heterogamety (XY) while species with female-specific markers have female heterogamety (ZW). In this issue, Fowler & Buonaccorsi () illustrate the ease by which RAD-seq data can generate sex-specific genetic markers in rockfish (Sebastes). Moreover, by examining RAD-seq data from two closely related rockfish species, Sebastes chrysomelas and Sebastes carnatus (Fig. ), Fowler & Buonaccorsi () uncover shared sex-specific markers and a conserved sex chromosome system. © 2016 John Wiley & Sons Ltd.

  7. Gene co-expression networks in liver and muscle transcriptome reveal sex-specific gene expression in lambs fed with a mix of essential oils

    DEFF Research Database (Denmark)

    Sabino, Marcella; Carmelo, Victor Adriano Okstoft; Mazzoni, Gianluca

    2018-01-01

    the potential of RNA-Sequencing data in order to evaluate the effect of an EO supplementary diet on gene expression in both lamb liver and muscle. Using a treatment and sex interaction model, 13 and 4 differentially expressed genes were identified in liver and muscle respectively. Sex-specific differentially...... on the expression profile of both liver and muscle tissues. We hypothesize that the presence of EOs could have beneficial effects on wellness of male lamb and further analyses are needed to understand the biological mechanisms behind the different effect of EO metabolites based on sex. Using lamb as a model...

  8. Sex-specific sleep patterns among university students in Lebanon: impact on depression and academic performance

    Directory of Open Access Journals (Sweden)

    Kabrita CS

    2016-06-01

    .221, P<0.01 on weekdays. GPA of males was significantly correlated with bedtime on weekends (r=-0.159, P<0.05. We conclude that sex differences in sleep timing, such as bedtime/rise time and nocturnal sleep duration, rather than sleep quality exist among Lebanese university students. Sex-specific sleep patterns have differential impact on psychological and academic well-being. Keywords: bedtime-rise time, CES-D, grade point average, PSQI, young adults

  9. Skeletal muscle gene expression in response to resistance exercise: sex specific regulation

    Directory of Open Access Journals (Sweden)

    Burant Charles F

    2010-11-01

    Full Text Available Abstract Background The molecular mechanisms underlying the sex differences in human muscle morphology and function remain to be elucidated. The sex differences in the skeletal muscle transcriptome in both the resting state and following anabolic stimuli, such as resistance exercise (RE, might provide insight to the contributors of sexual dimorphism of muscle phenotypes. We used microarrays to profile the transcriptome of the biceps brachii of young men and women who underwent an acute unilateral RE session following 12 weeks of progressive training. Bilateral muscle biopsies were obtained either at an early (4 h post-exercise or late recovery (24 h post-exercise time point. Muscle transcription profiles were compared in the resting state between men (n = 6 and women (n = 8, and in response to acute RE in trained exercised vs. untrained non-exercised control muscle for each sex and time point separately (4 h post-exercise, n = 3 males, n = 4 females; 24 h post-exercise, n = 3 males, n = 4 females. A logistic regression-based method (LRpath, following Bayesian moderated t-statistic (IMBT, was used to test gene functional groups and biological pathways enriched with differentially expressed genes. Results This investigation identified extensive sex differences present in the muscle transcriptome at baseline and following acute RE. In the resting state, female muscle had a greater transcript abundance of genes involved in fatty acid oxidation and gene transcription/translation processes. After strenuous RE at the same relative intensity, the time course of the transcriptional modulation was sex-dependent. Males experienced prolonged changes while females exhibited a rapid restoration. Most of the biological processes involved in the RE-induced transcriptional regulation were observed in both males and females, but sex specificity was suggested for several signaling pathways including activation of notch signaling and TGF-beta signaling in females

  10. Predicting survival for well-differentiated liposarcoma: the importance of tumor location.

    Science.gov (United States)

    Smith, Caitlin A; Martinez, Steve R; Tseng, Warren H; Tamurian, Robert M; Bold, Richard J; Borys, Dariusz; Canter, Robert J

    2012-06-01

    Although well-differentiated liposarcoma (WD Lipo) is a low grade neoplasm with a negligible risk of metastatic disease, it can be locally aggressive. We hypothesized that survival for WD Lipo varies significantly based on tumor location. We identified 1266 patients with WD Lipo in the Surveillance, Epidemiology, and End Results database from 1988-2004. After excluding patients diagnosed by autopsy only, those lacking histologic confirmation, those lacking data on tumor location, and those with metastatic disease or unknown staging information, we arrived at a final study cohort of 1130 patients. Clinical, pathologic, and treatment variables were analyzed for their association with overall survival (OS) and disease-specific survival (DSS) using Kaplan-Meier analysis and Cox proportional hazards multivariate models. Mean age was 61 y (± 14.6), 72.2% were white, and 60.4% were male. Eighty-one percent of patients were treated with surgical therapy alone, 4.6% were treated with radiotherapy (RT) alone, and 12.9% were treated with both surgery and RT. Extremity location was most common (41.6%), followed by trunk (29%), retroperitoneal/intra-abdominal (RIA, 21.6%), thorax (4.2%), and head/neck (3.6%). With a median follow-up of 45 mo, median OS was 115 mo (95% confidence interval [CI] 92-138 mo) for RIA tumors compared to not reached for other tumor locations (P = 0.002). On multivariate analysis, increasing age and RIA location both predicted worse OS and DSS while tumor size, race, sex, receipt of RT, and Surveillance, Epidemiology, and End Results (SEER) stage did not. Tumor size became a significant predictor of worse DSS, but not OS, only when site, SEER stage, and extent of resection were removed from the multivariate model. Non-RIA locations, including extremity, experienced statistically similar OS, but 5-y DSS for trunk location was intermediate [92.3%, (95% CI 88.5%-96.1%) compared with 98.0% (95% CI, 96.2%-99.8%) for extremity and 86.6 (95% CI 81

  11. Maternal diets trigger sex-specific divergent trajectories of gene expression and epigenetic systems in mouse placenta.

    Directory of Open Access Journals (Sweden)

    Anne Gabory

    Full Text Available Males and females responses to gestational overnutrition set the stage for subsequent sex-specific differences in adult onset non communicable diseases. Placenta, as a widely recognized programming agent, contibutes to the underlying processes. According to our previous findings, a high-fat diet during gestation triggers sex-specific epigenetic alterations within CpG and throughout the genome, together with the deregulation of clusters of imprinted genes. We further investigated the impact of diet and sex on placental histology, transcriptomic and epigenetic signatures in mice. Both basal gene expression and response to maternal high-fat diet were sexually dimorphic in whole placentas. Numerous genes showed sexually dimorphic expression, but only 11 genes regardless of the diet. In line with the key role of genes belonging to the sex chromosomes, 3 of these genes were Y-specific and 3 were X-specific. Amongst all the genes that were differentially expressed under a high-fat diet, only 16 genes were consistently affected in both males and females. The differences were not only quantitative but remarkably qualitative. The biological functions and networks of genes dysregulated differed markedly between the sexes. Seven genes of the epigenetic machinery were dysregulated, due to effects of diet, sex or both, including the Y- and X-linked histone demethylase paralogues Kdm5c and Kdm5d, which could mark differently male and female epigenomes. The DNA methyltransferase cofactor Dnmt3l gene expression was affected, reminiscent of our previous observation of changes in global DNA methylation. Overall, this striking sexual dimorphism of programming trajectories impose a considerable revision of the current dietary interventions protocols.

  12. Low intensity radiation in diapazone of high frequency as factor of the survival modification of differentiated plant cells

    International Nuclear Information System (INIS)

    Tordiya, N.V.

    2005-01-01

    The combined effect of low intensity electromagnetic emission in high frequency range (EMI HF) and ionizing radiation on survival of the differential cells of high plant water Elodea canadensis is investigated. It was established, that EMI HF is radioprotective modification of the radiation injury of plant cell

  13. Plasma Rich in Growth Factors Induces Cell Proliferation, Migration, Differentiation, and Cell Survival of Adipose-Derived Stem Cells.

    Science.gov (United States)

    Mellado-López, Maravillas; Griffeth, Richard J; Meseguer-Ripolles, Jose; Cugat, Ramón; García, Montserrat; Moreno-Manzano, Victoria

    2017-01-01

    Adipose-derived stem cells (ASCs) are a promising therapeutic alternative for tissue repair in various clinical applications. However, restrictive cell survival, differential tissue integration, and undirected cell differentiation after transplantation in a hostile microenvironment are complications that require refinement. Plasma rich in growth factors (PRGF) from platelet-rich plasma favors human and canine ASC survival, proliferation, and delaying human ASC senescence and autophagocytosis in comparison with serum-containing cultures. In addition, canine and human-derived ASCs efficiently differentiate into osteocytes, adipocytes, or chondrocytes in the presence of PRGF. PRGF treatment induces phosphorylation of AKT preventing ASC death induced by lethal concentrations of hydrogen peroxide. Indeed, AKT inhibition abolished the PRGF apoptosis prevention in ASC exposed to 100  μ M of hydrogen peroxide. Here, we show that canine ASCs respond to PRGF stimulus similarly to the human cells regarding cell survival and differentiation postulating the use of dogs as a suitable translational model. Overall, PRGF would be employed as a serum substitute for mesenchymal stem cell amplification to improve cell differentiation and as a preconditioning agent to prevent oxidative cell death.

  14. Plasma Rich in Growth Factors Induces Cell Proliferation, Migration, Differentiation, and Cell Survival of Adipose-Derived Stem Cells

    Directory of Open Access Journals (Sweden)

    Maravillas Mellado-López

    2017-01-01

    Full Text Available Adipose-derived stem cells (ASCs are a promising therapeutic alternative for tissue repair in various clinical applications. However, restrictive cell survival, differential tissue integration, and undirected cell differentiation after transplantation in a hostile microenvironment are complications that require refinement. Plasma rich in growth factors (PRGF from platelet-rich plasma favors human and canine ASC survival, proliferation, and delaying human ASC senescence and autophagocytosis in comparison with serum-containing cultures. In addition, canine and human-derived ASCs efficiently differentiate into osteocytes, adipocytes, or chondrocytes in the presence of PRGF. PRGF treatment induces phosphorylation of AKT preventing ASC death induced by lethal concentrations of hydrogen peroxide. Indeed, AKT inhibition abolished the PRGF apoptosis prevention in ASC exposed to 100 μM of hydrogen peroxide. Here, we show that canine ASCs respond to PRGF stimulus similarly to the human cells regarding cell survival and differentiation postulating the use of dogs as a suitable translational model. Overall, PRGF would be employed as a serum substitute for mesenchymal stem cell amplification to improve cell differentiation and as a preconditioning agent to prevent oxidative cell death.

  15. Sex-Specific Effects of Combined Exposure to Chemical and Non-chemical Stressors on Neuroendocrine Development: a Review of Recent Findings and Putative Mechanisms.

    Science.gov (United States)

    Cowell, Whitney J; Wright, Rosalind J

    2017-12-01

    Environmental toxicants and psychosocial stressors share many biological substrates and influence overlapping physiological pathways. Increasing evidence indicates stress-induced changes to the maternal milieu may prime rapidly developing physiological systems for disruption by concurrent or subsequent exposure to environmental chemicals. In this review, we highlight putative mechanisms underlying sex-specific susceptibility of the developing neuroendocrine system to the joint effects of stress or stress correlates and environmental toxicants (bisphenol A, alcohol, phthalates, lead, chlorpyrifos, and traffic-related air pollution). We provide evidence indicating that concurrent or tandem exposure to chemical and non-chemical stressors during windows of rapid development is associated with sex-specific synergistic, potentiated and reversed effects on several neuroendocrine endpoints related to hypothalamic-pituitary-adrenal axis function, sex steroid levels, neurotransmitter circuits, and innate immune function. We additionally identify gaps, such as the role that the endocrine-active placenta plays, in our understanding of these complex interactions. Finally, we discuss future research needs, including the investigation of non-hormonal biomarkers of stress. We demonstrate multiple physiologic systems are impacted by joint exposure to chemical and non-chemical stressors differentially among males and females. Collectively, the results highlight the importance of evaluating sex-specific endpoints when investigating the neuroendocrine system and underscore the need to examine exposure to chemical toxicants within the context of the social environment.

  16. Facial Resemblance Exaggerates Sex-Specific Jealousy-Based Decisions1

    OpenAIRE

    Steven M. Platek; Jaime W. Thomson

    2007-01-01

    Sex differences in reaction to a romantic partner's infidelity are well documented and are hypothesized to be attributable to sex-specific jealousy mechanisms which are utilized to solve adaptive problems associated with risk of extra-pair copulation. Males, because of the risk of cuckoldry become more upset by sexual infidelity, while females, because of loss of resources and biparental investment tend to become more distressed by emotional infidelity. However, the degree to which these sex-...

  17. Grazing, differential size-class dynamics and survival of the Mediterranean sponge Corticium candelabrum

    NARCIS (Netherlands)

    Caralt, de S.; Uriz, M.J.; Wijffels, R.H.

    2008-01-01

    The growth dynamics and survival of the sponge Corticium candelabrum (Demospongiae: Homosclerophorida) were surveyed in the northwestern Mediterranean for more than 3 yr. Growth and regeneration rates, fission and fusion events and survival were monitored monthly. Moreover, in situ punctual

  18. Sex-specific differences in the synaptonemal complex in the genus Oreochromis (Cichlidae).

    Science.gov (United States)

    Campos-Ramos, Rafael; Harvey, Simon C; Penman, David J

    2009-04-01

    Total synaptonemal complex (SC) lengths were estimated from Oreochromis aureus Steindachner (which has a WZ/ZZ sex determination system), O. mossambicus Peters and O. niloticus L. (both of which have XX/XY sex determination systems). The total SC length in oocytes was greater than that in spermatocytes in all three species (194 +/- 30 microm and 134 +/- 13 microm, 187 +/- 22 microm and 127 +/- 17 microm, 193 +/- 37 microm and 144 +/- 19 microm, respectively). These sex-specific differences did not appear to be influenced by the type of sex determination system (the female/male total SC length ratio was 1.45 in O. aureus, 1.47 in O. mossambicus and 1.34 in O. niloticus) and do not correlate with the lack of any overall sex-specific length differences in the current Oreochromis linkage map. Although based on data from relatively few species, there appears to be no consistent relationship between sex-specific SC lengths and linkage map lengths in fish. Neomale (hormonally masculinized genetic female) O. aureus and O. mossambicus had total SC lengths of 138 +/- 13 microm and 146 +/- 13 microm respectively, more similar to normal males than to normal females. These findings agree with data from other vertebrate species that suggest that phenotypic sex, rather than genotype, determines traits such as total SC length, chiasmata position and recombination pattern, at least for the autosomes.

  19. Sex-Specificity of Oxidative Stress in Newborns Leading to a Personalized Antioxidant Nutritive Strategy

    Directory of Open Access Journals (Sweden)

    Jean-Claude Lavoie

    2018-03-01

    Full Text Available Oxidative stress is a critical process that triggers several diseases observed in premature infants. Growing recognition of the detriment of oxidative stress in newborns warrants the use of an antioxidant strategy that is likely to be nutritional in order to restore redox homeostasis. It appears essential to have a personalized approach that will take into account the age of gestation at birth and the sex of the infant. However, the link between sex and oxidative stress remains unclear. The aim of this study was to find a common denominator explaining the discrepancy between studies related to sex-specific effects of oxidative stress. Results highlight a specificity of sex in the levels of oxidative stress markers linked to the metabolism of glutathione, as measured in the intracellular compartments. Levels of all sex-dependent oxidative stress markers are greater and markers associated to a better antioxidant defense are lower in boys compared to girls during the neonatal period. This sex-specific discrepancy is likely to be related to estrogen metabolism, which is more active in baby-girls and promotes the activation of glutathione metabolism. Conclusion: our observations suggest that nutritive antioxidant strategies need to target glutathione metabolism and, therefore, should be personalized considering, among others, the sex specificity.

  20. Prenatal stress challenge impairs fetal lung development and asthma severity sex-specifically in mice.

    Science.gov (United States)

    Zazara, Dimitra E; Perani, Clara V; Solano, María E; Arck, Petra C

    2018-02-01

    Allergic asthma is an increasing health problem worldwide. Interestingly, prenatal challenges such as stress have been associated with an increased risk for asthma during childhood. The underlying pathogenesis of how prenatal stress increases the risk for asthma still remains unclear. Potential targets could be that the fetal immune ontogeny or fetal lung development are compromised by prenatal challenges. Here, we aimed to identify whether prenatal stress challenge affects fetal lung development in mice. C57BL/6 pregnant mice were challenged with sound stress and fetal lung development was assessed histologically. Whilst prenatal stress challenge did not profoundly affect lung development in male fetuses, it resulted in less extensive terminal sacs, surrounded by thicker mesenchymal tissue in female fetuses. Thus, prenatal stress disrupted fetal lung development sex-specifically. Interestingly, upon prenatal stress challenge, the airway hyperresponsiveness and eosinophilic inflammation- two hallmarks of asthma - were significantly increased in adult female offspring, whilst regulatory CD4+ T cells were reduced. These findings strongly underpin the sex-specific association between s challenged fetal development and a sex-specific altered severity of asthma in adult offspring. Our model now allows to identify maternal markers through which the risk for asthma and possible other diseases is vertically transferred before birth in response to challenges. Such identification then opens avenues for primary disease prevention. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Sex-Specificity of Oxidative Stress in Newborns Leading to a Personalized Antioxidant Nutritive Strategy.

    Science.gov (United States)

    Lavoie, Jean-Claude; Tremblay, André

    2018-03-27

    Oxidative stress is a critical process that triggers several diseases observed in premature infants. Growing recognition of the detriment of oxidative stress in newborns warrants the use of an antioxidant strategy that is likely to be nutritional in order to restore redox homeostasis. It appears essential to have a personalized approach that will take into account the age of gestation at birth and the sex of the infant. However, the link between sex and oxidative stress remains unclear. The aim of this study was to find a common denominator explaining the discrepancy between studies related to sex-specific effects of oxidative stress. Results highlight a specificity of sex in the levels of oxidative stress markers linked to the metabolism of glutathione, as measured in the intracellular compartments. Levels of all sex-dependent oxidative stress markers are greater and markers associated to a better antioxidant defense are lower in boys compared to girls during the neonatal period. This sex-specific discrepancy is likely to be related to estrogen metabolism, which is more active in baby-girls and promotes the activation of glutathione metabolism. our observations suggest that nutritive antioxidant strategies need to target glutathione metabolism and, therefore, should be personalized considering, among others, the sex specificity.

  2. Sex-specific metabolic profiles of androgens and its main binding protein SHBG in a middle aged population without diabetes

    DEFF Research Database (Denmark)

    Piontek, Uwe; Wallaschofski, Henri; Kastenmüller, Gabi

    2017-01-01

    The role of androgens in metabolism with respect to sex-specific disease associations is poorly understood. Therefore, we aimed to provide molecular signatures in plasma and urine of androgen action in a sex-specific manner using state-of-the-art metabolomics techniques. Our study population...

  3. Age- and sex-specific thorax finite element model development and simulation.

    Science.gov (United States)

    Schoell, Samantha L; Weaver, Ashley A; Vavalle, Nicholas A; Stitzel, Joel D

    2015-01-01

    The shape, size, bone density, and cortical thickness of the thoracic skeleton vary significantly with age and sex, which can affect the injury tolerance, especially in at-risk populations such as the elderly. Computational modeling has emerged as a powerful and versatile tool to assess injury risk. However, current computational models only represent certain ages and sexes in the population. The purpose of this study was to morph an existing finite element (FE) model of the thorax to depict thorax morphology for males and females of ages 30 and 70 years old (YO) and to investigate the effect on injury risk. Age- and sex-specific FE models were developed using thin-plate spline interpolation. In order to execute the thin-plate spline interpolation, homologous landmarks on the reference, target, and FE model are required. An image segmentation and registration algorithm was used to collect homologous rib and sternum landmark data from males and females aged 0-100 years. The Generalized Procrustes Analysis was applied to the homologous landmark data to quantify age- and sex-specific isolated shape changes in the thorax. The Global Human Body Models Consortium (GHBMC) 50th percentile male occupant model was morphed to create age- and sex-specific thoracic shape change models (scaled to a 50th percentile male size). To evaluate the thoracic response, 2 loading cases (frontal hub impact and lateral impact) were simulated to assess the importance of geometric and material property changes with age and sex. Due to the geometric and material property changes with age and sex, there were observed differences in the response of the thorax in both the frontal and lateral impacts. Material property changes alone had little to no effect on the maximum thoracic force or the maximum percent compression. With age, the thorax becomes stiffer due to superior rotation of the ribs, which can result in increased bone strain that can increase the risk of fracture. For the 70-YO models

  4. Neurogenesis and Increase in Differentiated Neural Cell Survival via Phosphorylation of Akt1 after Fluoxetine Treatment of Stem Cells

    Directory of Open Access Journals (Sweden)

    Anahita Rahmani

    2013-01-01

    Full Text Available Fluoxetine (FLX is a selective serotonin reuptake inhibitor (SSRI. Its action is possibly through an increase in neural cell survival. The mechanism of improved survival rate of neurons by FLX may relate to the overexpression of some kinases such as Akt protein. Akt1 (a serine/threonine kinase plays a key role in the modulation of cell proliferation and survival. Our study evaluated the effects of FLX on mesenchymal stem cell (MSC fate and Akt1 phosphorylation levels in MSCs. Evaluation tests included reverse transcriptase polymerase chain reaction, western blot, and immunocytochemistry assays. Nestin, MAP-2, and β-tubulin were detected after neurogenesis as neural markers. Ten μM of FLX upregulated phosphorylation of Akt1 protein in induced hEnSC significantly. Also FLX did increase viability of these MSCs. Continuous FLX treatment after neurogenesis elevated the survival rate of differentiated neural cells probably by enhanced induction of Akt1 phosphorylation. This study addresses a novel role of FLX in neurogenesis and differentiated neural cell survival that may contribute to explaining the therapeutic action of fluoxetine in regenerative pharmacology.

  5. Ferulic acid promotes survival and differentiation of neural stem cells to prevent gentamicin-induced neuronal hearing loss.

    Science.gov (United States)

    Gu, Lintao; Cui, Xinhua; Wei, Wei; Yang, Jia; Li, Xuezhong

    2017-11-15

    Neural stem cells (NSCs) have exhibited promising potential in therapies against neuronal hearing loss. Ferulic acid (FA) has been widely reported to enhance neurogenic differentiation of different stem cells. We investigated the role of FA in promoting NSC transplant therapy to prevent gentamicin-induced neuronal hearing loss. NSCs were isolated from mouse cochlear tissues to establish in vitro culture, which were then treated with FA. The survival and differentiation of NSCs were evaluated. Subsequently, neurite outgrowth and excitability of the in vitro neuronal network were assessed. Gentamicin was used to induce neuronal hearing loss in mice, in the presence and absence of FA, followed by assessments of auditory brainstem response (ABR) and distortion product optoacoustic emissions (DPOAE) amplitude. FA promoted survival, neurosphere formation and differentiation of NSCs, as well as neurite outgrowth and excitability of in vitro neuronal network. Furthermore, FA restored ABR threshold shifts and DPOAE in gentamicin-induced neuronal hearing loss mouse model in vivo. Our data, for the first time, support potential therapeutic efficacy of FA in promoting survival and differentiation of NSCs to prevent gentamicin-induced neuronal hearing loss. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Pediatric differentiated thyroid carcinoma in stage I: risk factor analysis for disease free survival

    International Nuclear Information System (INIS)

    Wada, Nobuyuki; Rino, Yasushi; Masuda, Munetaka; Ito, Koichi; Sugino, Kiminori; Mimura, Takashi; Nagahama, Mitsuji; Kitagawa, Wataru; Shibuya, Hiroshi; Ohkuwa, Keiko; Nakayama, Hirotaka; Hirakawa, Shohei

    2009-01-01

    To examine the outcomes and risk factors in pediatric differentiated thyroid carcinoma (DTC) patients who were defined as TNM stage I because some patients develop disease recurrence but treatment strategy for such stage I pediatric patients is still controversial. We reviewed 57 consecutive TNM stage I patients (15 years or less) with DTC (46 papillary and 11 follicular) who underwent initial treatment at Ito Hospital between 1962 and 2004 (7 males and 50 females; mean age: 13.1 years; mean follow-up: 17.4 years). Clinicopathological results were evaluated in all patients. Multivariate analysis was performed to reveal the risk factors for disease-free survival (DFS) in these 57 patients. Extrathyroid extension and clinical lymphadenopathy at diagnosis were found in 7 and 12 patients, respectively. Subtotal/total thyroidectomy was performed in 23 patients, modified neck dissection in 38, and radioactive iodine therapy in 10. Pathological node metastasis was confirmed in 37 patients (64.9%). Fifteen patients (26.3%) exhibited local recurrence and 3 of them also developed metachronous lung metastasis. Ten of these 15 achieved disease-free after further treatments and no patients died of disease. In multivariate analysis, male gender (p = 0.017), advanced tumor (T3, 4a) stage (p = 0.029), and clinical lymphadenopathy (p = 0.006) were risk factors for DFS in stage I pediatric patients. Male gender, tumor stage, and lymphadenopathy are risk factors for DFS in stage I pediatric DTC patients. Aggressive treatment (total thyroidectomy, node dissection, and RI therapy) is considered appropriate for patients with risk factors, whereas conservative or stepwise approach may be acceptable for other patients

  7. Sex-specific life history responses to nymphal diet quality and immune status in a field cricket.

    Science.gov (United States)

    Kelly, C D; Neyer, A A; Gress, B E

    2014-02-01

    Individual fitness is expected to benefit from earlier maturation at a larger body size and higher body condition. However, poor nutritional quality or high prevalence of disease make this difficult because individuals either cannot acquire sufficient resources or must divert resources to other fitness-related traits such as immunity. Under such conditions, individuals are expected to mature later at a smaller body size and in poorer body condition. Moreover, the juvenile environment can also produce longer-term effects on adult fitness by causing shifts in resource allocation strategies that could alter investment in immune function and affect adult lifespan. We manipulated diet quality and immune status of juvenile Texas field crickets, Gryllus texensis, to investigate how poor developmental conditions affect sex-specific investment in fitness-related traits. As predicted, a poor juvenile diet was related to smaller mass and body size at eclosion in both sexes. However, our results also reveal sexually dimorphic responses to different facets of the rearing environment: female life history decisions are affected more by diet quality, whereas males are affected more by immune status. We suggest that females respond to decreased nutritional income because this threatens their ability to achieve a large adult body size, whereas male fitness is more dependent on reaching adulthood and so they invest in immunity and survival to eclosion. © 2013 The Authors. Journal of Evolutionary Biology © 2013 European Society For Evolutionary Biology.

  8. Proteomic profiling of human keratinocytes undergoing UVB-induced alternative differentiation reveals TRIpartite Motif Protein 29 as a survival factor.

    Directory of Open Access Journals (Sweden)

    Véronique Bertrand-Vallery

    Full Text Available BACKGROUND: Repeated exposures to UVB of human keratinocytes lacking functional p16(INK-4a and able to differentiate induce an alternative state of differentiation rather than stress-induced premature senescence. METHODOLOGY/PRINCIPAL FINDINGS: A 2D-DIGE proteomic profiling of this alternative state of differentiation was performed herein at various times after the exposures to UVB. Sixty-nine differentially abundant protein species were identified by mass spectrometry, many of which are involved in keratinocyte differentiation and survival. Among these protein species was TRIpartite Motif Protein 29 (TRIM29. Increased abundance of TRIM29 following UVB exposures was validated by Western blot using specific antibody and was also further analysed by immunochemistry and by RT-PCR. TRIM29 was found very abundant in keratinocytes and reconstructed epidermis. Knocking down the expression of TRIM29 by short-hairpin RNA interference decreased the viability of keratinocytes after UVB exposure. The abundance of involucrin mRNA, a marker of late differentiation, increased concomitantly. In TRIM29-knocked down reconstructed epidermis, the presence of picnotic cells revealed cell injury. Increased abundance of TRIM29 was also observed upon exposure to DNA damaging agents and PKC activation. The UVB-induced increase of TRIM29 abundance was dependent on a PKC signaling pathway, likely PKCdelta. CONCLUSIONS/SIGNIFICANCE: These findings suggest that TRIM29 allows keratinocytes to enter a protective alternative differentiation process rather than die massively after stress.

  9. Deletion of Fmr1 results in sex-specific changes in behavior.

    Science.gov (United States)

    Nolan, Suzanne O; Reynolds, Conner D; Smith, Gregory D; Holley, Andrew J; Escobar, Brianna; Chandler, Matthew A; Volquardsen, Megan; Jefferson, Taylor; Pandian, Ashvini; Smith, Tileena; Huebschman, Jessica; Lugo, Joaquin N

    2017-10-01

    In this study, we used a systemic Fmr1 knockout in order to investigate both genotype- and sex-specific differences across multiple measures of sociability, repetitive behaviors, activity levels, anxiety, and fear-related learning and memory. Fragile X syndrome is the most common monogenic cause of intellectual disability and autism. Few studies to date have examined sex differences in a mouse model of Fragile X syndrome, though clinical data support the idea of differences in both overall prevalence and phenotype between the sexes. Using wild-type and systemic homozygous Fmr1 knockout mice, we assessed a variety of behavioral paradigms in adult animals, including the open field test, elevated plus maze, nose-poke assay, accelerating rotarod, social partition task, three-chambered social task, and two different fear conditioning paradigms. Tests were ordered such that the most invasive tests were performed last in the sequence, and testing paradigms for similar behaviors were performed in separate cohorts to minimize testing effects. Our results indicate several sex-specific changes in Fmr1 knockout mice, including male-specific increases in activity levels, and female-specific increases in repetitive behaviors on both the nose-poke assay and motor coordination on the accelerating rotarod task. The results also indicated that Fmr1 deletion results in deficits in fear learning and memory across both sexes, and no changes in social behavior across two tasks. These findings highlight the importance of including female subjects in preclinical studies, as simply studying the impact of genetic mutations in males does not yield a complete picture of the phenotype. Further research should explore these marked phenotypic differences among the sexes. Moreover, given that treatment strategies are typically equivalent between the sexes, the results highlight a potential need for sex-specific therapeutics.

  10. Sex specific effects of heat induced hormesis in Hsf-deficient Drosophila melanogaster

    DEFF Research Database (Denmark)

    Sørensen, J G; Kristensen, Torsten Nygård; Kristensen, K V

    2007-01-01

    In insects mild heat stress early in life has been reported to increase life span and heat resistance later in life, a phenomenon termed hormesis. Here, we test if the induction of the heat shock response by mild heat stress is mediating hormesis in longevity and heat resistance at older age...... line, seemingly mediated by the production of heat shock proteins (Hsps). The results indicate that heat inducible Hsps are important for heat induced hormesis in longevity and heat stress resistance. However, the results also suggest that other processes are involved and that different mechanisms...... might have marked sex specific impact...

  11. Fetal sex-specific differences in gestational age at delivery in pre-eclampsia

    DEFF Research Database (Denmark)

    Schalekamp-Timmermans, Sarah; Arends, Lidia R.; Alsaker, Elin

    2017-01-01

    Background: Pre-eclampsia (PE) is a major pregnancy disorder complicating up to 8% of pregnancies. Increasing evidence indicates a sex-specific interplay between the mother,placenta and fetus. This may lead to different adaptive mechanisms during pregnancy. Methods: We performed an individual...... fetus as compared with pregnancies with a male fetus (OR 1.36, 95% CI 1.17-1.59). Conclusions: Sexual dimorphic differences in the occurrence of PE exist, with preterm PE being more prevalent among pregnancies with a female fetus as compared with pregnancies with a male fetus and with no differences...

  12. Sex-specific expression of the X-linked histone demethylase gene Jarid1c in brain.

    Directory of Open Access Journals (Sweden)

    Jun Xu

    Full Text Available Jarid1c, an X-linked gene coding for a histone demethylase, plays an important role in brain development and function. Notably, JARID1C mutations cause mental retardation and increased aggression in humans. These phenotypes are consistent with the expression patterns we have identified in mouse brain where Jarid1c mRNA was detected in hippocampus, hypothalamus, and cerebellum. Jarid1c expression and associated active histone marks at its 5'end are high in P19 neurons, indicating that JARID1C demethylase plays an important role in differentiated neuronal cells. We found that XX mice expressed Jarid1c more highly than XY mice, independent of their gonadal types (testes versus ovaries. This increased expression in XX mice is consistent with Jarid1c escape from X inactivation and is not compensated by expression from the Y-linked paralogue Jarid1d, which is expressed at a very low level compared to the X paralogue in P19 cells. Our observations suggest that sex-specific expression of Jarid1c may contribute to sex differences in brain function.

  13. Analysis of sex-specific injury patterns and risk factors in young high-level athletes.

    Science.gov (United States)

    Frisch, A; Seil, R; Urhausen, A; Croisier, J L; Lair, M L; Theisen, D

    2009-12-01

    This study analyzed sex-specific injury patterns and risk factors in young athletes (n=256) from 12 sport disciplines practicing at the national or the international level in the Grand-Duchy of Luxembourg. Injury occurrence as a result of sport practice was analyzed retrospectively over the year 2006 using a standardized self-administered questionnaire. Overall incidence was not different between girls and boys (1.20 and 1.21 injuries/1000 athlete-hours, respectively), but in the context of team sport competition girls tended to be at a greater risk (rate ratio 2.05, P=0.053). Girls had a higher proportion of injuries in the ankle/foot region compared with boys (34.8% vs 16.8%). No sex-related differences were found regarding injury severity. Multivariate logistic regression (controlling for age and practice volume) revealed that girls' team sports were associated with a greater injury risk compared with individual sports [odds ratio (OR) of 4.76], while in boys this was observed for racket sports (OR=3.31). Furthermore, physical or emotional stress tended to be a specific risk factor in girls. There was a tendency for injury outside sports to be coupled to a higher injury risk in girls and boys. Consideration of sex-specific injury patterns and risk factors could be of importance for effective injury prevention.

  14. Sex-Specific Sociodemographic Correlates of Dietary Patterns in a Large Sample of French Elderly Individuals

    Directory of Open Access Journals (Sweden)

    Valentina A. Andreeva

    2016-08-01

    Full Text Available This cross-sectional analysis provides up-to-date information about dietary patterns (DP and their sociodemographic correlates in European elderly individuals. We studied 6686 enrollees aged 65+ (55% women in the ongoing French population-based NutriNet-Santé e-cohort. Diet was assessed via three 24 h records. The sex-specific correlates of factor analysis derived DP were identified with multivariable linear regression. Using 22 pre-defined food groups, three DP were extracted. The “healthy” DP (fruit, vegetables, grains, nuts, fish was positively associated with education, living alone, and being a former smoker (women, and negatively associated with being overweight, current smoker (men, age 75+ years, having hypertension, and obesity (women. The “western” DP (meat, appetizers, cheese, alcohol was positively associated with BMI (men and being a former/current smoker; it was negatively associated with age 75+ years (women and living alone. The “traditional” DP (bread, potatoes, milk, vegetables, butter, stock was positively associated with age and negatively associated with being a former/current smoker, education (men, and residing in an urban/semi-urban area. The findings support the diversity of DP among the elderly, highlighting sex-specific differences. The “healthy” DP explained the largest amount of variance in intake. Future studies could replicate the models in longitudinal and international contexts.

  15. Piloting a Sex-Specific, Technology-Enhanced, Active Learning Intervention for Stroke Prevention in Women.

    Science.gov (United States)

    Dirickson, Amanda; Stutzman, Sonja E; Alberts, Mark J; Novakovic, Roberta L; Stowe, Ann M; Beal, Claudia C; Goldberg, Mark P; Olson, DaiWai M

    2017-12-01

    Recent studies reveal deficiencies in stroke awareness and knowledge of risk factors among women. Existing stroke education interventions may not address common and sex-specific risk factors in the population with the highest stroke-related rate of mortality. This pilot study assessed the efficacy of a technology-enhanced, sex-specific educational program ("SISTERS") for women's knowledge of stroke. This was an experimental pretest-posttest design. The sample consisted of 150 women (mean age, 55 years) with at least 1 stroke risk factor. Participants were randomized to either the intervention (n = 75) or control (n = 75) group. Data were collected at baseline and at a 2-week posttest. There was no statistically significant difference in mean knowledge score (P = .67), mean confidence score (P = .77), or mean accuracy score (P = .75) between the intervention and control groups at posttest. Regression analysis revealed that older age was associated with lower knowledge scores (P < .001) and lower confidence scores (P < .001). After controlling for age, the SISTERS program was associated with a statistically significant difference in knowledge (P < .001) and confidence (P < .001). Although no change occurred overall, after controlling for age, there was a statistically significant benefit. Older women may have less comfort with technology and require consideration for cognitive differences.

  16. Sex-specific features of emphysema among current and former smokers with COPD.

    Science.gov (United States)

    Hardin, Megan; Foreman, Marilyn; Dransfield, Mark T; Hansel, Nadia; Han, MeiLan K; Cho, Michael H; Bhatt, Surya P; Ramsdell, Joe; Lynch, David; Curtis, Jeffrey L; Silverman, Edwin K; Washko, George; DeMeo, Dawn

    2016-01-01

    Recent studies suggest that males with chronic obstructive pulmonary disease (COPD) have more emphysema than females. It is not known if these differences persist across degrees of COPD severity. Our aim was to identify sex-specific differences in quantitative emphysema within COPD subgroups based on COPD severity.We included non-Hispanic white and African-American subjects from the COPDGene study with at least 10 pack-years of smoking and COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometry grade II or greater. We examined sex-specific differences in log-transformed emphysema (log per cent low-attenuation area (%LAA)) by GOLD spirometry grade among subjects with early-onset COPD (25% emphysema).Compared with females, males had higher log %LAA: overall (1.97±1.4 versus 1.69±1.6, β=0.32 (0.04), p=1.34×10(-14)), and among non-Hispanic white (p=8.37×10(-14)) and African-American subjects (p=0.002). Females with early-onset COPD, severe emphysema and GOLD grade IV COPD had similar emphysema as males, but markedly fewer pack-years smoking (early-onset, p=0.01; severe emphysema and GOLD grade IV, psmokers with COPD who are particularly susceptible to parenchymal destruction. Copyright ©ERS 2016.

  17. Sex-specific incidence and temporal trends in solid tumours in young people from Northern England, 1968–2005

    International Nuclear Information System (INIS)

    Magnanti, Brooke L; Dorak, M Tevfik; Parker, Louise; Craft, Alan W; James, Peter W; McNally, Richard JQ

    2008-01-01

    .2%–7.1%). This study has highlighted notable differences between the sexes in incidence patterns and trends for solid tumours. Some of these sex-specific differences could have been obscured if males and females had been analysed together. Furthermore, they suggest aetiological differences or differential susceptibility to environmental factors between males and females

  18. Protecting and rescuing the effectors: roles of differentiation and survival in the control of memory T cell development

    Directory of Open Access Journals (Sweden)

    Sema eKurtulus

    2013-01-01

    Full Text Available Vaccines, arguably the single most important intervention in improving human health, have exploited the phenomenon of immunological memory. The elicitation of memory T cells is often an essential part of successful long-lived protective immunity. Our understanding of T cell memory has been greatly aided by the development of TCR Tg mice and MHC tetrameric staining reagents that have allowed the precise tracking of antigen-specific T cell responses. Indeed, following acute infection or immunization, naïve T cells undergo a massive expansion culminating in the generation of a robust effector T cell population. This peak effector response is relatively short-lived and, while most effector T cells die by apoptosis, some remain and develop into memory cells. Although the molecular mechanisms underlying this cell fate decision remain incompletely defined, substantial progress has been made, particularly with regards to CD8+ T cells. For example, the effector CD8+ T cells generated during a response are heterogeneous, consisting of cells with more or less potential to develop into full-fledged memory cells. Development of CD8+ T cell memory is regulated by the transcriptional programs that control the differentiation and survival of effector T cells. While the type of antigenic stimulation and level of inflammation control effector CD8+ T cell differentiation, availability of cytokines and their ability to control expression and function of Bcl-2 family members governs their survival. These distinct differentiation and survival programs may allow for finer therapeutic intervention to control both the quality and quantity of CD8+ T cell memory. Effector to memory transition of CD4+ T cells is less well characterized than CD8+ T cells, emerging details will be discussed. This review will focus on the recent progress made in our understanding of the mechanisms underlying the development of T cell memory with an emphasis on factors controlling survival of

  19. Hepatocyte nuclear factor 4A improves hepatic differentiation of immortalized adult human hepatocytes and improves liver function and survival.

    Science.gov (United States)

    Hang, Hua-Lian; Liu, Xin-Yu; Wang, Hai-Tian; Xu, Ning; Bian, Jian-Min; Zhang, Jian-Jun; Xia, Lei; Xia, Qiang

    2017-11-15

    Immortalized human hepatocytes (IHH) could provide an unlimited supply of hepatocytes, but insufficient differentiation and phenotypic instability restrict their clinical application. This study aimed to determine the role of hepatocyte nuclear factor 4A (HNF4A) in hepatic differentiation of IHH, and whether encapsulation of IHH overexpressing HNF4A could improve liver function and survival in rats with acute liver failure (ALF). Primary human hepatocytes were transduced with lentivirus-mediated catalytic subunit of human telomerase reverse transcriptase (hTERT) to establish IHH. Cells were analyzed for telomerase activity, proliferative capacity, hepatocyte markers, and tumorigenicity (c-myc) expression. Hepatocyte markers, hepatocellular functions, and morphology were studied in the HNF4A-overexpressing IHH. Hepatocyte markers and karyotype analysis were completed in the primary hepatocytes using shRNA knockdown of HNF4A. Nuclear translocation of β-catenin was assessed. Rat models of ALF were treated with encapsulated IHH or HNF4A-overexpressing IHH. A HNF4A-positive IHH line was established, which was non-tumorigenic and conserved properties of primary hepatocytes. HNF4A overexpression significantly enhanced mRNA levels of genes related to hepatic differentiation in IHH. Urea levels were increased by the overexpression of HNF4A, as measured 24h after ammonium chloride addition, similar to that of primary hepatocytes. Chromosomal abnormalities were observed in primary hepatocytes transfected with HNF4A shRNA. HNF4α overexpression could significantly promote β-catenin activation. Transplantation of HNF4A overexpressing IHH resulted in better liver function and survival of rats with ALF compared with IHH. HNF4A improved hepatic differentiation of IHH. Transplantation of HNF4A-overexpressing IHH could improve the liver function and survival in a rat model of ALF. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Correlation Between Ki-67 Index, World Health Organization Grade and Patient Survival in Glial Tumors With Astrocytic Differentiation

    Science.gov (United States)

    Dzhenkov, Deyan L; Kitanova, Martina; Donev, Ivan S; Ghenev, Peter

    2017-01-01

    Background Glioblastoma multiforme (GBM) is a class IV astrocytic tumor, the most malignant of the four groups of World Health Organization (WHO) tumors with astrocytic differentiation. Aim The aim of this study was to estab­lish whether a correlation exists between the Ki-67 index of tumors with astrocytic differentiation, WHO grade, and patient survival. Materials and methods A retrospective non-clinical approach to patient selection was chosen for the aim of the study. A total of 47 patients diagnosed and treated for CNS tumors with astrocytic differentiation in the St. Marina University Hospital, Varna, Bulgaria, from September 2012 to July 2016 were retrospectively included into the study cohort. The cases were tested for their immunohistochemistry (IHC) reaction with Ki-67 after their original Hematoxylin and Eosin and IHC slides were reviewed by a single author and blind coded. The Ki-67 positivity index of the nuclei was estimated after digitalization of the slides and calculated by the ImmunoRatio automated count­ing tool. The individual Ki-67 index and patient survival of each case were statistically compared. Results The histopathological groups, after the blind Ki-67 index automated calculation was carried out, revealed no WHO grade I, two WHO grade II samples, four WHO grade III samples and 41 WHO grade IV cases, and these were included in the analysis. The two samples of WHO grade II astrocytic tumors had a mean Ki-67 index of 25%; however, they comprised tumors with an individual index of 43% and 7%, both individual values with a highly unlikely index for this group. The four samples of WHO grade III had a mean Ki-67 index of 4%, standard deviation ±2.16 (p>0.05), with the lowest index being 1% and the highest one being 6%. Both WHO grade II and III did not include enough samples to allow for a proper statistical analysis of patient survival. The 41 GBM cases had a mean Ki-67 index of 17.34%, standard deviation ±10.79 (p>0

  1. Age and sex-specific relationships between phthalate exposures and obesity in Chinese children at puberty.

    Directory of Open Access Journals (Sweden)

    Yunhui Zhang

    Full Text Available To examine the age and sex-specific associations of urine levels of six mono-phthalates with body size and fat distribution in Chinese children at puberty.Four hundred and ninety-three school-aged children (247 boys, 246 girls were recruited. Obesity related anthropometric indices were measured and body fat proportion (BF% was calculated. Spot urine samples were collected and phthalate monoesters were detected by an API 2000 electrospray triple quadrupole mass spectrometer (ESI-MS/MS. Associations between phthalate exposure and overweight/obesity measures and their trends were examined by multiple linear regression and Logistic regression analyses, respectively.Di-2-ethylhexyl phthalate (DEHP metabolites and monobutyl phthalate (MBP were found to be the most detectable chemicals. In 8-10 years (yrs group, concentrations of MEHP and MBP were significantly higher in girls than those in boys. However, concentrations of all phthalate monoesters, except for MEP and MEHP, in 11-13 yrs boys were significantly higher than those in girls. After adjusting for confounders including puberty onset, urinary concentrations of MBP and sum of low molecular-weight phthalate metabolites (∑LMP were positively associated with boys' obesity in a concentration-effect manner, while concentrations of MEHP, MEHHP and sum of DEHP metabolites (∑MEHP were negatively associated with girls' obesity. Associations between phthalate exposure levels and BMI z-score changes were age- and sex-specific in school-age children.There are age and sex-specific concentration-effect associations between phthalate exposure and fat distribution in Chinese children. Urinary phthalate levels in 11-13 yrs boys were about 30 percent higher than those in girls, and ∑MEHP levels in younger boys (10 yrs. Associations were positive for MBP and ∑LMP with both BMI z-score and fat distribution in boys >10 years of age, and negative for ∑MEHP with fat distribution in girls <10 years of age.

  2. HIV-1 and recombinant gp120 affect the survival and differentiation of human vessel wall-derived mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Pasquinelli Gianandrea

    2011-05-01

    Full Text Available Abstract Background HIV infection elicits the onset of a progressive immunodeficiency and also damages several other organs and tissues such as the CNS, kidney, heart, blood vessels, adipose tissue and bone. In particular, HIV infection has been related to an increased incidence of cardiovascular diseases and derangement in the structure of blood vessels in the absence of classical risk factors. The recent characterization of multipotent mesenchymal cells in the vascular wall, involved in regulating cellular homeostasis, suggests that these cells may be considered a target of HIV pathogenesis. This paper investigated the interaction between HIV-1 and vascular wall resident human mesenchymal stem cells (MSCs. Results MSCs were challenged with classical R5 and X4 HIV-1 laboratory strains demonstrating that these strains are able to enter and integrate their retro-transcribed proviral DNA in the host cell genome. Subsequent experiments indicated that HIV-1 strains and recombinant gp120 elicited a reliable increase in apoptosis in sub-confluent MSCs. Since vascular wall MSCs are multipotent cells that may be differentiated towards several cell lineages, we challenged HIV-1 strains and gp120 on MSCs differentiated to adipogenesis and endotheliogenesis. Our experiments showed that the adipogenesis is increased especially by upregulated PPARγ activity whereas the endothelial differentiation induced by VEGF treatment was impaired with a downregulation of endothelial markers such as vWF, Flt-1 and KDR expression. These viral effects in MSC survival and adipogenic or endothelial differentiation were tackled by CD4 blockade suggesting an important role of CD4/gp120 interaction in this context. Conclusions The HIV-related derangement of MSC survival and differentiation may suggest a direct role of HIV infection and gp120 in impaired vessel homeostasis and in genesis of vessel damage observed in HIV-infected patients.

  3. Direct and indirect genetic effects of sex-specific mitonuclear epistasis on reproductive ageing

    DEFF Research Database (Denmark)

    Immonen, Elina; Collet, Marie; Goenaga, Julieta

    2016-01-01

    Mitochondria are involved in ageing and their function requires coordinated action of both mitochondrial and nuclear genes. Epistasis between the two genomes can influence lifespan but whether this also holds for reproductive senescence is unclear. Maternal inheritance of mitochondria predicts sex...... to slower senescence relative to novel mitonuclear combinations. We found no evidence for mitonuclear coadaptation in males. Mitonuclear epistasis not only affected age-specific ejaculate weight, but also influenced male age-dependent indirect effects on traits expressed by their female partners (fecundity...... beetle Callosobruchus maculatus, using introgression lines harbouring distinct mitonuclear genotypes. Our results reveal both direct and indirect sex-specific effects of mitonuclear epistasis on reproductive ageing. Females harbouring coadapted mitonuclear genotypes showed higher lifetime fecundity due...

  4. Similar cold stress induces sex-specific neuroendocrine and working memory responses.

    Science.gov (United States)

    Solianik, Rima; Skurvydas, Albertas; Urboniene, Daiva; Eimantas, Nerijus; Daniuseviciute, Laura; Brazaitis, Marius

    2015-01-01

    Men have higher cold-induced neuroendocrine response than women; nevertheless, it is not known whether a different stress hormone rise elicits different effects on cognition during whole body cooling. The objective was to compare the effect of cold-induced neuroendocrine responses on the performance of working memory sensitive tasks between men and women. The cold stress continued until rectal temperature reached 35.5 degree C or for a maximum of 170 min. Working memory performance and stress hormone concentrations were monitored. During cold stress, body temperature variables dropped in all subjects (P < 0.001) and did not differ between sexes. Cold stress raised plasma epinephrine and serum cortisol levels only in men (P < 0.05). Cold stress adversely affected memory performance in men but not in women (P < 0.05). The present study indicated that similar moderate cold stress in men and women induces sex-specific neuroendocrine and working memory responses.

  5. Purification and Initial Functions of Sex-Specific Storage Protein 2 in Bombyx mori.

    Science.gov (United States)

    Chen, Jianqing; Shu, Tejun; Chen, Jian; Ye, Man; Lv, Zhengbing; Nie, Zuoming; Gai, Qijing; Yu, Wei; Zhang, Yaozhou

    2015-08-01

    In this study, we identified a heat-resistant protein from the chrysalis stage of the silkworm which we named sex-specific storage protein 2 (SSP2). This protein was stable even at 80 °C, and has an amino acid sequence that is 90.65 % homologous to SP2. We utilized the heat-resistant characteristics of SSP2 to purify the protein and maintain its biological activity. In addition, using flow cytometry and the MTT assay, we found that SSP2 had anti-apoptotic effects on BmN cells, and that SSP2 could also inhibit cell apoptosis induced by chemical factors. These results suggest that SSP2 has a cell-protective function, and provides a basis for future work on the function of storage proteins in silkworm.

  6. Sex-specific criteria for interpretation of thallium-201 myocardial uptake and washout studies

    International Nuclear Information System (INIS)

    Rabinovitch, M.; Suissa, S.; Elstein, J.

    1986-01-01

    A study was undertaken to determine the effect of gender on criteria for the quantitative analysis of exercise-redistribution 201 Tl myocardial scintigraphy. The studies of 26 normal females and 23 normal males were subjected to bilinear interpolative background subtraction and horizontal profile analysis. Significant sexual differences were found in both regional uptake ratios and washout rates. These differences primarily reflected a proportionately decreased anterior and upper septal uptake in females, and faster washout in females. Faster myocardial 201 Tl washout rates in females could not be clearly ascribed to either a physiological or artifactual explanation. It is concluded that since important differences exist between males and females in the detected pattern of 201 Tl myocardial uptake and washout, sex-specific criteria may enhance the predictive accuracy of exercise-redistribution 201 Tl myocardial scintigraphy

  7. Sex-specific weight loss mediates sexual size dimorphism in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Nicholas D Testa

    Full Text Available The selective pressures leading to the evolution of Sexual Size Dimorphism (SSD have been well studied in many organisms, yet, the underlying developmental mechanisms are poorly understood. By generating a complete growth profile by sex in Drosophila melanogaster, we describe the sex-specific pattern of growth responsible for SSD. Growth rate and critical size for pupariation significantly contributed to adult SSD, whereas duration of growth did not. Surprisingly, SSD at peak larval mass was twice that of the uneclosed adult SSD with weight loss between peak larval mass and pupariation playing an important role in generating the final SSD. Our finding that weight loss is an important regulator of SSD adds additional complexity to our understanding of how body size is regulated in different sexes. Collectively, these data allow for the elucidation of the molecular-genetic mechanisms that generate SSD, an important component of understanding how SSD evolves.

  8. Absence of survival benefit of radioactive iodine (RAI) after thyroidectomy in low risk differentiated thyroid cancer (DTC) patients

    International Nuclear Information System (INIS)

    Schwartz, C.; Fieffe, S.; Pochart, J.M.; Bonnetain, F.; Gauthier, M.; Cueff, A.; Crevisy, E.; Dygai-Cochet, I.; Toubeau, M.

    2012-01-01

    After thyroidectomy, the goal of the first dose of radioactive iodine (RAI) is remnant ablation to facilitate the initial staging with the post-therapy scan and to facilitate the early detection of recurrences. The purpose of this study is to the survival benefit of RAI in low-risk thyroid cancer patients. Using Cancer thyroid registry of Marne Ardennes (1041 patients) and hospital data base of centre Leclerc (257 patients), we included all differentiated thyroid cancer (DTC) patients at low risk from 1975 to 2005. Median follow-up was 10.3 years, during which 19 recurrences, 61 other malignant diseases and 105 deaths were registered. 387 patients (30%) received no RAI and 911 had RAI (70%). If we confirmed that some clinical characteristics were associated with RAI intake, the study failed to demonstrate any survival benefit of RAI in low risk DTC patients

  9. Absence of survival benefit of radioactive iodine (RAI) after thyroidectomy in low risk differentiated thyroid cancer (DTC) patients

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, C.; Fieffe, S.; Pochart, J.M. [Endocrinology Nuclear Medicine, Institut Jean Godinot, Reims (France); Bonnetain, F.; Gauthier, M.; Cueff, A. [Statistics and Epidemiology, Centre Georges Francois Leclerc, Dijon (France); Crevisy, E.; Dygai-Cochet, I.; Toubeau, M. [Nuclear Medicine, Centre Georges Francois Leclerc, Dijon (France)

    2012-07-01

    After thyroidectomy, the goal of the first dose of radioactive iodine (RAI) is remnant ablation to facilitate the initial staging with the post-therapy scan and to facilitate the early detection of recurrences. The purpose of this study is to the survival benefit of RAI in low-risk thyroid cancer patients. Using Cancer thyroid registry of Marne Ardennes (1041 patients) and hospital data base of centre Leclerc (257 patients), we included all differentiated thyroid cancer (DTC) patients at low risk from 1975 to 2005. Median follow-up was 10.3 years, during which 19 recurrences, 61 other malignant diseases and 105 deaths were registered. 387 patients (30%) received no RAI and 911 had RAI (70%). If we confirmed that some clinical characteristics were associated with RAI intake, the study failed to demonstrate any survival benefit of RAI in low risk DTC patients

  10. Sex-specific responses of Populus yunnanensis exposed to elevated CO{sub 2} and salinity

    Energy Technology Data Exchange (ETDEWEB)

    Ling Li; Yuanbin Zhang; Chunyang Li [Chinese Academy of Sciences. Chengdu Institute of Biology, Chengdu (Switzerland); Jianxun Luo, Sichuan Academy of Forestry, Chengdu (Switzerland)); Korpelainen, H. [Univ. of Helsinki. Dept. of Agricultural Sciences, Helsinki (Finland)

    2013-04-15

    Populus yunnanensis Dode., a native dioecious woody plant in southwestern China, was employed as a model species to study sex-specific morphological, physiological and biochemical responses to elevated CO{sub 2} and salinity. To investigate the effects of elevated CO{sub 2}, salinity and their combination, the cuttings were exposed to two CO{sub 2} regimes (ambient CO{sub 2} and double ambient CO{sub 2}) and two salt treatments in growth chambers. Males exhibited greater downregulation of net photosynthesis rate (A{sub net}) and carboxylation efficiency (CE) than females at elevated CO{sub 2}, whereas these sexual differences were lessened under salt stress. On the other hand, salinity induced a higher decrease in Anet and CE, more growth inhibition and leaf Cl{sup -} accumulation and more damage to cell organelles in females than in males, whereas the sexual differences in photosynthesis and growth were lessened at elevated CO{sub 2}. Moreover, elevated CO{sub 2} exacerbated membrane lipid peroxidation and organelle damage in females but not in males under salt stress. Our results indicated that: (1) females are more sensitive and suffer from greater negative effects than do males under salt stress, and elevated CO{sub 2} lessens the sexual differences in photosynthesis and growth under salt stress; (2) elevated CO{sub 2} tends to aggravate the negative effects of salinity in females; and (3) sex-specific reactions under the combination of elevated CO{sub 2} and salinity are distinct from single-stress responses. Therefore, these results provide evidence for different adaptive responses between plants of different sexes exposed to elevated CO{sub 2} and salinity. (Author)

  11. Cattle Sex-Specific Recombination and Genetic Control from a Large Pedigree Analysis.

    Science.gov (United States)

    Ma, Li; O'Connell, Jeffrey R; VanRaden, Paul M; Shen, Botong; Padhi, Abinash; Sun, Chuanyu; Bickhart, Derek M; Cole, John B; Null, Daniel J; Liu, George E; Da, Yang; Wiggans, George R

    2015-11-01

    Meiotic recombination is an essential biological process that generates genetic diversity and ensures proper segregation of chromosomes during meiosis. From a large USDA dairy cattle pedigree with over half a million genotyped animals, we extracted 186,927 three-generation families, identified over 8.5 million maternal and paternal recombination events, and constructed sex-specific recombination maps for 59,309 autosomal SNPs. The recombination map spans for 25.5 Morgans in males and 23.2 Morgans in females, for a total studied region of 2,516 Mb (986 kb/cM in males and 1,085 kb/cM in females). The male map is 10% longer than the female map and the sex difference is most pronounced in the subtelomeric regions. We identified 1,792 male and 1,885 female putative recombination hotspots, with 720 hotspots shared between sexes. These hotspots encompass 3% of the genome but account for 25% of the genome-wide recombination events in both sexes. During the past forty years, males showed a decreasing trend in recombination rate that coincided with the artificial selection for milk production. Sex-specific GWAS analyses identified PRDM9 and CPLX1 to have significant effects on genome-wide recombination rate in both sexes. Two novel loci, NEK9 and REC114, were associated with recombination rate in both sexes, whereas three loci, MSH4, SMC3 and CEP55, affected recombination rate in females only. Among the multiple PRDM9 paralogues on the bovine genome, our GWAS of recombination hotspot usage together with linkage analysis identified the PRDM9 paralogue on chromosome 1 to be associated in the U.S. Holstein data. Given the largest sample size ever reported for such studies, our results reveal new insights into the understanding of cattle and mammalian recombination.

  12. Sex-Specific Effects of Organophosphate Diazinon on the Gut Microbiome and Its Metabolic Functions.

    Science.gov (United States)

    Gao, Bei; Bian, Xiaoming; Mahbub, Ridwan; Lu, Kun

    2017-02-01

    There is growing recognition of the significance of the gut microbiome to human health, and the association between a perturbed gut microbiome with human diseases has been established. Previous studies also show the role of environmental toxicants in perturbing the gut microbiome and its metabolic functions. The wide agricultural use of diazinon, an organophosphate insecticide, has raised serious environmental health concerns since it is a potent neurotoxicant. With studies demonstrating the presence of a microbiome-gut-brain axis, it is possible that gut microbiome perturbation may also contribute to diazinon toxicity. We investigated the impact of diazinon exposure on the gut microbiome composition and its metabolic functions in C57BL/6 mice. We used a combination of 16S rRNA gene sequencing, metagenomics sequencing, and mass spectrometry-based metabolomics profiling in a mouse model to examine the functional impact of diazinon on the gut microbiome. 16S rRNA gene sequencing revealed that diazinon exposure significantly perturbed the gut microbiome, and metagenomic sequencing found that diazinon exposure altered the functional metagenome. Moreover, metabolomics profiling revealed an altered metabolic profile arising from exposure. Of particular significance, these changes were more pronounced for male mice than for female mice. Diazinon exposure perturbed the gut microbiome community structure, functional metagenome, and associated metabolic profiles in a sex-specific manner. These findings may provide novel insights regarding perturbations of the gut microbiome and its functions as a potential new mechanism contributing to diazinon neurotoxicity and, in particular, its sex-selective effects. Citation: Gao B, Bian X, Mahbub R, Lu K. 2017. Sex-specific effects of organophosphate diazinon on the gut microbiome and its metabolic functions. Environ Health Perspect 125:198-206; http://dx.doi.org/10.1289/EHP202.

  13. Phylogeography and recolonization of the Swiss Alps by the Valais shrew (Sorex antinorii), inferred with autosomal and sex-specific markers.

    Science.gov (United States)

    Yannic, G; Basset, P; Hausser, J

    2008-09-01

    Using one male-inherited, one female-inherited and eight biparentally inherited markers, we investigate the population genetic structure of the Valais shrew (Sorex antinorii) in the Swiss Alps. Bayesian analysis on autosomal microsatellites suggests a clear genetic differentiation between two groups of populations. This geographically based structure is consistent with two separate postglacial recolonization routes of the species into Switzerland from Italian refugia after the last Pleistocene glaciations. Sex-specific markers also confirm genetic structuring among western and eastern areas, since very few haplotypes for either Y chromosome or mtDNA genome are shared between the two regions. Overall, these results suggest that two already well-differentiated genetic lineages colonized the Swiss Alps and came into secondary contact in the Rhône Valley. Low level of admixture between the two lineages is likely explained by the mountainous landscape structure of lateral valleys orthogonal to the main Rhône valley.

  14. Sex-specific differences in hemodialysis prevalence and practices and the male-to-female mortality rate: the Dialysis Outcomes and Practice Patterns Study (DOPPS.

    Directory of Open Access Journals (Sweden)

    Manfred Hecking

    2014-10-01

    differences and does not provide information about patients not treated with dialysis or dying prior to a planned start of dialysis. CONCLUSIONS: Women's survival advantage was markedly diminished in hemodialysis patients. The finding that fewer women than men were being treated with dialysis for end-stage renal disease merits detailed further study, as the large discrepancies in sex-specific hemodialysis prevalence by country and age group are likely explained by factors beyond biology. Modifiable variables, such as catheter use, showing significant sex interactions suggest interventional targeting. Please see later in the article for the Editors' Summary.

  15. TRANSGENIC GDNF POSITIVELY INFLUENCES PROLIFERATION, DIFFERENTIATION, MATURATION AND SURVIVAL OF MOTOR NEURONS PRODUCED FROM MOUSE EMBRYONIC STEM CELLS.

    Directory of Open Access Journals (Sweden)

    Daniel Édgar Cortés

    2016-09-01

    Full Text Available Embryonic stem cells (ESC are pluripotent and thus can differentiate into every cell type present in the body. Directed differentiation into motor neurons has been described for pluripotent cells. Although neurotrophic factors promote neuronal survival, their role in neuronal commitment is elusive. Here, we developed double-transgenic lines of mouse ESC that constitutively produce Glial cell-derived neurotrophic factor (GDNF and also contain a GFP reporter, driven by HB9, which is expressed only by postmitotic motor neurons. After lentiviral transduction, ESC lines integrated and expressed the human GDNF gene without altering pluripotency markers before differentiation. Further, GDNF-ESC showed significantly higher spontaneous release of this neurotrophin to the medium, when compared to controls. To study motor neuron induction, control and GDNF cell lines were grown as embryoid bodies and stimulated with retinoic acid and Sonic Hedgehog. In GDNF-overexpressing cells, a significant increase of proliferative Olig2+ precursors, which are specified as spinal motor neurons, was found. Accordingly, GDNF increases the yield of cells with the pan motor neuronal markers HB9, monitored by GFP expression, and Isl1. At terminal differentiation, almost all differentiated neurons express phenotypic markers of motor neurons in GDNF cultures, with lower proportions in control cells. To test if the effects of GDNF were present at early differentiation stages, exogenous recombinant human GDNF was added to control ESC, also resulting in enhanced motor neuron differentiation. This effect was abolished by the co-addition of neutralizing anti-GDNF antibodies, strongly suggesting that differentiating ESC are responsive to GDNF. Using the HB9::GFP reporter, motor neurons were selected for electrophysiological recordings. Motor neurons differentiated from GDNF-ESC, compared to control motor neurons, showed greater electrophysiological maturation, characterized by

  16. Intermittent, low dose carbon monoxide exposure enhances survival and dopaminergic differentiation of human neural stem cells

    DEFF Research Database (Denmark)

    Dreyer-Andersen, Nanna; Almeida, Ana Sofia; Jensen, Pia

    2018-01-01

    cells constitute an alternative source of cells for transplantation in Parkinson's disease, but efficient protocols for controlled dopaminergic differentiation need to be developed. Short-term, low-level carbon monoxide (CO) exposure has been shown to affect signaling in several tissues, resulting...... in both protection and generation of reactive oxygen species. The present study investigated the effect of CO produced by a novel CO-releasing molecule on dopaminergic differentiation of human neural stem cells. Short-term exposure to 25 ppm CO at days 0 and 4 significantly increased the relative content...... of β-tubulin III-immunoreactive immature neurons and tyrosine hydroxylase expressing catecholaminergic neurons, as assessed 6 days after differentiation. Also the number of microtubule associated protein 2-positive mature neurons had increased significantly. Moreover, the content of apoptotic cells...

  17. Differential impact of obesity and diabetes mellitus on survival after liver resection for colorectal cancer metastases.

    Science.gov (United States)

    Amptoulach, Sousana; Gross, Gillis; Kalaitzakis, Evangelos

    2015-12-01

    Data on the potential effect of obesity and diabetes mellitus on survival after liver resection due to colorectal cancer (CRC) metastases are very limited. Patients undergoing liver resection for CRC metastases in a European institution in 2004-2011 were retrospectively enrolled. Relevant data, such as body mass index, extent of resection, chemotherapy, and perioperative outcome, were collected from medical records. The relation of obesity and diabetes mellitus with overall and disease-free survival was assessed using adjusted Cox models. Thirty of 207 patients (14.4%) included in the study were obese (BMI ≥30 kg/m(2)) and 25 (12%) had diabetes mellitus. Major hepatectomy was performed in 46%. Although both obese patients and those with diabetes had higher American Society of Anesthesiologist scores (P diabetes was significantly related to primary tumor characteristics, liver metastasis features, extent or radicality of resection, extrahepatic disease at hepatectomy, preoperative or postoperative oncologic therapy, or perioperative outcome (P > 0.05 for all). Patients were followed up for a median of 39 mo posthepatectomy (interquartile range, 13-56 mo). After adjustment for confounders, obesity was an independent predictor of improved (hazard ratio, 0.305, 95% confidence interval, 0.103-0.902) and diabetes of worse overall survival (hazard ratio, 3.298, 95% confidence interval, 1.306-8.330). Obese patients with diabetes had also worse disease-free survival compared with the rest of the cohort (P diabetes mellitus has a negative impact on prognosis. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Differential improvement in survival among patients with AIDS after the introduction of HAART

    OpenAIRE

    2007-01-01

    Abstract We explored changes in the survival of patients with AIDS (PWA) according to the availability of antiretroviral drugs (1994-2002). We tested whether changes in the hazard ratio of progression to death (HR) have been homogeneous among various groups of PWA. We included 4158 PWA diagnosed in Paris, notified to the French National Surveillance Institute by 2002. Four calendar periods were defined: monotherapy (1994-1995), bitherapy-HAART transition (1996), early HAART (19...

  19. Yeast Colony Survival Depends on Metabolic Adaptation and Cell Differentiation Rather Than on Stress Defense

    Czech Academy of Sciences Publication Activity Database

    Čáp, M.; Váchová, Libuše; Palková, Z.

    2009-01-01

    Roč. 284, č. 47 (2009), s. 32572-32581 ISSN 0021-9258 R&D Projects: GA ČR GA525/05/0297; GA ČR GA204/08/0718; GA MŠk(CZ) LC531 Institutional research plan: CEZ:AV0Z50200510 Keywords : LONG-TERM SURVIVAL * SACCHAROMYCES-CEREVISIAE * SUPEROXIDE-DISMUTASE Subject RIV: EE - Microbiology, Virology Impact factor: 5.328, year: 2009

  20. PARP activity and inhibition in fetal and adult oligodendrocyte precursor cells: Effect on cell survival and differentiation.

    Science.gov (United States)

    Baldassarro, Vito A; Marchesini, Alessandra; Giardino, Luciana; Calzà, Laura

    2017-07-01

    Poly (ADP-ribose) polymerase (PARP) family members are ubiquitously expressed and play a key role in cellular processes, including DNA repair and cell death/survival balance. Accordingly, PARP inhibition is an emerging pharmacological strategy for cancer and neurodegenerative diseases. Consistent evidences support the critical involvement of PARP family members in cell differentiation and phenotype maturation. In this study we used an oligodendrocyte precursor cells (OPCs) enriched system derived from fetal and adult brain to investigate the role of PARP in OPCs proliferation, survival, and differentiation. The PARP inhibitors PJ34, TIQ-A and Olaparib were used as pharmacological tools. The main results of the study are: (i) PARP mRNA expression and PARP activity are much higher in fetal than in adult-derived OPCs; (ii) the culture treatment with PARP inhibitors is cytotoxic for OPCs derived from fetal, but not from adult, brain; (iii) PARP inhibition reduces cell number, according to the inhibitory potency of the compounds; (iv) PARP inhibition effect on fetal OPCs is a slow process; (v) PARP inhibition impairs OPCs maturation into myelinating OL in fetal, but not in adult cultures, according to the inhibitory potency of the compounds. These results have implications for PARP-inhibition therapies for diseases and lesions of the central nervous system, in particular for neonatal hypoxic/ischemic encephalopathy. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Survival of partially differentiated mouse embryonic stem cells in the scala media of the guinea pig cochlea.

    Science.gov (United States)

    Hildebrand, Michael S; Dahl, Hans-Henrik M; Hardman, Jennifer; Coleman, Bryony; Shepherd, Robert K; de Silva, Michelle G

    2005-12-01

    The low regenerative capacity of the hair cells of the mammalian inner ear is a major obstacle for functional recovery following sensorineural hearing loss. A potential treatment is to replace damaged tissue by transplantation of stem cells. To test this approach, undifferentiated and partially differentiated mouse embryonic stem (ES) cells were delivered into the scala media of the deafened guinea pig cochlea. Transplanted cells survived in the scala media for a postoperative period of at least nine weeks, evidenced by histochemical and direct fluorescent detection of enhanced green fluorescent protein (EGFP). Transplanted cells were discovered near the spiral ligament and stria vascularis in the endolymph fluid of the scala media. In some cases, cells were observed close to the damaged organ of Corti structure. There was no evidence of significant immunological rejection of the implanted ES cells despite the absence of immunosuppression. Our surgical approach allowed efficient delivery of ES cells to the scala media while preserving the delicate structures of the cochlea. This is the first report of the survival of partially differentiated ES cells in the scala media of the mammalian cochlea, and it provides support for the potential of cell-based therapies for sensorineural hearing impairment.

  2. Sex-specific relationships between adverse childhood experiences and chronic obstructive pulmonary disease in five states.

    Science.gov (United States)

    Cunningham, Timothy J; Ford, Earl S; Croft, Janet B; Merrick, Melissa T; Rolle, Italia V; Giles, Wayne H

    2014-01-01

    Adverse childhood experiences (ACEs) before age 18 have been repeatedly associated with several chronic diseases in adulthood such as depression, heart disease, cancer, diabetes, and stroke. We examined sex-specific relationships between individual ACEs and the number of ACEs with chronic obstructive pulmonary disease (COPD) in the general population. Data from 26,546 women and 19,015 men aged ≥18 years in five states of the 2011 Behavioral Risk Factor Surveillance System were analyzed. We used log-linear regression to estimate prevalence ratios (PRs) and their corresponding 95% confidence intervals (CIs) for the relationship of eight ACEs with COPD after adjustment for age group, race/ethnicity, marital status, educational attainment, employment, asthma history, health insurance coverage, and smoking status. Some 63.8% of women and 62.2% of men reported ≥1 ACE. COPD was reported by 4.9% of women and 4.0% of men. In women, but not in men, there was a higher likelihood of COPD associated with verbal abuse (PR =1.30, 95% CI: 1.05, 1.61), sexual abuse (PR =1.69, 95% CI: 1.36, 2.10), living with a substance abusing household member (PR =1.49, 95% CI: 1.23, 1.81), witnessing domestic violence (PR =1.40, 95% CI: 1.14, 1.72), and parental separation/divorce (PR =1.47, 95% CI: 1.21, 1.80) during childhood compared to those with no individual ACEs. Reporting ≥5 ACEs (PR =2.08, 95% CI: 1.55, 2.80) compared to none was associated with a higher likelihood of COPD among women only. ACEs are related to COPD, especially among women. These findings underscore the need for further research that examines sex-specific differences and the possible mechanisms linking ACEs and COPD. This work adds to a growing body of research suggesting that ACEs may contribute to health problems later in life and suggesting a need for program and policy solutions.

  3. Sex-specific differences in the presenting location of a first venous thromboembolism.

    Science.gov (United States)

    Scheres, L J J; Brekelmans, M P A; Beenen, L F M; Büller, H R; Cannegieter, S C; Middeldorp, S

    2017-07-01

    Essentials Whether the location of venous thromboembolism (VTE) differs between the sexes is not known. Pulmonary embolism as presenting location was relatively more common in women than in men. The difference was consistent among age groups and most prominent in unprovoked VTE. The underlying mechanism remains to be elucidated. Background The risk of venous thromboembolism (VTE) differs between men and women. Some risk factors seem to influence the presenting location of VTE. Sex-specific differences in the presenting VTE location have not been studied extensively. Methods We analyzed data from the MEGA case-control study and the Hokusai-VTE study, and used published data from the RIETE registry. Data from patients with a symptomatic first VTE were included (MEGA, n = 4953; Hokusai-VTE, n = 6720; RIETE, n = 40 028). Distributions of deep vein thrombosis (DVT), pulmonary embolism (PE) and combined DVT and PE as the presenting VTE location were calculated for men and women, and presented as proportions with 95% confidence intervals (CIs). Sex-specific differences were explored for different age categories and for unprovoked and provoked events. Results In the MEGA study, PE was the presenting location in 35.5% of women and in 29.5% of men with VTE (difference 6.0%, 95% CI 3.4-8.6). In the Hokusai-VTE study, these proportions were 35.1% for women and 25.2% for men (difference 10.0%, 95% CI 7.8-12.2). In the RIETE registry, PE (with or without DVT) was also observed more often as the presenting location in women (53.3%) than in men (47.7%), with a difference of 5.6% (95% CI 4.7-6.6). The observed higher proportion of PE as the presenting location in women was present in all age groups and was most prominent among unprovoked VTE events. Conclusions In three large studies, the distribution of the presenting VTE location differed consistently between the sexes, whereby PE was more often the primary location of presentation in women than in men. © 2017

  4. Sex-specific genetic determinants for arterial stiffness in Dahl salt-sensitive hypertensive rats.

    Science.gov (United States)

    Decano, Julius L; Pasion, Khristine A; Black, Nicole; Giordano, Nicholas J; Herrera, Victoria L; Ruiz-Opazo, Nelson

    2016-01-11

    Arterial stiffness is an independent predictor of cardiovascular outcomes in hypertensive patients including myocardial infarction, fatal stroke, cerebral micro-bleeds which predicts cerebral hemorrhage in hypertensive patients, as well as progression to hypertension in non-hypertensive subjects. The association between arterial stiffness and various cardiovascular outcomes (coronary heart disease, stroke) remains after adjusting for age, sex, blood pressure, body mass index and other known predictors of cardiovascular disease, suggesting that arterial stiffness, measured via carotid-femoral pulse wave velocity, has a better predictive value than each of these factors. Recent evidence shows that arterial stiffening precedes the onset of high blood pressure; however their molecular genetic relationship (s) and sex-specific determinants remain uncertain. We investigated whether distinct or shared genetic determinants might underlie susceptibility to arterial stiffening in male and female Dahl salt-sensitive rats. Thus, we performed a genome-wide scan for quantitative trait loci (QTLs) affecting arterial stiffness in six-week old F2 (Dahl S x R)-intercross male and female rats characterized for abdominal aortic pulse wave velocity and aortic strain by high-resolution ultrasonography. We detected five highly significant QTLs affecting aortic stiffness: two interacting QTLs (AS-m1 on chromosome 4 and AS-m2 on chromosome16, LOD 8.8) in males and two distinct interacting QTLs (AS-f1 on chromosome 9 and AS-f2 on chromosome11, LOD 8.9) in females affecting pulse wave velocity. One QTL (AS-1 on chromosome 3, LOD 4.3) was found to influence aortic strain in a sex-independent manner. None of these arterial stiffness QTLs co-localized with previously reported blood pressure QTLs detected in equivalent genetic intercrosses. These data reveal sex-specific genetic determinants for aortic pulse wave velocity and suggest distinct polygenic susceptibility for arterial stiffness and

  5. Retinoic acid-loaded polymeric nanoparticles enhance vascular regulation of neural stem cell survival and differentiation after ischaemia

    Science.gov (United States)

    Ferreira, R.; Fonseca, M. C.; Santos, T.; Sargento-Freitas, J.; Tjeng, R.; Paiva, F.; Castelo-Branco, M.; Ferreira, L. S.; Bernardino, L.

    2016-04-01

    Stroke is one of the leading causes of death and disability worldwide. However, current therapies only reach a small percentage of patients and may cause serious side effects. We propose the therapeutic use of retinoic acid-loaded nanoparticles (RA-NP) to safely and efficiently repair the ischaemic brain by creating a favourable pro-angiogenic environment that enhances neurogenesis and neuronal restitution. Our data showed that RA-NP enhanced endothelial cell proliferation and tubule network formation and protected against ischaemia-induced death. To evaluate the effect of RA-NP on vascular regulation of neural stem cell (NSC) survival and differentiation, endothelial cell-conditioned media (EC-CM) were collected. EC-CM from healthy RA-NP-treated cells reduced NSC death and promoted proliferation while EC-CM from ischaemic RA-NP-treated cells decreased cell death, increased proliferation and neuronal differentiation. In parallel, human endothelial progenitor cells (hEPC), which are part of the endogenous repair response to vascular injury, were collected from ischaemic stroke patients. hEPC treated with RA-NP had significantly higher proliferation, which further highlights the therapeutic potential of this formulation. To conclude, RA-NP protected endothelial cells from ischaemic death and stimulated the release of pro-survival, proliferation-stimulating factors and differentiation cues for NSC. RA-NP were shown to be up to 83-fold more efficient than free RA and to enhance hEPC proliferation. These data serve as a stepping stone to use RA-NP as vasculotrophic and neurogenic agents for vascular disorders and neurodegenerative diseases with compromised vasculature.

  6. Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) promotes lung fibroblast proliferation, survival and differentiation to myofibroblasts.

    Science.gov (United States)

    Hasaneen, Nadia A; Cao, Jian; Pulkoski-Gross, Ashleigh; Zucker, Stanley; Foda, Hussein D

    2016-02-17

    Idiopathic pulmonary fibrosis (IPF) is a chronic progressively fatal disease. Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) is a glycosylated transmembrane protein that induces the expression of some matrix metalloproteinase (MMP) in neighboring stromal cells through direct epithelial-stromal interactions. EMMPRIN is highly expressed in type II alveolar epithelial cells at the edges of the fibrotic areas in IPF lung sections. However, the exact role of EMMPRIN in IPF is unknown. To determine if EMMPRIN contributes to lung fibroblast proliferation, resistance to apoptosis, and differentiation to myofibroblasts, normal Human lung fibroblasts (NHLF) transiently transfected with either EMMPRIN/GFP or GFP were treated with TGF- β1 from 0 to 10 ng/ml for 48 h and examined for cell proliferation (thymidine incorporation), apoptosis (FACS analysis and Cell Death Detection ELISA assay), cell migration (Modified Boyden chamber) and differentiation to myofibroblasts using Western blot for α-smooth actin of cell lysates. The effect of EMMPRIN inhibition on NHLF proliferation, apoptosis, migration and differentiation to myofibroblasts after TGF- β1 treatment was examined using EMMPRIN blocking antibody. We examined the mechanism by which EMMPRIN induces its effects on fibroblasts by studying the β-catenin/canonical Wnt signaling pathway using Wnt luciferase reporter assays and Western blot for total and phosphorylated β-catenin. Human lung fibroblasts overexpressing EMMPRIN had a significant increase in cell proliferation and migration compared to control fibroblasts. Furthermore, EMMPRIN promoted lung fibroblasts resistance to apoptosis. Lung fibroblasts overexpressing EMMPRIN showed a significantly increased expression of α- smooth muscle actin, a marker of differentiation to myofibroblasts compared to control cells. TGF-β1 increased the expression of EMMPRIN in lung fibroblasts in a dose-dependent manner. Attenuation of EMMPRIN expression with the use of an

  7. Differential survival of mosquitofish exposed to radionuclides is dependent on RAPD genotype

    International Nuclear Information System (INIS)

    Theodorakis, C.W.; Shugart, L.R.

    1995-01-01

    In previous studies, it was found that certain RAPD (Randomly Amplified Polymorphic DNA) markers were present at higher frequencies in radionuclide-contaminated mosquitofish (Gambusia affinis) populations than in reference populations. These markers will be referred to as contaminant specific markers. In the present study, fish with and without these markers were collected from non-contaminated populations and exposed in situ to radionuclides by caging them in one of the contaminated sites. Forty fish were exposed for 1--6 weeks, after which the survivors were collected and DNA was extracted for genotypic analysis. In one experiment, the frequencies of contaminant specific markers in the survivors were compared to the frequencies of these markers in the native contaminated and uncontaminated (the source of the caged fish) populations. It was found that the genotypic distributions were more similar to the native contaminated population. In another experiment, samples of caudal fin tissue were collected for DNA extraction before and after placing fish in the cages, in order to compare survival rates of different genotypes. It was found that fish with the contaminant indicative bands had higher percent survival than the other fish. Experiments are underway or are being planned in order to determine the molecular identity of these bands and the ecological significance of altered band frequencies in hopes of developing population-level biomarkers of contaminant exposure and ecological affects

  8. NHE10, a novel osteoclast-specific member of the Na+/H+ exchanger family, regulates osteoclast differentiation and survival

    International Nuclear Information System (INIS)

    Lee, Seoung Hoon; Kim, Taesoo; Park, Eui-Soon; Yang, Sujeong; Jeong, Daewon; Choi, Yongwon; Rho, Jaerang

    2008-01-01

    Bone homeostasis is tightly regulated by the balanced actions of osteoblasts (OBs) and osteoclasts (OCs). We previously analyzed the gene expression profile of OC differentiation using a cDNA microarray, and identified a novel osteoclastogenic gene candidate, clone OCL-1-E7 [J. Rho, C.R. Altmann, N.D. Socci, L. Merkov, N. Kim, H. So, O. Lee, M. Takami, A.H. Brivanlou, Y. Choi, Gene expression profiling of osteoclast differentiation by combined suppression subtractive hybridization (SSH) and cDNA microarray analysis, DNA Cell Biol. 21 (2002) 541-549]. In this study, we have isolated full-length cDNAs corresponding to this clone from mice and humans to determine the functional roles of this gene in osteoclastogenesis. The full-length cDNA of OCL-1-E7 encodes 12 membrane-spanning domains that are typical of isoforms of the Na + /H + exchangers (NHEs), indicating that this clone is a novel member of the NHE family (hereafter referred to as NHE10). Here, we show that NHE10 is highly expressed in OCs in response to receptor activator of nuclear factor-κB ligand signaling and is required for OC differentiation and survival

  9. Exposure to 4100K fluorescent light elicits sex specific transcriptional responses in Xiphophorus maculatus skin.

    Science.gov (United States)

    Boswell, William T; Boswell, Mikki; Walter, Dylan J; Navarro, Kaela L; Chang, Jordan; Lu, Yuan; Savage, Markita G; Shen, Jianjun; Walter, Ronald B

    2018-06-01

    It has been reported that exposure to artificial light may affect oxygen intake, heart rate, absorption of vitamins and minerals, and behavioral responses in humans. We have reported specific gene expression responses in the skin of Xiphophorus fish after exposure to ultraviolet light (UV), as well as, both broad spectrum and narrow waveband visible light. In regard to fluorescent light (FL), we have shown that male X. maculatus exposed to 4100K FL (i.e. "cool white") rapidly suppress transcription of many genes involved with DNA replication and repair, chromosomal segregation, and cell cycle progression in skin. We have also detailed sex specific transcriptional responses of Xiphophorus skin after exposure to UVB. However, investigation of gender differences in global gene expression response after exposure to 4100K FL has not been reported, despite common use of this FL source for residential, commercial, and animal facility illumination. Here, we compare RNA-Seq results analyzed to assess changes in the global transcription profiles of female and male X. maculatus skin in response to 4100K FL exposure. Our results suggest 4100K FL exposure incites a sex-biased genetic response including up-modulation of inflammation in females and down modulation of DNA repair/replication in males. In addition, we identify clusters of genes that become oppositely modulated in males and females after FL exposure that are principally involved in cell death and cell proliferation. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Sex-specific differences in pathogen susceptibility in honey bees (Apis mellifera).

    Science.gov (United States)

    Retschnig, Gina; Williams, Geoffrey R; Mehmann, Marion M; Yañez, Orlando; de Miranda, Joachim R; Neumann, Peter

    2014-01-01

    Sex-related differences in susceptibility to pathogens are a common phenomenon in animals. In the eusocial Hymenoptera the two female castes, workers and queens, are diploid and males are haploid. The haploid susceptibility hypothesis predicts that haploid males are more susceptible to pathogen infections compared to females. Here we test this hypothesis using adult male (drone) and female (worker) honey bees (Apis mellifera), inoculated with the gut endoparasite Nosema ceranae and/or black queen cell virus (BQCV). These pathogens were chosen due to previously reported synergistic interactions between Nosema apis and BQCV. Our data do not support synergistic interactions between N. ceranae and BQCV and also suggest that BQCV has limited effect on both drone and worker health, regardless of the infection level. However, the data clearly show that, despite lower levels of N. ceranae spores in drones than in workers, Nosema-infected drones had both a higher mortality and a lower body mass than non-infected drones, across all treatment groups, while the mortality and body mass of worker bees were largely unaffected by N. ceranae infection, suggesting that drones are more susceptible to this pathogen than workers. In conclusion, the data reveal considerable sex-specific differences in pathogen susceptibility in honey bees and highlight the importance of ultimate measures for determining susceptibility, such as mortality and body quality, rather than mere infection levels.

  11. Targeting brain tumor cAMP: the case for sex-specific therapeutics

    Directory of Open Access Journals (Sweden)

    Nicole M Warrington

    2015-07-01

    Full Text Available A relationship between cyclic adenosine 3’, 5’-monophosphate (cAMP levels and brain tumor biology has been evident for nearly as long as cAMP and its synthetase, adenylate cyclase (ADCY have been known. The importance of the pathway in brain tumorigenesis has been demonstrated in vitro and in multiple animal models. Recently, we provided human validation for a cooperating oncogenic role for cAMP in brain tumorigenesis when we found that SNPs in ADCY8 were correlated with glioma (brain tumor risk in individuals with Neurofibromatosis type 1 (NF1. Together, these studies provide a strong rationale for targeting cAMP in brain tumor therapy. However, the cAMP pathway is well known to be sexually dimorphic, and SNPs in ADCY8 affected glioma risk in a sex-specific fashion, elevating the risk for females while protecting males. The cAMP pathway can be targeted at multiple levels in the regulation of its synthesis and degradation. Sex differences in response to drugs that target cAMP regulators indicate that successful targeting of the cAMP pathway for brain tumor patients is likely to require matching specific mechanisms of drug action with patient sex.

  12. Sex-specific effects of a parasite evolving in a female-biased host population.

    Science.gov (United States)

    Duneau, David; Luijckx, Pepijn; Ruder, Ludwig F; Ebert, Dieter

    2012-12-18

    Males and females differ in many ways and might present different opportunities and challenges to their parasites. In the same way that parasites adapt to the most common host type, they may adapt to the characteristics of the host sex they encounter most often. To explore this hypothesis, we characterized host sex-specific effects of the parasite Pasteuria ramosa, a bacterium evolving in naturally, strongly, female-biased populations of its host Daphnia magna. We show that the parasite proliferates more successfully in female hosts than in male hosts, even though males and females are genetically identical. In addition, when exposure occurred when hosts expressed a sexual dimorphism, females were more infected. In both host sexes, the parasite causes a similar reduction in longevity and leads to some level of castration. However, only in females does parasite-induced castration result in the gigantism that increases the carrying capacity for the proliferating parasite. We show that mature male and female Daphnia represent different environments and reveal one parasite-induced symptom (host castration), which leads to increased carrying capacity for parasite proliferation in female but not male hosts. We propose that parasite induced host castration is a property of parasites that evolved as an adaptation to specifically exploit female hosts.

  13. Sex-specific effects of a parasite evolving in a female-biased host population

    Directory of Open Access Journals (Sweden)

    Duneau David

    2012-12-01

    Full Text Available Abstract Background Males and females differ in many ways and might present different opportunities and challenges to their parasites. In the same way that parasites adapt to the most common host type, they may adapt to the characteristics of the host sex they encounter most often. To explore this hypothesis, we characterized host sex-specific effects of the parasite Pasteuria ramosa, a bacterium evolving in naturally, strongly, female-biased populations of its host Daphnia magna. Results We show that the parasite proliferates more successfully in female hosts than in male hosts, even though males and females are genetically identical. In addition, when exposure occurred when hosts expressed a sexual dimorphism, females were more infected. In both host sexes, the parasite causes a similar reduction in longevity and leads to some level of castration. However, only in females does parasite-induced castration result in the gigantism that increases the carrying capacity for the proliferating parasite. Conclusions We show that mature male and female Daphnia represent different environments and reveal one parasite-induced symptom (host castration, which leads to increased carrying capacity for parasite proliferation in female but not male hosts. We propose that parasite induced host castration is a property of parasites that evolved as an adaptation to specifically exploit female hosts.

  14. Altering the sex determination pathway in Drosophila fat body modifies sex-specific stress responses.

    Science.gov (United States)

    Argue, Kathryn J; Neckameyer, Wendi S

    2014-07-01

    The stress response in Drosophila melanogaster reveals sex differences in behavior, similar to what has been observed in mammals. However, unlike mammals, the sex determination pathway in Drosophila is well established, making this an ideal system to identify factors involved in the modulation of sex-specific responses to stress. In this study, we show that the Drosophila fat body, which has been shown to be important for energy homeostasis and sex determination, is a dynamic tissue that is altered in response to stress in a sex and time-dependent manner. We manipulated the sex determination pathway in the fat body via targeted expression of transformer and transformer-2 and analyzed these animals for changes in their response to stress. In the majority of cases, manipulation of transformer or transformer-2 was able to change the physiological output in response to starvation and oxidative stress to that of the opposite sex. Our data also uncover the possibility of additional downstream targets for transformer and transformer-2 that are separate from the sex determination pathway and can influence behavioral and physiological responses. Copyright © 2014 the American Physiological Society.

  15. Sex-specific consequences of an induced immune response on reproduction in a moth.

    Science.gov (United States)

    Barthel, Andrea; Staudacher, Heike; Schmaltz, Antje; Heckel, David G; Groot, Astrid T

    2015-12-16

    Immune response induction benefits insects in combatting infection by pathogens. However, organisms have a limited amount of resources available and face the dilemma of partitioning resources between immunity and other life-history traits. Since males and females differ in their life histories, sex-specific resource investment strategies to achieve an optimal immune response following an infection can be expected. We investigated immune response induction of females and males of Heliothis virescens in response to the entomopathogenic bacterium Serratia entomophila, and its effects on mating success and the female sexual signal. We found that females had higher expression levels of immune-related genes after bacterial challenge than males. However, males maintained a higher baseline expression of immune-related genes than females. The increased investment in immunity of female moths was negatively correlated with mating success and the female sexual signal. Male mating success was unaffected by bacterial challenge. Our results show that the sexes differed in their investment strategies: females invested in immune defense after a bacterial challenge, indicating facultative immune deployment, whereas males had higher baseline immunity than females, indicating immune maintenance. Interestingly, these differences in investment were reflected in the mate choice assays. As female moths are the sexual signallers, females need to invest resources in their attractiveness. However, female moths appeared to invest in immunity at the cost of reproductive effort.

  16. Sex-specific effects of a parasite evolving in a female-biased host population

    Science.gov (United States)

    2012-01-01

    Background Males and females differ in many ways and might present different opportunities and challenges to their parasites. In the same way that parasites adapt to the most common host type, they may adapt to the characteristics of the host sex they encounter most often. To explore this hypothesis, we characterized host sex-specific effects of the parasite Pasteuria ramosa, a bacterium evolving in naturally, strongly, female-biased populations of its host Daphnia magna. Results We show that the parasite proliferates more successfully in female hosts than in male hosts, even though males and females are genetically identical. In addition, when exposure occurred when hosts expressed a sexual dimorphism, females were more infected. In both host sexes, the parasite causes a similar reduction in longevity and leads to some level of castration. However, only in females does parasite-induced castration result in the gigantism that increases the carrying capacity for the proliferating parasite. Conclusions We show that mature male and female Daphnia represent different environments and reveal one parasite-induced symptom (host castration), which leads to increased carrying capacity for parasite proliferation in female but not male hosts. We propose that parasite induced host castration is a property of parasites that evolved as an adaptation to specifically exploit female hosts. PMID:23249484

  17. Preconception paternal bisphenol A exposure induces sex-specific anxiety and depression behaviors in adult rats.

    Directory of Open Access Journals (Sweden)

    Ying Fan

    Full Text Available Bisphenol A (BPA, an environmental endocrine-disrupting compound, has drawn a great attention for its adverse effect on behavioral development. Maternal exposure to this compound has been reported to induce anxiety and depression in offspring, but the effect of its paternal exposure is rarely discussed. This study investigated whether preconception paternal BPA exposure can affect the emotions of male rats and their offspring. Eighteen adult male rats (F0 received either a vehicle or 50 μg/kg/day BPA diet for 21 weeks and were then mated with non-exposed females to produce offspring (F1. The affective behaviors of F0 and F1 rats were evaluated in the open-field test, the elevated-plus maze and the forced swimming test, and their serum corticosterone were then examined. BPA exposure induced increased anxiety behaviors along with increased serum corticosterone in F0 rats. This paternal exposure also led to increased anxiety behaviors in F1 females and aggravated depression behaviors in both sexes of F1 rats. Furthermore, only F1 females exhibited increased serum corticosterone. Overall, these data indicate that preconception paternal exposure to a low dose of BPA may induce transgenerational sex-specific impairments in the affection of adult rats.

  18. Sex-Specific Muscular Maturation Responses Following Prenatal Exposure to Methylation-Related Micronutrients in Pigs

    Directory of Open Access Journals (Sweden)

    Michael Oster

    2017-01-01

    Full Text Available Supplementation of micronutrients involved in DNA methylation, particularly during pregnancy, is recommended because of its impacts on human health, but further evidence is needed regarding the effects of over-supplementation and differences between sexes. Here, a porcine model was used to assess effects of maternal supplementation with one-carbon-cycle compounds during prenatal and postnatal stages on offspring muscle development. Sows received either a standard diet (CON or a standard diet supplemented with folate, B6, B12, methionine, choline, and zinc (MET throughout gestation. Myogenesis-, growth-, and nutrient utilization-related transcript expression was assessed using quantitative PCR. Organismal phenotype and gene expression effects differed significantly between males and females. Male MET-offspring showed increased fetal weight during late pregnancy but decreased live weight postnatally, with compensatory transcriptional responses comprising myogenic key drivers (Pax7, MyoD1, myogenin. In contrast, female weights were unaffected by diet, and mRNA abundances corresponded to a phenotype of cellular reorganization via FABP3, FABP4, SPP1 and Insulin-like Growth Factor-signaling. These findings in an animal model suggest that supplementation during pregnancy with methylation-related micronutrients can promote sex-specific myogenic maturation processes related to organismal growth and muscle metabolism. The usage of maternal dietary supplements should be more carefully considered regarding its ability to promote fetal and postnatal health.

  19. Maternal programming of sex-specific responses to predator odor stress in adult rats.

    Science.gov (United States)

    St-Cyr, Sophie; Abuaish, Sameera; Sivanathan, Shathveekan; McGowan, Patrick O

    2017-08-01

    Prenatal stress mediated through the mother can lead to long-term adaptations in stress-related phenotypes in offspring. This study tested the long-lasting effect of prenatal exposure to predator odor, an ethologically relevant and psychogenic stressor, in the second half of pregnancy. As adults, the offspring of predator odor-exposed mothers showed increased anxiety-like behaviors in commonly used laboratory tasks assessing novelty-induced anxiety, increased defensive behavior in males and increased ACTH stress reactivity in females in response to predator odor. Female offspring from predator odor-exposed dams showed increased transcript abundance of glucocorticoid receptor (NR3C1) on the day of birth and FK506 binding protein 5 (FKBP5) in adulthood in the amygdala. The increase in FKBP5 expression was associated with decreased DNA methylation in Fkbp5 intron V. These results indicate a sex-specific response to maternal programming by prenatal predator odor exposure and a potential epigenetic mechanism linking these responses with modifications of the stress axis in females. These results are in accordance with the mismatch hypothesis stating that an animal's response to cues within its life history reflects environmental conditions anticipated during important developmental periods and should be adaptive when these conditions are concurring. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Sex-specific associations between peripheral oxytocin and emotion perception in schizophrenia.

    Science.gov (United States)

    Rubin, Leah H; Carter, C Sue; Drogos, Lauren; Jamadar, Rhoda; Pournajafi-Nazarloo, Hossein; Sweeney, John A; Maki, Pauline M

    2011-08-01

    We previously reported that higher levels of peripheral oxytocin are associated with lower levels of positive, general, and overall symptoms in women but not in men with schizophrenia. Here we investigate the influence of sex, sex steroid hormone fluctuations, and peripheral oxytocin levels on emotional processing in men and women with schizophrenia. Twenty-two women with schizophrenia and 31 female controls completed the Penn Emotion Acuity Test (PEAT), a facial emotion recognition and perception task, during two menstrual cycle phases: 1) early follicular (Days 2-4; low estrogen/progesterone) and 2) midluteal (Days 20-22; high estrogen/progesterone). Twenty-six males with schizophrenia and 26 male controls completed testing at comparable intervals. We obtained plasma hormone assays of estrogen, progesterone, testosterone, and oxytocin. No sex differences were noted on the PEAT. Plasma oxytocin levels did not fluctuate across phases of the menstrual cycle. However, female patients and controls more accurately identified facial emotions during the early follicular versus midluteal phase (pmen. Like healthy women, women with schizophrenia demonstrate menstrual-cycle dependent fluctuations in recognizing emotional cues. Like healthy women, female patients with higher levels of oxytocin perceived faces as happier. Future studies need to address whether this sex-specific relationship is associated with trust and other positive emotions, and whether exogenous oxytocin might enhance mood states and social interaction in female or all schizophrenia patients. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Sex-specific neural circuits of emotion regulation in the centromedial amygdala.

    Science.gov (United States)

    Wu, Yan; Li, Huandong; Zhou, Yuan; Yu, Jian; Zhang, Yuanchao; Song, Ming; Qin, Wen; Yu, Chunshui; Jiang, Tianzi

    2016-03-23

    Sex-related differences in emotion regulation (ER) in the frequency power distribution within the human amygdala, a brain region involved in emotion processing, have been reported. However, how sex differences in ER are manifested in the brain networks which are seeded on the amygdala subregions is unclear. The goal of this study was to investigate this issue from a brain network perspective. Utilizing resting-state functional connectivity (RSFC) analysis, we found that the sex-specific functional connectivity patterns associated with ER trait level were only seeded in the centromedial amygdala (CM). Women with a higher trait-level ER had a stronger negative RSFC between the right CM and the medial superior frontal gyrus (mSFG), and stronger positive RSFC between the right CM and the anterior insula (AI) and the superior temporal gyrus (STG). But men with a higher trait-level ER was associated with weaker negative RSFC of the right CM-mSFG and positive RSFCs of the right CM-left AI, right CM-right AI/STG, and right CM-left STG. These results provide evidence for the sex-related effects in ER based on CM and indicate that men and women may differ in the neural circuits associated with emotion representation and integration.

  2. Intermittent, low dose carbon monoxide exposure enhances survival and dopaminergic differentiation of human neural stem cells

    DEFF Research Database (Denmark)

    Dreyer-Andersen, Nanna; Almeida, Ana Sofia; Jensen, Pia

    2018-01-01

    Exploratory studies using human fetal tissue have suggested that intrastriatal transplantation of dopaminergic neurons may become a future treatment for patients with Parkinson's disease. However, the use of human fetal tissue is compromised by ethical, regulatory and practical concerns. Human stem...... cells constitute an alternative source of cells for transplantation in Parkinson's disease, but efficient protocols for controlled dopaminergic differentiation need to be developed. Short-term, low-level carbon monoxide (CO) exposure has been shown to affect signaling in several tissues, resulting...... in Parkinson's disease....

  3. Differential Survival between Visual Environments Supports a Role of Divergent Sensory Drive in Cichlid Fish Speciation.

    Science.gov (United States)

    Maan, Martine E; Seehausen, Ole; Groothuis, Ton G G

    2017-01-01

    Identifying the selective forces that initiate ecological speciation is a major challenge in evolutionary biology. Sensory drive has been implicated in speciation in various taxa, largely based on phenotype-environment correlations and signatures of selection in sensory genes. Here, we present a reciprocal transplant experiment revealing species differences in performance in alternative visual environments, consistent with speciation by divergent sensory drive. The closely related cichlids Pundamilia pundamilia and Pundamilia nyererei inhabit different visual environments in Lake Victoria and show associated differences in visual system properties. Mimicking the two light environments in the laboratory, we find a substantial reduction in survival of both species when reared in the other species' visual environment. This implies that the observed differences in Pundamilia color vision are indeed adaptive and substantiates the implicit assumption in sensory drive speciation models that divergent environmental selection is strong enough to drive divergence in sensory properties.

  4. Differential survival of Ichthyophonus isolates indicates parasite adaptation to its host environment.

    Science.gov (United States)

    Hershberger, P K; Pacheco, C A; Gregg, J L; Purcell, M K; LaPatra, S E

    2008-10-01

    In vitro viability of Ichthyophonus spp. spores in seawater and freshwater corresponded with the water type of the host from which the spores were isolated. Among Ichthyophonus spp. spores from both marine and freshwater fish hosts (Pacific herring, Clupea pallasii, and rainbow trout, Oncorhynchus mykiss, respectively), viability was significantly greater (P < 0.05) after incubation in seawater than in freshwater at all time points from 1 to 60 min after immersion; however, magnitude of the spore tolerances to water type differed with host origin. Ichthyophonus sp. adaptation to its host environment was indicated by greater seawater tolerance of spores from the marine host and greater freshwater tolerance of spores from the freshwater host. Prolonged aqueous survival of Ichthyophonus spp. spores in the absence of a host provides insight into routes of transmission, particularly among planktivorous fishes, and should be considered when designing strategies to dispose of infected fish carcasses and tissues.

  5. The ageing phenome: caloric restriction and hormones promote neural cell survival, growth, and de-differentiation.

    Science.gov (United States)

    Timiras, Paola S; Yaghmaie, Farzin; Saeed, Omar; Thung, Elaine; Chinn, Garrett

    2005-01-01

    The phenome represents the observable properties of an organism that have developed under the continued influences of both genome and environmental factors. Phenotypic properties are expressed through the functions of cells, organs and body systems that operate optimally, close to equilibrium. In complex organisms, maintenance of the equilibrium is achieved by the interplay of several regulatory mechanisms. In the elderly, dynamic instability may lead to progressive loss of normal function, failure of adaptation and increased pathology. Extensive research (reported elsewhere in this journal) has demonstrated that genetic manipulations of endocrine signaling in flies, worms and mice increase longevity. Another effective strategy for prolonging the lifespan is caloric restriction: in data presented here, the persistence of estrogen-sensitive cells in the hypothalamus of caloric restricted 22-month-old female mice, may explain the persistence of reproductive function at an age, when reproductive function has long ceased in ad libitum fed controls. Still another strategy utilizes the effects of epidermal growth factor (EGF) to promote in vitro proliferation of neuroglia, astrocytes and oligodendrocytes. Their subsequent de-differentiation generates immature precursor cells potentially capable of differentiating into neuroblasts and neurons. These and other examples suggest that, in terms of functional outcomes, "the genome proposes but the phenome disposes".

  6. Radiation-Induced Differentiated Thyroid Cancer Is Associated with Improved Overall Survival but Not Thyroid Cancer-Specific Mortality or Disease-Free Survival.

    Science.gov (United States)

    White, Michael G; Cipriani, Nicole A; Abdulrasool, Layth; Kaplan, Sharone; Aschebrook-Kilfoy, Briseis; Angelos, Peter; Kaplan, Edwin L; Grogan, Raymon H; Onel, Kenan

    2016-08-01

    Radiation is a well-described risk factor for differentiated thyroid carcinoma (DTC). Although the natural history of DTC following nuclear disasters and in healthcare workers with chronic radiation exposure (RE) has been described, little is known about DTC following short-term exposure to therapeutic medical radiation for benign disease. This study compares DTC morphology and outcomes in patients with and without a prior history of therapeutic external RE. A retrospective review was performed of patients with DTC treated at The University of Chicago between 1951 and 1987, with a median follow-up of 27 years (range 0.3-60 years). Patients were classified as either having (RE+) or not having (RE-) a history of therapeutic RE. Variables examined included sex, age at RE, dose of RE, indication for RE, DTC histology, and outcome. Morphology was determined by blinded retrospective review of all available histologic slides. Outcomes were assessed using Cox proportional hazards model and Kaplan-Meier curves. Of 257 DTC patients, 165 (64%) were RE- and 92 (36%) were RE+, with males comprising a greater proportion of the RE+ group (43.5% vs. 27.3%; p = 0.01). A total of 94.2% of DTC cases were classic papillary cancers; histology did not differ between RE+ and RE- cohorts (p = 0.73). RE was associated with an increased median overall survival (OS; 43 years vs. 38 years; hazard ratio [HR] = 0.55 [confidence interval (CI) 0.34-0.89]; p = 0.01). Survival for males in the RE- group was significantly worse than it was for RE- females (HR = 1.78 [CI 1.05-3.03]; p = 0.03) or RE+ males (HR = 2.98 [CI 1.39-6.38]; p = 0.01). Recurrence did not differ between the RE+ and RE- groups (HR = 0.85 [CI 0.52-1.41]; p = 0.54), nor did DTC-specific mortality (HR = 0.54 [CI 0.21-1.37]; p = 0.20). While DTC following RE has historically been considered a more aggressive variant than DTC in the absence of RE, the present data indicate that RE+ DTC

  7. Rewiring carbohydrate catabolism differentially affects survival of pancreatic cancer cell lines with diverse metabolic profiles

    Science.gov (United States)

    Tataranni, Tiziana; Agriesti, Francesca; Ruggieri, Vitalba; Mazzoccoli, Carmela; Simeon, Vittorio; Laurenzana, Ilaria; Scrima, Rosella; Pazienza, Valerio; Capitanio, Nazzareno; Piccoli, Claudia

    2017-01-01

    An increasing body of evidence suggests that targeting cellular metabolism represents a promising effective approach to treat pancreatic cancer, overcome chemoresistance and ameliorate patient's prognosis and survival. In this study, following whole-genome expression analysis, we selected two pancreatic cancer cell lines, PANC-1 and BXPC-3, hallmarked by distinct metabolic profiles with specific concern to carbohydrate metabolism. Functional comparative analysis showed that BXPC-3 displayed a marked deficit of the mitochondrial respiratory and oxidative phosphorylation activity and a higher production of reactive oxygen species and a reduced NAD+/NADH ratio, indicating their bioenergetic reliance on glycolysis and a different redox homeostasis as compared to PANC-1. Both cell lines were challenged to rewire their metabolism by substituting glucose with galactose as carbon source, a condition inhibiting the glycolytic flux and fostering full oxidation of the sugar carbons. The obtained data strikingly show that the mitochondrial respiration-impaired-BXPC-3 cell line was unable to sustain the metabolic adaptation required by glucose deprivation/substitution, thereby resulting in a G2\\M cell cycle shift, unbalance of the redox homeostasis, apoptosis induction. Conversely, the mitochondrial respiration-competent-PANC-1 cell line did not show clear evidence of cell sufferance. Our findings provide a strong rationale to candidate metabolism as a promising target for cancer therapy. Defining the metabolic features at time of pancreatic cancer diagnosis and likely of other tumors, appears to be crucial to predict the responsiveness to therapeutic approaches or coadjuvant interventions affecting metabolism. PMID:28476035

  8. Differential effects of synthetic progestagens on neuron survival and estrogen neuroprotection in cultured neurons.

    Science.gov (United States)

    Jayaraman, Anusha; Pike, Christian J

    2014-03-25

    Progesterone and other progestagens are used in combination with estrogens for clinical purposes, including contraception and postmenopausal hormone therapy. Progesterone and estrogens have interactive effects in brain, however interactions between synthetic progestagens and 17β-estradiol (E2) in neurons are not well understood. In this study, we investigated the effects of seven clinically relevant progestagens on estrogen receptor (ER) mRNA expression, E2-induced neuroprotection, and E2-induced BDNF mRNA expression. We found that medroxyprogesterone acetate decreased both ERα and ERβ expression and blocked E2-mediated neuroprotection and BDNF expression. Conversely, levonorgestrel and nesterone increased ERα and or ERβ expression, were neuroprotective, and failed to attenuate E2-mediated increases in neuron survival and BDNF expression. Other progestagens tested, including norethindrone, norethindrone acetate, norethynodrel, and norgestimate, had variable effects on the measured endpoints. Our results demonstrate a range of qualitatively different actions of progestagens in cultured neurons, suggesting significant variability in the neural effects of clinically utilized progestagens. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Sex-specific relationships between adverse childhood experiences and chronic obstructive pulmonary disease in five states

    Directory of Open Access Journals (Sweden)

    Cunningham TJ

    2014-09-01

    Full Text Available Timothy J Cunningham,1 Earl S Ford,1 Janet B Croft,1 Melissa T Merrick,2 Italia V Rolle,3 Wayne H Giles1 1Division of Population Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA, USA; 2Division of Violence Prevention, National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, Atlanta, GA, USA; 3Office on Smoking and Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA, USA Purpose: Adverse childhood experiences (ACEs before age 18 have been repeatedly associated with several chronic diseases in adulthood such as depression, heart disease, cancer, diabetes, and stroke. We examined sex-specific relationships between individual ACEs and the number of ACEs with chronic obstructive pulmonary disease (COPD in the general population. Materials and methods: Data from 26,546 women and 19,015 men aged ≥18 years in five states of the 2011 Behavioral Risk Factor Surveillance System were analyzed. We used log-linear regression to estimate prevalence ratios (PRs and their corresponding 95% confidence intervals (CIs for the relationship of eight ACEs with COPD after adjustment for age group, race/ethnicity, marital status, educational attainment, employment, asthma history, health insurance coverage, and smoking status. Results: Some 63.8% of women and 62.2% of men reported ≥1 ACE. COPD was reported by 4.9% of women and 4.0% of men. In women, but not in men, there was a higher likelihood of COPD associated with verbal abuse (PR =1.30, 95% CI: 1.05, 1.61, sexual abuse (PR =1.69, 95% CI: 1.36, 2.10, living with a substance abusing household member (PR =1.49, 95% CI: 1.23, 1.81, witnessing domestic violence (PR =1.40, 95% CI: 1.14, 1.72, and parental separation/divorce (PR =1.47, 95% CI: 1.21, 1.80 during childhood compared to those with no individual ACEs

  10. BISPHENOL A EXPOSURE DURING EARLY DEVELOPMENT INDUCES SEX-SPECIFIC CHANGES IN ADULT ZEBRAFISH SOCIAL INTERACTIONS

    Science.gov (United States)

    Weber, Daniel N.; Hoffmann, Raymond G.; Hoke, Elizabeth S.; Tanguay, Robert L.

    2014-01-01

    Developmental bisphenol A (BPA) exposure is associated with adverse behavioral effects, although underlying modes of action remain unclear. Because BPA is a suspected xenoestrogen, the objective was to identify sex-based changes in adult zebrafish social behavior developmentally exposed to BPA (0.0, 0.1 or 1 μM) or one of two control compounds (0.1μM 17β-estradiol [E2], and 0.1 μM GSK4716, a synthetic estrogen-related receptor γ ligand). A test chamber was divided lengthwise so each arena held one fish unable to detect the presence of the other fish. A mirror was inserted at one end of each arena; baseline activity levels were determined without mirror. Arenas were divided into 3, computer-generated zones to represent different distances from mirror image. Circadian rhythm patterns were evaluated at 1–3 (= AM) and 5–8 (= PM) hr postprandial. Adult zebrafish were placed into arenas and monitored by digital camera for 5 min. Total distance traveled, % time spent at mirror image, and number of attacks on mirror image were quantified. E2, GSK4716, and all BPA treatments dampened male activity and altered male circadian activity patterns; there was no marked effect on female activity. BPA induced non-monotonic effects (response curve changes direction within range of concentrations examined) on male % time at mirror only in AM. All treatments produced increased % time at the mirror during PM. Male attacks on the mirror were reduced by BPA exposure only during AM. There were sex-specific effects of developmental BPA on social interactions and time-of-day of observation affected results. PMID:25424546

  11. Pre- and postnatal stress and asthma in children: Temporal- and sex-specific associations

    Science.gov (United States)

    Lee, Alison; Chiu, Yueh-Hsiu Mathilda; Rosa, Maria José; Jara, Calvin; Wright, Robert O.; Coull, Brent A.; Wright, Rosalind J.

    2016-01-01

    BACKGROUND Temporal- and sex-specific effects of perinatal stress have not been examined for childhood asthma. OBJECTIVES We examined associations between pre- and/or postnatal stress and children's asthma (n=765) and effect modification by sex in a prospective cohort study. METHODS Maternal negative life events (NLEs) were ascertained prenatally and postpartum. NLEs scores were categorized as 0, 1-2, 3-4, or ≥5 to assess exposure-response relationships. We examined effects of pre- and postnatal stress on children's asthma by age 6 years modeling each as independent predictors; mutually adjusting for prenatal and postnatal stress; and finally considering interactions between pre- and postnatal stress. Effect modification by sex was examined in stratified analyses and by fitting interaction terms. RESULTS When considering stress in each period independently, among boys a dose-response relationship was evident for each level increase on the ordinal scale prenatally (OR=1.38, 95% CI 1.06, 1.79; p-for-trend=0.03) and postnatally (OR=1.53, 95% CI 1.16, 2.01; p-for-trend=0.001); among girls only the postnatal trend was significant (OR=1.60, 95% CI 1.14, 2.22; p-for-trend=0.005). Higher stress in both the pre- and postnatal periods was associated with increased odds of being diagnosed with asthma in girls [OR=1.37, 95% CI 0.98, 1.91 (pinteraction=0.07)] but not boys [OR=1.08, 95% CI 0.82, 1.42 (pinteraction=0.61)]. CONCLUSIONS While boys were more vulnerable to stress during the prenatal period, girls were more impacted by postnatal stress and cumulative stress across both periods in relation to asthma. Understanding sex and temporal differences in response to early life stress may provide unique insight into asthma etiology and natural history. PMID:26953156

  12. Sex-specific neuroanatomical correlates of fear expression in prefrontal-amygdala circuits.

    Science.gov (United States)

    Gruene, Tina M; Roberts, Elian; Thomas, Virginia; Ronzio, Ashley; Shansky, Rebecca M

    2015-08-01

    The neural projections from the infralimbic region of the prefrontal cortex to the amygdala are important for the maintenance of conditioned fear extinction. Neurons in this pathway exhibit a unique pattern of structural plasticity that is sex-dependent, but the relationship between the morphologic characteristics of these neurons and successful extinction in male and female subjects is unknown. Using classic cued fear conditioning and an extinction paradigm in large cohorts of male and female rats, we identified subpopulations of both sexes that exhibited high (HF) or low (LF) levels of freezing on an extinction retrieval test, representing failed or successful extinction maintenance, respectively. We combined retrograde tracing with fluorescent intracellular microinjections to perform three-dimensional reconstructions of infralimbic neurons that project to the basolateral amygdala in these groups. The HF and LF male rats exhibited neuroanatomical distinctions that were not observed in HF or LF female rats. A retrospective analysis of behavior during fear conditioning and extinction revealed that despite no overall sex differences in freezing behavior, HF and LF phenotypes emerged in male rats during extinction and in female rats during fear conditioning, which does not involve infralimbic-basolateral amygdala neurons. Our results suggest that the neural processes underlying successful or failed extinction maintenance may be sex-specific. These findings are relevant not only to future basic research on sex differences in fear conditioning and extinction but also to exposure-based clinical therapies, which are similar in premise to fear extinction and which are primarily used to treat disorders that are more common in women than in men. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  13. Anti-aging drugs reduce hypothalamic inflammation in a sex-specific manner.

    Science.gov (United States)

    Sadagurski, Marianna; Cady, Gillian; Miller, Richard A

    2017-08-01

    Aging leads to hypothalamic inflammation, but does so more slowly in mice whose lifespan has been extended by mutations that affect GH/IGF-1 signals. Early-life exposure to GH by injection, or to nutrient restriction in the first 3 weeks of life, also modulate both lifespan and the pace of hypothalamic inflammation. Three drugs extend lifespan of UM-HET3 mice in a sex-specific way: acarbose (ACA), 17-α-estradiol (17αE2), and nordihydroguaiaretic acid (NDGA), with more dramatic longevity increases in males in each case. In this study, we examined the effect of these anti-aging drugs on neuro-inflammation in hypothalamus and hippocampus. We found that age-associated hypothalamic inflammation is reduced in males but not in females at 12 months of age by ACA and 17αE2 and at 22 months of age in NDGA-treated mice. The three drugs blocked indices of hypothalamic reactive gliosis associated with aging, such as Iba-1-positive microglia and GFAP-positive astrocytes, as well as age-associated overproduction of TNF-α. This effect was not observed in drug-treated female mice or in the hippocampus of the drug-treated animals. On the other hand, caloric restriction (CR; an intervention that extends the lifespan in both sexes) significantly reduced hypothalamic microglia and TNF-α in both sexes at 12 months of age. Together, these results suggest that the extent of drug-induced changes in hypothalamic inflammatory processes is sexually dimorphic in a pattern that parallels the effects of these agents on mouse longevity and that mimics the changes seen, in both sexes, of long-lived nutrient restricted or mutant mice. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  14. Sex-specific substance abuse treatment for female healthcare professionals: implications.

    Science.gov (United States)

    Koos, Erin; Brand, Michael; Rojas, Julio; Li, Ji

    2014-01-01

    Gender plays a significant role in the development and treatment of substance abuse disorders. Sex-specific treatment for girls and women has recurrently proven more effective, with better outcomes than traditional treatment. Research on impaired healthcare professionals (HCPs) has largely focused on men, garnering little attention for women and sex differences. With the increasing numbers of female HCPs, it is imperative to identify potential sex differences that may have implications for treatment. Our study compared a convenience sample of male and female HCPs with substance abuse disorders treated in an outpatient program to identify sex differences that may have implications for treatment. Our sample consisted of 96 HCPs (54 men, 42 women) and 17 non-healthcare professional (N-HCP) women. All of the participants were evaluated using the program's clinical interview and the Personality Assessment Inventory (PAI). Chart review data contained categorical variables, qualitative variables, diagnoses, and psychological test scores. A second analysis was conducted through two separate comparisons: the PAI results of comparing impaired female HCPs with impaired male HCPs and the PAI results of comparing impaired female HCPs with impaired female N-HCPs. Statistically significant differences indicated more male participants received prior treatment and more intensive treatment than female participants. More female subjects reported being diagnosed as having a comorbid psychiatric condition and taking psychotropic medications. Several statistically significant differences in the PAI scores were found. Among female HCPs, elevations were found in anxiety, depression, paranoia, and borderline personality disorder. Substantive differences, although not statistically significant, were elevations in somatic complaints and anxiety disorders in female HCPs. In the comparison of female HCPs and N-HCPs, the only statistically significant difference was the significantly higher

  15. Sex-specific Gray Matter Volume Differences in Females with Developmental Dyslexia

    Science.gov (United States)

    Evans, Tanya M.; Flowers, D. Lynn; Napoliello, Eileen M.; Eden, Guinevere F.

    2013-01-01

    Developmental dyslexia, characterized by unexpected reading difficulty, is associated with anomalous brain anatomy and function. Previous structural neuroimaging studies have converged in reports of less gray matter volume (GMV) in dyslexics within left hemisphere regions known to subserve language. Due to the higher prevalence of dyslexia in males, these studies are heavily weighted towards males, raising the question whether studies of dyslexia in females only and using the same techniques, would generate the same findings. In a replication study of men we obtained the same findings of less GMV in dyslexics in left middle/inferior temporal gyri and right postcentral/supramarginal gyri as reported in the literature. However, comparisons in women with and without dyslexia did not yield left hemisphere differences and instead we found less GMV in right precuneus and paracentral lobule/medial frontal gyrus. In boys, we found less GMV in left inferior parietal cortex (supramarginal/angular gyri), again consistent with previous work, while in girls differences were within right central sulcus, spanning adjacent gyri, and left primary visual cortex. Our investigation into anatomical variants in dyslexia replicates existing studies in males, but at the same time shows that dyslexia in females is not characterized by involvement of left hemisphere language regions but rather early sensory and motor cortices (i.e. motor and premotor cortex, primary visual cortex). Our findings suggest that models on the brain basis of dyslexia, primarily developed through the study of males, may not be appropriate for females and suggest a need for more sex-specific investigations into dyslexia. PMID:23625146

  16. Timing of Maternal Depression and Sex-Specific Child Growth, the Upstate KIDS Study.

    Science.gov (United States)

    Park, Hyojun; Sundaram, Rajeshwari; Gilman, Stephen E; Bell, Griffith; Louis, Germaine M Buck; Yeung, Edwina H

    2018-01-01

    Equivocal findings have been reported on the association between maternal depression and children's growth, possibly because of the limited attention to its disproportionate impact by child sex. The relationship between the timing of maternal depression and children's growth was assessed in a population-based prospective birth cohort, with particular attention to sex differences. The Upstate KIDS Study comprised 4,394 children followed through 3 years of age from 2008 to 2010. Maternal depression was measured antenatally by linkage with hospital discharge records before delivery and postnatally by depressive symptoms reported from questionnaires. Children's growth was measured by sex- and age-specific weight, height, weight for height, and BMI. Adjusted linear mixed effects models were used to estimate growth outcomes for the full sample and separately by plurality and sex. Antenatal depression was associated with lower weight for age (-0.24 z score units; 95% confidence interval [CI]: -0.43, -0.05) and height for age (-0.26 z score units; 95% CI: -0.51, -0.02) among singleton boys. Postnatal depressive symptoms were associated with higher weight for height (0.21 z score units; 95% CI: 0.01, 0.42) among singleton girls. The findings of this study suggest that antenatal depression was associated with lower weight and smaller height only for boys, whereas postnatal depressive symptoms were associated with higher weight for height only for girls. The timing of depression and the mechanisms of sex-specific responses require further examination. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  17. Spatial and sex-specific dissection of the Anopheles gambiae midgut transcriptome

    Directory of Open Access Journals (Sweden)

    Mahairaki Vassiliki

    2007-01-01

    Full Text Available Abstract Background The midgut of hematophagous insects, such as disease transmitting mosquitoes, carries out a variety of essential functions that mostly relate to blood feeding. The midgut of the female malaria vector mosquito Anopheles gambiae is a major site of interactions between the parasite and the vector. Distinct compartments and cell types of the midgut tissue carry out specific functions and vector borne pathogens interact and infect different parts of the midgut. Results A microarray based global gene expression approach was used to compare transcript abundance in the four major female midgut compartments (cardia, anterior, anterior part of posterior and posterior part of posterior midgut and between the male and female Anopheles gambiae midgut. Major differences between the female and male midgut gene expression relate to digestive processes and immunity. Each compartment has a distinct gene function profile with the posterior midgut expressing digestive enzyme genes and the cardia and anterior midgut expressing high levels of antimicrobial peptide and other immune gene transcripts. Interestingly, the cardia expressed several known anti-Plasmodium factors. A parallel peptidomic analysis of the cardia identified known mosquito antimicrobial peptides as well as several putative short secreted peptides that are likely to represent novel antimicrobial factors. Conclusion The A. gambiae sex specific midgut and female midgut compartment specific transcriptomes correlates with their known functions. The significantly greater functional diversity of the female midgut relate to hematophagy that is associated with digestion and nutrition uptake as well as exposes it to a variety of pathogens, and promotes growth of its endogenous microbial flora. The strikingly high proportion of immunity related factors in the cardia tissue most likely serves the function to increase sterility of ingested sugar and blood. A detailed characterization of the

  18. Enhancement of trophoblast differentiation and survival by low molecular weight heparin requires heparin-binding EGF-like growth factor.

    Science.gov (United States)

    Bolnick, Alan D; Bolnick, Jay M; Kohan-Ghadr, Hamid-Reza; Kilburn, Brian A; Pasalodos, Omar J; Singhal, Pankaj K; Dai, Jing; Diamond, Michael P; Armant, D Randall; Drewlo, Sascha

    2017-06-01

    Does low molecular weight heparin (LMWH) require heparin-binding epidermal growth factor (EGF)-like growth factor (HBEGF) signaling to induce extravillous trophoblast differentiation and decrease apoptosis during oxidative stress? LMWH increased HBEGF expression and secretion, and HBEGF signaling was required to stimulate trophoblast extravillous differentiation, increase invasion in vitro and reduce trophoblast apoptosis during oxidative stress. Abnormal trophoblast differentiation and survival contribute to placental insufficiency syndromes, including preeclampsia and intrauterine growth restriction. Preeclampsia often manifests as a pro-thrombotic state, with unsuccessful transformation of the spiral arteries that reduces oxygen supply and can produce placental infarction. LMWH improves placental function by increasing blood flow. Recent data suggest that the actions of LMWH transcend its anti-coagulative properties, but the molecular mechanism is unknown. There is evidence that LMWH alters the expression of human HBEGF in trophoblast cells, which regulates human trophoblast pathophysiology. HBEGF, itself, is capable of increasing trophoblast survival and invasiveness. First-trimester placental explants and the HTR-8/SVneo cell line, established using extravillous trophoblast outgrowths from first-trimester villous explants, were treated in vitro with LMWH to examine the effects on HBEGF signaling and trophoblast function under normal physiological and pathological conditions. A highly specific antagonist of HBEGF and other inhibitors of HBEGF downstream signaling were used to determine the relationship between LMWH treatment and HBEGF. Placental tissues (n = 5) were obtained with IRB approval and patient consent from first-trimester terminations. Placental explants and HTR-8/SVneo cells were cultured on plastic or Matrigel™ and treated with a therapeutic dose of LMWH (Enoxaparin; 10 IU/ml), with or without CRM197, pan Erb-B2 Receptor Tyrosine Kinase (ERBB

  19. Non-coding changes cause sex-specific wing size differences between closely related species of Nasonia

    NARCIS (Netherlands)

    Loehlin, David W.; Oliveira, Deodoro C. S. G.; Edwards, Rachel; Giebel, Jonathan D.; Clark, Michael E.; Cattani, M. Victoria; van de Zande, Louis; Verhulst, Eveline C.; Beukeboom, Leo W.; Munoz-Torres, Monica; Werren, John H.

    The genetic basis of morphological differences among species is still poorly understood. We investigated the genetic basis of sex-specific differences in wing size between two closely related species of Nasonia by positional cloning a major male-specific locus, wing-size1 (ws1). Male wing size

  20. Sex-specific biotransformation and detoxification after xenobiotic exposure of primary cultured hepatocytes of European flounder (Platichthys flesus L.)

    NARCIS (Netherlands)

    Winzer, Katja; van Noorden, Cornelis J. F.; Köhler, Angela

    2002-01-01

    Sex-specific effects of sublethal concentrations of known effective pro-oxidants such as 100, 200 and 400 muM benzo[a]pyrene (B[a]p), 50 M nitrofurantoin (NF) and 100 muM hydrogen peroxide (H2O2) on biotransformation pathways were studied in isolated hepatocytes of immature female and male European

  1. Maternal provision of non-sex-specific transformer messenger RNA in sex determination of the wasp Asobara tabida.

    Science.gov (United States)

    Geuverink, E; Verhulst, E C; van Leussen, M; van de Zande, L; Beukeboom, L W

    2018-02-01

    In many insect species maternal provision of sex-specifically spliced messenger RNA (mRNA) of sex determination genes is an essential component of the sex determination mechanism. In haplodiploid Hymenoptera, maternal provision in combination with genomic imprinting has been shown for the parasitoid Nasonia vitripennis, known as maternal effect genomic imprinting sex determination (MEGISD). Here, we characterize the sex determination cascade of Asobara tabida, another hymenopteran parasitoid. We show the presence of the conserved sex determination genes doublesex (dsx), transformer (tra) and transformer-2 (tra2) orthologues in As. tabida. Of these, At-dsx and At-tra are sex-specifically spliced, indicating a conserved function in sex determination. At-tra and At-tra2 mRNA is maternally provided to embryos but, in contrast to most studied insects, As. tabida females transmit a non-sex-specific splice form of At-tra mRNA to the eggs. In this respect, As. tabida sex determination differs from the MEGISD mechanism. How the paternal genome can induce female development in the absence of maternal provision of sex-specifically spliced mRNA remains an open question. Our study reports a hitherto unknown variant of maternal effect sex determination and accentuates the diversity of insect sex determination mechanisms. © 2017 The Authors. Insect Molecular Biology published by John Wiley & Sons Ltd on behalf of Royal Entomological Society.

  2. Heavy Episodic Drinking and Alcohol-Related Consequences: Sex-Specific Differences in Parental Influences among Ninth-Grade Students

    Science.gov (United States)

    Doumas, Diana M.; Hausheer, Robin; Esp, Susan

    2015-01-01

    Parents impact adolescent substance abuse, but sex-specific influences are not well-understood. This study examined parental influences on adolescent drinking behavior in a sample of ninth-grade students (N = 473). Hierarchical regression analyses indicated parental monitoring, disapproval of teen alcohol use, and quality of parent-teen general…

  3. Type I vs type II spiral ganglion neurons exhibit differential survival and neuritogenesis during cochlear development

    Directory of Open Access Journals (Sweden)

    Housley Gary D

    2011-10-01

    Full Text Available Abstract Background The mechanisms that consolidate neural circuitry are a major focus of neuroscience. In the mammalian cochlea, the refinement of spiral ganglion neuron (SGN innervation to the inner hair cells (by type I SGNs and the outer hair cells (by type II SGNs is accompanied by a 25% loss of SGNs. Results We investigated the segregation of neuronal loss in the mouse cochlea using β-tubulin and peripherin antisera to immunolabel all SGNs and selectively type II SGNs, respectively, and discovered that it is the type II SGN population that is predominately lost within the first postnatal week. Developmental neuronal loss has been attributed to the decline in neurotrophin expression by the target hair cells during this period, so we next examined survival of SGN sub-populations using tissue culture of the mid apex-mid turn region of neonatal mouse cochleae. In organotypic culture for 48 hours from postnatal day 1, endogenous trophic support from the organ of Corti proved sufficient to maintain all type II SGNs; however, a large proportion of type I SGNs were lost. Culture of the spiral ganglion as an explant, with removal of the organ of Corti, led to loss of the majority of both SGN sub-types. Brain-derived neurotrophic factor (BDNF added as a supplement to the media rescued a significant proportion of the SGNs, particularly the type II SGNs, which also showed increased neuritogenesis. The known decline in BDNF production by the rodent sensory epithelium after birth is therefore a likely mediator of type II neuron apoptosis. Conclusion Our study thus indicates that BDNF supply from the organ of Corti supports consolidation of type II innervation in the neonatal mouse cochlea. In contrast, type I SGNs likely rely on additional sources for trophic support.

  4. Conservation and Sex-Specific Splicing of the transformer Gene in the Calliphorids Cochliomyia hominivorax, Cochliomyia macellaria and Lucilia sericata

    Science.gov (United States)

    Li, Fang; Vensko, Steven P.; Belikoff, Esther J.; Scott, Maxwell J.

    2013-01-01

    Transformer (TRA) promotes female development in several dipteran species including the Australian sheep blowfly Lucilia cuprina, the Mediterranean fruit fly, housefly and Drosophila melanogaster. tra transcripts are sex-specifically spliced such that only the female form encodes full length functional protein. The presence of six predicted TRA/TRA2 binding sites in the sex-specific female intron of the L. cuprina gene suggested that tra splicing is auto-regulated as in medfly and housefly. With the aim of identifying conserved motifs that may play a role in tra sex-specific splicing, here we have isolated and characterized the tra gene from three additional blowfly species, L. sericata, Cochliomyia hominivorax and C. macellaria. The blowfly adult male and female transcripts differ in the choice of splice donor site in the first intron, with males using a site downstream of the site used in females. The tra genes all contain a single TRA/TRA2 site in the male exon and a cluster of four to five sites in the male intron. However, overall the sex-specific intron sequences are poorly conserved in closely related blowflies. The most conserved regions are around the exon/intron junctions, the 3′ end of the intron and near the cluster of TRA/TRA2 sites. We propose a model for sex specific regulation of tra splicing that incorporates the conserved features identified in this study. In L. sericata embryos, the male tra transcript was first detected at around the time of cellular blastoderm formation. RNAi experiments showed that tra is required for female development in L. sericata and C. macellaria. The isolation of the tra gene from the New World screwworm fly C. hominivorax, a major livestock pest, will facilitate the development of a “male-only” strain for genetic control programs. PMID:23409170

  5. Regulation of normal B-cell differentiation and malignant B-cell survival by OCT2.

    Science.gov (United States)

    Hodson, Daniel J; Shaffer, Arthur L; Xiao, Wenming; Wright, George W; Schmitz, Roland; Phelan, James D; Yang, Yandan; Webster, Daniel E; Rui, Lixin; Kohlhammer, Holger; Nakagawa, Masao; Waldmann, Thomas A; Staudt, Louis M

    2016-04-05

    The requirement for the B-cell transcription factor OCT2 (octamer-binding protein 2, encoded by Pou2f2) in germinal center B cells has proved controversial. Here, we report that germinal center B cells are formed normally after depletion of OCT2 in a conditional knockout mouse, but their proliferation is reduced and in vivo differentiation to antibody-secreting plasma cells is blocked. This finding led us to examine the role of OCT2 in germinal center-derived lymphomas. shRNA knockdown showed that almost all diffuse large B-cell lymphoma (DLBCL) cell lines are addicted to the expression of OCT2 and its coactivator OCA-B. Genome-wide chromatin immunoprecipitation (ChIP) analysis and gene-expression profiling revealed the broad transcriptional program regulated by OCT2 that includes the expression of STAT3, IL-10, ELL2, XBP1, MYC, TERT, and ADA. Importantly, genetic alteration of OCT2 is not a requirement for cellular addiction in DLBCL. However, we detected amplifications of the POU2F2 locus in DLBCL tumor biopsies and a recurrent mutation of threonine 223 in the DNA-binding domain of OCT2. This neomorphic mutation subtly alters the DNA-binding preference of OCT2, leading to the transactivation of noncanonical target genes including HIF1a and FCRL3 Finally, by introducing mutations designed to disrupt the OCT2-OCA-B interface, we reveal a requirement for this protein-protein interface that ultimately might be exploited therapeutically. Our findings, combined with the predominantly B-cell-restricted expression of OCT2 and the absence of a systemic phenotype in our knockout mice, suggest that an OCT2-targeted therapeutic strategy would be efficacious in both major subtypes of DLBCL while avoiding systemic toxicity.

  6. Systemic administration of valproic acid and zonisamide promotes the survival and differentiation of induced pluripotent stem cell–derived dopaminergic neurons

    OpenAIRE

    Tatsuya eYoshikawa; Tatsuya eYoshikawa; Tatsuya eYoshikawa; Bumpei eSamata; Bumpei eSamata; Aya eOgura; Aya eOgura; Susumu eMiyamoto; Jun eTakahashi; Jun eTakahashi; Jun eTakahashi

    2013-01-01

    Cell replacement therapy using embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) is a promising strategy for the treatment of neurologic diseases such as Parkinson’s disease (PD). However, a limiting factor for effective cell transplantation is the low survival rate of grafted cells, especially neurons. In this study, we modified the host environment and investigated whether the simultaneous administration of soluble factors can improve the survival and differentiation of...

  7. Sex-specific differences of craniofacial traits in Croatia: the impact of environment in a small geographic area.

    Science.gov (United States)

    Buretic-Tomljanovic, Alena; Giacometti, Jasminka; Ostojic, Sasa; Kapovic, Miljenko

    2007-01-01

    , characterized by higher average sunshine duration, higher average precipitation and higher average air temperatures, was associated with longer, higher and narrower skulls, higher head circumference, lower cephalic index, and higher and narrower faces (lower facial index). Calcium concentrations in drinking water did not correlate significantly with any dependent variable. A significant effect of environmental factors on body height and craniofacial variability was found in Croatian young adult population. This effect was more pronounced in females, revealing sex-specific craniofacial differentiation. However, the impact of environment was low and may explain only 1.0-7.32% variation of the investigated traits.

  8. Sex-Specific Prediction Models for Sleep Apnea From the Hispanic Community Health Study/Study of Latinos.

    Science.gov (United States)

    Shah, Neomi; Hanna, David B; Teng, Yanping; Sotres-Alvarez, Daniela; Hall, Martica; Loredo, Jose S; Zee, Phyllis; Kim, Mimi; Yaggi, H Klar; Redline, Susan; Kaplan, Robert C

    2016-06-01

    We developed and validated the first-ever sleep apnea (SA) risk calculator in a large population-based cohort of Hispanic/Latino subjects. Cross-sectional data on adults from the Hispanic Community Health Study/Study of Latinos (2008-2011) were analyzed. Subjective and objective sleep measurements were obtained. Clinically significant SA was defined as an apnea-hypopnea index ≥ 15 events per hour. Using logistic regression, four prediction models were created: three sex-specific models (female-only, male-only, and a sex × covariate interaction model to allow differential predictor effects), and one overall model with sex included as a main effect only. Models underwent 10-fold cross-validation and were assessed by using the C statistic. SA and its predictive variables; a total of 17 variables were considered. A total of 12,158 participants had complete sleep data available; 7,363 (61%) were women. The population-weighted prevalence of SA (apnea-hypopnea index ≥ 15 events per hour) was 6.1% in female subjects and 13.5% in male subjects. Male-only (C statistic, 0.808) and female-only (C statistic, 0.836) prediction models had the same predictor variables (ie, age, BMI, self-reported snoring). The sex-interaction model (C statistic, 0.836) contained sex, age, age × sex, BMI, BMI × sex, and self-reported snoring. The final overall model (C statistic, 0.832) contained age, BMI, snoring, and sex. We developed two websites for our SA risk calculator: one in English (https://www.montefiore.org/sleepapneariskcalc.html) and another in Spanish (http://www.montefiore.org/sleepapneariskcalc-es.html). We created an internally validated, highly discriminating, well-calibrated, and parsimonious prediction model for SA. Contrary to the study hypothesis, the variables did not have different predictive magnitudes in male and female subjects. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  9. Long-Term Impact of Intrauterine Neuroinflammation and Treatment with Magnesium Sulphate and Betamethasone: Sex-Specific Differences in a Preterm Labor Murine Model

    Science.gov (United States)

    2017-12-20

    intrauterine neuroinflammation and treatment with magnesium sulphate and betamethasone: Sex -specific differences in a preterm labor murine model...widespread use of Mg504 in clinical practice, its effects on adult offspring are not well known nor have sex -specific differences in therapeutic...injury. Prenatal treatment with MgSOJbetamethasone confers long-term benefits beyond cerebral palsy prevention with sex -specific differences in

  10. Species- and sex-specific connectivity effects of habitat fragmentation in a suite of woodland birds.

    Science.gov (United States)

    Amos, Nevil; Harrisson, Katherine A; Radford, James Q; White, Matt; Newell, Graeme; Mac Nally, Ralph; Sunnucks, Paul; Pavlova, Alexandra

    2014-06-01

    Loss of functional connectivity following habitat loss and fragmentation could drive species declines. A comprehensive understanding of fragmentation effects on functional connectivity of an ecological assemblage requires investigation of multiple species with different mobilities, at different spatial scales, for each sex, and in different landscapes. Based on published data on mobility and ecological responses to fragmentation of 10 woodland-dependent birds, and using simulation studies, we predicted that (1) fragmentation would impede dispersal and gene flow of eight "decliners" (species that disappear from suitable patches when landscape-level tree cover falls below species-specific thresholds), but not of two "tolerant" species (whose occurrence in suitable habitat patches is independent of landscape tree cover); and that fragmentation effects would be stronger (2) in the least mobile species, (3) in the more philopatric sex, and (4) in the more fragmented region. We tested these predictions by evaluating spatially explicit isolation-by-landscape-resistance models of gene flow in fragmented landscapes across a 50 x 170 km study area in central Victoria, Australia, using individual and population genetic distances. To account for sex-biased dispersal and potential scale- and configuration-specific effects, we fitted models specific to sex and geographic zones. As predicted, four of the least mobile decliners showed evidence of reduced genetic connectivity. The responses were strongly sex specific, but in opposite directions in the two most sedentary species. Both tolerant species and (unexpectedly) four of the more mobile decliners showed no reduction in gene flow. This is unlikely to be due to time lags because more mobile species develop genetic signatures of fragmentation faster than do less mobile ones. Weaker genetic effects were observed in the geographic zone with more aggregated vegetation, consistent with gene flow being unimpeded by landscape

  11. Prenatal and postnatal stress and asthma in children: Temporal- and sex-specific associations.

    Science.gov (United States)

    Lee, Alison; Mathilda Chiu, Yueh-Hsiu; Rosa, Maria José; Jara, Calvin; Wright, Robert O; Coull, Brent A; Wright, Rosalind J

    2016-09-01

    Temporal- and sex-specific effects of perinatal stress have not been examined for childhood asthma. We examined associations between prenatal and/or postnatal stress and children's asthma (n = 765) and effect modification by sex in a prospective cohort study. Maternal negative life events were ascertained prenatally and postpartum. Negative life event scores were categorized as 0, 1 to 2, 3 to 4, or 5 or greater to assess exposure-response relationships. We examined effects of prenatal and postnatal stress on children's asthma by age 6 years, modeling each as independent predictors, mutually adjusting for prenatal and postnatal stress, and finally considering interactions between prenatal and postnatal stress. Effect modification by sex was examined in stratified analyses and by fitting interaction terms. When considering stress in each period independently, among boys, a dose-response relationship was evident for each level increase on the ordinal scale prenatally (odds ratio [OR], 1.38; 95% CI, 1.06-1.79; P value for trend = .03) and postnatally (OR, 1.53; 95% CI, 1.16-2.01; P value for trend = .001); among girls, only the postnatal trend was significant (OR, 1.60; 95% CI, 1.14-2.22; P value for trend = .005). Higher stress in both the prenatal and postnatal periods was associated with increased odds of receiving a diagnosis of asthma in girls (OR, 1.37; 95% CI, 0.98-1.91; Pinteraction = .07) but not boys (OR, 1.08; 95% CI, 0.82-1.42; Pinteraction = .61). Although boys were more vulnerable to stress during the prenatal period, girls were more affected by postnatal stress and cumulative stress across both periods in relation to asthma. Understanding sex and temporal differences in response to early-life stress might provide unique insight into the cause and natural history of asthma. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  12. Predicting psychiatric readmission: sex-specific models to predict 30-day readmission following acute psychiatric hospitalization.

    Science.gov (United States)

    Barker, Lucy Church; Gruneir, Andrea; Fung, Kinwah; Herrmann, Nathan; Kurdyak, Paul; Lin, Elizabeth; Rochon, Paula A; Seitz, Dallas; Taylor, Valerie H; Vigod, Simone N

    2018-02-01

    Psychiatric readmission is a common negative outcome. Predictors of readmission may differ by sex. This study aimed to derive and internally validate sex-specific models to predict 30-day psychiatric readmission. We used population-level health administrative data to identify predictors of 30-day psychiatric readmission among women (n = 33,353) and men (n = 32,436) discharged from all psychiatric units in Ontario, Canada (2008-2011). Predictor variables included sociodemographics, health service utilization, and clinical characteristics. Using derivation data sets, multivariable logistic regression models were fit to determine optimal predictive models for each sex separately. Results were presented as adjusted odds ratios (aORs) and 95% confidence intervals (CI). The multivariable models were then applied in the internal validation data sets. The 30-day readmission rates were 9.3% (women) and 9.1% (men). Many predictors were consistent between women and men. For women only, personality disorder (aOR 1.21, 95% CI 1.03-1.42) and positive symptom score (aOR 1.41, 95% CI 1.09-1.82 for score of 1 vs. 0; aOR 1.44, 95% CI 1.26-1.64 for ≥ 2 vs. 0) increased odds of readmission. For men only, self-care problems at admission (aOR 1.20, 95% CI 1.06-1.36) and discharge (aOR 1.44, 95% CI 1.26-1.64 for score of 1 vs. 0; aOR 1.79, 95% CI 1.17-2.74 for 2 vs. 0), and mild anxiety rating (score of 1 vs. 0: aOR 1.30, 95% CI 1.02-1.64, derivation model only) increased odds of readmission. Models had moderate discriminative ability in derivation and internal validation samples for both sexes (c-statistics 0.64-0.65). Certain key predictors of psychiatric readmission differ by sex. This knowledge may help to reduce psychiatric hospital readmission rates by focusing interventions.

  13. The women's heart health programme: a pilot trial of sex-specific cardiovascular management.

    Science.gov (United States)

    Low, Ting Ting; Chan, Siew Pang; Wai, Shin Hnin; Ang, Zhou; Kyu, Kyu; Lee, Kim Yee; Ching, Anne; Comer, Sarah; Tan, Naomi Qiu Pin; Thong, Elizabeth Grace Hui En; Nang, Tracy; Dutta, Mohan; Lam, Carolyn S P

    2018-04-16

    There is increasing knowledge of sex-specific differences in cardiovascular disease and recognition of sex disparities in management. In our study, we investigated whether a cardiovascular programme tailored to the specific needs of women could lead to improved outcomes. We randomised 100 female patients to receive cardiology follow-up with the conventional sex-neutral cardiac programme (control), or the sex-tailored Women's Heart Health Programme (intervention). The intervention group was managed by an all-women multidisciplinary team and received culture-centred health intervention workshops, designed through in-depth interviews with the participants. The primary outcome was cardiovascular risk factor improvement at 1 year. Secondary outcomes include cardiovascular event rates, quality of life scores, and self-reported improvement in knowledge, attitudes, intentions and practices. Generalised structural equation model analysis was used to determine if the intervention group had better outcomes at alpha level 0.1. The mean age was 67.3 ± 12.7 years, with an ethnic distribution of 70% Chinese, 18% Malays, and 12% Indians. The majority of these patients had no formal or primary level of education (63%), and were mostly unemployed (78%). Patients in intervention group had better control of diabetes mellitus (lower HbA1c of 0.63% [CI 0.21-1.04], p = 0.015) and lower body-mass-index (0.74 kg/m 2 [CI 0.02-1.46], p = 0.092) at 1 year, but there was no significant difference in blood pressure or lipid control. Overall, there was a trend towards better risk factor control, 31.6% of intervention group versus 26.5% of control group achieved improvement in at least 1 CV risk factor control to target range. There was no significant difference in incidence of cardiovascular events, quality of life, or domains in knowledge, attitudes, intention and practices. This pilot study is the first of its kind evaluating a new model of care for women with heart disease

  14. Mosquito control pesticides and sea surface temperatures have differential effects on the survival and oxidative stress response of coral larvae.

    Science.gov (United States)

    Ross, Cliff; Olsen, Kevin; Henry, Michael; Pierce, Richard

    2015-04-01

    The declining health of coral reefs is intensifying worldwide at an alarming rate due to the combined effects of land-based sources of pollution and climate change. Despite the persistent use of mosquito control pesticides in populated coastal areas, studies examining the survival and physiological impacts of early life-history stages of non-targeted marine organisms are limited. In order to better understand the combined effects of mosquito pesticides and rising sea surface temperatures, we exposed larvae from the coral Porites astreoides to selected concentrations of two major mosquito pesticide ingredients, naled and permethrin, and seawater elevated +3.5 °C. Following 18-20 h of exposure, larvae exposed to naled concentrations of 2.96 µg L(-1) or greater had significantly reduced survivorship compared to controls. These effects were not detected in the presence of permethrin or elevated temperature. Furthermore, larval settlement, post-settlement survival and zooxanthellae density were not impacted by any treatment. To evaluate the sub-lethal stress response of larvae, several oxidative stress endpoints were utilized. Biomarker responses to pesticide exposure were variable and contingent upon pesticide type as well as the specific biomarker being employed. In some cases, such as with protein carbonylation and catalase gene expression, the effects of naled exposure and temperature were interactive. In other cases pesticide exposure failed to induce any sub-lethal stress response. Overall, these results demonstrate that P. astreoides larvae have a moderate degree of resistance against short-term exposure to ecologically relevant concentrations of pesticides even in the presence of elevated temperature. In addition, this work highlights the importance of considering the complexity and differential responses encountered when examining the impacts of combined stressors that occur on varying spatial scales.

  15. Maturation of the human fetal startle response: Evidence for sex-specific maturation of the human fetus1

    Science.gov (United States)

    Buss, Claudia; Davis, Elysia Poggi; Class, Quetzal A.; Gierczak, Matt; Pattillo, Carol; Glynn, Laura M.; Sandman, Curt A.

    2009-01-01

    Despite the evidence for early fetal experience exerting programming influences on later neurological development and health risk, very few prospective studies of human fetal behavior have been reported. In a prospective longitudinal study, fetal nervous system maturation was serially assessed by monitoring fetal heart rate (FHR) responses to vibroacoustic stimulation (VAS) in 191 maternal/fetal dyads. Responses were not detected at 26 weeks gestational age (GA). Sex-specific, age-characteristic changes in the FHR response to VAS were observed by 31 weeks’ GA. Males showed larger responses and continued to exhibit maturational changes until 37 weeks’ GA, females however, presented with a mature FHR startle response by 31 weeks’ GA. The results indicate that there are different rates of maturation in the male and female fetus that may have implications for sex-specific programming influences. PMID:19726143

  16. Maturation of the human fetal startle response: evidence for sex-specific maturation of the human fetus.

    Science.gov (United States)

    Buss, Claudia; Davis, Elysia Poggi; Class, Quetzal A; Gierczak, Matt; Pattillo, Carol; Glynn, Laura M; Sandman, Curt A

    2009-10-01

    Despite the evidence for early fetal experience exerting programming influences on later neurological development and health risk, very few prospective studies of human fetal behavior have been reported. In a prospective longitudinal study, fetal nervous system maturation was serially assessed by monitoring fetal heart rate (FHR) responses to vibroacoustic stimulation (VAS) in 191 maternal/fetal dyads. Responses were not detected at 26 weeks gestational age (GA). Sex-specific, age-characteristic changes in the FHR response to VAS were observed by 31 weeks' GA. Males showed larger responses and continued to exhibit maturational changes until 37 weeks' GA, females however, presented with a mature FHR startle response by 31 weeks' GA. The results indicate that there are different rates of maturation in the male and female fetuses that may have implications for sex-specific programming influences.

  17. Sex-specific signaling in the blood-brain barrier is required for male courtship in Drosophila.

    Directory of Open Access Journals (Sweden)

    Valbona Hoxha

    Full Text Available Soluble circulating proteins play an important role in the regulation of mating behavior in Drosophila melanogaster. However, how these factors signal through the blood-brain barrier (bbb to interact with the sex-specific brain circuits that control courtship is unknown. Here we show that male identity of the blood-brain barrier is necessary and that male-specific factors in the bbb are physiologically required for normal male courtship behavior. Feminization of the bbb of adult males significantly reduces male courtship. We show that the bbb-specific G-protein coupled receptor moody and bbb-specific Go signaling in adult males are necessary for normal courtship. These data identify sex-specific factors and signaling processes in the bbb as important regulators of male mating behavior.

  18. Knee joint biomechanics and neuromuscular control during gait before and after total knee arthroplasty are sex-specific.

    Science.gov (United States)

    Astephen Wilson, Janie L; Dunbar, Michael J; Hubley-Kozey, Cheryl L

    2015-01-01

    The future of total knee arthroplasty (TKA) surgery will involve planning that incorporates more patient-specific characteristics. Despite known biological, morphological, and functional differences between men and women, there has been little investigation into knee joint biomechanical and neuromuscular differences between men and women with osteoarthritis, and none that have examined sex-specific biomechanical and neuromuscular responses to TKA surgery. The objective of this study was to examine sex-associated differences in knee kinematics, kinetics and neuromuscular patterns during gait before and after TKA. Fifty-two patients with end-stage knee OA (28 women, 24 men) underwent gait and neuromuscular analysis within the week prior to and one year after surgery. A number of sex-specific differences were identified which suggest a different manifestation of end-stage knee OA between the sexes. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Risk of sex-specific cancers in opposite-sex and same-sex twins in Denmark and Sweden

    DEFF Research Database (Denmark)

    Ahrenfeldt, Linda Juel; Skytthe, Axel; Möller, Sören

    2015-01-01

    -scale prospective twin study compared opposite-sex (OS) and same-sex (SS) twins to test the impact of intrauterine exposures on cancer risk. Based on the Danish and Swedish twin and cancer registries, we calculated incidence rate ratios for OS and SS twins while standardized incidence ratios (SIRs) with 95......% confidence intervals (CIs) were calculated for OS/SS twins compared with the general population. RESULTS: A total of 18,001 cancers were identified during 1943-2009. No significant differences were observed between OS and SS twins, neither for the sex-specific cancers nor for cancer at all sites. All...... to prenatal testosterone - does not increase the risk of sex-specific cancers in OS females. Furthermore, the study supports that twinning per se is not a risk factor of cancer. IMPACT: Findings are reassuring as they fail to provide evidence for the hypothesis that endocrine or other difference...

  20. Variation in extracellular matrix genes is associated with weight regain after weight loss in a sex-specific manner

    DEFF Research Database (Denmark)

    Roumans, Nadia J T; Vink, Roel G; Gielen, Marij

    2015-01-01

    The extracellular matrix (ECM) of adipocytes is important for body weight regulation. Here, we investigated whether genetic variation in ECM-related genes is associated with weight regain among participants of the European DiOGenes study. Overweight and obese subjects (n = 469, 310 females, 159 m.......40-5.63). Concluding, variants of ECM genes are associated with weight regain after weight loss in a sex-specific manner....

  1. Fungal Infection Induces Sex-Specific Transcriptional Changes and Alters Sexual Dimorphism in the Dioecious Plant Silene latifolia.

    Directory of Open Access Journals (Sweden)

    Niklaus Zemp

    2015-10-01

    Full Text Available Sexual dimorphism, including differences in morphology, behavior and physiology between females and males, is widespread in animals and plants and is shaped by gene expression differences between the sexes. Such expression differences may also underlie sex-specific responses of hosts to pathogen infections, most notably when pathogens induce partial sex reversal in infected hosts. The genetic changes associated with sex-specific responses to pathogen infections on the one hand, and sexual dimorphism on the other hand, remain poorly understood. The dioecious White Campion (Silene latifolia displays sexual dimorphism in floral traits and infection with the smut fungus Micobrotryum lychnidis-dioicae induces a partial sex reversal in females. We find strong sex-specific responses to pathogen infection and reduced sexual dimorphism in infected S. latifolia. This provides a direct link between pathogen-mediated changes in sex-biased gene expression and altered sexual dimorphism in the host. Expression changes following infection affected mainly genes with male-biased expression in healthy plants. In females, these genes were up-regulated, leading to a masculinization of the transcriptome. In contrast, infection in males was associated with down-regulation of these genes, leading to a demasculinization of the transcriptome. To a lesser extent, genes with female-biased expression in healthy plants were also affected in opposite directions in the two sexes. These genes were overall down-regulated in females and up-regulated in males, causing, respectively, a defeminization in infected females and a feminization of the transcriptome in infected males. Our results reveal strong sex-specific responses to pathogen infection in a dioecious plant and provide a link between pathogen-induced changes in sex-biased gene expression and sexual dimorphism.

  2. Fungal Infection Induces Sex-Specific Transcriptional Changes and Alters Sexual Dimorphism in the Dioecious Plant Silene latifolia.

    Science.gov (United States)

    Zemp, Niklaus; Tavares, Raquel; Widmer, Alex

    2015-10-01

    Sexual dimorphism, including differences in morphology, behavior and physiology between females and males, is widespread in animals and plants and is shaped by gene expression differences between the sexes. Such expression differences may also underlie sex-specific responses of hosts to pathogen infections, most notably when pathogens induce partial sex reversal in infected hosts. The genetic changes associated with sex-specific responses to pathogen infections on the one hand, and sexual dimorphism on the other hand, remain poorly understood. The dioecious White Campion (Silene latifolia) displays sexual dimorphism in floral traits and infection with the smut fungus Micobrotryum lychnidis-dioicae induces a partial sex reversal in females. We find strong sex-specific responses to pathogen infection and reduced sexual dimorphism in infected S. latifolia. This provides a direct link between pathogen-mediated changes in sex-biased gene expression and altered sexual dimorphism in the host. Expression changes following infection affected mainly genes with male-biased expression in healthy plants. In females, these genes were up-regulated, leading to a masculinization of the transcriptome. In contrast, infection in males was associated with down-regulation of these genes, leading to a demasculinization of the transcriptome. To a lesser extent, genes with female-biased expression in healthy plants were also affected in opposite directions in the two sexes. These genes were overall down-regulated in females and up-regulated in males, causing, respectively, a defeminization in infected females and a feminization of the transcriptome in infected males. Our results reveal strong sex-specific responses to pathogen infection in a dioecious plant and provide a link between pathogen-induced changes in sex-biased gene expression and sexual dimorphism.

  3. Sex-specific responses to winter flooding, spring waterlogging and post-flooding recovery in Populus deltoides

    OpenAIRE

    Ling-Feng Miao; Fan Yang; Chun-Yu Han; Yu-Jin Pu; Yang Ding; Li-Jia Zhang

    2017-01-01

    Winter flooding events are common in some rivers and streams due to dam constructions, and flooding and waterlogging inhibit the growth of trees in riparian zones. This study investigated sex-specific morphological, physiological and ultrastructural responses to various durations of winter flooding and spring waterlogging stresses, and post-flooding recovery characteristics in Populus deltoides. There were no significant differences in the morphological, ultrastructural and the majority of ph...

  4. Sex-Specific Effects of Childhood Poverty on Neurocircuitry of Processing of Emotional Cues: A Neuroimaging Study

    Directory of Open Access Journals (Sweden)

    Arash Javanbakht

    2016-12-01

    Full Text Available Background: There is accumulating evidence on the negative impacts of childhood poverty on physical and mental health. Previous work has suggested hyperactive neural response to social fear cues, as well as impairment in neural regulatory functions. However, despite differences found between males and females in stress-related and anxiety disorders, possible sex-specific effects of poverty on emotional processing have not been explored. Methods: We analyzed data from three previously reported experiments of childhood poverty effects on emotional processing and regulation, for sex-specific effects. Participants were 52 healthy Caucasian males and females, from a longitudinal cohort of poverty development study, who were recruited for examining the long-term effects of childhood poverty and stress. The three functional MRI studies included emotion regulation task, emotional face assessment task, and shifted attention emotion appraisal task. Brain activations that associated with childhood poverty previously were entered into a regression analysis with interaction of gender by childhood income-to-need ratio as the independent variable, and age and current income-to-need ratio as variables of no interest, separately for males and females. Results: Amygdala reactivity to implicitly processed fearful faces was positively correlated with childhood income-to-need in adult females but not males. On the other hand, activation in dorsolateral and ventrolateral prefrontal regions during emotion regulation by reappraisal was positively correlated with childhood income-to-need in males. Conclusion: Childhood poverty may exert sex-specific effects in adulthood as presented by hypersensitive emotional reactivity of the amygdala in females, and impaired emotion regulatory function of the prefrontal cortex in males. Results suggest further focus on sex-specific effects of childhood poverty.

  5. Sex-specific influences of mtDNA mitotype and diet on mitochondrial functions and physiological traits in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Wen C Aw

    Full Text Available Here we determine the sex-specific influence of mtDNA type (mitotype and diet on mitochondrial functions and physiology in two Drosophila melanogaster lines. In many species, males and females differ in aspects of their energy production. These sex-specific influences may be caused by differences in evolutionary history and physiological functions. We predicted the influence of mtDNA mutations should be stronger in males than females as a result of the organelle's maternal mode of inheritance in the majority of metazoans. In contrast, we predicted the influence of diet would be greater in females due to higher metabolic flexibility. We included four diets that differed in their protein: carbohydrate (P:C ratios as they are the two-major energy-yielding macronutrients in the fly diet. We assayed four mitochondrial function traits (Complex I oxidative phosphorylation, reactive oxygen species production, superoxide dismutase activity, and mtDNA copy number and four physiological traits (fecundity, longevity, lipid content, and starvation resistance. Traits were assayed at 11 d and 25 d of age. Consistent with predictions we observe that the mitotype influenced males more than females supporting the hypothesis of a sex-specific selective sieve in the mitochondrial genome caused by the maternal inheritance of mitochondria. Also, consistent with predictions, we found that the diet influenced females more than males.

  6. The Mitochondrial Lon Protease Is Required for Age-Specific and Sex-Specific Adaptation to Oxidative Stress.

    Science.gov (United States)

    Pomatto, Laura C D; Carney, Caroline; Shen, Brenda; Wong, Sarah; Halaszynski, Kelly; Salomon, Matthew P; Davies, Kelvin J A; Tower, John

    2017-01-09

    Multiple human diseases involving chronic oxidative stress show a significant sex bias, including neurodegenerative diseases, cancer, immune dysfunction, diabetes, and cardiovascular disease. However, a possible molecular mechanism for the sex bias in physiological adaptation to oxidative stress remains unclear. Here, we report that Drosophila melanogaster females but not males adapt to hydrogen peroxide stress, whereas males but not females adapt to paraquat (superoxide) stress. Stress adaptation in each sex requires the conserved mitochondrial Lon protease and is associated with sex-specific expression of Lon protein isoforms and proteolytic activity. Adaptation to oxidative stress is lost with age in both sexes. Transgenic expression of transformer gene during development transforms chromosomal males into pseudo-females and confers the female-specific pattern of Lon isoform expression, Lon proteolytic activity induction, and H 2 O 2 stress adaptation; these effects were also observed using adult-specific transformation. Conversely, knockdown of transformer in chromosomal females eliminates the female-specific Lon isoform expression, Lon proteolytic activity induction, and H 2 O 2 stress adaptation and produces the male-specific paraquat (superoxide) stress adaptation. Sex-specific expression of alternative Lon isoforms was also observed in mouse tissues. The results develop Drosophila melanogaster as a model for sex-specific stress adaptation regulated by the Lon protease, with potential implications for understanding sexual dimorphism in human disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Sex-Specific Effects of Chronic Fluoxetine Treatment on Neuroplasticity and Pharmacokinetics in Mice

    OpenAIRE

    Hodes, Georgia E.; Hill-Smith, Tiffany E.; Suckow, Raymond F.; Cooper, Thomas B.; Lucki, Irwin

    2010-01-01

    Neurogenesis is a mechanism through which antidepressants may produce therapeutic effects. There is a dearth of information regarding the effects of antidepressants on neurogenesis and neurotrophin mobilization in females. This study examined sex differences in the alteration of cell proliferation and survival in multiple regions of the brain. Additional experiments examined brain-derived neurotrophic factor (BDNF) levels and pharmacokinetics of fluoxetine to determine whether they mediate se...

  8. Identification of sex-specific urinary biomarkers for major depressive disorder by combined application of NMR- and GC-MS-based metabonomics.

    Science.gov (United States)

    Zheng, P; Chen, J-J; Zhou, C-J; Zeng, L; Li, K-W; Sun, L; Liu, M-L; Zhu, D; Liang, Z-H; Xie, P

    2016-11-15

    Women are more vulnerable to major depressive disorder (MDD) than men. However, molecular biomarkers of sex differences are limited. Here we combined gas chromatography-mass spectrometry (GC-MS)- and nuclear magnetic resonance (NMR)-based metabonomics to investigate sex differences of urinary metabolite markers in MDD, and further explore their potential of diagnosing MDD. Consequently, the metabolite signatures of women and men MDD subjects were significantly different from of that in their respective healthy controls (HCs). Twenty seven women and 36 men related differentially expressed metabolites were identified in MDD. Fourteen metabolites were changed in both women and men MDD subjects. Significantly, the women-specific (m-Hydroxyphenylacetate, malonate, glycolate, hypoxanthine, isobutyrate and azelaic acid) and men-specific (tyrosine, N-acetyl-d-glucosamine, N-methylnicotinamide, indoxyl sulfate, citrate and succinate) marker panels were further identified, which could differentiate men and women MDD patients from their respective HCs with higher accuracy than previously reported sex-nonspecific marker panels. Our findings demonstrate that men and women MDD patients have distinct metabonomic signatures and sex-specific biomarkers have promising values in diagnosing MDD.

  9. Promoting long-term survival of insulin-producing cell grafts that differentiate from adipose tissue-derived stem cells to cure type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    Shuzi Zhang

    Full Text Available BACKGROUND: Insulin-producing cell clusters (IPCCs have recently been generated in vitro from adipose tissue-derived stem cells (ASCs to circumvent islet shortage. However, it is unknown how long they can survive upon transplantation, whether they are eventually rejected by recipients, and how their long-term survival can be induced to permanently cure type 1 diabetes. IPCC graft survival is critical for their clinical application and this issue must be systematically addressed prior to their in-depth clinical trials. METHODOLOGY/PRINCIPAL FINDINGS: Here we found that IPCC grafts that differentiated from murine ASCs in vitro, unlike their freshly isolated islet counterparts, did not survive long-term in syngeneic mice, suggesting that ASC-derived IPCCs have intrinsic survival disadvantage over freshly isolated islets. Indeed, β cells retrieved from IPCC syngrafts underwent faster apoptosis than their islet counterparts. However, blocking both Fas and TNF receptor death pathways inhibited their apoptosis and restored their long-term survival in syngeneic recipients. Furthermore, blocking CD40-CD154 costimulation and Fas/TNF signaling induced long-term IPCC allograft survival in overwhelming majority of recipients. Importantly, Fas-deficient IPCC allografts exhibited certain immune privilege and enjoyed long-term survival in diabetic NOD mice in the presence of CD28/CD40 joint blockade while their islet counterparts failed to do so. CONCLUSIONS/SIGNIFICANCE: Long-term survival of ASC-derived IPCC syngeneic grafts requires blocking Fas and TNF death pathways, whereas blocking both death pathways and CD28/CD40 costimulation is needed for long-term IPCC allograft survival in diabetic NOD mice. Our studies have important clinical implications for treating type 1 diabetes via ASC-derived IPCC transplantation.

  10. Sex-specific differences in fetal germ cell apoptosis induced by ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Guerquin, M.J.; Duquenne, C.; Coffigny, H.; Rouiller-Fabre, V.; Lambrot, R.; Habert, R.; Livera, G. [CEA, DSV/DRR/SEGG/LDRG, Laboratory of Differentiation and Radiobiology of the Gonads, Unit of Gametogenesis and Genotoxicity, F-92265 Fontenay aux Roses (France); Guerquin, M.J.; Duquenne, C.; Coffigny, H.; Rouiller-Fabre, V.; Lambrot, R.; Habert, R.; Livera, G. [Univ. Paris 7-Denis Diderot, UFR of Biology, UMR-S 566, F-92265 Fontenay aux Roses (France); Guerquin, M.J.; Duquenne, C.; Coffigny, H.; Rouiller-Fabre, V.; Lambrot, R.; Habert, R.; Livera, G. [INSERM, U566, F-92265 Fontenay aux Roses (France); Bakalska, M. [Institute of Experimental Morphology and Anthropology, Bulgarian Academy of Sciences, Sofia (Bulgaria); Frydman, R. [Univ Paris-Sud, Clamart F-92140 (France); Frydman, R. [AP-HP, Service de Gynecologie-Obstetrique et Medecine de la Reproduction, Hopital Antoine Beclere, Clamart F-92141 (France); Frydman, R. [INSERM, U782, Clamart F-92140 (France)

    2009-07-01

    Background: We have previously shown that male human fetal germ cells are highly radiosensitive and that their death depends on p53 activation. Male germ cell apoptosis was initiated with doses as low as 0.1 Gy and was prevented by pifithrin {alpha}, a p53 inhibitor. In this study, we investigated the radiosensitivity of early female and male fetal proliferating germ cells. Methods and results: Both male and female fetal germ cells displayed a similar number of {gamma}H2AX foci in response to ionizing radiation (IR). In organ culture of human fetal ovaries, the germ cells underwent apoptosis only when exposed to high doses of IR (1.5 Gy and above). Accumulation of p53 was detected in irradiated male human fetal germ cells but not in female ones. Inhibition of p53 with pifithrin {alpha} did not affect oogonia apoptosis following irradiation. IR induced apoptosis similarly in mouse fetal ovaries in organ culture and in vivo during oogonial proliferation. Germ cell survival in testes from p53 knockout or p63 knockout mice exposed to IR was better than wild-type, whereas female germ cell survival was unaffected by p53 or p63 knockout. Conclusions: These findings show that pre-meiotic male and female fetal germ cells behave differently in response to a genotoxic stress-irradiation with oogonia being less sensitive and undergoing p53-independent apoptosis. (authors)

  11. Sex-specific differences in fetal germ cell apoptosis induced by ionizing radiation

    International Nuclear Information System (INIS)

    Guerquin, M.J.; Duquenne, C.; Coffigny, H.; Rouiller-Fabre, V.; Lambrot, R.; Habert, R.; Livera, G.; Guerquin, M.J.; Duquenne, C.; Coffigny, H.; Rouiller-Fabre, V.; Lambrot, R.; Habert, R.; Livera, G.; Guerquin, M.J.; Duquenne, C.; Coffigny, H.; Rouiller-Fabre, V.; Lambrot, R.; Habert, R.; Livera, G.; Bakalska, M.; Frydman, R.; Frydman, R.; Frydman, R.

    2009-01-01

    Background: We have previously shown that male human fetal germ cells are highly radiosensitive and that their death depends on p53 activation. Male germ cell apoptosis was initiated with doses as low as 0.1 Gy and was prevented by pifithrin α, a p53 inhibitor. In this study, we investigated the radiosensitivity of early female and male fetal proliferating germ cells. Methods and results: Both male and female fetal germ cells displayed a similar number of γH2AX foci in response to ionizing radiation (IR). In organ culture of human fetal ovaries, the germ cells underwent apoptosis only when exposed to high doses of IR (1.5 Gy and above). Accumulation of p53 was detected in irradiated male human fetal germ cells but not in female ones. Inhibition of p53 with pifithrin α did not affect oogonia apoptosis following irradiation. IR induced apoptosis similarly in mouse fetal ovaries in organ culture and in vivo during oogonial proliferation. Germ cell survival in testes from p53 knockout or p63 knockout mice exposed to IR was better than wild-type, whereas female germ cell survival was unaffected by p53 or p63 knockout. Conclusions: These findings show that pre-meiotic male and female fetal germ cells behave differently in response to a genotoxic stress-irradiation with oogonia being less sensitive and undergoing p53-independent apoptosis. (authors)

  12. Activation of transglutaminase 2 by nerve growth factor in differentiating neuroblastoma cells: A role in cell survival and neurite outgrowth.

    Science.gov (United States)

    Algarni, Alanood S; Hargreaves, Alan J; Dickenson, John M

    2018-02-05

    NGF (nerve growth factor) and tissue transglutaminase (TG2) play important roles in neurite outgrowth and modulation of neuronal cell survival. In this study, we investigated the regulation of TG2 transamidase activity by NGF in retinoic acid-induced differentiating mouse N2a and human SH-SY5Y neuroblastoma cells. TG2 transamidase activity was determined using an amine incorporation and a peptide cross linking assay. In situ TG2 activity was assessed by visualising the incorporation of biotin-X-cadaverine using confocal microscopy. The role of TG2 in NGF-induced cytoprotection and neurite outgrowth was investigated by monitoring hypoxia-induced cell death and appearance of axonal-like processes, respectively. The amine incorporation and protein crosslinking activity of TG2 increased in a time and concentration-dependent manner following stimulation with NGF in N2a and SH-SY5Y cells. NGF mediated increases in TG2 activity were abolished by the TG2 inhibitors Z-DON (Z-ZON-Val-Pro-Leu-OMe; Benzyloxycarbonyl-(6-Diazo-5-oxonorleucinyl)-l-valinyl-l-prolinyl-l-leucinmethylester) and R283 (1,3,dimethyl-2[2-oxo-propyl]thio)imidazole chloride) and by pharmacological inhibition of extracellular signal-regulated kinases 1 and 2 (ERK1/2), protein kinase B (PKB) and protein kinase C (PKC), and removal of extracellular Ca 2+ . Fluorescence microscopy demonstrated NGF induced in situ TG2 activity. TG2 inhibition blocked NGF-induced attenuation of hypoxia-induced cell death and neurite outgrowth in both cell lines. Together, these results demonstrate that NGF stimulates TG2 transamidase activity via a ERK1/2, PKB and PKC-dependent pathway in differentiating mouse N2a and human SH-SY5Y neuroblastoma cells. Furthermore, NGF-induced cytoprotection and neurite outgrowth are dependent upon TG2. These results suggest a novel and important role of TG2 in the cellular functions of NGF. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Temporal trends and gender differentials in causes of childhood deaths at Ballabgarh, India - Need for revisiting child survival strategies

    Directory of Open Access Journals (Sweden)

    Krishnan Anand

    2012-07-01

    Full Text Available Abstract Background Relating Information on causes of deaths to implementation of health interventions provides vital information for program planning and evaluation. This paper from Ballabgarh Health and Demographic Surveillance System (HDSS site in north India looks at temporal trends and gender differentials in the causes of death among under-five children. Methods Data on causes of death for 1972-74, 1982-84, 1992-94, 2002-04 were taken from existing HDSS publications and database. Physicians’ assigned causes of death were based on narratives by lay health worker till 1994 and later by verbal autopsy. Cause Specific Mortality Fractions (CSMF and Cause Specific Mortality Rates (CSMR per 1000 live births were calculated for neonatal ( Results The CSMF of prematurity and sepsis was 32% and 17.6% during neonatal period in 2002-04. The share of infections in all childhood deaths decreased from 55.2% in 1972-74 to 43.6% in 2002-04. All major causes of mortality (malnutrition, diarrhea and acute lower respiratory infection except injuries showed a steep decline among children and seem to have plateued in last decade. Most of disease specific public health interventions were launched in mid eighties. . Girls reported significantly higher mortality rates for prematurity (RR 1.52; 95% CI 1.01-2.29; diarrhea (2.29; 1.59 – 3.29, and malnutrition (3.37; 2.05 – 5.53. Conclusions The findings of the study point out to the need to move away from disease-specific to a comprehensive approach and to address gender inequity in child survival through socio-behavioural approaches.

  14. Sex-Specific Effects of Unpredictable Variable Prenatal Stress: Implications for Mammalian Developmental Programming During Spaceflight

    Science.gov (United States)

    Talyansky, Y.; Moyer, E. L.; Oijala, E.; Baer, L. A.; Ronca, A. E.

    2016-01-01

    During adaptation to the microgravity environment, adult mammals experience stress mediated by the Hypothalamic-Pituitary-Adrenal axis. In our previous studies of pregnant rats exposed to 2-g hypergravity via centrifugation, we reported decreased corticosterone and increased body mass and leptin in adult male, but not female, offspring. In this study, we utilized Unpredictable Variable Prenatal Stress to simulate the stressors of spaceflight by exposing dams to different stressors. Stress response modulation occurs via both positive and negative feedback in the hypothalamus, anterior pituitary gland, and adrenal cortex resulting in the differential release of corticosterone (CORT), a murine analog to human cortisol.

  15. Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

    Energy Technology Data Exchange (ETDEWEB)

    Lingappan, Krithika, E-mail: lingappa@bcm.edu [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I. [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Barrios, Roberto [Department of Pathology and Genomic Medicine, The Methodist Hospital Physician Organization, 6565 Fannin Street, Suite M227, Houston, TX 77030 (United States); Moorthy, Bhagavatula [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States)

    2013-10-15

    Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO{sub 2} > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F{sub 2} alpha (8-iso-PGF 2α) (LC–MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: • Male mice were more susceptible to hyperoxic lung injury than females. • Sex differences in inflammatory markers were observed. • CYP1A expression was higher in females after hyperoxia exposure.

  16. Sex-specific association between functional neuropeptide S receptor gene (NPSR1) variants and cortisol and central stress responses.

    Science.gov (United States)

    Streit, Fabian; Akdeniz, Ceren; Haddad, Leila; Kumsta, Robert; Entringer, Sonja; Frank, Josef; Yim, Ilona S; Zänkert, Sandra; Witt, Stephanie H; Kirsch, Peter; Rietschel, Marcella; Wüst, Stefan

    2017-02-01

    The brain neuropeptide S (NPS) system has recently generated substantial interest and may be of major relevance for central stress regulation. The NPS receptor (NPSR1) is highly expressed in the limbic system, exogenous NPS exerts pronounced anxiolytic and fear-attenuating effects in rodents and extensive close crosstalk between the NPS system and the hypothalamic-pituitary-adrenal (HPA) axis has been demonstrated. In humans, associations between NPSR1 variants and anxiety and panic disorder, as well as amygdala responsiveness to fear- relevant faces and prefrontal cortex activity in a fear conditioning paradigm have been reported. Moreover, a NPSR1 sequence variant was found to be associated with cortisol stress responses in males. Here, we performed a haplotype-based analysis covering three functional NPSR1 single nucleotide polymorphisms in the promoter (rs2530547), in exon 3 (rs324981) and exon 6 (rs727162) in 277 healthy subjects who were exposed to the Trier Social Stress Test (TSST). A significant sex-specific association with salivary cortisol responses to acute psychosocial stress was detected for the common TTC haplotype 2 (frequency of about 20%). In an additional study using an imaging genetics approach, 65 healthy subjects were exposed to a stress paradigm for scanner environments (“ScanSTRESS”). We found a significant and, again, sex-specific interaction between rs324981 (whose minor T-allele is harbored by haplotype 2) and the neural stress response in a cluster close to the parahippocampal gyrus (whole brain corrected). Moreover, as in the TSST sample, NPSR1 variation was associated with salivary cortisol responses (on a trend level) in a sex-specific way. In summary, our preliminary findings in two independent cohorts exposed to different stress paradigms suggest that the NPS system significantly influences acute stress responses and that sequence variation in NPSR1 may contribute to sex differences in stress regulation. Copyright © 2016

  17. Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

    International Nuclear Information System (INIS)

    Lingappan, Krithika; Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I.; Barrios, Roberto; Moorthy, Bhagavatula

    2013-01-01

    Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO 2 > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F 2 alpha (8-iso-PGF 2α) (LC–MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: • Male mice were more susceptible to hyperoxic lung injury than females. • Sex differences in inflammatory markers were observed. • CYP1A expression was higher in females after hyperoxia exposure

  18. Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex-specific regulation of social behavior.

    Science.gov (United States)

    Dumais, Kelly M; Veenema, Alexa H

    2016-01-01

    The neuropeptides vasopressin (VP) and oxytocin (OT) and their receptors in the brain are involved in the regulation of various social behaviors and have emerged as drug targets for the treatment of social dysfunction in several sex-biased neuropsychiatric disorders. Sex differences in the VP and OT systems may therefore be implicated in sex-specific regulation of healthy as well as impaired social behaviors. We begin this review by highlighting the sex differences, or lack of sex differences, in VP and OT synthesis in the brain. We then discuss the evidence showing the presence or absence of sex differences in VP and OT receptors in rodents and humans, as well as showing new data of sexually dimorphic V1a receptor binding in the rat brain. Importantly, we find that there is lack of comprehensive analysis of sex differences in these systems in common laboratory species, and we find that, when sex differences are present, they are highly brain region- and species-specific. Interestingly, VP system parameters (VP and V1aR) are typically higher in males, while sex differences in the OT system are not always in the same direction, often showing higher OT expression in females, but higher OT receptor expression in males. Furthermore, VP and OT receptor systems show distinct and largely non-overlapping expression in the rodent brain, which may cause these receptors to have either complementary or opposing functional roles in the sex-specific regulation of social behavior. Though still in need of further research, we close by discussing how manipulations of the VP and OT systems have given important insights into the involvement of these neuropeptide systems in the sex-specific regulation of social behavior in rodents and humans. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Density-dependent sex ratio and sex-specific preference for host traits in parasitic bat flies.

    Science.gov (United States)

    Szentiványi, Tamara; Vincze, Orsolya; Estók, Péter

    2017-08-29

    Deviation of sex ratios from unity in wild animal populations has recently been demonstrated to be far more prevalent than previously thought. Ectoparasites are prominent examples of this bias, given that their sex ratios vary from strongly female- to strongly male-biased both among hosts and at the metapopulation level. To date our knowledge is very limited on how and why these biased sex ratios develop. It was suggested that sex ratio and sex-specific aggregation of ectoparasites might be shaped by the ecology, behaviour and physiology of both hosts and their parasites. Here we investigate a highly specialised, hematophagous bat fly species with strong potential to move between hosts, arguably limited inbreeding effects, off-host developmental stages and extended parental care. We collected a total of 796 Nycteribia kolenatii bat flies from 147 individual bats using fumigation and subsequently determined their sex. We report a balanced sex ratio at the metapopulation level and a highly variable sex ratio among infrapopulations ranging from 100% male to 100% female. We show that infrapopulation sex ratio is not random and is highly correlated with infrapopulation size. Sex ratio is highly male biased in small and highly female biased in large infrapopulations. We show that this pattern is most probably the result of sex-specific preference in bat flies for host traits, most likely combined with a higher mobility of males. We demonstrate that female bat flies exert a strong preference for high host body condition and female hosts, while the distribution of males is more even. Our results suggest that locally biased sex ratios can develop due to sex-specific habitat preference of parasites. Moreover, it is apparent that the sex of both hosts and parasites need to be accounted for when a better understanding of host-parasite systems is targeted.

  20. Chronic stress induces sex-specific alterations in methylation and expression of corticotropin-releasing factor gene in the rat.

    Directory of Open Access Journals (Sweden)

    Linda Sterrenburg

    Full Text Available BACKGROUND: Although the higher prevalence of depression in women than in men is well known, the neuronal basis of this sex difference is largely elusive. METHODS: Male and female rats were exposed to chronic variable mild stress (CVMS after which immediate early gene products, corticotropin-releasing factor (CRF mRNA and peptide, various epigenetic-associated enzymes and DNA methylation of the Crf gene were determined in the hypothalamic paraventricular nucleus (PVN, oval (BSTov and fusiform (BSTfu parts of the bed nucleus of the stria terminalis, and central amygdala (CeA. RESULTS: CVMS induced site-specific changes in Crf gene methylation in all brain centers studied in female rats and in the male BST and CeA, whereas the histone acetyltransferase, CREB-binding protein was increased in the female BST and the histone-deacetylase-5 decreased in the male CeA. These changes were accompanied by an increased amount of c-Fos in the PVN, BSTfu and CeA in males, and of FosB in the PVN of both sexes and in the male BSTov and BSTfu. In the PVN, CVMS increased CRF mRNA in males and CRF peptide decreased in females. CONCLUSIONS: The data confirm our hypothesis that chronic stress affects gene expression and CRF transcriptional, translational and secretory activities in the PVN, BSTov, BSTfu and CeA, in a brain center-specific and sex-specific manner. Brain region-specific and sex-specific changes in epigenetic activity and neuronal activation may play, too, an important role in the sex specificity of the stress response and the susceptibility to depression.

  1. Vasopressin and oxytocin receptor systems in the brain: sex differences and sex-specific regulation of social behavior

    Science.gov (United States)

    Dumais, Kelly M.; Veenema, Alexa H.

    2015-01-01

    The neuropeptides vasopressin (VP) and oxytocin (OT) and their receptors in the brain are involved in the regulation of various social behaviors and have emerged as drug targets for the treatment of social dysfunction in several sex-biased neuropsychiatric disorders. Sex differences in the VP and OT systems may therefore be implicated in sex-specific regulation of healthy as well as impaired social behaviors. We begin this review by highlighting the sex differences, or lack of sex differences, in VP and OT synthesis in the brain. We then discuss the evidence showing the presence or absence of sex differences in VP and OT receptors in rodents and humans, as well as showing new data of sexually dimorphic V1a receptor binding in the rat brain. Importantly, we find that there is lack of comprehensive analysis of sex differences in these systems in common laboratory species, and we find that, when sex differences are present, they are highly brain region- and species- specific. Interestingly, VP system parameters (VP and V1aR) are typically higher in males, while sex differences in the OT system are not always in the same direction, often showing higher OT expression in females, but higher OT receptor expression in males. Furthermore, VP and OT receptor systems show distinct and largely non-overlapping expression in the rodent brain, which may cause these receptors to have either complementary or opposing functional roles in the sex-specific regulation of social behavior. Though still in need of further research, we close by discussing how manipulations of the VP and OT systems have given important insights into the involvement of these neuropeptide systems in the sex-specific regulation of social behavior in rodents and humans. PMID:25951955

  2. Sex-specific heritability of spontaneous lipid levels in an extended pedigree of Indian-origin rhesus macaques (Macaca mulatta.

    Directory of Open Access Journals (Sweden)

    Amanda Vinson

    Full Text Available The rhesus macaque is an important model for human atherosclerosis but genetic determinants of relevant phenotypes have not yet been investigated in this species. Because lipid levels are well-established and heritable risk factors for human atherosclerosis, our goal was to assess the heritability of lipoprotein cholesterol and triglyceride levels in a single, extended pedigree of 1,289 Indian-origin rhesus macaques. Additionally, because increasing evidence supports sex differences in the genetic architecture of lipid levels and lipid metabolism in humans and macaques, we also explored sex-specific heritability for all lipid measures investigated in this study. Using standard methods, we measured lipoprotein cholesterol and triglyceride levels from fasted plasma in a sample of 193 pedigreed rhesus macaques selected for membership in large, paternal half-sib cohorts, and maintained on a low-fat, low cholesterol chow diet. Employing a variance components approach, we found moderate heritability for total cholesterol (h²=0.257, P=0.032, LDL cholesterol (h²=0.252, P=0.030, and triglyceride levels (h²=0.197, P=0.034 in the full sample. However, stratification by sex (N=68 males, N=125 females revealed substantial sex-specific heritability for total cholesterol (0.644, P=0.004, females only, HDL cholesterol (0.843, P=0.0008, females only, VLDL cholesterol (0.482, P=0.018, males only, and triglyceride levels (0.705, P=0.001, males only that was obscured or absent when sexes were combined in the full sample. We conclude that genes contribute to spontaneous variation in circulating lipid levels in the Indian-origin rhesus macaque in a sex-specific manner, and that the rhesus macaque is likely to be a valuable model for sex-specific genetic effects on lipid risk factors for human atherosclerosis. These findings are a first-ever report of heritability for cholesterol levels in this species, and support the need for expanded analysis of these traits in

  3. Genetic detection of sex-specific dispersal in historical and contemporary populations of anadromous brown trout Salmo trutta

    DEFF Research Database (Denmark)

    Bekkevold, Dorte; Hansen, Michael Møller; Mensberg, Karen-Lise Dons

    2004-01-01

    The study of sex-biased dispersal has attracted considerable attention in birds and mammals, but less in other taxa, including fishes. We analysed sex-specific dispersal in historical (1910s and 1950s) and contemporary (1990s) samples of anadromous brown trout Salmo trutta. We tested the hypothesis...... that dispersal is unbiased using information from microsatellite DNA and applying an assignment index for 11 temporally and spatially separated samples. Our results are most consistent with brown trout dispersal being male biased, and provide no evidence of female bias. We found no evidence that dispersal...

  4. Antenatal glucocorticoid treatment alters Na+ uptake in renal proximal tubule cells from adult offspring in a sex-specific manner

    OpenAIRE

    Su, Yixin; Bi, Jianli; Pulgar, Victor M.; Figueroa, Jorge; Chappell, Mark; Rose, James C.

    2015-01-01

    We have shown a sex-specific effect of fetal programming on Na+ excretion in adult sheep. The site of this effect in the kidney is unknown. Therefore, we tested the hypothesis that renal proximal tubule cells (RPTCs) from adult male sheep exposed to betamethasone (Beta) before birth have greater Na+ uptake than do RPTCs from vehicle-exposed male sheep and that RPTCs from female sheep similarly exposed are not influenced by antenatal Beta. In isolated RPTCs from 1- to 1.5-yr-old male and femal...

  5. Sex-specific patterns and deregulation of endocrine pathways in the gene expression profiles of Bangladeshi adults exposed to arsenic contaminated drinking water

    Energy Technology Data Exchange (ETDEWEB)

    Muñoz, Alexandra; Chervona, Yana [New York University School of Medicine, Nelson Institute of Environmental Medicine, Tuxedo, NY (United States); Hall, Megan [Department of Epidemiology, Mailman School of Public Health, Columbia University, New York (United States); Kluz, Thomas [New York University School of Medicine, Nelson Institute of Environmental Medicine, Tuxedo, NY (United States); Gamble, Mary V., E-mail: mvg7@columbia.edu [Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York (United States); Costa, Max, E-mail: Max.Costa@nyumc.org [New York University School of Medicine, Nelson Institute of Environmental Medicine, Tuxedo, NY (United States)

    2015-05-01

    Arsenic contamination of drinking water occurs globally and is associated with numerous diseases including skin, lung and bladder cancers, and cardiovascular disease. Recent research indicates that arsenic may be an endocrine disruptor. This study was conducted to evaluate the nature of gene expression changes among males and females exposed to arsenic contaminated water in Bangladesh at high and low doses. Twenty-nine (55% male) Bangladeshi adults with water arsenic exposure ranging from 50 to 1000 μg/L were selected from the Folic Acid Creatinine Trial. RNA was extracted from peripheral blood mononuclear cells for gene expression profiling using Affymetrix 1.0 ST arrays. Differentially expressed genes were assessed between high and low exposure groups for males and females separately and findings were validated using quantitative real-time PCR. There were 534 and 645 differentially expressed genes (p < 0.05) in the peripheral blood mononuclear cells of males and females, respectively, when high and low water arsenic exposure groups were compared. Only 43 genes overlapped between the two sexes, with 29 changing in opposite directions. Despite the difference in gene sets both males and females exhibited common biological changes including deregulation of 17β-hydroxysteroid dehydrogenase enzymes, deregulation of genes downstream of Sp1 (specificity protein 1) transcription factor, and prediction of estrogen receptor alpha as a key hub in cardiovascular networks. Arsenic-exposed adults exhibit sex-specific gene expression profiles that implicate involvement of the endocrine system. Due to arsenic's possible role as an endocrine disruptor, exposure thresholds for arsenic may require different parameters for males and females. - Highlights: • Males and females exhibit unique gene expression changes in response to arsenic. • Only 23 genes are common among the differentially expressed genes for the sexes. • Male and female gene lists exhibit common

  6. Sex-specific patterns and deregulation of endocrine pathways in the gene expression profiles of Bangladeshi adults exposed to arsenic contaminated drinking water

    International Nuclear Information System (INIS)

    Muñoz, Alexandra; Chervona, Yana; Hall, Megan; Kluz, Thomas; Gamble, Mary V.; Costa, Max

    2015-01-01

    Arsenic contamination of drinking water occurs globally and is associated with numerous diseases including skin, lung and bladder cancers, and cardiovascular disease. Recent research indicates that arsenic may be an endocrine disruptor. This study was conducted to evaluate the nature of gene expression changes among males and females exposed to arsenic contaminated water in Bangladesh at high and low doses. Twenty-nine (55% male) Bangladeshi adults with water arsenic exposure ranging from 50 to 1000 μg/L were selected from the Folic Acid Creatinine Trial. RNA was extracted from peripheral blood mononuclear cells for gene expression profiling using Affymetrix 1.0 ST arrays. Differentially expressed genes were assessed between high and low exposure groups for males and females separately and findings were validated using quantitative real-time PCR. There were 534 and 645 differentially expressed genes (p < 0.05) in the peripheral blood mononuclear cells of males and females, respectively, when high and low water arsenic exposure groups were compared. Only 43 genes overlapped between the two sexes, with 29 changing in opposite directions. Despite the difference in gene sets both males and females exhibited common biological changes including deregulation of 17β-hydroxysteroid dehydrogenase enzymes, deregulation of genes downstream of Sp1 (specificity protein 1) transcription factor, and prediction of estrogen receptor alpha as a key hub in cardiovascular networks. Arsenic-exposed adults exhibit sex-specific gene expression profiles that implicate involvement of the endocrine system. Due to arsenic's possible role as an endocrine disruptor, exposure thresholds for arsenic may require different parameters for males and females. - Highlights: • Males and females exhibit unique gene expression changes in response to arsenic. • Only 23 genes are common among the differentially expressed genes for the sexes. • Male and female gene lists exhibit common

  7. Sex-Specific Associations between Telomere Dynamics and Oxidative Status in Adult and Nestling Pied Flycatchers.

    Science.gov (United States)

    López-Arrabé, Jimena; Monaghan, Pat; Cantarero, Alejandro; Boner, Winnie; Pérez-Rodríguez, Lorenzo; Moreno, Juan

    Oxidative stress can contribute to an acceleration of telomere erosion, leading to cellular senescence and aging. Increased investment in reproduction is known to accelerate senescence, generally resulting in reduced future reproductive potential and survival. To better understand the role played by oxidative status and telomere dynamics in the conflict between maintenance and reproduction, it is important to determine how these factors are related in parents and their offspring. We investigated the relationship between oxidative status and telomere measurements in pied flycatchers (Ficedula hypoleuca). Total antioxidant status (TAS) in plasma, total levels of glutathione in red blood cells (RBCs), and oxidative damage in plasma lipids (malondialdehyde [MDA]) were assessed in both parents and nestlings. Telomeres were measured in RBCs in adults. Our results showed sex differences in oxidative variables in adults that are likely to be mediated by sex steroids, with testosterone and estrogens increasing and reducing, respectively, the production of reactive oxygen and nitrogen species. We found a negative association between telomere length (TL) and MDA in adults in the previous season. Moreover, TL was positively associated with TAS in females, while telomere shortening (ΔTL) correlated positively with MDA in males in the current year. These associations could be reflecting differences between sexes in reproductive physiology. We found a positive correlation between parental ΔTL and nestling MDA, an example of how parental physiological aging could affect offspring quality in terms of oxidative stress that highlights the constraints imposed by higher rates of ΔTL during reproduction and rearing.

  8. Determination of the most appropriate method for extrapolating overall survival data from a placebo-controlled clinical trial of lenvatinib for progressive, radioiodine-refractory differentiated thyroid cancer

    Directory of Open Access Journals (Sweden)

    Tremblay G

    2016-06-01

    Full Text Available Gabriel Tremblay,1 Christopher Livings,2 Lydia Crowe,2 Venediktos Kapetanakis,2 Andrew Briggs3 1Global Health Economics and Health Technology Assessment, Eisai Inc., Woodcliff Lake, NJ, USA; 2Health Economics, Decision Resources Group, Bicester, Oxfordshire, 3Health Economics and Health Technology Assessment, Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK Background: Cost-effectiveness models for the treatment of long-term conditions often require information on survival beyond the period of available data. Objectives: This paper aims to identify a robust and reliable method for the extrapolation of overall survival (OS in patients with radioiodine-refractory differentiated thyroid cancer receiving lenvatinib or placebo. Methods: Data from 392 patients (lenvatinib: 261, placebo: 131 from the SELECT trial are used over a 34-month period of follow-up. A previously published criterion-based approach is employed to ascertain credible estimates of OS beyond the trial data. Parametric models with and without a treatment covariate and piecewise models are used to extrapolate OS, and a holistic approach, where a series of statistical and visual tests are considered collectively, is taken in determining the most appropriate extrapolation model. Results: A piecewise model, in which the Kaplan–Meier survivor function is used over the trial period and an extrapolated tail is based on the Exponential distribution, is identified as the optimal model. Conclusion: In the absence of long-term survival estimates from clinical trials, survival estimates often need to be extrapolated from the available data. The use of a systematic method based on a priori determined selection criteria provides a transparent approach and reduces the risk of bias. The extrapolated OS estimates will be used to investigate the potential long-term benefits of lenvatinib in the treatment of radioiodine-refractory differentiated thyroid cancer patients and

  9. Survival, differentiation, and neuroprotective mechanisms of human stem cells complexed with neurotrophin-3-releasing pharmacologically active microcarriers in an ex vivo model of Parkinson's disease.

    Science.gov (United States)

    Daviaud, Nicolas; Garbayo, Elisa; Sindji, Laurence; Martínez-Serrano, Alberto; Schiller, Paul C; Montero-Menei, Claudia N

    2015-06-01

    Stem cell-based regenerative therapies hold great potential for the treatment of degenerative disorders such as Parkinson's disease (PD). We recently reported the repair and functional recovery after treatment with human marrow-isolated adult multilineage inducible (MIAMI) cells adhered to neurotrophin-3 (NT3) releasing pharmacologically active microcarriers (PAMs) in hemiparkinsonian rats. In order to comprehend this effect, the goal of the present work was to elucidate the survival, differentiation, and neuroprotective mechanisms of MIAMI cells and human neural stem cells (NSCs), both adhering to NT3-releasing PAMs in an ex vivo organotypic model of nigrostriatal degeneration made from brain sagittal slices. It was shown that PAMs led to a marked increase in MIAMI cell survival and neuronal differentiation when releasing NT3. A significant neuroprotective effect of MIAMI cells adhering to PAMs was also demonstrated. NSCs barely had a neuroprotective effect and differentiated mostly into dopaminergic neuronal cells when adhering to PAM-NT3. Moreover, those cells were able to release dopamine in a sufficient amount to induce a return to baseline levels. Reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay analyses identified vascular endothelial growth factor (VEGF) and stanniocalcin-1 as potential mediators of the neuroprotective effect of MIAMI cells and NSCs, respectively. It was also shown that VEGF locally stimulated tissue vascularization, which might improve graft survival, without excluding a direct neuroprotective effect of VEGF on dopaminergic neurons. These results indicate a prospective interest of human NSC/PAM and MIAMI cell/PAM complexes in tissue engineering for PD. Stem cell-based regenerative therapies hold great potential for the treatment of degenerative disorders such as Parkinson's disease (PD). The present work elucidates and compares the survival, differentiation, and neuroprotective mechanisms

  10. Determination of the most appropriate method for extrapolating overall survival data from a placebo-controlled clinical trial of lenvatinib for progressive, radioiodine-refractory differentiated thyroid cancer.

    Science.gov (United States)

    Tremblay, Gabriel; Livings, Christopher; Crowe, Lydia; Kapetanakis, Venediktos; Briggs, Andrew

    2016-01-01

    Cost-effectiveness models for the treatment of long-term conditions often require information on survival beyond the period of available data. This paper aims to identify a robust and reliable method for the extrapolation of overall survival (OS) in patients with radioiodine-refractory differentiated thyroid cancer receiving lenvatinib or placebo. Data from 392 patients (lenvatinib: 261, placebo: 131) from the SELECT trial are used over a 34-month period of follow-up. A previously published criterion-based approach is employed to ascertain credible estimates of OS beyond the trial data. Parametric models with and without a treatment covariate and piecewise models are used to extrapolate OS, and a holistic approach, where a series of statistical and visual tests are considered collectively, is taken in determining the most appropriate extrapolation model. A piecewise model, in which the Kaplan-Meier survivor function is used over the trial period and an extrapolated tail is based on the Exponential distribution, is identified as the optimal model. In the absence of long-term survival estimates from clinical trials, survival estimates often need to be extrapolated from the available data. The use of a systematic method based on a priori determined selection criteria provides a transparent approach and reduces the risk of bias. The extrapolated OS estimates will be used to investigate the potential long-term benefits of lenvatinib in the treatment of radioiodine-refractory differentiated thyroid cancer patients and populate future cost-effectiveness analyses.

  11. Caste-Specific and Sex-Specific Expression of Chemoreceptor Genes in a Termite.

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    Yuki Mitaka

    Full Text Available The sophisticated colony organization of eusocial insects is primarily maintained through the utilization of pheromones. The regulation of these complex social interactions requires intricate chemoreception systems. The recent publication of the genome of Zootermopsis nevadensis opened a new avenue to study molecular basis of termite caste systems. Although there has been a growing interest in the termite chemoreception system that regulates their sophisticated caste system, the relationship between division of labor and expression of chemoreceptor genes remains to be explored. Using high-throughput mRNA sequencing (RNA-seq, we found several chemoreceptors that are differentially expressed among castes and between sexes in a subterranean termite Reticulitermes speratus. In total, 53 chemoreception-related genes were annotated, including 22 odorant receptors, 7 gustatory receptors, 12 ionotropic receptors, 9 odorant-binding proteins, and 3 chemosensory proteins. Most of the chemoreception-related genes had caste-related and sex-related expression patterns; in particular, some chemoreception genes showed king-biased or queen-biased expression patterns. Moreover, more than half of the genes showed significant age-dependent differences in their expression in female and/or male reproductives. These results reveal a strong relationship between the evolution of the division of labor and the regulation of chemoreceptor gene expression, thereby demonstrating the chemical communication and underlining chemoreception mechanism in social insects.

  12. Sex-specific effects of prenatal and postnatal nutritional conditions on the oxidative status of great tit nestlings.

    Science.gov (United States)

    Giordano, M; Costantini, D; Tschirren, B

    2015-01-01

    The early life period is characterized by fast growth and development, which can lead to high reactive oxygen species (ROS) production. Young animals thus have to balance their investment in growth versus ROS defence, and this balance is likely mediated by resource availability. Consequently resources transferred prenatally by the mother and nutritional conditions experienced shortly after birth may crucially determine the oxidative status of young animals. Here, we experimentally investigated the relative importance of pre- and early postnatal nutritional conditions on the oxidative status of great tit nestlings (Parus major). We show that resources transferred by the mother through the egg and nutritional conditions encountered after hatching affect the oxidative status of nestling in a sex-specific way. Daughters of non-supplemented mothers and daughters which did not receive extra food during the early postnatal period had higher oxidative damage than sons, while no differences between sons and daughters were found when extra food was provided pre- or postnatally. No effect of the food supplementations on growth, fledging mass or tarsus length was observed, indicating that female nestlings maintained their investment in growth at the expense of ROS defence mechanisms when resources were limited. The lower priority of the antioxidant defence system for female nestlings was also evidenced by lower levels of specific antioxidant components. These results highlight the important role of early parental effects in shaping oxidative stress in the offspring, and show that the sensitivity to these parental effects is sex-specific.

  13. The political economy of urban homicide: assessing the relative impact of gender inequality on sex-specific victimization.

    Science.gov (United States)

    DeWees, Mari A; Parker, Karen F

    2003-02-01

    This research examines the ways in which the changing political economy of urban areas has contributed differently to the homicide victimization rates of females and males across US cities. Recent research, while relatively limited, has presented disparate results regarding the effect of gender inequality on urban sex-specific victimization. Our work further explores this relationship by taking into account relative gender disparities in income, education, labor market opportunities, and politics in an examination of sex-specific homicide victimization in 1990. Key to this current investigation is the evaluation of feminist and lifestyle arguments that suggest that structural gender inequality has a unique effect on female victimization. Overall, our findings reveal gender inequality to be a significant predictor of both male and female urban homicide. While these findings suggest mixed support for theoretical arguments regarding gender inequality, further analyses reveal significant differences in specific types of gender inequality on victimization patterns across genders. These additional results highlight the need for greater attention toward both methodological and theoretical issues when examining the interconnections between gender, political economy, and violence in research.

  14. An Estrogen-Responsive Module in the Ventromedial Hypothalamus Selectively Drives Sex-Specific Activity in Females

    Directory of Open Access Journals (Sweden)

    Stephanie M. Correa

    2015-01-01

    Full Text Available Estrogen-receptor alpha (ERα neurons in the ventrolateral region of the ventromedial hypothalamus (VMHVL control an array of sex-specific responses to maximize reproductive success. In females, these VMHVL neurons are believed to coordinate metabolism and reproduction. However, it remains unknown whether specific neuronal populations control distinct components of this physiological repertoire. Here, we identify a subset of ERα VMHVL neurons that promotes hormone-dependent female locomotion. Activating Nkx2-1-expressing VMHVL neurons via pharmacogenetics elicits a female-specific burst of spontaneous movement, which requires ERα and Tac1 signaling. Disrupting the development of Nkx2-1+ VMHVL neurons results in female-specific obesity, inactivity, and loss of VMHVL neurons coexpressing ERα and Tac1. Unexpectedly, two responses controlled by ERα+ neurons, fertility and brown adipose tissue thermogenesis, are unaffected. We conclude that a dedicated subset of VMHVL neurons marked by ERα, NKX2-1, and Tac1 regulates estrogen-dependent fluctuations in physical activity and constitutes one of several neuroendocrine modules that drive sex-specific responses.

  15. Sex-specific responses to winter flooding, spring waterlogging and post-flooding recovery in Populus deltoides.

    Science.gov (United States)

    Miao, Ling-Feng; Yang, Fan; Han, Chun-Yu; Pu, Yu-Jin; Ding, Yang; Zhang, Li-Jia

    2017-05-31

    Winter flooding events are common in some rivers and streams due to dam constructions, and flooding and waterlogging inhibit the growth of trees in riparian zones. This study investigated sex-specific morphological, physiological and ultrastructural responses to various durations of winter flooding and spring waterlogging stresses, and post-flooding recovery characteristics in Populus deltoides. There were no significant differences in the morphological, ultrastructural and the majority of physiological traits in trees subjected to medium and severe winter flooding stresses, suggesting that males and females of P. deltoides were winter flooding tolerant, and insensitive to winter flooding duration. Males were more tolerant to winter flooding stress in terms of photosynthesis and chlorophyll fluorescence than females. Females displayed greater oxidative damage due to flooding stress than males. Males developed more efficient antioxidant enzymatic systems to control reactive oxygen species. Both sexes had similarly strong post-flooding recovery capabilities in terms of plant growth, and physiological and ultrastructural parameters. However, Males had better recovery capabilities in terms of pigment content. These results increase the understanding of poplars's adaptation to winter flooding stress. They also elucidate sex-specific differences in response to flooding stress during the dormant season, and during post-flooding recovery periods.

  16. Transgenic over-expression of YY1 induces pathologic cardiac hypertrophy in a sex-specific manner

    Science.gov (United States)

    Stauffer, Brian L.; Dockstader, Karen; Russell, Gloria; Hijmans, Jamie; Walker, Lisa; Cecil, Mackenzie; Demos-Davies, Kimberly; Medway, Allen; McKinsey, Timothy A.; Sucharov, Carmen C.

    2015-01-01

    YY1 can activate or repress transcription of various genes. In cardiac myocytes in culture YY1 has been shown to regulate expression of several genes involved in myocyte pathology. YY1 can also acutely protect the heart against detrimental changes in gene expression. In this study we show that cardiac over-expression of YY1 induces pathologic cardiac hypertrophy in male mice, measured by changes in gene expression and lower ejection fraction/fractional shortening. In contrast, female animals are protected against pathologic gene expression changes and cardiac dysfunction. Furthermore, we show that YY1 regulates, in a sex-specific manner, the expression of mammalian enable (Mena), a factor that regulates cytoskeletal actin dynamics and whose expression is increased in several models of cardiac pathology, and that Mena expression in humans with heart failure is sex-dependent. Finally, we show that sex differences in YY1 expression are also observed in human heart failure. In summary, this is the first work to show that YY1 has a sex-specific effect in the regulation of cardiac pathology. PMID:25935483

  17. Age and sex specific variation in hematological and serum biochemical parameters of Beluga (Huso huso Linnaeus, 1758

    Directory of Open Access Journals (Sweden)

    Reza Akrami

    2013-05-01

    Full Text Available In the present study, the age- and sex-specific changes of various haematological and blood serum biochemical blood parameters of Beluga (Huso huso were investigated. Blood samples were collected from 4-, 6-, 7-, and 8-year-old beluga (n = 7 for each sex and age. The specimens were fed at a rate of 0.5-3% body weight per day. AST and LDH levels in 7- and 8-year-old fish of both sexes were significantly higher (P<0.05 than those in 4- and 6-year-old individuals. The mean ALT were significantly different (P<0.05 in both sexes of 4-, 6-, and 7-year-old sturgeon. However, the 6-, 7-, and 8-year-old female sturgeon had higher ALP levels (P<0.05. Additionally, mean RBC, PCV, and Hb values were significantly higher (P<0.05 in 7- and 8-year-old females and males than the others. Two-tailed Pearson’s correlation between the biochemical and haematological parameters obtained for beluga sturgeon indicated significant positive correlations between AST and ALP, AST and LDH, ALP and LDH, RBC and Hb, RBC and PCV, Hb and PCV, MCH and MCHC, and MCV and MCH. However, significant negative correlations were found between RBC and MCV and MCH. These results suggest that the blood parameters of beluga are influenced by age- and sex-specific factors.

  18. Sex-Specific Patterns of Aberrant Brain Function in First-Episode Treatment-Naive Patients with Schizophrenia.

    Science.gov (United States)

    Lei, Wei; Li, Mingli; Deng, Wei; Zhou, Yi; Ma, Xiaohong; Wang, Qiang; Guo, Wanjun; Li, Yinfei; Jiang, Lijun; Han, Yuanyuan; Huang, Chaohua; Hu, Xun; Li, Tao

    2015-07-16

    Male and female patients with schizophrenia show significant differences in a number of important clinical features, yet the neural substrates of these differences are still poorly understood. Here we explored the sex differences in the brain functional aberrations in 124 treatment-naïve patients with first-episode schizophrenia (61 males), compared with 102 age-matched healthy controls (50 males). Maps of degree centrality (DC) and amplitude of low-frequency fluctuations (ALFF) were constructed using resting-state functional magnetic resonance imaging data and compared between groups. We found that: (1) Selective DC reduction was observed in the right putamen (Put_R) in male patients and the left middle frontal gyrus (MFG) in female patients; (2) Functional connectivity analysis (using Put_R and MFG as seeds) found that male and female patients have disturbed functional integration in two separate networks, i.e., the sensorimotor network and the default mode network; (3) Significant ALFF alterations were also observed in these two networks in both genders; (4) Sex specific brain functional alterations were associated with various symptoms in patients. These results suggested that sex-specific patterns of functional aberration existed in schizophrenia, and these patterns were associated with the clinical features both in male and female patients.

  19. Sex-specific incidence of EGFR mutation and its association with age and obesity in lung adenocarcinomas: a retrospective analysis.

    Science.gov (United States)

    Kim, Hye-Ryoun; Kim, Seo Yun; Kim, Cheol Hyeon; Yang, Sung Hyun; Lee, Jae Cheol; Choi, Chang-Min; Na, Im Il

    2017-11-01

    Age and obesity are well-known risk factors for various cancers, but the potential roles of age and obesity in lung cancer, especially in those with activating EGFR mutations, have not been thoroughly evaluated. The aim of this retrospective study is to evaluate the associations between the sex-specific incidence of EGFR mutations and age and obesity. We conducted a retrospective study based on the data from 1378 lung adenocarcinoma cases. The degree of obesity was categorized by body mass index (BMI). The associations between EGFR mutational status and clinical factors, including stage, smoking history, age group (≤45 years, 46-55, 56-65 and >65), and BMI group (obesity (adjusted OR for BMI group = 1.23, p-trend = 0.04). In contrast, in women, the incidence of EGFR mutation was positively associated with age (adjusted OR for age group = 1.19, p-trend = 0.02). However, the incidence of EGFR mutation was not statistically associated with obesity (adjusted OR for BMI group = 1.03, p-trend = 0.76). Our data suggests that age and obesity may contribute to the sex-specific incidence of EGFR mutation in lung adenocarcinoma in different manners.

  20. Sex-Specific Patterns of Aberrant Brain Function in First-Episode Treatment-Naive Patients with Schizophrenia

    Directory of Open Access Journals (Sweden)

    Wei Lei

    2015-07-01

    Full Text Available Male and female patients with schizophrenia show significant differences in a number of important clinical features, yet the neural substrates of these differences are still poorly understood. Here we explored the sex differences in the brain functional aberrations in 124 treatment-naïve patients with first-episode schizophrenia (61 males, compared with 102 age-matched healthy controls (50 males. Maps of degree centrality (DC and amplitude of low-frequency fluctuations (ALFF were constructed using resting-state functional magnetic resonance imaging data and compared between groups. We found that: (1 Selective DC reduction was observed in the right putamen (Put_R in male patients and the left middle frontal gyrus (MFG in female patients; (2 Functional connectivity analysis (using Put_R and MFG as seeds found that male and female patients have disturbed functional integration in two separate networks, i.e., the sensorimotor network and the default mode network; (3 Significant ALFF alterations were also observed in these two networks in both genders; (4 Sex specific brain functional alterations were associated with various symptoms in patients. These results suggested that sex-specific patterns of functional aberration existed in schizophrenia, and these patterns were associated with the clinical features both in male and female patients.

  1. IGFBP-4 regulates adult skeletal growth in a sex-specific manner.

    Science.gov (United States)

    Maridas, David E; DeMambro, Victoria E; Le, Phuong T; Nagano, Kenichi; Baron, Roland; Mohan, Subburaman; Rosen, Clifford J

    2017-04-01

    Insulin-like growth factor-1 (IGF-1) and its binding proteins are critical mediators of skeletal growth. Insulin-like growth factor-binding protein 4 (IGFBP-4) is highly expressed in osteoblasts and inhibits IGF-1 actions in vitro Yet, in vivo studies suggest that it could potentiate IGF-1 and IGF-2 actions. In this study, we hypothesized that IGFBP-4 might potentiate the actions of IGF-1 on the skeleton. To test this, we comprehensively studied 8- and 16-week-old Igfbp4 -/- mice. Both male and female adult Igfbp4 -/- mice had marked growth retardation with reductions in body weight, body and femur lengths, fat proportion and lean mass at 8 and 16 weeks. Marked reductions in aBMD and aBMC were observed in 16-week-old Igfbp4 -/- females, but not in males. Femoral trabecular BV/TV and thickness, cortical fraction and thickness in 16-week-old Igfbp4 -/- females were significantly reduced. However, surprisingly, males had significantly more trabeculae with higher connectivity density than controls. Concordantly, histomorphometry revealed higher bone resorption and lower bone formation in Igfbp4 -/- females. In contrast, Igfbp4 -/- males had lower mineralized surface/bone surface. Femoral expression of Sost and circulating levels of sclerostin were reduced but only in Igfbp4 -/- males. Bone marrow stromal cultures from mutants showed increased osteogenesis, whereas osteoclastogenesis was markedly increased in cells from Igfbp4 -/- females but decreased in males. In sum, our results indicate that loss of Igfbp4 affects mesenchymal stromal cell differentiation, regulates osteoclastogenesis and influences both skeletal development and adult bone maintenance. Thus, IGFBP-4 modulates the skeleton in a gender-specific manner, acting as both a cell autonomous and cell non-autonomous factor. © 2017 The authors.

  2. Sex-specific functional adaptation of the femoral diaphysis to body composition.

    Science.gov (United States)

    Lacoste Jeanson, Alizé; Santos, Frédéric; Dupej, Ján; Velemínská, Jana; Brůžek, Jaroslav

    2018-03-24

    The human femoral diaphysis is often used to reconstruct loading histories (mobility, activity, body mass). The proximal femur is known to be differentially affected by changes in total fat-mass (FM), fat-free mass (FFM), and body fat percentage (BF%), but the adaptation of the entire diaphysis to body composition has not been thoroughly characterized to date. Understanding how the femoral diaphysis adapts to body components would benefit biomechanical interpretations of the femoral variation and nutrition-related studies. Combining various methods from clinical nutrition, biological anthropology, and geometric morphometrics, we evaluated the correlation of measures taken on the entire femoral diaphysis with estimated FM, FFM, and BF% from 61 CT scans (17 females, 44 males). The sample was predominantly composed of people with obesity. Cortical area of the cross-sections and local cortical thickness showed high correlation with BF% in particular, in females only. The curvature significantly decreased with FM and BF% in both sexes. The lowest correlations are found with FFM. The observed sexual dimorphism is consistent with differing aging processes; cortical bone decreases in females through endosteal resorption while it remains almost constant in males who compensate for endosteal resorption by periosteal apposition on the diaphyseal surface. The functional adaptation to compressive forces indicates a systemic endosteal apposition of bone material with increased BF% and FM in females only. FM and BF% are linked to a straighter femur in both sexes, suggesting an optimization of the resistance to compressive loads by distributing them more linearly along the entire diaphysis. © 2018 Wiley Periodicals, Inc.

  3. DIFFERENTIAL IMPACT OF HLA-A, HLA-B AND HLA-DR COMPATIBILITY ON THE RENAL ALLOGRAFT SURVIVAL

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    V. Y. Abramov

    2012-01-01

    Full Text Available We studied the long-term results of 532 deceased donor kidney transplantations to investigate the impact of HLA match on the survival of renal allograft. All transplants were performed in our center in 1996–2009 and moni- tored prospectively for 1–14 years. We found, the survival of 58 kidneys grafted with 0–2 mismatch for HLA- ABDR to be significantly better (Plogrank = 0,016 than the survival of the kidneys grafted with 3–6 HLA-ABDR mismatch. The full compatibility for HLA-A (n = 75 did not influence the long-term survival (Plogrank = 0,48. The absence of HLA-DR mismatch had a beneficial effect for survival of 68 kidneys (Plogrank = 0,07. Eighteen cases with the full HLA-B compatibility between graft and recipient demonstrated excellent long-term survival (Plogrank = 0,007. HLA-B compatibility influenced significantly (P = 0,042 the survival of transplanted kidney in the Cox regression model adjusted for donor and recipient age, panel-reactive antibody level, re-transplant, and immunosuppression protocol. The data obtained support the conclusion, that HLA compatibility should be one of the criteria of deceased donor kidney allocation. 

  4. BDNF Increases Survival and Neuronal Differentiation of Human Neural Precursor Cells Cotransplanted with a Nanofiber Gel to the Auditory Nerve in a Rat Model of Neuronal Damage

    Directory of Open Access Journals (Sweden)

    Yu Jiao

    2014-01-01

    Full Text Available Objectives. To study possible nerve regeneration of a damaged auditory nerve by the use of stem cell transplantation. Methods. We transplanted HNPCs to the rat AN trunk by the internal auditory meatus (IAM. Furthermore, we studied if addition of BDNF affects survival and phenotypic differentiation of the grafted HNPCs. A bioactive nanofiber gel (PA gel, in selected groups mixed with BDNF, was applied close to the implanted cells. Before transplantation, all rats had been deafened by a round window niche application of β-bungarotoxin. This neurotoxin causes a selective toxic destruction of the AN while keeping the hair cells intact. Results. Overall, HNPCs survived well for up to six weeks in all groups. However, transplants receiving the BDNF-containing PA gel demonstrated significantly higher numbers of HNPCs and neuronal differentiation. At six weeks, a majority of the HNPCs had migrated into the brain stem and differentiated. Differentiated human cells as well as neurites were observed in the vicinity of the cochlear nucleus. Conclusion. Our results indicate that human neural precursor cells (HNPC integration with host tissue benefits from additional brain derived neurotrophic factor (BDNF treatment and that these cells appear to be good candidates for further regenerative studies on the auditory nerve (AN.

  5. Datasets in Gene Expression Omnibus used in the study ORD-020969: Genomic effects of androstenedione and sex-specific liver cancer susceptibility in mice

    Data.gov (United States)

    U.S. Environmental Protection Agency — Datasets in Gene Expression Omnibus used in the study ORD-020969: Genomic effects of androstenedione and sex-specific liver cancer susceptibility in mice. This...

  6. Sex-Specific Effects of Gender Identification on Pain Study Recruitment.

    Science.gov (United States)

    Mattos Feijó, Larissa; Tarman, Guliz Zeynep; Fontaine, Charlotte; Harrison, Richard; Johnstone, Tom; Salomons, Tim

    2018-02-01

    Epidemiological, clinical, and laboratory studies show sex differences in pain responses, with women more sensitive to nociceptive stimulation and more vulnerable to long-term pain conditions than men. Because of evidence that men are culturally reinforced for the ability to endure (or under-report) pain, some of these findings might be explained by sociocultural beliefs about gender-appropriate behavior. One potential manifestation of these effects might be differential participation in pain studies, with men adhering to stereotypical masculine roles viewing participation as a way to demonstrate their masculinity. To test this possibility, we assessed gender identification in 137 healthy participants. At the end of the assessment, they were asked if they would like to participate in other research studies. Interested participants were then asked to participate in a study involving administration of pain-evoking stimulation. We compared individuals who agreed to participate in the pain study with those who declined. We observed a significant Sex × Participation interaction in masculine gender identification, such that men (but not women) who agreed to participate identified significantly more with masculine gender. Among masculine gender traits examined, we found that high levels of aggression and competitiveness were the strongest predictors of pain study participation. Our results suggest that men in pain studies might have higher levels of masculine gender identification than the wider male population. Taken together with previous findings of lower levels of pain sensitivity (or reporting) in masculine-identifying male participants, these results suggest an explanation for some of the sex-related differences observed in pain responses. To examine whether sex and gender affect willingness to participate in pain studies, we assessed gender identification in men and women, then attempted to recruit them to participate in a pain study. Men who agree to participate

  7. Clinical features and prognostic factors for survival in patients with poorly differentiated thyroid carcinoma and comparison to the patients with the aggressive variants of papillary thyroid carcinoma

    International Nuclear Information System (INIS)

    Jung, Tae-Sik; Kim, Tae-Yong; Kim, Kyung-Won

    2007-01-01

    We performed this study to compare the clinicopathologic features and outcomes between the patients with poorly differentiated thyroid carcinoma (PDTC) and the patients with the aggressive variants of papillary thyroid carcinoma (PTC). To evaluate the prognostic factors for survival of the patients with PDTC, we selected 49 patients with PDTC and 23 patients with the aggressive variants of PTC from three hospitals during the recent 15 years. The five-year survival rate and clinicopathologic features of the patients with PDTC were not different from those of the patients with the aggressive variants of PTC. Univariate analysis revealed the significant poor prognostic factors for survival of the patients with PDTC and the aggressive variants of PTC as follows: an age more than 45 years, a tumor size larger than 4 cm, the presence of tumor invasion to extrathyroidal tissue or the trachea, the presence of cervical lymph node invasion, the presence of distant metastasis, the absence of high-dose radioactive iodine (RAI) therapy, and tumor, nodes and metastasis (TNM) stage II, III and IV. Distant metastasis and high-dose RAI therapy were independent significant predictors for survival of the patients with PDTC and the aggressive variants of PTC on multivariate analysis. However, distant metastasis was the only independent significant predictors for survival of the patients with PDTC excluding patients with the aggressive variants of PTC. (author)

  8. Naturally occurring genetic variability in expression of Gsta4 is associated with differential survival of axotomized rat motoneurons

    DEFF Research Database (Denmark)

    Mikael, Ström; Al Nimer, Faiez; Lindblom, Rickard

    2012-01-01

    A large number of molecular pathways have been implicated in the degeneration of axotomized motoneurons. We previously have demonstrated substantial differences in the survival rate of axotomized motoneurons across different rat strains. Identification of genetic differences underlying such natur...

  9. Who perpetrates violence against children? A systematic analysis of age-specific and sex-specific data.

    Science.gov (United States)

    Devries, Karen; Knight, Louise; Petzold, Max; Merrill, Katherine G; Maxwell, Lauren; Williams, Abigail; Cappa, Claudia; Chan, Ko Ling; Garcia-Moreno, Claudia; Hollis, NaTasha; Kress, Howard; Peterman, Amber; Walsh, Sophie D; Kishor, Sunita; Guedes, Alessandra; Bott, Sarah; Butron Riveros, Betzabe C; Watts, Charlotte; Abrahams, Naeemah

    2018-01-01

    The epidemiology of violence against children is likely to differ substantially by sex and age of the victim and the perpetrator. Thus far, investment in effective prevention strategies has been hindered by lack of clarity in the burden of childhood violence across these dimensions. We produced the first age-specific and sex-specific prevalence estimates by perpetrator type for physical, sexual and emotional violence against children globally. We used random effects meta-regression to estimate prevalence. Estimates were adjusted for relevant quality covariates, variation in definitions of violence and weighted by region-specific, age-specific and sex-specific population data to ensure estimates reflect country population structures. Secondary data from 600 population or school-based representative datasets and 43 publications obtained via systematic literature review, representing 13 830 estimates from 171 countries. Estimates for recent violence against children aged 0-19 were included. The most common perpetrators of physical and emotional violence for both boys and girls across a range of ages are household members, with prevalence often surpassing 50%, followed by student peers. Children reported experiencing more emotional than physical violence from both household members and students. The most common perpetrators of sexual violence against girls aged 15-19 years are intimate partners; however, few data on other perpetrators of sexual violence against children are systematically collected internationally. Few age-specific and sex-specific data are available on violence perpetration by schoolteachers; however, existing data indicate high prevalence of physical violence from teachers towards students. Data from other authority figures, strangers, siblings and other adults are limited, as are data on neglect of children. Without further investment in data generation on violence exposure from multiple perpetrators for boys and girls of all ages, progress

  10. Sex-specific effects of docosahexaenoic acid (DHA) on the microbiome and behavior of socially-isolated mice.

    Science.gov (United States)

    Davis, Daniel J; Hecht, Patrick M; Jasarevic, Eldin; Beversdorf, David Q; Will, Matthew J; Fritsche, Kevin; Gillespie, Catherine H

    2017-01-01

    Dietary supplementation with the long-chain omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) has been shown to have a beneficial effect on reducing the symptoms associated with several neuropsychiatric conditions including anxiety and depression. However, the mechanisms underlying this effect remain largely unknown. Increasing evidence suggests that the vast repertoire of commensal bacteria within the gut plays a critical role in regulating various biological processes in the brain and may contribute to neuropsychiatric disease risk. The present study determined the contribution of DHA on anxiety and depressive-like behaviors through modulation of the gut microbiota in a paradigm of social isolation. Adult male and female mice were subjected to social isolation for 28days and then placed either on a control diet or a diet supplemented with 0.1% or 1.0% DHA. Fecal pellets were collected both 24h and 7days following the introduction of the new diets. Behavioral testing revealed that male mice fed a DHA diet, regardless of dose, exhibited reduced anxiety and depressive-like behaviors compared to control fed mice while no differences were observed in female mice. As the microbiota-brain-axis has been recently implicated in behavior, composition of microbial communities were analyzed to examine if these sex-specific effects of DHA may be associated with changes in the gut microbiota (GM). Clear sex differences were observed with males and females showing distinct microbial compositions prior to DHA supplementation. The introduction of DHA into the diet also induced sex-specific interactions on the GM with the fatty acid producing a significant effect on the microbial profiles in males but not in females. Interestingly, levels of Allobaculum and Ruminococcus were found to significantly correlate with the behavioral changes observed in the male mice. Predictive metagenome analysis using PICRUSt was performed on the fecal samples collected from males and

  11. Who perpetrates violence against children? A systematic analysis of age-specific and sex-specific data

    Science.gov (United States)

    Devries, Karen; Knight, Louise; Petzold, Max; Merrill, Katherine G; Maxwell, Lauren; Williams, Abigail; Cappa, Claudia; Chan, Ko Ling; Garcia-Moreno, Claudia; Hollis, NaTasha; Kress, Howard; Peterman, Amber; Walsh, Sophie D; Kishor, Sunita; Guedes, Alessandra; Bott, Sarah; Butron Riveros, Betzabe C; Watts, Charlotte; Abrahams, Naeemah

    2018-01-01

    Objective The epidemiology of violence against children is likely to differ substantially by sex and age of the victim and the perpetrator. Thus far, investment in effective prevention strategies has been hindered by lack of clarity in the burden of childhood violence across these dimensions. We produced the first age-specific and sex-specific prevalence estimates by perpetrator type for physical, sexual and emotional violence against children globally. Design We used random effects meta-regression to estimate prevalence. Estimates were adjusted for relevant quality covariates, variation in definitions of violence and weighted by region-specific, age-specific and sex-specific population data to ensure estimates reflect country population structures. Data sources Secondary data from 600 population or school-based representative datasets and 43 publications obtained via systematic literature review, representing 13 830 estimates from 171 countries. Eligibility criteria for selecting studies Estimates for recent violence against children aged 0–19 were included. Results The most common perpetrators of physical and emotional violence for both boys and girls across a range of ages are household members, with prevalence often surpassing 50%, followed by student peers. Children reported experiencing more emotional than physical violence from both household members and students. The most common perpetrators of sexual violence against girls aged 15–19 years are intimate partners; however, few data on other perpetrators of sexual violence against children are systematically collected internationally. Few age-specific and sex-specific data are available on violence perpetration by schoolteachers; however, existing data indicate high prevalence of physical violence from teachers towards students. Data from other authority figures, strangers, siblings and other adults are limited, as are data on neglect of children. Conclusions Without further investment in data

  12. Electro-acupuncture promotes survival, differentiation of the bone marrow mesenchymal stem cells as well as functional recovery in the spinal cord-transected rats

    Science.gov (United States)

    Ding, Ying; Yan, Qing; Ruan, Jing-Wen; Zhang, Yan-Qing; Li, Wen-Jie; Zhang, Yu-Jiao; Li, Yan; Dong, Hongxin; Zeng, Yuan-Shan

    2009-01-01

    Background Bone marrow mesenchymal stem cells (MSCs) are one of the potential tools for treatment of the spinal cord injury; however, the survival and differentiation of MSCs in an injured spinal cord still need to be improved. In the present study, we investigated whether Governor Vessel electro-acupuncture (EA) could efficiently promote bone marrow mesenchymal stem cells (MSCs) survival and differentiation, axonal regeneration and finally, functional recovery in the transected spinal cord. Results The spinal cords of adult Sprague-Dawley (SD) rats were completely transected at T10, five experimental groups were performed: 1. sham operated control (Sham-control); 2. operated control (Op-control); 3. electro-acupuncture treatment (EA); 4. MSCs transplantation (MSCs); and 5. MSCs transplantation combined with electro-acupuncture (MSCs+EA). After 2-8 weeks of MSCs transplantation plus EA treatment, we found that the neurotrophin-3 (NT-3), cAMP level, the differentiation of MSCs, the 5-HT positive and CGRP positive nerve fibers in the lesion site and nearby tissue of injured spinal cord were significantly increased in the MSCs+EA group as compared to the group of the MSCs transplantation or the EA treated alone. Furthermore, behavioral test and spinal cord evoked potentials detection demonstrated a significantly functional recovery in the MSCs +EA group. Conclusion These results suggest that EA treatment may promote grafted MSCs survival and differentiation; MSCs transplantation combined with EA treatment could promote axonal regeneration and partial locomotor functional recovery in the transected spinal cord in rats and indicate a promising avenue of treatment of spinal cord injury. PMID:19374777

  13. Adolescents show sex-specific preferences on media when pornography is a major source of sexual knowledge

    DEFF Research Database (Denmark)

    Rasmussen, Anna Lund; Svarrer, Rebekka; Lauszus, Finn Friis

    2017-01-01

    photographs;thus, these magazines constituted a major source of adolescent girls. Girls knew the gestational age of legal abortion in Denmark and had their knowledge from non-explicit magazines while this was not the case for boys (p=0.004). Pupils who stated their knowledge on sex from these magazines knew...... the first sign of pregnancy (menostasia), the correct facts of legal abortion, and STI.Conclusions: Pornography in different media is used in the vast majority of adolescents and its use is sex-specific. Knowledge on STI, pregnancy, legal abortion was variably associated with the type of media....... with focus on pornography and what media was used. Pornography was divided according to five media subcategories. Knowledge on sexually transmitted infection (STI), pregnancy and abortion and their associations with pornography were explored.Results: Pornography was reported as the second largest source...

  14. Evaluation of sex specificity on oxidative stress induced in lungs of mice irradiated by 12C6+ ions

    International Nuclear Information System (INIS)

    Liu Yang; Zhang Hong; Zhang Luwei

    2008-01-01

    The aim of this work is to identify if there is sex specificity on 12 C 6+ ion-induced oxidative damage in mouse lung at different time points. Kun-Ming mice were divided into two groups, each composed of six males and six females: control group and irradiation group with a single acute dose of 4 Gy. Animals were sacrificed at 2, 4 and 12 h respectively, there lungs were removed immediately, and the oxidative stress-related biomarkers were measured by Diagnostic Reagent Kits. The results showed that the relative activities of superoxide dismutase (4 h), catalase (2 h) and Se-dependent glutathione peroxidase (12 h) have significant changes (P 12 C 6+ ion is pronounced in the lungs of males. We thought that these sex-responded differences may be attributed to the influence of sex hormones. (authors)

  15. Low-carbohydrate, high-fat diets have sex-specific effects on bone health in rats

    DEFF Research Database (Denmark)

    Zengin, Ayse; Kropp, Benedikt; Chevalier, Yan

    2016-01-01

    the effects in female rats remain unknown. Therefore, we investigated whether sex-specific effects of LC-HF diets on bone health exist. METHODS: Twelve-week-old male and female Wistar rats were isoenergetically pair-fed either a control diet (CD), "Atkins-style" protein-matched diet (LC-HF-1), or ketogenic......PURPOSE: Studies in humans suggest that consumption of low-carbohydrate, high-fat diets (LC-HF) could be detrimental for growth and bone health. In young male rats, LC-HF diets negatively affect bone health by impairing the growth hormone/insulin-like growth factor axis (GH/IGF axis), while...... low-protein diet (LC-HF-2) for 4 weeks. In females, microcomputed tomography and histomorphometry analyses were performed on the distal femur. Sex hormones were analysed with liquid chromatography-tandem mass spectrometry, and endocrine parameters including GH and IGF-I were measured by immunoassay...

  16. Sex-specific associations between birth weight and adult primary liver cancer in a large cohort of Danish children

    DEFF Research Database (Denmark)

    Zimmermann, Esther; Berentzen, Tina L.; Gamborg, Michael

    2016-01-01

    Whether the prenatal period is critical for the development of adult primary liver cancer (PLC) is sparsely investigated. Recently, attention has been drawn to potential sex-differences in the early origins of adult disease. We investigated the association between birth weight and adult PLC...... separately in men and women, using a large cohort of 217,227 children (51% boys), born from 1936 to 1980, from the Copenhagen School Health Records Register, and followed them until 2010 in national registers. Hazard ratios (95% confidence intervals) of PLC (30 years or older) were estimated by Cox...... regression models stratified by birth cohort. During 5.1 million person-years of follow-up, 185 men and 65 women developed PLC. Sex modified the association between birth weight and adult PLC (p-value for interaction=0.0005). Compared with a sex-specific reference group of birth weights between 3.25-3.75 kg...

  17. Identification and Validation of a New Male Sex-Specific ISSR Marker in Pointed Gourd (Trichosanthes dioica Roxb.

    Directory of Open Access Journals (Sweden)

    Sinchan Adhikari

    2014-01-01

    Full Text Available The aim of the present study was to develop a genetic sex marker for the pointed gourd (Trichosanthes dioica Roxb. to allow gender determination at any stage in the life cycle. Screening of genomic DNA with intersimple sequence repeat (ISSR primers was used to discover sex-specific touch-down polymerase chain reaction (Td-PCR amplification products. Using pooled DNA from male and female genotypes and 42 ISSR primers, a putative male specific marker (~550 bp was identified. DNA marker specific to male is an indication of existence of nonepigenetic factors involved in gender development in pointed gourd. The ISSR technique has proved to be a reliable technique in gender determination of pointed gourd genotypes at the seedling phenophase. The sex marker developed here could also be used as a starting material towards sequence characterization of sex linked genes for better understanding the developmental as well as evolutionary pathways in sexual dimorphism.

  18. No evidence for sex-specific effects of the maternal social environment on offspring development in Japanese quail (Coturnix japonica).

    Science.gov (United States)

    Langen, Esther M A; von Engelhardt, Nikolaus; Goerlich-Jansson, Vivian C

    2018-07-01

    The social environment of reproducing females can cause physiological changes, with consequences for reproductive investment and offspring development. These prenatal maternal effects are often found to be sex-specific and may have evolved as adaptations, maximizing fitness of male and female offspring for their future environment. Female hormone levels during reproduction are considered a potential mechanism regulating sex allocation in vertebrates: high maternal androgens have repeatedly been linked to increased investment in sons, whereas high glucocorticoid levels are usually related to increased investment in daughters. However, results are not consistent across studies and therefore still inconclusive. In Japanese quail (Coturnix japonica), we previously found that pair-housed females had higher plasma androgen levels and tended to have higher plasma corticosterone levels than group-housed females. In the current study we investigate whether these differences in maternal social environment and physiology affect offspring sex allocation and physiology. Counter to our expectations, we find no effects of the maternal social environment on offspring sex ratio, sex-specific mortality, growth, circulating androgen or corticosterone levels. Also, maternal corticosterone or androgen levels do not correlate with offspring sex ratio or mortality. The social environment during reproduction therefore does not necessarily modify sex allocation and offspring physiology, even if it causes differences in maternal physiology. We propose that maternal effects of the social environment strongly depend upon the type of social stimuli and the timing of changes in the social environment and hormones with respect to the reproductive cycle and meiosis. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Sex-specific interactions between the IRS1 polymorphism and intakes of carbohydrates and fat on incident type 2 diabetes.

    Science.gov (United States)

    Ericson, Ulrika; Rukh, Gull; Stojkovic, Ivana; Sonestedt, Emily; Gullberg, Bo; Wirfält, Elisabet; Wallström, Peter; Orho-Melander, Marju

    2013-01-01

    The minor T allele of rs2943641 near the gene encoding for insulin receptor substrate 1 (IRS1) has been associated with decreased risk of type 2 diabetes (T2D) and adiposity in genome-wide association studies. Dietary intake can influence the regulation of IRS1, and studies have indicated sex-specific associations between IRS1 and adiposity. The objective was to examine the interaction between IRS1 rs2943641 and macronutrient intakes on incident T2D and percentage body fat in the Malmö Diet and Cancer cohort. The study included 15,227 women and 9614 men aged 45-74 y without prevalent diabetes. Dietary data were collected with a modified diet history method. During 12 y of follow-up, 1567 incident T2D cases were identified. The T allele was associated with lower incidence of T2D (P-trend = 0.003) and, in men, with higher percentage body fat (P-trend = 0.00002). We observed 3-way interactions between sex, rs2943641, and carbohydrate intake (P = 0.01) as well as between sex, rs2943641, and fat intake (P = 0.01) on incident T2D. Among women, the T allele was associated with decreased risk only in the lower tertiles of carbohydrate intake (P-trend = 0.01, P-interaction = 0.01). In contrast, among men, the T allele was associated with decreased risk in the lowest tertile of fat intake (P-trend = 0.01, P-interaction = 0.02). No interaction was observed between macronutrient intakes and rs2943641 on percentage body fat. Our results indicate that IRS1 rs2943641 interacts with carbohydrate and fat intakes on incident T2D in a sex-specific fashion. A protective association between the rs2943641 T allele and T2D was restricted to women with low carbohydrate intake and to men with low fat intake.

  20. Sex Specific Association of Physical Activity on Proximal Femur BMD in 9 to 10 Year-Old Children

    Science.gov (United States)

    Cardadeiro, Graça; Baptista, Fátima; Ornelas, Rui; Janz, Kathleen F.; Sardinha, Luís B.

    2012-01-01

    The results of physical activity (PA) intervention studies suggest that adaptation to mechanical loading at the femoral neck (FN) is weaker in girls than in boys. Less is known about gender differences associated with non-targeted PA levels at the FN or other clinically relevant regions of the proximal femur. Understanding sex-specific relationships between proximal femur sensitivity and mechanical loading during non-targeted PA is critical to planning appropriate public health interventions. We examined sex-specific associations between non-target PA and bone mineral density (BMD) of three sub-regions of the proximal femur in pre- and early-pubertal boys and girls. BMD at the FN, trochanter (TR) and intertrochanter (IT) regions, and lean mass of the whole body were assessed using dual-energy x-ray absorptiometry in 161 girls (age: 9.7±0.3 yrs) and 164 boys (age: 9.7±0.3 yrs). PA was measured using accelerometry. Multiple linear regression analyses (adjusted for body height, total lean mass and pubertal status) revealed that vigorous PA explained 3–5% of the variability in BMD at all three sub-regions in boys. In girls, vigorous PA explained 4% of the variability in IT BMD and 6% in TR BMD. PA did not contribute to the variance in FN BMD in girls. An additional 10 minutes per day of vigorous PA would be expected to result in a ∼1% higher FN, TR, and IT BMD in boys (pgirls. In conclusion, vigorous PA can be expected to contribute positively to bone health outcomes for boys and girls. However, the association of vigorous PA to sub-regions of the proximal femur varies by sex, such that girlś associations are heterogeneous and the lowest at the FN, but stronger at the TR and the IT, when compared to boys. PMID:23209801

  1. Sex-Specific Associations Between Self-reported Sleep Duration, Cardiovascular Disease, Hypertension, and Mortality in an Elderly Population.

    Science.gov (United States)

    Broström, Anders; Wahlin, Ake; Alehagen, Urban; Ulander, Martin; Johansson, Peter

    2017-01-05

    Both short and long sleep durations have been associated to increased mortality. Knowledge about sex-specific differences among elderly regarding associations between sleep duration, cardiovascular health, and mortality is sparse. The aims of this study are to examine the association between self-reported sleep duration and mortality and to investigate whether this association is sex specific and/or moderated by cardiovascular morbidity, and also to explore potential mediators of sleep duration effects on mortality. A population-based, observational, cross-sectional design with 6-year follow-up with mortality as primary outcome was conducted. Self-rated sleep duration, clinical examinations, echocardiography, and blood samples (N-terminal fragment of proBNP) were collected. A total of 675 persons (50% women; mean age, 78 years) were divided into short sleepers (≤6 hours; n = 231), normal sleepers (7-8 hours; n = 338), and long sleepers (≥9 hours; n = 61). Data were subjected to principal component analyses. Cardiovascular disease (CVD) and hypertension factors were extracted and used as moderators and as mediators in the regression analyses. During follow-up, 55 short sleepers (24%), 68 normal sleepers (20%), and 21 long sleepers (34%) died. Mediator analyses showed that long sleep was associated with mortality in men (hazard ratio [HR], 1.8; P = .049), independently of CVD and hypertension. In men with short sleep, CVD acted as a moderator of the association with mortality (HR, 4.1; P = .025). However, when using N-terminal fragment of proBNP, this effect became nonsignificant (HR, 3.1; P = .06). In woman, a trend to moderation involving the hypertension factor and short sleep was found (HR, 4.6; P = .09). Short and long sleep duration may be seen as risk markers, particularly among older men with cardiovascular morbidity.

  2. Human disturbances, habitat characteristics and social environment generate sex-specific responses in vigilance of Mediterranean mouflon.

    Directory of Open Access Journals (Sweden)

    Stéphanie Benoist

    Full Text Available In prey species, vigilance is an important part of the decision making process related to predation risk effects. Therefore, understanding the mechanisms shaping vigilance behavior provides relevant insights on factors influencing individual fitness. We investigated the role of extrinsic and intrinsic factors on vigilance behavior in Mediterranean mouflon (Ovis gmelini musimon×Ovis sp. in a study site spatially and temporally contrasted in human pressures. Both sexes were less vigilant in the wildlife reserve compared to surrounding unprotected areas, except for males during the hunting period. During this period, males tended to be less strictly restricted to the reserve than females what might lead to a pervasive effect of hunting within the protected area, resulting in an increase in male vigilance. It might also be a rutting effect that did not occur in unprotected areas because males vigilance was already maximal in response to human disturbances. In both sexes, yearlings were less vigilant than adults, probably because they traded off vigilance for learning and energy acquisition and/or because they relied on adult experience present in the group. Similarly, non-reproductive females benefited of the vigilance effort provided by reproductive females when belonging to the same group. However, in the absence of reproductive females, non-reproductive females were as vigilant as reproductive females. Increasing group size was only found to reduce vigilance in females (up to 17.5%, not in males. We also showed sex-specific responses to habitat characteristics. Females increased their vigilance when habitat visibility decreased (up to 13.8% whereas males increased their vigilance when feeding on low quality sites, i.e., when concomitant increase in chewing time can be devoted to vigilance with limited costs. Our global approach was able to disentangle the sex-specific sources of variation in mouflon vigilance and stressed the importance of

  3. Differential Survival among Batches of Atlantic Cod (Gadus morhua L. from Fertilisation through to Post-Metamorphosis.

    Directory of Open Access Journals (Sweden)

    Petra E Petersen

    Full Text Available Aquaculture production of cod has decreased from over 20,000 tonnes in 2009 to less than 2,000 tonnes in 2014 and the industry faces many challenges, one of which is high and unpredictably variable mortality rates in the early life stages. Hence, full-cycle farming with hatchery produced juveniles is still considered unprofitable compared to fisheries and on-growing of wild cod. In the present study, potential batch differences in progeny survival of wild-caught, hatchery-spawned Faroe Bank cod (Gadus morhua L. were investigated at two defined periods during early life history; i the embryo stage (60 day degrees post fertilisation and ii the fry stage (110 days post hatch, post metamorphosis. The fry stage experiment was conducted in three replicates (N = 300 per replicate, and a panel of three polymorphic microsatellite markers was used for parental analysis. Mean survival rate at the embryo stage was 69% (± 20% SD. Survival was positively associated with egg diameter (P < 0.01, explaining 90% of the variation in egg survival rates. The data were too scarce to conclude either way concerning a possible correlation between survival rates between the two periods (P < 0.10. Offspring from three batches (from a total of eight dominated in the fry stage, contributing over 90% of the progeny, and results were consistent over all three replicate tanks. The skewed batch representation observed may be of relevance to the effective management of selective breeding programmes for cod.

  4. Artichoke compound cynarin differentially affects the survival, growth and stress response of normal, immortalized and cancerous human cells

    DEFF Research Database (Denmark)

    Gezer, Ceren; Yücecan, Sevinç; Rattan, Suresh Inder Singh

    2015-01-01

    of CYN on the proliferative potential, survival, morphology, and stress response (SR) markers haemoxygenase-1 (HO-1) and heat shock protein-70 (HSP70) in normal human skin fibroblasts (FSF-1), telomerase-immortalized mesenchymal stem cells (hTERT-MSC) and cervical cancer cells, HeLa. Effects of CYN...

  5. Improved Survival and Initiation of Differentiation of Human Induced Pluripotent Stem Cells to Hepatocyte-Like Cells upon Culture in William's E Medium followed by Hepatocyte Differentiation Inducer Treatment.

    Directory of Open Access Journals (Sweden)

    Minoru Tomizawa

    Full Text Available Hepatocyte differentiation inducer (HDI lacks both glucose and arginine, but is supplemented with galactose and ornithine, and is added together with other reagents such as apoptosis inhibitor and oncostatin M. Although human induced pluripotent stem (iPS cells initiate hepatocyte differentiation, most die within 7 days. In this study, we investigated both HDI and conventional media for their potential to improve cell survival.201B7 iPS cells were cultured in conventional media. This consisted of three cycles of 5-day culture in William's E (WE medium, followed by a 2-day culture in HDI.Expression levels of α-feto protein (AFP were higher in cells cultured in WE and in Dulbecco's Modified Eagle's Medium/Nutrient F-12 Ham (DF12. 201B7 cells expressed the highest AFP and albumin (ALB when cultured in HDI for 2 days following 7-day culture in WE. After three cycles of 5-day culture in WE followed by 2 days in HDI, 201B7 cells expressed AFP and ALB 54 ± 2.3 (average ± standard deviation and 73 ± 15.1 times higher, respectively, than those cultured in ReproFF (feeder-free condition.201B7 cells survived culture in WE for 7 days followed HDI for 2 days. After three cycles of culture under these conditions, hepatocyte differentiation was enhanced, as evidenced by increased AFP and ALB expression.

  6. Sex-specific genotype-by-environment interactions for cuticular hydrocarbon expression in decorated crickets, Gryllodes sigillatus: implications for the evolution of signal reliability.

    Science.gov (United States)

    Weddle, C B; Mitchell, C; Bay, S K; Sakaluk, S K; Hunt, J

    2012-10-01

    Phenotypic traits that convey information about individual identity or quality are important in animal social interactions, and the degree to which such traits are influenced by environmental variation can have profound effects on the reliability of these cues. Using inbred genetic lines of the decorated cricket, Gryllodes sigillatus, we manipulated diet quality to test how the cuticular hydrocarbon (CHC) profiles of males and females respond across two different nutritional rearing environments. There were significant differences between lines in the CHC profiles of females, but the effect of diet was not quite statistically significant. There was no significant genotype-by-environment interaction (GEI), suggesting that environmental effects on phenotypic variation in female CHCs are independent of genotype. There was, however, a significant effect of GEI for males, with changes in both signal quantity and content, suggesting that environmental effects on phenotypic expression of male CHCs are dependent on genotype. The differential response of male and female CHC expression to variation in the nutritional environment suggests that these chemical cues may be under sex-specific selection for signal reliability. Female CHCs show the characteristics of reliable cues of identity: high genetic variability, low condition dependence and a high degree of genetic determination. This supports earlier work showing that female CHCs are used in self-recognition to identify previous mates and facilitate polyandry. In contrast, male CHCs show the characteristics of reliable cues of quality: condition dependence and a relatively higher degree of environmental determination. This suggests that male CHCs are likely to function as cues of underlying quality during mate choice and/or male dominance interactions. © 2012 The Authors. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.

  7. Beta-hydroxy-beta-methylbutyrate (HMB) stimulates myogenic cell proliferation, differentiation and survival via the MAPK/ERK and PI3K/Akt pathways.

    Science.gov (United States)

    Kornasio, Reut; Riederer, Ingo; Butler-Browne, Gillian; Mouly, Vincent; Uni, Zehava; Halevy, Orna

    2009-05-01

    Beta-hydroxy-beta-methylbutyrate (HMB), a leucine catabolite, has been shown to prevent exercise-induced protein degradation and muscle damage. We hypothesized that HMB would directly regulate muscle-cell proliferation and differentiation and would attenuate apoptosis, the latter presumably underlying satellite-cell depletion during muscle degradation or atrophy. Adding various concentrations of HMB to serum-starved myoblasts induced cell proliferation and MyoD expression as well as the phosphorylation of MAPK/ERK. HMB induced differentiation-specific markers, increased IGF-I mRNA levels and accelerated cell fusion. Its inhibition of serum-starvation- or staurosporine-induced apoptosis was reflected by less apoptotic cells, reduced BAX expression and increased levels of Bcl-2 and Bcl-X. Annexin V staining and flow cytometry analysis showed reduced staurosporine-induced apoptosis in human myoblasts in response to HMB. HMB enhanced the association of the p85 subunit of PI3K with tyrosine-phosphorylated proteins. HMB elevated Akt phosphorylation on Thr308 and Ser473 and this was inhibited by Wortmannin, suggesting that HMB acts via Class I PI3K. Blocking of the PI3K/Akt pathway with specific inhibitors revealed its requirement in mediating the promotive effects of HMB on muscle cell differentiation and fusion. These direct effects of HMB on myoblast differentiation and survival resembling those of IGF-I, at least in culture, suggest its positive influence in preventing muscle wasting.

  8. Doublecortin (DCX is not essential for survival and differentiation of newborn neurons in the adult mouse dentate gyrus

    Directory of Open Access Journals (Sweden)

    Jagroop eDhaliwal

    2016-01-01

    Full Text Available In the adult brain, expression of the microtubule-associated protein Doublecortin (DCX is associated with neural progenitor cells (NPCs that give rise to new neurons in the dentate gyrus. Many studies quantify the number of DCX-expressing cells as a proxy for the level of adult neurogenesis, yet no study has determined the effect of removing DCX from adult hippocampal NPCs. Here, we use a retroviral and inducible mouse transgenic approach to either knockdown or knockout DCX from adult NPCs in the dentate gyrus and examine how this affects cell survival and neuronal maturation. Our results demonstrate that shRNA-mediated knockdown of DCX or Cre-mediated recombination in floxed DCX mice does not alter hippocampal neurogenesis and does not change the neuronal fate of the NPCs. Together these findings show that the survival and maturation of adult-generated hippocampal neurons does not require DCX.

  9. Prenatal particulate air pollution exposure and body composition in urban preschool children: Examining sensitive windows and sex-specific associations.

    Science.gov (United States)

    Chiu, Yueh-Hsiu Mathilda; Hsu, Hsiao-Hsien Leon; Wilson, Ander; Coull, Brent A; Pendo, Mathew P; Baccarelli, Andrea; Kloog, Itai; Schwartz, Joel; Wright, Robert O; Taveras, Elsie M; Wright, Rosalind J

    2017-10-01

    Evolving animal studies and limited epidemiological data show that prenatal air pollution exposure is associated with childhood obesity. Timing of exposure and child sex may play an important role in these associations. We applied an innovative method to examine sex-specific sensitive prenatal windows of exposure to PM 2.5 on anthropometric measures in preschool-aged children. Analyses included 239 children born ≥ 37 weeks gestation in an ethnically-mixed lower-income urban birth cohort. Prenatal daily PM 2.5 exposure was estimated using a validated satellite-based spatio-temporal model. Body mass index z-score (BMI-z), fat mass, % body fat, subscapular and triceps skinfold thickness, waist and hip circumferences and waist-to-hip ratio (WHR) were assessed at age 4.0 ± 0.7 years. Using Bayesian distributed lag interaction models (BDLIMs), we examined sex differences in sensitive windows of weekly averaged PM 2.5 levels on these measures, adjusting for child age, maternal age, education, race/ethnicity, and pre-pregnancy BMI. Mothers were primarily Hispanic (55%) or Black (26%), had ≤ 12 years of education (66%) and never smoked (80%). Increased PM 2.5 exposure 8-17 and 15-22 weeks gestation was significantly associated with increased BMI z-scores and fat mass in boys, but not in girls. Higher PM 2.5 exposure 10-29 weeks gestation was significantly associated with increased WHR in girls, but not in boys. Prenatal PM 2.5 was not significantly associated with other measures of body composition. Estimated cumulative effects across pregnancy, accounting for sensitive windows and within-window effects, were 0.21 (95%CI = 0.01-0.37) for BMI-z and 0.36 (95%CI = 0.12-0.68) for fat mass (kg) in boys, and 0.02 (95%CI = 0.01-0.03) for WHR in girls, all per µg/m 3 increase in PM 2.5 . Increased prenatal PM 2.5 exposure was more strongly associated with indices of increased whole body size in boys and with an indicator of body shape in girls. Methods to better characterize

  10. Sex-specific effects of low-dose gestational estradiol-17β exposure on bone development in porcine offspring

    International Nuclear Information System (INIS)

    Flöter, Veronika L.; Galateanu, Gabriela; Fürst, Rainer W.; Seidlová-Wuttke, Dana; Wuttke, Wolfgang; Möstl, Erich; Hildebrandt, Thomas B.

    2016-01-01

    Highlights: • Sex-specific effects and non-monotonic dose responses were demonstrated after low-dose in utero E2 treatment in offspring. • Alterations in bone parameters were found in prepubertal male but not female offspring. • In postpubertal female offspring, cortical and total cross-sectional area were higher at the femoral midpoint. • In utero E2 treatment did neither significantly affect hormone concentrations nor puberty onset in offspring. • The results substantiate the high sensitivity of developing organisms to exogenous estrogens. - Abstract: Estrogens are important for the bone development and health. Exposure to endocrine disrupting chemicals during the early development has been shown to affect the bone phenotype later in life. Several studies have been performed in rodents, while in larger animals that are important to bridge the gap to humans there is a paucity of data. To this end, the pig as large animal model was used in the present study to assess the influence of gestational estradiol-17β (E2) exposure on the bone development of the prepubertal and adult offspring. Two low doses (0.05 and 10 μg E2/kg body weight) referring to the ‘acceptable daily intake’ (ADI) and the ‘no observed effect level’ (NOEL) as stated for humans, and a high-dose (1000 μg E2/kg body weight), respectively, were fed to the sows every day from insemination until delivery. In the male prepubertal offspring, the ADI dose group had a lower strength strain index (p = 0.002) at the proximal tibia compared to controls, which was determined by peripheral quantitative computed tomography. Prepubertal females were not significantly affected. However, there was a higher cortical cross-sectional area (CSA) (p = 0.03) and total CSA (p = 0.02) at the femur midpoint in the adult female offspring of the NOEL dose group as measured by computed tomography. These effects were independent from plasma hormone concentrations (leptin, IGF1, estrogens), which remained

  11. Sex specific association of physical activity on proximal femur BMD in 9 to 10 year-old children.

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    Graça Cardadeiro

    Full Text Available The results of physical activity (PA intervention studies suggest that adaptation to mechanical loading at the femoral neck (FN is weaker in girls than in boys. Less is known about gender differences associated with non-targeted PA levels at the FN or other clinically relevant regions of the proximal femur. Understanding sex-specific relationships between proximal femur sensitivity and mechanical loading during non-targeted PA is critical to planning appropriate public health interventions. We examined sex-specific associations between non-target PA and bone mineral density (BMD of three sub-regions of the proximal femur in pre- and early-pubertal boys and girls. BMD at the FN, trochanter (TR and intertrochanter (IT regions, and lean mass of the whole body were assessed using dual-energy x-ray absorptiometry in 161 girls (age: 9.7±0.3 yrs and 164 boys (age: 9.7±0.3 yrs. PA was measured using accelerometry. Multiple linear regression analyses (adjusted for body height, total lean mass and pubertal status revealed that vigorous PA explained 3-5% of the variability in BMD at all three sub-regions in boys. In girls, vigorous PA explained 4% of the variability in IT BMD and 6% in TR BMD. PA did not contribute to the variance in FN BMD in girls. An additional 10 minutes per day of vigorous PA would be expected to result in a ∼1% higher FN, TR, and IT BMD in boys (p<0.05 and a ∼2% higher IT and TR BMD in girls. In conclusion, vigorous PA can be expected to contribute positively to bone health outcomes for boys and girls. However, the association of vigorous PA to sub-regions of the proximal femur varies by sex, such that girlś associations are heterogeneous and the lowest at the FN, but stronger at the TR and the IT, when compared to boys.

  12. Sex-Specific Association between Metabolic Abnormalities and Elevated Alanine Aminotransferase Levels in a Military Cohort: The CHIEF Study

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    Kai-Wen Chen

    2018-03-01

    Full Text Available The association of metabolic syndrome (MetS components with elevated serum alanine aminotransferase (ALT levels, a marker of hepatic injury, may differ between men and women. However, the sex-specific association in a military young population which has a low prevalence of MetS was unclear. We conducted a cross-sectional examination in 6738 men and 766 women, aged 18–50 years, from the cardiorespiratory fitness study in armed forces (CHIEF in eastern Taiwan. The components of MetS were defined according to the updated International Diabetes Federation (IDF ethnic criteria for Asians. Elevated ALT levels were defined as ≥40 U/L for both sexes and ≥30 U/L for women alternatively. Multivariate logistic regression analysis was performed to determine the sex-specific association between MetS components and elevated ALT. The prevalence of MetS and elevated ALT in men were 11.9% and 12.7% respectively, and in women were 3.5%, and 3.8% respectively. In men, high-density lipoprotein < 40 mg/dL, blood pressures ≥ 130/85 mmHg, serum triglycerides ≥ 150 mg/dL, and waist size ≥ 90 cm were associated with elevated ALT (odds ratios (OR and 95% confidence intervals: 1.59 (1.34–1.90, 1.40 (1.19–1.65, 2.00 (1.68–2.39, and 1.68 (1.38–2.04; all p < 0.001; whereas in women, only fasting plasma glucose ≥ 100 mg/dL was associated with elevated ALT ≥ 40 U/L (OR: 7.59 (2.35–24.51, p = 0.001 and ALT ≥ 30 U/L (2.67 (0.89–7.95, p = 0.08. Our findings suggest that the relationship between metabolic abnormalities and elevated ALT may differ by sex, possibly due to the MetS more prevalent in young adult men than in women.

  13. IRF8 Transcription Factor Controls Survival and Function of Terminally Differentiated Conventional and Plasmacytoid Dendritic Cells, Respectively

    DEFF Research Database (Denmark)

    Sichien, Dorine; Scott, Charlotte L; Martens, Liesbet

    2016-01-01

    Interferon regulatory factor-8 (IRF8) has been proposed to be essential for development of monocytes, plasmacytoid dendritic cells (pDCs) and type 1 conventional dendritic cells (cDC1s) and remains highly expressed in differentiated DCs. Transcription factors that are required to maintain the ide...

  14. High maternal sodium intake alters sex-specific renal renin-angiotensin system components in newborn Wistar offspring.

    Science.gov (United States)

    Maia, D R R; Lopes, K L; Heimann, J C; Furukawa, L N S

    2016-01-28

    This study aimed to evaluate the systemic and renal renin-angiotensin-aldosterone system (RAAS) at birth in male and female offspring and in mothers fed a high sodium diet (HSD) before and during gestation. Female Wistar rats were fed a HSD (8.0% NaCl) or a normal sodium diet (1.3% NaCl) from 8 weeks of age until delivery of their first litter. Maternal body weight, tail blood pressure, and food and water intake were evaluated. The litter sizes were assessed, and the body and kidney weights of the offspring were measured. Both mothers and offspring were euthanized immediately following the birth of the pups to evaluate plasma renin activity (PRA), renal renin content (RRC), renal angiotensin-converting enzyme (ACE) activity, renal angiotensin (Ang) II content, serum aldosterone (ALDO) levels, and renal cortical and medullary renin messenger RNA expression. In mothers in the HSD group, water intake and kidney mass were higher, whereas renal ACE activity, Ang II, PRA, ALDO and RRC were decreased. In the offspring of HSD-fed dams, the body and kidney mass were lower in both genders, renal ACE activity was lower in females and renal Ang II was lower in males. PRA, RRC, renin gene expression and ALDO levels did not differ between the groups of offspring. The data presented herein showed that a maternal HSD during pregnancy induces low birth weight and a sex-specific response in the RAAS in offspring.

  15. Sex-specific asymmetries in communication sound perception are not related to hand preference in an early primate

    Directory of Open Access Journals (Sweden)

    Scheumann Marina

    2008-01-01

    Full Text Available Abstract Background Left hemispheric dominance of language processing and handedness, previously thought to be unique to humans, is currently under debate. To gain an insight into the origin of lateralization in primates, we have studied gray mouse lemurs, suggested to represent the most ancestral primate condition. We explored potential functional asymmetries on the behavioral level by applying a combined handedness and auditory perception task. For testing handedness, we used a forced food-grasping task. For testing auditory perception, we adapted the head turn paradigm, originally established for exploring hemispheric specializations in conspecific sound processing in Old World monkeys, and exposed 38 subjects to control sounds and conspecific communication sounds of positive and negative emotional valence. Results The tested mouse lemur population did not show an asymmetry in hand preference or in orientation towards conspecific communication sounds. However, males, but not females, exhibited a significant right ear-left hemisphere bias when exposed to conspecific communication sounds of negative emotional valence. Orientation asymmetries were not related to hand preference. Conclusion Our results provide the first evidence for sex-specific asymmetries for conspecific communication sound perception in non-human primates. Furthermore, they suggest that hemispheric dominance for communication sound processing evolved before handedness and independently from each other.

  16. Sex-specific nonlinear associations between serum lipids and different domains of cognitive function in middle to older age individuals.

    Science.gov (United States)

    Lu, Yanhui; An, Yu; Yu, Huanling; Che, Fengyuan; Zhang, Xiaona; Rong, Hongguo; Xi, Yuandi; Xiao, Rong

    2017-08-01

    To examine how serum lipids relates to specific cognitive ability domains between the men and women in Chinese middle to older age individuals. A complete lipid panel was obtained from 1444 individuals, ages 50-65, who also underwent a selection of cognitive tests. Participants were 584 men and 860 women from Linyi city, Shandong province. Multiple linear regression analyses examined serum lipids level as quadratic predictors of sex-specific measure of performance in different cognitive domains, which were adjusted for sociodemographic and lifestyle characteristics. In men, a significant quadratic effect of total cholesterol (TC) was identified for Digit Symbol (B = -0.081, P = 0.044) and also quadratic effect of low density lipoprotein-cholesterol (LDL-C) was identified for Trail Making Test B (B = -0.082, P = 0.045). Differently in women, there were significant quadratic associations between high density lipoprotein-cholesterol (HDL-C) and multiple neuropsychological tests. The nonlinear lipid-cognition associations differed between men and women and were specific to certain cognitive domains and might be of potential relevance for prevention and therapy of cognitive decline.

  17. Sex-specific effects of intranasal oxytocin on autonomic nervous system and emotional responses to couple conflict

    Science.gov (United States)

    Nater, Urs M.; Schaer, Marcel; La Marca, Roberto; Bodenmann, Guy; Ehlert, Ulrike; Heinrichs, Markus

    2013-01-01

    Unhappy couple relationships are associated with impaired individual health, an effect thought to be mediated through ongoing couple conflicts. Little is known, however, about the underlying mechanisms regulating psychobiological stress, and particularly autonomic nervous system (ANS) reactivity, during negative couple interaction. In this study, we tested the effects of the neuropeptide oxytocin on ANS reactivity during couple conflict in a standardized laboratory paradigm. In a double-blind, placebo-controlled design, 47 heterosexual couples (total n = 94) received oxytocin or placebo intranasally prior to instructed couple conflict. Participants’ behavior was videotaped and salivary alpha-amylase (sAA), a measure of sympathetic activity, and emotional arousal were repeatedly measured during the experiment. Oxytocin significantly reduced sAA during couple conflict in women, whereas men showed increases in sAA levels (sex × group interaction: B = −49.36, t = −2.68, P = 0.009). In men, these increases were related to augmented emotional arousal (r = 0.286, P = 0.028) and more positive behavior (r = 0.291, P = 0.026), whereas there was no such association in women. Our results imply sex-specific effects of oxytocin on sympathetic activity, to negative couple interaction, with the neuropeptide reducing sAA responses and emotional arousal in women while increasing them in men. PMID:22842905

  18. A Novel Method for Assessing Sex-Specific and Genotype-Specific Response to Injury in Astrocyte Culture

    Science.gov (United States)

    Liu, Mingyue; Oyarzabal, Esteban; Yang, Rui; Murphy, Stephanie J; Hurn, Patricia D.

    2008-01-01

    Female astrocytes sustain less cell death from oxygen-glucose deprivation (OGD) than male astrocytes. Arimidex, an aromatase inhibitor, abolishes these sex differences. To verify sex-dependent differences in P450 aromatase function in astrocyte cell death following OGD, we developed a novel method that uses sex-specific and genotype-specific single pup primary astrocyte cultures from wild-type (WT) and aromatase-knockout (ArKO) mice. After determining sex by external and internal examination as well as PCR and genotype by PCR amplification of tail cDNA, we established cultures from 1−3 day-old male and female, WT and ArKO mice pups and grew them to confluence in estrogen-free media. Cell death was measured by lactate dehydrogenase (LDH) assay. Our study shows that, while WT female astrocytes are more resistant to OGD than WT male cells, sex differences disappear in ArKO cells. Cell death is significantly increased in ArKO compared to WT in female astrocytes but not male cells. Therefore, P450 aromatase appears to be essential in endogenous neuroprotection in females, and this finding may have clinical implications. This innovative technique may also be applied to other in vitro studies of sex-related functional differences. PMID:18436308

  19. Sex-specific patterns of morphological diversification: evolution of reaction norms and static allometries in neriid flies.

    Science.gov (United States)

    Cassidy, Elizabeth J; Bath, Eleanor; Chenoweth, Stephen F; Bonduriansky, Russell

    2014-02-01

    The consequences of sex-specific selection for patterns of diversification remain poorly known. Because male secondary sexual traits are typically costly to express, and both costs and benefits are likely to depend on ambient environment and individual condition, such traits may be expected to diversify via changes in reaction norms as well as the scaling of trait size with body size (static allometry). We investigated morphological diversification within two species of Australian neriid flies (Telostylinus angusticollis, Telostylinus lineolatus) by rearing larvae from several populations on larval diets varying sixfold in nutrient concentration. Mean body size varied among populations of T. angusticollis, but body size reaction norms did not vary within either species. However, we detected diversification of reaction norms for body shape in males and females within both species. Moreover, unlike females, males also diversified in static allometry slope and reaction norms for static allometry slope of sexual and nonsexual traits. Our findings reveal qualitative sex differences in patterns of morphological diversification, whereby shape-size relationships diversify extensively in males, but remain conserved in females despite extensive evolution of trait means. Our results highlight the importance of incorporating plasticity and allometry in studies of adaptation and diversification. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

  20. ALKBH7 drives a tissue and sex-specific necrotic cell death response following alkylation-induced damage

    Science.gov (United States)

    Jordan, Jennifer J; Chhim, Sophea; Margulies, Carrie M; Allocca, Mariacarmela; Bronson, Roderick T; Klungland, Arne; Samson, Leona D; Fu, Dragony

    2017-01-01

    Regulated necrosis has emerged as a major cell death mechanism in response to different forms of physiological and pharmacological stress. The AlkB homolog 7 (ALKBH7) protein is required for regulated cellular necrosis in response to chemotherapeutic alkylating agents but its role within a whole organism is unknown. Here, we show that ALKBH7 modulates alkylation-induced cellular death through a tissue and sex-specific mechanism. At the whole-animal level, we find that ALKBH7 deficiency confers increased resistance to MMS-induced toxicity in male but not female mice. Moreover, ALKBH7-deficient mice exhibit protection against alkylation-mediated cytotoxicity in retinal photoreceptor and cerebellar granule cells, two cell types that undergo necrotic death through the initiation of the base excision repair pathway and hyperactivation of the PARP1/ARTD1 enzyme. Notably, the protection against alkylation-induced cerebellar degeneration is specific to ALKBH7-deficient male but not female mice. Our results uncover an in vivo role for ALKBH7 in mediating a sexually dimorphic tissue response to alkylation damage that could influence individual responses to chemotherapies based upon alkylating agents. PMID:28726787

  1. Sex-specific effects of mindfulness on romantic partners' cortisol responses to conflict and relations with psychological adjustment.

    Science.gov (United States)

    Laurent, Heidemarie; Laurent, Sean; Hertz, Robin; Egan-Wright, Dorianne; Granger, Douglas A

    2013-12-01

    Mindfulness is known to improve individuals' and couples' subjective stress regulation, but little is known about how it impacts hypothalamic-pituitary-adrenal (HPA) axis responses to acute psychosocial stress. The current study tested effects of dispositional mindfulness facets on young adult couples' cortisol responses to a conflict discussion stressor, as well as associations with psychological adjustment. One hundred heterosexual couples completed the five facet mindfulness questionnaire one week before engaging in a conflict discussion task. Each partner provided five saliva samples from pre- to post-conflict, which were assayed for cortisol. Measures of adjustment - depression and anxiety symptoms and global well-being - were also completed at this session. Hierarchical linear modeling of cortisol trajectories revealed sex-specific effects; whereas women's mindfulness (nonreactivity facet) predicted higher conflict stress cortisol levels, men's mindfulness (describing facet) predicted less pronounced cortisol reactivity/recovery curves. These patterns were related to better adjustment-lower depression symptoms for women and greater well-being for men. Implications for sex differences in mindfulness benefits are discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Electrotonic Coupling in the Pituitary Supports the Hypothalamic-Pituitary-Gonadal Axis in a Sex Specific Manner

    Directory of Open Access Journals (Sweden)

    Christina Göngrich

    2016-08-01

    Full Text Available Gap junctions are present in many cell types throughout the animal kingdom and allow fast intercellular electrical and chemical communication between neighboring cells. Connexin-36 (Cx36, the major neuronal gap junction protein, synchronizes cellular activity in the brain, but also in other organs. Here we identify a sex-specific role for Cx36 within the hypothalamic-pituitary-gonadal (HPG axis at the level of the anterior pituitary gland (AP. We show that Cx36 is expressed in gonadotropes of the AP sustaining their synchronous activity. Cx36 ablation affects the entire downstream HPG axis in females, but not in males. We demonstrate that Cx36-mediated coupling between gonadotropes in the AP supports gonadotropin-releasing hormone-induced secretion of luteinizing hormone. Furthermore, we provide evidence for negative feedback regulation of Cx36 expression in the AP by estradiol. We thus conclude that hormonally-controlled plasticity of gap junction communication at the level of the AP constitutes an additional mechanism affecting female reproduction.

  3. Effects of Early-Life Stress on Social and Anxiety-Like Behaviors in Adult Mice: Sex-Specific Effects

    Directory of Open Access Journals (Sweden)

    Natalya P. Bondar

    2018-01-01

    Full Text Available Stressful events in an early postnatal period have critical implications for the individual’s life and can increase later risk for psychiatric disorders. The aim of this study was to investigate the influence of early-life stress on the social behavior of adult male and female mice. C57Bl/6 mice were exposed to maternal separation (MS, 3 h once a day or handling (HD, 15 min once a day on postnatal day 2 through 14. Adult male and female mice were tested for social behavior in the social interaction test and for individual behavior in the plus-maze and open-field tests. Female mice exposed to maternal separation had increased social behavior and increased anxiety. MS male mice had no changes in social behavior but had significantly disrupted individual behavior, including locomotor and exploratory activity. Handling had positive effects on social behavior in males and females and decreased anxiety in males. Our results support the hypothesis that brief separation of pups from their mothers (handling, which can be considered as moderate stress, may result in future positive changes in behavior. Maternal separation has deleterious effects on individual behavior and significant sex-specific effects on social behavior.

  4. Maternal exposure to environmental enrichment before and during gestation influences behaviour of rat offspring in a sex-specific manner.

    Science.gov (United States)

    Zuena, Anna Rita; Zinni, Manuela; Giuli, Chiara; Cinque, Carlo; Alemà, Giovanni Sebastiano; Giuliani, Alessandro; Catalani, Assia; Casolini, Paola; Cozzolino, Roberto

    2016-09-01

    The beneficial effects of Environmental Enrichment (EE) applied immediately after weaning or even in adulthood have been widely demonstrated. Less is known about the possible changes in behaviour and brain development of the progeny following the exposure of dams to EE. In order to further investigate this matter, female rats were reared in EE for 12weeks, from weaning until delivery. After having confirmed the presence of relevant behavioural effects of EE, both control and EE females underwent mating. Maternal behaviour was observed and male and female offspring were then administered a battery of behavioural test at different ages. EE mothers showed a decreased frequency of total nursing and, during the first 2days of lactation, an increase in licking/grooming behaviour. Maternal exposure to EE affected offspring behaviour in a sex-specific manner: social play behaviour and anxiety-like behaviour were increased in males but not in females and learning ability was improved only in females. As a general trend, maternal EE had a marked influence on motility in male and female offspring in both locomotor activity and swimming speed. Overall, this study highlights the importance of environmental stimulation, not only in the animals directly experiencing EE, but for their progeny too, opening the way to new hypothesis on the heritability mechanisms of behavioural traits. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Sex-specific predictors of hearing-aid use in older persons: The age, gene/environment susceptibility - Reykjavik study

    Science.gov (United States)

    Fisher, Diana E.; Li, Chuan-Ming; Hoffman, Howard J.; Chiu, May S.; Themann, Christa L.; Petersen, Hannes; Jonsson, Palmi V.; Jonsson, Helgi; Jonasson, Fridbert; Sverrisdottir, Johanna Eyrun; Launer, Lenore J.; Eiriksdottir, Gudny; Gudnason, Vilmundur; Cotch, Mary Frances

    2015-01-01

    Objective We estimate the prevalence of hearing-aid use in Iceland and identify sex-specific factors associated with use. Design Population-based cohort study. Study sample A total of 5172 age, gene/environment susceptibility - Reykjavik study (AGES-RS) participants, aged 67 to 96 years (mean age 76.5 years), who completed air-conduction and pure-tone audiometry. Results Hearing-aid use was reported by 23.0% of men and 15.9% of women in the cohort, although among participants with at least moderate hearing loss in the better ear (pure-tone average [PTA] of thresholds at 0.5, 1, 2, and 4 kHz ≥ 35 dB hearing level [HL]) it was 49.9% and did not differ by sex. Self-reported hearing loss was the strongest predictor of hearing-aid use in men [OR: 2.68 (95% CI: 1.77, 4.08)] and women [OR: 3.07 (95% CI: 1.94, 4.86)], followed by hearing loss severity based on audiometry. Having diabetes or osteoarthritis were significant positive predictors of use in men, whereas greater physical activity and unimpaired cognitive status were important in women. Conclusions Hearing-aid use was comparable in Icelandic men and women with moderate or greater hearing loss. Self-recognition of hearing loss was the factor most predictive of hearing-aid use; other influential factors differed for men and women. PMID:25816699

  6. Bulked segregant analysis of the pirarucu (Arapaima gigas) genome for identification of sex-specific molecular markers.

    Science.gov (United States)

    Almeida, I G; Ianella, P; Faria, M T; Paiva, S R; Caetano, A R

    2013-12-04

    Arapaima gigas (Osteoglossidae) is one of the largest fish species in the Amazon Basin, attaining lengths of over 2.5 m and weights of over 100 kg. Its flesh is prized, and it has great potential for production in aquaculture systems. However, live pirarucu cannot be reliably sexed visually, even after sexual development, since this species does not have clear external sexual dimorphism. Simple and inexpensive methods for sexing immature pirarucu based on DNA markers would facilitate production of this species in commercial operations. We analyzed A. gigas male and female DNA pools with 566 RAPD primers, generating 2609 fragments, with an estimated 1341 segregating polymorphic markers, and an estimated average spacing of 714 kb, which corresponds to less than 0.1% of the species' genome. Two putative sex-specific fragments were initially identified in bulked samples; but they were not confirmed in a study of individual male and female samples. We suggest that A. gigas has developed a non-chromosomal system of sex determination or, alternatively, that the species has undergone a recent loss of the chromosome carrying the sex-determining locus.

  7. Local and sex-specific biases in crossover vs. noncrossover outcomes at meiotic recombination hot spots in mice

    Science.gov (United States)

    de Boer, Esther; Jasin, Maria; Keeney, Scott

    2015-01-01

    Meiotic recombination initiated by programmed double-strand breaks (DSBs) yields two types of interhomolog recombination products, crossovers and noncrossovers, but what determines whether a DSB will yield a crossover or noncrossover is not understood. In this study, we analyzed the influence of sex and chromosomal location on mammalian recombination outcomes by constructing fine-scale recombination maps in both males and females at two mouse hot spots located in different regions of the same chromosome. These include the most comprehensive maps of recombination hot spots in oocytes to date. One hot spot, located centrally on chromosome 1, behaved similarly in male and female meiosis: Crossovers and noncrossovers formed at comparable levels and ratios in both sexes. In contrast, at a distal hot spot, crossovers were recovered only in males even though noncrossovers were obtained at similar frequencies in both sexes. These findings reveal an example of extreme sex-specific bias in recombination outcome. We further found that estimates of relative DSB levels are surprisingly poor predictors of relative crossover frequencies between hot spots in males. Our results demonstrate that the outcome of mammalian meiotic recombination can be biased, that this bias can vary depending on location and cellular context, and that DSB frequency is not the only determinant of crossover frequency. PMID:26251527

  8. Sex-specific local life-history adaptation in surface- and cave-dwelling Atlantic mollies (Poecilia mexicana).

    Science.gov (United States)

    Riesch, Rüdiger; Reznick, David N; Plath, Martin; Schlupp, Ingo

    2016-03-10

    Cavefishes have long been used as model organisms showcasing adaptive diversification, but does adaptation to caves also facilitate the evolution of reproductive isolation from surface ancestors? We raised offspring of wild-caught surface- and cave-dwelling ecotypes of the neotropical fish Poecilia mexicana to sexual maturity in a 12-month common garden experiment. Fish were raised under one of two food regimes (high vs. low), and this was crossed with differences in lighting conditions (permanent darkness vs. 12:12 h light:dark cycle) in a 2 × 2 factorial design, allowing us to elucidate potential patterns of local adaptation in life histories. Our results reveal a pattern of sex-specific local life-history adaptation: Surface molly females had the highest fitness in the treatment best resembling their habitat of origin (high food and a light:dark cycle), and suffered from almost complete reproductive failure in darkness, while cave molly females were not similarly affected in any treatment. Males of both ecotypes, on the other hand, showed only weak evidence for local adaptation. Nonetheless, local life-history adaptation in females likely contributes to ecological diversification in this system and other cave animals, further supporting the role of local adaptation due to strong divergent selection as a major force in ecological speciation.

  9. Sex-specific ecophysiological responses to environmental fluctuations of free-ranging Hermann's tortoises: implication for conservation.

    Science.gov (United States)

    Sibeaux, Adélaïde; Michel, Catherine Louise; Bonnet, Xavier; Caron, Sébastien; Fournière, Kévin; Gagno, Stephane; Ballouard, Jean-Marie

    2016-01-01

    Physiological parameters provide indicators to evaluate how organisms respond to conservation actions. For example, individuals translocated during reinforcement programmes may not adapt to their novel host environment and may exhibit elevated chronic levels of stress hormones and/or decreasing body condition. Conversely, successful conservation actions should be associated with a lack of detrimental physiological perturbation. However, physiological references fluctuate over time and are influenced by various factors (e.g. sex, age, reproductive status). It is therefore necessary to determine the range of natural variations of the selected physiological metrics to establish useful baselines. This study focuses on endangered free-ranging Hermann's tortoises ( Testudo hermanni hermanni ), where conservation actions have been preconized to prevent extinction of French mainland populations. The influence of sex and of environmental factors (site, year and season) on eight physiological parameters (e.g. body condition, corticosterone concentrations) was assessed in 82 individuals from two populations living in different habitats. Daily displacements were monitored by radio-tracking. Most parameters varied between years and seasons and exhibited contrasting sex patterns but with no or limited effect of site. By combining behavioural and physiological traits, this study provides sex-specific seasonal baselines that can be used to monitor the health status of Hermann's tortoises facing environmental threats (e.g. habitat changes) or during conservation actions (e.g. translocation). These results might also assist in selection of the appropriate season for translocation.

  10. Common genetic variation near MC4R has a sex-specific impact on human brain structure and eating behavior.

    Directory of Open Access Journals (Sweden)

    Annette Horstmann

    Full Text Available Obesity is associated with genetic and environmental factors but the underlying mechanisms remain poorly understood. Recent genome-wide association studies (GWAS identified obesity- and type 2 diabetes-associated genetic variants located within or near genes that modulate brain activity and development. Among the top hits is rs17782313 near MC4R, encoding for the melanocortin-4-receptor, which is expressed in brain regions that regulate eating. Here, we hypothesized rs17782313-associated changes in human brain regions that regulate eating behavior. Therefore, we examined effects of common variants at rs17782313 near MC4R on brain structure and eating behavior. Only in female homozygous carriers of the risk allele we found significant increases of gray matter volume (GMV in the right amygdala, a region known to influence eating behavior, and the right hippocampus, a structure crucial for memory formation and learning. Further, we found bilateral increases in medial orbitofrontal cortex, a multimodal brain structure encoding the subjective value of reinforcers, and bilateral prefrontal cortex, a higher order regulation area. There was no association between rs17782313 and brain structure in men. Moreover, among female subjects only, we observed a significant increase of 'disinhibition', and, more specifically, on 'emotional eating' scores of the Three Factor Eating Questionnaire in carriers of the variant rs17782313's risk allele. These findings suggest that rs17782313's effect on eating behavior is mediated by central mechanisms and that these effects are sex-specific.

  11. Antitumor and chemosensitizing action of dichloroacetate implicates modulation of tumor microenvironment: A role of reorganized glucose metabolism, cell survival regulation and macrophage differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Ajay; Kant, Shiva; Singh, Sukh Mahendra, E-mail: sukhmahendrasingh@yahoo.com

    2013-11-15

    Targeting of tumor metabolism is emerging as a novel therapeutic strategy against cancer. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been shown to exert a potent tumoricidal action against a variety of tumor cells. The main mode of its antineoplastic action implicates a shift of glycolysis to oxidative metabolism of glucose, leading to generation of cytotoxic reactive oxygen intermediates. However, the effect of DCA on tumor microenvironment, which in turn regulates tumor cell survival; remains speculative to a large extent. It is also unclear if DCA can exert any modulatory effect on the process of hematopoiesis, which is in a compromised state in tumor-bearing hosts undergoing chemotherapy. In view of these lacunas, the present study was undertaken to investigate the so far unexplored aspects with respect to the molecular mechanisms of DCA-dependent tumor growth retardation and chemosensitization. BALB/c mice were transplanted with Dalton's lymphoma (DL) cells, a T cell lymphoma of spontaneous origin, followed by administration of DCA with or without cisplatin. DCA-dependent tumor regression and chemosensitization to cisplatin was found to be associated with altered repertoire of key cell survival regulatory molecules, modulated glucose metabolism, accompanying reconstituted tumor microenvironment with respect to pH homeostasis, cytokine balance and alternatively activated TAM. Moreover, DCA administration also led to an alteration in the MDR phenotype of tumor cells and myelopoietic differentiation of macrophages. The findings of this study shed a new light with respect to some of the novel mechanisms underlying the antitumor action of DCA and thus may have immense clinical applications. - Highlights: • DCA modulates tumor progression and chemoresistance. • DCA alters molecules regulating cell survival, glucose metabolism and MDR. • DCA reconstitutes biophysical and cellular composition of tumor microenvironment.

  12. Antitumor and chemosensitizing action of dichloroacetate implicates modulation of tumor microenvironment: A role of reorganized glucose metabolism, cell survival regulation and macrophage differentiation

    International Nuclear Information System (INIS)

    Kumar, Ajay; Kant, Shiva; Singh, Sukh Mahendra

    2013-01-01

    Targeting of tumor metabolism is emerging as a novel therapeutic strategy against cancer. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been shown to exert a potent tumoricidal action against a variety of tumor cells. The main mode of its antineoplastic action implicates a shift of glycolysis to oxidative metabolism of glucose, leading to generation of cytotoxic reactive oxygen intermediates. However, the effect of DCA on tumor microenvironment, which in turn regulates tumor cell survival; remains speculative to a large extent. It is also unclear if DCA can exert any modulatory effect on the process of hematopoiesis, which is in a compromised state in tumor-bearing hosts undergoing chemotherapy. In view of these lacunas, the present study was undertaken to investigate the so far unexplored aspects with respect to the molecular mechanisms of DCA-dependent tumor growth retardation and chemosensitization. BALB/c mice were transplanted with Dalton's lymphoma (DL) cells, a T cell lymphoma of spontaneous origin, followed by administration of DCA with or without cisplatin. DCA-dependent tumor regression and chemosensitization to cisplatin was found to be associated with altered repertoire of key cell survival regulatory molecules, modulated glucose metabolism, accompanying reconstituted tumor microenvironment with respect to pH homeostasis, cytokine balance and alternatively activated TAM. Moreover, DCA administration also led to an alteration in the MDR phenotype of tumor cells and myelopoietic differentiation of macrophages. The findings of this study shed a new light with respect to some of the novel mechanisms underlying the antitumor action of DCA and thus may have immense clinical applications. - Highlights: • DCA modulates tumor progression and chemoresistance. • DCA alters molecules regulating cell survival, glucose metabolism and MDR. • DCA reconstitutes biophysical and cellular composition of tumor microenvironment.

  13. Cdc42 and Rab8a are critical for intestinal stem cell division, survival, and differentiation in mice

    DEFF Research Database (Denmark)

    Sakamori, Ryotaro; Das, Soumyashree; Yu, Shiyan

    2012-01-01

    The constant self renewal and differentiation of adult intestinal stem cells maintains a functional intestinal mucosa for a lifetime. However, the molecular mechanisms that regulate intestinal stem cell division and epithelial homeostasis are largely undefined. We report here that the small GTPases...... reminiscent of human microvillus inclusion disease (MVID), a devastating congenital intestinal disorder that results in severe nutrient deprivation. Further analysis revealed that Cdc42-deficient stem cells had cell division defects, reduced capacity for clonal expansion and differentiation into Paneth cells...... suggest that defects of the stem cell niche can cause MVID. This hypothesis represents a conceptual departure from the conventional view of this disease, which has focused on the affected enterocytes, and suggests stem cell-based approaches could be beneficial to infants with this often lethal condition....

  14. Stroke promotes survival of nearby transplanted neural stem cells by decreasing their activation of caspase 3 while not affecting their differentiation.

    Science.gov (United States)

    Kosi, Nina; Alić, Ivan; Salamon, Iva; Mitrečić, Dinko

    2018-02-14

    Although transplantation of stem cells improves recovery of the nervous tissue, little is known about the influence of different brain regions on transplanted cells. After we confirmed that cells with uniform differentiation potential can be generated in independent experiments, one million of neural stem cells isolated from B6.Cg-Tg(Thy1-YFP)16Jrs/J mouse embryos were transplanted into the brain 24 h after induction of stroke. The lateral ventricles, the corpus callosum and the striatum were tested. Two and four weeks after the transplantation, the cells transplanted in all three regions have been attracted to the ischemic core. The largest number of attracted cells has been observed after transplantation into the striatum. Their differentiation pattern and expression of neuroligin 1, SynCAM 1, postsynaptic density protein 95 and synapsin 1 followed the same pattern observed during in vitro cultivation and it did not differ among the tested regions. Differentiation pattern of the cells transplanted in the stroke-affected and healthy animals was the same. On the other hand, neural stem cells transplanted in the striatum of the animals affected by stroke exhibited significantly increased survival rates reaching 260 ± 19%, when compared to cells transplanted in their wild type controls. Surprisingly, improved survival two and four weeks after transplantation was not due to increased proliferation of the grafted cells and it was accompanied by decreased levels of activity of Casp3 (19.56 ± 3.1% in the stroke-affected vs. 30.14 ± 2.4% in healthy animals after four weeks). We assume that the decreased levels of Casp3 in cells transplanted near the ischemic region was linked to increased vasculogenesis, synaptogenesis, astrocytosis and axonogenesis detected in the host tissue affected by ischemia. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. NF-κB2 mutation targets survival, proliferation and differentiation pathways in the pathogenesis of plasma cell tumors

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    McCarthy Brian A

    2012-05-01

    Full Text Available Abstract Background Abnormal NF-κB2 activation has been implicated in the pathogenesis of multiple myeloma, a cancer of plasma cells. However, a causal role for aberrant NF-κB2 signaling in the development of plasma cell tumors has not been established. Also unclear is the molecular mechanism that drives the tumorigenic process. We investigated these questions by using a transgenic mouse model with lymphocyte-targeted expression of p80HT, a lymphoma-associated NF-κB2 mutant, and human multiple myeloma cell lines. Methods We conducted a detailed histopathological characterization of lymphomas developed in p80HT transgenic mice and microarray gene expression profiling of p80HT B cells with the goal of identifying genes that drive plasma cell tumor development. We further verified the significance of our findings in human multiple myeloma cell lines. Results Approximately 40% of p80HT mice showed elevated levels of monoclonal immunoglobulin (M-protein in the serum and developed plasma cell tumors. Some of these mice displayed key features of human multiple myeloma with accumulation of plasma cells in the bone marrow, osteolytic bone lesions and/or diffuse osteoporosis. Gene expression profiling of B cells from M-protein-positive p80HT mice revealed aberrant expression of genes known to be important in the pathogenesis of multiple myeloma, including cyclin D1, cyclin D2, Blimp1, survivin, IL-10 and IL-15. In vitro assays demonstrated a critical role of Stat3, a key downstream component of IL-10 signaling, in the survival of human multiple myeloma cells. Conclusions These findings provide a mouse model for human multiple myeloma with aberrant NF-κB2 activation and suggest a molecular mechanism for NF-κB2 signaling in the pathogenesis of plasma cell tumors by coordinated regulation of plasma cell generation, proliferation and survival.

  16. Epigenetics and sex-specific fitness: an experimental test using male-limited evolution in Drosophila melanogaster.

    Science.gov (United States)

    Abbott, Jessica K; Innocenti, Paolo; Chippindale, Adam K; Morrow, Edward H

    2013-01-01

    When males and females have different fitness optima for the same trait but share loci, intralocus sexual conflict is likely to occur. Epigenetic mechanisms such as genomic imprinting (in which expression is altered according to parent-of-origin) and sex-specific maternal effects have been suggested as ways by which this conflict can be resolved. However these ideas have not yet been empirically tested. We designed an experimental evolution protocol in Drosophila melanogaster that enabled us to look for epigenetic effects on the X-chromosome-a hotspot for sexually antagonistic loci. We used special compound-X females to enforce father-to-son transmission of the X-chromosome for many generations, and compared fitness and gene expression levels between Control males, males with a Control X-chromosome that had undergone one generation of father-son transmission, and males with an X-chromosome that had undergone many generations of father-son transmission. Fitness differences were dramatic, with experimentally-evolved males approximately 20% greater than controls, and with males inheriting a non-evolved X from their father about 20% lower than controls. These data are consistent with both strong intralocus sexual conflict and misimprinting of the X-chromosome under paternal inheritance. However, expression differences suggested that reduced fitness under paternal X inheritance was largely due to deleterious maternal effects. Our data confirm the sexually-antagonistic nature of Drosophila's X-chromosome and suggest that the response to male-limited X-chromosome evolution entails compensatory evolution for maternal effects, and perhaps modification of other epigenetic effects via coevolution of the sex chromosomes.

  17. Sex-specific effects of social networks on the prevalence, awareness, and control of hypertension among older Korean adults.

    Science.gov (United States)

    Baek, Jiwon; Hur, Nam Wook; Kim, Hyeon Chang; Youm, Yoosik

    2016-07-01

    Hypertension is a common chronic disease among older adults, and is associated with medical complications and mortality. This study aimed to examine the effects of social network characteristics on the prevalence, awareness, and control of hypertension among older adults. The Korean Social Life, Health, and Aging Project (KSHAP) interviewed 814 ≥ 60-year-old residents and their spouses from a rural township between December 2011 and March 2012 (response rate: 95%). We evaluated the data from 595 participants. Multivariate logistic regression models were used to assess the effects of network characteristics on hypertension. We observed strong sex-specific network effects on the prevalence, awareness, and control of hypertension. Among older women, network density was associated with hypertension awareness [odds ratio (OR): 2.63, 95% confidence interval (CI): 1.03-5.37] and control (OR: 1.72; 95% CI: 0.94-3.13). Among older men, large networks were associated with a lower prevalence of hypertension (OR: 0.75; 95% CI: 0.58-0.96). Compared to older women, older men with coarse networks exhibited better hypertension awareness (OR: 0.37; 95% CI: 0.14-0.95) and control (OR: 0.42; 95% CI: 0.19-0.91). Network size interacted with density for hypertension control (P = 0.051), with controlled hypertension being associated with large and course networks. A large network was associated with a lower risk for hypertension, and a coarse network was associated with hypertension awareness and control among older men. Older women with dense networks were most likely to exhibit hypertension awareness and control.

  18. Effects of prenatal stress on anxiety- and depressive-like behaviors are sex-specific in prepubertal rats.

    Science.gov (United States)

    Iturra-Mena, Ann Mary; Arriagada-Solimano, Marcia; Luttecke-Anders, Ariane; Dagnino-Subiabre, Alexies

    2018-05-17

    The fetal brain is highly susceptible to stress in late pregnancy, with lifelong effects of stress on physiology and behavior. The aim of this study was to determine the physiological and behavioral effects of prenatal stress during the prepubertal period of female and male rats. We subjected pregnant Sprague-Dawley rats to a restraint stress protocol from gestational day 14 until 21, a critical period for fetal brain susceptibility to stress effects. Male and female offspring were subsequently assessed at postnatal day 24 for anxiety- and depressive-like behaviors, and spontaneous social interaction. We also assessed maternal behaviors and two stress markers: basal vs. acute-evoked stress levels of serum corticosterone and body weight gain. Prenatal stress did not affect the maternal behavior, while both female and male offspring had higher body weight gain. On the other hand, lower levels of corticosterone after acute stress stimulation as well as anxiety- and depressive-like behaviors were only evident in stressed males compared to control males. These results suggest that prenatal stress induced sex-specific effects on the hypothalamus-pituitary-adrenal (HPA) axis activity and on behavior during prepuberty. The HPA axis of prenatally stressed male rats was less active compared to control males, as well as they were more anxious and experienced depressive-like behaviors. Our results can be useful to study the neurobiological basis of childhood depression at a pre-clinical level. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  19. Sex-specific effects of early life stress on social interaction and prefrontal cortex dendritic morphology in young rats.

    Science.gov (United States)

    Farrell, M R; Holland, F H; Shansky, R M; Brenhouse, H C

    2016-09-01

    Early life stress has been linked to depression, anxiety, and behavior disorders in adolescence and adulthood. The medial prefrontal cortex (mPFC) is implicated in stress-related psychopathology, is a target for stress hormones, and mediates social behavior. The present study investigated sex differences in early-life stress effects on juvenile social interaction and adolescent mPFC dendritic morphology in rats using a maternal separation (MS) paradigm. Half of the rat pups of each sex were separated from their mother for 4h a day between postnatal days 2 and 21, while the other half remained with their mother in the animal facilities and were exposed to minimal handling. At postnatal day 25 (P25; juvenility), rats underwent a social interaction test with an age and sex matched conspecific. Distance from conspecific, approach and avoidance behaviors, nose-to-nose contacts, and general locomotion were measured. Rats were euthanized at postnatal day 40 (P40; adolescence), and randomly selected infralimbic pyramidal neurons were filled with Lucifer yellow using iontophoretic microinjections, imaged in 3D, and then analyzed for dendritic arborization, spine density, and spine morphology. Early-life stress increased the latency to make nose-to-nose contact at P25 in females but not males. At P40, early-life stress increased infralimbic apical dendritic branch number and length and decreased thin spine density in stressed female rats. These results indicate that MS during the postnatal period influenced juvenile social behavior and mPFC dendritic arborization in a sex-specific manner. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Sex-Specific Consequences of Neonatal Stress on Cardio-Respiratory Inhibition Following Laryngeal Stimulation in Rat Pups

    Science.gov (United States)

    Baldy, Cécile; Chamberland, Simon

    2017-01-01

    Abstract The presence of liquid near the larynx of immature mammals triggers prolonged apneas with significant O2 desaturations and bradycardias. When excessive, this reflex (the laryngeal chemoreflex; LCR) can be fatal. Our understanding of the origins of abnormal LCR are limited; however, perinatal stress and male sex are risk factors for cardio-respiratory failure in infants. Because exposure to stress during early life has deleterious and sex-specific consequences on brain development it is plausible that respiratory reflexes are vulnerable to neuroendocrine dysfunction. To address this issue, we tested the hypothesis that neonatal maternal separation (NMS) is sufficient to exacerbate LCR-induced cardio-respiratory inhibition in anesthetized rat pups. Stressed pups were separated from their mother 3 h/d from postnatal days 3 to 12. At P14–P15, pups were instrumented to monitor breathing, O2 saturation (Spo2), and heart rate. The LCR was activated by water injections near the larynx (10 µl). LCR-induced apneas were longer in stressed pups than controls; O2 desaturations and bradycardias were more profound, especially in males. NMS increased the frequency and amplitude of spontaneous EPSCs (sEPSCs) in the dorsal motor nucleus of the vagus (DMNV) of males but not females. The positive relationship between corticosterone and testosterone observed in stressed pups (males only) suggests that disruption of neuroendocrine function by stress is key to sex-based differences in abnormal LCR. Because testosterone application onto medullary slices augments EPSC amplitude only in males, we propose that testosterone-mediated enhancement of synaptic connectivity within the DMNV contributes to the male bias in cardio-respiratory inhibition following LCR activation in stressed pups. PMID:29308430

  1. KCNE1 D85N polymorphism — a sex-specific modifier in type 1 long QT syndrome?

    Directory of Open Access Journals (Sweden)

    Marjamaa Annukka

    2011-01-01

    Full Text Available Abstract Background Long QT syndrome (LQTS is an inherited ion channel disorder manifesting with prolongation of the cardiac repolarization phase and severe ventricular arrhythmias. The common KCNE1 D85N potassium channel variant prolongs QT interval by inhibiting IKs (KCNQ1 and IKr (KCNH2 currents and is therefore a suitable candidate for a modifier gene in LQTS. Methods We studied the effect of D85N on age-, sex-, and heart rate-adjusted QT-interval duration by linear regression in LQTS patients carrying the Finnish founder mutations KCNQ1 G589D (n = 492, KCNQ1 IVS7-2A>G (n = 66, KCNH2 L552S (n = 73, and KCNH2 R176W (n = 88. We also investigated the association between D85N and clinical variables reflecting the severity of the disease. Results D85N was associated with a QT prolongation by 26 ms (SE 8.6, p = 0.003 in males with KCNQ1 G589D (n = 213, but not in females with G589D (n = 279. In linear regression, the interaction between D85N genotype and sex was significant (p = 0.028. Within the KCNQ1 G589D mutation group, KCNE1 D85N carriers were more often probands of the family (p = 0.042 and were more likely to use beta blocker medication (p = 0.010 than non-carriers. The number of D85N carriers in other founder mutation groups was too small to assess its effects. Conclusions We propose that KCNE1 D85N is a sex-specific QT-interval modifier in type 1 LQTS and may also associate with increased severity of disease. Our data warrant additional studies on the role of KCNE1 D85N in other genetically homogeneous groups of LQTS patients.

  2. Sex-specific patterns in cortical and trabecular bone microstructure in the Kirsten Skeletal Collection, South Africa.

    Science.gov (United States)

    Beresheim, Amy C; Pfeiffer, Susan K; Grynpas, Marc D; Alblas, Amanda

    2018-02-07

    The purpose of this study was to provide bone histomorphometric reference data for South Africans of the Western Cape who likely dealt with health issues under the apartheid regime. The 206 adult individuals ( n female = 75, n male = 131, mean = 47.9 ± 15.8 years) from the Kirsten Skeletal Collection, U. Stellenbosch, lived in the Cape Town metropole from the late 1960s to the mid-1990s. To study age-related changes in cortical and trabecular bone microstructure, photomontages of mid-thoracic rib cross-sections were quantitatively examined. Variables include relative cortical area (Rt.Ct.Ar), osteon population density (OPD), osteon area (On.Ar), bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular spacing (Tb.Sp). All cortical variables demonstrated significant relationships with age in both sexes, with women showing stronger overall age associations. Peak bone mass was compromised in some men, possibly reflecting poor nutritional quality and/or substance abuse issues throughout adolescence and early adulthood. In women, greater predicted decrements in On.Ar and Rt.Ct.Ar suggest a structural disadvantage with age, consistent with postmenopausal bone loss. Age-related patterns in trabecular bone microarchitecture are variable and difficult to explain. Except for Tb.Th, there are no statistically significant relationships with age in women. Men demonstrate significant negative correlations between BV/TV, Tb.N, and age, and a significant positive correlation between Tb.Sp and age. This research highlights sex-specific differences in patterns of age-related bone loss, and provides context for discussion of contemporary South African bone health. While the study sample demonstrates indicators of poor bone quality, osteoporosis research continues to be under-prioritized in South Africa. © 2018 Wiley Periodicals, Inc.

  3. Hepatic overexpression of steroid sulfatase ameliorates mouse models of obesity and type 2 diabetes through sex-specific mechanisms.

    Science.gov (United States)

    Jiang, Mengxi; He, Jinhan; Kucera, Heidi; Gaikwad, Nilesh W; Zhang, Bin; Xu, Meishu; O'Doherty, Robert M; Selcer, Kyle W; Xie, Wen

    2014-03-21

    The steroid sulfatase (STS)-mediated desulfation is a critical metabolic mechanism that regulates the chemical and functional homeostasis of endogenous and exogenous molecules. In this report, we first showed that the liver expression of Sts was induced in both the high fat diet (HFD) and ob/ob models of obesity and type 2 diabetes and during the fed to fasting transition. In defining the functional relevance of STS induction in metabolic disease, we showed that overexpression of STS in the liver of transgenic mice alleviated HFD and ob/ob models of obesity and type 2 diabetes, including reduced body weight, improved insulin sensitivity, and decreased hepatic steatosis and inflammation. Interestingly, STS exerted its metabolic benefit through sex-specific mechanisms. In female mice, STS may have increased hepatic estrogen activity by converting biologically inactive estrogen sulfates to active estrogens and consequently improved the metabolic functions, whereas ovariectomy abolished this protective effect. In contrast, the metabolic benefit of STS in males may have been accounted for by the male-specific decrease of inflammation in white adipose tissue and skeletal muscle as well as a pattern of skeletal muscle gene expression that favors energy expenditure. The metabolic benefit in male STS transgenic mice was retained after castration. Treatment with the STS substrate estrone sulfate also improved metabolic functions in both the HFD and ob/ob models. Our results have uncovered a novel function of STS in energy metabolism and type 2 diabetes. Liver-specific STS induction or estrogen/estrogen sulfate delivery may represent a novel approach to manage metabolic syndrome.

  4. Effect of childhood trauma on adult depression and neuroendocrine function: sex-specific moderation by CRH receptor 1 gene

    Directory of Open Access Journals (Sweden)

    Christine Heim

    2009-11-01

    Full Text Available Variations of the corticotropin-releasing hormone receptor 1 (CRHR1 gene appear to moderate the development of depression after childhood trauma. Depression more frequently affects women than men. We examined sex differences in the effects of the CRHR1 gene on the relationship between childhood trauma and adult depression. Methods: We recruited 1,063 subjects from the waiting rooms of a public urban hospital. Childhood trauma exposure and symptoms of depression were assessed using dimensional rating scales. Subjects were genotyped for rs110402 within the CRHR1 gene. An independent sample of 78 subjects underwent clinical assessment, genotyping, and a dexamethasone/CRH test. The age range at recruitment was 18-77 years and 18-45, for the two studies respectively. Results: In the hospital sample, the protective effect of the rs110402 A-allele against developing depression after childhood trauma was observed in men (N=424, but not in women (N=635. In the second sample, the rs110402 A-allele was associated with decreased cortisol response in the dexamethasone/CRH test only in men. In A-allele carriers with childhood trauma exposure women exhibited increased cortisol response compared men; there were no sex differences in A-allele carriers without trauma exposure. This effect may, however, not be related to gender-differences per se, but to differences in the type of experienced abuse between men and women. CRHR x environment interactions in the hospital sample were observed with exposure to physical, but not sexual or emotional abuse. Physical abuse was the most common type of abuse in men in this cohort, while sexual abuse was most commonly suffered by women. Conclusion: Our results suggest that the CRHR1 gene may only moderate the effects of specific types of childhood trauma on depression. Gender differences in environmental exposures could thus be reflected in sex-specific CRHR1 x child abuse interactions.

  5. Effect of Childhood Trauma on Adult Depression and Neuroendocrine Function: Sex-Specific Moderation by CRH Receptor 1 Gene.

    Science.gov (United States)

    Heim, Christine; Bradley, Bekh; Mletzko, Tanja C; Deveau, Todd C; Musselman, Dominique L; Nemeroff, Charles B; Ressler, Kerry J; Binder, Elisabeth B

    2009-01-01

    Variations of the corticotropin-releasing hormone receptor 1 (CRHR1) gene appear to moderate the development of depression after childhood trauma. Depression more frequently affects women than men. We examined sex differences in the effects of the CRHR1 gene on the relationship between childhood trauma and adult depression. We recruited 1,063 subjects from the waiting rooms of a public urban hospital. Childhood trauma exposure and symptoms of depression were assessed using dimensional rating scales. Subjects were genotyped for rs110402 within the CRHR1 gene. An independent sample of 78 subjects underwent clinical assessment, genotyping, and a dexamethasone/CRH test. The age range at recruitment was 18-77 years and 18-45, for the two studies respectively. In the hospital sample, the protective effect of the rs110402 A-allele against developing depression after childhood trauma was observed in men (N = 424), but not in women (N = 635). In the second sample, the rs110402 A-allele was associated with decreased cortisol response in the dexamethasone/CRH test only in men. In A-allele carriers with childhood trauma exposure women exhibited increased cortisol response compared men; there were no sex differences in A-allele carriers without trauma exposure. This effect may, however, not be related to gender differences per se, but to differences in the type of experienced abuse between men and women. CRHR x environment interactions in the hospital sample were observed with exposure to physical, but not sexual or emotional abuse. Physical abuse was the most common type of abuse in men in this cohort, while sexual abuse was most commonly suffered by women. Our results suggest that the CRHR1 gene may only moderate the effects of specific types of childhood trauma on depression. Gender differences in environmental exposures could thus be reflected in sex-specific CRHR1 x child abuse interactions.

  6. Chronic metals ingestion by prairie voles produces sex-specific deficits in social behavior: an animal model of autism.

    Science.gov (United States)

    Curtis, J Thomas; Hood, Amber N; Chen, Yue; Cobb, George P; Wallace, David R

    2010-11-12

    We examined the effects of chronic metals ingestion on social behavior in the normally highly social prairie vole to test the hypothesis that metals may interact with central dopamine systems to produce the social withdrawal characteristic of autism. Relative to water-treated controls, 10 weeks of chronic ingestion of either Hg(++) or Cd(++) via drinking water significantly reduced social contact by male voles when they were given a choice between isolation or contact with an unfamiliar same-sex conspecific. The effects of metals ingestion were specific to males: no effects of metals exposure were seen in females. Metals ingestion did not alter behavior of males allowed to choose between isolation or their familiar cage-mates, rather than strangers. We also examined the possibility that metals ingestion affects central dopamine functioning by testing the voles' locomotor responses to peripheral administration of amphetamine. As with the social behavior, we found a sex-specific effect of metals on amphetamine responses. Males that consumed Hg(++) did not increase their locomotor activity in response to amphetamine, whereas similarly treated females and males that ingested only water significantly increased their locomotor activities. Thus, an ecologically relevant stimulus, metals ingestion, produced two of the hallmark characteristics of autism - social avoidance and a male-oriented bias. These results suggest that metals exposure may contribute to the development of autism, possibly by interacting with central dopamine function, and support the use of prairie voles as a model organism in which to study autism. (c) 2010 Elsevier B.V. All rights reserved.

  7. Sex-specific antidepressant effects of dietary creatine with and without sub-acute fluoxetine in rats

    Science.gov (United States)

    Allen, Patricia J.; D'Anci, Kristen E.; Kanarek, Robin B.; Renshaw, Perry F.

    2013-01-01

    The potential role of metabolic impairments in the pathophysiology of depression is motivating researchers to evaluate the treatment efficacy of creatine, a naturally occurring energetic and neuroprotective compound found in brain and muscle tissues. Growing evidence is demonstrating the benefit of oral creatine supplements for reducing depressive symptoms in humans and animals. A novel question is whether dietary creatine, when combined with antidepressant drug therapy, would be more effective than either compound alone. To answer this question, four studies were conducted to investigate the behavioral effects of combined creatine and low-dose fluoxetine treatment using the forced swim test in male and female rats. Sprague-Dawley rats were fed powdered rodent chow supplemented with 0%, 2% or 4% w/w creatine monohydrate for 5 weeks. Rats were injected with fluoxetine (5.0 or 10.0 mg/kg) or saline according to a sub-acute dosing schedule. Female rats maintained on a 4% creatine diet displayed antidepressant-like effects compared to non-supplemented females prior to fluoxetine treatment. In contrast, creatine did not alter behavior reliably in males. Following drug treatment and a second forced swim trial, the antidepressant-like profile of creatine remained significant only in females co-administered 5.0 mg/kg fluoxetine. Moreover, in females only, supplementation with 4% creatine produced a more robust antidepressant-like behavioral profile compared to either dose of fluoxetine alone. Estrous cycle data indicated that ovarian hormones influenced the antidepressant-like effects of creatine. Addressing the issue of sex differences in response to treatment may affect our understanding of creatine, its relationship with depressive behavior, and may lead to sex-specific therapeutic strategies. PMID:22429992

  8. Sex-specific differences in mitochondria biogenesis, morphology, respiratory function, and ROS homeostasis in young mouse heart and brain.

    Science.gov (United States)

    Khalifa, Abdel Rahman M; Abdel-Rahman, Engy A; Mahmoud, Ali M; Ali, Mohamed H; Noureldin, Maha; Saber, Saber H; Mohsen, Mahmoud; Ali, Sameh S

    2017-03-01

    Sex-specific differences in mitochondrial function and free radical homeostasis are reported in the context of aging but not well-established in pathogeneses occurring early in life. Here, we examine if sex disparity in mitochondria function, morphology, and redox status starts early and hence can be implicated in sexual dimorphism in cardiac as well as neurological disorders prevalent at young age. Although mitochondrial activity in the heart did not significantly vary between sexes, female brain exhibited enhanced respiration and higher reserve capacity. This was associated with lower H 2 O 2 production in female cardiac and brain tissues. Using transmission electron microscopy, we found that the number of female cardiac mitochondria is moderately greater (117 ± 3%, P  = 0.049, N  = 4) than male's, which increased significantly for cortical mitochondria (134 ± 4%, P  = 0.001, N  = 4). However, male's cardiac mitochondria exhibited fragmented, circular, and smaller mitochondria relative to female's mitochondria, while no morphologic sex-dependent differences were observed in cortical mitochondria. No sex differences were detected in Nox2 and Nox4 proteins or O 2 -consuming/H 2 O 2 -producing activities in brain homogenate or synaptosomes. However, a strong trend of increased EPR-detected NOX superoxide in male synaptosomes hinted at higher superoxide dismutase activity in female brains, which was confirmed by two independent protocols. We also provide direct evidence that respiring mitochondria generally produce an order-of-magnitude lower reactive oxygen species (ROS) proportions than currently estimated. Our results indicate that sex differences in mitochondrial biogenesis, bioenergetics, and morphology may start at young age and that sex-dependent SOD capacity may be responsible for differences in ROS homeostasis in heart and brain. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological

  9. Offspring risk of obesity in childhood, adolescence and adulthood in relation to gestational diabetes mellitus: a sex-specific association.

    Science.gov (United States)

    Li, Shanshan; Zhu, Yeyi; Yeung, Edwina; Chavarro, Jorge E; Yuan, Changzheng; Field, Alison E; Missmer, Stacey A; Mills, James L; Hu, Frank B; Zhang, Cuilin

    2017-10-01

    Animal data suggest sexually dimorphic programming of obesity in response to altered intrauterine environment, but the longitudinal impact of gestational diabetes mellitus (GDM) on sex-specific risk of offspring obesity in humans is unclear. We conducted a prospective analysis of 15 009 US individuals (7946 female and 7063 male) from the Growing-Up Today Study, who were followed from 1996 (ages 9-14 years) through 2010. Height and weight from validated questionnaires were used to derive body mass index (BMI) at different ages. Obesity during childhood (Obesity Task Force and the World Health Organization criteria. GDM exposure was identified through self-reported questionnaires from mothers. Relative risks were estimated using multivariable log-binomial regression models with generalized estimating equations accounting for clustering within the same family. Male offspring born from pregnancies complicated by GDM had higher BMI compared with non-GDM offspring and had increased risk of obesity; the adjusted relative risk [RR, 95% confidence interval (CI)] was 1.47 (1.11-1.95) for all age groups, 1.59 (1.05-2.41) for late childhood, 1.48 (1.06-2.06) for adolescence and 1.39 (1.00-1.94) for early adulthood. No significant association between obesity and maternal GDM was observed among female participants (RR = 0.97, 95% CI: 0.71-1.33). The association of GDM with offspring obesity from late childhood through early adulthood may differ by sex; a significant association was observed among male but not female offspring. Published by Oxford University Press on behalf of the International Epidemiological Association 2017. This work is written by US Government employees and is in the public domain in the United States.

  10. Involvement of the oxytocin system in the bed nucleus of the stria terminalis in the sex-specific regulation of social recognition

    Science.gov (United States)

    Dumais, Kelly M.; Alonso, Andrea G.; Immormino, Marisa A.; Bredewold, Remco; Veenema, Alexa H.

    2015-01-01

    Sex differences in the oxytocin (OT) system in the brain may explain why OT often regulates social behaviors in sex-specific ways. However, a link between sex differences in the OT system and sex-specific regulation of social behavior has not been tested. Here, we determined whether sex differences in the OT receptor (OTR) or in OT release in the posterior bed nucleus of the stria terminalis (pBNST) mediates sex-specific regulation of social recognition in rats. We recently showed that, compared to female rats, male rats have a three-fold higher OTR binding density in the pBNST, a sexually dimorphic area implicated in the regulation of social behaviors. We now demonstrate that OTR antagonist (5 ng/0.5 μl/side) administration into the pBNST impairs social recognition in both sexes, while OT (100 pg/0.5 μl/side) administration into the pBNST prolongs the duration of social recognition in males only. These effects seem specific to social recognition, as neither treatment altered total social investigation time in either sex. Moreover, baseline OT release in the pBNST, as measured with in vivo microdialysis, did not differ between the sexes. However, males showed higher OT release in the pBNST during social recognition compared to females. These findings suggest a sex-specific role of the OT system in the pBNST in the regulation of social recognition. PMID:26630388

  11. Woman's Profession and Female Role--The Development of Sex-specific Structures of Education and of the Labor Market before the First World War.

    Science.gov (United States)

    Klinger, Vera

    1989-01-01

    Examines the intrusion of female employees into the traditionally male domain of office work from 1860 to 1914. Shows that sex-specific segregation was supported by a lack of training facilities for girls and by fact that these facilities supported the dominant sex-role structure. Focuses on the development of vocational schools for girls.…

  12. Global, regional, and national age–sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013

    NARCIS (Netherlands)

    Geleijnse, J.M.

    2015-01-01

    Background

    Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188

  13. Whole blood gene expression in adolescent chronic fatigue syndrome: an exploratory cross-sectional study suggesting altered B cell differentiation and survival.

    Science.gov (United States)

    Nguyen, Chinh Bkrong; Alsøe, Lene; Lindvall, Jessica M; Sulheim, Dag; Fagermoen, Even; Winger, Anette; Kaarbø, Mari; Nilsen, Hilde; Wyller, Vegard Bruun

    2017-05-11

    Chronic fatigue syndrome (CFS) is a prevalent and disabling condition affecting adolescents. The pathophysiology is poorly understood, but immune alterations might be an important component. This study compared whole blood gene expression in adolescent CFS patients and healthy controls, and explored associations between gene expression and neuroendocrine markers, immune markers and clinical markers within the CFS group. CFS patients (12-18 years old) were recruited nation-wide to a single referral center as part of the NorCAPITAL project. A broad case definition of CFS was applied, requiring 3 months of unexplained, disabling chronic/relapsing fatigue of new onset, whereas no accompanying symptoms were necessary. Healthy controls having comparable distribution of gender and age were recruited from local schools. Whole blood samples were subjected to RNA sequencing. Immune markers were blood leukocyte counts, plasma cytokines, serum C-reactive protein and immunoglobulins. Neuroendocrine markers encompassed plasma and urine levels of catecholamines and cortisol, as well as heart rate variability indices. Clinical markers consisted of questionnaire scores for symptoms of post-exertional malaise, inflammation, fatigue, depression and trait anxiety, as well as activity recordings. A total of 29 CFS patients and 18 healthy controls were included. We identified 176 genes as differentially expressed in patients compared to controls, adjusting for age and gender factors. Gene set enrichment analyses suggested impairment of B cell differentiation and survival, as well as enhancement of innate antiviral responses and inflammation in the CFS group. A pattern of co-expression could be identified, and this pattern, as well as single gene transcripts, was significantly associated with indices of autonomic nervous activity, plasma cortisol, and blood monocyte and eosinophil counts. Also, an association with symptoms of post-exertional malaise was demonstrated. Adolescent CFS is

  14. Uhrf1 Controls iNKT Cell Survival and Differentiation through the Akt-mTOR Axis

    Directory of Open Access Journals (Sweden)

    Yu Cui

    2016-04-01

    Full Text Available Uhrf1 (also known as Np95 is a regulator of DNA methylation and histone ubiquitination and plays an important role in embryogenesis and tumorigenesis. Here, we report that Uhrf1 is essential for invariant natural killer T (iNKT cell development. We found that Uhrf1 was significantly upregulated in stage 1 iNKT cells. Targeted disruption of Uhrf1 resulted in stage 1-specific transition defects as observed by not only increased apoptosis, but also aberrant effector differentiation, which eventually led to the impaired generation of iNKT cells in Uhrf1-deficient mice. Notably, Uhrf1 deficiency resulted in attenuated activation of Akt-mTOR signaling in stage 1 iNKT cells and overexpression of active Akt rescued iNKT cell developmental defects. Collectively, our results suggest that Uhrf1 regulation of the Akt-mTOR signaling pathway is required for iNKT cell development.

  15. No survival difference after successful {sup 131}I ablation between patients with initially low-risk and high-risk differentiated thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Verburg, Frederik Anton [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); University Medical Center Utrecht, Department of Radiology and Nuclear Medicine, Utrecht (Netherlands); Stokkel, Marcel P.M.; Verkooijen, Robbert B.T. [Leiden University Medical Center, Department of Radiology, Division of Nuclear Medicine, Leiden (Netherlands); Dueren, Christian; Reiners, Christoph [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Maeder, Uwe [University of Wuerzburg, Comprehensive Cancer Center, Wuerzburg (Germany); Isselt, Johannes W. van [University Medical Center Utrecht, Department of Radiology and Nuclear Medicine, Utrecht (Netherlands); Marlowe, Robert J. [Spencer-Fontayne Corporation, Jersey City, NJ (United States); Smit, Johannes W. [Leiden University Medical Center, Department of Endocrinology, Leiden (Netherlands); Luster, Markus [University of Ulm, Department of Nuclear Medicine, Ulm (Germany)

    2010-02-15

    To compare disease-specific survival and recurrence-free survival (RFS) after successful {sup 131}I ablation in patients with differentiated thyroid carcinoma (DTC) between those defined before ablation as low-risk and those defined as high-risk according to the European Thyroid Association 2006 consensus statement. Retrospective data from three university hospitals were pooled. Of 2009 consecutive patients receiving ablation, 509 were identified as successfully ablated based on both undetectable stimulated serum thyroglobulin in the absence of antithyroglobulin antibodies and a negative diagnostic whole-body scan in a follow-up examination conducted 8.1{+-}4.6 months after ablation. Of these 509 patients, 169 were defined as high-risk. After a mean follow-up of 81{+-}64 months (range 4-306 months), only three patients had died of DTC, rendering assessment of disease-specific survival differences impossible. Of the 509 patients, 12 (2.4%) developed a recurrence a mean 35 months (range 12-59 months) after ablation. RFS for the duration of follow-up was 96.6% according to the Kaplan-Meier method. RFS did not differ between high-risk and low-risk patients (p=0.68). RFS differed slightly but significantly between those with papillary and those with follicular thyroid carcinoma (p=0.03) and between those aged {<=}45 years those aged >45 years at diagnosis (p=0.018). After (near) total thyroidectomy and successful {sup 131}I ablation, RFS does not differ between patients classified as high-risk and those classified as low-risk based on TNM stage at diagnosis. Consequently, the follow-up protocol should be determined on the basis of the result of initial treatment rather than on the initial tumour classification. (orig.)

  16. Cell survival and differentiation with nanocrystalline glass-like carbon using substantia nigra dopaminergic cells derived from transgenic mouse embryos.

    Directory of Open Access Journals (Sweden)

    Noela Rodriguez-Losada

    Full Text Available Regenerative medicine requires, in many cases, physical supports to facilitate appropriate cellular architecture, cell polarization and the improvement of the correct differentiation processes of embryonic stem cells, induced pluripotent cells or adult cells. Because the interest in carbon nanomaterials has grown within the last decade in light of a wide variety of applications, the aim of this study was to test and evaluate the suitability and cytocompatibility of a particular nanometer-thin nanocrystalline glass-like carbon film (NGLC composed of curved graphene flakes joined by an amorphous carbon matrix. This material is a disordered structure with high transparency and electrical conductivity. For this purpose, we used a cell line (SN4741 from substantia nigra dopaminergic cells derived from transgenic mouse embryos. Cells were cultured either in a powder of increasing concentrations of NGLC microflakes (82±37μm in the medium or on top of nanometer-thin films bathed in the same culture medium. The metabolism activity of SN4741 cells in presence of NGLC was assessed using methylthiazolyldiphenyl-tetrazolium (MTT and apoptosis/necrosis flow cytometry assay respectively. Growth and proliferation as well as senescence were demonstrated by western blot (WB of proliferating cell nuclear antigen (PCNA, monoclonal phosphorylate Histone 3 (serine 10 (PH3 and SMP30 marker. Specific dopaminergic differentiation was confirmed by the WB analysis of tyrosine hydroxylase (TH. Cell maturation and neural capability were characterized using specific markers (SYP: synaptophysin and GIRK2: G-protein-regulated inward-rectifier potassium channel 2 protein via immunofluorescence and coexistence measurements. The results demonstrated cell positive biocompatibility with different concentrations of NGLC. The cells underwent a process of adaptation of SN4741 cells to NGLC where their metabolism decreases. This process is related to a decrease of PH3 expression and

  17. 24S-hydroxycholesterol and 25-hydroxycholesterol differentially impact hippocampal neuronal survival following oxygen-glucose deprivation.

    Directory of Open Access Journals (Sweden)

    Min-Yu Sun

    Full Text Available N-methyl-D-aspartate receptors (NMDARs, a major subtype of glutamate receptor mediating excitatory transmission throughout the CNS, participate in ischemia-induced neuronal death. Unfortunately, undesired side effects have limited the strategy of inhibiting/blocking NMDARs as therapy. Targeting endogenous positive allosteric modulators of NMDAR function may offer a strategy with fewer downsides. Here, we explored whether 24S-hydroxycholesterol (24S-HC, an endogenous positive NMDAR modulator characterized recently by our group, participates in NMDAR-mediated excitotoxicity following oxygen-glucose deprivation (OGD in primary neuron cultures. 24S-HC is the major brain cholesterol metabolite produced exclusively in neurons near sites of glutamate transmission. By selectively potentiating NMDAR current, 24S-HC may participate in NMDAR-mediated excitotoxicity following energy failure, thus impacting recovery after stroke. In support of this hypothesis, our findings indicate that exogenous application of 24S-HC exacerbates NMDAR-dependent excitotoxicity in primary neuron culture following OGD, an ischemic-like challenge. Similarly, enhancement of endogenous 24S-HC synthesis reduced survival rate. On the other hand, reducing endogenous 24S-HC synthesis alleviated OGD-induced cell death. We found that 25-HC, another oxysterol that antagonizes 24S-HC potentiation, partially rescued OGD-mediated cell death in the presence or absence of exogenous 24S-HC application, and 25-HC exhibited NMDAR-dependent/24S-HC-dependent neuroprotection, as well as NMDAR-independent neuroprotection in rat tissue but not mouse tissue. Our findings suggest that both endogenous and exogenous 24S-HC exacerbate OGD-induced damage via NMDAR activation, while 25-HC exhibits species dependent neuroprotection through both NMDAR-dependent and independent mechanisms.

  18. Social chromosome variants differentially affect queen determination and the survival of workers in the fire ant Solenopsis invicta.

    Science.gov (United States)

    Buechel, Séverine D; Wurm, Yanick; Keller, Laurent

    2014-10-01

    Intraspecific variation in social organization is common, yet the underlying causes are rarely known. An exception is the fire ant Solenopsis invicta in which the existence of two distinct forms of social colony organization is under the control of the two variants of a pair of social chromosomes, SB and Sb. Colonies containing exclusively SB/SB workers accept only one single queen and she must be SB/SB. By contrast, when colonies contain more than 10% of SB/Sb workers, they accept several queens but only SB/Sb queens. The variants of the social chromosome are associated with several additional important phenotypic differences, including the size, fecundity and dispersal strategies of queens, aggressiveness of workers, and sperm count in males. However, little is known about whether social chromosome variants affect fitness in other life stages. Here, we perform experiments to determine whether differential selection occurs during development and in adult workers. We find evidence that the Sb variant of the social chromosome increases the likelihood of female brood to develop into queens and that adult SB/Sb workers, the workers that cull SB/SB queens, are overrepresented in comparison to SB/SB workers. This demonstrates that supergenes such as the social chromosome can have complex effects on phenotypes at various stages of development. © 2014 John Wiley & Sons Ltd.

  19. Inhibition of connective tissue growth factor (CTGF/CCN2) expression decreases the survival and myogenic differentiation of human rhabdomyosarcoma cells.

    Science.gov (United States)

    Croci, Stefania; Landuzzi, Lorena; Astolfi, Annalisa; Nicoletti, Giordano; Rosolen, Angelo; Sartori, Francesca; Follo, Matilde Y; Oliver, Noelynn; De Giovanni, Carla; Nanni, Patrizia; Lollini, Pier-Luigi

    2004-03-01

    Connective tissue growth factor (CTGF/CCN2), a cysteine-rich protein of the CCN (Cyr61, CTGF, Nov) family of genes, emerged from a microarray screen of genes expressed by human rhabdomyosarcoma cells. Rhabdomyosarcoma is a soft tissue sarcoma of childhood deriving from skeletal muscle cells. In this study, we investigated the role of CTGF in rhabdomyosarcoma. Human rhabdomyosarcoma cells of the embryonal (RD/12, RD/18, CCA) and the alveolar histotype (RMZ-RC2, SJ-RH4, SJ-RH30), rhabdomyosarcoma tumor specimens, and normal skeletal muscle cells expressed CTGF. To determine the function of CTGF, we treated rhabdomyosarcoma cells with a CTGF antisense oligonucleotide or with a CTGF small interfering RNA (siRNA). Both treatments inhibited rhabdomyosarcoma cell growth, suggesting the existence of a new autocrine loop based on CTGF. CTGF antisense oligonucleotide-mediated growth inhibition was specifically due to a significant increase in apoptosis, whereas cell proliferation was unchanged. CTGF antisense oligonucleotide induced a strong decrease in the level of myogenic differentiation of rhabdomyosarcoma cells, whereas the addition of recombinant CTGF significantly increased the proportion of myosin-positive cells. CTGF emerges as a survival and differentiation factor and could be a new therapeutic target in human rhabdomyosarcoma.

  20. Sex-specific differences in corticosterone secretion, behavioral phenotypes and expression of TrkB.T1 and TrkB.FL receptor isoforms: Impact of systemic TrkB inhibition and combinatory stress exposure in adolescence.

    Science.gov (United States)

    Azogu, Idu; Liang, Jacky; Plamondon, Helene

    2018-05-09

    Stress exposure has been implicated in the development of mood disorders, although little is known about the lasting effects of repeated stress during the adolescent period on sex-specific differences in endocrine and plasticity-signaling responses in adulthood. Using a 10-day combinatory stress paradigm (postnatal day (PND) 26 to 35), we examined sex-specific impact of adolescent stress and inhibition of tyrosine-related kinase B (TrkB) receptor (ANA-12; 0.5 mg/kg, i.p.) on 1) adolescent blood corticosterone levels, 2) adult locomotion and anxiety-like behavior, and 3) region-specific differences in endogenous TrkB full-length (TrkB.FL) and truncated (TrkB.T1) receptor isoforms. Blood collected on days 1, 5 and 10 revealed elevated basal and stress-induced CORT secretion in females compared to males, while ANA-12 attenuated CORT elevations post stress in both sexes. As adults, all females exhibited higher locomotor and exploratory activity than males in the open field test and elevated plus maze, and differences were comparable in the forced swim within stress-naïve and stress groups. Biochemically, vehicle-treated males showed elevated TrkB.T1 and TrkB.FL compared to vehicle-treated females in the PFC, hippocampus and NAc, and levels were consistently attenuated by ANA-12 treatment in non-stress males. With regards to stress exposure, expression of both isoforms was strongly down-regulated in the NAc of males only and was associated with increased TrkB.T1 in the PFC. ANA-12 enhanced expression in females, independent of stress exposure, compared to vehicle-treated counterparts, expression being increased for TrkB.T1 versus TrkB.FL and magnitude of the changes being region-specific. In contrast, ANA-12 effects in stressed males were restricted to inhibition of both isoforms in the hippocampus. Together, our findings support that TrkB activation, contingent on stress exposure, differentially affects TrkB isoform regulation during adulthood. Sex-specific

  1. Sex-specific modulation of juvenile social play behavior by vasopressin and oxytocin depends on social context

    Science.gov (United States)

    Bredewold, Remco; Smith, Caroline J. W.; Dumais, Kelly M.; Veenema, Alexa H.

    2014-01-01

    We recently demonstrated that vasopressin (AVP) in the lateral septum modulates social play behavior differently in male and female juvenile rats. However, the extent to which different social contexts (i.e., exposure to an unfamiliar play partner in different environments) affect the regulation of social play remains largely unknown. Given that AVP and the closely related neuropeptide oxytocin (OXT) modulate social behavior as well as anxiety-like behavior, we hypothesized that these neuropeptides may regulate social play behavior differently in novel (novel cage) as opposed to familiar (home cage) social environments. Administration of the specific AVP V1a receptor (V1aR) antagonist (CH2)5Tyr(Me2)AVP into the lateral septum enhanced home cage social play behavior in males but reduced it in females, confirming our previous findings. These effects were context-specific because V1aR blockade did not alter novel cage social play behavior in either sex. Furthermore, social play in females was reduced by AVP in the novel cage and by OXT in the home cage. Additionally, females administered the specific OXT receptor antagonist desGly-NH2,d(CH2)5−[Tyr(Me)2,Thr4]OVT showed less social play in the novel as compared to the home cage. AVP enhanced anxiety-related behavior in males (tested on the elevated plus-maze), but failed to do so in females, suggesting that exogenous AVP alters social play and anxiety-related behavior via distinct and sex-specific mechanisms. Moreover, none of the other drug treatments that altered social play had an effect on anxiety, suggesting that these drug-induced behavioral alterations are relatively specific to social behavior. Overall, we showed that AVP and OXT systems in the lateral septum modulate social play in juvenile rats in neuropeptide-, sex- and social context-specific ways. These findings underscore the importance of considering not only sex, but also social context, in how AVP and OXT modulate social behavior. PMID:24982623

  2. Oceanic, Latitudinal, and Sex-Specific Variation in Demography of a Tropical Deepwater Snapper across the Indo-Pacific Region

    Directory of Open Access Journals (Sweden)

    Ashley J. Williams

    2017-12-01

    Full Text Available Deepwater tropical fisheries provide an important source of income and protein to Pacific and Indian Ocean coastal communities who are highly dependent on fish for food security. The development of quantitative assessments and management strategies for these deepwater fisheries has been hindered by insufficient biological and fisheries data. We examine the age-specific demography of the pygmy ruby snapper Etelis carbunculus, an important target species in tropical deepwater fisheries, across 90° of longitude and 20° of latitude in the Pacific and Indian Oceans. Our results show that growth of E. carbunculus varies significantly between oceans and sexes and across latitudes in both oceans. Estimates of natural and fishing mortality were similar between oceans, but higher for females than males in both oceans. Evidence of greater fishing pressure on females than males is likely due to the larger size-at-age of females compared to males, assuming that selectivity of the fishing gear is related directly to fish size. Sex ratios were significantly female biased in both oceans despite this species being gonochoristic, and maturity schedules were similar between sexes in the Pacific Ocean. This species exhibits a protracted spawning season from mid-spring to autumn (i.e., October to May in the Pacific Ocean. These results represent the first estimates of age-specific demographic parameters for E. carbunculus, and provide the foundation for the development of the first species-specific assessment models and harvest strategies for the species. Future stock assessment models for E. carbunculus should consider sex-specific demographic parameters and spatial variation in demography. Our results reveal substantial differences in biology between E. carbunculus and the giant ruby snapper E. sp., a cryptic congeneric species, and thus contribute to greater clarity in managing fisheries that are dependent on these two species. Furthermore, the improved

  3. Sex-specific modulation of juvenile social play behavior by vasopressin and oxytocin depends on social context

    Directory of Open Access Journals (Sweden)

    Remco eBredewold

    2014-06-01

    Full Text Available We recently demonstrated that vasopressin (AVP in the lateral septum modulates social play behavior differently in male and female juvenile rats. However, the extent to which different social contexts (i.e., exposure to an unfamiliar play partner in different environments affect the regulation of social play remains largely unknown. Given that AVP and the closely related neuropeptide oxytocin (OXT modulate social behavior as well as anxiety-like behavior, we hypothesized that these neuropeptides may regulate social play behavior differently in novel (novel cage as opposed to familiar (home cage social environments. Administration of the specific AVP V1a receptor (V1aR antagonist (CH25Tyr(Me2AVP into the lateral septum enhanced home cage social play behavior in males but reduced it in females, confirming our previous findings. These effects were context-specific because V1aR blockade did not alter novel cage social play behavior in either sex. Furthermore, social play in females was reduced by AVP in the novel cage and by OXT in the home cage. Additionally, females administered the specific OXT receptor antagonist desGly-NH2,d(CH25-[Tyr(Me2,Thr4]OVT showed less social play in the novel as compared to the home cage. AVP enhanced anxiety-related behavior in males (tested on the elevated plus-maze, but failed to do so in females, suggesting that exogenous AVP alters social play and anxiety-related behavior via distinct and sex-specific mechanisms. Moreover, none of the other drug treatments that altered social play had an effect on anxiety, suggesting that these drug-induced behavioral alterations are relatively specific to social behavior. Overall, we showed that AVP and OXT systems in the lateral septum modulate social play in juvenile rats in neuropeptide-, sex- and social context-specific ways. These findings underscore the importance of considering not only sex, but also social context, in how AVP and OXT modulate social behavior.

  4. Age- and sex-specific reference limits for creatinine, cystatin C and the estimated glomerular filtration rate.

    Science.gov (United States)

    Hannemann, Anke; Friedrich, Nele; Dittmann, Kathleen; Spielhagen, Christin; Wallaschofski, Henri; Völzke, Henry; Rettig, Rainer; Endlich, Karlhans; Lendeckel, Uwe; Stracke, Sylvia; Nauck, Matthias

    2011-11-14

    Early detection of patients with chronic kidney disease is of great importance. This study developed reference limits for serum creatinine and serum cystatin C concentrations and for the estimated glomerular filtration rate (eGFR) in healthy subjects from the general population aged 25-65 years. This study defined a reference population including 985 subjects from the first follow-up of the Study of Health in Pomerania. Serum creatinine was measured with a modified kinetic Jaffé method. Serum cystatin C was measured with a nephelometric assay. The eGFR was calculated from serum creatinine according to the Cockcroft-Gault (eGFR(CG)) and the Modification of Diet in Renal Disease (eGFR(MDRD)) equation, respectively, as well as from serum cystatin C according to the formula by Larsson (eGFR(Larsson)). Non-parametric quantile regression was used to estimate the reference limits. For serum creatinine and serum cystatin C the 95th percentile and for eGFR(CG), eGFR(MDRD) and eGFR(Larsson) the 5th percentile were selected as reference limits. All data was weighted to reflect the age- and sex-structure of the German population in 2008. The reference limits for serum creatinine (men: 1.11-1.23 mg/dL; women: 0.93-1.00 mg/dL) and serum cystatin C levels (men: 0.92-1.04 mg/L; women: 0.84-1.02 mg/L) increased with advancing age. The reference limits for eGFR decreased with increasing age (eGFR(CG) men: 106.0-64.7 mL/min, women 84.4-57.9 mL/min; eGFR(MDRD) men: 82.5-62.2 mL/min/1.73 m², women 75.0-58.2 mL/min/1.73 m²; eGFR(Larsson) men: 85.5-72.9 mL/min, women 94.5-75.7 mL/min). This study presents age- and sex-specific reference limits for five measures of renal function based on quantile regression models.

  5. Sex-specific impact of early-life adversity on chronic pain: a large population-based study in Japan

    Directory of Open Access Journals (Sweden)

    Yamada K

    2017-02-01

    Full Text Available Keiko Yamada,1,2 Ko Matsudaira,3,4 Eizaburo Tanaka,1,5 Hiroyuki Oka,3 Junji Katsuhira,3,6 Hiroyasu Iso1 1Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, 2Center for Pain Management, Osaka University Hospital, Suita, Osaka, 3Department of Medical Research and Management for Musculoskeletal Pain, 22nd Century Medical and Research Center, Faculty of Medicine, The University of Tokyo, Tokyo, 4Japan Labour Health & Welfare Organization, Tokyo, 5Hyogo Institute for Traumatic Stress, Kobe, 6Department of Prosthetics & Orthotics and Assistive Technology, Faculty of Medical Technology, Niigata University of Health and Welfare, Niigata, Japan Background: Responses to early-life adversity may differ by sex. We investigated the ­sex-specific impact of early-life adversity on chronic pain, chronic multisite pain, and somatizing tendency with chronic pain. Methods: We examined 4229 respondents aged 20–79 years who participated in the Pain Associated Cross-Sectional Epidemiological Survey in Japan. Outcomes were: 1 chronic pain prevalence, 2 multisite pain (≥3 sites prevalence, and 3 multiple somatic symptoms (≥3 symptoms among respondents with chronic pain related to the presence or absence of early-life adversity. Multivariable-adjusted odds ratios (ORs were calculated with 95% confidence intervals using a logistic regression model including age, smoking status, exercise routine, sleep time, body mass index, household expenditure, and the full distribution of scores on the Mental Health Inventory-5. We further adjusted for pain intensity when we analyzed the data for respondents with chronic pain. Results: The prevalence of chronic pain was higher among respondents reporting the presence of early-life adversity compared with those reporting its absence, with multivariable ORs of 1.62 (1.22–2.15, p<0.01 in men and 1.47 (1.13–1.90, p<0.01 in women. Among women with chronic pain, early

  6. Sex-specific effects of weight-affecting gene variants in a life course perspective--The HUNT Study, Norway.

    Science.gov (United States)

    Kvaløy, K; Kulle, B; Romundstad, P; Holmen, T L

    2013-09-01

    The impact of previously identified genetic variants directly or indirectly associated with obesity, were investigated at birth, adolescence and adulthood to provide knowledge concerning timing and mechanisms of obesity susceptibility with focus on sex differences. Twenty four previously identified obesity- and eating disorder susceptibility loci were tested for association with adiposity traits at birth (ponderal index (PI)), adolescence and young adulthood (body mass index (BMI), waist circumference (WC) and waist-hip ratio (WHR)) in 1782 individuals from the HUNT study. Single-nucleotide polymorphism (SNPs) were evaluated individually and by haplotype sliding-window approach for windows50 kb (near-MC4R, FTO and near-BDNF). The analyses were performed on the total and sex stratified samples. The most substantial effect on BMI was observed for the near-MC4R variants at adolescence and adulthood (adjusted P-values in adolescence: 0.002 and 0.003 for rs17782313 and rs571312, respectively). The same variants showed inverse association with PI in males (adjusted P-values: 0.019-0.036). Furthermore, significant effects were observed at adolescence with BMI for the near-KCTD15 variant (rs11084753) (adjusted P=0.038) in the combined sample. The near-INSIG2 (rs7566605) was significantly associated to WHR in males and near-BDNF (rs925946) in the combined sample (adjusted P=0.027 and P=0.033, respectively). The OPRD1 locus was associated to BMI and WC in males both at adolescence and adulthood with highest effect in adults (adjusted P=0.058). Interaction with sex was identified for near-MC4R, OPRD1, COMT, near-BDNF and DRD2. Most obesity susceptibility variants show stronger effect at adolescence than at birth and adulthood with a clear sex-specific effect at some loci. The near-MC4R locus exhibit inverse effect on weight at birth in boys compared with findings at adolescence and adulthood. Some variants less known for obesity-susceptibility such as OPRD1 were found to

  7. Climatic conditions and child height: Sex-specific vulnerability and the protective effects of sanitation and food markets in Nepal.

    Science.gov (United States)

    Mulmi, Prajula; Block, Steven A; Shively, Gerald E; Masters, William A

    2016-12-01

    Environmental conditions in early life are known to have impacts on later health outcomes, but causal mechanisms and potential remedies have been difficult to discern. This paper uses the Nepal Demographic and Health Surveys of 2006 and 2011, combined with earlier NASA satellite observations of variation in the Normalized Difference Vegetation Index (NDVI) at each child's location and time of birth to identify the trimesters of gestation and periods of infancy when climate variation is linked to attained height later in life. We find significant differences by sex: males are most affected by conditions in their second trimester of gestation, and females in the first three months after birth. Each 100-point difference in NDVI at those times is associated with a difference in height-for-age z-score (HAZ) measured at age 12-59 months of 0.088 for boys and 0.054 for girls, an effect size similar to that of moving within the distribution of household wealth by close to one quintile for boys and one decile for girls. The entire seasonal change in NDVI from peak to trough is approximately 200-300 points during the 2000-2011 study period, implying a seasonal effect on HAZ similar to one to three quintiles of household wealth. This effect is observed only in households without toilets; in households with toilets, there is no seasonal fluctuation, implying protection against climatic conditions that facilitate disease transmission. We also use data from the Nepal Living Standards Surveys on district-level agricultural production and marketing, and find a climate effect on child growth only in districts where households' food consumption derives primarily from their own production. Robustness tests find no evidence of selection effects, and placebo regression results reveal no significant artefactual correlations. The timing and sex-specificity of climatic effects are consistent with previous studies, while the protective effects of household sanitation and food markets are

  8. Endogenous TSH levels at the time of 131I ablation do not influence ablation success, recurrence-free survival or differentiated thyroid cancer-related mortality

    International Nuclear Information System (INIS)

    Vrachimis, Alexis; Riemann, Burkhard; Maeder, Uwe; Reiners, Christoph; Verburg, Frederik A.

    2016-01-01

    Based on a single older study it is established dogma that TSH levels should be ≥30 mU/l at the time of postoperative 131 I ablation in differentiated thyroid cancer (DTC) patients. We sought to determine whether endogenous TSH levels, i.e. after levothyroxine withdrawal, at the time of ablation influence ablation success rates, recurrence-free survival and DTC-related mortality. A total of 1,873 patients without distant metastases referred for postoperative adjuvant 131 I therapy were retrospectively included from 1991 onwards. Successful ablation was defined as stimulated Tg <1 μg/l. Age, gender and the presence of lymph node metastases were independent determinants of TSH levels at the time of ablation. TSH levels were not significantly related to ablation success rates (p = 0.34), recurrence-free survival (p = 0.29) or DTC -elated mortality (p = 0.82), but established risk factors such as T-stage, lymph node metastases and age were. Ablation was successful in 230 of 275 patients (83.6 %) with TSH <30 mU/l and in 1,359 of 1,598 patients (85.0 %) with TSH ≥30 mU/l. The difference was not significant (p = 0.55). Of the whole group of 1,873 patients, 21 had recurrent disease. There were no significant differences in recurrence rates between patients with TSH <30 mU/l and TSH ≥30 mU/l (p = 0.16). Ten of the 1,873 patients died of DTC. There were no significant differences in DTC-specific survival between patients with TSH <30 mU/l and TSH ≥30 mU/l (p = 0.53). The precise endogenous TSH levels at the time of 131 I ablation are not related to the ablation success rates, recurrence free survival and DTC related mortality. The established dogma that TSH levels need to be ≥30 mU/l at the time of 131 I ablation can be discarded. (orig.)

  9. Endogenous TSH levels at the time of {sup 131}I ablation do not influence ablation success, recurrence-free survival or differentiated thyroid cancer-related mortality

    Energy Technology Data Exchange (ETDEWEB)

    Vrachimis, Alexis; Riemann, Burkhard [University Hospital Muenster, Department of Nuclear Medicine, Muenster (Germany); Maeder, Uwe; Reiners, Christoph [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Verburg, Frederik A. [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); RWTH University Hospital Aachen, Department of Nuclear Medicine, Aachen (Germany)

    2016-02-15

    Based on a single older study it is established dogma that TSH levels should be ≥30 mU/l at the time of postoperative {sup 131}I ablation in differentiated thyroid cancer (DTC) patients. We sought to determine whether endogenous TSH levels, i.e. after levothyroxine withdrawal, at the time of ablation influence ablation success rates, recurrence-free survival and DTC-related mortality. A total of 1,873 patients without distant metastases referred for postoperative adjuvant {sup 131}I therapy were retrospectively included from 1991 onwards. Successful ablation was defined as stimulated Tg <1 μg/l. Age, gender and the presence of lymph node metastases were independent determinants of TSH levels at the time of ablation. TSH levels were not significantly related to ablation success rates (p = 0.34), recurrence-free survival (p = 0.29) or DTC -elated mortality (p = 0.82), but established risk factors such as T-stage, lymph node metastases and age were. Ablation was successful in 230 of 275 patients (83.6 %) with TSH <30 mU/l and in 1,359 of 1,598 patients (85.0 %) with TSH ≥30 mU/l. The difference was not significant (p = 0.55). Of the whole group of 1,873 patients, 21 had recurrent disease. There were no significant differences in recurrence rates between patients with TSH <30 mU/l and TSH ≥30 mU/l (p = 0.16). Ten of the 1,873 patients died of DTC. There were no significant differences in DTC-specific survival between patients with TSH <30 mU/l and TSH ≥30 mU/l (p = 0.53). The precise endogenous TSH levels at the time of {sup 131}I ablation are not related to the ablation success rates, recurrence free survival and DTC related mortality. The established dogma that TSH levels need to be ≥30 mU/l at the time of {sup 131}I ablation can be discarded. (orig.)

  10. Testing the Effects of DL-Alpha-Tocopherol Supplementation on Oxidative Damage, Total Antioxidant Protection and the Sex-Specific Responses of Reproductive Effort and Lifespan to Dietary Manipulation in Australian Field Crickets (Teleogryllus commodus

    Directory of Open Access Journals (Sweden)

    C. Ruth Archer

    2015-12-01

    Full Text Available The oxidative stress theory predicts that the accumulation of oxidative damage causes aging. More generally, oxidative damage could be a cost of reproduction that reduces survival. Both of these hypotheses have mixed empirical support. To better understand the life-history consequences of oxidative damage, we fed male and female Australian field crickets (Teleogryllus commodus four diets differing in their protein and carbohydrate content, which have sex-specific effects on reproductive effort and lifespan. We supplemented half of these crickets with the vitamin E isoform DL-alpha-tocopherol and measured the effects of nutrient intake on lifespan, reproduction, oxidative damage and antioxidant protection. We found a clear trade-off between reproductive effort and lifespan in females but not in males. In direct contrast to the oxidative stress theory, crickets fed diets that improved their lifespan had high levels of oxidative damage to proteins. Supplementation with DL-alpha-tocopherol did not significantly improve lifespan or reproductive effort. However, males fed diets that increased their reproductive investment experienced high oxidative damage to proteins. While this suggests that male reproductive effort could elevate oxidative damage, this was not associated with reduced male survival. Overall, these results provide little evidence that oxidative damage plays a central role in mediating life-history trade-offs in T. commodus.

  11. Global, regional, and national age–sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013

    DEFF Research Database (Denmark)

    Peterson, Carrie Beth

    2015-01-01

    BACKGROUND: Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries...... between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. METHODS: We estimated age-sex-specific all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey...... informed by meta-regression of prevalence studies. For pathogen-specific causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini...

  12. Global, regional, and national age–sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013

    DEFF Research Database (Denmark)

    Moesgaard Iburg, Kim

    2015-01-01

    Background Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries...... between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specific all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey...... informed by meta-regression of prevalence studies. For pathogen-specific causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini...

  13. Sex-specific interaction effects of age, occupational status, and workplace stress on psychiatric symptoms and allostatic load among healthy Montreal workers.

    Science.gov (United States)

    Juster, Robert-Paul; Moskowitz, D S; Lavoie, Joel; D'Antono, Bianca

    2013-11-01

    Socio-demographics and workplace stress may affect men and women differently. The aim of this cross-sectional study was to assess sex-specific interactions among age, occupational status, and workplace Demand-Control-Support (D-C-S) factors in relation to psychiatric symptoms and allostatic load levels representing multi-systemic "wear and tear". It was hypothesized that beyond main effects, D-C-S factors would be moderated by occupational status and age in sex-specific directions predictive of subjective psychiatric symptoms and objective physiological dysregulations. Participants included healthy male (n = 81) and female (n = 118) Montreal workers aged 20 to 64 years (Men: M = 39.4 years, SD = 11.3; Women: M = 42.8 years, SD = 11.38). The Job Content Questionnaire was administered to assess workplace D-C-S factors that included psychological demands, decisional latitude, and social support. Occupational status was coded using the Nam--Powers--Boyd system derived from the Canadian census. Psychiatric symptoms were assessed using the Beck Anxiety Scale and the Beck Depression Inventory II. Sex-specific allostatic load indices were calculated based on fifteen biomarkers. Regression analyses revealed that higher social support was associated with less depressive symptoms in middle aged (p = 0.033) and older men (p = 0.027). Higher occupational status was associated with higher allostatic load levels for men (p = 0.035), while the reverse occurred for women (p = 0.048). Women with lower occupational status but with higher decision latitude had lower allostatic load levels, as did middle-aged (p = 0.031) and older women (p = 0.003) with higher psychological demands. In summary, age and occupational status moderated workplace stress in sex-specific ways that have occupational health implications.

  14. Involvement of the oxytocin system in the bed nucleus of the stria terminalis in the sex-specific regulation of social recognition.

    Science.gov (United States)

    Dumais, Kelly M; Alonso, Andrea G; Immormino, Marisa A; Bredewold, Remco; Veenema, Alexa H

    2016-02-01

    Sex differences in the oxytocin (OT) system in the brain may explain why OT often regulates social behaviors in sex-specific ways. However, a link between sex differences in the OT system and sex-specific regulation of social behavior has not been tested. Here, we determined whether sex differences in the OT receptor (OTR) or in OT release in the posterior bed nucleus of the stria terminalis (pBNST) mediates sex-specific regulation of social recognition in rats. We recently showed that, compared to female rats, male rats have a three-fold higher OTR binding density in the pBNST, a sexually dimorphic area implicated in the regulation of social behaviors. We now demonstrate that OTR antagonist (5 ng/0.5 μl/side) administration into the pBNST impairs social recognition in both sexes, while OT (100 pg/0.5 μl/side) administration into the pBNST prolongs the duration of social recognition in males only. These effects seem specific to social recognition, as neither treatment altered total social investigation time in either sex. Moreover, baseline OT release in the pBNST, as measured with in vivo microdialysis, did not differ between the sexes. However, males showed higher OT release in the pBNST during social recognition compared to females. These findings suggest a sex-specific role of the OT system in the pBNST in the regulation of social recognition. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Three Antagonistic Cyclic di-GMP-Catabolizing Enzymes Promote Differential Dot/Icm Effector Delivery and Intracellular Survival at the Early Steps of Legionella pneumophila Infection

    Science.gov (United States)

    Allombert, Julie; Lazzaroni, Jean-Claude; Baïlo, Nathalie; Gilbert, Christophe; Charpentier, Xavier; Doublet, Patricia

    2014-01-01

    Legionella pneumophila is an intracellular pathogen which replicates within protozoan cells and can accidently infect alveolar macrophages, causing an acute pneumonia in humans. The second messenger cyclic di-GMP (c-di-GMP) has been shown to play key roles in the regulation of various bacterial processes, including virulence. While investigating the function of the 22 potential c-di-GMP-metabolizing enzymes of the L. pneumophila Lens strain, we found three that directly contribute to its ability to infect both protozoan and mammalian cells. These three enzymes display diguanylate cyclase (Lpl0780), phosphodiesterase (Lpl1118), and bifunctional diguanylate cyclase/phosphodiesterase (Lpl0922) activities, which are all required for the survival and intracellular replication of L. pneumophila. Mutants with deletions of the corresponding genes are efficiently taken up by phagocytic cells but are partially defective for the escape of the Legionella-containing vacuole (LCV) from the host degradative endocytic pathway and result in lower survival. In addition, Lpl1118 is required for efficient endoplasmic reticulum recruitment to the LCV. Trafficking and biogenesis of the LCV are dependent upon the orchestrated actions of several type 4 secretion system Dot/Icm effectors proteins, which exhibit differentially altered translocation in the three mutants. While translocation of some effectors remained unchanged, others appeared over- and undertranslocated. A general translocation offset of the large repertoire of Dot/Icm effectors may be responsible for the observed defects in the trafficking and biogenesis of the LCV. Our results suggest that L. pneumophila uses cyclic di-GMP signaling to fine-tune effector delivery and ensure effective evasion of the host degradative pathways and establishment of a replicative vacuole. PMID:24379287

  16. Cytological studies of human meiosis: sex-specific differences in recombination originate at, or prior to, establishment of double-strand breaks.

    Directory of Open Access Journals (Sweden)

    Jennifer R Gruhn

    Full Text Available Meiotic recombination is sexually dimorphic in most mammalian species, including humans, but the basis for the male:female differences remains unclear. In the present study, we used cytological methodology to directly compare recombination levels between human males and females, and to examine possible sex-specific differences in upstream events of double-strand break (DSB formation and synaptic initiation. Specifically, we utilized the DNA mismatch repair protein MLH1 as a marker of recombination events, the RecA homologue RAD51 as a surrogate for DSBs, and the synaptonemal complex proteins SYCP3 and/or SYCP1 to examine synapsis between homologs. Consistent with linkage studies, genome-wide recombination levels were higher in females than in males, and the placement of exchanges varied between the sexes. Subsequent analyses of DSBs and synaptic initiation sites indicated similar male:female differences, providing strong evidence that sex-specific differences in recombination rates are established at or before the formation of meiotic DSBs. We then asked whether these differences might be linked to variation in the organization of the meiotic axis and/or axis-associated DNA and, indeed, we observed striking male:female differences in synaptonemal complex (SC length and DNA loop size. Taken together, our observations suggest that sex specific differences in recombination in humans may derive from chromatin differences established prior to the onset of the recombination pathway.

  17. Sex-specific markers developed by next-generation sequencing confirmed an XX/XY sex determination system in bighead carp (Hypophthalmichehys nobilis) and silver carp (Hypophthalmichthys molitrix).

    Science.gov (United States)

    Liu, Haiyang; Pang, Meixia; Yu, Xiaomu; Zhou, Ying; Tong, Jingou; Fu, Beide

    2018-01-05

    Sex-specific markers are powerful tools for identifying sex-determination system in various animals. Bighead carp (Hypophthalmichehys nobilis) and silver carp (Hypophthalmichthys molitrix) are two of the most important edible fish in Asia, which have a long juvenility period that can lasts for 4-5 years. In this study, we found one sex-specific marker by next-generation sequencing together with bioinformatics analysis in bighead carp. The male-specific markers were used to perform molecular sexing in the progenies of artificial gynogenetic diploids and found all progenies (n = 160) were females. Meanwhile, around 1 : 1 sex ratio was observed in a total of 579 juvenile offspring from three other families. To further extend the male-specific region, we performed genome walking and got a male-specific sequence of 8,661 bp. Five pairs of primers were designed and could be used to efficiently distinguish males from females in bighead carp and silver carp. The development of these male-specific markers and results of their molecular sexing in different populations provide strong evidence for a sex determination system of female homogametry or male heterogametry (XX/XY) in bighead carp and silver carp. To the best of our knowledge, this is the first report of effective sex-specific markers in these two large carp species. © The Author(s) 2018. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

  18. Sex-specific metabolic interactions between liver and adipose tissue in MCD diet-induced non-alcoholic fatty liver disease.

    Science.gov (United States)

    Lee, Yun-Hee; Kim, Sou Hyun; Kim, Sang-Nam; Kwon, Hyun-Jung; Kim, Jeong-Dong; Oh, Ji Youn; Jung, Young-Suk

    2016-07-26

    Higher susceptibility to metabolic disease in male exemplifies the importance of sexual dimorphism in pathogenesis. We hypothesized that the higher incidence of non-alcoholic fatty liver disease in males involves sex-specific metabolic interactions between liver and adipose tissue. In the present study, we used a methionine-choline deficient (MCD) diet-induced fatty liver mouse model to investigate sex differences in the metabolic response of the liver and adipose tissue. After 2 weeks on an MCD-diet, fatty liver was induced in a sex-specific manner, affecting male mice more severely than females. The MCD-diet increased lipolytic enzymes in the gonadal white adipose tissue (gWAT) of male mice, whereas it increased expression of uncoupling protein 1 and other brown adipocyte markers in the gWAT of female mice. Moreover, gWAT from female mice demonstrated higher levels of oxygen consumption and mitochondrial content compared to gWAT from male mice. FGF21 expression was increased in liver tissue by the MCD diet, and the degree of upregulation was significantly higher in the livers of female mice. The endocrine effect of FGF21 was responsible, in part, for the sex-specific browning of gonadal white adipose tissue. Collectively, these data demonstrated that distinctively female-specific browning of white adipose tissue aids in protecting female mice against MCD diet-induced fatty liver disease.

  19. Testing the hypothesis that diphtheria-tetanus-pertussis vaccine has negative non-specific and sex-differential effects on child survival in high-mortality countries.

    Science.gov (United States)

    Aaby, Peter; Benn, Christine; Nielsen, Jens; Lisse, Ida Maria; Rodrigues, Amabelia; Ravn, Henrik

    2012-01-01

    Measles vaccines (MV) have sex-differential effects on mortality not explained by protection against measles infection. The authors examined whether whole-cell diphtheria-tetanus-pertussis (DTP) vaccine has sex-differential and non-specific effects. Following previous reviews and a new search, the effect of DTP on mortality up to the next vaccination was assessed in all studies where DTP was given after BCG or DTP was given after MV and there was prospective follow-up after ascertainment of vaccination status. High-mortality countries in Africa and Asia. The initial observation of negative effect of DTP generated six hypotheses, which were examined in all available studies and two randomised trials reducing the time of exposure to DTP. Consistency between studies. In the first study, DTP had negative effects on survival in contrast to the beneficial effects of BCG and MV. This pattern was repeated in the six other studies available. Second, the two 'natural experiments' found significantly higher mortality for DTP-vaccinated compared with DTP-unvaccinated children. Third, the female-male mortality ratio was increased after DTP in all nine studies; in contrast, the ratio was decreased after BCG and MV in all studies. Fourth, the increased female mortality associated with high-titre measles vaccine was found only among children who had received DTP after high-titre measles vaccine. Fifth, in six randomised trials of early MV, female but not male mortality was increased if DTP was likely to be given after MV. Sixth, the mortality rate declined markedly for girls but not for boys when DTP-vaccinated children received MV. The authors reduced exposure to DTP as most recent vaccination by administering a live vaccine (MV and BCG) shortly after DTP. Both trials reduced child mortality. These observations are incompatible with DTP merely protecting against the targeted diseases. With herd immunity to whooping cough, DTP is associated with higher mortality for girls

  20. Sex-specific developmental plasticity of generalist and specialist predatory mites (Acari: Phytoseiidae) in response to food stress.

    Science.gov (United States)

    Walzer, Andreas; Schausberger, Peter

    2011-03-01

    We studied developmental plasticity under food stress in three female-biased size dimorphic predatory mite species, Phytoseiulus persimilis, Neoseiulus californicus, and Amblyseius andersoni. All three species prey on two-spotted spider mites but differ in the degree of adaptation to this prey. Phytoseiulus persimilis is a specialized spider mite predator, N. californicus is a generalist with a preference for spider mites, and A. andersoni is a broad generalist. Immature predators were offered prey patches of varying density and their survival chances, dispersal tendencies, age and size at maturity measured. Amblyseius andersoni dispersed earlier from and had lower survival chances in low density prey patches than N. californicus and P. persimilis. Age at maturity was not affected by prey density in the generalist A. andersoni, whereas both the specialist P. persimilis and the generalist N. californicus accelerated development at low prey densities. Species-specific plasticity in age at maturity reflects opposite survival strategies when confronted with limited prey: to prematurely leave and search for other food (A. andersoni) or to stay and accelerate development (P. persimilis, N. californicus). In all species, size at maturity was more plastic in females than males, indicating that males incur higher fitness costs from deviations from optimal body size.

  1. BODY SIZE AND HAREM SIZE IN MALE RED-WINGED BLACKBIRDS: MANIPULATING SELECTION WITH SEX-SPECIFIC FEEDERS.

    Science.gov (United States)

    Rohwer, Sievert; Langston, Nancy; Gori, Dave

    1996-10-01

    We experimentally manipulated the strength of selection in the field on red-winged blackbirds (Agelaius phoeniceus) to test hypotheses about contrasting selective forces that favor either large or small males in sexually size dimorphic birds. Selander (1972) argued that sexual selection favors larger males, while survival selection eventually stabilizes male size because larger males do not survive as well as smaller males during harsh winters. Searcy (1979a) proposed instead that sexual selection may be self limiting: male size might be stabilized not by overwinter mortality, but by breeding-season sexual selection that favors smaller males. Under conditions of energetic stress, smaller males should be able to display more and thus achieve higher reproductive success. Using feeders that provisioned males or females but not both, we produced conditions that mimicked the extremes of natural conditions. We found experimental support for the hypothesis that when food is abundant, sexual selection favors larger males. But even under conditions of severe energetic stress, smaller males did not gain larger harems, as the self-limiting hypothesis predicted. Larger males were more energetically stressed than smaller males, but in ways that affected their future reproductive output rather than their current reproductive performance. Stressed males that returned had smaller wings and tails than those that did not return; among returning stressed males, relative harem sizes were inversely related to wing and tail length. Thus, male body size may be stabilized not by survival costs during the non-breeding season, nor by energetic costs during the breeding season, but by costs of future reproduction that larger males pay for their increased breeding-season effort. © 1996 The Society for the Study of Evolution.

  2. Age and sex-specific mortality of wild and captive populations of a monogamous pair-bonded primate (Aotus azarae)

    DEFF Research Database (Denmark)

    Larson, Sam; Colchero, Fernando; Jones, Owen

    2016-01-01

    In polygynous primates, a greater reproductive variance in males has been linked to their reduced life expectancy relative to females. The mortality patterns of monogamous pair-bonded primates, however, are less clear. We analyzed the sex differences in mortality within wild (NMales = 70, NFemales...... = 73) and captive (NMales = 25, NFemales = 29) populations of Azara's owl monkeys (Aotus azarae), a socially and genetically monogamous primate exhibiting bi-parental care. We used Bayesian Survival Trajectory Analysis (BaSTA) to test age-dependent models of mortality. The wild and captive populations...

  3. Sex-specific variation in signaling pathways and gene expression patterns in human leukocytes in response to endotoxin and exercise.

    Science.gov (United States)

    Abbasi, Asghar; de Paula Vieira, Rodolfo; Bischof, Felix; Walter, Michael; Movassaghi, Masoud; Berchtold, Nicole C; Niess, Andreas M; Cotman, Carl W; Northoff, Hinnak

    2016-11-10

    While exercise effects on the immune system have received increasing attention in recent years, it remains unclear to what extent gender and fluctuations in sex hormones during menstrual cycle influence immunological responses to exercise. We investigated mRNA changes induced through exhaustive exercise (half-marathon; pre-exercise and post-exercise [30 min, 3 h, 24 h] on whole blood cultures ± lipopolysaccharide [LPS] [1 h]) with a specific focus on sex differences (men vs women in luteal phase) as an extension of our previous study. Inflammation related signaling pathways, TLRs, cytosolic DNA sensing and RIG-I like receptors were differentially activated between sexes in LPS-stimulated cultures. Genes differentially regulated between sexes included TNIP-1, TNIP-3, IL-6, HIVEP1, CXCL3, CCR3, IL-8, and CD69, revealing a bias towards less anti-inflammatory gene regulation in women compared to men. In addition, several genes relevant to brain function (KMO, DDIT4, VEGFA, IGF1R, IGF2R, and FGD4) showed differential activation between sexes. Some of these genes (e.g., KMO in women, DDIT4 in both sexes) potentially constitute neuroprotective mechanisms. These data reveal that the exercise-induced change in gene expression might be gender and menstrual cycle phase dependent.

  4. Eicosapentaenoic acid and docosahexaenoic acid in whole blood are differentially and sex-specifically associated with cardiometabolic risk markers in 8-11-year-old danish children

    DEFF Research Database (Denmark)

    Damsgaard, Camilla T.; Eidner, Maj B.; Stark, Ken D.

    2014-01-01

    -day dietary records, physical activity by accelerometry and measured anthropometry, blood pressure, and heart rate. Blood samples were analyzed for whole blood fatty acid composition, cholesterols, triacylglycerol, insulin resistance by the homeostatic model of assessment (HOMA-IR), and inflammatory...

  5. Eicosapentaenoic acid and docosahexaenoic acid in whole blood are differentially and sex-specifically associated with cardiometabolic risk markers in 8-11-year-old danish children

    DEFF Research Database (Denmark)

    Damsgaard, Camilla T.; Eidner, Maj B.; Stark, Ken D.

    2014-01-01

    ) investigated associations between EPA and DHA in whole blood and early cardiometabolic risk markers in 713 children aged 8-11 years and 2) explored potential mediation through waist circumference and physical activity and potential dietary confounding. We collected data on parental education, pubertal stage, 7......n-3 long-chain polyunsaturated fatty acids improve cardiovascular risk markers in adults. These effects may differ between eicosapentaenoic acid (EPA, 20∶5n-3) and docosahexaenoic acid (DHA, 22∶6n-3), but we lack evidence in children. Using baseline data from the OPUS School Meal Study we 1......-day dietary records, physical activity by accelerometry and measured anthropometry, blood pressure, and heart rate. Blood samples were analyzed for whole blood fatty acid composition, cholesterols, triacylglycerol, insulin resistance by the homeostatic model of assessment (HOMA-IR), and inflammatory...

  6. Systemic administration of valproic acid and zonisamide promotes the survival and differentiation of induced pluripotent stem cell–derived dopaminergic neurons

    Directory of Open Access Journals (Sweden)

    Tatsuya eYoshikawa

    2013-02-01

    Full Text Available Cell replacement therapy using embryonic stem cells (ESCs and induced pluripotent stem cells (iPSCs is a promising strategy for the treatment of neurologic diseases such as Parkinson’s disease (PD. However, a limiting factor for effective cell transplantation is the low survival rate of grafted cells, especially neurons. In this study, we modified the host environment and investigated whether the simultaneous administration of soluble factors can improve the survival and differentiation of murine iPSC-derived dopaminergic (DA neurons in host brains. With the goal of applying this technology in clinical settings in the near future, we selected drugs that were already approved for clinical use. The drugs included two commonly used anticonvulsants, valproic acid (VPA and zonisamide (ZNS, and estradiol (E2, also known as biologically active estrogen. Following neural induction of murine iPSCs, we collected neural progenitor cells by sorting PSA-NCAM+ cells, then treated the PSA-NCAM+ cells with drugs for four days. An immunofluorescence study revealed that 0.01 mM and 0.1 mM of VPA and 10 nM of E2 increased the percentage of tyrosine hydroxylase+ (TH: a DA neuron marker cells in vitro. Furthermore, 0.1 mM of VPA increased the percentage of TH+ cells that simultaneously express the midbrain markers FOXA2 and NURR1. Next, in order to determine the effects of the drugs in vivo, the iPSC-derived NPCs were transplanted into the striata of intact SD rats. The animals received intraperitoneal injections of one of the drugs for four weeks, then were subjected to an immunofluorescence study. VPA administration (150 mg/kg/daily increased the number of NeuN+ postmitotic neurons and TH+ DA neurons in the grafts. Furthermore, VPA (150 mg/kg/daily and ZNS (30 mg/kg/daily increased the number of TH+FOXA2+ midbrain DA neurons. These results suggest that the systemic administration of VPA and ZNS may improve the efficiency of cell replacement therapy using i

  7. Early differential cell death and survival mechanisms initiate and contribute to the development of OPIDN: A study of molecular, cellular, and anatomical parameters

    International Nuclear Information System (INIS)

    Damodaran, T.V.; Attia, M.K.; Abou-Donia, M.B.

    2011-01-01

    Organophosphorus-ester induced delayed neurotoxicity (OPIDN) is a neurodegenerative disorder characterized by ataxia progressing to paralysis with a concomitant central and peripheral, distal axonapathy. Diisopropylphosphorofluoridate (DFP) produces OPIDN in the chicken that results in mild ataxia in 7–14 days and severe paralysis as the disease progresses with a single dose. White leghorn layer hens were treated with DFP (1.7 mg/kg, sc) after prophylactic treatment with atropine (1 mg/kg, sc) in normal saline and eserine (1 mg/kg, sc) in dimethyl sulfoxide. Control groups were treated with vehicle propylene glycol (0.1 ml/kg, sc), atropine in normal saline and eserine in dimethyl sulfoxide. The hens were euthanized at different time points such as 1, 2, 5, 10 and 20 days, and the tissues from cerebrum, midbrain, cerebellum, brainstem and spinal cord were quickly dissected and frozen for mRNA (northern) studies. Northern blots were probed with BCL2, GADD45, beta actin, and 28S RNA to investigate their expression pattern. Another set of hens was treated for a series of time points and perfused with phosphate buffered saline and fixative for histological studies. Various staining protocols such as Hematoxylin and Eosin (H and E); Sevier-Munger; Cresyl echt Violet for Nissl substance; and Gallocynin stain for Nissl granules were used to assess various patterns of cell death and degenerative changes. Complex cell death mechanisms may be involved in the neuronal and axonal degeneration. These data indicate altered and differential mRNA expressions of BCL2 (anti apoptotic gene) and GADD45 (DNA damage inducible gene) in various tissues. Increased cell death and other degenerative changes noted in the susceptible regions (spinal cord and cerebellum) than the resistant region (cerebrum), may indicate complex molecular pathways via altered BCL2 and GADD45 gene expression, causing the homeostatic imbalance between cell survival and cell death mechanisms. Semi quantitative

  8. Sex specific molecular responses of quick-to-court protein in Indian malarial vector Anopheles culicifacies: conflict of mating versus blood feeding behaviour

    Directory of Open Access Journals (Sweden)

    Tanwee Das De

    2017-07-01

    Full Text Available Understanding the molecular basis of mosquito behavioural complexity plays a central role in designing novel molecular tools to fight against their vector-borne diseases. Although the olfactory system plays an important role in guiding and managing many behavioural responses including feeding and mating, but the sex-specific regulation of olfactory responses remain poorly investigated. From our ongoing transcriptomic data annotation of olfactory tissue of blood fed adult female An. culicifacies mosquitoes; we have identified a 383 bp long unique transcript encoding a Drosophila homolog of the quick-to-court protein. Previously this was shown to regulate courtship behaviour in adult male Drosophila. A comprehensive in silico analysis of the quick-to-court (qtc gene of An. culicifacies (Ac-qtc predicts a 1536 bp single copy gene encoding 511 amino acid protein, having a high degree of conservation with other insect homologs. The age-dependent increased expression of putative Ac-qtc correlated with the maturation of the olfactory system, necessary to meet the sex-specific conflicting demand of mating (mate finding versus host-seeking behavioural responses. Sixteen to eighteen hours of starvation did not alter Ac-qtc expression in both sexes, however, blood feeding significantly modulated its response in the adult female mosquitoes, confirming that it may not be involved in sugar feeding associated behavioural regulation. Finally, a dual behavioural and molecular assay indicated that natural dysregulation of Ac-qtc in the late evening might promote the mating events for successful insemination. We hypothesize that Ac-qtc may play a unique role to regulate the sex-specific conflicting demand of mosquito courtship behaviour versus blood feeding behaviour in the adult female mosquitoes. Further elucidation of this molecular mechanism may provide further information to evaluate Ac-qtc as a key molecular target for mosquito-borne disease management.

  9. Sex-specific associations between particulate matter exposure and gene expression in independent discovery and validation cohorts of middle-aged men and women

    DEFF Research Database (Denmark)

    Vrijens, Karen; Winckelmans, Ellen; Tsamou, Maria

    2017-01-01

    Background: Particulate matter (PM) exposure leads to premature death, mainly due to respiratory and cardiovascular diseases. Objectives: Identification of transcriptomic biomarkers of air pollution exposure and effect in a healthy adult population. Methods: Microarray analyses were performed in 98...... healthy volunteers (48 men, 50 women). The expression of eight sex-specific candidate biomarker genes (significantly associated with PM10 in the discovery cohort and with a reported link to air pollution-related disease) was measured with qPCR in an independent validation cohort (75 men, 94 women...

  10. Identification of sex-specific DNA methylation changes driven by specific chemicals in cord blood in a Faroese birth cohort

    DEFF Research Database (Denmark)

    Leung, Yuet-Kin; Ouyang, Bin; Niu, Liang

    2018-01-01

    Faroe islanders consume marine foods contaminated with methylmercury (MeHg), polychlorinated biphenyls (PCBs), and other toxicants associated with chronic disease risks. Differential DNA methylation at specific CpG sites in cord blood may serve as a surrogate biomarker of health impacts from...... chemical exposures. We aimed to identify key environmental chemicals in cord blood associated with DNA methylation changes in a population with elevated exposure to chemical mixtures. We studied 72 participants of a Faroese birth cohort recruited between 1986 and 1987 and followed until adulthood. The cord...... blood DNA methylome was profiled using Infinium HumanMethylation450 BeadChips. We determined the associations of CpG site changes with concentrations of MeHg, major PCBs, other organochlorine compounds [hexachlorobenzene (HCB), p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) and p...

  11. Acceleration of leukocytes' epigenetic age as an early tumor and sex-specific marker of breast and colorectal cancer.

    Science.gov (United States)

    Durso, Danielle Fernandes; Bacalini, Maria Giulia; Sala, Claudia; Pirazzini, Chiara; Marasco, Elena; Bonafé, Massimiliano; do Valle, Ítalo Faria; Gentilini, Davide; Castellani, Gastone; Faria, Ana Maria Caetano; Franceschi, Claudio; Garagnani, Paolo; Nardini, Christine

    2017-04-04

    Changes in blood epigenetic age have been associated with several pathological conditions and have recently been described to anticipate cancer development. In this work, we analyze a publicly available leukocytes methylation dataset to evaluate the relation between DNA methylation age and the prospective development of specific types of cancer. We calculated DNA methylation age acceleration using five state-of-the-art estimators (three multi-site: Horvath, Hannum, Weidner; and two CpG specific: ELOV2 and FHL2) in a cohort including 845 subjects from the EPIC-Italy project and we compared 424 samples that remained cancer-free over the approximately ten years of follow-up with 235 and 166 subjects who developed breast and colorectal cancer, respectively. We show that the epigenetic age estimated from blood DNA methylation data is statistically significantly associated to future breast and male colorectal cancer development. These results are corroborated by survival analysis that shows significant association between age acceleration and cancer incidence suggesting that the chance of developing age-related diseases may be predicted by circulating epigenetic markers, with a dependence upon tumor type, sex and age estimator. These are encouraging results towards the non-invasive and perspective usage of epigenetic biomarkers.

  12. Sex-specific cardiopulmonary exercise testing indices to estimate the severity of inoperable chronic thromboembolic pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Chen TX

    2018-01-01

    Full Text Available Tian-Xiang Chen,1 Bigyan Pudasaini,1 Jian Guo,2 Su-Gang Gong,1 Rong Jiang,1 Lan Wang,1 Qin-Hua Zhao,1 Wen-Hui Wu,1 Ping Yuan,1 Jin-Ming Liu1 1Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China; 2Department of Pulmonary Function Test, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China Background: Sex differences in chronic thromboembolic pulmonary hypertension (CTEPH have been revealed in few studies. Although right heart catheterization (RHC is the gold standard for clinical diagnosis and assessment of prognosis in pulmonary hypertension (PH, cardiopulmonary exercise testing (CPET has been a more widely used assessment of functional capacity, disease severity, prognosis, and treatment response in PH. We hypothesized that the “sex-specific” CPET indices could estimate the severity of inoperable CTEPH.Methods: Data were retrieved for 33 male (age, mean ± standard deviation [SD] =62.5±13.4 years and 40 female (age, mean ± SD =56.3±11.8 years patients with stable CTEPH who underwent both RHC and CPET at Shanghai Pulmonary Hospital from February 2010 to February 2016. Univariate and forward/backward multiple stepwise regression analysis was performed to assess the predictive value of CPET indices to hemodynamic parameters. Event-free survival was estimated using the Kaplan–Meier method and analyzed with the log-rank test. Cox proportional hazards models were performed to determine the independent event-free survival predictors.Results: Numerous CPET parameters were different between male and female patients with CTEPH and the control group. There were no significant differences in both clinical variables and RHC parameters between male and female patients with CTEPH. O2 pulse, workload, minute ventilation (VE, and end-tidal partial pressure of O2 (PETO2 at anaerobic threshold, as well as peak O2 pulse, workload, VE, and nadir

  13. Age- and sex-specific mortality patterns in an emerging wildlife epidemic: the phocine distemper in European harbour seals.

    Directory of Open Access Journals (Sweden)

    Tero Härkönen

    Full Text Available Analyses of the dynamics of diseases in wild populations typically assume all individuals to be identical. However, profound effects on the long-term impact on the host population can be expected if the disease has age and sex dependent dynamics. The Phocine Distemper Virus (PDV caused two mass mortalities in European harbour seals in 1988 and in 2002. We show the mortality patterns were highly age specific on both occasions, where young of the year and adult (>4 yrs animals suffered extremely high mortality, and sub-adult seals (1-3 yrs of both sexes experienced low mortality. Consequently, genetic differences cannot have played a main role explaining why some seals survived and some did not in the study region, since parents had higher mortality levels than their progeny. Furthermore, there was a conspicuous absence of animals older than 14 years among the victims in 2002, which strongly indicates that the survivors from the previous disease outbreak in 1988 had acquired and maintained immunity to PDV. These specific mortality patterns imply that contact rates and susceptibility to the disease are strongly age and sex dependent variables, underlining the need for structured epidemic models for wildlife diseases. Detailed data can thus provide crucial information about a number of vital parameters such as functional herd immunity. One of many future challenges in understanding the epidemiology of the PDV and other wildlife diseases is to reveal how immune system responses differ among animals in different stages during their life cycle. The influence of such underlying mechanisms may also explain the limited evidence for abrupt disease thresholds in wild populations.

  14. Postzygotic isolation involves strong mitochondrial and sex-specific effects in Tigriopus californicus, a species lacking heteromorphic sex chromosomes.

    Science.gov (United States)

    Foley, B R; Rose, C G; Rundle, D E; Leong, W; Edmands, S

    2013-11-01

    Detailed studies of the genetics of speciation have focused on a few model systems, particularly Drosophila. The copepod Tigriopus californicus offers an alternative that differs from standard animal models in that it lacks heteromorphic chromosomes (instead, sex determination is polygenic) and has reduced opportunities for sexual conflict, because females mate only once. Quantitative trait loci (QTL) mapping was conducted on reciprocal F2 hybrids between two strongly differentiated populations, using a saturated linkage map spanning all 12 autosomes and the mitochondrion. By comparing sexes, a possible sex ratio distorter was found but no sex chromosomes. Although studies of standard models often find an excess of hybrid male sterility factors, we found no QTL for sterility and multiple QTL for hybrid viability (indicated by non-Mendelian adult ratios) and other characters. Viability problems were found to be stronger in males, but the usual explanations for weaker hybrid males (sex chromosomes, sensitivity of spermatogenesis, sexual selection) cannot fully account for these male viability problems. Instead, higher metabolic rates may amplify deleterious effects in males. Although many studies of standard speciation models find the strongest genetic incompatibilities to be nuclear-nuclear (specifically X chromosome-autosome), we found the strongest deleterious interaction in this system was mito-nuclear. Consistent with the snowball theory of incompatibility accumulation, we found that trigenic interactions in this highly divergent cross were substantially more frequent (>6×) than digenic interactions. This alternative system thus allows important comparisons to studies of the genetics of reproductive isolation in more standard model systems.

  15. High Gestational Folic Acid Supplementation Alters Expression of Imprinted and Candidate Autism Susceptibility Genes in a sex-Specific Manner in Mouse Offspring.

    Science.gov (United States)

    Barua, Subit; Kuizon, Salomon; Brown, W Ted; Junaid, Mohammed A

    2016-02-01

    Maternal nutrients play critical roles in modulating epigenetic events and exert long-term influences on the progeny's health. Folic acid (FA) supplementation during pregnancy has decreased the incidence of neural tube defects in newborns, but the influence of high doses of maternal FA supplementation on infants' brain development is unclear. The present study was aimed at investigating the effects of a high dose of gestational FA on the expression of genes in the cerebral hemispheres (CHs) of 1-day-old pups. One week prior to mating and throughout the entire period of gestation, female C57BL/6J mice were fed a diet, containing FA at either 2 mg/kg (control diet (CD)) or 20 mg/kg (high maternal folic acid (HMFA)). At postnatal day 1, pups from different dams were sacrificed and CH tissues were collected. Quantitative RT-PCR and Western blot analysis confirmed sex-specific alterations in the expression of several genes that modulate various cellular functions (P < 0.05) in pups from the HMFA group. Genomic DNA methylation analysis showed no difference in the level of overall methylation in pups from the HMFA group. These findings demonstrate that HMFA supplementation alters offsprings' CH gene expression in a sex-specific manner. These changes may influence infants' brain development.

  16. Untangling the Contributions of Sex-Specific Gene Regulation and X-Chromosome Dosage to Sex-Biased Gene Expression in Caenorhabditis elegans

    Science.gov (United States)

    Kramer, Maxwell; Rao, Prashant; Ercan, Sevinc

    2016-01-01

    Dosage compensation mechanisms equalize the level of X chromosome expression between sexes. Yet the X chromosome is often enriched for genes exhibiting sex-biased, i.e., imbalanced expression. The relationship between X chromosome dosage compensation and sex-biased gene expression remains largely unexplored. Most studies determine sex-biased gene expression without distinguishing between contributions from X chromosome copy number (dose) and the animal’s sex. Here, we uncoupled X chromosome dose from sex-specific gene regulation in Caenorhabditis elegans to determine the effect of each on X expression. In early embryogenesis, when dosage compensation is not yet fully active, X chromosome dose drives the hermaphrodite-biased expression of many X-linked genes, including several genes that were shown to be responsible for hermaphrodite fate. A similar effect is seen in the C. elegans germline, where X chromosome dose contributes to higher hermaphrodite X expression, suggesting that lack of dosage compensation in the germline may have a role in supporting higher expression of X chromosomal genes with female-biased functions in the gonad. In the soma, dosage compensation effectively balances X expression between the sexes. As a result, somatic sex-biased expression is almost entirely due to sex-specific gene regulation. These results suggest that lack of dosage compensation in different tissues and developmental stages allow X chromosome copy number to contribute to sex-biased gene expression and function. PMID:27356611

  17. Hematology and Clinical Chemistry Measures During and After Pregnancy and Age- and Sex-Specific Reference Intervals in African Green Monkeys (Chlorocebus aethiops sabaeus).

    Science.gov (United States)

    Chichester, Lee; Gee, Melaney K; Jorgensen, Matthew J; Kaplan, Jay R

    2015-07-01

    Clinical decisions and experimental analyses often involve the assessment of hematology and clinical chemistry. Using clinical pathology to assess the health status of NHP in breeding colonies or data from studies than involve pregnancy can often be complicated by pregnancy status. This study had 2 objectives regarding the hematology and clinical chemistry of African green monkeys (AGM, Chlorocebus aethiops sabaeus): 1) to compare pregnant or recently postpartum animals with nonpregnant, nonlactating animals and 2) to create age- and sex-specific reference intervals. Subjects in this study were 491 AGM from the Vervet Research Colony of the Wake Forest University Primate Center. Results indicated that changes in BUN, serum total protein, albumin, ALP, GGT, calcium, phosphorus, sodium, potassium, cholesterol, total CO2, globulins, lipase, amylase, WBC, neutrophils, lymphocytes, platelets, RBC, Hgb, and Hct occur during pregnancy and the postpartum period. Age- and sex-specific reference intervals consistent with guidelines from the American Society for Veterinary Clinical Pathology were established and further expand the understanding of how to define health in AGM on the basis of clinical pathology. The combination of understanding the changes that occur in pregnancy and postpartum and expansive reference intervals will help guide clinical and experimental decisions.

  18. The sex-specific associations of the aromatase gene with Alzheimer's disease and its interaction with IL10 in the Epistasis Project.

    Science.gov (United States)

    Medway, Christopher; Combarros, Onofre; Cortina-Borja, Mario; Butler, Helen T; Ibrahim-Verbaas, Carla A; de Bruijn, Renée F A G; Koudstaal, Peter J; van Duijn, Cornelia M; Ikram, M Arfan; Mateo, Ignacio; Sánchez-Juan, Pascual; Lehmann, Michael G; Heun, Reinhard; Kölsch, Heike; Deloukas, Panos; Hammond, Naomi; Coto, Eliecer; Alvarez, Victoria; Kehoe, Patrick G; Barber, Rachel; Wilcock, Gordon K; Brown, Kristelle; Belbin, Olivia; Warden, Donald R; Smith, A David; Morgan, Kevin; Lehmann, Donald J

    2014-02-01

    Epistasis between interleukin-10 (IL10) and aromatase gene polymorphisms has previously been reported to modify the risk of Alzheimer's disease (AD). However, although the main effects of aromatase variants suggest a sex-specific effect in AD, there has been insufficient power to detect sex-specific epistasis between these genes to date. Here we used the cohort of 1757 AD patients and 6294 controls in the Epistasis Project. We replicated the previously reported main effects of aromatase polymorphisms in AD risk in women, for example, adjusted odds ratio of disease for rs1065778 GG=1.22 (95% confidence interval: 1.01-1.48, P=0.03). We also confirmed a reported epistatic interaction between IL10 rs1800896 and aromatase (CYP19A1) rs1062033, again only in women: adjusted synergy factor=1.94 (1.16-3.25, 0.01). Aromatase, a rate-limiting enzyme in the synthesis of estrogens, is expressed in AD-relevant brain regions ,and is downregulated during the disease. IL-10 is an anti-inflammatory cytokine. Given that estrogens have neuroprotective and anti-inflammatory activities and regulate microglial cytokine production, epistasis is biologically plausible. Diminishing serum estrogen in postmenopausal women, coupled with suboptimal brain estrogen synthesis, may contribute to the inflammatory state, that is a pathological hallmark of AD.

  19. [Age- and sex-specific reference intervals for 10 health examination items: mega-data from a Japanese Health Service Association].

    Science.gov (United States)

    Suka, Machi; Yoshida, Katsumi; Kawai, Tadashi; Aoki, Yoshikazu; Yamane, Noriyuki; Yamauchi, Kuniaki

    2005-07-01

    To determine age- and sex-specific reference intervals for 10 health examination items in Japanese adults. Health examination data were accumulated from 24 different prefectural health service associations affiliated with the Japan Association of Health Service. Those who were non-smokers, drank less than 7 days/week, and had a body mass index of 18.5-24.9kg/m2 were sampled as a reference population (n = 737,538; 224,947 men and 512,591 women). After classified by age and sex, reference intervals for 10 health examination items (systolic blood pressure, diastolic blood pressure, total cholesterol, triglyceride, glucose, uric acid, AST, ALT, gamma-GT, and hemoglobin) were estimated using the parametric and nonparametric methods. In every item except for hemoglobin, men had higher reference intervals than women. Systolic blood pressure, total cholesterol, and glucose showed an upward trend in values with increasing age. Hemoglobin showed a downward trend in values with increasing age. Triglyceride, ALT, and gamma-GT reached a peak in middle age. Overall, parametric estimates showed narrower reference intervals than non-parametric estimates. Reference intervals vary with age and sex. Age- and sex-specific reference intervals may contribute to better assessment of health examination data.

  20. Age-specific and sex-specific mortality in 187 countries, 1970-2010: a systematic analysis for the Global Burden of Disease Study 2010.

    Science.gov (United States)

    Wang, Haidong; Dwyer-Lindgren, Laura; Lofgren, Katherine T; Rajaratnam, Julie Knoll; Marcus, Jacob R; Levin-Rector, Alison; Levitz, Carly E; Lopez, Alan D; Murray, Christopher J L

    2012-12-15

    Estimation of the number and rate of deaths by age and sex is a key first stage for calculation of the burden of disease in order to constrain estimates of cause-specific mortality and to measure premature mortality in populations. We aimed to estimate life tables and annual numbers of deaths for 187 countries from 1970 to 2010. We estimated trends in under-5 mortality rate (children aged 0-4 years) and probability of adult death (15-59 years) for each country with all available data. Death registration data were available for more than 100 countries and we corrected for undercount with improved death distribution methods. We applied refined methods to survey data on sibling survival that correct for survivor, zero-sibling, and recall bias. We separately estimated mortality from natural disasters and wars. We generated final estimates of under-5 mortality and adult mortality from the data with Gaussian process regression. We used these results as input parameters in a relational model life table system. We developed a model to extrapolate mortality to 110 years of age. All death rates and numbers have been estimated with 95% uncertainty intervals (95% UIs). From 1970 to 2010, global male life expectancy at birth increased from 56·4 years (95% UI 55·5-57·2) to 67·5 years (66·9-68·1) and global female life expectancy at birth increased from 61·2 years (60·2-62·0) to 73·3 years (72·8-73·8). Life expectancy at birth rose by 3-4 years every decade from 1970, apart from during the 1990s (increase in male life expectancy of 1·4 years and in female life expectancy of 1·6 years). Substantial reductions in mortality occurred in eastern and southern sub-Saharan Africa since 2004, coinciding with increased coverage of antiretroviral therapy and preventive measures against malaria. Sex-specific changes in life expectancy from 1970 to 2010 ranged from gains of 23-29 years in the Maldives and Bhutan to declines of 1-7 years in Belarus, Lesotho, Ukraine, and Zimbabwe

  1. Sex-Specific Arrival Times on the Breeding Grounds: Hybridizing Migratory Skuas Provide Empirical Support for the Role of Sex Ratios.

    Science.gov (United States)

    Lisovski, Simeon; Fröhlich, Anne; von Tersch, Matthew; Klaassen, Marcel; Peter, Hans-Ulrich; Ritz, Markus S

    2016-04-01

    In migratory animals, protandry (earlier arrival of males on the breeding grounds) prevails over protogyny (females preceding males). In theory, sex differences in timing of arrival should be driven by the operational sex ratio, shifting toward protogyny in female-biased populations. However, empirical support for this hypothesis is, to date, lacking. To test this hypothesis, we analyzed arrival data from three populations of the long-distance migratory south polar skua (Catharacta maccormicki). These populations differed in their operational sex ratio caused by the unidirectional hybridization of male south polar skuas with female brown skuas (Catharacta antarctica lonnbergi). We found that arrival times were protandrous in allopatry, shifting toward protogyny in female-biased populations when breeding in sympatry. This unique observation is consistent with theoretical predictions that sex-specific arrival times should be influenced by sex ratio and that protogyny should be observed in populations with female-biased operational sex ratio.

  2. The mediating sex-specific effect of psychological distress on the relationship between adverse childhood experiences and current smoking among adults.

    Science.gov (United States)

    Strine, Tara W; Edwards, Valerie J; Dube, Shanta R; Wagenfeld, Morton; Dhingra, Satvinder; Prehn, Angela Witt; Rasmussen, Sandra; McKnight-Eily, Lela; Croft, Janet B

    2012-07-13

    Research suggests that ACEs have a long-term impact on the behavioral, emotional, and cognitive development of children. These disruptions can lead to adoption of unhealthy coping behaviors throughout the lifespan. The present study sought to examine psychological distress as a potential mediator of sex-specific associations between adverse childhood experiences (ACEs) and adult smoking. Data from 7,210 Kaiser-Permanente members in San Diego California collected between April and October 1997 were used. Among women, psychological distress mediated a significant portion of the association between ACEs and smoking (21% for emotional abuse, 16% for physical abuse, 15% for physical neglect, 10% for parental separation or divorce). Among men, the associations between ACEs and smoking were not significant. These findings suggest that for women, current smoking cessation strategies may benefit from understanding the potential role of childhood trauma.

  3. Mendelian randomization shows sex-specific associations between long-chain PUFA-related genotypes and cognitive performance in Danish schoolchildren

    DEFF Research Database (Denmark)

    Lauritzen, Lotte; Sorensen, Louise B.; Harslof, Laurine B.

    2017-01-01

    , and performance in the d2 Test of Attention and a reading test were analyzed in multiple regression models including all SNPs, SNP-sex interactions, and covariates related to testing conditions.Results:FADS, rs1535 minor allele carriage associated with lower whole-blood arachidonic acid (P ≤ 0.002), and minor...... alleles of rs174448 tended to associate with lower docosahexaenoic acid (DHA) (P = 0.052). We identified sex interactions in 50% of the SNP performance sets. Sex-dependent associations were observed for rs174448 and rs1535 on the d2 Test of Attention outcomes (P ... reading scores and rs174448 and rs2397142 (P sex-specific analyses showed associations in opposite directions in girls and boys. The minor allele carriage of rs174448 was associated with lower d2 Test of Attention performance (P

  4. The mediating sex-specific effect of psychological distress on the relationship between adverse childhood experiences and current smoking among adults

    Directory of Open Access Journals (Sweden)

    Strine Tara W

    2012-07-01

    Full Text Available Abstract Background Research suggests that ACEs have a long-term impact on the behavioral, emotional, and cognitive development of children. These disruptions can lead to adoption of unhealthy coping behaviors throughout the lifespan. The present study sought to examine psychological distress as a potential mediator of sex-specific associations between adverse childhood experiences (ACEs and adult smoking. Method Data from 7,210 Kaiser-Permanente members in San Diego California collected between April and October 1997 were used. Results Among women, psychological distress mediated a significant portion of the association between ACEs and smoking (21% for emotional abuse, 16% for physical abuse, 15% for physical neglect, 10% for parental separation or divorce. Among men, the associations between ACEs and smoking were not significant. Conclusions These findings suggest that for women, current smoking cessation strategies may benefit from understanding the potential role of childhood trauma.

  5. Maternal corticosterone exposure in the mouse programs sex-specific renal adaptations in the renin-angiotensin-aldosterone system in 6-month offspring.

    Science.gov (United States)

    Cuffe, James S M; Burgess, Danielle J; O'Sullivan, Lee; Singh, Reetu R; Moritz, Karen M

    2016-04-01

    Short-term maternal corticosterone (Cort) administration at mid-gestation in the mouse reduces nephron number in both sexes while programming renal and cardiovascular dysfunction in 12-month male but not female offspring. The renal renin-angiotensin-aldosterone system (RAAS), functions in a sexually dimorphic manner to regulate both renal and cardiovascular physiology. This study aimed to identify if there are sex-specific differences in basal levels of the intrarenal RAAS and to determine the impact of maternal Cort exposure on the RAAS in male and female offspring at 6 months of age. While intrarenal renin concentrations were higher in untreated females compared to untreated males, renal angiotensin II concentrations were higher in males than females. Furthermore, basal plasma aldosterone concentrations were greater in females than males. Cort exposed male but not female offspring had reduced water intake and urine excretion. Cort exposure increased renal renin concentrations and elevated mRNA expression of Ren1, Ace2, and Mas1 in male but not female offspring. In addition, male Cort exposed offspring had increased expression of the aldosterone receptor, Nr3c2 and renal sodium transporters. In contrast, Cort exposure increased Agtr1a mRNA levels in female offspring only. This study demonstrates that maternal Cort exposure alters key regulators of renal function in a sex-specific manner at 6 months of life. These finding likely contribute to the disease outcomes in male but not female offspring in later life and highlights the importance of renal factors other than nephron number in the programming of renal and cardiovascular disease. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  6. Annual variation in the levels of transcripts of sex-specific genes in the mantle of the common mussel, Mytilus edulis.

    Directory of Open Access Journals (Sweden)

    Sandhya Anantharaman

    Full Text Available Mytilus species are used as sentinels for the assessment of environmental health but sex or stage in the reproduction cycle is rarely considered even though both parameters are likely to influence responses to pollution. We have validated the use of a qPCR assay for sex identification and related the levels of transcripts to the reproductive cycle. A temporal study of mantle of Mytilus edulis found transcripts of male-specific vitelline coat lysin (VCL and female-specific vitelline envelope receptor for lysin (VERL could identify sex over a complete year. The levels of VCL/VERL were proportional to the numbers of sperm/ova and are indicative of the stage of the reproductive cycle. Maximal levels of VCL and VERL were found in February 2009 declining to minima between July - August before increasing and re-attaining a peak in February 2010. Water temperature may influence these transitions since they coincide with minimal water temperature in February and maximal temperature in August. An identical pattern of variation was found for a cryptic female-specific transcript (H5 but a very different pattern was observed for oestrogen receptor 2 (ER2. ER2 varied in a sex-specific way with male > female for most of the cycle, with a female maxima in July and a male maxima in December. Using artificially spawned animals, the transcripts for VCL, VERL and H5 were shown to be present in gametes and thus their disappearance from mantle is indicative of spawning. VCL and VERL are present at equivalent levels in February and July-August but during gametogenesis (August to January and spawning (March to June VCL is present at lower relative amounts than VERL. This may indicate sex-specific control mechanisms for these processes and highlight a potential pressure point leading to reduced reproductive output if environmental factors cause asynchrony to gamete maturation or release.

  7. A dense SNP-based linkage map for Atlantic salmon (Salmo salar reveals extended chromosome homeologies and striking differences in sex-specific recombination patterns

    Directory of Open Access Journals (Sweden)

    Lien Sigbjørn

    2011-12-01

    Full Text Available Abstract Background The Atlantic salmon genome is in the process of returning to a diploid state after undergoing a whole genome duplication (WGD event between 25 and100 million years ago. Existing data on the proportion of paralogous sequence variants (PSVs, multisite variants (MSVs and other types of complex sequence variation suggest that the rediplodization phase is far from over. The aims of this study were to construct a high density linkage map for Atlantic salmon, to characterize the extent of rediploidization and to improve our understanding of genetic differences between sexes in this species. Results A linkage map for Atlantic salmon comprising 29 chromosomes and 5650 single nucleotide polymorphisms (SNPs was constructed using genotyping data from 3297 fish belonging to 143 families. Of these, 2696 SNPs were generated from ESTs or other gene associated sequences. Homeologous chromosomal regions were identified through the mapping of duplicated SNPs and through the investigation of syntenic relationships between Atlantic salmon and the reference genome sequence of the threespine stickleback (Gasterosteus aculeatus. The sex-specific linkage maps spanned a total of 2402.3 cM in females and 1746.2 cM in males, highlighting a difference in sex specific recombination rate (1.38:1 which is much lower than previously reported in Atlantic salmon. The sexes, however, displayed striking differences in the distribution of recombination sites within linkage groups, with males showing recombination strongly localized to telomeres. Conclusion The map presented here represents a valuable resource for addressing important questions of interest to evolution (the process of re-diploidization, aquaculture and salmonid life history biology and not least as a resource to aid the assembly of the forthcoming Atlantic salmon reference genome sequence.

  8. Sex-Specific Life Course Changes in the Neuro-Metabolic Phenotype of Glut3 Null Heterozygous Mice: Ketogenic Diet Ameliorates Electroencephalographic Seizures and Improves Sociability.

    Science.gov (United States)

    Dai, Yun; Zhao, Yuanzi; Tomi, Masatoshi; Shin, Bo-Chul; Thamotharan, Shanthie; Mazarati, Andrey; Sankar, Raman; Wang, Elizabeth A; Cepeda, Carlos; Levine, Michael S; Zhang, Jingjing; Frew, Andrew; Alger, Jeffry R; Clark, Peter M; Sondhi, Monica; Kositamongkol, Sudatip; Leibovitch, Leah; Devaskar, Sherin U

    2017-04-01

    We tested the hypothesis that exposure of glut3+/- mice to a ketogenic diet ameliorates autism-like features, which include aberrant behavior and electrographic seizures. We first investigated the life course sex-specific changes in basal plasma-cerebrospinal fluid (CSF)-brain metabolic profile, brain glucose transport/uptake, glucose and monocarboxylate transporter proteins, and adenosine triphosphate (ATP) in the presence or absence of systemic insulin administration. Glut3+/- male but not female mice (5 months of age) displayed reduced CSF glucose/lactate concentrations with no change in brain Glut1, Mct2, glucose uptake or ATP. Exogenous insulin-induced hypoglycemia increased brain glucose uptake in glut3+/- males alone. Higher plasma-CSF ketones (β-hydroxybutyrate) and lower brain Glut3 in females vs males proved protective in the former while enhancing vulnerability in the latter. As a consequence, increased synaptic proteins (neuroligin4 and SAPAP1) with spontaneous excitatory postsynaptic activity subsequently reduced hippocampal glucose content and increased brain amyloid β1-40 deposition in an age-dependent manner in glut3+/- males but not females (4 to 24 months of age). We then explored the protective effect of a ketogenic diet on ultrasonic vocalization, sociability, spatial learning and memory, and electroencephalogram seizures in male mice (7 days to 6 to 8 months of age) alone. A ketogenic diet partially restored sociability without affecting perturbed vocalization, spatial learning and memory, and reduced seizure events. We conclude that (1) sex-specific and age-dependent perturbations underlie the phenotype of glut3+/- mice, and (2) a ketogenic diet ameliorates seizures caused by increased cortical excitation and improves sociability, but fails to rescue vocalization and cognitive deficits in glut3+/- male mice. Copyright © 2017 Endocrine Society.

  9. Does the silver moss Bryum argenteum exhibit sex-specific patterns in vegetative growth rate, asexual fitness or prezygotic reproductive investment?

    Science.gov (United States)

    Horsley, Kimberly; Stark, Lloyd R; McLetchie, D Nicholas

    2011-05-01

    Expected life history trade-offs associated with sex differences in reproductive investment are often undetected in seed plants, with the difficulty arising from logistical issues of conducting controlled experiments. By controlling genotype, age and resource status of individuals, a bryophyte was assessed for sex-specific and location-specific patterns of vegetative, asexual and sexual growth/reproduction across a regional scale. Twelve genotypes (six male, six female) of the dioecious bryophyte Bryum argenteum were subcultured to remove environmental effects, regenerated asexually to replicate each genotype 16 times, and grown over a period of 92 d. Plants were assessed for growth rates, asexual and sexual reproductive traits, and allocation to above- and below-ground regenerative biomass. The degree of sexual versus asexual reproductive investment appears to be under genetic control, with three distinct ecotypes found in this study. Protonemal growth rate was positively correlated with asexual reproduction and sexual reproduction, whereas asexual reproduction was negatively correlated (appeared to trade-off) with vegetative growth (shoot production). No sex-specific trade-offs were detected. Female sex-expressing shoots were longer than males, but the sexes did not differ in growth traits, asexual traits, sexual induction times, or above- and below-ground biomass. Males, however, had much higher rates of inflorescence production than females, which translated into a significantly higher (24x) prezygotic investment for males relative to females. Evidence for three distinct ecotypes is presented for a bryophyte based on regeneration traits. Prior to zygote production, the sexes of this bryophyte did not differ in vegetative growth traits but significantly differed in reproductive investment, with the latter differences potentially implicated in the strongly biased female sex ratio. The disparity between males and females for prezygotic reproductive investment is

  10. Metallothionein and a peptide modeled after metallothionein, EmtinB, induce neuronal differentiation and survival through binding to receptors of the low-density lipoprotein receptor family

    DEFF Research Database (Denmark)

    Ambjørn, Malene; Asmussen, Johanne W; Lindstam, Mats

    2007-01-01

    outgrowth and survival. MT-mediated neurite outgrowth was furthermore inhibited by an anti-megalin serum. EmtinB-mediated inhibition of apoptosis occurred without a reduction of caspase-3 activity, but was associated with reduced expression of the pro-apoptotic B-cell leukemia/lymphoma-2 interacting member...

  11. Differential impacts of clinical variables and 5-fluorouracil-based adjuvant chemotherapy on 5-year disease-free survival of patients with stage IIa and IIb colon cancer

    Directory of Open Access Journals (Sweden)

    Yi-Hung Kuo

    2018-01-01

    Conclusion: Different predictors of DFS were observed in stage IIa and IIb colon cancer; adjuvant chemotherapy could provide a survival benefit for patients with stage IIb colon cancer who have one of the four factors that were studied in our hospital-based analysis.

  12. Differential games

    CERN Document Server

    Friedman, Avner

    2006-01-01

    This volume lays the mathematical foundations for the theory of differential games, developing a rigorous mathematical framework with existence theorems. It begins with a precise definition of a differential game and advances to considerations of games of fixed duration, games of pursuit and evasion, the computation of saddle points, games of survival, and games with restricted phase coordinates. Final chapters cover selected topics (including capturability and games with delayed information) and N-person games.Geared toward graduate students, Differential Games will be of particular interest

  13. Prenatal chronic mild stress induces depression-like behavior and sex-specific changes in regional glutamate receptor expression patterns in adult rats.

    Science.gov (United States)

    Wang, Y; Ma, Y; Hu, J; Cheng, W; Jiang, H; Zhang, X; Li, M; Ren, J; Li, X

    2015-08-20

    Chronic stress during critical periods of human fetal brain development is associated with cognitive, behavioral, and mood disorders in later life. Altered glutamate receptor (GluR) expression has been implicated in the pathogenesis of stress-dependent disorders. To test whether prenatal chronic mild stress (PCMS) enhances offspring's vulnerability to stress-induced behavioral and neurobiological abnormalities and if this enhanced vulnerability is sex-dependent, we measured depression-like behavior in the forced swimming test (FST) and regional changes in GluR subunit expression in PCMS-exposed adult male and female rats. Both male and female PCMS-exposed rats exhibited stronger depression-like behavior than controls. Males and females exhibited unique regional changes in GluR expression in response to PCMS alone, FST alone (CON-FST), and PCMS with FST (PCMS-FST). In females, PCMS alone did not alter N-methyl-d-aspartate receptor (NMDAR) or metabotropic glutamate receptor (mGluR) expression, while in PCMS males, higher mGluR2/3, mGluR5, and NR1 expression levels were observed in the prefrontal cortex. In addition, PCMS altered the change in GluR expression induced by acute stress (the FST test), and this too was sex-specific. Male PCMS-FST rats expressed significantly lower mGluR5 levels in the hippocampus, lower mGluR5, NR1, postsynaptic density protein (PSD)95, and higher mGluR2/3 in the prefrontal cortex, and higher mGluR5 and PSD95 in the amygdala than male CON-FST rats. Female PCMS-FST rats expressed lower NR1 in the hippocampus, lower NR2B and PSD95 in the prefrontal cortex, lower mGluR2/3 in the amygdala, and higher PSD95 in the amygdala than female CON-FST rats. PCMS may increase the offspring's vulnerability to depression by altering sex-specific stress-induced changes in glutamatergic signaling. Copyright © 2015. Published by Elsevier Ltd.

  14. Modelling survival

    DEFF Research Database (Denmark)

    Ashauer, Roman; Albert, Carlo; Augustine, Starrlight

    2016-01-01

    The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test...

  15. A sex-specific trade-off between mating preferences for genetic compatibility and body size in a cichlid fish with mutual mate choice.

    Science.gov (United States)

    Thünken, Timo; Meuthen, Denis; Bakker, Theo C M; Baldauf, Sebastian A

    2012-08-07

    Mating preferences for genetic compatibility strictly depend on the interplay of the genotypes of potential partners and are therein fundamentally different from directional preferences for ornamental secondary sexual traits. Thus, the most compatible partner is on average not the one with most pronounced ornaments and vice versa. Hence, mating preferences may often conflict. Here, we present a solution to this problem while investigating the interplay of mating preferences for relatedness (a compatibility criterion) and large body size (an ornamental or quality trait). In previous experiments, both sexes of Pelvicachromis taeniatus, a cichlid fish with mutual mate choice, showed preferences for kin and large partners when these criteria were tested separately. In the present study, test fish were given a conflicting choice between two potential mating partners differing in relatedness as well as in body size in such a way that preferences for both criteria could not simultaneously be satisfied. We show that a sex-specific trade-off occurs between mating preferences for body size and relatedness. For females, relatedness gained greater importance than body size, whereas the opposite was true for males. We discuss the potential role of the interplay between mating preferences for relatedness and body size for the evolution of inbreeding preference.

  16. Sex-specific role of education on the associations of socioeconomic status indicators with obesity risk: A population-based study in South Korea.

    Science.gov (United States)

    Chung, Woojin; Kim, Jaeyeun; Lim, Seung-Ji; Lee, Sunmi

    2018-01-01

    No study of obesity risk for people in developed countries has conducted a multi-dimensional analysis of the association of socioeconomic status with obesity. In this paper, we investigated if education functions as either a confounder or an effect modifier in the association of another socioeconomic status indicator with obesity. This cross-sectional study analyzed data of an adult population sample (10,905 men and 14,580 women) from the Korea National Health and Nutrition Examination Survey (2010-2014). The study performed multivariate logistic regression analyses for three education levels and four indicators of socioeconomic status (i.e., marital status, residential area, occupation, and income). The overall prevalence of obesity was 38.1% in men and 29.1% in women (p status and obesity (p for interaction = 0.006), it functioned as both a confounder (p socioeconomic indicator groups in men; for example, in a rural resident group, a higher level of education increased the probability of being obese by 19.7%. The present study suggests the need to examine sex-specific studies regarding the role of education on the association between other socioeconomic status indicators and obesity. This should be considered in planning education policies to reduce the risk of obesity.

  17. Sex-specific effects of daily gavage with a mixed progesterone and glucocorticoid receptor antagonist on hypoxic ventilatory response in newborn rats.

    Science.gov (United States)

    Fournier, Stéphanie; Doan, Van Diep; Joseph, Vincent

    2012-01-01

    We tested the hypothesis that daily gavage with mifepristone, a mixed progesterone/glucocorticoid receptor antagonist would alter hypoxic ventilatory response (HVR) in newborn male and female rats. Rats were treated with mifepristone (40µg/g/day), or vehicle between postnatal days 3-12, and used at 10-12 days of age to record baseline ventilatory and metabolic values using whole body plethysmography. HVR was tested by exposing the animals to 14% and 12% O(2) for 20 minutes each. HVR was enhanced by mifepristone treatment, mainly due to an effect on tidal volume that remained higher in mifepristone treated rats during both levels of hypoxic exposure. This effect was sex-specific being apparent only in male rats. In Vehicle treated rats, HVR was higher in females than in males, which was also due to a higher tidal volume in hypoxia (at 14 and 12% O(2)). We conclude that the activity of the progesterone and/or glucocorticoid receptors modulates respiratory control in rat pups, and that these effects are different in males and females.

  18. Fish oil supplementation from 9 to 18 months of age affects the insulin-like growth factor axis in a sex-specific manner in Danish infants

    DEFF Research Database (Denmark)

    Damsgaard, Camilla T.; Harsløf, Laurine B. S.; Andersen, Anders D.

    2016-01-01

    Several studies have investigated the effects of fish oil (FO) on infant growth, but little is known about the effects of FO and sex on insulin-like growth factor-1 (IGF-1), the main regulator of growth in childhood. We explored whether FO v. sunflower oil (SO) supplementation from 9 to 18 months...... of age affected IGF-1 and its binding protein-3 (IGFBP-3) and whether the potential effects were sex specific. Danish infants (n 115) were randomly allocated to 5 ml/d FO (1·2 g/d n-3 long-chain PUFA (n-3 LCPUFA)) or SO. We measured growth, IGF-1, IGFBP-3 and erythrocyte EPA, a biomarker of n-3 LCPUFA...... intake and status, at 9 and 18 months. Erythrocyte EPA increased strongly with FO compared with SO (PIGF-1 in the total population, but a sex×group interaction (P=0·02). Baseline-adjusted IGF-1 at 18 months was 11·1 µg/l (95 % CI 0·4, 21·8;P=0...

  19. Survival analysis

    International Nuclear Information System (INIS)

    Badwe, R.A.

    1999-01-01

    The primary endpoint in the majority of the studies has been either disease recurrence or death. This kind of analysis requires a special method since all patients in the study experience the endpoint. The standard method for estimating such survival distribution is Kaplan Meier method. The survival function is defined as the proportion of individuals who survive beyond certain time. Multi-variate comparison for survival has been carried out with Cox's proportional hazard model

  20. Laser bioprinting of human induced pluripotent stem cells-the effect of printing and biomaterials on cell survival, pluripotency, and differentiation.

    Science.gov (United States)

    Koch, Lothar; Deiwick, Andrea; Franke, Annika; Schwanke, Kristin; Haverich, Axel; Zweigerdt, Robert; Chichkov, Boris

    2018-04-25

    Research on human induced pluripotent stem cells (hiPSCs) is one of the fastest growing fields in biomedicine. Generated from patient's own somatic cells, hiPSCs can be differentiated towards all functional cell types and returned to the patient without immunological concerns. 3D printing of hiPSCs could enable the generation of functional organs for replacement therapies or realization of organ-on-chip systems for individualized medicine. Printing of living cells was demonstrated with immortalized cell lines, primary cells, and adult stem cells with different printing technologies and biomaterials. However, hiPSCs are more sensitive to handling procedures, in particular, when dissociated into single cells. Both pluripotency and directed differentiation are influenced by numerous environmental factors including culture media, biomaterials, and cell density. Notably, existing literature on the effect of applied biomaterials on pluripotency is rather ambiguous. In this study, laser bioprinting of undifferentiated hiPSCs in combination with different biomaterials was performed and the impact on cells' behavior, pluripotency, and differentiation was investigated. Our findings suggest that hiPSCs are indeed more sensitive to the applied biomaterials, but not to laser printing itself. With appropriate biomaterials, such as the hyaluronic acid based solutions applied in this study, hiPSCs can be successfully laser printed without losing their pluripotency.

  1. Comparative analysis of differential gene expression in kidney tissues of moribund and surviving crucian carp (Carassius auratus gibelio) in response to cyprinid herpesvirus 2 infection.

    Science.gov (United States)

    Xu, Lijuan; Podok, Patarida; Xie, Jun; Lu, Liqun

    2014-08-01

    Cyprinid herpesvirus 2 (CyHV-2) has recently been associated with high mortality of cultured crucian carp (Carassius auratus gibelio) in eastern China. In this study, we established a real-time PCR method to confirm viral infection of crucian carp and to quantify CyHV-2 particles obtained by sucrose gradient centrifugation from diseased fish. Virus-free crucian carp were artificially infected with CyHV-2 using an injection method, which resulted in a dose-dependent death rate. In situ hybridization analysis indicated that there was extensive viral replication and lysis in the kidneys of moribund fish, in contrast to very limited replication in surviving fish. To probe the host immune response to viral infection at the level of gene expression, we identified virus-responsive genes using suppression subtractive hybridization (SSH) in head kidney tissues, the principal immune organ of fish, from moribund and surviving crucian carps after viral challenge. From the moribund SSH library, 363 expressed sequence tags (ESTs) were clustered to 234 unigenes (including 15 singletons and 45 contigs). From the survivor SSH library, 599 ESTs was clustered to 549 unigenes (including 107 singletons and 105 contigs). We further analyzed the transcriptional levels of all immune-related genes by quantitative real-time RT-PCR, which confirmed the upregulation of 90.48 % of these genes. The significantly upregulated immune-related genes identified in this study can serve as candidate marker genes for acute CyHV-2 infection.

  2. Sex-specific effects of dietary fatty acids on saliva cortisol and social behavior in guinea pigs under different social environmental conditions.

    Science.gov (United States)

    Nemeth, Matthias; Millesi, Eva; Puehringer-Sturmayr, Verena; Kaplan, Arthur; Wagner, Karl-Heinz; Quint, Ruth; Wallner, Bernard

    2016-01-01

    Unbalanced dietary intakes of saturated (SFAs) and polyunsaturated (PUFAs) fatty acids can profoundly influence the hypothalamic-pituitary-adrenal (HPA)-axis and glucocorticoid secretions in relation to behavioral performances. The beneficial effects of higher dietary PUFA intakes and PUFA:SFA ratios may also affect social interactions and social-living per se, where adequate physiological and behavioral responses are essential to cope with unstable social environmental conditions. Effects of diets high in PUFAs or SFAs and a control diet were investigated in male and female guinea pigs after 60 days of supplementation. Plasma fatty acid patterns served as an indicator of the general fatty acid status. HPA-axis activities, determined by measuring saliva cortisol concentrations, social behaviors, and hierarchy ranks were analyzed during group housing of established single-sexed groups and during challenging social confrontations with unfamiliar individuals of the other groups. The plasma PUFA:SFA ratio was highest in PUFA supplemented animals, with female levels significantly exceeding males, and lowest in SFA animals. SFA males and females showed increased saliva cortisol levels and decreased aggressiveness during group housing, while sociopositive behaviors were lowest in PUFA males. Males generally showed higher cortisol increases in response to the challenging social confrontations with unfamiliar individuals than females. While increasing cortisol concentrations were detected in control and PUFA animals, no such effect was found in SFA animals. During social confrontations, PUFA males showed higher levels of agonistic and sociopositive behaviors and also gained higher dominance ranks among males, which was not detected for females. While SFAs seemingly impaired cortisol responses and social behaviors, PUFAs enabled adequate behavioral responses in male individuals under stressful new social environmental conditions. This sex-specific effect was possibly

  3. New age- and sex-specific criteria for QT prolongation based on rate correction formulas that minimize bias at the upper normal limits.

    Science.gov (United States)

    Rautaharju, Pentti M; Mason, Jay W; Akiyama, Toshio

    2014-07-01

    Existing formulas for rate-corrected QT (QTc) commonly fail to properly adjust the upper normal limits which are more critical than the mean QTc for evaluation of prolonged QT. Age- and sex-related differences in QTc are also often overlooked. Our goal was to establish criteria for prolonged QTc using formulas that minimize QTc bias at the upper normal limits. Strict criteria were used in selecting a study group of 57,595 persons aged 5 to 89 years (54% women) and to exclude electrocardiograms (ECG) with possible disease-associated changes. Two QT rate adjustment formulas were identified which both minimized rate-dependency in the 98 th percentile limits: QTcmod, based on an electrophysiological model (QTcMod = QTx(120 + HR)/180)), and QTcLogLin, a power function of the RR interval with exponents 0.37 for men and 0.38 for women. QTc shortened in men during adolescence and QTcMod became 13 ms shorter than in women at age 20-29 years. The sex difference was maintained through adulthood although decreasing with age. The criteria established for prolonged QTc were: Age < 40 years, men 430 ms, women 440 ms; Age 40 to 69, men 440 ms, women 450 ms; Age ≥ 70 years, men 455 ms, and women 460 ms. Sex difference in QTc originates from shortened QT in adolescent males. Upper normal limits for QTc vary substantially by age and sex, and it is essential to use age- and sex-specific criteria for evaluation of QT prolongation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Whole-genome in-silico subtractive hybridization (WISH - using massive sequencing for the identification of unique and repetitive sex-specific sequences: the example of Schistosoma mansoni

    Directory of Open Access Journals (Sweden)

    Parrinello Hugues

    2010-06-01

    Full Text Available Abstract Background Emerging methods of massive sequencing that allow for rapid re-sequencing of entire genomes at comparably low cost are changing the way biological questions are addressed in many domains. Here we propose a novel method to compare two genomes (genome-to-genome comparison. We used this method to identify sex-specific sequences of the human blood fluke Schistosoma mansoni. Results Genomic DNA was extracted from male and female (heterogametic S. mansoni adults and sequenced with a Genome Analyzer (Illumina. Sequences are available at the NCBI sequence read archive http://www.ncbi.nlm.nih.gov/Traces/sra/ under study accession number SRA012151.6. Sequencing reads were aligned to the genome, and a pseudogenome composed of known repeats. Straightforward comparative bioinformatics analysis was performed to compare male and female schistosome genomes and identify female-specific sequences. We found that the S. mansoni female W chromosome contains only few specific unique sequences (950 Kb i.e. about 0.2% of the genome. The majority of W-specific sequences are repeats (10.5 Mb i.e. about 2.5% of the genome. Arbitrarily selected W-specific sequences were confirmed by PCR. Primers designed for unique and repetitive sequences allowed to reliably identify the sex of both larval and adult stages of the parasite. Conclusion Our genome-to-genome comparison method that we call "whole-genome in-silico subtractive hybridization" (WISH allows for rapid identification of sequences that are specific for a certain genotype (e.g. the heterogametic sex. It can in principle be used for the detection of any sequence differences between isolates (e.g. strains, pathovars or even closely related species.

  5. Zinc, vitamin A, and glutamine supplementation in Brazilian shantytown children at risk for diarrhea results in sex-specific improvements in verbal learning

    Directory of Open Access Journals (Sweden)

    Aldo A. M. Lima

    2013-01-01

    Full Text Available OBJECTIVE: To identify the impact of supplemental zinc, vitamin A, and glutamine, alone or in combination, on long-term cognitive outcomes among Brazilian shantytown children with low median height-for-age z-scores. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in children aged three months to nine years old from the urban shanty compound community of Fortaleza, Brazil. Demographic and anthropometric information was assessed. The random treatment groups available for cognitive testing (total of 167 children were: (1 placebo, n = 25; (2 glutamine, n = 23; (3 zinc, n = 18; (4 vitamin A, n = 19; (5 glutamine+zinc, n = 20; (6 glutamine+vitamin A, n = 21; (7 zinc+vitamin A, n = 23; and (8 glutamine+zinc+vitamin A, n = 18. Neuropsychological tests were administered for the cognitive domains of non-verbal intelligence and abstraction, psychomotor speed, verbal memory and recall ability, and semantic and phonetic verbal fluency. Statistical analyses were performed using SPSS, version 16.0. ClinicalTrials.gov: NCT00133406. RESULTS: Girls receiving a combination of glutamine, zinc, and vitamin A had higher mean age-adjusted verbal learning scores than girls receiving only placebo (9.5 versus 6.4, p = 0.007 and girls receiving zinc+vitamin A (9.5 versus 6.5, p = 0.006. Similar group differences were not found between male study children. CONCLUSIONS: The findings suggest that combination therapy offers a sex-specific advantage on tests of verbal learning, similar to that seen among female patients following traumatic brain injury.

  6. Cardiomyocyte-specific deletion of the G protein-coupled estrogen receptor (GPER) leads to left ventricular dysfunction and adverse remodeling: A sex-specific gene profiling analysis.

    Science.gov (United States)

    Wang, Hao; Sun, Xuming; Chou, Jeff; Lin, Marina; Ferrario, Carlos M; Zapata-Sudo, Gisele; Groban, Leanne

    2017-08-01

    Activation of G protein-coupled estrogen receptor (GPER) by its agonist, G1, protects the heart from stressors such as pressure-overload, ischemia, a high-salt diet, estrogen loss, and aging, in various male and female animal models. Due to nonspecific effects of G1, the exact functions of cardiac GPER cannot be concluded from studies using systemic G1 administration. Moreover, global knockdown of GPER affects glucose homeostasis, blood pressure, and many other cardiovascular-related systems, thereby confounding interpretation of its direct cardiac actions. We generated a cardiomyocyte-specific GPER knockout (KO) mouse model to specifically investigate the functions of GPER in cardiomyocytes. Compared to wild type mice, cardiomyocyte-specific GPER KO mice exhibited adverse alterations in cardiac structure and impaired systolic and diastolic function, as measured by echocardiography. Gene deletion effects on left ventricular dimensions were more profound in male KO mice compared to female KO mice. Analysis of DNA microarray data from isolated cardiomyocytes of wild type and KO mice revealed sex-based differences in gene expression profiles affecting multiple transcriptional networks. Gene Set Enrichment Analysis (GSEA) revealed that mitochondrial genes are enriched in GPER KO females, whereas inflammatory response genes are enriched in GPER KO males, compared to their wild type counterparts of the same sex. The cardiomyocyte-specific GPER KO mouse model provides us with a powerful tool to study the functions of GPER in cardiomyocytes. The gene expression profiles of the GPER KO mice provide foundational information for further study of the mechanisms underlying sex-specific cardioprotection by GPER. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Candidate genes have sex-specific effects on timing of spring migration and moult speed in a long-distance migratory bird.

    Science.gov (United States)

    Bazzi, Gaia; Podofillini, Stefano; Gatti, Emanuele; Gianfranceschi, Luca; Cecere, Jacopo G; Spina, Fernando; Saino, Nicola; Rubolini, Diego

    2017-10-01

    The timing of major life-history events, such as migration and moult, is set by endogenous circadian and circannual clocks, that have been well characterized at the molecular level. Conversely, the genetic sources of variation in phenology and in other behavioral traits have been sparsely addressed. It has been proposed that inter-individual variability in the timing of seasonal events may arise from allelic polymorphism at phenological candidate genes involved in the signaling cascade of the endogenous clocks. In this study of a long-distance migratory passerine bird, the willow warbler Phylloscopus trochilus , we investigated whether allelic variation at 5 polymorphic loci of 4 candidate genes ( Adcyap1 , Clock , Creb1 , and Npas2 ), predicted 2 major components of the annual schedule, namely timing of spring migration across the central Mediterranean sea and moult speed, the latter gauged from ptilochronological analyses of tail feathers moulted in the African winter quarters. We identified a novel Clock gene locus ( Clock region 3) showing polyQ polymorphism, which was however not significantly associated with any phenotypic trait. Npas2 allele size predicted male (but not female) spring migration date, with males bearing longer alleles migrating significantly earlier than those bearing shorter alleles. Creb1 allele size significantly predicted male (but not female) moult speed, longer alleles being associated with faster moult. All other genotype-phenotype associations were statistically non-significant. These findings provide new evidence for a role of candidate genes in modulating the phenology of different circannual activities in long-distance migratory birds, and for the occurrence of sex-specific candidate gene effects.

  8. Early-life lead exposure results in dose- and sex-specific effects on weight and epigenetic gene regulation in weanling mice

    Science.gov (United States)

    Faulk, Christopher; Barks, Amanda; Liu, Kevin; Goodrich, Jaclyn M; Dolinoy, Dana C

    2013-01-01

    Aims Epidemiological and animal data suggest that the development of adult chronic conditions is influenced by early-life exposure-induced changes to the epigenome. This study investigates the effects of perinatal lead (Pb) exposure on DNA methylation and bodyweight in weanling mice. Materials & methods Viable yellow agouti (Avy) mouse dams were exposed to 0, 2.1, 16 and 32 ppm Pb acetate before conception through weaning. Epigenetic effects were evaluated by scoring coat color of Avy/a offspring and quantitative bisulfite sequencing of two retrotransposon-driven (Avy and CDK5 activator-binding protein intracisternal A particle element) and two imprinted (Igf2 and Igf2r) loci in tail DNA. Results Maternal blood Pb levels were below the limit of detection in controls, and 4.1, 25.1 and 32.1 μg/dl for each dose, respectively. Pb exposure was associated with a trend of increased wean bodyweight in males (p = 0.03) and altered coat color in Avy/a offspring. DNA methylation at Avy and the CDK5 activator-binding protein intracisternal A-particle element was significantly different from controls following a cubic trend (p = 0.04; p = 0.01), with male-specific effects at the Avy locus. Imprinted genes did not shift in methylation across exposures. Conclusion Dose- and sex-specific responses in bodyweight and DNA methylation indicate that Pb acts on the epigenome in a locus-specific fashion, dependent on the genomic feature hosting the CpG site of interest, and that sex is a factor in epigenetic response. PMID:24059796

  9. Marine omega-3 polyunsaturated fatty acids induce sex-specific changes in reinforcer-controlled behaviour and neurotransmitter metabolism in a spontaneously hypertensive rat model of ADHD

    Directory of Open Access Journals (Sweden)

    Dervola Kine S

    2012-12-01

    Full Text Available Abstract Background Previous reports suggest that omega-3 (n-3 polyunsaturated fatty acids (PUFA supplements may reduce ADHD-like behaviour. Our aim was to investigate potential effects of n-3 PUFA supplementation in an animal model of ADHD. Methods We used spontaneously hypertensive rats (SHR. SHR dams were given n-3 PUFA (EPA and DHA-enriched feed (n-6/n-3 of 1:2.7 during pregnancy, with their offspring continuing on this diet until sacrificed. The SHR controls and Wistar Kyoto (WKY control rats were given control-feed (n-6/n-3 of 7:1. During postnatal days (PND 25–50, offspring were tested for reinforcement-dependent attention, impulsivity and hyperactivity as well as spontaneous locomotion. The animals were then sacrificed at PND 55–60 and their neostriata were analysed for monoamine and amino acid neurotransmitters with high performance liquid chromatography. Results n-3 PUFA supplementation significantly enhanced reinforcement-controlled attention and reduced lever-directed hyperactivity and impulsiveness in SHR males whereas the opposite or no effects were observed in females. Analysis of neostriata from the same animals showed significantly enhanced dopamine and serotonin turnover ratios in the male SHRs, whereas female SHRs showed no change, except for an intermediate increase in serotonin catabolism. In contrast, both male and female SHRs showed n-3 PUFA-induced reduction in non-reinforced spontaneous locomotion, and sex-independent changes in glycine levels and glutamate turnover. Conclusions Feeding n-3 PUFAs to the ADHD model rats induced sex-specific changes in reinforcement-motivated behaviour and a sex-independent change in non-reinforcement-associated behaviour, which correlated with changes in presynaptic striatal monoamine and amino acid signalling, respectively. Thus, dietary n-3 PUFAs may partly ameliorate ADHD-like behaviour by reinforcement-induced mechanisms in males and partly via reinforcement-insensitive mechanisms

  10. Antidepressant-like effects of guanfacine and sex-specific differences in effects on c-fos immunoreactivity and paired-pulse ratio in male and female mice.

    Science.gov (United States)

    Mineur, Yann S; Bentham, Matthew P; Zhou, Wen-Liang; Plantenga, Margreet E; McKee, Sherry A; Picciotto, Marina R

    2015-10-01

    The a2A-noradrenergic agonist guanfacine can decreases stress-induced smoking in female, but not male, human smokers. It is not known whether these effects are due to effects on mood regulation and/or result from nicotinic-cholinergic interactions. The objective of the study was to determine whether there are sex differences in the effect of guanfacine in tests of anxiolytic and antidepressant efficacy in mice at baseline and in a hypercholinergic model of depression induced by the acetylcholinesterase inhibitor physostigmine. The effects of guanfacine were measured in the light/dark box, tail suspension, and the forced swim test in female and male C57BL/6J mice. In parallel, electrophysiological properties were evaluated in the prefrontal cortex, a critical brain region involved in stress responses. c-fos immunoreactivity was measured in other brain regions known to regulate mood. Despite a baseline sex difference in behavior in the forced swim test (female mice were more immobile), guanfacine had similar, dose-dependent, antidepressant-like effects in mice of both sexes (optimal dose, 0.15 mg/kg). An antidepressant-like effect of guanfacine was also observed following pre-treatment with physostigmine. A sex difference in the paired-pulse ratio in the prefrontal cortex (PFC) (male, 1.4; female, 2.1) was observed at baseline that was normalized by guanfacine. Other brain areas involved in cholinergic control of depression-like behaviors, including the basolateral amygdala and lateral septum, showed sex-specific changes in c-fos expression. Guanfacine has a robust antidepressant-like effect and can reverse a depression-like state induced by increased acetylcholine (ACh) signaling. These data suggest that different brain areas are recruited in female and male mice, despite similar behavioral responses to guanfacine.

  11. Age- and sex-specific relationships between household income, education, and diabetes mellitus in Korean adults: the Korea National Health and Nutrition Examination Survey, 2008-2010.

    Directory of Open Access Journals (Sweden)

    So-Ra Kim

    Full Text Available To investigate the effects of age and sex on the relationship between socioeconomic status (SES and the prevalence and control status of diabetes mellitus (DM in Korean adults.Data came from 16,175 adults (6,951 men and 9,227 women over the age of 30 who participated in the 2008-2010 Korea National Health and Nutrition Examination Survey. SES was measured by household income or education level. The adjusted odds ratios (ORs and corresponding 95% confidence intervals (95% CI for the prevalence or control status of diabetes were calculated using multiple logistic regression analyses across household income quartiles and education levels.The household income-DM and education level-DM relationships were significant in younger age groups for both men and women. The adjusted ORs and 95% CI for diabetes were 1.51 (0.97, 2.34 and 2.28 (1.29, 4.02 for the lowest vs. highest quartiles of household income and education level, respectively, in women younger than 65 years of age (both P for linear trend < 0.05 with Bonferroni adjustment. The adjusted OR and 95% CI for diabetes was 2.28 (1.53, 3.39 for the lowest vs. highest quartile of household income in men younger than 65 (P for linear trend < 0.05 with Bonferroni adjustment. However, in men and women older than 65, no associations were found between SES and the prevalence of DM. No significant association between SES and the status of glycemic control was detected.We found age- and sex-specific differences in the relationship of household income and education with the prevalence of DM in Korea. DM preventive care is needed for groups with a low SES, particularly in young or middle-aged populations.

  12. Sex-specific relationships of physical activity, body composition, and muscle quality with lower-extremity physical function in older men and women.

    Science.gov (United States)

    Straight, Chad R; Brady, Anne O; Evans, Ellen

    2015-03-01

    This study aims to determine the sex-specific relationships of physical activity, body composition, and muscle quality with lower-extremity physical function in older men and women. Seventy-nine community-dwelling men (n = 39; mean [SD] age, 76.1 [6.2] y; mean [SD] body mass index, 27.3 [3.8] kg/m(2)) and women (n = 40; mean [SD] age, 75.8 [5.5] y; mean [SD] body mass index, 27.0 [3.8] kg/m(2)) were assessed for physical activity via questionnaire, body composition via dual-energy x-ray absorptiometry scanning, leg extension power using the Nottingham power rig, and muscle quality (W/kg; the ratio of leg extension power [W] to lower-body mineral-free lean mass [kg]). A composite measure of physical function was obtained by summing Z scores from the 6-minute walk, 8-ft up-and-go test, and 30-second chair-stand test. As expected, men had significantly greater levels of physical activity, lower adiposity, greater lean mass, higher leg extension power, and greater muscle quality compared with women (all P physical activity were the strongest predictors of lower-extremity physical function in men and independently explained 42% and 29% of the variance, respectively. In women, muscle quality (16%) and percent body fat (12%) were independent predictors after adjustment for covariates. Muscle quality is the strongest predictor of lower-extremity physical function in men and women, but sex impacts the importance of physical activity and adiposity. These findings suggest that older men and women may benefit from different intervention strategies for preventing physical disability and also highlight the importance of weight management for older women to preserve physical function.

  13. Sex-specific trade-offs and compensatory mechanisms: bite force and sprint speed pose conflicting demands on the design of geckos (Hemidactylus frenatus).

    Science.gov (United States)

    Cameron, S F; Wynn, M L; Wilson, R S

    2013-10-15

    One of the more intuitive viability costs that can result from the possession of exaggerated sexually selected traits is increased predation pressure as a result of reduced locomotor capacity. Despite mixed empirical support for such locomotor costs, recent studies suggest that such costs may be masked by compensatory traits that effectively offset any detrimental effects. In this study, we provide a comprehensive assessment of the locomotor costs associated with improved male-male competitive ability by simultaneously testing for locomotor trade-offs and potential compensatory mechanisms in territorial male and non-territorial female geckos. Fighting capacity and escape performance of male Asian house geckos (Hemidactylus frenatus) are likely to pose conflicting demands on the optimum phenotype for each task. Highly territorial and aggressive males may require greater investment in head size/strength but such an enhancement may affect overall escape performance. Among male geckos, we found that greater biting capacity because of larger head size was associated with reduced sprint performance; this trade-off was further exacerbated when sprinting on an incline. Females, however, showed no evidence of this trade-off on either flat or inclined surfaces. The sex specificity of this trade-off suggests that the sexes differ in their optimal strategies for dealing with the conflicting requirements of bite force and sprint speed. Unlike males, female H. frenatus had a positive association between hind-limb length and head size, suggesting that they have utilised a compensatory mechanism to alleviate the possible locomotor costs of larger head sizes. It appears that there is greater selection on traits that improve fighting ability (bite force) for males, but it is viability traits (sprint speed) that appear to be of greater importance for females. Our results emphasise that only by examining both functional trade-offs and potential compensatory mechanisms is it possible

  14. Embryonic GABA(B receptor blockade alters cell migration, adult hypothalamic structure, and anxiety- and depression-like behaviors sex specifically in mice.

    Directory of Open Access Journals (Sweden)

    Matthew S Stratton

    Full Text Available Neurons of the paraventricular nucleus of the hypothalamus (PVN regulate the hypothalamic- pituitary-adrenal (HPA axis and the autonomic nervous system. Females lacking functional GABA(B receptors because of a genetic disruption of the R1 subunit have altered cellular characteristics in and around the PVN at birth. The genetic disruption precluded appropriate assessments of physiology or behavior in adulthood. The current study was conducted to test the long term impact of a temporally restricting pharmacological blockade of the GABA(B receptor to a 7-day critical period (E11-E17 during embryonic development. Experiments tested the role of GABA(B receptor signaling in fetal development of the PVN and later adult capacities for adult stress related behaviors and physiology. In organotypic slices containing fetal PVN, there was a female specific, 52% increase in cell movement speeds with GABA(B receptor antagonist treatment that was consistent with a sex-dependent lateral displacement of cells in vivo following 7 days of fetal exposure to GABA(B receptor antagonist. Anxiety-like and depression-like behaviors, open-field activity, and HPA mediated responses to restraint stress were measured in adult offspring of mothers treated with GABA(B receptor antagonist. Embryonic exposure to GABA(B receptor antagonist resulted in reduced HPA axis activation following restraint stress and reduced depression-like behaviors. There was also increased anxiety-like behavior selectively in females and hyperactivity in males. A sex dependent response to disruptions of GABA(B receptor signaling was identified for PVN formation and key aspects of physiology and behavior. These changes correspond to sex specific prevalence in similar human disorders, namely anxiety disorders and hyperactivity.

  15. The Wnt Signaling Pathway Is Differentially Expressed during the Bovine Herpesvirus 1 Latency-Reactivation Cycle: Evidence That Two Protein Kinases Associated with Neuronal Survival, Akt3 and BMPR2, Are Expressed at Higher Levels during Latency.

    Science.gov (United States)

    Workman, Aspen; Zhu, Liqian; Keel, Brittney N; Smith, Timothy P L; Jones, Clinton

    2018-04-01

    Sensory neurons in trigeminal ganglia (TG) of calves latently infected with bovine herpesvirus 1 (BoHV-1) abundantly express latency-related (LR) gene products, including a protein (ORF2) and two micro-RNAs. Recent studies in mouse neuroblastoma cells (Neuro-2A) demonstrated ORF2 interacts with β-catenin and a β-catenin coactivator, high-mobility group AT-hook 1 (HMGA1) protein, which correlates with increased β-catenin-dependent transcription and cell survival. β-Catenin and HMGA1 are readily detected in a subset of latently infected TG neurons but not TG neurons from uninfected calves or reactivation from latency. Consequently, we hypothesized that the Wnt/β-catenin signaling pathway is differentially expressed during the latency and reactivation cycle and an active Wnt pathway promotes latency. RNA-sequencing studies revealed that 102 genes associated with the Wnt/β-catenin signaling pathway were differentially expressed in TG during the latency-reactivation cycle in calves. Wnt agonists were generally expressed at higher levels during latency, but these levels decreased during dexamethasone-induced reactivation. The Wnt agonist bone morphogenetic protein receptor 2 (BMPR2) was intriguing because it encodes a serine/threonine receptor kinase that promotes neuronal differentiation and inhibits cell death. Another differentially expressed gene encodes a protein kinase (Akt3), which is significant because Akt activity enhances cell survival and is linked to herpes simplex virus 1 latency and neuronal survival. Additional studies demonstrated ORF2 increased Akt3 steady-state protein levels and interacted with Akt3 in transfected Neuro-2A cells, which correlated with Akt3 activation. Conversely, expression of Wnt antagonists increased during reactivation from latency. Collectively, these studies suggest Wnt signaling cooperates with LR gene products, in particular ORF2, to promote latency. IMPORTANCE Lifelong BoHV-1 latency primarily occurs in sensory neurons

  16. Differential effect of age on survival in advanced NSCLC in women versus men: analysis of recent Eastern Cooperative Oncology Group (ECOG) studies, with and without bevacizumab.

    Science.gov (United States)

    Wakelee, H A; Dahlberg, S E; Brahmer, J R; Schiller, J H; Perry, M C; Langer, C J; Sandler, A B; Belani, C P; Johnson, D H

    2012-06-01

    The impact of age on prognosis in advanced stage non-small cell lung cancer (NSCLC) may differ by sex. Eligible patients (N=1590) from E1594, a 4-arm platinum-based chemotherapy trial, and E4599 (carboplatin/paclitaxel ± bevacizumab) chemotherapy arm were divided into male and female cohorts and separated into age groups of women ≥60 years old treated with chemotherapy alone on E1594 and E4599 was 11.6 months versus 9.0 months for women women (younger had greater benefit), with no age effect in men. In this unplanned, exploratory subgroup analysis of advanced stage NSCLC ECOG trials, women ≥60 years old treated with chemotherapy live longer than men and younger women. In contrast, bevacizumab survival benefit was more pronounced in men of any age and in younger women on E4599. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  17. Reassessment of the differential effects of ultraviolet and ionizing radiation on HIV promoter: the use of cell survival as the basis for comparisons

    International Nuclear Information System (INIS)

    Beer, J.Z.; Olvey, K.M.; Lee, W.; Zmudzka, B.Z.

    1994-01-01

    Effects of different radiation treatments on the human immunodeficiency virus-1 (HIV) promoter were reassessed for exposures comparable to those encountered in clinical or cosmetic practice, using survival of the host cell as a basis for comparisons. The exposures were performed with two ultraviolet radiation sources commonly used as medical or cosmetic devices (UVASUN 2000 and FS20 lamps), a germicidal (G15T8) lamp and an X-ray machine. The UVC component of the FS20 lamp was filtered out. The emission spectra of the lamps were determined. The characteristics of these sources allowed us to discriminate among effects of UVA1 (340-400 nm), UVB + UVA2 (280-340 nm) and UVC (254 nm) radiations. Effects of irradiation were ascertained using cultures of HeLa cells stably transfected with the HIV promoter linked to a reporter-chloramphenicol acetyl transferase-gene. (Author)

  18. Microarray-Based Screening of Differentially Expressed Genes of E. coli O157:H7 Sakai during Preharvest Survival on Butterhead Lettuce

    Directory of Open Access Journals (Sweden)

    Inge Van der Linden

    2016-01-01

    Full Text Available Numerous outbreaks of Escherichia coli O157:H7 have been linked to the consumption of leafy vegetables. However, up to the present, little has been known about E. coli O157:H7’s adaptive responses to survival on actively growing (and thus responsive plants. In this study, whole genome transcriptional profiles were generated from E. coli O157:H7 cells (isolate Sakai, stx- one hour and two days after inoculation on the leaves of growing butterhead lettuce, and compared with an inoculum control. A total of 273 genes of E. coli O157:H7 Sakai (5.04% of the whole genome were significantly induced or repressed by at least two-fold (p < 0.01 in at least one of the analyzed time points in comparison with the control. Several E. coli O157:H7 genes associated with oxidative stress and antimicrobial resistance were upregulated, including the iron-sulfur cluster and the multiple antibiotic resistance (mar operon, whereas the Shiga toxin virulence genes were downregulated. Nearly 40% of the genes with significantly different expression were poorly characterized genes or genes with unknown functions. These genes are of special interest for future research as they may play an important role in the pathogens’ adaptation to a lifestyle on plants. In conclusion, these findings suggest that the pathogen actively interacts with the plant environment by adapting its metabolism and responding to oxidative stress.

  19. Differential effects of 18- and 24-Gy cranial irradiation on growth rate and growth hormone release in children with prolonged survival after acute lymphocytic leukemia

    International Nuclear Information System (INIS)

    Cicognani, A.; Cacciari, E.; Vecchi, V.; Cau, M.; Balsamo, A.; Pirazzoli, P.; Tosi, M.T.; Rosito, P.; Paolucci, G.

    1988-01-01

    To evaluate the effects of two different doses of cranial irradiation on growth and growth hormone (GH) release, we studied 61 children with acute lymphocytic leukemia who had survived at least five years in continuous complete remission. Forty-three children received 24 Gy (group 1) and 18 children received 18 Gy (group 2). Height was evaluated at diagnosis, at the end of treatment, and 6, 12, and 24 months later. Growth hormone release was evaluated by arginine and levodopa tests after the end of treatment. After diagnosis, the height SD score decreased significantly in both groups; two years after the end of treatment, only group 1 showed an SD score for height that was still significantly lower than at diagnosis. Group 1 showed impaired GH responses to the tests and, compared with controls, group 1 in fact included a percentage of subjects with a normal response to levodopa (ie, greater than 8 micrograms/L) that was significantly lower (56.4% vs 83.3%) and a percentage of nonresponders to both tests that was significantly higher (21.6% vs 0%). These data indicate that only patients treated with lower cranial irradiation dosage (18 Gy) had complete growth recovery and normal GH responses to pharmacologic tests

  20. Positive and negative early life experiences differentially modulate long term survival and amyloid protein levels in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Lesuis, Sylvie L; Maurin, Herve; Borghgraef, Peter; Lucassen, Paul J; Van Leuven, Fred; Krugers, Harm J

    2016-06-28

    Stress has been implicated as a risk factor for the severity and progression of sporadic Alzheimer's disease (AD). Early life experiences determine stress responsivity in later life, and modulate age-dependent cognitive decline. Therefore, we examined whether early life experiences influence AD outcome in a bigenic mouse model which progressively develops combined tau and amyloid pathology (biAT mice).Mice were subjected to either early life stress (ELS) or to 'positive' early handling (EH) postnatally (from day 2 to 9). In biAT mice, ELS significantly compromised long term survival, in contrast to EH which increased life expectancy. In 4 month old mice, ELS-reared biAT mice displayed increased hippocampal Aβ levels, while these levels were reduced in EH-reared biAT mice. No effects of ELS or EH were observed on the brain levels of APP, protein tau, or PSD-95. Dendritic morphology was moderately affected after ELS and EH in the amygdala and medial prefrontal cortex, while object recognition memory and open field performance were not affected. We conclude that despite the strong transgenic background, early life experiences significantly modulate the life expectancy of biAT mice. Parallel changes in hippocampal Aβ levels were evident, without affecting cognition of young adult biAT mice.

  1. Genome-Wide Association Study Identifies Two Novel Loci with Sex-Specific Effects for Type 2 Diabetes Mellitus and Glycemic Traits in a Korean Population

    Directory of Open Access Journals (Sweden)

    Min Jin Go

    2014-10-01

    Full Text Available BackgroundUntil recently, genome-wide association study (GWAS-based findings have provided a substantial genetic contribution to type 2 diabetes mellitus (T2DM or related glycemic traits. However, identification of allelic heterogeneity and population-specific genetic variants under consideration of potential confounding factors will be very valuable for clinical applicability. To identify novel susceptibility loci for T2DM and glycemic traits, we performed a two-stage genetic association study in a Korean population.MethodsWe performed a logistic analysis for T2DM, and the first discovery GWAS was analyzed for 1,042 cases and 2,943 controls recruited from a population-based cohort (KARE, n=8,842. The second stage, de novo replication analysis, was performed in 1,216 cases and 1,352 controls selected from an independent population-based cohort (Health 2, n=8,500. A multiple linear regression analysis for glycemic traits was further performed in a total of 14,232 nondiabetic individuals consisting of 7,696 GWAS and 6,536 replication study participants. A meta-analysis was performed on the combined results using effect size and standard errors estimated for stage 1 and 2, respectively.ResultsA combined meta-analysis for T2DM identified two new (rs11065756 and rs2074356 loci reaching genome-wide significance in CCDC63 and C12orf51 on the 12q24 region. In addition, these variants were significantly associated with fasting plasma glucose and homeostasis model assessment of β-cell function. Interestingly, two independent single nucleotide polymorphisms were associated with sex-specific stratification in this study.ConclusionOur study showed a strong association between T2DM and glycemic traits. We further observed that two novel loci with multiple diverse effects were highly specific to males. Taken together, these findings may provide additional insights into the clinical assessment or subclassification of disease risk in a Korean population.

  2. Association of Differentiation-Related Gene-1 (DRG1) with Breast Cancer Survival and in Vitro Impact of DRG1 Suppression

    International Nuclear Information System (INIS)

    Baig, Ruqia Mehmood; Sanders, Andrew J.; Kayani, Mahmood Akhtar; Jiang, Wen G.

    2012-01-01

    Differentiation-related gene-1, DRG1, is a metastasis suppressor gene whose expression has been shown to be dysregulated in a number of malignancies. The current study examines the expression of DRG1 in a clinical breast cohort and its association with a number of clinical pathological factors using quantitative polymerase chain reaction. Additionally, DRG1 expression is targeted in vitro using ribozyme transgene technology to explore the function of DRG1 in two human breast cancer cell lines. Low levels of DRG1 were found in patients who developed metastasis (p = 0.036) and who died of breast cancer (p = 0.0048) compared to disease free patients. Knockdown of DRG1 also resulted in significantly increased invasion and motility, but decreased matrix-adhesion in MCF7 cells. Knockdown of DRG1 seemed to have minimal impact on the cellular functions of the MDA-MB-231 breast cancer cell line causing no significant differences in cell growth, invasion, motility or matrix-adhesion. Thus, DRG1 appears to be linked to development of metastasis and death in patients who died as a result of breast cancer and may be useful as a prognostic factor as its knockdown appears to be linked with increased invasion and motility and decreased adhesion in MCF7 breast cancer cells

  3. Differential effects of early weaning for HIV-free survival of children born to HIV-infected mothers by severity of maternal disease.

    Directory of Open Access Journals (Sweden)

    Louise Kuhn

    2009-06-01

    Full Text Available We previously reported no benefit of early weaning for HIV-free survival of children born to HIV-infected mothers in intent-to-treat analyses. Since early weaning was poorly accepted, we conducted a secondary analysis to investigate whether beneficial effects may have been hidden.958 HIV-infected women in Lusaka, Zambia, were randomized to abrupt weaning at 4 months (intervention or to continued breastfeeding (control. Children were followed to 24 months with regular HIV PCR tests and examinations to determine HIV infection or death. Detailed behavioral data were collected on when all breastfeeding ended. Most participants were recruited before antiretroviral treatment (ART became available. We compared outcomes among mother-child pairs who weaned earlier or later than intended by study design adjusting for potential confounders.Of infants alive, uninfected and still breastfeeding at 4 months in the intervention group, 16.1% who weaned as instructed acquired HIV or died by 24 months compared to 16.0% who did not comply (p = 0.98. Children of women with less severe disease during pregnancy (not eligible for ART had worse outcomes if their mothers weaned as instructed (RH = 2.60 95% CI: 1.06-6.36 compared to those who continued breastfeeding. Conversely, children of mothers with more severe disease (eligible for ART but did not receive it who weaned early had better outcomes (p-value interaction = 0.002. In the control group, weaning before 15 months was associated with 3.94-fold (95% CI: 1.65-9.39 increase in HIV infection or death among infants of mothers with less severe disease.Incomplete adherence did not mask a benefit of early weaning. On the contrary, for women with less severe disease, early weaning was harmful and continued breastfeeding resulted in better outcomes. For women with more advanced disease, ART should be given during pregnancy for maternal health and to reduce transmission, including through breastfeeding

  4. Evidence from a homosexual sample for a sex-specific rival-oriented mechanism : Jealousy as a function of a rival's physical attractiveness and dominance

    NARCIS (Netherlands)

    Buunk, BP; Dijkstra, P

    2001-01-01

    Among heterosexual women in particular. a rival's physical attractiveness evokes jealousy, whereas among heterosexual men in particular. a rival's dominance evokes feelings of jealousy. The present study conducted with gay men and lesbian women examined whether these sex-differentiated responses

  5. Survival Analysis

    CERN Document Server

    Miller, Rupert G

    2011-01-01

    A concise summary of the statistical methods used in the analysis of survival data with censoring. Emphasizes recently developed nonparametric techniques. Outlines methods in detail and illustrates them with actual data. Discusses the theory behind each method. Includes numerous worked problems and numerical exercises.

  6. A maternal high-fat, high-sucrose diet has sex-specific effects on fetal glucocorticoids with little consequence for offspring metabolism and voluntary locomotor activity in mice.

    Directory of Open Access Journals (Sweden)

    Eunice H Chin

    Full Text Available Maternal overnutrition and obesity during pregnancy can have long-term effects on offspring physiology and behaviour. These developmental programming effects may be mediated by fetal exposure to glucocorticoids, which is regulated in part by placental 11β-hydroxysteroid dehydrogenase (11β-HSD type 1 and 2. We tested whether a maternal high-fat, high-sucrose diet would alter expression of placental 11β-HSD1 and 2, thereby increasing fetal exposure to maternal glucocorticoids, with downstream effects on offspring physiology and behaviour. C57BL/6J mice were fed a high-fat, high-sucrose (HFHS diet or a nutrient-matched low-fat, no-sucrose control diet prior to and during pregnancy and lactation. At day 17 of gestation, HFHS dams had ~20% lower circulating corticosterone levels than controls. Furthermore, there was a significant interaction between maternal diet and fetal sex for circulating corticosterone levels in the fetuses, whereby HFHS males tended to have higher corticosterone than control males, with no effect in female fetuses. However, placental 11β-HSD1 or 11β-HSD2 expression did not differ between diets or show an interaction between diet and sex. To assess potential long-term consequences of this sex-specific effect on fetal corticosterone, we studied locomotor activity and metabolic traits in adult offspring. Despite a sex-specific effect of maternal diet on fetal glucocorticoids, there was little evidence of sex-specific effects on offspring physiology or behaviour, although HFHS offspring of both sexes had higher circulating corticosterone at 9 weeks of age. Our results suggest the existence of as yet unknown mechanisms that mitigate the effects of altered glucocorticoid exposure early in development, making offspring resilient to the potentially negative effects of a HFHS maternal diet.

  7. Diagnosis of type 1 and type 2 myocardial infarction using a high-sensitivity cardiac troponin I assay with sex-specific 99th percentiles based on the third universal definition of myocardial infarction classification system.

    Science.gov (United States)

    Sandoval, Yader; Smith, Stephen W; Schulz, Karen M; Murakami, MaryAnn M; Love, Sara A; Nicholson, Jennifer; Apple, Fred S

    2015-04-01

    The frequency and characteristics of myocardial infarction (MI) subtypes per the Third Universal Definition of MI (TUDMI) classification system using high-sensitivity (hs) cardiac troponin assays with sex-specific cutoffs is not well known. We sought to describe the diagnostic characteristics of type 1 (T1MI) and type 2 (T2MI) MI using an hs-cardiac troponin I (hs-cTnI) assay with sex-specific cutoffs. A total of 310 consecutive patients with serial cTnI measurements obtained on clinical indication were studied with contemporary and hs-cTnI assays. Ninety-ninth percentile sex-specific upper reference limits (URLs) for the hs-cTnI assay were 16 ng/L for females and 34 ng/L for males. The TUDMI consensus recommendations were used to define and adjudicate MI based on each URL. A total of 127 (41%) patients had at least 1 hs-cTnI exceeding the sex-specific 99th percentiles, whereas 183 (59%) had hs-cTnI within the reference interval. Females had more myocardial injury related to supply/demand ischemia than males (39% vs 18%, P = 0.01), whereas males had more multifactorial or indeterminate injury (52% vs 33%, P = 0.05). By hs-cTnI, there were 32 (10%) acute MIs, among which 10 (3%) were T1MI and 22 (7%) were T2MI. T2MI represented 69% (22 out of 32) of all acute MIs, whereas T1MI represented 31% (10 out of 32). Ninety-five patients (31%) had an increased hs-cTnI above the 99th percentile but did not meet criteria for acute MI. The most common triggers for T2MI were tachyarrhythmias, hypotension/shock, and hypertension. By contemporary cTnI, more MIs (14 T1MI and 29 T2MI) were diagnosed. By contemporary cTnI, there were 43 MIs, 14 T1MI, and 29 T2MI. Fewer MI diagnoses were found with the hs-cTnI assay, contrary to the commonly accepted idea that hs-cTnI will lead to excessive false-positive diagnoses. © 2015 American Association for Clinical Chemistry.

  8. The fetal programming effect of prenatal smoking on Igf1r and Igf1 methylation is organ- and sex-specific.

    Science.gov (United States)

    Meyer, Karolin F; Verkaik-Schakel, Rikst Nynke; Timens, Wim; Kobzik, Lester; Plösch, Torsten; Hylkema, Machteld N

    2017-01-01

    The impact of prenatal smoke exposure (PSE) on DNA methylation has been demonstrated in blood samples from children of smoking mothers, but evidence for sex-dependent smoke-induced effects is limited. As the identified differentially methylated genes can be associated with developmental processes, and insulin-like growth factors (IGFs) play a critical role in prenatal tissue growth, we hypothesized that PSE induces fetal programming of Igf1r and Igf1. Using a mouse model of smoking during pregnancy, we show that PSE alters promoter methylation of Igf1r and Igf1 and deregulates their gene expression in lung and liver of fetal (E17.5) and neonatal (D3) mouse offspring. By further comparing female versus male, lung versus liver, or fetal versus neonatal time point, our results demonstrate that CpG site-specific aberrant methylation patterns sex-dependently vary per organ and time point. Moreover, PSE reduces gene expression of Igf1r and Igf1, dependent on organ, sex, and offspring's age. Our results indicate that PSE may be a source of organ-specific rather than general systemic fetal programming. This is exemplified here by gene promoter methylation and mRNA levels of Igf1r and Igf1, together with a sex- and organ-specific naturally established correlation of both parameters that is affected by prenatal smoke exposure. Moreover, the comparison of fetuses with neonates suggests a CpG site-dependent reversibility/persistence of PSE-induced differential methylation patterns.

  9. Early stress causes sex-specific, life-long changes in behaviour, levels of gonadal hormones, and gene expression in chickens.

    Directory of Open Access Journals (Sweden)

    Magnus Elfwing

    Full Text Available Early stress can have long-lasting phenotypic effects. Previous research shows that male and female chickens differ in many behavioural aspects, and respond differently to chronic stress. The present experiment aimed to broadly characterize long-term sex differences in responses to brief events of stress experienced during the first weeks of life. Chicks from a commercial egg-laying hybrid were exposed to stress by inducing periods of social isolation during their first three weeks of life, followed by a broad behavioural, physiological and genomic characterization throughout life. Early stressed males, but not females, where more anxious in an open field-test, stayed shorter in tonic immobility and tended to have delayed sexual maturity, as shown by a tendency for lower levels of testosterone compared to controls. While early stressed females did not differ from non-stressed in fear and sexual maturation, they were more socially dominant than controls. The differential gene expression profile in hypothalamus was significantly correlated from 28 to 213 days of age in males, but not in females. In conclusion, early stress had a more pronounced long-term effect on male than on female chickens, as evidenced by behavioral, endocrine and genomic responses. This may either be attributed to inherent sex differences due to evolutionary causes, or possibly to different stress related selection pressures on the two sexes during commercial chicken breeding.

  10. Prenatal stress increases the obesogenic effects of a high-fat-sucrose diet in adult rats in a sex-specific manner.

    Science.gov (United States)

    Paternain, L; de la Garza, A L; Batlle, M A; Milagro, F I; Martínez, J A; Campión, J

    2013-03-01

    Stress during pregnancy can induce metabolic disorders in adult offspring. To analyze the possible differential response to a high-fat-sucrose (HFS) diet in offspring affected by prenatal stress (PNS) or not, pregnant Wistar rats (n = 11) were exposed to a chronic mild stress during the third week of gestation. The aim of this study was to model a chronic depressive-like state that develops over time in response to exposure of rats to a series of mild and unpredictable stressors. Control dams (n = 11) remained undisturbed. Adult offspring were fed chow or HFS diet (20% protein, 35% carbohydrate, 45% fat) for 10 weeks. Changes in adiposity, biochemical profile, and retroperitoneal adipose tissue gene expression by real-time polymerase chain reaction were analyzed. An interaction was observed between HFS and PNS concerning visceral adiposity, with higher fat mass in HFS-fed stressed rats, statistically significant only in females. HFS modified lipid profile and increased insulin resistance biomarkers, while PNS reduced insulin concentrations and the homeostasis model assessment index. HFS diet increased gene (mRNA) expression for leptin and apelin and decreased cyclin-dependent kinase inhibitor 1A and fatty acid synthase (Fasn), whereas PNS increased Fasn and stearoyl-CoA desaturase1. An interaction between diet and PNS was observed for adiponutrin (Adpn) and peroxisome proliferator-activated receptor-γ coactivator1-α (Ppargc1a) gene expression: Adpn was increased by the PNS only in HFS-fed rats, whereas Ppargc1a was increased by the PNS only in chow-fed rats. From these results, it can be concluded that experience of maternal stress during intrauterine development can enhance predisposition to obesity induced by a HFS diet intake.

  11. Sex specific recruitment of a medial prefrontal cortex-hippocampal-thalamic system during context-dependent renewal of responding to food cues in rats.

    Science.gov (United States)

    Anderson, Lauren C; Petrovich, Gorica D

    2017-03-01

    Renewal, or reinstatement, of responding to food cues after extinction may explain the inability to resist palatable foods and change maladaptive eating habits. Previously, we found sex differences in context-dependent renewal of extinguished Pavlovian conditioned responding to food cues. Context-induced renewal involves cue-food conditioning and extinction in different contexts and the renewal of conditioned behavior is induced by return to the conditioning context (ABA renewal). Male rats showed renewal of responding while females did not. In the current study we sought to identify recruitment of key neural systems underlying context-mediated renewal and sex differences. We examined Fos induction within the ventromedial prefrontal cortex (vmPFC), hippocampal formation, thalamus and amygdala in male and female rats during the test for renewal. We found sex differences in vmPFC recruitment during renewal. Male rats in the experimental condition showed renewal of responding and had more Fos induction within the infralimbic and prelimbic vmPFC areas compared to controls that remained in the same context throughout training and testing. Females in the experimental condition did not show renewal or an increase in Fos induction. Additionally, Fos expression differed between experimental and control groups and between the sexes in the hippocampal formation, thalamus and amygdala. Within the ventral subiculum, the experimental groups of both sexes had more Fos compared to control groups. Within the dorsal CA1 and the anterior region of the paraventricular nucleus of the thalamus, in males, the experimental group had higher Fos induction, while both females groups had similar number of Fos-positive neurons. Within the capsular part of the central amygdalar nucleus, females in the experimental group had higher Fos induction, while males groups had similar amounts. The differential recruitment corresponded to the behavioral differences between males and females and suggests

  12. Trends in incidence and in short term survival following a subarachnoid haemorrhage in Scotland, 1986 - 2005: a retrospective cohort study

    OpenAIRE

    Walters Matthew; Briggs Andrew; Redpath Adam; Chalmers Jim WT; Gillies Michelle; Jhund Pardeep S; Lewsey James D; Macpherson Karen J; Langhorne Peter; Capewell Simon; McMurray John JV; MacIntyre Kate

    2011-01-01

    Abstract Background To examine age and sex specific incidence and 30 day case fatality for subarachnoid haemorrhage (SAH) in Scotland over a 20 year period. Methods A retrospective cohort study using routine hospital discharge data linked to death records. Results Between 1986 and 2005, 12,056 individuals experienced an incident SAH. Of these 10,113 (84%) survived to reach hospital. Overall age-standardised incidence rates were greater in women than men and remained relatively stable over the...

  13. Surviving Sengstaken.

    Science.gov (United States)

    Jayakumar, S; Odulaja, A; Patel, S; Davenport, M; Ade-Ajayi, N

    2015-07-01

    To report the outcomes of children who underwent Sengstaken-Blakemore tube (SBT) insertion for life-threatening haemetemesis. Single institution retrospective review (1997-2012) of children managed with SBT insertion. Patient demographics, diagnosis and outcomes were noted. Data are expressed as median (range). 19 children [10 male, age 1 (0.4-16) yr] were identified; 18 had gastro-oesophageal varices and 1 aorto-oesophageal fistula. Varices were secondary to: biliary atresia (n=8), portal vein thrombosis (n=5), alpha-1-anti-trypsin deficiency (n=1), cystic fibrosis (n=1), intrahepatic cholestasis (n=1), sclerosing cholangitis (n=1) and nodular hyperplasia with arterio-portal shunt (n=1). Three children deteriorated rapidly and did not survive to have post-SBT endoscopy. The child with an aortooesophageal fistula underwent aortic stent insertion and subsequently oesophageal replacement. Complications included gastric mucosal ulceration (n=3, 16%), pressure necrosis at lips and cheeks (n=6, 31%) and SBT dislodgment (n=1, 6%). Six (31%) children died. The remaining 13 have been followed up for 62 (2-165) months; five required liver transplantation, two underwent a mesocaval shunt procedure and 6 have completed endoscopic variceal obliteration and are under surveillance. SBT can be an effective, albeit temporary, life-saving manoeuvre in children with catastrophic haematemesis. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Poorer right ventricular systolic function and exercise capacity in women after repair of tetralogy of fallot: a sex comparison of standard deviation scores based on sex-specific reference values in healthy control subjects.

    Science.gov (United States)

    Sarikouch, Samir; Boethig, Dietmar; Peters, Brigitte; Kropf, Siegfried; Dubowy, Karl-Otto; Lange, Peter; Kuehne, Titus; Haverich, Axel; Beerbaum, Philipp

    2013-11-01

    In repaired congenital heart disease, there is increasing evidence of sex differences in cardiac remodeling, but there is a lack of comparable data for specific congenital heart defects such as in repaired tetralogy of Fallot. In a prospective multicenter study, a cohort of 272 contemporary patients (158 men; mean age, 14.3±3.3 years [range, 8-20 years]) with repaired tetralogy of Fallot underwent cardiac magnetic resonance for ventricular function and metabolic exercise testing. All data were transformed to standard deviation scores according to the Lambda-Mu-Sigma method by relating individual values to their respective 50th percentile (standard deviation score, 0) in sex-specific healthy control subjects. No sex differences were observed in age at repair, type of repair conducted, or overall hemodynamic results. Relative to sex-specific controls, repaired tetralogy of Fallot in women had larger right ventricular end-systolic volumes (standard deviation scores: women, 4.35; men, 3.25; P=0.001), lower right ventricular ejection fraction (women, -2.83; men, -2.12; P=0.011), lower right ventricular muscle mass (women, 1.58; men 2.45; P=0.001), poorer peak oxygen uptake (women, -1.65; men, -1.14; Pstandard deviation scores in repaired tetralogy of Fallot suggest that women perform poorer than men in terms of right ventricular systolic function as tested by cardiac magnetic resonance and exercise capacity. This effect cannot be explained by selection bias. Further outcome data are required from longitudinal cohort studies.

  15. A Genome-wide Association Study Provides Evidence of Sex-specific Involvement of Chr1p35.1 (ZSCAN20-TLR12P and Chr8p23.1 (HMGB1P46 With Diabetic Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Weihua Meng

    2015-10-01

    Full Text Available Neuropathic pain is defined as pain arising as a direct consequence of a lesion or a disease affecting the somatosensory system and it affects around 1 in 4 diabetic patients in the UK. The purpose of this genome-wide association study (GWAS was to identify genetic contributors to this disorder. Cases of neuropathic pain were defined as diabetic patients with a multiple prescription history of at least one of five drugs specifically indicated for the treatment of neuropathic pain. Controls were diabetic individuals who were not prescribed any of these drugs, nor amitriptyline, carbamazepine, or nortriptyline. Overall, 961 diabetic neuropathic pain cases and 3260 diabetic controls in the Genetics of Diabetes Audit and Research Tayside (GoDARTS cohort were identified. We found a cluster in the Chr1p35.1 (ZSCAN20-TLR12P with a lowest P value of 2.74 × 10−7 at rs71647933 in females and a cluster in the Chr8p23.1, next to HMGB1P46 with a lowest P value of 8.02 × 10−7 at rs6986153 in males. Sex-specific narrow sense heritability was higher in males (30.0% than in females (14.7%. This GWAS on diabetic neuropathic pain provides evidence for the sex-specific involvement of Chr1p35.1 (ZSCAN20-TLR12P and Chr8p23.1 (HMGB1P46 with the disorder, indicating the need for further research.

  16. Sex-specific mediation effect of the right fusiform face area volume on the association between variants in repeat length of AVPR1A RS3 and altruistic behavior in healthy adults.

    Science.gov (United States)

    Wang, Junping; Qin, Wen; Liu, Feng; Liu, Bing; Zhou, Yuan; Jiang, Tianzi; Yu, Chunshui

    2016-07-01

    Microsatellite variants in the arginine vasopressin receptor 1A gene (AVPR1A) RS3 have been associated with normal social behaviors variation and autism spectrum disorders (ASDs) in a sex-specific manner. However, neural mechanisms underlying these associations remain largely unknown. We hypothesized that AVPR1A RS3 variants affect altruistic behavior by modulating the gray matter volume (GMV) of specific brain regions in a sex-specific manner. We investigated 278 young healthy adults using the Dictator Game to assess altruistic behavior. All subjects were genotyped and main effect of AVPR1A RS3 repeat polymorphisms and interaction of genotype-by-sex on the GMV were assessed in a voxel-wise manner. We observed that male subjects with relatively short repeats allocated less money to others and exhibited a significantly smaller GMV in the right fusiform face area (FFA) compared with male long homozygotes. In male subjects, the GMV of the right FFA exhibited a significant positive correlation with altruistic behavior. A mixed mediation and moderation analysis further revealed both a significant mediation effect of the GMV of the right FFA on the association between AVPR1A RS3 repeat polymorphisms and allocation sums and a significant moderation effect of sex (only in males) on the mediation effect. Post hoc analysis showed that the GMV of the right FFA was significantly smaller in male subjects carrying allele 426 than in non-426 carriers. These results suggest that the GMV of the right FFA may be a potential mediator whereby the genetic variants in AVPR1A RS3 affect altruistic behavior in healthy male subjects. Hum Brain Mapp 37:2700-2709, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Compared to Sucrose, Previous Consumption of Fructose and Glucose Monosaccharides Reduces Survival and Fitness of Female Mice123

    Science.gov (United States)

    Ruff, James S; Hugentobler, Sara A; Suchy, Amanda K; Sosa, Mirtha M; Tanner, Ruth E; Hite, Megumi E; Morrison, Linda C; Gieng, Sin H; Shigenaga, Mark K; Potts, Wayne K

    2015-01-01

    Background: Intake of added sugar has been shown to correlate with many human metabolic diseases, and rodent models have characterized numerous aspects of the resulting disease phenotypes. However, there is a controversy about whether differential health effects occur because of the consumption of either of the two common types of added sugar—high-fructose corn syrup (fructose and glucose monosaccharides; F/G) or table sugar (sucrose, a fructose and glucose disaccharide). Objectives: We tested the equivalence of sucrose- vs. F/G-containing diets on mouse (Mus musculus) longevity, reproductive success, and social dominance. Methods: We fed wild-derived mice, outbred mice descended from wild-caught ancestors, a diet in which 25% of the calories came from either an equal ratio of F/G or an isocaloric amount of sucrose (both diets had 63% of total calories as carbohydrates). Exposure lasted 40 wk, starting at weaning (21 d of age), and then mice (104 females and 56 males) were released into organismal performances assays—seminatural enclosures where mice competed for territories, resources, and mates for 32 wk. Within enclosures all mice consumed the F/G diet. Results: Females initially fed the F/G diet experienced a mortality rate 1.9 times the rate (P = 0.012) and produced 26.4% fewer offspring than females initially fed sucrose (P = 0.001). This reproductive deficiency was present before mortality differences, suggesting the F/G diet was causing physiologic performance deficits prior to mortality. No differential patterns in survival, reproduction, or social dominance were observed in males, indicating a sex-specific outcome of exposure. Conclusion: This study provides experimental evidence that the consumption of human-relevant levels of F/G is more deleterious than an isocaloric amount of sucrose for key organism-level health measures in female mice. PMID:25733457

  18. Compared to sucrose, previous consumption of fructose and glucose monosaccharides reduces survival and fitness of female mice.

    Science.gov (United States)

    Ruff, James S; Hugentobler, Sara A; Suchy, Amanda K; Sosa, Mirtha M; Tanner, Ruth E; Hite, Megumi E; Morrison, Linda C; Gieng, Sin H; Shigenaga, Mark K; Potts, Wayne K

    2015-03-01

    Intake of added sugar has been shown to correlate with many human metabolic diseases, and rodent models have characterized numerous aspects of the resulting disease phenotypes. However, there is a controversy about whether differential health effects occur because of the consumption of either of the two common types of added sugar-high-fructose corn syrup (fructose and glucose monosaccharides; F/G) or table sugar (sucrose, a fructose and glucose disaccharide). We tested the equivalence of sucrose- vs. F/G-containing diets on mouse (Mus musculus) longevity, reproductive success, and social dominance. We fed wild-derived mice, outbred mice descended from wild-caught ancestors, a diet in which 25% of the calories came from either an equal ratio of F/G or an isocaloric amount of sucrose (both diets had 63% of total calories as carbohydrates). Exposure lasted 40 wk, starting at weaning (21 d of age), and then mice (104 females and 56 males) were released into organismal performances assays-seminatural enclosures where mice competed for territories, resources, and mates for 32 wk. Within enclosures all mice consumed the F/G diet. Females initially fed the F/G diet experienced a mortality rate 1.9 times the rate (P = 0.012) and produced 26.4% fewer offspring than females initially fed sucrose (P = 0.001). This reproductive deficiency was present before mortality differences, suggesting the F/G diet was causing physiologic performance deficits prior to mortality. No differential patterns in survival, reproduction, or social dominance were observed in males, indicating a sex-specific outcome of exposure. This study provides experimental evidence that the consumption of human-relevant levels of F/G is more deleterious than an isocaloric amount of sucrose for key organism-level health measures in female mice. © 2015 American Society for Nutrition.

  19. Sex-specific aspects of venous thrombosis

    NARCIS (Netherlands)

    Roach, Rachel Elizabeth Jo

    2014-01-01

    Venous thrombosis is a disease that occurs in 1-2 per 1000 people per year. At the time of their first venous thrombosis, approximately 50% of women are exposed to reproductive risk factors (oral contraception, postmenopausal hormone therapy, pregnancy and the puerperium). In this thesis, we showed

  20. Compound- and sex-specific effects on programming of energy and immune homeostasis in adult C57BL/6JxFVB mice after perinatal TCDD and PCB 153

    Energy Technology Data Exchange (ETDEWEB)

    Esterik, J.C.J. van, E-mail: joantine.van.esterik@rivm.nl [Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands); Department of Chemistry and Biology, Institute for Environmental Studies (IVM), VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Verharen, H.W., E-mail: henny.verharen@rivm.nl [Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands); Hodemaekers, H.M., E-mail: hennie.hodemaekers@rivm.nl [Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands); Gremmer, E.R., E-mail: eric.gremmer@rivm.nl [Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands); Nagarajah, B., E-mail: bhawani.nagarajah@rivm.nl [Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands); Kamstra, J.H., E-mail: jorke.kamstra@vu.nl [Department of Chemistry and Biology, Institute for Environmental Studies (IVM), VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Dollé, M.E.T., E-mail: martijn.dolle@rivm.nl [Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands); Legler, J., E-mail: juliette.legler@vu.nl [Department of Chemistry and Biology, Institute for Environmental Studies (IVM), VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Ven, L.T.M. van der, E-mail: leo.van.der.ven@rivm.nl [Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands)

    2015-12-01

    Early life exposure to endocrine disrupting compounds has been linked to chronic diseases later in life, like obesity and related metabolic disorders. We exposed C57BL/6JxFVB hybrid mice to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the constitutive androstane receptor/pregnane X receptor agonist polychlorinated biphenyl 153 (PCB 153) in an experimental design relevant for human exposure. Exposure occurred during gestation and lactation via maternal feed to a wide dose range (TCDD: 10–10,000 pg/kg body weight/day; PCB 153: 0.09–1406 μg/kg body weight/d). Then exposure was ceased and offspring were followed up to 1 year of age. Metabolic parameters like body weight, fat pad weights, glucose tolerance, endocrine serum profile, and neurobehavioral and immunological parameters were determined. Body weight was transiently affected by both compounds throughout the follow-up. TCDD-exposed males showed decreased fat pad and spleen weights and an increase in IL-4 production of splenic immune cells. In contrast, females showed increased fat pad weights and production of IFNγ. PCB 153-exposed males showed an increase in glucose, whereas females showed an increase in glucagon, a decrease in pancreas weight, and an increase in thymus weight. In conclusion, early life exposure to TCDD appears to affect programming of energy and immune homeostasis in offspring, whereas the effects of perinatal PCB 153 were mainly on programming of glucose homeostasis. Both compounds act sex-specifically. Lowest derived BMDLs (lower bounds of the (two sided) 90%-confidence interval for the benchmark dose) for both compounds are not lower than current tolerable daily intakes. - Highlights: • Early life exposure to TCDD affects programming of energy and immune homeostasis. • Early life exposure to PCB 153 affects programming of energy homeostasis. • Both compounds act sex-specifically. • Lowest derived BMDLs for both TCDD and PCB 153 are not

  1. Compound- and sex-specific effects on programming of energy and immune homeostasis in adult C57BL/6JxFVB mice after perinatal TCDD and PCB 153

    International Nuclear Information System (INIS)

    Esterik, J.C.J. van; Verharen, H.W.; Hodemaekers, H.M.; Gremmer, E.R.; Nagarajah, B.; Kamstra, J.H.; Dollé, M.E.T.; Legler, J.; Ven, L.T.M. van der

    2015-01-01

    Early life exposure to endocrine disrupting compounds has been linked to chronic diseases later in life, like obesity and related metabolic disorders. We exposed C57BL/6JxFVB hybrid mice to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the constitutive androstane receptor/pregnane X receptor agonist polychlorinated biphenyl 153 (PCB 153) in an experimental design relevant for human exposure. Exposure occurred during gestation and lactation via maternal feed to a wide dose range (TCDD: 10–10,000 pg/kg body weight/day; PCB 153: 0.09–1406 μg/kg body weight/d). Then exposure was ceased and offspring were followed up to 1 year of age. Metabolic parameters like body weight, fat pad weights, glucose tolerance, endocrine serum profile, and neurobehavioral and immunological parameters were determined. Body weight was transiently affected by both compounds throughout the follow-up. TCDD-exposed males showed decreased fat pad and spleen weights and an increase in IL-4 production of splenic immune cells. In contrast, females showed increased fat pad weights and production of IFNγ. PCB 153-exposed males showed an increase in glucose, whereas females showed an increase in glucagon, a decrease in pancreas weight, and an increase in thymus weight. In conclusion, early life exposure to TCDD appears to affect programming of energy and immune homeostasis in offspring, whereas the effects of perinatal PCB 153 were mainly on programming of glucose homeostasis. Both compounds act sex-specifically. Lowest derived BMDLs (lower bounds of the (two sided) 90%-confidence interval for the benchmark dose) for both compounds are not lower than current tolerable daily intakes. - Highlights: • Early life exposure to TCDD affects programming of energy and immune homeostasis. • Early life exposure to PCB 153 affects programming of energy homeostasis. • Both compounds act sex-specifically. • Lowest derived BMDLs for both TCDD and PCB 153 are not

  2. Expression of prostaglandin synthases (pgds and pges) during zebrafish gonadal differentiation

    DEFF Research Database (Denmark)

    Jørgensen, Anne; Nielsen, John E; Nielsen, Betina Frydenlund

    2010-01-01

    The present study aimed at elucidating whether the expression pattern of the membrane bound form of prostaglandin E2 synthase (pges) and especially the lipocalin-type prostaglandin D2 synthase (pgds) indicates involvement in gonadal sex differentiation in zebrafish as has previously been found....... In this study, a sexually dimorphic expression of pgds was found in gonads of adult zebrafish with expression in testis but not in ovaries. To determine whether the sex-specific expression pattern of pgds was present in gonads of juvenile zebrafish and therefore could be an early marker of sex in zebrafish, we...... microdissected gonads from four randomly selected individual zebrafish for every second day in the period 2-20 days post hatch (dph) and 0-1 dph. The temporal expression of pgds and pges was investigated in the microdissected gonads, however, no differential expression that could indicate sex-specific difference...

  3. Expression of prostaglandin synthases (pgds and pges) duringzebrafishgonadal differentiation

    DEFF Research Database (Denmark)

    Jørgensen, Anne; Nielsen, John E.; Nielsen, Betina F.

    2010-01-01

    The present study aimed at elucidating whether the expression pattern of the membrane bound form of prostaglandin E-2 synthase (pges) and especially the lipocalin-type prostaglandin D-2 synthase (pgds) indicates involvement in gonadal sex differentiation in zebrafish as has previously been found...... In this study, a sexually dimorphic expression of pgds was found in gonads of adult zebrafish with expression in testis but not in ovaries. To determine whether the sex-specific expression pattern of pgds was present in gonads of juvenile zebrafish and therefore could be an early marker of sex in zebrafish, we...... microdissected gonads from four randomly selected individual zebrafish for every second day in the period 2-20 days post hatch (dph) and 0-1 dph The temporal expression of pgds and pges was investigated in the microdissected gonads, however, no differential expression that could indicate sex-specific difference...

  4. Regulation of meiotic entry and gonadal sex differentiation in the human

    DEFF Research Database (Denmark)

    Jørgensen, Anne; Rajpert-De Meyts, Ewa

    2014-01-01

    Meiosis is a unique type of cell division that is performed only by germ cells to form haploid gametes. The switch from mitosis to meiosis exhibits a distinct sex-specific difference in timing, with female germ cells entering meiosis during fetal development and male germ cells at puberty when...... spermatogenesis is initiated. During early fetal development, bipotential primordial germ cells migrate to the forming gonad where they remain sexually indifferent until the sex-specific differentiation of germ cells is initiated by cues from the somatic cells. This irreversible step in gonadal sex...... in the context of fetal gonad development and germ cell differentiation, with emphasis on results obtained in humans. Furthermore, the consequences of dysregulated meiosis signaling in humans are briefly discussed in the context of selected pathologies, including testicular germ cell cancer and some forms...

  5. Early paternal deprivation alters levels of hippocampal brain-derived neurotrophic factor and glucocorticoid receptor and serum corticosterone and adrenocorticotropin in a sex-specific way in socially monogamous mandarin voles.

    Science.gov (United States)

    Wu, Ruiyong; Song, Zhenzhen; Wang, Siyang; Shui, Li; Tai, Fadao; Qiao, Xufeng; He, Fengqin

    2014-01-01

    In monogamous mammals, fathers play an important role in the development of the brain and typical behavior in offspring, but the exact nature of this process is not well understood. In particular, little research has addressed whether the presence or absence of paternal care alters levels of hippocampal glucocorticoid receptor (GR) and brain-derived neurotrophic factor (BDNF), and basal levels of serum corticosterone (CORT) and adrenocorticotropin (ACTH). Here, we explored this concept using socially monogamous mandarin voles (Microtus mandarinus), a species in which fathers display high levels of paternal care toward their pups. Our immunohistochemical study shows that paternal deprivation (PD) significantly decreased levels of GR and BDNF protein in the CA1 and CA2/3 of the hippocampus. In the dental gyrus, decreases in GR and BDNF induced by PD were evident in females but not in males. Additionally, enzyme-linked immunosorbent assay results show that PD significantly upregulated levels of serum CORT and ACTH in females, but not males. These findings demonstrate that PD alters HPA axis activity in a sex-specific way. The changes in stress hormones documented here may be associated with alteration in hippocampal BDNF and GR levels. © 2014 S. Karger AG, Basel.

  6. Naloxone treatment alters gene expression in the mesolimbic reward system in 'junk food' exposed offspring in a sex-specific manner but does not affect food preferences in adulthood.

    Science.gov (United States)

    Gugusheff, J R; Ong, Z Y; Muhlhausler, B S

    2014-06-22

    We have previously reported that the opioid receptor blocker, naloxone, is less effective in reducing palatable food intake in offspring exposed to a maternal cafeteria diet during the perinatal period, implicating a desensitization of the central opioid pathway in the programming of food preferences. The present study aimed to investigate the effect of a maternal cafeteria diet and naloxone treatment on the development of the mesolimbic reward pathway and food choices in adulthood. We measured mRNA expression of key components of the reward pathway (mu-opioid receptor, proenkephalin, tyrosine hydroxylase, D1 and D2 receptors and the dopamine active transporter (DAT)) in the nucleus accumbens (NAc) and ventral tegmental area (VTA) of the offspring of control and cafeteria fed (JF) dams at weaning and after a 10-day naloxone treatment post-weaning and determined food preferences in adulthood in the remaining offspring. Naloxone treatment decreased the expression of DAT by 8.2 fold in female control offspring but increased it by 4.3 fold in female offspring of JF dams relative to the saline-injected reference groups. Proenkephalin mRNA expression was higher in the NAc of female JF offspring compared to controls, independent of naloxone treatment (Pfood preferences in adulthood in either control or JF offspring. These data indicate that prenatal exposure to a cafeteria diet alters the impact of opioid signaling blockade in the early post-weaning period on gene expression in the central reward pathway in a sex specific manner, but that these changes in gene expression do not appear to have any persistent impact on food preferences in adulthood. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Impact of gene variants on sex-specific regulation of human Scavenger receptor class B type 1 (SR-BI expression in liver and association with lipid levels in a population-based study

    Directory of Open Access Journals (Sweden)

    Barrett-Connor Elizabeth

    2010-01-01

    Full Text Available Abstract Background Several studies have noted that genetic variants of SCARB1, a lipoprotein receptor involved in reverse cholesterol transport, are associated with serum lipid levels in a sex-dependent fashion. However, the mechanism underlying this gene by sex interaction has not been explored. Methods We utilized both epidemiological and molecular methods to study how estrogen and gene variants interact to influence SCARB1 expression and lipid levels. Interaction between 35 SCARB1 haplotype-tagged polymorphisms and endogenous estradiol levels was assessed in 498 postmenopausal Caucasian women from the population-based Rancho Bernardo Study. We further examined associated variants with overall and SCARB1 splice variant (SR-BI and SR-BII expression in 91 human liver tissues using quantitative real-time PCR. Results Several variants on a haplotype block spanning intron 11 to intron 12 of SCARB1 showed significant gene by estradiol interaction affecting serum lipid levels, the strongest for rs838895 with HDL-cholesterol (p = 9.2 × 10-4 and triglycerides (p = 1.3 × 10-3 and the triglyceride:HDL cholesterol ratio (p = 2.7 × 10-4. These same variants were associated with expression of the SR-BI isoform in a sex-specific fashion, with the strongest association found among liver tissue from 52 young women Conclusions Estrogen and SCARB1 genotype may act synergistically to regulate expression of SCARB1 isoforms and impact serum levels of HDL cholesterol and triglycerides. This work highlights the importance of considering sex-dependent effects of gene variants on serum lipid levels.

  8. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

    Science.gov (United States)

    2015-01-10

    Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policie