Sample records for integration regulating male

  1. Sensory integration regulating male courtship behavior in Drosophila.

    PubMed

    Krstic, Dimitrije; Boll, Werner; Noll, Markus

    2009-01-01

    The courtship behavior of Drosophila melanogaster serves as an excellent model system to study how complex innate behaviors are controlled by the nervous system. To understand how the underlying neural network controls this behavior, it is not sufficient to unravel its architecture, but also crucial to decipher its logic. By systematic analysis of how variations in sensory inputs alter the courtship behavior of a naïve male in the single-choice courtship paradigm, we derive a model describing the logic of the network that integrates the various sensory stimuli and elicits this complex innate behavior. This approach and the model derived from it distinguish (i) between initiation and maintenance of courtship, (ii) between courtship in daylight and in the dark, where the male uses a scanning strategy to retrieve the decamping female, and (iii) between courtship towards receptive virgin females and mature males. The last distinction demonstrates that sexual orientation of the courting male, in the absence of discriminatory visual cues, depends on the integration of gustatory and behavioral feedback inputs, but not on olfactory signals from the courted animal. The model will complement studies on the connectivity and intrinsic properties of the neurons forming the circuitry that regulates male courtship behavior.

  2. Sensory regulation of C. elegans male mate-searching behaviour

    PubMed Central

    Barrios, Arantza; Nurrish, Stephen; Emmons, Scott W.

    2009-01-01

    Summary How do animals integrate internal drives and external environmental cues to coordinate behaviours? We address this question studying mate-searching behaviour in C. elegans. C. elgans males explore their environment in search of mates (hermaphrodites) and will leave food if mating partners are absent. However, when mates and food coincide, male exploratory behaviour is suppressed and males are retained on the food source. We show that the drive to explore is stimulated by male specific neurons in the tail, the ray neurons. Periodic contact with the hermaphrodite detected through ray neurons changes the male’s behaviour during periods of no contact and prevents the male from leaving the food source. The hermaphrodite signal is conveyed by male-specific interneurons that are post-synaptic to the rays and that send processes to the major integrative center in the head. This study identifies key parts of the neural circuit that regulates a sexual appetitive behaviour in C. elegans. PMID:19062284

  3. E-type cyclins modulate telomere integrity in mammalian male meiosis.

    PubMed

    Manterola, Marcia; Sicinski, Piotr; Wolgemuth, Debra J

    2016-06-01

    We have shown that E-type cyclins are key regulators of mammalian male meiosis. Depletion of cyclin E2 reduced fertility in male mice due to meiotic defects, involving abnormal pairing and synapsis, unrepaired DNA, and loss of telomere structure. These defects were exacerbated by additional loss of cyclin E1, and complete absence of both E-type cyclins produces a meiotic catastrophe. Here, we investigated the involvement of E-type cyclins in maintaining telomere integrity in male meiosis. Spermatocytes lacking cyclin E2 and one E1 allele (E1+/-E2-/-) displayed a high rate of telomere abnormalities but can progress to pachytene and diplotene stages. We show that their telomeres exhibited an aberrant DNA damage repair response during pachynema and that the shelterin complex proteins TRF2 and RAP2 were significantly decreased in the proximal telomeres. Moreover, the insufficient level of these proteins correlated with an increase of γ-H2AX foci in the affected telomeres and resulted in telomere associations involving TRF1 and telomere detachment in later prophase-I stages. These results suggest that E-type cyclins are key modulators of telomere integrity during meiosis by, at least in part, maintaining the balance of shelterin complex proteins, and uncover a novel role of E-type cyclins in regulating chromosome structure during male meiosis.

  4. Mammalian target of rapamycin (mTOR): a central regulator of male fertility?

    PubMed

    Jesus, Tito T; Oliveira, Pedro F; Sousa, Mário; Cheng, C Yan; Alves, Marco G

    2017-06-01

    Mammalian target of rapamycin (mTOR) is a central regulator of cellular metabolic phenotype and is involved in virtually all aspects of cellular function. It integrates not only nutrient and energy-sensing pathways but also actin cytoskeleton organization, in response to environmental cues including growth factors and cellular energy levels. These events are pivotal for spermatogenesis and determine the reproductive potential of males. Yet, the molecular mechanisms by which mTOR signaling acts in male reproductive system remain a matter of debate. Here, we review the current knowledge on physiological and molecular events mediated by mTOR in testis and testicular cells. In recent years, mTOR inhibition has been explored as a prime strategy to develop novel therapeutic approaches to treat cancer, cardiovascular disease, autoimmunity, and metabolic disorders. However, the physiological consequences of mTOR dysregulation and inhibition to male reproductive potential are still not fully understood. Compelling evidence suggests that mTOR is an arising regulator of male fertility and better understanding of this atypical protein kinase coordinated action in testis will provide insightful information concerning its biological significance in other tissues/organs. We also discuss why a new generation of mTOR inhibitors aiming to be used in clinical practice may also need to include an integrative view on the effects in male reproductive system.

  5. Mammalian target of rapamycin (mTOR): a central regulator of male fertility?

    PubMed Central

    Jesus, Tito T.; Oliveira, Pedro F.; Sousa, M ario; Cheng, C. Yan; Alves, Marco G.

    2017-01-01

    Mammalian target of rapamycin (mTOR) is a central regulator of cellular metabolic phenotype and is involved in virtually all aspects of cellular function. It integrates not only nutrient and energy-sensing pathways but also actin cytoskeleton organization, in response to environmental cues including growth factors and cellular energy levels. These events are pivotal for spermato-genesis and determine the reproductive potential of males. Yet, the molecular mechanisms by which mTOR signaling acts in male reproductive system remain a matter of debate. Here, we review the current knowledge on physiological and molecular events mediated by mTOR in testis and testicular cells. In recent years, mTOR inhibition has been explored as a prime strategy to develop novel therapeutic approaches to treat cancer, cardiovascular disease, autoimmunity, and metabolic disorders. However, the physiological consequences of mTOR dysregulation and inhibition to male reproductive potential are still not fully understood. Compelling evidence suggests that mTOR is an arising regulator of male fertility and better understanding of this atypical protein kinase coordinated action in testis will provide insightful information concerning its biological significance in other tissues/organs. We also discuss why a new generation of mTOR inhibitors aiming to be used in clinical practice may also need to include an integrative view on the effects in male reproductive system. PMID:28124577

  6. Hierarchical chemosensory regulation of male-male social interactions in Drosophila

    PubMed Central

    Wang, Liming; Han, Xiaoqing; Mehren, Jennifer; Hiroi, Makoto; Billeter, Jean-Christophe; Miyamoto, Tetsuya; Amrein, Hubert; Levine, Joel D.; Anderson, David J.

    2011-01-01

    Pheromones regulate male social behaviors in Drosophila, but the identities and behavioral role(s) of these chemosensory signals, and how they interact, are incompletely understood. Here we show that (Z)-7-tricosene (7-T), a male-enriched cuticular hydrocarbon (CH) previously shown to inhibit male-male courtship, is also essential for normal levels of aggression. The opposite influences of 7-T on aggression and courtship are independent, but both require the gustatory receptor Gr32a. Surprisingly, sensitivity to 7-T is required for the aggression-promoting effect of 11-cis-vaccenyl acetate (cVA), an olfactory pheromone, but 7-T sensitivity is independent of cVA. 7-T and cVA therefore regulate aggression in a hierarchical manner. Furthermore, the increased courtship caused by depletion of male CHs is suppressed by a mutation in the olfactory receptor Or47b. Thus, male social behaviors are controlled by gustatory pheromones that promote and suppress aggression and courtship, respectively, and whose influences are dominant to olfactory pheromones that enhance these behaviors. PMID:21516101

  7. Review: neuroestrogen regulation of socio-sexual behavior of males.

    PubMed

    Ubuka, Takayoshi; Tsutsui, Kazuyoshi

    2014-01-01

    It is thought that estrogen (neuroestrogen) synthesized by the action of aromatase in the brain from testosterone activates male socio-sexual behaviors, such as aggression and sexual behavior in birds. We recently found that gonadotropin-inhibitory hormone (GnIH), a hypothalamic neuropeptide, inhibits socio-sexual behaviors of male quail by directly activating aromatase and increasing neuroestrogen synthesis in the preoptic area (POA). The POA is thought to be the most critical site of aromatization and neuroestrogen action for the regulation of socio-sexual behavior of male birds. We concluded that GnIH inhibits socio-sexual behaviors of male quail by increasing neuroestrogen concentration beyond its optimal concentration in the brain for expression of socio-sexual behavior. On the other hand, it has been reported that dopamine and glutamate, which stimulate male socio-sexual behavior in birds and mammals, inhibit the activity of aromatase in the POA. Multiple studies also report that the activity of aromatase or neuroestrogen is negatively correlated with changes in male socio-sexual behavior in fish, birds, and mammals including humans. Here, we review previous studies that investigated the role of neuroestrogen in the regulation of male socio-sexual behavior and reconsider the hypothesis that neuroestrogen activates male socio-sexual behavior in vertebrates. It is considered that basal concentration of neuroestrogen is required for the maintenance of male socio-sexual behavior but higher concentration of neuroestrogen may inhibit male socio-sexual behavior.

  8. Review: neuroestrogen regulation of socio-sexual behavior of males

    PubMed Central

    Ubuka, Takayoshi; Tsutsui, Kazuyoshi

    2014-01-01

    It is thought that estrogen (neuroestrogen) synthesized by the action of aromatase in the brain from testosterone activates male socio-sexual behaviors, such as aggression and sexual behavior in birds. We recently found that gonadotropin-inhibitory hormone (GnIH), a hypothalamic neuropeptide, inhibits socio-sexual behaviors of male quail by directly activating aromatase and increasing neuroestrogen synthesis in the preoptic area (POA). The POA is thought to be the most critical site of aromatization and neuroestrogen action for the regulation of socio-sexual behavior of male birds. We concluded that GnIH inhibits socio-sexual behaviors of male quail by increasing neuroestrogen concentration beyond its optimal concentration in the brain for expression of socio-sexual behavior. On the other hand, it has been reported that dopamine and glutamate, which stimulate male socio-sexual behavior in birds and mammals, inhibit the activity of aromatase in the POA. Multiple studies also report that the activity of aromatase or neuroestrogen is negatively correlated with changes in male socio-sexual behavior in fish, birds, and mammals including humans. Here, we review previous studies that investigated the role of neuroestrogen in the regulation of male socio-sexual behavior and reconsider the hypothesis that neuroestrogen activates male socio-sexual behavior in vertebrates. It is considered that basal concentration of neuroestrogen is required for the maintenance of male socio-sexual behavior but higher concentration of neuroestrogen may inhibit male socio-sexual behavior. PMID:25352775

  9. Integrated proteomics and metabolomics analysis of rat testis: Mechanism of arsenic-induced male reproductive toxicity

    NASA Astrophysics Data System (ADS)

    Huang, Qingyu; Luo, Lianzhong; Alamdar, Ambreen; Zhang, Jie; Liu, Liangpo; Tian, Meiping; Eqani, Syed Ali Musstjab Akber Shah; Shen, Heqing

    2016-09-01

    Arsenic is a widespread metalloid in environment, whose exposure has been associated with a broad spectrum of toxic effects. However, a global view of arsenic-induced male reproductive toxicity is still lack, and the underlying mechanisms remain largely unclear. Our results revealed that arsenic exposure decreased testosterone level and reduced sperm quality in rats. By conducting an integrated proteomics and metabolomics analysis, the present study aims to investigate the global influence of arsenic exposure on the proteome and metabolome in rat testis. The abundance of 70 proteins (36 up-regulated and 34 down-regulated) and 13 metabolites (8 increased and 5 decreased) were found to be significantly altered by arsenic treatment. Among these, 19 proteins and 2 metabolites were specifically related to male reproductive system development and function, including spermatogenesis, sperm function and fertilization, fertility, internal genitalia development, and mating behavior. It is further proposed that arsenic mainly impaired spermatogenesis and fertilization via aberrant modulation of these male reproduction-related proteins and metabolites, which may be mediated by the ERK/AKT/NF-κB-dependent signaling pathway. Overall, these findings will aid our understanding of the mechanisms responsible for arsenic-induced male reproductive toxicity, and from such studies useful biomarkers indicative of arsenic exposure could be discovered.

  10. Integrated proteomics and metabolomics analysis of rat testis: Mechanism of arsenic-induced male reproductive toxicity.

    PubMed

    Huang, Qingyu; Luo, Lianzhong; Alamdar, Ambreen; Zhang, Jie; Liu, Liangpo; Tian, Meiping; Eqani, Syed Ali Musstjab Akber Shah; Shen, Heqing

    2016-09-02

    Arsenic is a widespread metalloid in environment, whose exposure has been associated with a broad spectrum of toxic effects. However, a global view of arsenic-induced male reproductive toxicity is still lack, and the underlying mechanisms remain largely unclear. Our results revealed that arsenic exposure decreased testosterone level and reduced sperm quality in rats. By conducting an integrated proteomics and metabolomics analysis, the present study aims to investigate the global influence of arsenic exposure on the proteome and metabolome in rat testis. The abundance of 70 proteins (36 up-regulated and 34 down-regulated) and 13 metabolites (8 increased and 5 decreased) were found to be significantly altered by arsenic treatment. Among these, 19 proteins and 2 metabolites were specifically related to male reproductive system development and function, including spermatogenesis, sperm function and fertilization, fertility, internal genitalia development, and mating behavior. It is further proposed that arsenic mainly impaired spermatogenesis and fertilization via aberrant modulation of these male reproduction-related proteins and metabolites, which may be mediated by the ERK/AKT/NF-κB-dependent signaling pathway. Overall, these findings will aid our understanding of the mechanisms responsible for arsenic-induced male reproductive toxicity, and from such studies useful biomarkers indicative of arsenic exposure could be discovered.

  11. Integrating Membrane Transport with Male Gametophyte Development and Function through Transcriptomics.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bock KW; D Honys; JM. Ward

    Male fertility depends on the proper development of the male gametophyte, successful pollen germination, tube growth and delivery of the sperm cells to the ovule. Previous studies have shown that nutrients like boron, and ion gradients or currents of Ca2+, H+, and K+ are critical for pollen tube growth. However, the molecular identities of transporters mediating these fluxes are mostly unknown. As a first step to integrate transport with pollen development and function, a genome-wide analysis of transporter genes expressed in the male gametophyte at four developmental stages was conducted. About 1269 genes encoding classified transporters were collected from themore » Arabidopsis thaliana genome. Of 757 transporter genes expressed in pollen, 16% or 124 genes, including AHA6, CNGC18, TIP1.3 and CHX08, are specifically or preferentially expressed relative to sporophytic tissues. Some genes are highly expressed in microspores and bicellular pollen (COPT3, STP2, OPT9); while others are activated only in tricellular or mature pollen (STP11, LHT7). Analyses of entire gene families showed that a subset of genes, including those expressed in sporophytic tissues, were developmentally-regulated during pollen maturation. Early and late expression patterns revealed by transcriptome analysis are supported by promoter::GUS analyses of CHX genes and by other methods. Recent genetic studies based on a few transporters, including plasma membrane H+ pump AHA3, Ca2+ pump ACA9, and K+ channel SPIK, further support the expression patterns and the inferred functions revealed by our analyses. Thus, revealing the distinct expression patterns of specific transporters and unknown polytopic proteins during microgametogenesis provides new insights for strategic mutant analyses necessary to integrate the roles of transporters and potential receptors with male gametophyte development.« less

  12. Integrating membrane transport with male gametophyte development and function through transcriptomics.

    PubMed

    Bock, Kevin W; Honys, David; Ward, John M; Padmanaban, Senthilkumar; Nawrocki, Eric P; Hirschi, Kendal D; Twell, David; Sze, Heven

    2006-04-01

    Male fertility depends on the proper development of the male gametophyte, successful pollen germination, tube growth, and delivery of the sperm cells to the ovule. Previous studies have shown that nutrients like boron, and ion gradients or currents of Ca2+, H+, and K+ are critical for pollen tube growth. However, the molecular identities of transporters mediating these fluxes are mostly unknown. As a first step to integrate transport with pollen development and function, a genome-wide analysis of transporter genes expressed in the male gametophyte at four developmental stages was conducted. Approximately 1,269 genes encoding classified transporters were collected from the Arabidopsis (Arabidopsis thaliana) genome. Of 757 transporter genes expressed in pollen, 16% or 124 genes, including AHA6, CNGC18, TIP1.3, and CHX08, are specifically or preferentially expressed relative to sporophytic tissues. Some genes are highly expressed in microspores and bicellular pollen (COPT3, STP2, OPT9), while others are activated only in tricellular or mature pollen (STP11, LHT7). Analyses of entire gene families showed that a subset of genes, including those expressed in sporophytic tissues, was developmentally regulated during pollen maturation. Early and late expression patterns revealed by transcriptome analysis are supported by promoter::beta-glucuronidase analyses of CHX genes and by other methods. Recent genetic studies based on a few transporters, including plasma membrane H+ pump AHA3, Ca2+ pump ACA9, and K+ channel SPIK, further support the expression patterns and the inferred functions revealed by our analyses. Thus, revealing the distinct expression patterns of specific transporters and unknown polytopic proteins during microgametogenesis provides new insights for strategic mutant analyses necessary to integrate the roles of transporters and potential receptors with male gametophyte development.

  13. Bodily Integrity and Male Circumcision: An Islamic Perspective

    PubMed Central

    Alahmad, Ghiath; Dekkers, Wim

    2012-01-01

    The notion of bodily integrity forms an important part of the value-structure of many religions and cultures. In this paper, we explore the notion of bodily integrity in Islam using male circumcision as the focus of the discussion. Our aim is to contribute to a better understanding of the Muslim perspective and of the differences and similarities between Western and Islamic ethical structures, in particular, regarding the concept of bodily integrity. PMID:23610746

  14. Dietary glucose regulates yeast consumption in adult Drosophila males.

    PubMed

    Lebreton, Sébastien; Witzgall, Peter; Olsson, Marie; Becher, Paul G

    2014-01-01

    The adjustment of feeding behavior in response to hunger and satiety contributes to homeostatic regulation in animals. The fruit fly Drosophila melanogaster feeds on yeasts growing on overripe fruit, providing nutrients required for adult survival, reproduction and larval growth. Here, we present data on how the nutritional value of food affects subsequent yeast consumption in Drosophila adult males. After a period of starvation, flies showed intensive yeast consumption. In comparison, flies stopped feeding after having access to a nutritive cornmeal diet. Interestingly, dietary glucose was equally efficient as the complex cornmeal diet. In contrast, flies fed with sucralose, a non-metabolizable sweetener, behaved as if they were starved. The adipokinetic hormone and insulin-like peptides regulate metabolic processes in insects. We did not find any effect of the adipokinetic hormone pathway on this modulation. Instead, the insulin pathway was involved in these changes. Flies lacking the insulin receptor (InR) did not respond to nutrient deprivation by increasing yeast consumption. Together these results show the importance of insulin in the regulation of yeast consumption in response to starvation in adult D. melanogaster males.

  15. Semantic integration of data on transcriptional regulation.

    PubMed

    Baitaluk, Michael; Ponomarenko, Julia

    2010-07-01

    Experimental and predicted data concerning gene transcriptional regulation are distributed among many heterogeneous sources. However, there are no resources to integrate these data automatically or to provide a 'one-stop shop' experience for users seeking information essential for deciphering and modeling gene regulatory networks. IntegromeDB, a semantic graph-based 'deep-web' data integration system that automatically captures, integrates and manages publicly available data concerning transcriptional regulation, as well as other relevant biological information, is proposed in this article. The problems associated with data integration are addressed by ontology-driven data mapping, multiple data annotation and heterogeneous data querying, also enabling integration of the user's data. IntegromeDB integrates over 100 experimental and computational data sources relating to genomics, transcriptomics, genetics, and functional and interaction data concerning gene transcriptional regulation in eukaryotes and prokaryotes. IntegromeDB is accessible through the integrated research environment BiologicalNetworks at http://www.BiologicalNetworks.org baitaluk@sdsc.edu Supplementary data are available at Bioinformatics online.

  16. Semantic integration of data on transcriptional regulation

    PubMed Central

    Baitaluk, Michael; Ponomarenko, Julia

    2010-01-01

    Motivation: Experimental and predicted data concerning gene transcriptional regulation are distributed among many heterogeneous sources. However, there are no resources to integrate these data automatically or to provide a ‘one-stop shop’ experience for users seeking information essential for deciphering and modeling gene regulatory networks. Results: IntegromeDB, a semantic graph-based ‘deep-web’ data integration system that automatically captures, integrates and manages publicly available data concerning transcriptional regulation, as well as other relevant biological information, is proposed in this article. The problems associated with data integration are addressed by ontology-driven data mapping, multiple data annotation and heterogeneous data querying, also enabling integration of the user's data. IntegromeDB integrates over 100 experimental and computational data sources relating to genomics, transcriptomics, genetics, and functional and interaction data concerning gene transcriptional regulation in eukaryotes and prokaryotes. Availability: IntegromeDB is accessible through the integrated research environment BiologicalNetworks at http://www.BiologicalNetworks.org Contact: baitaluk@sdsc.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:20427517

  17. Functions of TAM RTKs in regulating spermatogenesis and male fertility in mice.

    PubMed

    Chen, Yongmei; Wang, Huizhen; Qi, Nan; Wu, Hui; Xiong, Weipeng; Ma, Jing; Lu, Qingxian; Han, Daishu

    2009-10-01

    Mice lacking TYRO3, AXL and MER (TAM) receptor tyrosine kinases (RTKs) are male sterile. The mechanism of TAM RTKs in regulating male fertility remains unknown. In this study, we analyzed in more detail the testicular phenotype of TAM triple mutant (TAM(-/-)) mice with an effort to understand the mechanism. We demonstrate that the three TAM RTKs cooperatively regulate male fertility, and MER appears to be more important than AXL and TYRO3. TAM(-/-) testes showed a progressive loss of germ cells from elongated spermatids to spermatogonia. Young adult TAM(-/-) mice exhibited oligo-astheno-teratozoospermia and various morphological malformations of sperm cells. As the mice aged, the germ cells were eventually depleted from the seminiferous tubules. Furthermore, we found that TAM(-/-) Sertoli cells have an impaired phagocytic activity and a large number of differentially expressed genes compared to wild-type controls. By contrast, the function of Leydig cells was not apparently affected by the mutation of TAM RTKs. Therefore, we conclude that the suboptimal function of Sertoli cells leads to the impaired spermatogenesis in TAM(-/-) mice. The results provide novel insight into the mechanism of TAM RTKs in regulating male fertility.

  18. Dietary glucose regulates yeast consumption in adult Drosophila males

    PubMed Central

    Lebreton, Sébastien; Witzgall, Peter; Olsson, Marie; Becher, Paul G.

    2014-01-01

    The adjustment of feeding behavior in response to hunger and satiety contributes to homeostatic regulation in animals. The fruit fly Drosophila melanogaster feeds on yeasts growing on overripe fruit, providing nutrients required for adult survival, reproduction and larval growth. Here, we present data on how the nutritional value of food affects subsequent yeast consumption in Drosophila adult males. After a period of starvation, flies showed intensive yeast consumption. In comparison, flies stopped feeding after having access to a nutritive cornmeal diet. Interestingly, dietary glucose was equally efficient as the complex cornmeal diet. In contrast, flies fed with sucralose, a non-metabolizable sweetener, behaved as if they were starved. The adipokinetic hormone and insulin-like peptides regulate metabolic processes in insects. We did not find any effect of the adipokinetic hormone pathway on this modulation. Instead, the insulin pathway was involved in these changes. Flies lacking the insulin receptor (InR) did not respond to nutrient deprivation by increasing yeast consumption. Together these results show the importance of insulin in the regulation of yeast consumption in response to starvation in adult D. melanogaster males. PMID:25566097

  19. Tribolium castaneum Transformer-2 regulates sex determination and development in both males and females

    PubMed Central

    Shukla, Jayendra Nath; Palli, Subba Reddy

    2014-01-01

    Tribolium castaneum Transformer (TcTra) is essential for female sex determination and maintenance through the regulation of sex-specific splicing of doublesex (dsx) pre-mRNA. In females, TcTra also regulates the sex-specific splicing of its own pre-mRNA to ensure continuous production of functional Tra protein. Transformer protein is absent in males and hence dsx pre-mRNA is spliced in a default mode. The mechanisms by which males inhibit the production of functional Tra protein are not known. Here, we report on functional characterization of transformer-2 (tra-2) gene (an ortholog of Drosophila transformer-2) in T. castaneum. RNA interference-mediated knockdown in the expression of gene coding for tra-2 in female pupae or adults resulted in the production of male-specific isoform of dsx and both female and male isoforms of tra suggesting that Tra-2 is essential for the female-specific splicing of tra and dsx pre-mRNAs. Interestingly, knockdown of tra-2 in males did not affect the splicing of dsx but resulted in the production of both female and male isoforms of tra suggesting that Tra-2 suppresses female-specific splicing of tra pre-mRNA in males. This dual regulation of sex-specific splicing of tra pre-mRNA ensures a tight regulation of sex determination and maintenance. These data suggest a critical role for Tra-2 in suppression of female sex determination cascade in males. In addition, RNAi studies showed that Tra-2 is also required for successful embryonic and larval development in both sexes. PMID:24056158

  20. Tribolium castaneum Transformer-2 regulates sex determination and development in both males and females.

    PubMed

    Shukla, Jayendra Nath; Palli, Subba Reddy

    2013-12-01

    Tribolium castaneum Transformer (TcTra) is essential for female sex determination and maintenance through the regulation of sex-specific splicing of doublesex (dsx) pre-mRNA. In females, TcTra also regulates the sex-specific splicing of its own pre-mRNA to ensure continuous production of functional Tra protein. Transformer protein is absent in males and hence dsx pre-mRNA is spliced in a default mode. The mechanisms by which males inhibit the production of functional Tra protein are not known. Here, we report on functional characterization of transformer-2 (tra-2) gene (an ortholog of Drosophila transformer-2) in T. castaneum. RNA interference-mediated knockdown in the expression of gene coding for tra-2 in female pupae or adults resulted in the production of male-specific isoform of dsx and both female and male isoforms of tra suggesting that Tra-2 is essential for the female-specific splicing of tra and dsx pre-mRNAs. Interestingly, knockdown of tra-2 in males did not affect the splicing of dsx but resulted in the production of both female and male isoforms of tra suggesting that Tra-2 suppresses female-specific splicing of tra pre-mRNA in males. This dual regulation of sex-specific splicing of tra pre-mRNA ensures a tight regulation of sex determination and maintenance. These data suggest a critical role for Tra-2 in suppression of female sex determination cascade in males. In addition, RNAi studies showed that Tra-2 is also required for successful embryonic and larval development in both sexes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Genome-wide Integration Study of Circulating miRNAs and Peripheral Whole-Blood mRNAs of Male Acute Ischemic Stroke Patients.

    PubMed

    Xue, Yang; Yin, Pengqi; Li, Guozhong; Zhong, Di

    2018-06-01

    Several circulating microRNAs (miRNAs) have been proved to serve as stable biomarkers in blood for acute ischemic stroke (AIS). However, the functions of these biomarkers remain elusive. By conducting the integration analysis of circulating miRNAs and peripheral whole-blood mRNAs using bioinformatics methods, we explored the biological role of these circulating markers in peripheral whole blood at the genome-wide level. Stroke-related circulating miRNA profile data (GSE86291) and peripheral whole-blood mRNA expression data (GSE16561) were collected from the Gene Expression Omnibus (GEO) datasets. We selected male patients to avoid any gender differences in stroke pathology. Male stroke-related miRNAs (M-miRNAs) and mRNAs (M-mRNAs) were detected using GEO2R. Nine M-miRNAs (five up- and four down-regulated) were applied to TargetScan to predict the possible target mRNAs. Next, we intersected these targets with the M-mRNAs (38 up- and three down-regulated) to obtain the male stroke-related overlapped mRNAs (Mo-mRNAs). Finally, we analyzed biological functions of Mo-mRNAs using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and constructed networks among the Mo-mRNAs, overlapped M-miRNAs (Mo-miRNAs), and their functions. The Mo-mRNAs were enriched in functions such as platelet degranulation, immune response, and pathways associated with phagosome biology and Staphylococcus aureus infection. This study provides an integrated view of interactions among circulating miRNAs and peripheral whole-blood mRNAs involved in the pathophysiological processes of male AIS. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. A multi-process model of self-regulation: influences of mindfulness, integrative self-knowledge and self-control in Iran.

    PubMed

    Ghorbani, Nima; Watson, P J; Farhadi, Mehran; Chen, Zhuo

    2014-04-01

    Self-regulation presumably rests upon multiple processes that include an awareness of ongoing self-experience, enduring self-knowledge and self-control. The present investigation tested this multi-process model using the Five-Facet Mindfulness Questionnaire (FFMQ) and the Integrative Self-Knowledge and Brief Self-Control Scales. Using a sample of 1162 Iranian university students, we confirmed the five-factor structure of the FFMQ in Iran and documented its factorial invariance across males and females. Self-regulatory variables correlated negatively with Perceived Stress, Depression, and Anxiety and positively with Self-Esteem and Satisfaction with Life. Partial mediation effects confirmed that self-regulatory measures ameliorated the disturbing effects of Perceived Stress. Integrative Self-Knowledge and Self-Control interacted to partially mediate the association of Perceived Stress with lower levels of Satisfaction with Life. Integrative Self-Knowledge, alone or in interaction with Self-Control, was the only self-regulation variable to display the expected mediation of Perceived Stress associations with all other measures. Self-Control failed to be implicated in self-regulation only in the mediation of Anxiety. These data confirmed the need to further examine this multi-process model of self-regulation. © 2014 International Union of Psychological Science.

  3. Progressive effects of silver nanoparticles on hormonal regulation of reproduction in male rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dziendzikowska, K., E-mail: k.dziendzikowska@gmail

    The growing use of silver nanoparticles (AgNPs) in various applications, including consumer, agriculture and medicine products, has raised many concerns about the potential risks of nanoparticles (NPs) to human health and the environment. An increasing body of evidence suggests that AgNPs may have adverse effects of humans, thus the aim of this study was to investigate the effects of AgNPs on the male reproductive system. Silver particles (20 nm AgNPs (groups Ag I and Ag II) and 200 nm Ag sub-micron particles (SPs) (group Ag III)) were administered intravenously to male Wistar rats at a dose of 5 (groups Agmore » I and Ag III) or 10 (group Ag II) mg/kg of body weight. The biological material was sampled 24 h, 7 days and 28 days after injection. The obtained results revealed that the AgNPs had altered the luteinising hormone concentration in the plasma and the sex hormone concentration in the plasma and testes. Plasma and intratesticular levels of testosterone and dihydrotestosterone were significantly decreased both 7 and 28 days after treatment. No change in the prolactin and sex hormone-binding globulin concentration was observed. Exposure of the animals to AgNPs resulted in a considerable decrease in 5α-reductase type 1 and the aromatase protein level in the testis. Additionally, expression analysis of genes involved in steroidogenesis and the steroids metabolism revealed significant down-regulation of Star, Cyp11a1, Hsd3b1, Hsd17b3 and Srd5a1 mRNAs in AgNPs/AgSPs-exposed animals. The present study demonstrates the potential adverse effect on the hormonal regulation of the male reproductive function following AgNP/AgSP administration, in particular alterations of the sex steroid balance and expression of genes involved in steroidogenesis and the steroids metabolism. - Highlights: • Assessment of the toxic effects of AgNPs/AgSPs on the regulation of male reproductive function • AgNP −/AgSP-induced alterations of sex steroid status in male Wistar rats.

  4. Integrated treatment options for male perpetrators of intimate partner violence.

    PubMed

    Crane, Cory A; Easton, Caroline J

    2017-01-01

    Male-to-female intimate partner violence remains a worldwide public health issue with adverse physical and psychological consequences for victims, perpetrators and children. Personality disorders, addiction, trauma and mood symptoms are established risk factors for intimate partner violence perpetration and factor prominently into a recovery-oriented treatment approach. We reviewed the partner violence literature for detailed reports of traditional as well as innovative, integrated treatment approaches. Empirically based recommendations for intervention programs and the policies that guide intervention efforts are offered. Nascent research suggests that integrated treatment models utilising a holistic approach to account for psychological comorbidity and interventions that involve a motivational interviewing component appear promising in terms of significantly improving intimate partner violence treatment compliance and reducing subsequent acts of physical partner violence. Further, methodologically rigorous research is required to fully assess the benefits of traditional and integrated treatment options. We have advanced several recommendations, including the development of and exclusive reliance upon empirically supported treatments, conducting a thorough risk and needs assessment of the offender and the immediate family to facilitate appropriate treatment referrals, integrating content to foster the offender's internal motivation to change maladaptive behaviours, and attempting to minimise offender treatment burdens through the strategic use of integrated treatment models. Intimate partner violence is a complicated and nuanced problem that is perpetrated by a heterogeneous population and requires greater variability in integrated treatment options. [Crane CA, Easton CJ. Integrated treatment options for male perpetrators of intimate partner violence. Drug Alcohol Rev 2017;36:24-33]. © 2017 Australasian Professional Society on Alcohol and other Drugs.

  5. Turn the Wheel: Integral School Counseling for Male Adolescents.

    ERIC Educational Resources Information Center

    Forbes, David

    2003-01-01

    This article formulates an overarching, inclusive model of integral counseling that enables school counselors to help male adolescents challenge the norm of conventional masculinity. The model draws from 3 areas: transpersonal counseling, holistic education, and mindful social action. The aim is to move the students' level of self-development and…

  6. An integrative contextual developmental model of male stalking.

    PubMed

    White, J; Kowalski, R M; Lyndon, A; Valentine, S

    2000-01-01

    This article evaluates current research and theory on stalking as a form of male violence against women. The integrative contextual developmental model (White & Kowalski, 1998) suggests that stalking, as legally defined, is best understood as a multiply determined form of violence, with variables identifiable at several levels, the sociocultural, interpersonal, dyadic, situational and intrapersonal. The model also serves as a framework for identifying gaps in current research and suggests directions for further work.

  7. GDP-D-mannose epimerase regulates male gametophyte development, plant growth and leaf senescence in Arabidopsis.

    PubMed

    Qi, Tiancong; Liu, Zhipeng; Fan, Meng; Chen, Yan; Tian, Haixia; Wu, Dewei; Gao, Hua; Ren, Chunmei; Song, Susheng; Xie, Daoxin

    2017-09-04

    Plant GDP-D-mannose epimerase (GME) converts GDP-D-mannose to GDP-L-galactose, a precursor of both L-ascorbate (vitamin C) and cell wall polysaccharides. However, the genetic functions of GME in Arabidopsis are unclear. In this study, we found that mutations in Arabidopsis GME affect pollen germination, pollen tube elongation, and transmission and development of the male gametophyte through analysis of the heterozygous GME/gme plants and the homozygous gme plants. Arabidopsis gme mutants also exhibit severe growth defects and early leaf senescence. Surprisingly, the defects in male gametophyte in the gme plants are not restored by L-ascorbate, boric acid or GDP-L-galactose, though boric acid rescues the growth defects of the mutants, indicating that GME may regulate male gametophyte development independent of L-ascorbate and GDP-L-galactose. These results reveal key roles for Arabidopsis GME in reproductive development, vegetative growth and leaf senescence, and suggest that GME regulates plant growth and controls male gametophyte development in different manners.

  8. Male sex interspecies divergence and down regulation of expression of spermatogenesis genes in Drosophila sterile hybrids.

    PubMed

    Sundararajan, Vignesh; Civetta, Alberto

    2011-01-01

    Male sex genes have shown a pattern of rapid interspecies divergence at both the coding and gene expression level. A common outcome from crosses between closely-related species is hybrid male sterility. Phenotypic and genetic studies in Drosophila sterile hybrid males have shown that spermatogenesis arrest is postmeiotic with few exceptions, and that most misregulated genes are involved in late stages of spermatogenesis. Comparative studies of gene regulation in sterile hybrids and parental species have mainly used microarrays providing a whole genome representation of regulatory problems in sterile hybrids. Real-time PCR studies can reject or reveal differences not observed in microarray assays. Moreover, differences in gene expression between samples can be dependant on the source of RNA (e.g., whole body vs. tissue). Here we survey expression in D. simulans, D. mauritiana and both intra and interspecies hybrids using a real-time PCR approach for eight genes expressed at the four main stages of sperm development. We find that all genes show a trend toward under expression in the testes of sterile hybrids relative to parental species with only the two proliferation genes (bam and bgcn) and the two meiotic class genes (can and sa) showing significant down regulation. The observed pattern of down regulation for the genes tested can not fully explain hybrid male sterility. We discuss the down regulation of spermatogenesis genes in hybrids between closely-related species within the contest of rapid divergence experienced by the male genome, hybrid sterility and possible allometric changes due to subtle testes-specific developmental abnormalities.

  9. Attitudes of Male Unrestricted Line (URL) Officers Towards Integration of Women into Their Designators and Towards Women in Combat.

    DTIC Science & Technology

    1983-12-01

    APR 1 11984 THESIS D ,. *. ATTITUDES OF MALE UNRESTRICTED LINE (URL) OFFICERS𔃿 TOWARDS INTEGRATION OF WOMEN INTO THEIR DESIGNATORS AND TOWARDS WOMEN... Male Unrestricted Line (URL) Master’s Thesis Officers Towards Integration of Women into their December, 1983 ,- Designators and Towards Women in...Integration of Women sq. AMYRACT (CtMue an rew side i moeep and Idenllifr blekn mb ) Using Rand Survey data, this thesis examines the attitudes of male Unre

  10. Global identification predicts gay-male identity integration and well-being among Turkish gay men.

    PubMed

    Koc, Yasin; Vignoles, Vivian L

    2016-12-01

    In most parts of the world, hegemonic masculinity requires men to endorse traditional masculine ideals, one of which is rejection of homosexuality. Wherever hegemonic masculinity favours heterosexuality over homosexuality, gay males may feel under pressure to negotiate their conflicting male gender and gay sexual identities to maintain positive self-perceptions. However, globalization, as a source of intercultural interaction, might provide a beneficial context for people wishing to create alternative masculinities in the face of hegemonic masculinity. Hence, we tested if global identification would predict higher levels of gay-male identity integration, and indirectly subjective well-being, via alternative masculinity representations for gay and male identities. A community sample of 219 gay and bisexual men from Turkey completed the study. Structural equation modelling revealed that global identification positively predicted gay-male identity integration, and indirectly subjective well-being; however, alternative masculinity representations did not mediate this relationship. Our findings illustrate how identity categories in different domains can intersect and affect each other in complex ways. Moreover, we discuss mental health and well-being implications for gay men living in cultures where they experience high levels of prejudice and stigma. © 2016 The British Psychological Society.

  11. Genome-wide ENU mutagenesis for the discovery of novel male fertility regulators.

    PubMed

    Jamsai, Duangporn; O'Bryan, Moira K

    2010-06-01

    The completion of genome sequencing projects has provided an extensive knowledge of the contents of the genomes of human, mouse, and many other organisms. Despite this, the function of most of the estimated 25,000 human genes remains largely unknown. Attention has now turned to elucidating gene function and identifying biological pathways that contribute to human diseases, including male infertility. Our understanding of the genetic regulation of male fertility has been accelerated through the use of genetically modified mouse models including knockout, knock-in, gene-trapped, and transgenic mice. Such reverse genetic approaches however, require some fore-knowledge of a gene's function and, as such, bias against the discovery of completely novel genes and biological pathways. To facilitate high throughput gene discovery, genome-wide mouse mutagenesis via the use of a potent chemical mutagen, N-ethyl-N-nitrosourea (ENU), has been developed over the past decade. This forward genetic, or phenotype-driven, approach relies upon observing a phenotype first, then subsequently defining the underlining genetic defect. Mutations are randomly introduced into the mouse genome via ENU exposure. Through a controlled breeding scheme, mutations causing a phenotype of interest (e.g., male infertility) are then identified by linkage analysis and candidate gene sequencing. This approach allows for the possibility of revealing comprehensive phenotype-genotype relationships for a range of genes and pathways i.e. in addition to null alleles, mice containing partial loss of function or gain-of-function mutations, can be recovered. Such point mutations are likely to be more reflective of those that occur within the human population. Many research groups have successfully used this approach to generate infertile mouse lines and some novel male fertility genes have been revealed. In this review, we focus on the utility of ENU mutagenesis for the discovery of novel male fertility regulators.

  12. Mating and male pheromone kill Caenorhabditis males through distinct mechanisms.

    PubMed

    Shi, Cheng; Runnels, Alexi M; Murphy, Coleen T

    2017-03-14

    Differences in longevity between sexes is a mysterious yet general phenomenon across great evolutionary distances. To test the roles of responses to environmental cues and sexual behaviors in longevity regulation, we examined Caenorhabditis male lifespan under solitary, grouped, and mated conditions. We find that neurons and the germline are required for male pheromone-dependent male death. Hermaphrodites with a masculinized nervous system secrete male pheromone and are susceptible to male pheromone killing. Male pheromone-mediated killing is unique to androdioecious Caenorhabditis , and may reduce the number of males in hermaphroditic populations; neither males nor females of gonochoristic species are susceptible to male pheromone killing. By contrast, mating-induced death, which is characterized by germline-dependent shrinking, glycogen loss, and ectopic vitellogenin expression, utilizes distinct molecular pathways and is shared between the sexes and across species. The study of sex- and species-specific regulation of aging reveals deeply conserved mechanisms of longevity and population structure regulation.

  13. 7α-Hydroxypregnenolone regulates diurnal changes in sexual behavior of male quail.

    PubMed

    Ogura, Yuki; Haraguchi, Shogo; Nagino, Koki; Ishikawa, Kei; Fukahori, Yoko; Tsutsui, Kazuyoshi

    2016-02-01

    In the Japanese quail, 7α-hydroxypregnenolone, a previously undescribed avian neurosteroid, is actively produced in the brain. 7α-Hydroxypregnenolone acts as a novel neuronal activator to stimulate locomotor activity of quail. Therefore, in this study, we determined whether 7α-hydroxypregnenolone changes the expression of sexual behavior in Japanese quail. We first measured diurnal changes in sexual behavior of male quail exposed to a long-day photoperiod. We found that sexual behavior of male quail was high in the morning when endogenous 7α-hydroxypregnenolone level is high. Subsequently, we centrally administered 7α-hydroxypregnenolone in the evening when endogenous 7α-hydroxypregnenolone level is low. In the 30 min after intracerebroventricular (ICV) injection, 7α-hydroxypregnenolone dose dependently increased the frequency of sexual behavior of male quail. However, 7β-hydroxypregnenolone, a stereoisomer of 7α-hydroxypregnenolone, did not effect on the frequency of sexual behavior of male quail. In addition, to confirm the action of 7α-hydroxypregnenolone on sexual behavior, male birds received an ICV injection of ketoconazole, an inhibitor of cytochrome P450s, and behavioral experiments were performed in the morning. Ketoconazole significantly decreased the frequency of sexual behavior of male quail, whereas administration of 7α-hydroxypregnenolone to ketoconazole-treated males increased the frequency of their sexual behavior. These results indicate that 7α-hydroxypregnenolone regulates diurnal changes in sexual behavior of male quail. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Testosterone Regulates NUCB2 mRNA Expression in Male Mouse Hypothalamus and Pituitary Gland

    PubMed Central

    Seon, Sojeong; Jeon, Daun; Kim, Heejeong; Chung, Yiwa; Choi, Narae; Yang, Hyunwon

    2017-01-01

    ABSTRACT Nesfatin-1/NUCB2 is known to take part in the control of the appetite and energy metabolism. Recently, many reports have shown nesfatin-1/NUCB2 expression and function in various organs. We previously demonstrated that nesfatin-1/NUCB2 expression level is higher in the pituitary gland compared to other organs and its expression is regulated by 17β-estradiol and progesterone secreted from the ovary. However, currently no data exist on the expression of nesfatin-1/NUCB2 and its regulation mechanism in the pituitary of male mouse. Therefore, we examined whether nesfatin-1/NUCB2 is expressed in the male mouse pituitary and if its expression is regulated by testosterone. As a result of PCR and western blotting, we found that a large amount of nesfatin-1/NUCB2 was expressed in the pituitary and hypothalamus. The NUCB2 mRNA expression level in the pituitary was decreased after castration, but not in the hypothalamus. In addition, its mRNA expression level in the pituitary was increased after testosterone treatment in the castrated mice, whereas, the expression level in the hypothalamus was significantly decreased after the treatment with testosterone. The in vitro experiment to elucidate the direct effect of testosterone on NUCB2 mRNA expression showed that NUCB2 mRNA expression was significantly decreased with testosterone in cultured hypothalamus tissue, but increased with testosterone in cultured pituitary gland. The present study demonstrated that nesfatin-1/NUCB2 was highly expressed in the male mouse pituitary and was regulated by testosterone. This data suggests that reproductive-endocrine regulation through hypothalamus-pituitary-testis axis may contribute to NUCB2 mRNA expression in the mouse hypothalamus and pituitary gland. PMID:28484746

  15. Mating and male pheromone kill Caenorhabditis males through distinct mechanisms

    PubMed Central

    Shi, Cheng; Runnels, Alexi M; Murphy, Coleen T

    2017-01-01

    Differences in longevity between sexes is a mysterious yet general phenomenon across great evolutionary distances. To test the roles of responses to environmental cues and sexual behaviors in longevity regulation, we examined Caenorhabditis male lifespan under solitary, grouped, and mated conditions. We find that neurons and the germline are required for male pheromone-dependent male death. Hermaphrodites with a masculinized nervous system secrete male pheromone and are susceptible to male pheromone killing. Male pheromone-mediated killing is unique to androdioecious Caenorhabditis, and may reduce the number of males in hermaphroditic populations; neither males nor females of gonochoristic species are susceptible to male pheromone killing. By contrast, mating-induced death, which is characterized by germline-dependent shrinking, glycogen loss, and ectopic vitellogenin expression, utilizes distinct molecular pathways and is shared between the sexes and across species. The study of sex- and species-specific regulation of aging reveals deeply conserved mechanisms of longevity and population structure regulation. DOI: http://dx.doi.org/10.7554/eLife.23493.001 PMID:28290982

  16. Dopamine, the medial preoptic area, and male sexual behavior.

    PubMed

    Dominguez, Juan M; Hull, Elaine M

    2005-10-15

    The medial preoptic area (MPOA), at the rostral end of the hypothalamus, is important for the regulation of male sexual behavior. Results showing that male sexual behavior is impaired following MPOA lesions and enhanced with MPOA stimulation support this conclusion. The neurotransmitter dopamine (DA) facilitates male sexual behavior in all studied species, including rodents and humans. Here, we review data indicating that the MPOA is one site where DA may act to regulate male sexual behavior. DA agonists microinjected into the MPOA facilitate sexual behavior, whereas DA antagonists impair copulation, genital reflexes, and sexual motivation. Moreover, microdialysis experiments showed increased release of DA in the MPOA as a result of precopulatory exposure to an estrous female and during copulation. DA may remove tonic inhibition in the MPOA, thereby enhancing sensorimotor integration, and also coordinate autonomic influences on genital reflexes. In addition to sensory stimulation, other factors influence the release of DA in the MPOA, including testosterone, nitric oxide, and glutamate. Here we summarize and interpret these data.

  17. The DM domain transcription factor MAB-3 regulates male hypersensitivity to oxidative stress in Caenorhabditis elegans.

    PubMed

    Inoue, Hideki; Nishida, Eisuke

    2010-07-01

    Sex differences occur in most species and involve a variety of biological characteristics. The nematode Caenorhabditis elegans consists of two sexes, self-fertile hermaphrodites (XX) and males (XO). Males differ from hermaphrodites in morphology, behavior, and life span. Here, we find that male C. elegans worms are much more sensitive than hermaphrodites to oxidative stress and show that the DM domain transcription factor MAB-3 plays a pivotal role in determining this male hypersensitivity. The hypersensitivity to oxidative stress does not depend on the dosage of X chromosomes but is determined by the somatic sex determination pathway. Our analyses show that the male hypersensitivity is controlled by MAB-3, one of the downstream effectors of the master terminal switch TRA-1 in the sex determination pathway. Moreover, we find that MAB-3 suppresses expression of several transcriptional target genes of the ELT-2 GATA factor, which is a global regulator of transcription in the C. elegans intestine, and show that RNA interference (RNAi) against elt-2 increases sensitivity to oxidative stress. These results strongly suggest that the DM domain protein MAB-3 regulates oxidative stress sensitivity by repressing transcription of ELT-2 target genes in the intestine.

  18. HIV Risk and Protection among Gay Male Couples: The Role of Gay Community Integration

    ERIC Educational Resources Information Center

    Fergus, Stevenson; Lewis, Megan A.; Darbes, Lynae A.; Butterfield, Rita M.

    2005-01-01

    This study examined the association between different types of integration in the gay community and HIV risk among gay male couples. Previous research linking gay community integration and involvement among couples to HIV risk has been equivocal. Each partner in 59 gay couples completed a separate anonymous questionnaire that assessed two types of…

  19. Intrauterine Growth Restriction Programs the Hypothalamus of Adult Male Rats: Integrated Analysis of Proteomic and Metabolomic Data.

    PubMed

    Pedroso, Amanda P; Souza, Adriana P; Dornellas, Ana P S; Oyama, Lila M; Nascimento, Cláudia M O; Santos, Gianni M S; Rosa, José C; Bertolla, Ricardo P; Klawitter, Jelena; Christians, Uwe; Tashima, Alexandre K; Ribeiro, Eliane B

    2017-04-07

    Programming of hypothalamic functions regulating energy homeostasis may play a role in intrauterine growth restriction (IUGR)-induced adulthood obesity. The present study investigated the effects of IUGR on the hypothalamus proteome and metabolome of adult rats submitted to 50% protein-energy restriction throughout pregnancy. Proteomic and metabolomic analyzes were performed by data independent acquisition mass spectrometry and multiple reaction monitoring, respectively. At age 4 months, the restricted rats showed elevated adiposity, increased leptin and signs of insulin resistance. 1356 proteins were identified and 348 quantified while 127 metabolites were quantified. The restricted hypothalamus showed down-regulation of 36 proteins and 5 metabolites and up-regulation of 21 proteins and 9 metabolites. Integrated pathway analysis of the proteomics and metabolomics data indicated impairment of hypothalamic glucose metabolism, increased flux through the hexosamine pathway, deregulation of TCA cycle and the respiratory chain, and alterations in glutathione metabolism. The data suggest IUGR modulation of energy metabolism and redox homeostasis in the hypothalamus of male adult rats. The present results indicated deleterious consequences of IUGR on hypothalamic pathways involved in pivotal physiological functions. These results provide guidance for future mechanistic studies assessing the role of intrauterine malnutrition in the development of metabolic diseases later in life.

  20. Self- and Social Regulation in Learning Contexts: An Integrative Perspective

    ERIC Educational Resources Information Center

    Volet, Simone; Vauras, Marja; Salonen, Pekka

    2009-01-01

    This article outlines the rationale for an integrative perspective of self- and social regulation in learning contexts. The role of regulatory mechanisms in self- and social regulation models is examined, leading to the view that in real time collaborative learning, individuals and social entities should be conceptualized as self-regulating and…

  1. Male erectile dysfunction: integrating psychopharmacology and psychotherapy.

    PubMed

    Simopoulos, Eugene F; Trinidad, Anton C

    2013-01-01

    Erectile dysfunction (ED), defined as the inability to achieve or maintain an erection sufficient for satisfactory sexual performance, is the most common sexual problem in men. ED arises when there is disruption of the complex interplay between vascular, neurologic, hormonal and psychologic factors necessary for normal erectile function. It may have a significant effect on quality of life and portend undetected cardiovascular disease. Risk factors for development of ED include advancing age, tobacco use, a history of pelvic irradiation or surgery and antipsychotic use (Table 1) [1]. Treatment guidelines continue to evolve for optimal management of ED. In this article, we review diagnostic and treatment strategies for ED relevant to psychiatrists. We present an integrative approach to the treatment of ED based on a review of the urologic and psychiatric literature. ED is multifactorial in origin and responsive to a variety of therapeutic interventions, including psychopharmacology and psychotherapy in which cognitive underpinnings of poor sexual performance, including diminished self-esteem, lack of confidence and perceived failures in the male role, are examined. Psychiatrists can readily perform a basic workup for ED as they integrate both a medical and therapeutic model when confronted with such patients. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Hormonal regulation of steroid receptor coactivator-1 mRNA in the male and female green anole brain.

    PubMed

    Kerver, H N; Wade, J

    2015-03-01

    Green anole lizards are seasonal breeders, with male sexual behaviour primarily regulated by an annual increase in testosterone. Morphological, biochemical and behavioural changes associated with reproduction are activated by testosterone, generally with a greater effect in the breeding season (BS) than in the nonbreeding season (NBS). The present study investigates the possibility that differences in a steroid receptor coactivator may regulate this seasonal difference in responsiveness to testosterone. In situ hybridisation was used to examine the expression of steroid receptor coactivator-1 (SRC-1) in the brains of gonadally intact male and female green anoles across breeding states. A second experiment examined gonadectomised animals with and without testosterone treatment. Gonadally intact males had more SRC-1 expressing cells in the preoptic area and larger volumes of this region as defined by these cells than females. Main effects of both sex and season (males > females and BS > NBS) were present in cell number and volume of the ventromedial hypothalamus. An interaction between sex and season suggested that high expression in BS males was driving these effects. In hormone-manipulated animals, testosterone treatment increased both the number of SRC-1 expressing cells in and volumes of the preoptic area and amygdala. These results suggest that testosterone selectively regulates SRC-1, and that this coactivator may play a role in facilitating reproductive behaviours across both sexes. However, changes in SRC-1 expression are not likely responsible for the seasonal change in responsiveness to testosterone. © 2014 British Society for Neuroendocrinology.

  3. The C. elegans male exercises directional control during mating through cholinergic regulation of sex-shared command interneurons.

    PubMed

    Sherlekar, Amrita L; Janssen, Abbey; Siehr, Meagan S; Koo, Pamela K; Caflisch, Laura; Boggess, May; Lints, Robyn

    2013-01-01

    Mating behaviors in simple invertebrate model organisms represent tractable paradigms for understanding the neural bases of sex-specific behaviors, decision-making and sensorimotor integration. However, there are few examples where such neural circuits have been defined at high resolution or interrogated. Here we exploit the simplicity of the nematode Caenorhabditis elegans to define the neural circuits underlying the male's decision to initiate mating in response to contact with a mate. Mate contact is sensed by male-specific sensilla of the tail, the rays, which subsequently induce and guide a contact-based search of the hermaphrodite's surface for the vulva (the vulva search). Atypically, search locomotion has a backward directional bias so its implementation requires overcoming an intrinsic bias for forward movement, set by activity of the sex-shared locomotory system. Using optogenetics, cell-specific ablation- and mutant behavioral analyses, we show that the male makes this shift by manipulating the activity of command cells within this sex-shared locomotory system. The rays control the command interneurons through the male-specific, decision-making interneuron PVY and its auxiliary cell PVX. Unlike many sex-shared pathways, PVY/PVX regulate the command cells via cholinergic, rather than glutamatergic transmission, a feature that likely contributes to response specificity and coordinates directional movement with other cholinergic-dependent motor behaviors of the mating sequence. PVY/PVX preferentially activate the backward, and not forward, command cells because of a bias in synaptic inputs and the distribution of key cholinergic receptors (encoded by the genes acr-18, acr-16 and unc-29) in favor of the backward command cells. Our interrogation of male neural circuits reveals that a sex-specific response to the opposite sex is conferred by a male-specific pathway that renders subordinate, sex-shared motor programs responsive to mate cues. Circuit

  4. Integrating the Regulation of Affect, Behavior, and Cognition into Self-Regulated Learning Paradigms among Secondary and Post-Secondary Students

    ERIC Educational Resources Information Center

    Ben-Eliyahu, Adar; Linnenbrink-Garcia, Lisa

    2015-01-01

    An integrative framework for investigating self-regulated learning situated in students' favorite and least favorite courses was empirically tested in a sample of 178 high school and 280 college students. Building on cognitive, clinical, social, and educational conceptions of self-regulation, the current paper integrated affective (e.g.,…

  5. Specific down-regulation of spermatogenesis genes targeted by 22G RNAs in hybrid sterile males associated with an X-Chromosome introgression.

    PubMed

    Li, Runsheng; Ren, Xiaoliang; Bi, Yu; Ho, Vincy Wing Sze; Hsieh, Chia-Ling; Young, Amanda; Zhang, Zhihong; Lin, Tingting; Zhao, Yanmei; Miao, Long; Sarkies, Peter; Zhao, Zhongying

    2016-09-01

    Hybrid incompatibility (HI) prevents gene flow between species, thus lying at the heart of speciation genetics. One of the most common HIs is male sterility. Two superficially contradictory observations exist for hybrid male sterility. First, an introgression on the X Chromosome is more likely to produce male sterility than on autosome (so-called large-X theory); second, spermatogenesis genes are enriched on the autosomes but depleted on the X Chromosome (demasculinization of X Chromosome). Analysis of gene expression in Drosophila hybrids suggests a genetic interaction between the X Chromosome and autosomes that is essential for male fertility. However, the prevalence of such an interaction and its underlying mechanism remain largely unknown. Here we examine the interaction in nematode species by contrasting the expression of both coding genes and transposable elements (TEs) between hybrid sterile males and its parental nematode males. We use two lines of hybrid sterile males, each carrying an independent introgression fragment from Caenorhabditis briggsae X Chromosome in an otherwise Caenorhabditis nigoni background, which demonstrate similar defects in spermatogenesis. We observe a similar pattern of down-regulated genes that are specific for spermatogenesis between the two hybrids. Importantly, the down-regulated genes caused by the X Chromosome introgressions show a significant enrichment on the autosomes, supporting an epistatic interaction between the X Chromosome and autosomes. We investigate the underlying mechanism of the interaction by measuring small RNAs and find that a subset of 22G RNAs specifically targeting the down-regulated spermatogenesis genes is significantly up-regulated in hybrids, suggesting that perturbation of small RNA-mediated regulation may contribute to the X-autosome interaction. © 2016 Li et al.; Published by Cold Spring Harbor Laboratory Press.

  6. An integral projection model with YY-males and application to evaluating grass carp control

    USGS Publications Warehouse

    Erickson, Richard A.; Eager, Eric A.; Brey, Marybeth; Hansen, Michael J.; Kocovsky, Patrick

    2017-01-01

    Invasive fish species disrupt ecosystems and cause economic damage. Several methods have been discussed to control populations of invasive fish including the release of YY-males. YY-males are fish that have 2 male chromosomes compared to a XY-male. When YY-males mate, they only produce male (XY) offspring. This decreases the female proportion of the population and can, in theory, eradicate local populations by biasing the sex-ratio. YY-males have been used as a population control tool for brook trout in montane streams and lakes in Idaho, USA. The YY-male control method has been discussed for grass carp in Lake Erie, North America. We developed and presented an integral projection model for grass carp to model the use of YY-males as a control method for populations in this lake. Using only the YY-male control method, we found that high levels of YY-males would need to be release annually to control the species. Specifically, these levels were the same order of magnitude as the baseline adult population (e.g., 1000 YY-males needed to be released annual for 20 years to control a baseline adult population of 2500 grass carp). These levels may not be reasonable or obtainable for fisheries managers given the impacts of YY-males on aquatic vegetation and other constraints of natural resource management.

  7. Gene regulation by NMDA receptor activation in the SDN-POA neurons of male rats during sexual development.

    PubMed

    Hsu, Hseng-Kuang; Shao, Pei-Lin; Tsai, Ke-Li; Shih, Huei-Chuan; Lee, Tzu-Ying; Hsu, Chin

    2005-04-01

    The present study was designed to identify possible signaling pathways, which may play a role in prevention of neuronal apoptosis in the sexually dimorphic nucleus of the preoptic area (SDN-POA) after physiological activation of the N-methyl-D-aspartate (NMDA) receptor. Gene response to the blockage of the NMDA receptor by an antagonist (dizocilpine hydrogen maleate; MK-801) was screened after suppression subtractive hybridization (SSH). The results showed that differential screening after SSH detected the presence of some neurotrophic genes (RNA binding motif protein 3 (RBM3), alpha-tubulin) as well as apoptosis-related genes (Bcl-2, cytochrome oxidase subunit II, cytochrome oxidase subunit III) in the SDN-POA of male rats, which were down-regulated by blocking the NMDA receptor. The RT-PCR products of the aforementioned genes in MK-801-treated males were significantly less than that in untreated males. In particular, the expression of Bcl-2 mRNA, including Bcl-2 protein, in male rats were significantly suppressed by MK-801 treatment. Moreover, the binding activity of nuclear factor kappaB (NFkappaB) was significantly higher in male rats than in females, but significantly diminished by blocking the NMDA receptor with MK-801 in male rats. No significant difference in cAMP response element-binding protein (CREB) binding activity was observed among untreated male, MK-801-treated male, untreated female and MK-801-treated female groups. These results suggest that genes regulated by NMDA receptor activation might participate in neuronal growth and/or anti-apoptosis, and support an important signaling pathway of NFkappaB activation and its target gene, Bcl-2, in preventing neuronal apoptosis in the SDN-POA of male rats during sexual development.

  8. [Toward a deeper understanding of motivation towards exercise: measurement of integrated regulation in the Spanish context].

    PubMed

    González-Cutre, David; Sicilia, Álvaro; Fernández, Alberto

    2010-11-01

    The purpose of this study was to validate the Behavioural Regulation in Exercise Questionnaire in the Spanish context, including items to measure integrated regulation. Participants were 524 exercisers, mean age 29.59 years. The results revealed acceptable fit indices in the confirmatory factor analysis and good internal consistency (with a Cronbach alpha of .87 for integrated regulation). The diverse subscales also conformed to a simplex pattern and the factor structure was invariant across gender and age. Integrated regulation reflected high temporal stability over a 4-week period (ICC=.90). The criterion validity analysis of integrated regulation indicated that this variable was positively predicted by satisfaction of the needs for competence and autonomy. The results regarding the importance of measuring integrated regulation in exercise are discussed.

  9. Maladaptive and adaptive emotion regulation through music: a behavioral and neuroimaging study of males and females

    PubMed Central

    Carlson, Emily; Saarikallio, Suvi; Toiviainen, Petri; Bogert, Brigitte; Kliuchko, Marina; Brattico, Elvira

    2015-01-01

    Music therapists use guided affect regulation in the treatment of mood disorders. However, self-directed uses of music in affect regulation are not fully understood. Some uses of music may have negative effects on mental health, as can non-music regulation strategies, such as rumination. Psychological testing and functional magnetic resonance imaging (fMRI) were used explore music listening strategies in relation to mental health. Participants (n = 123) were assessed for depression, anxiety and Neuroticism, and uses of Music in Mood Regulation (MMR). Neural responses to music were measured in the medial prefrontal cortex (mPFC) in a subset of participants (n = 56). Discharge, using music to express negative emotions, related to increased anxiety and Neuroticism in all participants and particularly in males. Males high in Discharge showed decreased activity of mPFC during music listening compared with those using less Discharge. Females high in Diversion, using music to distract from negative emotions, showed more mPFC activity than females using less Diversion. These results suggest that the use of Discharge strategy can be associated with maladaptive patterns of emotional regulation, and may even have long-term negative effects on mental health. This finding has real-world applications in psychotherapy and particularly in clinical music therapy. PMID:26379529

  10. EPHRIN-A5 REGULATES INTER-MALE AGGRESSION IN MICE

    PubMed Central

    Sheleg, Michal; Yochum, Carrie L.; Richardson, Jason R.; Wagner, George C.; Zhou, Renping

    2015-01-01

    The Eph family of receptor tyrosine kinases play key roles in both the patterning of the developing nervous system and neural plasticity in the mature brain. To determine functions of ephrin-A5, a GPI-linked ligand to the Eph receptors, in animal behavior regulations, we examined effects of its inactivation on male mouse aggression. When tested in the resident-intruder paradigm for offensive aggression, ephrin-A5-mutant animals (ephrin-A5−/−) exhibited severe reduction in conspecific aggression compared to wild-type controls. On the contrary, defensive aggression in the form of target biting was higher in ephrin-A5−/− mice, indicating that the mutant mice are capable of attacking behavior. In addition, given the critical role of olfaction in aggressive behavior, we examined the ability of the ephrin-A5−/− mice to smell and found no differences between the mutant and control animals. Testosterone levels in the mutant mice were also found to be within the normal range. Taken together, our data reveal a new role of ephrin-A5 in the regulation of aggressive behavior in mice. PMID:25746458

  11. An Integrative Theory-Driven Positive Emotion Regulation Intervention

    PubMed Central

    Weytens, Fanny; Luminet, Olivier; Verhofstadt, Lesley L.; Mikolajczak, Moïra

    2014-01-01

    Over the past fifteen years, positive psychology research has validated a set of happiness enhancing techniques. These techniques are relatively simple exercises that allow happiness seekers to mimic thoughts and behavior of naturally happy people, in order to increase their level of well-being. Because research has shown that the joint use of these exercises increases their effects, practitioners who want to help happiness seekers need validated interventions that combine several of these techniques. To meet this need, we have developed and tested an integrative intervention (Positive Emotion Regulation program – PER program) incorporating a number of validated techniques structured around a theoretical model: the Process Model of Positive Emotion Regulation. To test the effectiveness of this program and to identify its added value relative to existing interventions, 113 undergraduate students were randomly assigned to a 6-week positive emotion regulation pilot program, a loving-kindness meditation training program, or a wait-list control group. Results indicate that fewer participants dropped out from the PER program than from the Loving-Kindness Meditation training. Furthermore, subjects in the PER group showed a significant increase in subjective well-being and life satisfaction and a significant decrease in depression and physical symptoms when compared to controls. Our results suggest that the Process Model of Positive Emotion Regulation can be an effective option to organize and deliver positive integrative interventions. PMID:24759870

  12. The C. elegans Male Exercises Directional Control during Mating through Cholinergic Regulation of Sex-Shared Command Interneurons

    PubMed Central

    Sherlekar, Amrita L.; Janssen, Abbey; Siehr, Meagan S.; Koo, Pamela K.; Caflisch, Laura; Boggess, May; Lints, Robyn

    2013-01-01

    Background Mating behaviors in simple invertebrate model organisms represent tractable paradigms for understanding the neural bases of sex-specific behaviors, decision-making and sensorimotor integration. However, there are few examples where such neural circuits have been defined at high resolution or interrogated. Methodology/Principal Findings Here we exploit the simplicity of the nematode Caenorhabditis elegans to define the neural circuits underlying the male’s decision to initiate mating in response to contact with a mate. Mate contact is sensed by male-specific sensilla of the tail, the rays, which subsequently induce and guide a contact-based search of the hermaphrodite’s surface for the vulva (the vulva search). Atypically, search locomotion has a backward directional bias so its implementation requires overcoming an intrinsic bias for forward movement, set by activity of the sex-shared locomotory system. Using optogenetics, cell-specific ablation- and mutant behavioral analyses, we show that the male makes this shift by manipulating the activity of command cells within this sex-shared locomotory system. The rays control the command interneurons through the male-specific, decision-making interneuron PVY and its auxiliary cell PVX. Unlike many sex-shared pathways, PVY/PVX regulate the command cells via cholinergic, rather than glutamatergic transmission, a feature that likely contributes to response specificity and coordinates directional movement with other cholinergic-dependent motor behaviors of the mating sequence. PVY/PVX preferentially activate the backward, and not forward, command cells because of a bias in synaptic inputs and the distribution of key cholinergic receptors (encoded by the genes acr-18, acr-16 and unc-29) in favor of the backward command cells. Conclusion/Significance Our interrogation of male neural circuits reveals that a sex-specific response to the opposite sex is conferred by a male-specific pathway that renders subordinate

  13. The social and ecological integration of captive-raised adolescent male African elephants (Loxodonta africana) into a wild population.

    PubMed

    Evans, Kate; Moore, Randall; Harris, Stephen

    2013-01-01

    A rapid rise in the number of captive African elephants (Loxodonta africana) used in the tourism industry in southern Africa and orphaned elephants in human care has led to concerns about their long-term management, particularly males. One solution is to release them into the wild at adolescence, when young males naturally leave their herd. However, this raises significant welfare concerns: little is known about how well released elephants integrate into wild populations and whether they pose a greater threat to humans than wild elephants. We document the release of three captive-raised adolescent male African elephants in the Okavango Delta, Botswana. Despite having been part of a herd of working elephants for at least eight years, the three males progressively integrated into the complex fission-fusion society of wild bull elephants. In the three years following release, they showed no tendency to be closer to human habitation, and there were no significant differences between wild and captive-raised adolescent males in the total number of social interactions, size of ranges and habitat use. However, the captive-raised elephants sparred less and vocalised more, and spent more time alone and in smaller social groups. Thereafter the released elephants continued to expand their ranges and interact with both mixed-sex herds and males. One male was shot by farmers 94 months after release, along with ten wild elephants, on a ranch outside the protected area. We show that captive-raised adolescent male elephants can integrate into a wild population. Long-term studies are required to determine the longevity, breeding success, and eventual fate of released male elephants, but we identified no significant short-term welfare problems for the released elephants or recipient population. Release of captive-raised mammals with complex social systems is a husbandry option that should be explored further.

  14. The Social and Ecological Integration of Captive-Raised Adolescent Male African Elephants (Loxodonta africana) into a Wild Population

    PubMed Central

    Evans, Kate; Moore, Randall; Harris, Stephen

    2013-01-01

    Background A rapid rise in the number of captive African elephants (Loxodonta africana) used in the tourism industry in southern Africa and orphaned elephants in human care has led to concerns about their long-term management, particularly males. One solution is to release them into the wild at adolescence, when young males naturally leave their herd. However, this raises significant welfare concerns: little is known about how well released elephants integrate into wild populations and whether they pose a greater threat to humans than wild elephants. We document the release of three captive-raised adolescent male African elephants in the Okavango Delta, Botswana. Methodology/Principal Findings Despite having been part of a herd of working elephants for at least eight years, the three males progressively integrated into the complex fission-fusion society of wild bull elephants. In the three years following release, they showed no tendency to be closer to human habitation, and there were no significant differences between wild and captive-raised adolescent males in the total number of social interactions, size of ranges and habitat use. However, the captive-raised elephants sparred less and vocalised more, and spent more time alone and in smaller social groups. Thereafter the released elephants continued to expand their ranges and interact with both mixed-sex herds and males. One male was shot by farmers 94 months after release, along with ten wild elephants, on a ranch outside the protected area. Conclusions/Significance We show that captive-raised adolescent male elephants can integrate into a wild population. Long-term studies are required to determine the longevity, breeding success, and eventual fate of released male elephants, but we identified no significant short-term welfare problems for the released elephants or recipient population. Release of captive-raised mammals with complex social systems is a husbandry option that should be explored further. PMID

  15. Life Goals Increase Self-regulation Among Male Patients with Alcohol Use Disorder.

    PubMed

    Won, Sung-Doo; Kim, Im-Yel

    2018-01-24

    Alcohol use disorder (AUD) has been conceptualized as a chronic self-regulation failure. The aim of this study was to examine the most probable pathways related to self-regulation among patients with AUD. In this study, a hypothetical model was proposed that focused on the relationship between risk factors (extrinsic life goals, emotion dysregulation) and protective factors (intrinsic life goals, self-control, and abstinence self-efficacy). Male patients with AUD (N = 188) were recruited from alcohol centers of four psychiatric hospitals between March 2015 and September 2015. All participants completed psychological assessments, including the Future Oriented Goals Scale (FOGS), the Alcohol Abstinence Self-Efficacy Scale (AASE), the Brief Self-Control Scale (BSCS), and the Difficulties in Emotion Regulation Scale (DERS) as well as sociodemographic characteristics. The final model was found to be a good fit to data. In testing indirect effects, it was shown that intrinsic life goals via emotion dysregulation, self-control, and alcohol abstinence self-efficacy decreased alcohol self-regulation failure. On the other hand, extrinsic life goals via these factors increased alcohol self-regulation failure. Conclusions/Importance: These results suggest that intrinsic goals might indirectly be the important and protective factors for AUD. Moreover, the findings implicate that self-regulation through goal setting may be necessary to alleviate symptoms and improve function among patients with AUD.

  16. Complementary transcriptome and proteome profiling in cabbage buds of a recessive male sterile mutant provides new insights into male reproductive development.

    PubMed

    Ji, Jialei; Yang, Limei; Fang, Zhiyuan; Zhuang, Mu; Zhang, Yangyong; Lv, Honghao; Liu, Yumei; Li, Zhansheng

    2018-05-15

    Plant male reproductive development is a very complex biological process that involves multiple metabolic pathways. To reveal novel insights into male reproductive development, we conducted an integrated profiling of gene activity in the developing buds of a cabbage recessive genetic male sterile mutant. Using RNA-Seq and label-free quantitative proteomics, 2881 transcripts and 1245 protein species were identified with significant differential abundance between the male sterile line 83121A and its isogenic maintainer line 83121B. Analyses of function annotations and correlations between transcriptome and proteome and protein interaction networks were also conducted, which suggested that the male sterility involves a complex regulatory pattern. Moreover, several key biological processes, such as fatty acid metabolism, tapetosome biosynthesis, amino acid metabolism and protein synthesis and degradation were identified as being of relevance to male reproductive development. A large number of protein species involved in sporopollenin synthesis, amino acid synthesis, ribosome assembly, protein processing in endoplasmic reticulum and lipid transfer were observed to be significantly down-accumulated in 83121A buds, indicating their potential roles in the regulation of cabbage microspore abortion. In summary, the conjoint analysis of the transcriptome and proteome provided a global picture regarding the molecular dynamics in male sterile buds of 83121A. Male sterile mutants are excellent materials for the study of plant male reproductive development. This study revealed the molecular dynamics of recessive male sterility in cabbage at the transcriptome and proteome levels, which deepens our understanding of the metabolic pathways involved in male development. Moreover, the male sterility-related genes identified in this study could provide a reference for the artificial regulation of cabbage fertility by using genetic engineering technology, which may result in potential

  17. Sexual experience affects reproductive behavior and preoptic androgen receptors in male mice

    PubMed Central

    Swaney, William T.; Dubose, Brittany N.; Curley, James P.; Champagne, Frances A.

    2012-01-01

    Reproductive behavior in male rodents is made up of anticipatory and consummatory elements which are regulated in the brain by sensory systems, reward circuits and hormone signaling. Gonadal steroids play a key role in the regulation of male sexual behavior via steroid receptors in the hypothalamus and preoptic area. Typical patterns of male reproductive behavior have been characterized, however these are not fixed but are modulated by adult experience. We assessed the effects of repeated sexual experience on male reproductive behavior of C57BL/6 mice; including measures of olfactory investigation of females, mounting, intromission and ejaculation. The effects of sexual experience on the number of cells expressing either androgen receptor (AR) or estrogen receptor alpha (ERα) in the primary brain nuclei regulating male sexual behavior was also measured. Sexually experienced male mice engaged in less sniffing of females before initiating sexual behavior and exhibited shorter latencies to mount and intromit, increased frequency of intromission, and increased duration of intromission relative to mounting. No changes in numbers of ERα-positive cells were observed, however sexually experienced males had increased numbers of AR-positive cells in the medial preoptic area (MPOA); the primary regulatory nucleus for male sexual behavior. These results indicate that sexual experience results in a qualitative change in male reproductive behavior in mice that is associated with increased testosterone sensitivity in the MPOA and that this nucleus may play a key integrative role in mediating the effects of sexual experience on male behavior. PMID:22266118

  18. An Automatic Baseline Regulation in a Highly Integrated Receiver Chip for JUNO

    NASA Astrophysics Data System (ADS)

    Muralidharan, P.; Zambanini, A.; Karagounis, M.; Grewing, C.; Liebau, D.; Nielinger, D.; Robens, M.; Kruth, A.; Peters, C.; Parkalian, N.; Yegin, U.; van Waasen, S.

    2017-09-01

    This paper describes the data processing unit and an automatic baseline regulation of a highly integrated readout chip (Vulcan) for JUNO. The chip collects data continuously at 1 Gsamples/sec. The Primary data processing which is performed in the integrated circuit can aid to reduce the memory and data processing efforts in the subsequent stages. In addition, a baseline regulator compensating a shift in the baseline is described.

  19. Transference and insight in psychotherapy with gay and bisexual male clients: the role of sexual orientation identity integration.

    PubMed

    Mohr, Jonathan J; Fuertes, Jairo N; Stracuzzi, Thomas I

    2015-03-01

    Clinical writing has suggested that the therapeutic process and relationship in work with lesbian, gay, and bisexual clients may be influenced by the extent to which clients have accepted their sexual orientation and developed a social network supportive of their sexual orientation, a construct we refer to as sexual orientation identity integration. The present cross-sectional study investigated this proposition by examining the identity integration ratings of 90 gay and bisexual male clients in relation to elements of treatment as rated by both the therapist (insight, negative transference, working alliance, session depth, and client improvement) and client (working alliance, session depth, and client improvement). Participants were male-male therapy dyads recruited from lesbian, gay, and bisexual-affirming practices. Client identity integration was negatively associated with transference, and positively associated with ratings of insight, alliance, depth, and improvement. Insight, but not transference, uniquely mediated the positive association between identity integration and most indicators of therapeutic quality. Results from an exploratory model suggested that transference may indirectly influence therapeutic quality by serving as a barrier to insight. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  20. 77 FR 52739 - Federal Acquisition Regulation; Information Collection; Integrity of Unit Prices

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-30

    ...; Information Collection; Integrity of Unit Prices AGENCY: Department of Defense (DOD), General Services... requirement concerning Integrity of Unit Prices. Public comments are particularly invited on: Whether this... Information Collection 9000- 0080, Integrity of Unit Prices by any of the following methods: Regulations.gov...

  1. Octopamine Neuromodulation Regulates Gr32a-Linked Aggression and Courtship Pathways in Drosophila Males

    PubMed Central

    Andrews, Jonathan C.; Fernández, María Paz; Yu, Qin; Leary, Greg P.; Leung, Adelaine K. W.; Kavanaugh, Michael P.; Kravitz, Edward A.; Certel, Sarah J.

    2014-01-01

    Chemosensory pheromonal information regulates aggression and reproduction in many species, but how pheromonal signals are transduced to reliably produce behavior is not well understood. Here we demonstrate that the pheromonal signals detected by Gr32a-expressing chemosensory neurons to enhance male aggression are filtered through octopamine (OA, invertebrate equivalent of norepinephrine) neurons. Using behavioral assays, we find males lacking both octopamine and Gr32a gustatory receptors exhibit parallel delays in the onset of aggression and reductions in aggression. Physiological and anatomical experiments identify Gr32a to octopamine neuron synaptic and functional connections in the suboesophageal ganglion. Refining the Gr32a-expressing population indicates that mouth Gr32a neurons promote male aggression and form synaptic contacts with OA neurons. By restricting the monoamine neuron target population, we show that three previously identified OA-FruM neurons involved in behavioral choice are among the Gr32a-OA connections. Our findings demonstrate that octopaminergic neuromodulatory neurons function as early as a second-order step in this chemosensory-driven male social behavior pathway. PMID:24852170

  2. Male genital tract antioxidant enzymes--their ability to preserve sperm DNA integrity.

    PubMed

    O, Wai-Sum; Chen, H; Chow, P H

    2006-05-16

    Male germ cells are unique because they lose a bulk of their cytoplasm as cytoplasmic droplets when they develop, leading to a decrease in endogenous antioxidant and hence a dependence on extracellular antioxidant system to overcome oxidative stress. Spermatozoa are particularly vulnerable to oxidative stress because their plasma membrane is rich in polyunsaturated fatty acids and membrane-bound NADPH oxidase. To protect spermatozoa from oxidative attack, an optimal amount of reactive oxygen species is maintained by balancing the reactive oxygen species generated during sperm maturation in the epididymidis and antioxidants in secretions of the male reproductive tract. The male accessory sex glands secretions have been shown to be the major source of antioxidant enzymes in the ejaculate and have the important function of preserving sperm DNA integrity from oxidative stress experienced in the uterine environment. In our in vivo golden hamster model, ablation of the five major male accessory sex glands, namely the ampullary glands, coagulating glands, dorsolateral prostate, ventral prostate and seminal vesicle, was found to cause higher incidence and greater degree of DNA damage in spermatozoa. These damaged sperm are able to undergo fertilization at the same rate as intact ones; however, the outcome of embryos sired is seriously affected.

  3. The Social Regulation of Emotion: An Integrative, Cross-Disciplinary Model.

    PubMed

    Reeck, Crystal; Ames, Daniel R; Ochsner, Kevin N

    2016-01-01

    Research in emotion regulation has largely focused on how people manage their own emotions, but there is a growing recognition that the ways in which we regulate the emotions of others also are important. Drawing on work from diverse disciplines, we propose an integrative model of the psychological and neural processes supporting the social regulation of emotion. This organizing framework, the 'social regulatory cycle', specifies at multiple levels of description the act of regulating another person's emotions as well as the experience of being a target of regulation. The cycle describes the processing stages that lead regulators to attempt to change the emotions of a target person, the impact of regulation on the processes that generate emotions in the target, and the underlying neural systems. Copyright © 2015. Published by Elsevier Ltd.

  4. The Social Regulation of Emotion: An Integrative, Cross-Disciplinary Model

    PubMed Central

    Reeck, Crystal; Ames, Daniel R.; Ochsner, Kevin N.

    2018-01-01

    Research in emotion regulation has largely focused on how people manage their own emotions, but there is a growing recognition that the ways in which we regulate the emotions of others also are important. Drawing on work from diverse disciplines, we propose an integrative model of the psychological and neural processes supporting the social regulation of emotion. This organizing framework, the ‘social regulatory cycle’, specifies at multiple levels of description the act of regulating another person’s emotions as well as the experience of being a target of regulation. The cycle describes the processing stages that lead regulators to attempt to change the emotions of a target person, the impact of regulation on the processes that generate emotions in the target, and the underlying neural systems. PMID:26564248

  5. Pituitary Androgen Receptor Signalling Regulates Prolactin but Not Gonadotrophins in the Male Mouse

    PubMed Central

    O’Hara, Laura; Curley, Michael; Tedim Ferreira, Maria; Cruickshanks, Lyndsey; Milne, Laura; Smith, Lee B.

    2015-01-01

    Production of the androgen testosterone is controlled by a negative feedback loop within the hypothalamic-pituitary-gonadal (HPG) axis. Stimulation of testicular Leydig cells by pituitary luteinising hormone (LH) is under the control of hypothalamic gonadotrophin releasing hormone (GnRH), while suppression of LH secretion by the pituitary is controlled by circulating testosterone. Exactly how androgens exert their feedback control of gonadotrophin secretion (and whether this is at the level of the pituitary), as well as the role of AR in other pituitary cell types remains unclear. To investigate these questions, we exploited a transgenic mouse line (Foxg1Cre/+; ARfl/y) which lacks androgen receptor in the pituitary gland. Both circulating testosterone and gonadotrophins are unchanged in adulthood, demonstrating that AR signalling is dispensable in the male mouse pituitary for testosterone-dependent regulation of LH secretion. In contrast, Foxg1Cre/+; ARfl/y males have a significant increase in circulating prolactin, suggesting that, rather than controlling gonadotrophins, AR-signalling in the pituitary acts to suppress aberrant prolactin production in males. PMID:25799562

  6. 75 FR 3178 - Defense Federal Acquisition Regulation Supplement; Lead System Integrators

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-20

    ... Government procurement. Amy G. Williams, Editor, Defense Acquisition Regulations System. 0 Accordingly, the..., without change, an interim rule amending the Defense Federal Acquisition Regulation Supplement (DFARS) to... limitations on the award of new contracts for lead system integrator functions in the acquisition of major DoD...

  7. Amyloid beta precursor protein regulates male sexual behavior.

    PubMed

    Park, Jin Ho; Bonthius, Paul J; Tsai, Houng-Wei; Bekiranov, Stefan; Rissman, Emilie F

    2010-07-28

    Sexual behavior is variable between individuals, ranging from celibacy to sexual addictions. Within normal populations of individual men, ranging from young to middle aged, testosterone levels do not correlate with libido. To study the genetic mechanisms that contribute to individual differences in male sexual behavior, we used hybrid B6D2F1 male mice, which are a cross between two common inbred strains (C57BL/6J and DBA/2J). Unlike most laboratory rodent species in which male sexual behavior is highly dependent upon gonadal steroids, sexual behavior in a large proportion of these hybrid male mice after castration is independent of gonadal steroid hormones and their receptors; thus, we have the ability to discover novel genes involved in this behavior. Gene expression arrays, validation of gene candidates, and transgenic mice that overexpress one of the genes of interest were used to reveal genes involved in maintenance of male sexual behavior. Several genes related to neuroprotection and neurodegeneration were differentially expressed in the hypothalamus of males that continued to mate after castration. Male mice overexpressing the human form of one of these candidate genes, amyloid beta precursor protein (APP), displayed enhanced sexual behavior before castration and maintained sexual activity for a longer duration after castration compared with controls. Our results reveal a novel and unexpected relationship between APP and male sexual behavior. We speculate that declining APP during normal aging in males may contribute to the loss of sexual function.

  8. Alcohol Use Among Female Sex Workers and Male Clients: An Integrative Review of Global Literature

    PubMed Central

    Li, Qing; Li, Xiaoming; Stanton, Bonita

    2010-01-01

    Aims: To review the patterns, contexts and impacts of alcohol use associated with commercial sex reported in the global literature. Methods: We identified peer-reviewed English-language articles from 1980 to 2008 reporting alcohol consumption among female sex workers (FSWs) or male clients. We retrieved 70 articles describing 76 studies, in which 64 were quantitative (52 for FSWs, 12 for male clients) and 12 qualitative. Results: Studies increased over the past three decades, with geographic concentration of the research in Asia and North America. Alcohol use was prevalent among FSWs and clients. Integrating quantitative and qualitative studies, multilevel contexts of alcohol use in the sex work environment were identified, including workplace and occupation-related use, the use of alcohol to facilitate the transition into and practice of commercial sex among both FSWs and male clients, and self-medication among FSWs. Alcohol use was associated with adverse physical health, illicit drug use, mental health problems, and victimization of sexual violence, although its associations with HIV/sexually transmitted infections and unprotected sex among FSWs were inconclusive. Conclusions: Alcohol use in the context of commercial sex is prevalent, harmful among FSWs and male clients, but under-researched. Research in this area in more diverse settings and with standardized measures is required. The review underscores the importance of integrated intervention for alcohol use and related problems in multilevel contexts and with multiple components in order to effectively reduce alcohol use and its harmful effects among FSWs and their clients. PMID:20089544

  9. Identification of Proteins Involved in Carbohydrate Metabolism and Energy Metabolism Pathways and Their Regulation of Cytoplasmic Male Sterility in Wheat.

    PubMed

    Geng, Xingxia; Ye, Jiali; Yang, Xuetong; Li, Sha; Zhang, Lingli; Song, Xiyue

    2018-01-23

    Cytoplasmic male sterility (CMS) where no functional pollen is produced has important roles in wheat breeding. The anther is a unique organ for male gametogenesis and its abnormal development can cause male sterility. However, the mechanisms and regulatory networks related to plant male sterility are poorly understood. In this study, we conducted comparative analyses using isobaric tags for relative and absolute quantification (iTRAQ) of the pollen proteins in a CMS line and its wheat maintainer. Differentially abundant proteins (DAPs) were analyzed based on Gene Ontology classifications, metabolic pathways and transcriptional regulation networks using Blast2GO. We identified 5570 proteins based on 23,277 peptides, which matched with 73,688 spectra, including proteins in key pathways such as glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase and 6-phosphofructokinase 1 in the glycolysis pathway, isocitrate dehydrogenase and citrate synthase in the tricarboxylic acid cycle and nicotinamide adenine dinucleotide (NADH)-dehydrogenase and adenosine-triphosphate (ATP) synthases in the oxidative phosphorylation pathway. These proteins may comprise a network that regulates male sterility in wheat. Quantitative real time polymerase chain reaction (qRT-PCR) analysis, ATP assays and total sugar assays validated the iTRAQ results. These DAPs could be associated with abnormal pollen grain formation and male sterility. Our findings provide insights into the molecular mechanism related to male sterility in wheat.

  10. Cytological, molecular mechanisms and temperature stress regulating production of diploid male gametes in Dianthus caryophyllus L.

    PubMed

    Zhou, Xuhong; Mo, Xijun; Gui, Min; Wu, Xuewei; Jiang, Yalian; Ma, Lulin; Shi, Ziming; Luo, Ying; Tang, Wenru

    2015-12-01

    In plant evolution, because of its key role in sexual polyploidization or whole genome duplication events, diploid gamete formation is considered as an important component in diversification and speciation. Environmental stress often triggers unreduced gamete production. However, the molecular, cellular mechanisms and adverse temperature regulating diplogamete production in carnation remain poorly understood. Here, we investigate the cytological basis for 2n male gamete formation and describe the isolation and characterization of the first gene, DcPS1 (Dianthus Caryophyllus Parallel Spindle 1). In addition, we analyze influence of temperature stress on diploid gamete formation and transcript levels of DcPS1. Cytological evidence indicated that 2n male gamete formation is attributable to abnormal spindle orientation at male meiosis II. DcPS1 protein is conserved throughout the plant kingdom and carries domains suggestive of a regulatory function. DcPS1 expression analysis show DcPS1 gene probably have a role in 2n pollen formation. Unreduced pollen formation in various cultivation was sensitive to high or low temperature which was probably regulated by the level of DcPS1 transcripts. In a broader perspective, these findings can have potential applications in fundamental polyploidization research and plant breeding programs. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  11. Integrating physiological regulation with stem cell and tissue homeostasis

    PubMed Central

    Nakada, Daisuke; Levi, Boaz P.; Morrison, Sean J.

    2015-01-01

    Summary Stem cells are uniquely able to self-renew, to undergo multilineage differentiation, and to persist throughout life in a number of tissues. Stem cells are regulated by a combination of shared and tissue-specific mechanisms and are distinguished from restricted progenitors by differences in transcriptional and epigenetic regulation. Emerging evidence suggests that other aspects of cellular physiology, including mitosis, signal transduction, and metabolic regulation also differ between stem cells and their progeny. These differences may allow stem cells to be regulated independently of differentiated cells in response to circadian rhythms, changes in metabolism, diet, exercise, mating, aging, infection, and disease. This allows stem cells to sustain homeostasis or to remodel relevant tissues in response to physiological change. Stem cells are therefore not only regulated by short-range signals that maintain homeostasis within their tissue of origin, but also by long-range signals that integrate stem cell function with systemic physiology. PMID:21609826

  12. The Sex Determination Gene transformer Regulates Male-Female Differences in Drosophila Body Size

    PubMed Central

    Rideout, Elizabeth J.; Narsaiya, Marcus S.; Grewal, Savraj S.

    2015-01-01

    Almost all animals show sex differences in body size. For example, in Drosophila, females are larger than males. Although Drosophila is widely used as a model to study growth, the mechanisms underlying this male-female difference in size remain unclear. Here, we describe a novel role for the sex determination gene transformer (tra) in promoting female body growth. Normally, Tra is expressed only in females. We find that loss of Tra in female larvae decreases body size, while ectopic Tra expression in males increases body size. Although we find that Tra exerts autonomous effects on cell size, we also discovered that Tra expression in the fat body augments female body size in a non cell-autonomous manner. These effects of Tra do not require its only known targets doublesex and fruitless. Instead, Tra expression in the female fat body promotes growth by stimulating the secretion of insulin-like peptides from insulin producing cells in the brain. Our data suggest a model of sex-specific growth in which body size is regulated by a previously unrecognized branch of the sex determination pathway, and identify Tra as a novel link between sex and the conserved insulin signaling pathway. PMID:26710087

  13. The Sex Determination Gene transformer Regulates Male-Female Differences in Drosophila Body Size.

    PubMed

    Rideout, Elizabeth J; Narsaiya, Marcus S; Grewal, Savraj S

    2015-12-01

    Almost all animals show sex differences in body size. For example, in Drosophila, females are larger than males. Although Drosophila is widely used as a model to study growth, the mechanisms underlying this male-female difference in size remain unclear. Here, we describe a novel role for the sex determination gene transformer (tra) in promoting female body growth. Normally, Tra is expressed only in females. We find that loss of Tra in female larvae decreases body size, while ectopic Tra expression in males increases body size. Although we find that Tra exerts autonomous effects on cell size, we also discovered that Tra expression in the fat body augments female body size in a non cell-autonomous manner. These effects of Tra do not require its only known targets doublesex and fruitless. Instead, Tra expression in the female fat body promotes growth by stimulating the secretion of insulin-like peptides from insulin producing cells in the brain. Our data suggest a model of sex-specific growth in which body size is regulated by a previously unrecognized branch of the sex determination pathway, and identify Tra as a novel link between sex and the conserved insulin signaling pathway.

  14. Mutation of Drosophila dopamine receptor DopR leads to male-male courtship behavior.

    PubMed

    Chen, Bin; Liu, He; Ren, Jing; Guo, Aike

    2012-07-06

    In Drosophila, dopamine plays important roles in many biological processes as a neuromodulator. Previous studies showed that dopamine level could affect fly courtship behaviors. Disturbed dopamine level leads to abnormal courtship behavior in two different ways. Dopamine up-regulation induces male-male courtship behavior, while down-regulation of dopamine level results in increased sexual attractiveness of males towards other male flies. Until now, the identity of the dopamine receptor involved in this abnormal male-male courtship behavior remains unknown. Here we used genetic approaches to investigate the role of dopamine receptors in fly courtship behavior. We found that a dopamine D1-like receptor, DopR, was involved in fly courtship behavior. DopR mutant male flies display male-male courtship behavior. This behavior is mainly due to the male's increased propensity to court other males. Expression of functional DopR successfully rescued this mutant phenotype. Knock-down of D2-like receptor D2R and another D1-like receptor, DAMB, did not induce male-male courtship behavior, indicating the receptor-type specificity of this phenomenon. Our findings provide insight into a possible link between dopamine level disturbance and the induced male-male courtship behavior. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. 7 CFR 4290.1940 - Integration of this part with other regulations applicable to USDA's programs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Integration of this part with other regulations applicable to USDA's programs. 4290.1940 Section 4290.1940 Agriculture Regulations of the Department of... AGRICULTURE RURAL BUSINESS INVESTMENT COMPANY (âRBICâ) PROGRAM Miscellaneous § 4290.1940 Integration of this...

  16. Dopamine D1 receptors and phosphorylation of dopamine- and cyclic AMP-regulated phosphoprotein-32 in the medial preoptic area are involved in experience-induced enhancement of male sexual behavior in rats.

    PubMed

    McHenry, Jenna A; Bell, Genevieve A; Parrish, Bradley P; Hull, Elaine M

    2012-08-01

    The medial preoptic area (MPOA) is an integral site for male sexual behavior. Dopamine is released in the MPOA before and during copulation and facilitates male rat sexual behavior. Repeated sexual experience and noncopulatory exposures to an estrous female facilitate subsequent copulation. However, the neurobiological mechanisms that mediate such enhancement remain unclear. Here, we examined the role of dopamine D₁ receptors in the MPOA in experience-induced enhancement of male sexual behavior in rats. In experiment 1, microinjections of the D₁ antagonist SCH-23390 into the MPOA before each of seven daily 30-min noncopulatory exposures to a receptive female impaired copulation on a drug-free test on Day 8, compared to vehicle-treated female-exposed animals. Copulatory performance in drug-treated animals was similar to that of vehicle-treated males that had not been preexposed to females. This effect was site specific. There were no group differences in locomotor activity in an open field on the copulation test day. In experiment 2, a separate cohort of animals was used to examine phosphorylation of dopamine- and cAMP-regulated phosphoprotein (DARPP-32) in the MPOA of animals with acute and/or chronic sexual experience. DARPP-32 is a downstream marker of D₁ receptor signaling and substrate of cAMP-dependent protein kinase (PKA). Western immunoblot analysis revealed that p-DARPP-32 expression was greatest in the MPOA of males that received both acute and chronic sexual experience, compared to all other mated conditions and naïve controls. These data suggest that D₁ receptors in the MPOA contribute to experience-induced enhancement of male sexual behavior, perhaps through a PKA regulated mechanism.

  17. Chronic depletion of gonadal testosterone leads to blood-brain barrier dysfunction and inflammation in male mice.

    PubMed

    Atallah, Afnan; Mhaouty-Kodja, Sakina; Grange-Messent, Valérie

    2017-09-01

    A dysfunction in the blood-brain barrier (BBB) is associated with many neurological and metabolic disorders. Although sex steroid hormones have been shown to impact vascular tone, endothelial function, oxidative stress, and inflammatory responses, there are still no data on the role of testosterone in the regulation of BBB structure and function. In this context, we investigated the effects of gonadal testosterone depletion on the integrity of capillary BBB and the surrounding parenchyma in male mice. Our results show increased BBB permeability for different tracers and endogenous immunoglobulins in chronically testosterone-depleted male mice. These results were associated with disorganization of tight junction structures shown by electron tomography and a lower amount of tight junction proteins such as claudin-5 and ZO-1. BBB leakage was also accompanied by activation of astrocytes and microglia, and up-regulation of inflammatory molecules such as inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), interleukin 1 beta (IL-1β), and tumor necrosis factor (TNF). Supplementation of castrated male mice with testosterone restored BBB selective permeability, tight junction integrity, and almost completely abrogated the inflammatory features. The present demonstration that testosterone transiently impacts cerebrovascular physiology in adult male mice should help gain new insights into neurological and metabolic diseases linked to hypogonadism in men of all ages.

  18. Sex differences in cognitive regulation of psychosocial achievement stress: brain and behavior.

    PubMed

    Kogler, Lydia; Gur, Ruben C; Derntl, Birgit

    2015-03-01

    Although cognitive regulation of emotion has been extensively examined, there is a lack of studies assessing cognitive regulation in stressful achievement situations. This study used functional magnetic resonance imaging in 23 females and 20 males to investigate cognitive downregulation of negative, stressful sensations during a frequently used psychosocial stress task. Additionally, subjective responses, cognitive regulation strategies, salivary cortisol, and skin conductance response were assessed. Subjective response supported the experimental manipulation by showing higher anger and negative affect ratings after stress regulation than after the mere exposure to stress. On a neural level, right middle frontal gyrus (MFG) and right superior temporal gyrus (STG) were more strongly activated during regulation than nonregulation, whereas the hippocampus was less activated during regulation. Sex differences were evident: after regulation females expressed higher subjective stress ratings than males, and these ratings were associated with right hippocampal activation. In the nonregulation block, females showed greater activation of the left amygdala and the right STG during stress than males while males recruited the putamen more robustly in this condition. Thus, cognitive regulation of stressful achievement situations seems to induce additional stress, to recruit regions implicated in attention integration and working memory and to deactivate memory retrieval. Stress itself is associated with greater activation of limbic as well as attention areas in females than males. Additionally, activation of the memory system during cognitive regulation of stress is associated with greater perceived stress in females. Sex differences in cognitive regulation strategies merit further investigation that can guide sex sensitive interventions for stress-associated disorders. © 2014 Wiley Periodicals, Inc.

  19. Sex chromosome-specific regulation in the Drosophila male germline but little evidence for chromosomal dosage compensation or meiotic inactivation.

    PubMed

    Meiklejohn, Colin D; Landeen, Emily L; Cook, Jodi M; Kingan, Sarah B; Presgraves, Daven C

    2011-08-01

    The evolution of heteromorphic sex chromosomes (e.g., XY in males or ZW in females) has repeatedly elicited the evolution of two kinds of chromosome-specific regulation: dosage compensation--the equalization of X chromosome gene expression in males and females--and meiotic sex chromosome inactivation (MSCI)--the transcriptional silencing and heterochromatinization of the X during meiosis in the male (or Z in the female) germline. How the X chromosome is regulated in the Drosophila melanogaster male germline is unclear. Here we report three new findings concerning gene expression from the X in Drosophila testes. First, X chromosome-wide dosage compensation appears to be absent from most of the Drosophila male germline. Second, microarray analysis provides no evidence for X chromosome-specific inactivation during meiosis. Third, we confirm the previous discovery that the expression of transgene reporters driven by autosomal spermatogenesis-specific promoters is strongly reduced when inserted on the X chromosome versus the autosomes; but we show that this chromosomal difference in expression is established in premeiotic cells and persists in meiotic cells. The magnitude of the X-autosome difference in transgene expression cannot be explained by the absence of dosage compensation, suggesting that a previously unrecognized mechanism limits expression from the X during spermatogenesis in Drosophila. These findings help to resolve several previously conflicting reports and have implications for patterns of genome evolution and speciation in Drosophila.

  20. Exploring the Relationships among Self-Regulation, Acculturation, and Academic and Social Integration for Asian International Doctoral Students

    ERIC Educational Resources Information Center

    Wu, Yi-Chin

    2015-01-01

    This dissertation examined the relationship between Asian international doctoral students' self-regulation on academic and social integration and explored how acculturation tendencies function as a mediator between self-regulated learning and academic and social integration. Previous research has indicated that self-regulated learning has a great…

  1. Melatonin and male reproduction.

    PubMed

    Li, Chunjin; Zhou, Xu

    2015-06-15

    Melatonin is a neurohormone secreted by the pineal gland whose concentrations in the body are regulated by both the dark-light and seasonal cycles. The reproductive function of seasonal breeding animals is clearly influenced by the circadian variation in melatonin levels. Moreover, a growing body of evidence indicates that melatonin has important effects in the reproduction of some non-seasonal breeding animals. In males, melatonin affects reproductive regulation in three main ways. First, it regulates the secretion of two key neurohormones, GnRH and LH. Second, it regulates testosterone synthesis and testicular maturation. Third, as a potent free radical scavenger that is both lipophilic and hydrophilic, it prevents testicular damage caused by environmental toxins or inflammation. This review summarizes the existing data on the possible biological roles of melatonin in male reproduction. Overall, the literature data indicate that melatonin affects the secretion of both gonadotropins and testosterone while also improving sperm quality. This implies that it has important effects on the regulation of testicular development and male reproduction. Copyright © 2015. Published by Elsevier B.V.

  2. Blood Pressure Regulation: Every Adaptation is an Integration?

    PubMed Central

    Joyner, Michael J.; Limberg, Jacqueline K.

    2013-01-01

    This focused review serves to explore relevant issues in regard to blood pressure regulation and by doing so, provides the initial stimulus paper for the Thematic Review series “Blood Pressure Regulation” to be published in the European Journal of Applied Physiology over the coming months. In this introduction, we highlight how variable normal blood pressure can be and challenge the reader to take another look at some key concepts related to blood pressure regulation. We point out that there is frequently an underappreciated balance between peripheral vasodilation and systemic blood pressure regulation and ask the question: Are changes in blood pressure, in effect, reasonable and integrated adaptations to the physiological challenge at hand? We conclude with the idea that blood pressure regulatory systems are both flexible and redundant; ensuring a wide variety of activities associated with life can be accompanied by a perfusion pressure that can serve multiple masters. PMID:23558925

  3. piRNA-mediated transposon regulation and the germ-line mutation rate in Drosophila melanogaster males.

    PubMed

    Simmons, Michael J; Peterson, Mark P; Thorp, Michael W; Buschette, Jared T; DiPrima, Stephanie N; Harter, Christine L; Skolnick, Matthew J

    2015-03-01

    Transposons, especially retrotransposons, are abundant in the genome of Drosophila melanogaster. These mobile elements are regulated by small RNAs that interact with the Piwi family of proteins-the piwi-interacting or piRNAs. The Piwi proteins are encoded by the genes argonaute3 (ago3), aubergine (aub), and piwi. Heterochromatin Protein 1 (HP1), a chromatin-organizing protein encoded by the Suppressor of variegation 205 [Su(var)205] gene, also plays a role in this regulation. To assess the mutational impact of weakening the system for transposon regulation, we measured the frequency of recessive X-linked lethal mutations occurring in the germ lines of males from stocks that were heterozygous for mutant alleles of the ago3, aub, piwi, or Su(var)205 genes. These mutant alleles are expected to deplete the wild-type proteins encoded by these genes by as much as 50%. The mutant alleles of piwi and Su(var)205 significantly increased the X-linked lethal mutation frequency, whereas the mutant alleles of ago3 did not. An increased mutation frequency was also observed in males from one of two mutant aub stocks, but this increase may not have been due to the aub mutant. The increased mutation frequency caused by depleting Piwi or HP1suggests that chromatin-organizing proteins play important roles in minimizing the germ-line mutation rate, possibly by stabilizing the structure of the heterochromatin in which many transposons are situated. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. An integrated network of Arabidopsis growth regulators and its use for gene prioritization.

    PubMed

    Sabaghian, Ehsan; Drebert, Zuzanna; Inzé, Dirk; Saeys, Yvan

    2015-12-01

    Elucidating the molecular mechanisms that govern plant growth has been an important topic in plant research, and current advances in large-scale data generation call for computational tools that efficiently combine these different data sources to generate novel hypotheses. In this work, we present a novel, integrated network that combines multiple large-scale data sources to characterize growth regulatory genes in Arabidopsis, one of the main plant model organisms. The contributions of this work are twofold: first, we characterized a set of carefully selected growth regulators with respect to their connectivity patterns in the integrated network, and, subsequently, we explored to which extent these connectivity patterns can be used to suggest new growth regulators. Using a large-scale comparative study, we designed new supervised machine learning methods to prioritize growth regulators. Our results show that these methods significantly improve current state-of-the-art prioritization techniques, and are able to suggest meaningful new growth regulators. In addition, the integrated network is made available to the scientific community, providing a rich data source that will be useful for many biological processes, not necessarily restricted to plant growth.

  5. Development and psychometric properties of a self-regulation scale about leisure time physical activity in Iranian male adolescents.

    PubMed

    Abasi, Mohammad Hadi; Eslami, Ahmad Ali; Rakhshani, Fatemeh; Shiri, Mansoor

    2016-01-01

    Self-regulation is one of the current psychological concepts that have been known as a determinant of leisure time physical activity. Due to cultural and social diversity in different societies and age groups, application of specific questionnaires is essential to perform investigations about physical activities. The aim of this study is development and evaluation of psychometric properties of a self-regulation questionnaire about leisure time physical activity in Iranian male adolescents. This cross-sectional study was conducted in 2013, and data of 603 male students from 12 high schools in Isfahan were collected. A comprehensive literature review and similar questionnaire review were conducted and 25 items were selected or developed to measure self-regulation. Comprehensibility of items was evaluated in a pilot study and an expert panel evaluated face and content validity. Exploratory factors analysis (EFA) was used for evaluation of construct validity and extraction of sub-constructs of self-regulation. Leisure time physical activity was assessed using International Physical Activity Questionnaire (IPAQ). The mean age of the participants was 16.3 years (SD =1.0) and the range was 15-19 years. Cronbach's α coefficient of the questionnaire in the pilot and main study was 0.84 and 0.90, respectively. EFA resulted in four sub-constructs including "enlistment of social support", "goal setting", "self-construction", and "self-monitoring", which explained 63.6% of the variance of self-regulation. Results of this investigation provide some support to the validity and reliability of the 16-item questionnaire of self-regulation abut leisure time physical activity in the target group.

  6. Pheromonal regulation of male mouse ultrasonic courtship (Mus musculus).

    PubMed

    Nyby, J; Wysocki, C J; Whitney, G; Dizinno, G

    1977-05-01

    Biochemicals from several sites on the body of female house mice (Mus musculus) were found to elicit 70-kHz ultrasonic calls from male mice. Experiment 1 demonstrated that an anaesthetized female wrapped in an odour-impermeable plastic bag elicited ultrasounds from males when either the front or rear of their body was left exposed. In experiment 2 cotton swabs rubbed on the face and cheeks of females but not from males elicited ultrasonic calls from males. The results of experiment 3 suggested that female vaginal odours also elicit calls. Experiments 4 and 5 demonstrated that males will also emit ultrasounds in response to female but not male urine. The source and chemical nature of this 'ultrasound-releasing pheromone' remain to be discovered.

  7. Integrating emotion regulation and emotional intelligence traditions: a meta-analysis

    PubMed Central

    Peña-Sarrionandia, Ainize; Mikolajczak, Moïra; Gross, James J.

    2015-01-01

    Two relatively independent research traditions have developed that address emotion management. The first is the emotion regulation (ER) tradition, which focuses on the processes which permit individuals to influence which emotions they have, when they have them, and how they experience and express these emotions. The second is the emotional intelligence (EI) tradition, which focuses—among other things—on individual differences in ER. To integrate these two traditions, we employed the process model of ER (Gross, 1998b) to review the literature on EI. Two key findings emerged. First, high EI individuals shape their emotions from the earliest possible point in the emotion trajectory and have many strategies at their disposal. Second, high EI individuals regulate their emotions successfully when necessary but they do so flexibly, thereby leaving room for emotions to emerge. We argue that ER and EI traditions stand to benefit substantially from greater integration. PMID:25759676

  8. Progressive effects of silver nanoparticles on hormonal regulation of reproduction in male rats.

    PubMed

    Dziendzikowska, K; Krawczyńska, A; Oczkowski, M; Królikowski, T; Brzóska, K; Lankoff, A; Dziendzikowski, M; Stępkowski, T; Kruszewski, M; Gromadzka-Ostrowska, J

    2016-12-15

    The growing use of silver nanoparticles (AgNPs) in various applications, including consumer, agriculture and medicine products, has raised many concerns about the potential risks of nanoparticles (NPs) to human health and the environment. An increasing body of evidence suggests that AgNPs may have adverse effects of humans, thus the aim of this study was to investigate the effects of AgNPs on the male reproductive system. Silver particles (20nm AgNPs (groups Ag I and Ag II) and 200nm Ag sub-micron particles (SPs) (group Ag III)) were administered intravenously to male Wistar rats at a dose of 5 (groups Ag I and Ag III) or 10 (group Ag II) mg/kg of body weight. The biological material was sampled 24h, 7days and 28days after injection. The obtained results revealed that the AgNPs had altered the luteinising hormone concentration in the plasma and the sex hormone concentration in the plasma and testes. Plasma and intratesticular levels of testosterone and dihydrotestosterone were significantly decreased both 7 and 28days after treatment. No change in the prolactin and sex hormone-binding globulin concentration was observed. Exposure of the animals to AgNPs resulted in a considerable decrease in 5α-reductase type 1 and the aromatase protein level in the testis. Additionally, expression analysis of genes involved in steroidogenesis and the steroids metabolism revealed significant down-regulation of Star, Cyp11a1, Hsd3b1, Hsd17b3 and Srd5a1 mRNAs in AgNPs/AgSPs-exposed animals. The present study demonstrates the potential adverse effect on the hormonal regulation of the male reproductive function following AgNP/AgSP administration, in particular alterations of the sex steroid balance and expression of genes involved in steroidogenesis and the steroids metabolism. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. miR-544 Regulates Dairy Goat Male Germline Stem Cell Self-Renewal via Targeting PLZF.

    PubMed

    Song, Wencong; Mu, Hailong; Wu, Jiang; Liao, Mingzhi; Zhu, Haijing; Zheng, Liming; He, Xin; Niu, Bowen; Zhai, Yuanxin; Bai, Chunling; Lei, Anmin; Li, Guangpeng; Hua, Jinlian

    2015-10-01

    The balance between the self-renewal and differentiation of male germline stem cells (mGSCs) is critical for the initiation and maintenance of mammalian spermatogenesis. The promyelocytic leukemia zinc finger (PLZF), a zinc finger protein, is a critical factor for maintaining the self-renewal of mGSCs, so, evaluation of the PLZF pathway in mGSCs may provide a deeper insight into mammalian spermatogenesis. miRNA was also an important regulating factor for the self-renewal and differentiation of mGSCs; however, there is currently no data indicating that which miRNA regulate the self-renewal and differentiation of mGSCs via PLZF. Here, we predicted the prospective miRNA targeting to PLZF using the online Bioinformatics database-Targetscan, and performed an analysis of the dual-luciferase recombinant vector, psiCHCEKTM-2-PLZF-3'UTR. miR-544 mimics (miR-544m), miR-544 inhibitors (miR-544i), Control (NC, scrambled oligonucleotides transfection), pPLZF-IRES2-EGFP or PLZF siRNA were transfected into mGSCs; the cells proliferation was evaluated by BRDU incorporation assay and flow cytometry, and the mGSC marker, GFRa1, PLZF, KIT, DAZL, and VASA expression were analyzed by RT-qPCR, immunofluorescence and Western blot. The results showed that miR-544 regulates dairy goat male germline stem cell self-renewal via targeting PLZF. Our study identifies a new regulatory pathway for PLZF and expands upon the PLZF regulatory network in mGSCs. © 2015 Wiley Periodicals, Inc.

  10. De novo sequencing and comparative transcriptome analysis of the male and hermaphroditic flowers provide insights into the regulation of flower formation in andromonoecious taihangia rupestris.

    PubMed

    Li, Weiguo; Zhang, Lihui; Ding, Zhan; Wang, Guodong; Zhang, Yandi; Gong, Hongmei; Chang, Tianjun; Zhang, Yanwen

    2017-02-28

    Taihangia rupestris, an andromonoecious plant species, bears both male and hermaphroditic flowers within the same individual. However, the establishment and development of male and hermaphroditic flowers in andromonoecious Taihangia remain poorly understood, due to the limited genetic and sequence information. To investigate the potential molecular mechanism in the regulation of Taihangia flower formation, we used de novo RNA sequencing to compare the transcriptome profiles of male and hermaphroditic flowers at early and late developmental stages. Four cDNA libraries, including male floral bud, hermaphroditic floral bud, male flower, and hermaphroditic flower, were constructed and sequenced by using the Illumina RNA-Seq method. Totally, 84,596,426 qualified Illumina reads were obtained and then assembled into 59,064 unigenes, of which 24,753 unigenes were annotated in the NCBI non-redundant protein database. In addition, 12,214, 7,153, and 8,115 unigenes were assigned into 53 Gene Ontology (GO) functional groups, 25 Clusters of Orthologous Group (COG) categories, and 126 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, respectively. By pairwise comparison of unigene abundance between the samples, we identified 1,668 differential expressed genes (DEGs), including 176 transcription factors (TFs) between the male and hermaphroditic flowers. At the early developmental stage, we found 263 up-regulated genes and 436 down-regulated genes expressed in hermaphroditic floral buds, while 844 up-regulated genes and 314 down-regulated genes were detected in hermaphroditic flowers at the late developmental stage. GO and KEGG enrichment analyses showed that a large number of DEGs were associated with a wide range of functions, including cell cycle, epigenetic processes, flower development, and biosynthesis of unsaturated fatty acid pathway. Finally, real-time quantitative PCR was conducted to validate the DEGs identified in the present study. In this study, transcriptome

  11. 77 FR 67804 - Federal Acquisition Regulation; Submission for OMB Review; Integrity of Unit Prices

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-14

    ...; Submission for OMB Review; Integrity of Unit Prices AGENCY: Department of Defense (DOD), General Services... requirement concerning Integrity of Unit Prices. A notice was published in the Federal Register at 77 FR 52739... Information Collection 9000- 0080, Integrity of Unit Prices by any of the following methods: Regulations.gov...

  12. Developing an Integrative Play Therapy Group Model for Middle School Male Students to Address Bullying Behaviors

    ERIC Educational Resources Information Center

    Jordan, Jakarla

    2016-01-01

    This research examines the systematic process of developing an integrative play therapy group model for middle school male students, ages 11-15 who participate in bullying behaviors. Play therapy approaches and evidence-based practices are documented as effective measures for addressing bullying behaviors with children and adolescents. This group…

  13. Intergenerational Transmission of Self-Regulation: A Multidisciplinary Review and Integrative Conceptual Framework

    PubMed Central

    Bridgett, David J.; Burt, Nicole M.; Edwards, Erin S.; Deater-Deckard, Kirby

    2014-01-01

    This review examines mechanisms contributing to the intergenerational transmission of self-regulation. To provide an integrated account of how self-regulation is transmitted across generations, we draw from over 75 years of accumulated evidence, spanning case studies to experimental approaches, in literatures covering developmental, social, and clinical psychology, and criminology, physiology, genetics, and human and animal neuroscience (among others). First, we present a taxonomy of what self-regulation is and then examine how it develops – overviews that guide the main foci of the review. Next, studies supporting an association between parent and child self-regulation are reviewed. Subsequently, literature that considers potential social mechanisms of transmission, specifically parenting behavior, inter-parental (i.e., marital) relationship behaviors, and broader rearing influences (e.g., household chaos) are considered. Finally, literature providing evidence that prenatal programming may be the starting point of the intergenerational transmission of self-regulation is covered, along with key findings from the behavioral and molecular genetics literatures. To integrate these literatures, we introduce the Self-Regulation Intergenerational Transmission Model, a framework that brings together prenatal, social, and neurobiological mechanisms (spanning endocrine, neural, and genetic levels, including gene-environment interplay and epigenetic processes) to explain the intergenerational transmission of self-regulation. This model also incorporates potential transactional processes between generations (e.g., children’s self-regulation and parent-child interaction dynamics that may affect parents’ self-regulation) that further influence intergenerational processes. In pointing the way forward, we note key future directions and ways to address limitations in existing work throughout the review and in closing. We also conclude by noting several implications for

  14. Development and psychometric properties of a self-regulation scale about leisure time physical activity in Iranian male adolescents

    PubMed Central

    Abasi, Mohammad Hadi; Eslami, Ahmad Ali; Rakhshani, Fatemeh; Shiri, Mansoor

    2016-01-01

    Background: Self-regulation is one of the current psychological concepts that have been known as a determinant of leisure time physical activity. Due to cultural and social diversity in different societies and age groups, application of specific questionnaires is essential to perform investigations about physical activities. The aim of this study is development and evaluation of psychometric properties of a self-regulation questionnaire about leisure time physical activity in Iranian male adolescents. Materials and Methods: This cross-sectional study was conducted in 2013, and data of 603 male students from 12 high schools in Isfahan were collected. A comprehensive literature review and similar questionnaire review were conducted and 25 items were selected or developed to measure self-regulation. Comprehensibility of items was evaluated in a pilot study and an expert panel evaluated face and content validity. Exploratory factors analysis (EFA) was used for evaluation of construct validity and extraction of sub-constructs of self-regulation. Leisure time physical activity was assessed using International Physical Activity Questionnaire (IPAQ). Results: The mean age of the participants was 16.3 years (SD =1.0) and the range was 15-19 years. Cronbach's α coefficient of the questionnaire in the pilot and main study was 0.84 and 0.90, respectively. EFA resulted in four sub-constructs including “enlistment of social support”, “goal setting”, “self-construction”, and “self-monitoring”, which explained 63.6% of the variance of self-regulation. Conclusions: Results of this investigation provide some support to the validity and reliability of the 16-item questionnaire of self-regulation abut leisure time physical activity in the target group. PMID:27095993

  15. Genomic integrity of the Y chromosome sequence-tagged-sites in infertile and Down syndrome Jordanian males.

    PubMed

    Yasin, S R; Tahtamouni, L H; Najeeb, N S; Issa, N M; Al-Mazaydeh, Z A; Alfaouri, A A

    2014-09-01

    The long arm of the Y chromosome contains nonoverlapping regions termed azoospermia factor (AZF) with great influence on male fertility. Microdeletions at these regions minimise the males' ability to father offsprings. In this preliminary study, we attempted to screen the presence or absence of twenty Y chromosome's sequence-tagged sites (STS) associated with fertility in infertile and Down syndrome (DS) males. Genomic DNA from 35 fertile, 74 infertile and 22 karyotyped DS males was extracted and amplified in multiplex polymerase chain reaction (PCR) containing 20 primer pairs that amplify Y-specific STS that cover functional regions associated with AZF and spermatogenesis-related genes. Our results indicated the integrity of the Y chromosome at the 20 fertility markers for both the fertile and Down syndrome males. However, the results of the infertile males showed the presence of microdeletions at these Y-specific STS. Three samples showed Y chromosome microdeletion when blood and seminal fluid genomic DNA were assayed, while two samples showed microdeletion only when seminal fluid genomic DNA was assayed. The current study demonstrated that the molecular genetic aspect of infertility should be given proper attention when dealing with infertility cases. Furthermore, our results indicate the importance of genetic counselling in managing infertility cases. © 2013 Blackwell Verlag GmbH.

  16. Environmental toxicants and male reproductive function

    PubMed Central

    Wong, Elissa W.P; Lie, Pearl P.Y; Li, Michelle W.M; Su, Linlin; Siu, Erica R; Yan, Helen H.N; Mannu, Jayakanthan; Mathur, Premendu P; Bonanomi, Michele; Silvestrini, Bruno; Mruk, Dolores D

    2011-01-01

    Environmental toxicants, such as cadmium and bisphenol A (BPA) are endocrine disruptors. In utero, perinatal or neonatal exposure of BPA to rats affect the male reproductive function, such as the blood-testis barrier (BTB) integrity. This effect of BPA on BTB integrity in immature rats is likely mediated via a loss of gap junction function at the BTB, failing to coordinate tight junction and anchoring junction function at the site to maintain the immunological barrier integrity. This in turn activates the extracellular signal-regulated kinases 1/2 (Erk1/2) downstream and an increase in protein endocytosis, destabilizing the BTB. The cadmium-induced disruption of testicular dysfunction is mediated initially via its effects on the occludin/ZO-1/focal adhesion kinase (FAK) complex at the BTB, causing redistribution of proteins at the Sertoli-Sertoli cell interface, leading to the BTB disruption. The damaging effects of these toxicants to testicular function are mediated by mitogen-activated protein kinases (MAPK) downstream, which in turn perturbs the actin bundling and accelerates the actin-branching activity, causing disruption of the Sertoli cell tight junction (TJ)-barrier function at the BTB and perturbing spermatid adhesion at the apical ectoplasmic specialization (apical ES, a testis-specific anchoring junction type) that leads to premature release of germ cells from the testis. However, the use of specific inhibitors against MAPK was shown to block or delay the cadmium-induced testicular injury, such as BTB disruption and germ cell loss. These findings suggest that there may be a common downstream p38 and/or Erk1/2 MAPK-based signaling pathway involving polarity proteins and actin regulators that is shared between different toxicants that induce male reproductive dysfunction. As such, the use of inhibitors and/or antagonists against specific MAPKs can possibly be used to “manage” the illnesses caused by these toxicants and/or “protect” industrial

  17. A mitogen-activated protein kinase regulates male gametogenesis and transmission of the malaria parasite Plasmodium berghei

    PubMed Central

    Rangarajan, Radha; Bei, Amy K; Jethwaney, Deepa; Maldonado, Priscilla; Dorin, Dominique; Sultan, Ali A; Doerig, Christian

    2005-01-01

    Differentiation of malaria parasites into sexual forms (gametocytes) in the vertebrate host and their subsequent development into gametes in the mosquito vector are crucial steps in the completion of the parasite's life cycle and transmission of the disease. The molecular mechanisms that regulate the sexual cycle are poorly understood. Although several signal transduction pathways have been implicated, a clear understanding of the pathways involved has yet to emerge. Here, we show that a Plasmodium berghei homologue of Plasmodium falciparum mitogen-activated kinase-2 (Pfmap-2), a gametocyte-specific mitogen-activated protein kinase (MAPK), is required for male gamete formation. Parasites lacking Pbmap-2 are competent for gametocytogenesis, but exflagellation of male gametocytes, the process that leads to male gamete formation, is almost entirely abolished in mutant parasites. Consistent with this result, transmission of mutant parasites to mosquitoes is grossly impaired. This finding identifies a crucial role for a MAPK pathway in malaria transmission. PMID:15864297

  18. Integrative Approaches to Enhance Understanding of Plant Metabolic Pathway Structure and Regulation1

    PubMed Central

    Tohge, Takayuki; Scossa, Federico; Fernie, Alisdair R.

    2015-01-01

    Huge insight into molecular mechanisms and biological network coordination have been achieved following the application of various profiling technologies. Our knowledge of how the different molecular entities of the cell interact with one another suggests that, nevertheless, integration of data from different techniques could drive a more comprehensive understanding of the data emanating from different techniques. Here, we provide an overview of how such data integration is being used to aid the understanding of metabolic pathway structure and regulation. We choose to focus on the pairwise integration of large-scale metabolite data with that of the transcriptomic, proteomics, whole-genome sequence, growth- and yield-associated phenotypes, and archival functional genomic data sets. In doing so, we attempt to provide an update on approaches that integrate data obtained at different levels to reach a better understanding of either single gene function or metabolic pathway structure and regulation within the context of a broader biological process. PMID:26371234

  19. Molecular Regulation of Sexual Preference Revealed by Genetic Studies of 5-HT in the Brain of Male Mice

    PubMed Central

    Liu, Yan; Jiang, Yun’ai; Si, Yunxia; Kim, Ji-Young; Chen, Zhou-Feng; Rao, Yi

    2014-01-01

    To whom should a male directs his mating? While it is a critical social interaction, little is known about molecular and cellular mechanisms controlling mammalian sexual preference. Here we report that the neurotransmitter 5-HT is required for male sexual preference. Male mice lacking central serotonergic neurons lost sexual preference but were not generally defective in olfaction. A role for 5-hydroxytryptamine (5-HT) was demonstrated by the phenotype of mice unable to synthesize 5-HT in the brain when lacking tryptophan hydroxylase 2 (Tph2). 5-hydroxytryptophan (5-HTP) injection rescued the phenotype of adult Tph2 knockout mice within 35 minutes. These results indicate that 5-HT and serotonergic neurons in the adult brain regulate mammalian sexual preference. PMID:21441904

  20. GABA regulates synaptic integration of newly generated neurons in the adult brain

    NASA Astrophysics Data System (ADS)

    Ge, Shaoyu; Goh, Eyleen L. K.; Sailor, Kurt A.; Kitabatake, Yasuji; Ming, Guo-Li; Song, Hongjun

    2006-02-01

    Adult neurogenesis, the birth and integration of new neurons from adult neural stem cells, is a striking form of structural plasticity and highlights the regenerative capacity of the adult mammalian brain. Accumulating evidence suggests that neuronal activity regulates adult neurogenesis and that new neurons contribute to specific brain functions. The mechanism that regulates the integration of newly generated neurons into the pre-existing functional circuitry in the adult brain is unknown. Here we show that newborn granule cells in the dentate gyrus of the adult hippocampus are tonically activated by ambient GABA (γ-aminobutyric acid) before being sequentially innervated by GABA- and glutamate-mediated synaptic inputs. GABA, the major inhibitory neurotransmitter in the adult brain, initially exerts an excitatory action on newborn neurons owing to their high cytoplasmic chloride ion content. Conversion of GABA-induced depolarization (excitation) into hyperpolarization (inhibition) in newborn neurons leads to marked defects in their synapse formation and dendritic development in vivo. Our study identifies an essential role for GABA in the synaptic integration of newly generated neurons in the adult brain, and suggests an unexpected mechanism for activity-dependent regulation of adult neurogenesis, in which newborn neurons may sense neuronal network activity through tonic and phasic GABA activation.

  1. BRDT is an essential epigenetic regulator for proper chromatin organization, silencing of sex chromosomes and crossover formation in male meiosis

    PubMed Central

    Oh, Min Young; Garyn, Corey

    2018-01-01

    The double bromodomain and extra-terminal domain (BET) proteins are critical epigenetic readers that bind to acetylated histones in chromatin and regulate transcriptional activity and modulate changes in chromatin structure and organization. The testis-specific BET member, BRDT, is essential for the normal progression of spermatogenesis as mutations in the Brdt gene result in complete male sterility. Although BRDT is expressed in both spermatocytes and spermatids, loss of the first bromodomain of BRDT leads to severe defects in spermiogenesis without overtly compromising meiosis. In contrast, complete loss of BRDT blocks the progression of spermatocytes into the first meiotic division, resulting in a complete absence of post-meiotic cells. Although BRDT has been implicated in chromatin remodeling and mRNA processing during spermiogenesis, little is known about its role in meiotic processes. Here we report that BRDT is an essential regulator of chromatin organization and reprograming during prophase I of meiosis. Loss of BRDT function disrupts the epigenetic state of the meiotic sex chromosome inactivation in spermatocytes, affecting the synapsis and silencing of the X and Y chromosomes. We also found that BRDT controls the global chromatin organization and histone modifications of the chromatin attached to the synaptonemal complex. Furthermore, the homeostasis of crossover formation and localization during pachynema was altered, underlining a possible epigenetic mechanism by which crossovers are regulated and differentially established in mammalian male genomes. Our observations reveal novel findings about the function of BRDT in meiosis and provide insight into how epigenetic regulators modulate the progression of male mammalian meiosis and the formation of haploid gametes. PMID:29513658

  2. A biomolecular proportional integral controller based on feedback regulations of protein level and activity.

    PubMed

    Mairet, Francis

    2018-02-01

    Homeostasis is the capacity of living organisms to keep internal conditions regulated at a constant level, despite environmental fluctuations. Integral feedback control is known to play a key role in this behaviour. Here, I show that a feedback system involving transcriptional and post-translational regulations of the same executor protein acts as a proportional integral (PI) controller, leading to enhanced transient performances in comparison with a classical integral loop. Such a biomolecular controller-which I call a level and activity-PI controller (LA-PI)-is involved in the regulation of ammonium uptake by Escherichia coli through the transporter AmtB. The P II molecules, which reflect the nitrogen status of the cell, inhibit both the production of AmtB and its activity (via the NtrB-NtrC system and the formation of a complex with GlnK, respectively). Other examples of LA-PI controller include copper and zinc transporters, and the redox regulation in photosynthesis. This scheme has thus emerged through evolution in many biological systems, surely because of the benefits it offers in terms of performances (rapid and perfect adaptation) and economy (protein production according to needs).

  3. A biomolecular proportional integral controller based on feedback regulations of protein level and activity

    PubMed Central

    2018-01-01

    Homeostasis is the capacity of living organisms to keep internal conditions regulated at a constant level, despite environmental fluctuations. Integral feedback control is known to play a key role in this behaviour. Here, I show that a feedback system involving transcriptional and post-translational regulations of the same executor protein acts as a proportional integral (PI) controller, leading to enhanced transient performances in comparison with a classical integral loop. Such a biomolecular controller—which I call a level and activity-PI controller (LA-PI)—is involved in the regulation of ammonium uptake by Escherichia coli through the transporter AmtB. The PII molecules, which reflect the nitrogen status of the cell, inhibit both the production of AmtB and its activity (via the NtrB-NtrC system and the formation of a complex with GlnK, respectively). Other examples of LA-PI controller include copper and zinc transporters, and the redox regulation in photosynthesis. This scheme has thus emerged through evolution in many biological systems, surely because of the benefits it offers in terms of performances (rapid and perfect adaptation) and economy (protein production according to needs). PMID:29515895

  4. Regulation of male germ cell cycle arrest and differentiation by DND1 is modulated by genetic background

    PubMed Central

    Cook, Matthew S.; Munger, Steven C.; Nadeau, Joseph H.; Capel, Blanche

    2011-01-01

    Human germ cell tumors show a strong sensitivity to genetic background similar to Dnd1Ter/Ter mutant mice, where testicular teratomas arise only on the 129/SvJ genetic background. The introduction of the Bax mutation onto mixed background Dnd1Ter/Ter mutants, where teratomas do not typically develop, resulted in a high incidence of teratomas. However, when Dnd1Ter/Ter; Bax–/– double mutants were backcrossed to C57BL/6J, no tumors arose. Dnd1Ter/Ter germ cells show a strong downregulation of male differentiation genes including Nanos2. In susceptible strains, where teratomas initiate around E15.5-E17.5, many mutant germ cells fail to enter mitotic arrest in G0 and do not downregulate the pluripotency markers NANOG, SOX2 and OCT4. We show that DND1 directly binds a group of transcripts that encode negative regulators of the cell cycle, including p27Kip1 and p21Cip1. P27Kip1 and P21Cip1 protein are both significantly decreased in Dnd1Ter/Ter germ cells on all strain backgrounds tested, strongly suggesting that DND1 regulates mitotic arrest in male germ cells through translational regulation of cell cycle genes. Nonetheless, in C57BL/6J mutants, germ cells arrest prior to M-phase of the cell cycle and downregulate NANOG, SOX2 and OCT4. Consistent with their ability to rescue cell cycle arrest, C57BL/6J germ cells overexpress negative regulators of the cell cycle relative to 129/SvJ. This work suggests that reprogramming of pluripotency in germ cells and prevention of tumor formation requires cell cycle arrest, and that differences in the balance of cell cycle regulators between 129/SvJ and C57BL/6 might underlie differences in tumor susceptibility. PMID:21115610

  5. Regulation of the X Chromosome in the Germline and Soma of Drosophila melanogaster Males.

    PubMed

    Argyridou, Eliza; Parsch, John

    2018-05-04

    During the evolution of heteromorphic sex chromosomes, the sex-specific Y chromosome degenerates, while the X chromosome evolves new mechanisms of regulation. Using bioinformatic and experimental approaches, we investigate the expression of the X chromosome in Drosophila melanogaster . We observe nearly complete X chromosome dosage compensation in male somatic tissues, but not in testis. The X chromosome contains disproportionately fewer genes with high expression in testis than the autosomes, even after accounting for the lack of dosage compensation, which suggests that another mechanism suppresses their expression in the male germline. This is consistent with studies of reporter genes and transposed genes, which find that the same gene has higher expression when autosomal than when X-linked. Using a new reporter gene that is expressed in both testis and somatic tissues, we find that the suppression of X-linked gene expression is limited to genes with high expression in testis and that the extent of the suppression is positively correlated with expression level.

  6. Integrative rodent models for assessing male reproductive toxicity of environmental endocrine active substances

    PubMed Central

    Auger, Jacques; Eustache, Florence; Rouiller-Fabre, Virginie; Canivenc-Lavier, Marie Chantal; Livera, Gabriel

    2014-01-01

    In the present review, we first summarize the main benefits, limitations and pitfalls of conventional in vivo approaches to assessing male reproductive structures and functions in rodents in cases of endocrine active substance (EAS) exposure from the postulate that they may provide data that can be extrapolated to humans. Then, we briefly present some integrated approaches in rodents we have recently developed at the organism level. We particularly focus on the possible effects and modes of action (MOA) of these substances at low doses and in mixtures, real-life conditions and at the organ level, deciphering the precise effects and MOA on the fetal testis. It can be considered that the in vivo experimental EAS exposure of rodents remains the first choice for studies and is a necessary tool (together with the epidemiological approach) for understanding the reproductive effects and MOA of EASs, provided the pitfalls and limitations of the rodent models are known and considered. We also provide some evidence that classical rodent models may be refined for studying the multiple consequences of EAS exposure, not only on the reproductive axis but also on various hormonally regulated organs and tissues, among which several are implicated in the complex process of mammalian reproduction. Such models constitute an interesting way of approaching human exposure conditions. Finally, we show that organotypic culture models are powerful complementary tools, especially when focusing on the MOA. All these approaches have contributed in a combinatorial manner to a better understanding of the impact of EAS exposure on human reproduction. PMID:24369134

  7. 77 FR 54843 - Integrated Mortgage Disclosures Under the Real Estate Settlement Procedure Act (Regulation X) and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-06

    ... Integrated Mortgage Disclosures Under the Real Estate Settlement Procedure Act (Regulation X) and the Truth... Consumer Protection Act (Dodd-Frank Act). The proposed rule, which would amend Regulation X (RESPA) and... rule would amend Regulation X (RESPA) and Regulation Z (TILA). The notice was published in the Federal...

  8. Abnormal inter- and intra-hemispheric integration in male paranoid schizophrenia: a graph-theoretical analysis.

    PubMed

    Chen, Jianhuai; Yao, Zhijian; Qin, Jiaolong; Yan, Rui; Hua, Lingling; Lu, Qing

    2015-06-25

    The human brain is a complex network of regions that are structurally interconnected by white matter (WM) tracts. Schizophrenia (SZ) can be conceptualized as a disconnection syndrome characterized by widespread disconnections in WM pathways. To assess whether or not anatomical disconnections are associated with disruption of the topological properties of inter- and intra-hemispheric networks in SZ. We acquired the diffusion tensor imaging data from 24 male patients with paranoid SZ during an acute phase of their illness and from 24 healthy age-matched male controls. The brain FA-weighted (fractional anisotropy-weighted) structural networks were constructed and the inter- and intra-hemispheric integration was assessed by estimating the average characteristic path lengths (CPLs) between and within the left and right hemisphere networks. The mean CPLs for all 18 inter-and intra-hemispheric CPLs assessed were longer in the SZ patient group than in the control group, but only some of these differences were significantly different: the CPLs for the overall inter-hemispheric and the left and right intra-hemispheric networks; the CPLs for the interhemisphere subnetworks of the frontal lobes, temporal lobes, and subcortical structures; and the CPL for the intra- frontal subnetwork in the right hemisphere. Among the 24 patients, the CPL of the inter-frontal subnetwork was positively associated with negative symptom severity, but this was the only significant result among 72 assessed correlations, so it may be a statistical artifact. Our findings suggest that the integrity of intra- and inter-hemispheric WM tracts is disrupted in males with paranoid SZ, supporting the brain network disconnection model (i.e., the (')connectivity hypothesis(')) of schizophrenia. Larger studies with less narrowly defined samples of individuals with schizophrenia are needed to confirm these results.

  9. Comprehensive Anti-error Study on Power Grid Dispatching Based on Regional Regulation and Integration

    NASA Astrophysics Data System (ADS)

    Zhang, Yunju; Chen, Zhongyi; Guo, Ming; Lin, Shunsheng; Yan, Yinyang

    2018-01-01

    With the large capacity of the power system, the development trend of the large unit and the high voltage, the scheduling operation is becoming more frequent and complicated, and the probability of operation error increases. This paper aims at the problem of the lack of anti-error function, single scheduling function and low working efficiency for technical support system in regional regulation and integration, the integrated construction of the error prevention of the integrated architecture of the system of dispatching anti - error of dispatching anti - error of power network based on cloud computing has been proposed. Integrated system of error prevention of Energy Management System, EMS, and Operation Management System, OMS have been constructed either. The system architecture has good scalability and adaptability, which can improve the computational efficiency, reduce the cost of system operation and maintenance, enhance the ability of regional regulation and anti-error checking with broad development prospects.

  10. The C. elegans tailless/Tlx homolog nhr-67 regulates a stage-specific program of linker cell migration in male gonadogenesis.

    PubMed

    Kato, Mihoko; Sternberg, Paul W

    2009-12-01

    Cell migration is a common event during organogenesis, yet little is known about how migration is temporally coordinated with organ development. We are investigating stage-specific programs of cell migration using the linker cell (LC), a migratory cell crucial for male gonadogenesis of C. elegans. During the L3 and L4 larval stages of wild-type males, the LC undergoes changes in its position along the migratory route, in transcriptional regulation of the unc-5 netrin receptor and zmp-1 zinc matrix metalloprotease, and in cell morphology. We have identified the tailless homolog nhr-67 as a cell-autonomous, stage-specific regulator of timing in LC migration programs. In nhr-67-deficient animals, each of the L3 and L4 stage changes is either severely delayed or never occurs, yet LC development before the early L3 stage or after the mid-L4 stage occurs with normal timing. We propose that there is a basal migration program utilized throughout LC migration that is modified by stage-specific regulators such as nhr-67.

  11. Genome-wide identification of physically clustered genes suggests chromatin-level co-regulation in male reproductive development in Arabidopsis thaliana

    PubMed Central

    Reimegård, Johan; Kundu, Snehangshu; Pendle, Ali; Irish, Vivian F.; Shaw, Peter

    2017-01-01

    Abstract Co-expression of physically linked genes occurs surprisingly frequently in eukaryotes. Such chromosomal clustering may confer a selective advantage as it enables coordinated gene regulation at the chromatin level. We studied the chromosomal organization of genes involved in male reproductive development in Arabidopsis thaliana. We developed an in-silico tool to identify physical clusters of co-regulated genes from gene expression data. We identified 17 clusters (96 genes) involved in stamen development and acting downstream of the transcriptional activator MS1 (MALE STERILITY 1), which contains a PHD domain associated with chromatin re-organization. The clusters exhibited little gene homology or promoter element similarity, and largely overlapped with reported repressive histone marks. Experiments on a subset of the clusters suggested a link between expression activation and chromatin conformation: qRT-PCR and mRNA in situ hybridization showed that the clustered genes were up-regulated within 48 h after MS1 induction; out of 14 chromatin-remodeling mutants studied, expression of clustered genes was consistently down-regulated only in hta9/hta11, previously associated with metabolic cluster activation; DNA fluorescence in situ hybridization confirmed that transcriptional activation of the clustered genes was correlated with open chromatin conformation. Stamen development thus appears to involve transcriptional activation of physically clustered genes through chromatin de-condensation. PMID:28175342

  12. Bioinformatics for spermatogenesis: annotation of male reproduction based on proteomics

    PubMed Central

    Zhou, Tao; Zhou, Zuo-Min; Guo, Xue-Jiang

    2013-01-01

    Proteomics strategies have been widely used in the field of male reproduction, both in basic and clinical research. Bioinformatics methods are indispensable in proteomics-based studies and are used for data presentation, database construction and functional annotation. In the present review, we focus on the functional annotation of gene lists obtained through qualitative or quantitative methods, summarizing the common and male reproduction specialized proteomics databases. We introduce several integrated tools used to find the hidden biological significance from the data obtained. We further describe in detail the information on male reproduction derived from Gene Ontology analyses, pathway analyses and biomedical analyses. We provide an overview of bioinformatics annotations in spermatogenesis, from gene function to biological function and from biological function to clinical application. On the basis of recently published proteomics studies and associated data, we show that bioinformatics methods help us to discover drug targets for sperm motility and to scan for cancer-testis genes. In addition, we summarize the online resources relevant to male reproduction research for the exploration of the regulation of spermatogenesis. PMID:23852026

  13. Estrogens in Male Physiology.

    PubMed

    Cooke, Paul S; Nanjappa, Manjunatha K; Ko, CheMyong; Prins, Gail S; Hess, Rex A

    2017-07-01

    Estrogens have historically been associated with female reproduction, but work over the last two decades established that estrogens and their main nuclear receptors (ESR1 and ESR2) and G protein-coupled estrogen receptor (GPER) also regulate male reproductive and nonreproductive organs. 17β-Estradiol (E2) is measureable in blood of men and males of other species, but in rete testis fluids, E2 reaches concentrations normally found only in females and in some species nanomolar concentrations of estrone sulfate are found in semen. Aromatase, which converts androgens to estrogens, is expressed in Leydig cells, seminiferous epithelium, and other male organs. Early studies showed E2 binding in numerous male tissues, and ESR1 and ESR2 each show unique distributions and actions in males. Exogenous estrogen treatment produced male reproductive pathologies in laboratory animals and men, especially during development, and studies with transgenic mice with compromised estrogen signaling demonstrated an E2 role in normal male physiology. Efferent ductules and epididymal functions are dependent on estrogen signaling through ESR1, whose loss impaired ion transport and water reabsorption, resulting in abnormal sperm. Loss of ESR1 or aromatase also produces effects on nonreproductive targets such as brain, adipose, skeletal muscle, bone, cardiovascular, and immune tissues. Expression of GPER is extensive in male tracts, suggesting a possible role for E2 signaling through this receptor in male reproduction. Recent evidence also indicates that membrane ESR1 has critical roles in male reproduction. Thus estrogens are important physiological regulators in males, and future studies may reveal additional roles for estrogen signaling in various target tissues. Copyright © 2017 the American Physiological Society.

  14. Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration.

    PubMed

    Matysiak, Julien; Lesbats, Paul; Mauro, Eric; Lapaillerie, Delphine; Dupuy, Jean-William; Lopez, Angelica P; Benleulmi, Mohamed Salah; Calmels, Christina; Andreola, Marie-Line; Ruff, Marc; Llano, Manuel; Delelis, Olivier; Lavigne, Marc; Parissi, Vincent

    2017-07-28

    Insertion of retroviral genome DNA occurs in the chromatin of the host cell. This step is modulated by chromatin structure as nucleosomes compaction was shown to prevent HIV-1 integration and chromatin remodeling has been reported to affect integration efficiency. LEDGF/p75-mediated targeting of the integration complex toward RNA polymerase II (polII) transcribed regions ensures optimal access to dynamic regions that are suitable for integration. Consequently, we have investigated the involvement of polII-associated factors in the regulation of HIV-1 integration. Using a pull down approach coupled with mass spectrometry, we have selected the FACT (FAcilitates Chromatin Transcription) complex as a new potential cofactor of HIV-1 integration. FACT is a histone chaperone complex associated with the polII transcription machinery and recently shown to bind LEDGF/p75. We report here that a tripartite complex can be formed between HIV-1 integrase, LEDGF/p75 and FACT in vitro and in cells. Biochemical analyzes show that FACT-dependent nucleosome disassembly promotes HIV-1 integration into chromatinized templates, and generates highly favored nucleosomal structures in vitro. This effect was found to be amplified by LEDGF/p75. Promotion of this FACT-mediated chromatin remodeling in cells both increases chromatin accessibility and stimulates HIV-1 infectivity and integration. Altogether, our data indicate that FACT regulates HIV-1 integration by inducing local nucleosomes dissociation that modulates the functional association between the incoming intasome and the targeted nucleosome.

  15. Brain oxytocin: a key regulator of emotional and social behaviours in both females and males.

    PubMed

    Neumann, I D

    2008-06-01

    In addition to various reproductive stimuli, the neuropeptide oxytocin (OXT) is released both from the neurohypophysial terminal into the blood stream and within distinct brain regions in response to stressful or social stimuli. Brain OXT receptor-mediated actions were shown to be significantly involved in the regulation of a variety of behaviours. Here, complementary methodological approaches are discussed which were utilised to reveal, for example, anxiolytic and anti-stress effects of OXT, both in females and in males, effects that were localised within the central amygdala and the hypothalamic paraventricular nucleus. Also, in male rats, activation of the brain OXT system is essential for the regulation of sexual behaviour, and increased OXT system activity during mating is directly linked to an attenuated anxiety-related behaviour. Moreover, in late pregnancy and during lactation, central OXT is involved in the establishment and fine-tuned maintenance of maternal care and maternal aggression. In monogamous prairie voles, brain OXT is important for mating-induced pair bonding, especially in females. Another example of behavioural actions of intracerebral OXT is the promotion of social memory processes and recognition of con-specifics, as revealed in rats, mice, sheep and voles. Experimental evidence suggests that, in humans, brain OXT exerts similar behavioural effects. Thus, the brain OXT system seems to be a potential target for the development of therapeutics to treat anxiety- and depression-related diseases or abnormal social behaviours including autism.

  16. Doing Your Own Time: Peer Integration, Aggression and Mental Health in Dutch Male Detainment Facilities

    PubMed Central

    Kreager, Derek A.; Palmen, Hanneke; Dirkzwager, Anja J.E.; Nieuwbeerta, Paul

    2016-01-01

    Background Prior research demonstrates a strong positive association between social integration (e.g., strong social ties) and individual health. However, researchers also emphasize that this correlation may vary by context and potentially reverse direction under certain conditions. In this study, we draw on competing criminological theories of peer relations to examine if social integration, measured by trust in peers, is positively or negatively associated with violence and mental health of men detained in pre-trial confinement facilities. Methods We test our hypotheses with peer network and health data from 502 Dutch male pre-trial detainees. Results Results suggest that peer trust has no direct association with reported rates of peer aggression while detained and low peer trust is generally protective for mental health. Conclusions Our study thus adds to a small body of literature finding that social integration within certain correctional settings may not operate in the same way that it does in the general population and may actually contribute to adverse mental health outcomes. PMID:26794247

  17. Regulation of mitosis-meiosis transition by the ubiquitin ligase β-TrCP in male germ cells.

    PubMed

    Nakagawa, Tadashi; Zhang, Teng; Kushi, Ryo; Nakano, Seiji; Endo, Takahiro; Nakagawa, Makiko; Yanagihara, Noriko; Zarkower, David; Nakayama, Keiko

    2017-11-15

    The mitosis-meiosis transition is essential for spermatogenesis. Specific and timely downregulation of the transcription factor DMRT1, and consequent induction of Stra8 expression, is required for this process in mammals, but the molecular mechanism has remained unclear. Here, we show that β-TrCP, the substrate recognition component of an E3 ubiquitin ligase complex, targets DMRT1 for degradation and thereby controls the mitosis-meiosis transition in mouse male germ cells. Conditional inactivation of β-TrCP2 in male germ cells of β-TrCP1 knockout mice resulted in sterility due to a lack of mature sperm. The β-TrCP-deficient male germ cells did not enter meiosis, but instead underwent apoptosis. The induction of Stra8 expression was also attenuated in association with the accumulation of DMRT1 at the Stra8 promoter in β-TrCP-deficient testes. DMRT1 contains a consensus β-TrCP degron sequence that was found to bind β-TrCP. Overexpression of β-TrCP induced the ubiquitylation and degradation of DMRT1. Heterozygous deletion of Dmrt1 in β-TrCP-deficient spermatogonia increased meiotic cells with a concomitant reduction of apoptosis. Collectively, our data indicate that β-TrCP regulates the transition from mitosis to meiosis in male germ cells by targeting DMRT1 for degradation. © 2017. Published by The Company of Biologists Ltd.

  18. [The function of ERα in male reproductive system].

    PubMed

    Dong, Yu-Hang; Wei, Jin-Hua; Li, Zhen

    2014-12-01

    Estrogen receptors (ERs), including two sub-types ERα and ERβ, belong to the steroid hormone superfamily of nuclear receptors. ERα distributes in the male reproductive system and plays a crucial role in the regulation of male reproduction through estrogen-dependent and -independent ways. In this article, we mainly reviewed the molecular structure, mode of action and location of ERα in the male reproductive system, and explored the mechanism of ERα in regulating the male reproductive system by analyzing different animal models of disrupted ERα.

  19. Estrogen treatment up-regulates female genes but does not suppress all early testicular markers during rainbow trout male-to-female gonadal transdifferentiation.

    PubMed

    Vizziano-Cantonnet, Denise; Baron, Daniel; Mahè, Sophie; Cauty, Chantal; Fostier, Alexis; Guiguen, Yann

    2008-11-01

    In non-mammalian vertebrates, estrogens are key players in ovarian differentiation, but the mechanisms by which they act remain poorly understood. The present study on rainbow trout was designed to investigate whether estrogens trigger the female pathway by activating a group of early female genes (i.e. cyp19a1, foxl2a, foxl2b, fst, bmp4, and fshb) and by repressing early testicular markers (i.e. dmrt1, nr0b1, sox9a1 and sox9a2). Feminization was induced in genetically all-male populations using 17alpha-ethynylestradiol (EE2, 20 mg/kg of food during 2 months). The expression profiles of 100 candidate genes were obtained by real-time RT-PCR and 45 expression profiles displayed a significant differential expression between control populations (males and females) and EE2-treated populations. These expression profiles were grouped in five temporally correlated expression clusters. The estrogen treatment induced most of the early ovarian differentiation genes (foxl2a, foxl2b, fst, bmp4, and fshb) and in particular foxl2a, which was strongly and quickly up-regulated. Simultaneously, Leydig cell genes, involved in androgen synthesis, as well as some Sertoli cell markers (amh, sox9a2) were strongly repressed. However, in contrast to our initial hypothesis, some genes considered as essential for mammalian and fish testis differentiation were not suppressed during the early process of estrogen-induced feminization (dmrt1, nr0b1, sox9a1 and pax2a) and some were even strongly up-regulated (nr0b1, sox9a1and pax2a). In conclusion, estrogens trigger male-to-female transdifferentiation by up-regulating most ovarian specific genes and this up-regulation appears to be crucial for an effective feminization, but estrogens do not concomitantly down-regulate all the testicular differentiation markers.

  20. Androgenic regulation of chemoinvestigatory behaviors in male and female hamsters.

    PubMed

    Powers, J B; Bergondy, M L

    1983-03-01

    In male hamsters, chemosensory responsiveness to sexually relevant female odors is facilitated by testosterone (T). Some evidence suggests that this is not a sexually dimorphic response in that adult females can respond similarly to males following administration of T. This was evaluated and additionally, the hypothesis that facilitation of chemosensory responsiveness by T might be mediated by the conversion of T to aromatized or 5 alpha-reduced metabolites was tested. In 2-min tests, we measured the time adult males or females investigated female hamster vaginal secretion (FHVS). These animals were gonadectomized and administered T, 5 alpha-dihydrotestosterone (DHT), estradiol (E2), or a combination of DHT and E2, by subcutaneous implantation of Silastic capsules. FHVS tests were conducted either 2 and 4 weeks, or 4 and 6 weeks subsequent to gonadectomy and hormone treatment. Comparisons among groups receiving different hormone doses indicated that (1) males and females are not equally responsive to the attractant properties of FHVS, and that (2) neither DHT, E2, nor their combination, can duplicate the effects of T in facilitating responsiveness to FHVS in either sex. The copulatory behavior of males under the hormone conditions described was also tested and it was found that variations in the rate at which the test males sniffed or licked the receptive female's anogenital region correlated with variations in measures of the males' sexual performance.

  1. Integrated regulation of PIKK-mediated stress responses by AAA+ proteins RUVBL1 and RUVBL2

    PubMed Central

    Izumi, Natsuko; Yamashita, Akio; Ohno, Shigeo

    2012-01-01

    Proteins of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family are activated by various cellular stresses, including DNA damage, premature termination codon and nutritional status, and induce appropriate cellular responses. The importance of PIKK functions in the maintenance of genome integrity, accurate gene expression and the proper control of cell growth/proliferation is established. Recently, ATPase associated diverse cellular activities (AAA+) proteins RUVBL1 and RUVBL2 (RUVBL1/2) have been shown to be common regulators of PIKKs. The RUVBL1/2 complex regulates PIKK-mediated stress responses through physical interactions with PIKKs and by controlling PIKK mRNA levels. In this review, the functions of PIKKs in stress responses are outlined and the physiological significance of the integrated regulation of PIKKs by the RUVBL1/2 complex is presented. We also discuss a putative “PIKK regulatory chaperone complex” including other PIKK regulators, Hsp90 and the Tel2 complex. PMID:22540023

  2. Integrated cellular network of transcription regulations and protein-protein interactions.

    PubMed

    Wang, Yu-Chao; Chen, Bor-Sen

    2010-03-08

    With the accumulation of increasing omics data, a key goal of systems biology is to construct networks at different cellular levels to investigate cellular machinery of the cell. However, there is currently no satisfactory method to construct an integrated cellular network that combines the gene regulatory network and the signaling regulatory pathway. In this study, we integrated different kinds of omics data and developed a systematic method to construct the integrated cellular network based on coupling dynamic models and statistical assessments. The proposed method was applied to S. cerevisiae stress responses, elucidating the stress response mechanism of the yeast. From the resulting integrated cellular network under hyperosmotic stress, the highly connected hubs which are functionally relevant to the stress response were identified. Beyond hyperosmotic stress, the integrated network under heat shock and oxidative stress were also constructed and the crosstalks of these networks were analyzed, specifying the significance of some transcription factors to serve as the decision-making devices at the center of the bow-tie structure and the crucial role for rapid adaptation scheme to respond to stress. In addition, the predictive power of the proposed method was also demonstrated. We successfully construct the integrated cellular network which is validated by literature evidences. The integration of transcription regulations and protein-protein interactions gives more insight into the actual biological network and is more predictive than those without integration. The method is shown to be powerful and flexible and can be used under different conditions and for different species. The coupling dynamic models of the whole integrated cellular network are very useful for theoretical analyses and for further experiments in the fields of network biology and synthetic biology.

  3. [Astaxanthin in male reproduction: Advances in studies].

    PubMed

    Liu, Wei; Kang, Xiao-Fang; Shang, Xue-Jun

    2016-10-01

    Astaxanthin (AST) is a carotenoid with a strong antioxidant activity and has many biological functions, such as anti-inflammation, immune regulation, anti-tumor, anti-oxidation, anti-aging, and anti-apoptosis. Recent studies show that AST can effectively regulate the dynamic balance between oxidation and antioxidants in the male reproductive system, protect sperm mitochondrial function, ameliorate testicular heat stress and reproductive poison damage, promote the occurrence of sperm capacitation and acrosome reaction, regulate reproductive endocrine hormone balance, and act favorably on primary infertility or metabolic syndrome-related infertility. It also helps the treatment of late-onset hypogonadism and prostate health care. This review updates the studies of AST in male reproductive health and provides some new ideas for the prevention and treatment of male reproductive problems.

  4. An Ichor-dependent apical extracellular matrix regulates seamless tube shape and integrity

    PubMed Central

    Rosa, Jeffrey B.; Metzstein, Mark M.

    2018-01-01

    During sprouting angiogenesis in the vertebrate vascular system, and primary branching in the Drosophila tracheal system, specialized tip cells direct branch outgrowth and network formation. When tip cells lumenize, they form subcellular (seamless) tubes. How these seamless tubes are made, shaped and maintained remains poorly understood. Here we characterize a Drosophila mutant called ichor (ich), and show that ich is essential for the integrity and shape of seamless tubes in tracheal terminal cells. We find that Ich regulates seamless tubulogenesis via its role in promoting the formation of a mature apical extracellular matrix (aECM) lining the lumen of the seamless tubes. We determined that ich encodes a zinc finger protein (CG11966) that acts, as a transcriptional activator required for the expression of multiple aECM factors, including a novel membrane-anchored trypsin protease (CG8213). Thus, the integrity and shape of seamless tubes are regulated by the aECM that lines their lumens. PMID:29309404

  5. Regulation of Cell Wall Biogenesis in Saccharomyces cerevisiae: The Cell Wall Integrity Signaling Pathway

    PubMed Central

    Levin, David E.

    2011-01-01

    The yeast cell wall is a strong, but elastic, structure that is essential not only for the maintenance of cell shape and integrity, but also for progression through the cell cycle. During growth and morphogenesis, and in response to environmental challenges, the cell wall is remodeled in a highly regulated and polarized manner, a process that is principally under the control of the cell wall integrity (CWI) signaling pathway. This pathway transmits wall stress signals from the cell surface to the Rho1 GTPase, which mobilizes a physiologic response through a variety of effectors. Activation of CWI signaling regulates the production of various carbohydrate polymers of the cell wall, as well as their polarized delivery to the site of cell wall remodeling. This review article centers on CWI signaling in Saccharomyces cerevisiae through the cell cycle and in response to cell wall stress. The interface of this signaling pathway with other pathways that contribute to the maintenance of cell wall integrity is also discussed. PMID:22174182

  6. How females of chirping and trilling field crickets integrate the 'what' and 'where' of male acoustic signals during decision making.

    PubMed

    Gabel, Eileen; Gray, David A; Matthias Hennig, R

    2016-11-01

    In crickets acoustic communication serves mate selection. Female crickets have to perceive and integrate male cues relevant for mate choice while confronted with several different signals in an acoustically diverse background. Overall female decisions are based on the attractiveness of the temporal pattern (informative about the 'what') and on signal intensity (informative about the 'where') of male calling songs. Here, we investigated how the relevant cues for mate choice are integrated during the decision process by females of five different species of chirping and trilling field crickets. Using a behavioral design, female preferences in no-choice and choice situations for male calling songs differing in pulse rate, modulation depth, intensities, chirp/trill arrangements and temporal shifts were examined. Sensory processing underlying decisions in female field crickets is rather similar as combined evidence suggested that incoming song patterns were analyzed separately by bilaterally paired networks for pattern attractiveness and pattern intensity. A downstream gain control mechanism leads to a weighting of the intensity cue by pattern attractiveness. While remarkable differences between species were observed with respect to specific processing steps, closely related species exhibited more similar preferences than did more distantly related species.

  7. Male involvement and prevention of mother-to-child transmission of HIV in Sub-Saharan Africa: an integrative review.

    PubMed

    Auvinen, Jaana; Kylmä, Jari; Suominen, Tarja

    2013-03-01

    The purpose of the study was to describe male involvement in programmes for preventing mother-tochild transmission (PMTCT) in Sub-Saharan Africa. The study questions guiding this review were: how are male partners involved in PMTCT programmes in Sub-Saharan Africa and what are the strategies for improvement of male involvement? An integrative review was conducted based on the data retrieved from the PubMed MEDLINE database. In all, 18 articles were included in this review. Qualitative content analysis was used as a method of data synthesis. Based on the findings of this review, some studies suggested that men had positive attitudes towards PMTCT programmes. However, also barriers to male involvement were identified. These barriers included negative attitude, lack of resources, fear of human immunodeficiency virus (HIV) test result, marital difficulties, problems with health care services and cultural barriers. Accepting HIV testing was associated with factors related to both wife and husband. Strategies for improving male involvement included ones that focus on men's and their wives' resources (sensitizing men about antenatal care (ANC) and PMTCT, focusing on the conjugal context and couples counselling), the development of health care services (tailoring the services to male needs, taking care of health care staff's resources, developing health care strategies) and the community (educating the community, testing, safer infant feeding). We should highlight the male participation in PMTCT programmes. However, more research is needed in order to evaluate their impact on PMTCT, as well as on broader family health outcomes.

  8. Role of the oxytocin system in amygdala subregions in the regulation of social interest in male and female rats.

    PubMed

    Dumais, Kelly M; Alonso, Andrea G; Bredewold, Remco; Veenema, Alexa H

    2016-08-25

    We previously found that oxytocin (OT) receptor (OTR) binding density in the medial amygdala (MeA) correlated positively with social interest (i.e., the motivation to investigate a conspecific) in male rats, while OTR binding density in the central amygdala (CeA) correlated negatively with social interest in female rats. Here, we determined the causal involvement of OTR in the MeA and CeA in the sex-specific regulation of social interest in adult rats by injecting an OTR antagonist (5ng/0.5μl/side) or OT (100pg/0.5μl/side) before the social interest test (4-min same-sex juvenile exposure). OTR blockade in the CeA decreased social interest in males but not females, while all other treatments had no behavioral effect. To further explore the sex-specific involvement of the OT system in the CeA in social interest, we used in vivo microdialysis to determine possible sex differences in endogenous OT release in the CeA during social interest. Interestingly, males and females showed similar levels of extracellular OT release at baseline and during social interest, suggesting that factors other than local OT release mediate the sex-specific role of CeA-OTR in social interest. Moreover, we found a positive correlation between CeA-OT release and social investigation time in females. This was further reflected by reduced CeA-OT release during social interest in females that expressed low compared to high social interest. We discuss the possibility that this reduction in OT release may be a consequence, rather than a cause, of exposure to a social stimulus. Overall, our findings show for the first time that extracellular OT release in the CeA is similar between males and females and that OTR in the CeA plays a causal role in the regulation of social interest toward juvenile conspecifics in males. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. Role of the oxytocin system in amygdala subregions in the regulation of social interest in male and female rats

    PubMed Central

    Dumais, Kelly M.; Alonso, Andrea G.; Bredewold, Remco; Veenema, Alexa H.

    2016-01-01

    We previously found that oxytocin (OT) receptor (OTR) binding density in the medial amygdala (MeA) correlated positively with social interest (i.e., the motivation to investigate a conspecific) in male rats, while OTR binding density in the central amygdala (CeA) correlated negatively with social interest in female rats. Here, we determined the causal involvement of OTR in the MeA and CeA in the sex-specific regulation of social interest in adult rats by injecting an OTR antagonist (5 ng/0.5 µl/side) or OT (100 pg/0.5 µl/side) before the social interest test (4-min same-sex juvenile exposure). OTR blockade in the CeA decreased social interest in males but not females, while all other treatments had no behavioral effect. To further explore the sex-specific involvement of the OT system in the CeA in social interest, we used in vivo microdialysis to determine possible sex differences in endogenous OT release in the CeA during social interest. Interestingly, males and females showed similar levels of extracellular OT release at baseline and during social interest, suggesting that factors other than local OT release mediate the sex-specific role of CeA-OTR in social interest. Moreover, we found a positive correlation between CeA-OT release and social investigation time in females. This was further reflected by reduced CeA-OT release during social interest in females that expressed low compared to high social interest. We discuss the possibility that this reduction in OT release may be a consequence, rather than a cause, of exposure to a social stimulus. Overall, our findings show for the first time that extracellular OT release in the CeA is similar between males and females and that OTR in the CeA plays a causal role in the regulation of social interest towards juvenile conspecifics in males. PMID:27235738

  10. Integrated cellular network of transcription regulations and protein-protein interactions

    PubMed Central

    2010-01-01

    Background With the accumulation of increasing omics data, a key goal of systems biology is to construct networks at different cellular levels to investigate cellular machinery of the cell. However, there is currently no satisfactory method to construct an integrated cellular network that combines the gene regulatory network and the signaling regulatory pathway. Results In this study, we integrated different kinds of omics data and developed a systematic method to construct the integrated cellular network based on coupling dynamic models and statistical assessments. The proposed method was applied to S. cerevisiae stress responses, elucidating the stress response mechanism of the yeast. From the resulting integrated cellular network under hyperosmotic stress, the highly connected hubs which are functionally relevant to the stress response were identified. Beyond hyperosmotic stress, the integrated network under heat shock and oxidative stress were also constructed and the crosstalks of these networks were analyzed, specifying the significance of some transcription factors to serve as the decision-making devices at the center of the bow-tie structure and the crucial role for rapid adaptation scheme to respond to stress. In addition, the predictive power of the proposed method was also demonstrated. Conclusions We successfully construct the integrated cellular network which is validated by literature evidences. The integration of transcription regulations and protein-protein interactions gives more insight into the actual biological network and is more predictive than those without integration. The method is shown to be powerful and flexible and can be used under different conditions and for different species. The coupling dynamic models of the whole integrated cellular network are very useful for theoretical analyses and for further experiments in the fields of network biology and synthetic biology. PMID:20211003

  11. Exercise motivational regulations and exercise addiction: The mediating role of passion.

    PubMed

    Sicilia, Álvaro; Alcaraz-Ibáñez, Manuel; Lirola, María-Jesús; Burgueño, Rafael; Maher, Anthony

    2018-05-23

    Background and aims The study explored the mediating role of forms of passion in the relationship between motivational regulations in exercise and exercise addiction (EA). Methods A total of 485 university students (368 males and 117 females; M age  = 20.43, SD = 3.21) completed a questionnaire measuring the frequency and intensity of exercise, motivational regulations in exercise, passion for exercise, and EA. Controlling the effects of age, frequency, and intensity of practice, the relationships between the study variables were examined though a path analysis. Results Both self-determined and non-self-determined forms of motivation showed positive association with EA. The forms of motivation with greatest predictive power for EA were introjected and integrated regulations. Both forms of motivation had positive direct and indirect effects through obsessive passion (OP) on EA; however, integrated regulation also showed negative indirect effects through harmonious passion on EA. Conclusions Both forms of passion and, especially, OP, seem to affect how motivational regulations are associated with EA. These findings clarify the association found in previous studies between self-determined forms of motivation and EA.

  12. Hypothalamic carnitine metabolism integrates nutrient and hormonal feedback to regulate energy homeostasis.

    PubMed

    Stark, Romana; Reichenbach, Alex; Andrews, Zane B

    2015-12-15

    The maintenance of energy homeostasis requires the hypothalamic integration of nutrient feedback cues, such as glucose, fatty acids, amino acids, and metabolic hormones such as insulin, leptin and ghrelin. Although hypothalamic neurons are critical to maintain energy homeostasis research efforts have focused on feedback mechanisms in isolation, such as glucose alone, fatty acids alone or single hormones. However this seems rather too simplistic considering the range of nutrient and endocrine changes associated with different metabolic states, such as starvation (negative energy balance) or diet-induced obesity (positive energy balance). In order to understand how neurons integrate multiple nutrient or hormonal signals, we need to identify and examine potential intracellular convergence points or common molecular targets that have the ability to sense glucose, fatty acids, amino acids and hormones. In this review, we focus on the role of carnitine metabolism in neurons regulating energy homeostasis. Hypothalamic carnitine metabolism represents a novel means for neurons to facilitate and control both nutrient and hormonal feedback. In terms of nutrient regulation, carnitine metabolism regulates hypothalamic fatty acid sensing through the actions of CPT1 and has an underappreciated role in glucose sensing since carnitine metabolism also buffers mitochondrial matrix levels of acetyl-CoA, an allosteric inhibitor of pyruvate dehydrogenase and hence glucose metabolism. Studies also show that hypothalamic CPT1 activity also controls hormonal feedback. We hypothesis that hypothalamic carnitine metabolism represents a key molecular target that can concurrently integrate nutrient and hormonal information, which is critical to maintain energy homeostasis. We also suggest this is relevant to broader neuroendocrine research as it predicts that hormonal signaling in the brain varies depending on current nutrient status. Indeed, the metabolic action of ghrelin, leptin or insulin

  13. The Process Model of Group-Based Emotion: Integrating Intergroup Emotion and Emotion Regulation Perspectives.

    PubMed

    Goldenberg, Amit; Halperin, Eran; van Zomeren, Martijn; Gross, James J

    2016-05-01

    Scholars interested in emotion regulation have documented the different goals and strategies individuals have for regulating their emotions. However, little attention has been paid to the regulation of group-based emotions, which are based on individuals' self-categorization as a group member and occur in response to situations perceived as relevant for that group. We propose a model for examining group-based emotion regulation that integrates intergroup emotions theory and the process model of emotion regulation. This synergy expands intergroup emotion theory by facilitating further investigation of different goals (i.e., hedonic or instrumental) and strategies (e.g., situation selection and modification strategies) used to regulate group-based emotions. It also expands emotion regulation research by emphasizing the role of self-categorization (e.g., as an individual or a group member) in the emotional process. Finally, we discuss the promise of this theoretical synergy and suggest several directions for future research on group-based emotion regulation. © 2015 by the Society for Personality and Social Psychology, Inc.

  14. A FEEDBACK MODEL FOR TESTICULAR-PITUITARY AXIS HORMONE KINETICS AND THEIR EFFECTS ON THE REGULATION OF THE PROSTATE IN ADULT MALE RATS

    EPA Science Inventory

    The testicular-hypothalamic-pituitary axis regulates male reproductive system functions. A model describing the kinetics and dynamics of testosterone (T), dihydrotestosterone (DHT) and luteinizing hormone (LH) was developed based on a model by Barton and Anderson (1997). The mode...

  15. Integration of light and circadian signals that regulate chloroplast transcription by a nuclear-encoded sigma factor.

    PubMed

    Belbin, Fiona E; Noordally, Zeenat B; Wetherill, Sarah J; Atkins, Kelly A; Franklin, Keara A; Dodd, Antony N

    2017-01-01

    We investigated the signalling pathways that regulate chloroplast transcription in response to environmental signals. One mechanism controlling plastid transcription involves nuclear-encoded sigma subunits of plastid-encoded plastid RNA polymerase. Transcripts encoding the sigma factor SIG5 are regulated by light and the circadian clock. However, the extent to which a chloroplast target of SIG5 is regulated by light-induced changes in SIG5 expression is unknown. Moreover, the photoreceptor signalling pathways underlying the circadian regulation of chloroplast transcription by SIG5 are unidentified. We monitored the regulation of chloroplast transcription in photoreceptor and sigma factor mutants under controlled light regimes in Arabidopsis thaliana. We established that a chloroplast transcriptional response to light intensity was mediated by SIG5; a chloroplast transcriptional response to the relative proportions of red and far red light was regulated by SIG5 through phytochrome and photosynthetic signals; and the circadian regulation of chloroplast transcription by SIG5 was predominantly dependent on blue light and cryptochrome. Our experiments reveal the extensive integration of signals concerning the light environment by a single sigma factor to regulate chloroplast transcription. This may originate from an evolutionarily ancient mechanism that protects photosynthetic bacteria from high light stress, which subsequently became integrated with higher plant phototransduction networks. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  16. The endosomal transcriptional regulator RNF11 integrates degradation and transport of EGFR

    PubMed Central

    Boncompain, Gaelle; Laketa, Vibor; Poser, Ina; Beck, Martin; Bork, Peer

    2016-01-01

    Stimulation of cells with epidermal growth factor (EGF) induces internalization and partial degradation of the EGF receptor (EGFR) by the endo-lysosomal pathway. For continuous cell functioning, EGFR plasma membrane levels are maintained by transporting newly synthesized EGFRs to the cell surface. The regulation of this process is largely unknown. In this study, we find that EGF stimulation specifically increases the transport efficiency of newly synthesized EGFRs from the endoplasmic reticulum to the plasma membrane. This coincides with an up-regulation of the inner coat protein complex II (COPII) components SEC23B, SEC24B, and SEC24D, which we show to be specifically required for EGFR transport. Up-regulation of these COPII components requires the transcriptional regulator RNF11, which localizes to early endosomes and appears additionally in the cell nucleus upon continuous EGF stimulation. Collectively, our work identifies a new regulatory mechanism that integrates the degradation and transport of EGFR in order to maintain its physiological levels at the plasma membrane. PMID:27872256

  17. Androgen Action via the Androgen Receptor in Neurons Within the Brain Positively Regulates Muscle Mass in Male Mice.

    PubMed

    Davey, Rachel A; Clarke, Michele V; Russell, Patricia K; Rana, Kesha; Seto, Jane; Roeszler, Kelly N; How, Jackie M Y; Chia, Ling Yeong; North, Kathryn; Zajac, Jeffrey D

    2017-10-01

    Although it is well established that exogenous androgens have anabolic effects on skeletal muscle mass in humans and mice, data from muscle-specific androgen receptor (AR) knockout (ARKO) mice indicate that myocytic expression of the AR is dispensable for hind-limb muscle mass accrual in males. To identify possible indirect actions of androgens via the AR in neurons to regulate muscle, we generated neuron-ARKO mice in which the dominant DNA binding-dependent actions of the AR are deleted in neurons of the cortex, forebrain, hypothalamus, and olfactory bulb. Serum testosterone and luteinizing hormone levels were elevated twofold in neuron-ARKO males compared with wild-type littermates due to disruption of negative feedback to the hypothalamic-pituitary-gonadal axis. Despite this increase in serum testosterone levels, which was expected to increase muscle mass, the mass of the mixed-fiber gastrocnemius (Gast) and the fast-twitch fiber extensor digitorum longus hind-limb muscles was decreased by 10% in neuron-ARKOs at 12 weeks of age, whereas muscle strength and fatigue of the Gast were unaffected. The mass of the soleus muscle, however, which consists of a high proportion of slow-twitch fibers, was unaffected in neuron-ARKOs, demonstrating a stimulatory action of androgens via the AR in neurons to increase the mass of fast-twitch hind-limb muscles. Furthermore, neuron-ARKOs displayed reductions in voluntary and involuntary physical activity by up to 60%. These data provide evidence for a role of androgens via the AR in neurons to positively regulate fast-twitch hind-limb muscle mass and physical activity in male mice. Copyright © 2017 Endocrine Society.

  18. Integrative Genomics-Based Discovery of Novel Regulators of the Innate Antiviral Response

    PubMed Central

    van der Lee, Robin; ter Horst, Rob; Szklarczyk, Radek; Netea, Mihai G.; Andeweg, Arno C.; van Kuppeveld, Frank J. M.; Huynen, Martijn A.

    2015-01-01

    The RIG-I-like receptor (RLR) pathway is essential for detecting cytosolic viral RNA to trigger the production of type I interferons (IFNα/β) that initiate an innate antiviral response. Through systematic assessment of a wide variety of genomics data, we discovered 10 molecular signatures of known RLR pathway components that collectively predict novel members. We demonstrate that RLR pathway genes, among others, tend to evolve rapidly, interact with viral proteins, contain a limited set of protein domains, are regulated by specific transcription factors, and form a tightly connected interaction network. Using a Bayesian approach to integrate these signatures, we propose likely novel RLR regulators. RNAi knockdown experiments revealed a high prediction accuracy, identifying 94 genes among 187 candidates tested (~50%) that affected viral RNA-induced production of IFNβ. The discovered antiviral regulators may participate in a wide range of processes that highlight the complexity of antiviral defense (e.g. MAP3K11, CDK11B, PSMA3, TRIM14, HSPA9B, CDC37, NUP98, G3BP1), and include uncharacterized factors (DDX17, C6orf58, C16orf57, PKN2, SNW1). Our validated RLR pathway list (http://rlr.cmbi.umcn.nl/), obtained using a combination of integrative genomics and experiments, is a new resource for innate antiviral immunity research. PMID:26485378

  19. Impact of radio frequency electromagnetic radiation on DNA integrity in the male germline.

    PubMed

    Aitken, R J; Bennetts, L E; Sawyer, D; Wiklendt, A M; King, B V

    2005-06-01

    Concern has arisen over human exposures to radio frequency electromagnetic radiation (RFEMR), including a recent report indicating that regular mobile phone use can negatively impact upon human semen quality. These effects would be particularly serious if the biological effects of RFEMR included the induction of DNA damage in male germ cells. In this study, mice were exposed to 900 MHz RFEMR at a specific absorption rate of approximately 90 mW/kg inside a waveguide for 7 days at 12 h per day. Following exposure, DNA damage to caudal epididymal spermatozoa was assessed by quantitative PCR (QPCR) as well as alkaline and pulsed-field gel electrophoresis. The treated mice were overtly normal and all assessment criteria, including sperm number, morphology and vitality were not significantly affected. Gel electrophoresis revealed no gross evidence of increased single- or double-DNA strand breakage in spermatozoa taken from treated animals. However, a detailed analysis of DNA integrity using QPCR revealed statistically significant damage to both the mitochondrial genome (p < 0.05) and the nuclear beta-globin locus (p < 0.01). This study suggests that while RFEMR does not have a dramatic impact on male germ cell development, a significant genotoxic effect on epididymal spermatozoa is evident and deserves further investigation.

  20. Teachers' Self-Regulated Learning Lesson Design: Integrating Learning from Problems and Successes

    ERIC Educational Resources Information Center

    Michalsky, Tova; Schechter, Chen

    2018-01-01

    Teachers' design of a lesson is critical for helping their students develop academically effective forms of self-regulating learning (SRL) in classrooms. Using a quasi-experimental design, the researchers integrated systematic collaborative learning from problematic and successful experiences into teachers' preparatory programs and examined how…

  1. Integrated regulation of motor-driven organelle transport by scaffolding proteins.

    PubMed

    Fu, Meng-meng; Holzbaur, Erika L F

    2014-10-01

    Intracellular trafficking pathways, including endocytosis, autophagy, and secretion, rely on directed organelle transport driven by the opposing microtubule motor proteins kinesin and dynein. Precise spatial and temporal targeting of vesicles and organelles requires the integrated regulation of these opposing motors, which are often bound simultaneously to the same cargo. Recent progress demonstrates that organelle-associated scaffolding proteins, including Milton/TRAKs (trafficking kinesin-binding protein), JIP1, JIP3 (JNK-interacting proteins), huntingtin, and Hook1, interact with molecular motors to coordinate activity and sustain unidirectional transport. Scaffolding proteins also bind to upstream regulatory proteins, including kinases and GTPases, to modulate transport in the cell. This integration of regulatory control with motor activity allows for cargo-specific changes in the transport or targeting of organelles in response to cues from the complex cellular environment. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. An Integrated Phosphoproteomics Work Flow Reveals Extensive Network Regulation in Early Lysophosphatidic Acid Signaling*

    PubMed Central

    Schreiber, Thiemo B.; Mäusbacher, Nina; Kéri, György; Cox, Jürgen; Daub, Henrik

    2010-01-01

    Lysophosphatidic acid (LPA) induces a variety of cellular signaling pathways through the activation of its cognate G protein-coupled receptors. To investigate early LPA responses and assess the contribution of epidermal growth factor (EGF) receptor transactivation in LPA signaling, we performed phosphoproteomics analyses of both total cell lysate and protein kinase-enriched fractions as complementary strategies to monitor phosphorylation changes in A498 kidney carcinoma cells. Our integrated work flow enabled the identification and quantification of more than 5,300 phosphorylation sites of which 224 were consistently regulated by LPA. In addition to induced phosphorylation events, we also obtained evidence for early dephosphorylation reactions due to rapid phosphatase regulation upon LPA treatment. Phosphorylation changes induced by direct heparin-binding EGF-like growth factor-mediated EGF receptor activation were typically weaker and only detected on a subset of LPA-regulated sites, indicating signal integration among EGF receptor transactivation and other LPA-triggered pathways. Our results reveal rapid phosphoregulation of many proteins not yet implicated in G protein-coupled receptor signaling and point to various additional mechanisms by which LPA might regulate cell survival and migration as well as gene transcription on the molecular level. Moreover, our phosphoproteomics analysis of both total lysate and kinase-enriched fractions provided highly complementary parts of the LPA-regulated signaling network and thus represents a useful and generic strategy toward comprehensive signaling studies on a system-wide level. PMID:20071362

  3. Co-regulation of pluripotency and genetic integrity at the genomic level.

    PubMed

    Cooper, Daniel J; Walter, Christi A; McCarrey, John R

    2014-11-01

    The Disposable Soma Theory holds that genetic integrity will be maintained at more pristine levels in germ cells than in somatic cells because of the unique role germ cells play in perpetuating the species. We tested the hypothesis that the same concept applies to pluripotent cells compared to differentiated cells. Analyses of transcriptome and cistrome databases, along with canonical pathway analysis and chromatin immunoprecipitation confirmed differential expression of DNA repair and cell death genes in embryonic stem cells and induced pluripotent stem cells relative to fibroblasts, and predicted extensive direct and indirect interactions between the pluripotency and genetic integrity gene networks in pluripotent cells. These data suggest that enhanced maintenance of genetic integrity is fundamentally linked to the epigenetic state of pluripotency at the genomic level. In addition, these findings demonstrate how a small number of key pluripotency factors can regulate large numbers of downstream genes in a pathway-specific manner. Copyright © 2014. Published by Elsevier B.V.

  4. GSK-3β Function in Bone Regulates Skeletal Development, Whole-Body Metabolism, and Male Life Span

    PubMed Central

    Gillespie, J. R.; Bush, J. R.; Bell, G. I.; Aubrey, L. A.; Dupuis, H.; Ferron, M.; Kream, B.; DiMattia, G.; Patel, S.; Woodgett, J. R.; Karsenty, G.; Hess, D. A.; Beier, F.

    2016-01-01

    Glycogen synthase kinase 3 β (GSK-3β) is an essential negative regulator or “brake” on many anabolic-signaling pathways including Wnt and insulin. Global deletion of GSK-3β results in peri-natal lethality and various skeletal defects. The goal of our research was to determine GSK-3β cell-autonomous effects and postnatal roles in the skeleton. We used the 3.6-kb Col1a1 promoter to inactivate the Gsk3b gene (Col1a1-Gsk3b knockout) in skeletal cells. Mutant mice exhibit decreased body fat and postnatal bone growth, as well as delayed development of several skeletal elements. Surprisingly, the mutant mice display decreased circulating glucose and insulin levels despite normal expression of GSK-3β in metabolic tissues. We showed that these effects are due to an increase in global insulin sensitivity. Most of the male mutant mice died after weaning. Prior to death, blood glucose changed from low to high, suggesting a possible switch from insulin sensitivity to resistance. These male mice die with extremely large bladders that are preceded by damage to the urogenital tract, defects that are also seen type 2 diabetes. Our data suggest that skeletal-specific deletion of GSK-3β affects global metabolism and sensitizes male mice to developing type 2 diabetes. PMID:23904355

  5. Stakeholders' perspectives on the regulation and integration of complementary and alternative medicine products in Lebanon: a qualitative study

    PubMed Central

    2011-01-01

    Background The regulation of the markets for Complementary and Alternative Medicine (CAM) products presents a global challenge. There is a dearth of studies that have examined or evaluated the regulatory policies of CAM products in the Eastern Mediterranean Region (EMR). We investigate the regulatory frameworks and the barriers for the proper regulation and integration of CAM products in Lebanon, as an example of an EMR country with a weak public infrastructure. Methods We utilized a qualitative study design involving a series of semi-structured interviews with stakeholders of the CAM market in Lebanon. Snowball sampling was used to identify interviewees; interviews continued until the "saturation" point was reached. A total of 16 interviews were carried out with decision makers, representatives of professional associations, academic researchers, CAM product importers, policy makers and a media representative. Interviews were transcribed and thematic analysis of scripts was carried out. Results There was a consensus among all stakeholders that the regulation of the market for CAM products in Lebanon needs to be strengthened. Thematic analysis identified a number of impediments jeopardizing the safety of public consumption and hindering the integration of CAM therapies into mainstream medicine; including: weak infrastructure, poor regulation, ineffective policies and politics, weak CAM awareness and sub-optimal coordination and cooperation among stakeholders. With respect to policy instruments, voluntary instruments (self regulation) were deemed ineffective by stakeholders due to poor awareness of both users and providers on safe use of CAM products. Stakeholders' rather recommended the adoption of a combination of mixed (enhancing public awareness and integration of CAM into medical and nursing curricula) and compulsory (stricter governmental regulation) policy instruments for the regulation of the market for CAM products. Conclusions The current status quo with

  6. 10 CFR 905.10 - Who must comply with the integrated resource planning and reporting regulations in this subpart?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Who must comply with the integrated resource planning and reporting regulations in this subpart? 905.10 Section 905.10 Energy DEPARTMENT OF ENERGY ENERGY PLANNING AND MANAGEMENT PROGRAM Integrated Resource Planning § 905.10 Who must comply with the integrated resource...

  7. 10 CFR 905.10 - Who must comply with the integrated resource planning and reporting regulations in this subpart?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Who must comply with the integrated resource planning and reporting regulations in this subpart? 905.10 Section 905.10 Energy DEPARTMENT OF ENERGY ENERGY PLANNING AND MANAGEMENT PROGRAM Integrated Resource Planning § 905.10 Who must comply with the integrated resource...

  8. Proportional plus integral MIMO controller for regulation and tracking with anti-wind-up features

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Puleston, P.F.; Mantz, R.J.

    1993-11-01

    A proportional plus integral matrix control structure for MIMO systems is proposed. Based on a standard optimal control structure with integral action, it permits a greater degree of independence of the design and tuning of the regulating and tracking features, without considerably increasing the controller complexity. Fast recovery from load disturbances is achieved, while large overshoots associated with set-point changes and reset wind-up problems can be reduced. A simple effective procedure for practical tuning is introduced.

  9. Hypothalamic integration of body fluid regulation.

    PubMed Central

    Denton, D A; McKinley, M J; Weisinger, R S

    1996-01-01

    The progression of animal life from the paleozoic ocean to rivers and diverse econiches on the planet's surface, as well as the subsequent reinvasion of the ocean, involved many different stresses on ionic pattern, osmotic pressure, and volume of the extracellular fluid bathing body cells. The relatively constant ionic pattern of vertebrates reflects a genetic "set" of many regulatory mechanisms--particularly renal regulation. Renal regulation of ionic pattern when loss of fluid from the body is disproportionate relative to the extracellular fluid composition (e.g., gastric juice with vomiting and pancreatic secretion with diarrhea) makes manifest that a mechanism to produce a biologically relatively inactive extracellular anion HCO3- exists, whereas no comparable mechanism to produce a biologically inactive cation has evolved. Life in the ocean, which has three times the sodium concentration of extracellular fluid, involves quite different osmoregulatory stress to that in freshwater. Terrestrial life involves risk of desiccation and, in large areas of the planet, salt deficiency. Mechanisms integrated in the hypothalamus (the evolutionary ancient midbrain) control water retention and facilitate excretion of sodium, and also control the secretion of renin by the kidney. Over and above the multifactorial processes of excretion, hypothalamic sensors reacting to sodium concentration, as well as circumventricular organs sensors reacting to osmotic pressure and angiotensin II, subserve genesis of sodium hunger and thirst. These behaviors spectacularly augment the adaptive capacities of animals. Instinct (genotypic memory) and learning (phenotypic memory) are melded to give specific behavior apt to the metabolic status of the animal. The sensations, compelling emotions, and intentions generated by these vegetative systems focus the issue of the phylogenetic emergence of consciousness and whether primal awareness initially came from the interoreceptors and vegetative

  10. The heart as a self-regulating system: integration of homeodynamic mechanisms.

    PubMed

    Kresh, J Y; Armour, J A

    1997-04-01

    In the past the study of mechanical and electrical properties of the heart has been disjointed with minimal overlap and unification. The fact remains that these features are tightly coupled and central to the functioning heart. The maintenance of adequate cardiac output relies upon the highly integrated autoregulatory mechanisms and modulation of cardiac myocyte function. Regional ventricular mechanics and energetics are dependent upon muscle fiber stress-strain rate, the passive properties of myocardial collagen matrix, adequate vascular perfusion, transcapillary transport and electrical activation pattern. Intramural hydraulic "loading" is regulated by coronary arterial and venous dynamics. All of these components are under the constant influence of intrinsic cardiac and extracardiac autonomic neurons, as well as circulating hormones. A brief overview of the putative regulation of these various components is presented in this paper.

  11. VITELLOGENIN MRNA REGULATION AND PLASMA CLEARANCE IN MALE SHEEPSHEAD MINNOWS, CYPRINODON VARIEGATUS AFTER CESSATION OF EXPOSURE TO 17B-ESTRADIOL AND P-NONYLPHENOL

    EPA Science Inventory

    Research was conducted to determine the kinetics of hepatic vitellogenin (VTG) mRNA regulation and plasma VTG accumulation and clearance in male sheepshead minnows (Cyprinodon variegatus) during and after cessation of exposure to either 17b-estradiol (E2) or para-nonylphenol (NP)...

  12. Crosstalk between intracellular and extracellular signals regulating interneuron production, migration and integration into the cortex.

    PubMed

    Peyre, Elise; Silva, Carla G; Nguyen, Laurent

    2015-01-01

    During embryogenesis, cortical interneurons are generated by ventral progenitors located in the ganglionic eminences of the telencephalon. They travel along multiple tangential paths to populate the cortical wall. As they reach this structure they undergo intracortical dispersion to settle in their final destination. At the cellular level, migrating interneurons are highly polarized cells that extend and retract processes using dynamic remodeling of microtubule and actin cytoskeleton. Different levels of molecular regulation contribute to interneuron migration. These include: (1) Extrinsic guidance cues distributed along migratory streams that are sensed and integrated by migrating interneurons; (2) Intrinsic genetic programs driven by specific transcription factors that grant specification and set the timing of migration for different subtypes of interneurons; (3) Adhesion molecules and cytoskeletal elements/regulators that transduce molecular signalings into coherent movement. These levels of molecular regulation must be properly integrated by interneurons to allow their migration in the cortex. The aim of this review is to summarize our current knowledge of the interplay between microenvironmental signals and cell autonomous programs that drive cortical interneuron porduction, tangential migration, and intergration in the developing cerebral cortex.

  13. Receptor-Like Kinase RUPO Interacts with Potassium Transporters to Regulate Pollen Tube Growth and Integrity in Rice

    PubMed Central

    Liu, Lingtong; Zheng, Canhui; Kuang, Baijan; Wei, Liqin; Yan, Longfeng; Wang, Tai

    2016-01-01

    During sexual reproduction of flowering plants, the pollen tube grows fast and over a long distance within the pistil to deliver two sperms for double fertilization. Growing plant cells need to communicate constantly with external stimuli as well as monitor changes in surface tension of the cell wall and plasma membrane to coordinate these signals and internal growth machinery; however, the underlying mechanisms remain largely unknown. Here we show that the rice member of plant-specific receptor-like kinase CrRLK1Ls subfamily, Ruptured Pollen tube (RUPO), is specifically expressed in rice pollen. RUPO localizes to the apical plasma membrane and vesicle of pollen tubes and is required for male gamete transmission. K+ levels were greater in pollen of homozygous CRISPR-knockout lines than wild-type plants, and pollen tubes burst shortly after germination. We reveal the interaction of RUPO with high-affinity potassium transporters. Phosphorylation of RUPO established and dephosphorylation abolished the interaction. These results have revealed the receptor-like kinase as a regulator of high-affinity potassium transporters via phosphorylation-dependent interaction, and demonstrated a novel receptor-like kinase signaling pathway that mediates K+ homeostasis required for pollen tube growth and integrity. PMID:27447945

  14. Using tablets to support self-regulated learning in a longitudinal integrated clerkship.

    PubMed

    Archbold Hufty Alegría, Dylan; Boscardin, Christy; Poncelet, Ann; Mayfield, Chandler; Wamsley, Maria

    2014-01-01

    Introduction The need to train physicians committed to learning throughout their careers has prompted medical schools to encourage the development and practice of self-regulated learning by students. Longitudinal integrated clerkships (LICs) require students to exercise self-regulated learning skills. As mobile tools, tablets can potentially support self-regulation among LIC students. Methods We provided 15 LIC students with tablet computers with access to the electronic health record (EHR), to track their patient cohort, and a multiplatform online notebook, to support documentation and retrieval of self-identified clinical learning issues. Students received a 1-hour workshop on the relevant features of the tablet and online notebook. Two focus groups with the students were used to evaluate the program, one early and one late in the year and were coded by two raters. Results Students used the tablet to support their self-regulated learning in ways that were unique to their learning styles and increased access to resources and utilization of down-time. Students who used the tablet to self-monitor and target learning demonstrated the utility of tablets as learning tools. Conclusions LICs are environments rich in opportunity for self-regulated learning. Tablets can enhance students' ability to develop and employ self-regulatory skills in a clinical context.

  15. Using tablets to support self-regulated learning in a longitudinal integrated clerkship.

    PubMed

    Alegría, Dylan Archbold Hufty; Boscardin, Christy; Poncelet, Ann; Mayfield, Chandler; Wamsley, Maria

    2014-01-01

    The need to train physicians committed to learning throughout their careers has prompted medical schools to encourage the development and practice of self-regulated learning by students. Longitudinal integrated clerkships (LICs) require students to exercise self-regulated learning skills. As mobile tools, tablets can potentially support self-regulation among LIC students. We provided 15 LIC students with tablet computers with access to the electronic health record (EHR), to track their patient cohort, and a multiplatform online notebook, to support documentation and retrieval of self-identified clinical learning issues. Students received a 1-hour workshop on the relevant features of the tablet and online notebook. Two focus groups with the students were used to evaluate the program, one early and one late in the year and were coded by two raters. Students used the tablet to support their self-regulated learning in ways that were unique to their learning styles and increased access to resources and utilization of down-time. Students who used the tablet to self-monitor and target learning demonstrated the utility of tablets as learning tools. LICs are environments rich in opportunity for self-regulated learning. Tablets can enhance students' ability to develop and employ self-regulatory skills in a clinical context.

  16. Using tablets to support self-regulated learning in a longitudinal integrated clerkship

    PubMed Central

    Alegría, Dylan Archbold Hufty; Boscardin, Christy; Poncelet, Ann; Mayfield, Chandler; Wamsley, Maria

    2014-01-01

    Introduction The need to train physicians committed to learning throughout their careers has prompted medical schools to encourage the development and practice of self-regulated learning by students. Longitudinal integrated clerkships (LICs) require students to exercise self-regulated learning skills. As mobile tools, tablets can potentially support self-regulation among LIC students. Methods We provided 15 LIC students with tablet computers with access to the electronic health record (EHR), to track their patient cohort, and a multiplatform online notebook, to support documentation and retrieval of self-identified clinical learning issues. Students received a 1-hour workshop on the relevant features of the tablet and online notebook. Two focus groups with the students were used to evaluate the program, one early and one late in the year and were coded by two raters. Results Students used the tablet to support their self-regulated learning in ways that were unique to their learning styles and increased access to resources and utilization of down-time. Students who used the tablet to self-monitor and target learning demonstrated the utility of tablets as learning tools. Conclusions LICs are environments rich in opportunity for self-regulated learning. Tablets can enhance students’ ability to develop and employ self-regulatory skills in a clinical context. PMID:24646438

  17. Ghrelin and GHS-R1A signaling within the ventral and laterodorsal tegmental area regulate sexual behavior in sexually naïve male mice.

    PubMed

    Prieto-Garcia, Luna; Egecioglu, Emil; Studer, Erik; Westberg, Lars; Jerlhag, Elisabet

    2015-12-01

    In addition to food intake and energy balance regulation, ghrelin mediate the rewarding and motivational properties of palatable food as well as addictive drugs. The ability of ghrelin to regulate reinforcement involves the cholinergic-dopaminergic reward link, which encompasses a cholinergic projection from the laterodorsal tegmental area (LDTg) to the ventral tegmental area (VTA) together with mesolimbic dopaminergic projections from the VTA to the nucleus accumbens (NAc). Recently, systemic ghrelin was shown to regulate sexual behavior and motivation in male mice via dopamine neurotransmission. The present study therefore elucidates the role of ghrelin and ghrelin receptor (GHS-R1A) antagonist treatment within NAc, VTA or LDTg for sexual behavior in sexually naïve male mice. Local administration of the GHSR-1A antagonist, JMV2959, into the VTA or LDTg was found to reduce the preference for female mice, the number of mounts and the duration of mounting as well as to prolong the latency to mount. This was further substantiated by the findings that ghrelin administration into the VTA or LDTg increased the number of mounts and the duration of mounting and decreased the latency to mount. Moreover, ghrelin administered into the LDTg increased the preference for female mice. Accumbal administration of ghrelin increased whereas GHS-R1A antagonist decreased the intake of palatable food, but did not alter sexual behavior. In males exposed to sexual interaction, systemic administration of ghrelin increases whereas JMV2959 decreases the turnover of dopamine in the VTA. These data suggest that ghrelin signaling within the tegmental areas is required for sexual behavior in sexually naïve male mice. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Integrated action of pheromone signals in promoting courtship behavior in male mice

    PubMed Central

    Haga-Yamanaka, Sachiko; Ma, Limei; He, Jie; Qiu, Qiang; Lavis, Luke D; Looger, Loren L; Yu, C Ron

    2014-01-01

    The mammalian vomeronasal organ encodes pheromone information about gender, reproductive status, genetic background and individual differences. It remains unknown how pheromone information interacts to trigger innate behaviors. In this study, we identify vomeronasal receptors responsible for detecting female pheromones. A sub-group of V1re clade members recognizes gender-identifying cues in female urine. Multiple members of the V1rj clade are cognate receptors for urinary estrus signals, as well as for sulfated estrogen (SE) compounds. In both cases, the same cue activates multiple homologous receptors, suggesting redundancy in encoding female pheromone cues. Neither gender-specific cues nor SEs alone are sufficient to promote courtship behavior in male mice, whereas robust courtship behavior can be induced when the two cues are applied together. Thus, integrated action of different female cues is required in pheromone-triggered mating behavior. These results suggest a gating mechanism in the vomeronasal circuit in promoting specific innate behavior. DOI: http://dx.doi.org/10.7554/eLife.03025.001 PMID:25073926

  19. [Inheritance of reversions to male fertility in male-sterile sorghum hybrids with 9E cytoplasm male sterility induced by environmental conditions].

    PubMed

    Elkonin, L A; Gerashchenkov, G A; Domanina, I V; Rozhnova, N A

    2015-03-01

    Heritable phenotypic alterations occurring during plant ontogenesis under the influence of environmental factors are among the most intriguing genetic phenomena. It was found that male-sterile sorghum hybrids in the 9E cytoplasm from the F1 and F2 generations, which were obtained by crossing CMS lines with different fertile lines grown in field conditions, were transferred to greenhouse produce fertile tillers. Lines created by the self-pollination of revertant tillers exhibit complete male fertility upon cultivation under various environments (in the field, Tdry plot,(y) Tirrigated plot(y)). In a number of test-crosses of revertants to CMS lines in the 9E cytoplasm, restoration of male fertility in F1 hybrids was found, indicating that revertants possess functional fertility-restoring genes. A high positive correlation was found between the fertility level of the test-cross hybrids and the hydrothermal coefficient (the ratio of the sum of precipitation to the sum of temperatures) during the booting stage and pollen maturation (r = 0.75...0.91; P<0.01), suggesting that a high level of plant water availability is needed for the expression of fertility-restoring genes of revertants. These data show that the fertility-restoring genes for the 9E cytoplasm are dominant in conditions of high water availability and recessive in drought conditions; reversions to male fertility are due to up-regulation of fertility-restoring genes by a high level of water availability. Comparative MSAP-analysis of DNA of male-sterile and male-fertile test-cross hybrids using HpaII/MspI restrictases and primers to polygalacturonase gene ADPG2, which is required for cell separation during reproductive development, and gene MYB46, the transcription factor regulating secondary wall biosynthesis, revealed differences in the number and the length of amplified fragments. Changes in the methylation of these genes in conditions of drought stress are apparently the reason for male sterility of

  20. Dominance relationships among siamang males living in multimale groups.

    PubMed

    Morino, Luca

    2016-03-01

    Intense intolerance among males is considered to be an important mechanism maintaining the uni-male organization traditionally attributed to socially monogamous gibbons. Long-term field work, however, has revealed the existence of stable, socially polyandrous groups in at least two populations, raising questions about the mechanism that allows two adult males to co-reside in the same group. I collected 21 months of behavioral data on 7 two-male groups of wild siamangs (Symphalangus syndactylus) in southern Sumatra (Indonesia) to test the hypothesis that dominance relationships regulate the interactions of adult male siamangs and ultimately facilitate multi-male social groups. A dominant male could clearly be identified in each dyad, based on a consistent direction of agonistic interactions, displacements and the maintenance of an advantageous position in the canopy. Males identified as dominant enjoyed greater social access to the resident female and monopolized copulations. These results suggest that gibbons possess the psycho-social flexibility to regulate intra-sexual aggression and live in multi-male social units under certain social conditions. I discuss the effects that relatedness between males and female choice have in determining this grouping pattern, and the role of male intolerance in the maintenance of primate mating systems. © 2015 Wiley Periodicals, Inc.

  1. The adaptor protein Cindr regulates JNK activity to maintain epithelial sheet integrity.

    PubMed

    Yasin, Hannah W R; van Rensburg, Samuel H; Feiler, Christina E; Johnson, Ruth I

    2016-02-15

    Epithelia are essential barrier tissues that must be appropriately maintained for their correct function. To achieve this a plethora of protein interactions regulate epithelial cell number, structure and adhesion, and differentiation. Here we show that Cindr (the Drosophila Cin85 and Cd2ap ortholog) is required to maintain epithelial integrity. Reducing Cindr triggered cell delamination and movement. Most delaminating cells died. These behaviors were consistent with JNK activation previously associated with loss of epithelial integrity in response to ectopic oncogene activity. We confirmed a novel interaction between Cindr and Drosophila JNK (dJNK), which when perturbed caused inappropriate JNK signaling. Genetically reducing JNK signaling activity suppressed the effects of reducing Cindr. Furthermore, ectopic JNK signaling phenocopied loss of Cindr and was partially rescued by concomitant cindr over-expression. Thus, correct Cindr-dJNK stoichiometry is essential to maintain epithelial integrity and disturbing this balance may contribute to the pathogenesis of disease states, including cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Nucleus Accumbens Dopamine Signaling Regulates Sexual Preference for Females in Male Mice.

    PubMed

    Beny-Shefer, Yamit; Zilkha, Noga; Lavi-Avnon, Yael; Bezalel, Nadav; Rogachev, Ilana; Brandis, Alexander; Dayan, Molly; Kimchi, Tali

    2017-12-12

    Sexual preference for the opposite sex is a fundamental behavior underlying reproductive success, but the neural mechanisms remain unclear. Here, we examined the role of dopamine signaling in the nucleus accumbens core (NAcc) in governing chemosensory-mediated preference for females in TrpC2 -/- and wild-type male mice. TrpC2 -/- males, deficient in VNO-mediated signaling, do not display mating or olfactory preference toward females. We found that, during social interaction with females, TrpC2 -/- males do not show increased NAcc dopamine levels, observed in wild-type males. Optogenetic stimulation of VTA-NAcc dopaminergic neurons in TrpC2 -/- males during exposure to a female promoted preference response to female pheromones and elevated copulatory behavior toward females. Additionally, we found that signaling through the D1 receptor in the NAcc is necessary for the olfactory preference for female-soiled bedding. Our study establishes a critical role for the mesolimbic dopaminergic system in governing pheromone-mediated responses and mate choice in male mice. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Membrane and Integrative Nuclear Fibroblastic Growth Factor Receptor (FGFR) Regulation of FGF-23*

    PubMed Central

    Han, Xiaobin; Xiao, Zhousheng; Quarles, L. Darryl

    2015-01-01

    Fibroblastic growth factor receptor 1 (FGFR1) signaling pathways are implicated in the regulation of FGF-23 gene transcription, but the molecular pathways remain poorly defined. We used low molecular weight (LMW, 18 kDa) FGF-2 and high molecular weight (HMW) FGF-2 isoforms, which, respectively, activate cell surface FGF receptors and intranuclear FGFR1, to determine the roles of membrane FGFRs and integrative nuclear FGFR1 signaling (INFS) in the regulation of FGF-23 gene transcription in osteoblasts. We found that LMW-FGF-2 induced NFAT and Ets1 binding to conserved cis-elements in the proximal FGF-23 promoter and stimulated FGF-23 promoter activity through PLCγ/calcineurin/NFAT and MAPK pathways in SaOS-2 and MC3T3-E1 osteoblasts. In contrast, HMW-FGF-2 stimulated FGF-23 promoter activity in osteoblasts through a cAMP-dependent binding of FGFR1 and cAMP-response element-binding protein (CREB) to a conserved cAMP response element (CRE) contiguous with the NFAT binding site in the FGF-23 promoter. Mutagenesis of the NFAT and CRE binding sites, respectively, inhibited the effects of LMW-FGF-2 and HMW-FGF-23 to stimulate FGF-23 promoter activity. FGF-2 activation of both membrane FGFRs and INFS-dependent FGFR1 pathways may provide a means to integrate systemic and local regulation of FGF-23 transcription under diverse physiological and pathological conditions. PMID:25752607

  4. Crosstalk between intracellular and extracellular signals regulating interneuron production, migration and integration into the cortex

    PubMed Central

    Peyre, Elise; Silva, Carla G.; Nguyen, Laurent

    2015-01-01

    During embryogenesis, cortical interneurons are generated by ventral progenitors located in the ganglionic eminences of the telencephalon. They travel along multiple tangential paths to populate the cortical wall. As they reach this structure they undergo intracortical dispersion to settle in their final destination. At the cellular level, migrating interneurons are highly polarized cells that extend and retract processes using dynamic remodeling of microtubule and actin cytoskeleton. Different levels of molecular regulation contribute to interneuron migration. These include: (1) Extrinsic guidance cues distributed along migratory streams that are sensed and integrated by migrating interneurons; (2) Intrinsic genetic programs driven by specific transcription factors that grant specification and set the timing of migration for different subtypes of interneurons; (3) Adhesion molecules and cytoskeletal elements/regulators that transduce molecular signalings into coherent movement. These levels of molecular regulation must be properly integrated by interneurons to allow their migration in the cortex. The aim of this review is to summarize our current knowledge of the interplay between microenvironmental signals and cell autonomous programs that drive cortical interneuron porduction, tangential migration, and intergration in the developing cerebral cortex. PMID:25926769

  5. The role of estrogens for male bone health.

    PubMed

    Ohlsson, Claes; Vandenput, Liesbeth

    2009-06-01

    Sex steroids are important for the growth and maintenance of both the female and the male skeleton. However, the relative contribution of androgens versus estrogens in the regulation of the male skeleton is unclear. Experiments using mice with inactivated sex steroid receptors demonstrated that both activation of the estrogen receptor (ER)alpha and activation of the androgen receptor result in a stimulatory effect on both the cortical and trabecular bone mass in males. ERbeta is of no importance for the skeleton in male mice while it modulates the ERalpha-action on bone in female mice. Previous in vitro studies suggest that the membrane G protein-coupled receptor GPR30 also might be a functional ER. Our in vivo analyses of GPR30-inactivated mice revealed no function of GPR30 for estrogen-mediated effects on bone mass but it is required for normal regulation of the growth plate and estrogen-mediated insulin-secretion. Recent clinical evidence suggests that a threshold exists for estrogen effects on bone in men: rates of bone loss and fracture risk seem to be the highest in men with estradiol levels below this threshold. Taken together, even though these findings do not exclude an important role for testosterone in male skeletal homeostasis, it is now well-established that estrogens are important regulators of bone health in men.

  6. Integrating HIV Prevention and Relationship Education for Young Same-Sex Male Couples: A Pilot Trial of the 2GETHER Intervention.

    PubMed

    Newcomb, Michael E; Macapagal, Kathryn R; Feinstein, Brian A; Bettin, Emily; Swann, Gregory; Whitton, Sarah W

    2017-08-01

    Young men who have sex with men are at high risk for HIV, and most new HIV infections occur in serious relationships. This pilot study assessed the feasibility, acceptability and preliminary efficacy of the 2GETHER couples-based HIV prevention and relationship education intervention for young same-sex male couples. We enrolled 57 young male couples (N = 114) into a four-session hybrid group and individual intervention. We assessed acceptability via post-session surveys and exit interviews, and we examined preliminary efficacy at a two week posttest. The vast majority of participants (93%) reported exclusively positive impressions of 2GETHER, and all components received high mean ratings. We observed decreases in HIV risk behavior, increases in information, motivation and behavioral skills related to HIV prevention, and improvement in relationship investment between pretest and posttest. Integrating relationship education and sexual health programming may be an effective way to reduce HIV transmissions in young male couples.

  7. Cloning and characterisation of two CTR1-like genes in Cucurbita pepo: regulation of their expression during male and female flower development.

    PubMed

    Manzano, Susana; Martínez, Cecilia; Gómez, Pedro; Garrido, Dolores; Jamilena, Manuel

    2010-12-01

    Ethylene is an essential regulator of flower development in Cucurbita pepo, controlling the sexual expression, and the differentiation and maturation of floral organs. To study the action mechanism of ethylene during the male and female flower development, we have identified two CTR1 homologues from C. pepo, CpCTR1 and CpCTR2, and analysed their expressions during female and male flower development and in response to external treatments with ethylene. CpCTR1 and CpCTR2 share a high homology with plant CTR1-like kinases, but differ from other related kinases such as the Arabidopsis EDR1 and the tomato LeCTR2. The C-terminal ends of both CpCTR1 and CpCTR2 have all the conserved motifs of Ser/Thr kinase domains, including the ATP-binding signature and the protein kinase active site consensus sequence, which suggests that CpCTR1 and CpCTR2 could have the same function as CTR1 in ethylene signalling. The transcripts of both genes were detected in different organs of the plant, including roots, leaves and shoots, but were mostly accumulated in mature flowers. During the development of male and female flowers, CpCTR1 and CpCTR2 expressions were concomitant with ethylene production, which indicates that both genes could be upregulated by ethylene, at least in flowers. Moreover, external treatments with ethylene, although did not alter the expression of these two genes in seedlings and leaves, were able to upregulate their expression in flowers. In the earlier stages of flower development, when ethylene production is very low, the expression of CpCTR1 and CpCTR2 is higher in male floral organs, which agrees with the role of these genes as negative regulators of ethylene signalling, and explain the lower ethylene sensitivity of male flowers in comparison with female flowers. The function of the upregulation of these two genes in later stages of female flower development, when the production of ethylene is also increased, is discussed.

  8. Regulation of centriolar satellite integrity and its physiology.

    PubMed

    Hori, Akiko; Toda, Takashi

    2017-01-01

    Centriolar satellites comprise cytoplasmic granules that are located around the centrosome. Their molecular identification was first reported more than a quarter of a century ago. These particles are not static in the cell but instead constantly move around the centrosome. Over the last decade, significant advances in their molecular compositions and biological functions have been achieved due to comprehensive proteomics and genomics, super-resolution microscopy analyses and elegant genetic manipulations. Centriolar satellites play pivotal roles in centrosome assembly and primary cilium formation through the delivery of centriolar/centrosomal components from the cytoplasm to the centrosome. Their importance is further underscored by the fact that mutations in genes encoding satellite components and regulators lead to various human disorders such as ciliopathies. Moreover, the most recent findings highlight dynamic structural remodelling in response to internal and external cues and unexpected positive feedback control that is exerted from the centrosome for centriolar satellite integrity.

  9. [Hormone regulation of male fertility].

    PubMed

    Anselmo, J G

    1975-01-01

    An innocuous, sure, reversible means of male fertility control which does not disturb the libido is being sought. 20 healthy volunteers from ages 20 to 36 participated, using a 2nd form of protection when necessary. 10 received implants of 60 mg testosterone equally divided into 3 tubes, and began oral ingestion of 100 mg weekly, divided into daily doses, of R2323 (13-ethyl-17-hydroxy-gonen 4,9,11, trien-3-one) until the sperm became ineffective. Then oral doses were given according to personal requirements from 50 to 25 mg. The 2nd series of 10 received no testosterone implants, but followed the same scheme for oral ingestion. All patients but 1 reduced their sperm count and 80% were low enough to consider the sperm inactive. For those who used the hormone treatment as the only protection against pregnancy, no pregnancy occurred. Of the 1st group, 2 had excessive weight gain, 3 felt their libido reduced, and 1 had pain in the nipples and 1 had pain in the hepatic region. Recuperation of normal sperm characteristics was slow, especially motility and vitality. The spermogram is so altered during treatment that any accidental pregnancy could result in a defective egg and serious complications. It should definitely be avoided.

  10. Inheritance of steroid-independent male sexual behavior in male offspring of B6D2F1 mice.

    PubMed

    McInnis, Christine M; Bonthuis, Paul J; Rissman, Emilie F; Park, Jin Ho

    2016-04-01

    The importance of gonadal steroids in modulating male sexual behavior is well established. Individual differences in male sexual behavior, independent of gonadal steroids, are prevalent across a wide range of species, including man. However, the genetic mechanisms underlying steroid-independent male sexual behavior are poorly understood. A high proportion of B6D2F1 hybrid male mice demonstrates steroid-independent male sexual behavior (identified as "maters"), providing a mouse model that opens up avenues of investigation into the mechanisms regulating male sexual behavior in the absence of gonadal hormones. Recent studies have revealed several proteins that play a significant factor in regulating steroid-independent male sexual behavior in B6D2F1 male mice, including amyloid precursor protein (APP), tau, and synaptophysin. The specific goals of our study were to determine whether steroid-independent male sexual behavior was a heritable trait by determining if it was dependent upon the behavioral phenotype of the B6D2F1 sire, and whether the differential expression of APP, tau, and synaptophysin in the medial preoptic area found in the B6D2F1 sires that did and did not mate after gonadectomy was similar to those found in their male offspring. After adult B6D2F1 male mice were bred with C57BL/6J female mice, they and their male offspring (BXB1) were orchidectomized and identified as either maters or "non-maters". A significant proportion of the BXB1 maters was sired only from B6D2F1 maters, indicating that the steroid-independent male sexual behavior behavioral phenotype of the B6D2F1 hybrid males, when crossed with C57BL/6J female mice, is inherited by their male offspring. Additionally, APP, tau, and synaptophysin were elevated in in the medial preoptic area in both the B6D2F1 and BXB1 maters relative to the B6D2F1 and BXB1 non-maters, respectively, suggesting a potential genetic mechanism for the inheritance of steroid-independent male sexual behavior. Copyright

  11. Inheritance of steroid-independent male sexual behavior in male offspring of B6D2F1 mice

    PubMed Central

    McInnis, Christine M.; Bonthuis, Paul J.; Rissman, Emilie F.; Park, Jin Ho

    2016-01-01

    The importance of gonadal steroids in modulating male sexual behavior is well established. Individual differences in male sexual behavior, independent of gonadal steroids, are prevalent across a wide range of species, including man. However, the genetic mechanisms underlying steroid-independent male sexual behavior are poorly understood. A high proportion of B6D2F1 hybrid male mice demonstrate steroid-independent male sexual behavior (identified as “maters”), providing a mouse model that opens up avenues of investigation into the mechanisms regulating male sexual behavior in the absence of gonadal hormones. Recent studies have revealed several proteins that play a significant factor in regulating steroid-independent male sexual behavior in B6D2F1 male mice, including amyloid precursor protein (APP), tau, and synaptophysin. The specific goals of our study were to determine whether steroid-independent male sexual behavior was a heritable trait by determining if it was dependent upon the behavioral phenotype of the B6D2F1 sire, and whether the differential expression of APP, tau, and synaptophysin in the medial preoptic area found in the B6D2F1 sires that did and did not mate after gonadectomy was similar to those found in their male offspring. After adult B6D2F1 male mice were bred with C57BL/6J female mice, they and their male offspring (BXB1) were orchidectomized and identified as either maters or “non-maters.” A significant proportion of the BXB1 maters were sired only from B6D2F1 maters, indicating that the steroid-independent male sexual behavior behavioral phenotype of the B6D2F1 hybrid males, when crossed with C57BL/6J female mice, is inherited by their male offspring. Additionally, APP, tau, and synaptophysin were elevated in in the medial preoptic area in both the B6D2F1 and BXB1 maters relative to the B6D2F1 and BXB1 non-maters, respectively, suggesting a potential genetic mechanism for the inheritance of steroid-independent male sexual behavior

  12. Integrative Analysis of DNA Methylation and Gene Expression Data Identifies EPAS1 as a Key Regulator of COPD

    PubMed Central

    Yoo, Seungyeul; Takikawa, Sachiko; Geraghty, Patrick; Argmann, Carmen; Campbell, Joshua; Lin, Luan; Huang, Tao; Tu, Zhidong; Feronjy, Robert; Spira, Avrum; Schadt, Eric E.; Powell, Charles A.; Zhu, Jun

    2015-01-01

    Chronic Obstructive Pulmonary Disease (COPD) is a complex disease. Genetic, epigenetic, and environmental factors are known to contribute to COPD risk and disease progression. Therefore we developed a systematic approach to identify key regulators of COPD that integrates genome-wide DNA methylation, gene expression, and phenotype data in lung tissue from COPD and control samples. Our integrative analysis identified 126 key regulators of COPD. We identified EPAS1 as the only key regulator whose downstream genes significantly overlapped with multiple genes sets associated with COPD disease severity. EPAS1 is distinct in comparison with other key regulators in terms of methylation profile and downstream target genes. Genes predicted to be regulated by EPAS1 were enriched for biological processes including signaling, cell communications, and system development. We confirmed that EPAS1 protein levels are lower in human COPD lung tissue compared to non-disease controls and that Epas1 gene expression is reduced in mice chronically exposed to cigarette smoke. As EPAS1 downstream genes were significantly enriched for hypoxia responsive genes in endothelial cells, we tested EPAS1 function in human endothelial cells. EPAS1 knockdown by siRNA in endothelial cells impacted genes that significantly overlapped with EPAS1 downstream genes in lung tissue including hypoxia responsive genes, and genes associated with emphysema severity. Our first integrative analysis of genome-wide DNA methylation and gene expression profiles illustrates that not only does DNA methylation play a ‘causal’ role in the molecular pathophysiology of COPD, but it can be leveraged to directly identify novel key mediators of this pathophysiology. PMID:25569234

  13. Integrative analysis of DNA methylation and gene expression data identifies EPAS1 as a key regulator of COPD.

    PubMed

    Yoo, Seungyeul; Takikawa, Sachiko; Geraghty, Patrick; Argmann, Carmen; Campbell, Joshua; Lin, Luan; Huang, Tao; Tu, Zhidong; Foronjy, Robert F; Feronjy, Robert; Spira, Avrum; Schadt, Eric E; Powell, Charles A; Zhu, Jun

    2015-01-01

    Chronic Obstructive Pulmonary Disease (COPD) is a complex disease. Genetic, epigenetic, and environmental factors are known to contribute to COPD risk and disease progression. Therefore we developed a systematic approach to identify key regulators of COPD that integrates genome-wide DNA methylation, gene expression, and phenotype data in lung tissue from COPD and control samples. Our integrative analysis identified 126 key regulators of COPD. We identified EPAS1 as the only key regulator whose downstream genes significantly overlapped with multiple genes sets associated with COPD disease severity. EPAS1 is distinct in comparison with other key regulators in terms of methylation profile and downstream target genes. Genes predicted to be regulated by EPAS1 were enriched for biological processes including signaling, cell communications, and system development. We confirmed that EPAS1 protein levels are lower in human COPD lung tissue compared to non-disease controls and that Epas1 gene expression is reduced in mice chronically exposed to cigarette smoke. As EPAS1 downstream genes were significantly enriched for hypoxia responsive genes in endothelial cells, we tested EPAS1 function in human endothelial cells. EPAS1 knockdown by siRNA in endothelial cells impacted genes that significantly overlapped with EPAS1 downstream genes in lung tissue including hypoxia responsive genes, and genes associated with emphysema severity. Our first integrative analysis of genome-wide DNA methylation and gene expression profiles illustrates that not only does DNA methylation play a 'causal' role in the molecular pathophysiology of COPD, but it can be leveraged to directly identify novel key mediators of this pathophysiology.

  14. Serum relaxin concentrations and reproduction in male bonnethead sharks, Sphyrna tiburo.

    PubMed

    Gelsleichter, James; Steinetz, Bernard G; Manire, Charles A; Ange, Cristal

    2003-06-01

    Relaxin is a 6-kd polypeptide hormone that is responsible for regulating several reproductive processes in female vertebrates, but its role in male reproduction remains unclear. To aid in clarifying this role, the objective of the present study was to investigate changes in endogenous relaxin levels associated with reproductive events in male elasmobranchs, which represent one of only three vertebrate groups known to possess this hormone. Serum relaxin concentrations were measured in 27 immature and 66 mature male bonnethead sharks (Sphyrna tiburo), a species with a well-characterized, seasonal reproductive cycle. Temporal changes in serum relaxin concentrations of immature male S. tiburo were not observed. In contrast, a temporal cycle in serum relaxin concentrations of mature male S. tiburo was observed in individuals from two sampling locations. Significant increases (P<0.05) in serum relaxin concentrations of mature male S. tiburo from both collection sites occurred during late spermatogenesis and the mating period, two critical stages of the reproductive cycle. The results from this study suggest that relaxin may play an important role in regulating semen quality, or other aspects of reproduction in male sharks. This is the first study to demonstrate a temporal pattern in endogenous serum Rlx concentrations associated with reproductive events in feral vertebrates. As such, it strengthens earlier hypotheses that suggested a role for this hormone in regulating male vertebrate fertility and copulatory success.

  15. Pheromone responsiveness threshold depends on temporal integration by antennal lobe projection neurons

    PubMed Central

    Tabuchi, Masashi; Sakurai, Takeshi; Mitsuno, Hidefumi; Namiki, Shigehiro; Minegishi, Ryo; Shiotsuki, Takahiro; Uchino, Keiro; Sezutsu, Hideki; Tamura, Toshiki; Haupt, Stephan Shuichi; Nakatani, Kei; Kanzaki, Ryohei

    2013-01-01

    The olfactory system of male moths has an extreme sensitivity with the capability to detect and recognize conspecific pheromones dispersed and greatly diluted in the air. Just 170 molecules of the silkmoth (Bombyx mori) sex pheromone bombykol are sufficient to induce sexual behavior in the male. However, it is still unclear how the sensitivity of olfactory receptor neurons (ORNs) is relayed through the brain to generate high behavioral responsiveness. Here, we show that ORN activity that is subthreshold in terms of behavior can be amplified to suprathreshold levels by temporal integration in antennal lobe projection neurons (PNs) if occurring within a specific time window. To control ORN inputs with high temporal resolution, channelrhodopsin-2 was genetically introduced into bombykol-responsive ORNs. Temporal integration in PNs was only observed for weak inputs, but not for strong inputs. Pharmacological dissection revealed that GABAergic mechanisms inhibit temporal integration of strong inputs, showing that GABA signaling regulates PN responses in a stimulus-dependent fashion. Our results show that boosting of the PNs’ responses by temporal integration of olfactory information occurs specifically near the behavioral threshold, effectively defining the lower bound for behavioral responsiveness. PMID:24006366

  16. Transcript levels of ten caste-related genes in adult diploid males of Melipona quadrifasciata (Hymenoptera, Apidae) - A comparison with haploid males, queens and workers

    PubMed Central

    Borges, Andreia A.; Humann, Fernanda C.; Oliveira Campos, Lucio A.; Tavares, Mara G.; Hartfelder, Klaus

    2011-01-01

    In Hymenoptera, homozygosity at the sex locus results in the production of diploid males. In social species, these pose a double burden by having low fitness and drawing resources normally spent for increasing the work force of a colony. Yet, diploid males are of academic interest as they can elucidate effects of ploidy (normal males are haploid, whereas the female castes, the queens and workers, are diploid) on morphology and life history. Herein we investigated expression levels of ten caste-related genes in the stingless bee Melipona quadrifasciata, comparing newly emerged and 5-day-old diploid males with haploid males, queens and workers. In diploid males, transcript levels for dunce and paramyosin were increased during the first five days of adult life, while those for diacylglycerol kinase and the transcriptional co-repressor groucho diminished. Two general trends were apparent, (i) gene expression patterns in diploid males were overall more similar to haploid ones and workers than to queens, and (ii) in queens and workers, more genes were up-regulated after emergence until day five, whereas in diploid and especially so in haploid males more genes were down-regulated. This difference between the sexes may be related to longevity, which is much longer in females than in males. PMID:22215977

  17. Transcript levels of ten caste-related genes in adult diploid males of Melipona quadrifasciata (Hymenoptera, Apidae) - A comparison with haploid males, queens and workers.

    PubMed

    Borges, Andreia A; Humann, Fernanda C; Oliveira Campos, Lucio A; Tavares, Mara G; Hartfelder, Klaus

    2011-10-01

    In Hymenoptera, homozygosity at the sex locus results in the production of diploid males. In social species, these pose a double burden by having low fitness and drawing resources normally spent for increasing the work force of a colony. Yet, diploid males are of academic interest as they can elucidate effects of ploidy (normal males are haploid, whereas the female castes, the queens and workers, are diploid) on morphology and life history. Herein we investigated expression levels of ten caste-related genes in the stingless bee Melipona quadrifasciata, comparing newly emerged and 5-day-old diploid males with haploid males, queens and workers. In diploid males, transcript levels for dunce and paramyosin were increased during the first five days of adult life, while those for diacylglycerol kinase and the transcriptional co-repressor groucho diminished. Two general trends were apparent, (i) gene expression patterns in diploid males were overall more similar to haploid ones and workers than to queens, and (ii) in queens and workers, more genes were up-regulated after emergence until day five, whereas in diploid and especially so in haploid males more genes were down-regulated. This difference between the sexes may be related to longevity, which is much longer in females than in males.

  18. [Environmental factors and male fertility].

    PubMed

    Köhn, F-M; Schuppe, H C

    2016-07-01

    The identification of potential environmental hazards may have clinical relevance for diagnosis of male infertility. Knowledge about these factors will improve prevention of fertility disorders. Apart from drugs or factors related to lifestyle such as alcohol and tobacco smoke, various environmental and occupational agents, both chemical and physical, may impair male reproductive functions. With regard to the complex regulation of the male reproductive system, the available information concerning single exogenous factors and their mechanisms of action in humans is limited. This is also due to the fact that extrapolation of results obtained from experimental animal studies remains difficult. Nevertheless, the assessment of relevant exposures to reproductive toxicants should be carefully evaluated during diagnostic procedures of andrological patients.

  19. Obesogens and male fertility.

    PubMed

    Cardoso, A M; Alves, M G; Mathur, P P; Oliveira, P F; Cavaco, J E; Rato, L

    2017-01-01

    In the last decades, several studies evidenced a decrease in male fertility in developed countries. Although the aetiology of this trend in male reproductive health remains a matter of debate, environmental compounds that predispose to weight gain, namely obesogens, are appointed as contributors because of their action as endocrine disruptors. Obesogens favour adipogenesis by an imbalance of metabolic processes and can be found virtually everywhere. These compounds easily accumulate in tissues with high lipid content. Obesogens change the functioning of male reproductive axis, and, consequently, the testicular physiology and metabolism that are pivotal for spermatogenesis. The disruption of these tightly regulated metabolic pathways leads to adverse reproductive outcomes. Notably, adverse effects of obesogens may also promote disturbances in the metabolic performance of the following generations, through epigenetic modifications passed by male gametes. Thus, unveiling the molecular pathways by which obesogens induce toxicity that may end up in epigenetic modifications is imperative. Otherwise, a transgenerational susceptibility to metabolic diseases may be favoured. We present an up-to-date overview of the impact of obesogens on testicular physiology, with a particular focus on testicular metabolism. We also address the effects of obesogens on male reproductive parameters and the subsequent consequences for male fertility. © 2016 World Obesity Federation.

  20. Levels of Leydig cell autophagy regulate the fertility of male naked mole-rats.

    PubMed

    Yang, Wenjing; Li, Li; Huang, Xiaofeng; Kan, Guanghan; Lin, Lifang; Cheng, Jishuai; Xu, Chen; Sun, Wei; Cong, Wei; Zhao, Shanmin; Cui, Shufang

    2017-11-17

    Fertility is abolished in nonbreeding males in colonies of natal naked mole-rats (NMRs). Although spermatogenesis occurs in both breeding and nonbreeding male NMRs, the mechanisms underlying the differences in fertility between breeders and nonbreeders remain unexplored. In this study, a significant decrease in autophagy was observed in Leydig cells of the testis from nonbreeding male NMRs. This alteration was visualised as a significant decrease in the levels of autophagy-related gene 7 (Atg7), Atg5, microtubule-associated protein 1A/B light chain 3 (LC3-II/I) and the number of autophagosomes and an increase in P62 levels using Western blotting analyses. Furthermore, monodansylcadaverine (MDC) staining and Western blot analyses revealed that testosterone production decreased in nonbreeding male NMR Leydig cells, this decrease was associated with a reduction in autophagy. Primary Leydig cells from breeding and nonbreeding male NMRs were processed to investigate the effect of an autophagy inhibitor (3-MA, 3-methyladenine) or an autophagy activator (rapamycin) on testosterone production. Rapamycin induced an increase in testosterone production in NMR Leydig cells, whereas 3-MA had the opposite effect. Consequently, spermatogenesis, the weight of the testis, and androgen levels were dramatically reduced in nonbreeding male NMRs. While rapamycin treatment restored the fertility of nonbreeding male NMRs. Based on these results, inadequate autophagy correlates with a decrease in steroid production in nonbreeding male NMR Leydig cells, which may ultimately influence the spermatogenesis and fertilities of these animals.

  1. Renal hypertension prevents run training modification of cardiomyocyte diastolic Ca2+ regulation in male rats.

    PubMed

    Palmer, B M; Lynch, J M; Snyder, S M; Moore, R L

    2001-06-01

    The combined effects of endurance run training and renal hypertension on cytosolic Ca2+ concentration ([Ca2+]c) dynamics and Na+-dependent Ca2+ regulation in rat left ventricular cardiomyocytes were examined. Male Fischer 344 rats underwent stenosis of the left renal artery [hypertensive (Ht), n = 18] or a sham operation [normotensive (Nt), n = 20]. One-half of the rats from each group were treadmill trained for >16 wk. Cardiomyocyte fura 2 fluorescence ratio transients were recorded for 7 min during electrical pacing at 0.5 Hz, 2 mM extracellular Ca2+ concentration, and 29 degrees C. The rate of [Ca2+]c decline was not changed by run training in the Nt group but was reduced in the Ht group. At 7 min, cardiomyocytes were exposed to 10 mM caffeine in the absence of Na+ and Ca2+, which triggered sarcoplasmic reticular Ca2+ release and suppressed Ca2+ efflux via Na+/Ca2+ exchanger. External Na+ was then added, and Na+-dependent Ca2+ efflux rate was recorded. Treadmill training significantly enhanced Na+-dependent Ca2+ efflux rate under these conditions in the Nt group but not in the Ht group. These data provide evidence that renal hypertension prevents the normal run training-induced modifications in diastolic [Ca2+]c regulation mechanisms, including Na+/Ca2+ exchanger.

  2. Emotion malleability beliefs, emotion regulation, and psychopathology: Integrating affective and clinical science.

    PubMed

    Kneeland, Elizabeth T; Dovidio, John F; Joormann, Jutta; Clark, Margaret S

    2016-04-01

    Beliefs that individuals hold about whether emotions are malleable or fixed, also referred to as emotion malleability beliefs, may play a crucial role in individuals' emotional experiences and their engagement in changing their emotions. The current review integrates affective science and clinical science perspectives to provide a comprehensive review of how emotion malleability beliefs relate to emotionality, emotion regulation, and specific clinical disorders and treatment. Specifically, we discuss how holding more malleable views of emotion could be associated with more active emotion regulation efforts, greater motivation to engage in active regulatory efforts, more effort expended regulating emotions, and lower levels of pathological distress. In addition, we explain how extending emotion malleability beliefs into the clinical domain can complement and extend current conceptualizations of major depressive disorder, social anxiety disorder, and generalized anxiety disorder. This may prove important given the increasingly central role emotion dysregulation has been given in conceptualization and intervention for these psychiatric conditions. Additionally, discussion focuses on how emotion beliefs could be more explicitly addressed in existing cognitive therapies. Promising future directions for research are identified throughout the review. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Sex-Related Neuroanatomical Basis of Emotion Regulation Ability

    PubMed Central

    Li, Jingguang; Huang, Lijie; Wang, Xu; Song, Yiying; Liu, Jia

    2014-01-01

    Behavioral research has demonstrated that males have a higher capability of regulating their own and others' emotions than females; however, little is known about the sex-specific brain mechanisms involved in emotion regulation ability. In the present study, we used voxel-based morphometry to investigate the neural basis underlying emotion regulation ability in a large sample of young adults. Assessment of emotion regulation ability was performed using the Wong and Law Emotional Intelligence Scale. As expected, males significantly scored higher in emotion regulation ability than females did. More importantly, we found the sex differences in the neuroanatomical basis of emotion regulation ability. Males showed a stronger positive relation between emotion regulation ability and regional gray matter volume (rGMV) in the right dorsolateral prefrontal cortex. In contrast, females demonstrated a stronger positive relation between emotion regulation ability and rGMV in an anatomical cluster that extends from the left brainstem to the left hippocampus, the left amygdala and the insular cortex. The present study provides the first empirical evidence regarding the sex-linked neuroanatomical correlates of emotion regulation ability. These findings may help understand why there is a higher prevalence of affective disorders in females and maladaptive behaviors in males. PMID:24835267

  4. Sex-related neuroanatomical basis of emotion regulation ability.

    PubMed

    Kong, Feng; Zhen, Zonglei; Li, Jingguang; Huang, Lijie; Wang, Xu; Song, Yiying; Liu, Jia

    2014-01-01

    Behavioral research has demonstrated that males have a higher capability of regulating their own and others' emotions than females; however, little is known about the sex-specific brain mechanisms involved in emotion regulation ability. In the present study, we used voxel-based morphometry to investigate the neural basis underlying emotion regulation ability in a large sample of young adults. Assessment of emotion regulation ability was performed using the Wong and Law Emotional Intelligence Scale. As expected, males significantly scored higher in emotion regulation ability than females did. More importantly, we found the sex differences in the neuroanatomical basis of emotion regulation ability. Males showed a stronger positive relation between emotion regulation ability and regional gray matter volume (rGMV) in the right dorsolateral prefrontal cortex. In contrast, females demonstrated a stronger positive relation between emotion regulation ability and rGMV in an anatomical cluster that extends from the left brainstem to the left hippocampus, the left amygdala and the insular cortex. The present study provides the first empirical evidence regarding the sex-linked neuroanatomical correlates of emotion regulation ability. These findings may help understand why there is a higher prevalence of affective disorders in females and maladaptive behaviors in males.

  5. Male reprotoxicity and endocrine disruption

    PubMed Central

    Campion, Sarah; Catlin, Natasha; Heger, Nicholas; McDonnell, Elizabeth V.; Pacheco, Sara E.; Saffarini, Camelia; Sandrof, Moses A.; Boekelheide, Kim

    2013-01-01

    Mammalian reproductive tract development is a tightly regulated process that can be disrupted following exposure to drugs, toxicants, endocrine disrupting chemicals or other compounds via alterations to gene and protein expression or epigenetic regulation. Indeed, the impacts of developmental exposure to certain toxicants may not be fully realized until puberty or adulthood when the reproductive tract becomes sexually mature and altered functionality is manifested. Exposures that occur later in life, once development is complete, can also disrupt the intricate hormonal and paracrine interactions responsible for adult functions, such as spermatogenesis. In this chapter, the biology and toxicology of the male reproductive tract is explored, proceeding through the various life stages including in utero development, puberty, adulthood and senescence. Special attention is given to the discussion of endocrine disrupting chemicals, chemical mixtures, low dose effects, transgenerational effects, and potential exposure-related causes of male reproductive tract cancers. PMID:22945574

  6. Pedagogical Work, Stress Regulation and Work-Related Well-Being among Early Childhood Professionals in Integrated Special Day-Care Groups

    ERIC Educational Resources Information Center

    Nislin, Mari A.; Sajaniemi, Nina K.; Sims, Margaret; Suhonen, Eira; Maldonado Montero, Enrique F.; Hirvonen, Ari; Hyttinen, Sirpa

    2016-01-01

    The aim of this study was to investigate the relationship between early childhood professionals' (ECPs) stress regulation (using salivary cortisol and alpha-amylase [AA] measurements), work engagement and the quality of their pedagogical work in integrated special day-care groups. Participants were 89 ECPs from 21 integrated special day-care…

  7. Conserved and Differential Effects of Dietary Energy Intake on the Hippocampal Transcriptomes of Females and Males

    PubMed Central

    Martin, Bronwen; Pearson, Michele; Brenneman, Randall; Golden, Erin; Keselman, Alex; Iyun, Titilola; Carlson, Olga D.; Egan, Josephine M.; Becker, Kevin G.; Wood, William; Prabhu, Vinayakumar; de Cabo, Rafael

    2008-01-01

    The level of dietary energy intake influences metabolism, reproductive function, the development of age-related diseases, and even cognitive behavior. Because males and females typically play different roles in the acquisition and allocation of energy resources, we reasoned that dietary energy intake might differentially affect the brains of males and females at the molecular level. To test this hypothesis, we performed a gene array analysis of the hippocampus in male and female rats that had been maintained for 6 months on either ad libitum (control), 20% caloric restriction (CR), 40% CR, intermittent fasting (IF) or high fat/high glucose (HFG) diets. These diets resulted in expected changes in body weight, and circulating levels of glucose, insulin and leptin. However, the CR diets significantly increased the size of the hippocampus of females, but not males. Multiple genes were regulated coherently in response to energy restriction diets in females, but not in males. Functional physiological pathway analyses showed that the 20% CR diet down-regulated genes involved in glycolysis and mitochondrial ATP production in males, whereas these metabolic pathways were up-regulated in females. The 40% CR diet up-regulated genes involved in glycolysis, protein deacetylation, PGC-1α and mTor pathways in both sexes. IF down-regulated many genes in males including those involved in protein degradation and apoptosis, but up-regulated many genes in females including those involved in cellular energy metabolism, cell cycle regulation and protein deacetylation. Genes involved in energy metabolism, oxidative stress responses and cell death were affected by the HFG diet in both males and females. The gender-specific molecular genetic responses of hippocampal cells to variations in dietary energy intake identified in this study may mediate differential behavioral responses of males and females to differences in energy availability. PMID:18545695

  8. [Dialectical Behavioral Therapy for Male Adolescents with Borderline Symptomatology].

    PubMed

    Heider, Jens; Fleck, Anna; Peteler, Christina; Anker, Sabine; Lieb, Susanne; Behrens, Michael; Schröder, Annette; In-Albon, Tina; Brünger, Michael

    2017-02-01

    Dialectical Behavioral Therapy for Male Adolescents with Borderline Symptomatology The efficacy of Dialectical Behavior Therapy for adolescents (DBT-A) in patients with borderline symptomatology has mainly been shown in female adolescents. However, male adolescents with borderline symptoms are characterized by more aggressive, disruptive, and antisocial behavior. Therefore, the efficacy of the DBT-A has to be investigated in male adolescents. The DBT-A manual was adopted for male adolescents in an inpatient setting. The program has been investigated using a pre-post design in seven male adolescents (on average 14 years of age) with an average of five borderline symptoms according to DSM-IV. Criteria for outcome are symptoms of psychopathology, emotion regulation, aggressive, and self-injurious behavior. After treatment a reduction in aggressive behavior (pre-post effect size d = 1.18) and an improvement in adaptive emotion regulation (d = 0.65) were shown. No improvement could be shown in general symptoms of psychopathology (d = 0.02). The results of these case studies of DBT-A in male adolescents are promising. However, further RCTs with larger sample sizes and a control group will be required.

  9. Gender-disturbed males.

    PubMed

    Levine, S B

    1993-01-01

    Adolescent and adult cross-dressing or "transvestism" is the most common antecedent behavioral pattern among those who request sex reassignment surgery. Transvestites are actually a diverse group of men who differ in their gender identities, orientation, and intention. They do, however, have in common a soothing image of themselves as women. Because of this, whether cross-dressing occurs among masculine or feminine males or heterosexuals, homosexuals, bisexuals, or asexuals, or among those with paraphilia, the behavior should be considered the expression of their consciously felt femininity. The confusing differences among cross-dressing males may be explained by their diversity along three dimensions: 1) the ambition for heterosexual intercourse; 2) the natural history of their sexual arousal to female clothing; 3) their current capacity to integrate their masculine and feminine strivings into separate compartments. When cross-dressers give up all vestiges of male gender role behaviors and successfully live and work full time as women, the appropriate descriptive term for them becomes "transsexual."

  10. Integrated pathway-based transcription regulation network mining and visualization based on gene expression profiles.

    PubMed

    Kibinge, Nelson; Ono, Naoaki; Horie, Masafumi; Sato, Tetsuo; Sugiura, Tadao; Altaf-Ul-Amin, Md; Saito, Akira; Kanaya, Shigehiko

    2016-06-01

    Conventionally, workflows examining transcription regulation networks from gene expression data involve distinct analytical steps. There is a need for pipelines that unify data mining and inference deduction into a singular framework to enhance interpretation and hypotheses generation. We propose a workflow that merges network construction with gene expression data mining focusing on regulation processes in the context of transcription factor driven gene regulation. The pipeline implements pathway-based modularization of expression profiles into functional units to improve biological interpretation. The integrated workflow was implemented as a web application software (TransReguloNet) with functions that enable pathway visualization and comparison of transcription factor activity between sample conditions defined in the experimental design. The pipeline merges differential expression, network construction, pathway-based abstraction, clustering and visualization. The framework was applied in analysis of actual expression datasets related to lung, breast and prostrate cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. A triallelic genetic male sterility locus in Brassica napus: an integrative strategy for its physical mapping and possible local chromosome evolution around it

    PubMed Central

    Lu, Wei; Liu, Jun; Xin, Qiang; Wan, Lili; Hong, Dengfeng; Yang, Guangsheng

    2013-01-01

    Background and Aims Spontaneous male sterility is an advantageous trait for both constructing efficient pollination control systems and for understanding the developmental process of the male reproductive unit in many crops. A triallelic genetic male-sterile locus (BnMs5) has been identified in Brassica napus; however, its complicated genome structure has greatly hampered the isolation of this locus. The aim of this study was to physically map BnMs5 through an integrated map-based cloning strategy and analyse the local chromosomal evolution around BnMs5. Methods A large F2 population was used to integrate the existing genetic maps around BnMs5. A map-based cloning strategy in combination with comparative mapping among B. napus, Arabidopsis, Brassica rapa and Brassica oleracea was employed to facilitate the identification of a target bacterial artificial chromosome (BAC) clone covering the BnMs5 locus. The genomic sequences from the Brassica species were analysed to reveal the regional chromosomal evolution around BnMs5. Key Results BnMs5 was finally delimited to a 0·3-cM genetic fragment from an integrated local genetic map, and was anchored on the B. napus A8 chromosome. Screening of a B. napus BAC clone library and identification of the positive clones validated that JBnB034L06 was the target BAC clone. The closest flanking markers restrict BnMs5 to a 21-kb region on JBnB034L06 containing six predicted functional genes. Good collinearity relationship around BnMs5 between several Brassica species was observed, while violent chromosomal evolutionary events including insertions/deletions, duplications and single nucleotide mutations were also found to have extensively occurred during their divergence. Conclusions This work represents major progress towards the molecular cloning of BnMs5, as well as presenting a powerful, integrative method to mapping loci in plants with complex genomic architecture, such as the amphidiploid B. napus. PMID:23243189

  12. Evolutionary insights into the regulation of courtship behavior in male amphibians and reptiles.

    PubMed

    Woolley, Sarah C; Sakata, Jon T; Crews, David

    2004-11-15

    Comparative studies of species differences and similarities in the regulation of courtship behavior afford an understanding of evolutionary pressures and constraints shaping reproductive processes and the relative contributions of hormonal, genetic, and ecological factors. Here, we review species differences and similarities in the control of courtship and copulatory behaviors in male amphibians and reptiles, focusing on the role of sex steroid hormones, the neurohormone arginine vasotocin (AVT), and catecholamines. We discuss species differences in the sensory modalities used during courtship and in the neural correlates of these differences, as well as the value of particular model systems for neural evolution studies with regard to reproductive processes. For example, in some genera of amphibians (e.g., Ambystoma) and reptiles (e.g., Cnemidophorus), interspecific hybridizations occur, making it possible to compare the ancestral with the descendant species, and these systems provide a window into the process of behavioral and neural evolution as well as the effect of genome size. Though our understanding of the hormonal and neural correlates of mating behavior in a variety of amphibian and reptilian species has advanced substantially, more studies that manipulate hormone or neurotransmitter systems are required to assess the functions of these systems.

  13. An Integrated Cell Purification and Genomics Strategy Reveals Multiple Regulators of Pancreas Development

    PubMed Central

    Benitez, Cecil M.; Qu, Kun; Sugiyama, Takuya; Pauerstein, Philip T.; Liu, Yinghua; Tsai, Jennifer; Gu, Xueying; Ghodasara, Amar; Arda, H. Efsun; Zhang, Jiajing; Dekker, Joseph D.; Tucker, Haley O.; Chang, Howard Y.; Kim, Seung K.

    2014-01-01

    The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus. PMID:25330008

  14. Vitamin D and male reproductive system.

    PubMed

    Costanzo, Pablo R; Knoblovits, Pablo

    2016-12-01

    Vitamin D deficiency is a highly prevalent worldwide condition and affects people of all ages. The most important role of vitamin D is the regulation of intestinal calcium absorption and metabolism of calcium and phosphorus to maintain muscle and bone homeostasis. Furthermore, in recent years it has been discovered that the vitamin D receptor (VDR) is widely distributed in many organs and tissues where vitamin D can perform other actions that include the modulation of the immune response, insulin secretion, anti-proliferative effect on cells of vascular smooth muscle, modulation of the renin-angiotensin-aldosterone system and regulates cell growth in several organs. The VDR is widely distributed in the male reproductive system. Vitamin D induces changes in the spermatozoa's calcium and cholesterol content and in protein phosphorylation to tyrosine/threonine residues. These changes could be involved in sperm capacitation. Vitamin D seems to regulate aromatase expression in different tissues. Studies analyzing seasonal variations of sex steroids in male populations yield conflicting results. This is probably due to the wide heterogeneity of the populations included according to age, systemic diseases and obesity.

  15. MECHANISMS OF MALE REPRODUCTIVE TOXICITY: BED, BATH AND BEYOND

    EPA Science Inventory

    Male reproductive function depends upon the integration of a great number of highly complex biological processes and their endocrine support. Therefore it is not surprising that male reproductive health can be impaired by exposures to drugs and environmental toxicants that impact...

  16. Differential neonatal imprinting and regulation by estrogen of estrogen receptor subtypes alpha and beta and of the truncated estrogen receptor product (TERP-1) mRNA expression in the male rat pituitary.

    PubMed

    Tena-Sempere, M; Barreiro, M L; González, L C; Pinilla, L; Aguilar, E

    2001-11-01

    Two distinct nuclear estrogen receptors (ERs) have been identified, the classical one, renamed ERalpha, and the more recently cloned ERbeta. In a variety of tissues, gene expression of both receptor subtypes results in the generation of multiple transcripts encoding the full-length as well as several alternately spliced isoforms. In the rat pituitary, a truncated, tissue-specific variant of ERalpha, called TERP-1, has been identified and found able to modulate ERalpha and ERbeta activity. So far, its pattern of expression and hormonal regulation have been mostly studied in females. The present study was designed to analyze the pattern of expression of TERP-1 mRNA in the male rat pituitary at different stages of postnatal development, and to evaluate the impact of neonatal imprinting and estrogen treatment upon TERP-1 expression in the male pituitary. Assessment of TERP-1 mRNA levels by semi-quantitative RT-PCR, using a variant-specific primer pair, revealed that TERP-1 is also expressed in the male rat pituitary. Relative mRNA expression levels changed markedly during postnatal development, with moderate expression of the TERP-1 transcript at birth, barely detectable levels during the infantile-prepubertal period, and maximal values in adulthood. Expression of TERP-1 was sensitive to neonatal estrogen exposure, which resulted in a significant, persistent increase in mRNA levels from the infantile period until puberty. This phenomenon was not mimicked by neonatal blockade of endogenous GnRH. In addition, estrogen was able to acutely up-regulate pituitary TERP-1 mRNA expression levels in prepubertal (30-day-old) and adult (75-day-old) males. Interestingly, neonatal imprinting as well as acute estrogen treatment resulted in opposite effects on TERP-1 and full-length ERalpha and ERbeta transcripts, the latter being decreased under both conditions. In conclusion, our data indicate that TERP-1 mRNA is expressed in a developmentally regulated manner in the male rat

  17. Volition Completes the Puzzle: Development and Evaluation of an Integrative Trait Model of Self-Regulated Learning

    ERIC Educational Resources Information Center

    Dörrenbächer, Laura; Perels, Franziska

    2015-01-01

    Most self-regulated learning theories are imbedded within a social-cognitive framework and comprise cognitive, metacognitive and motivational components. Nevertheless, these theories partly neglect volition, which is necessary for implementing learning intentions. Therefore, the present study is frontline as it aimed to integrate volition within a…

  18. Sex-related differences in neural activity during emotion regulation.

    PubMed

    Mak, Amanda K Y; Hu, Zhi-guo; Zhang, John X X; Xiao, Zhuangwei; Lee, Tatia M C

    2009-11-01

    The sex disparity in the development of depression has long been an important research topic, but the sex-related differences in neural activity during emotion regulation have been less thoroughly studied. It was hypothesized that, during the regulation of emotion, there would be more activation in the prefrontal regions implicated in cognitive processing for males, while there would be more activation in the prefrontal regions implicated in affective processing for females. This fMRI study recruited 12 females and 12 males who were required to view or to regulate the negative and positive emotion induced by some emotion-arousing pictures. During the regulation of negative emotion, both males and females had stronger activation in the left anterior cingulate gyrus, but males showed more activation in the prefrontal regions in general, including the left dorsolateral and lateral orbitofrontal gyrus as well as the right anterior cingulate gyrus, while females only showed stronger activation in the left medial orbitofrontal gyrus. For the regulation of positive emotion, both males and females showed stronger activation in the left dorsomedial prefrontal gyrus, but males were found to also have stronger activity in the left lateral orbitofrontal gyrus. It was concluded that there are common as well as sex-specific sets of brain regions involved in regulating negative and positive emotion, and the findings may have significant implications for females' vulnerability to developing depression.

  19. Cocaine-and-Amphetamine-Regulated-Transcript (CART) peptide attenuates dopamine- and cocaine-mediated locomotor activity in both male and female rats: lack of sex differences

    PubMed Central

    Job, Martin O.; Perry, JoAnna; Shen, Li L.; Kuhar, Michael J.

    2014-01-01

    Cocaine-and-Amphetamine Regulated Transcript peptide (CART peptide) is known for having an inhibitory effect on dopamine (DA)- and cocaine-mediated actions and is postulated to be a homeostatic, regulatory factor in the nucleus accumbens (NAc). Some sex differences in cocaine-mediated LMA and in the expression and function of CART peptide have been reported. However, it is not known if the inhibitory effect of CART peptide on cocaine-mediated locomotor activity (LMA) is sexually dimorphic. In this study, the effect of CART 55-102 on LMA due to intra-NAc DA and i.p. cocaine were determined in male and female Sprague-Dawley rats. The results show that CART 55-102 blunted or reduced both the DA- and cocaine-induced LMA in both males and females. In conclusion, CART peptide is effective in blunting DA- and cocaine-mediated LMA in both males and females. PMID:24630272

  20. Research on regulating technique of material flow for 2-person and 30-day integrated CELSS test

    NASA Astrophysics Data System (ADS)

    Guo, Shuangsheng; Dong, Wenping; Ai, Weidang; Feng, Hongqi; Tang, Yongkang; Huang, Zhide; Shen, Yunze; Ren, Jin; Qin, Lifeng; Zeng, Gu; Zhang, Lihong; Zhu, Jingtao; Fei, Jinxue; Xu, Guoxin

    2014-07-01

    A man-plant integration test was processed using the CELSS integration experiment platform in which 4 kinds of plants were grown (Lactuca sativa L var. Dasusheng, L. sativa L var. Youmaicai, Gynura bicolor and Cichorium endivia L) to exchange material with 2 persons in order to research the dynamic changing laws and balanced regulation of air and water between man and plant in an inclosed system. In the test the material flow was measured so that the dynamically changing laws and balanced regulation of air and water between man and plant in the closed system were mostly mastered. The material closure degree of air, water and food reached 100%, 90% and 13.9% respectively with the whole system closure degree up to 95.1%. Meanwhile, it was proved that a 13.5 m2 planting area could meet the demand of one person for O2 in the system, and the energy efficiency ratio of which reached 59.56 g/(kW m2 day). The material flow dynamic balance-regulating technology was initially mastered between man and plant through the test. The interaction was realized among man, plant and environment in the closed system, which is of great significance to the advancement of long-term manned environment control and life support technology for China.

  1. Dmrt1 is necessary for male sexual development in zebrafish

    PubMed Central

    Webster, Kaitlyn A.; Schach, Ursula; Ordaz, Angel; Steinfeld, Jocelyn S.; Draper, Bruce W.; Siegfried, Kellee R.

    2018-01-01

    The dmrt1 (doublesex and mab-3 related transcription factor 1) gene is a key regulator of sex determination and/or gonadal sex differentiation across metazoan animals. This is unusual given that sex determination genes are typically not well conserved. The mechanisms by which zebrafish sex is determined have remained elusive due to the lack of sex chromosomes and the complex polygenic nature of sex determination in domesticated strains. To investigate the role of dmrt1 in zebrafish sex determination and gonad development, we isolated mutations disrupting this gene. We found that the majority of dmrt1 mutant fish develop as fertile females suggesting a complete male-to-female sex reversal in mutant animals that would have otherwise developed as males. A small percentage of mutant animals became males, but were sterile and displayed testicular dysgenesis. Therefore zebrafish dmrt1 functions in male sex determination and testis development. Mutant males had aberrant gonadal development at the onset of gonadal sex-differentiation, displaying reduced oocyte apoptosis followed by development of intersex gonads and failed testis morphogenesis and spermatogenesis. By contrast, female ovaries developed normally. We found that Dmrt1 is necessary for normal transcriptional regulation of the amh (anti-Müllerian hormone) and foxl2 (forkhead box L2) genes, which are thought to be important for male or female sexual development respectively. Interestingly, we identified one dmrt1 mutant allele that cooperates with a linked segregation distorter locus to generate an apparent XY sex determination mechanism. We conclude that dmrt1 is dispensable for ovary development but necessary for testis development in zebrafish, and that dmrt1 promotes male development by transcriptionally regulating male and female genes as has been described in other animals. Furthermore, the strong sex-ratio bias caused by dmrt1 reduction-of-function points to potential mechanisms through which sex

  2. Chronic unpredictable stress regulates visceral adipocyte‐mediated glucose metabolism and inflammatory circuits in male rats

    PubMed Central

    Karagiannides, Iordanes; Golovatscka, Viktoriya; Bakirtzi, Kyriaki; Sideri, Aristea; Salas, Martha; Stavrakis, Dimitris; Polytarchou, Christos; Iliopoulos, Dimitrios; Pothoulakis, Charalabos; Bradesi, Sylvie

    2014-01-01

    Abstract Chronic psychological stress is a prominent risk factor involved in the pathogenesis of many complex diseases, including major depression, obesity, and type II diabetes. Visceral adipose tissue is a key endocrine organ involved in the regulation of insulin action and an important component in the development of insulin resistance. Here, we examined for the first time the changes on visceral adipose tissue physiology and on adipocyte‐associated insulin sensitivity and function after chronic unpredictable stress in rats. Male rats were subjected to chronic unpredictable stress for 35 days. Total body and visceral fat was measured. Cytokines and activated intracellular kinase levels were determined using high‐throughput multiplex assays. Adipocyte function was assessed via tritiated glucose uptake assay. Stressed rats showed no weight gain, and their fat/lean mass ratio increased dramatically compared to control animals. Stressed rats had significantly higher mesenteric fat content and epididymal fat pad weight and demonstrated reduced serum glucose clearing capacity following glucose challenge. Alterations in fat depot size were mainly due to changes in adipocyte numbers and not size. High‐throughput molecular screening in adipocytes isolated from stressed rats revealed activation of intracellular inflammatory, glucose metabolism, and MAPK networks compared to controls, as well as significantly reduced glucose uptake capacity in response to insulin stimulation. Our study identifies the adipocyte as a key regulator of the effects of chronic stress on insulin resistance, and glucose metabolism, with important ramifications in the pathophysiology of several stress‐related disease states. PMID:24819750

  3. Effects of six priority controlled phthalate esters with long-term low-dose integrated exposure on male reproductive toxicity in rats.

    PubMed

    Gao, Hai-Tao; Xu, Run; Cao, Wei-Xin; Qian, Liang-Liang; Wang, Min; Lu, Lingeng; Xu, Qian; Yu, Shu-Qin

    2017-03-01

    Human beings are inevitably exposed to ubiquitous phthalate esters (PEs) surroundings. The purposes of this study were to investigate the effects of long-term low-dose exposure to the mixture of six priority controlled phthalate esters (MIXPs): dimethyl phthalate (DMP), diethyl phthalate (DEP), di(n-butyl) phthalate (DBP), butyl benzyl phthalate (BBP), di(2-ethyhexyl) phthalate (DEHP) and di-n-octyl phthalate (DNOP), on male rat reproductive system and further to explore the underlying mechanisms of the reproductive toxicity. The male rats were orally exposed to either sodium carboxymethyl cellulose as controls or MIXPs at three different low-doses by gavage for 15 weeks. Testosterone and luteinizing hormone (LH) in serum were analyzed, and pathological examinations were performed for toxicity evaluation. Steroidogenic proteins (StAR, P450scc, CYP17A1 and 17β-HSD), cell cycle and apoptosis-related proteins (p53, Chk1, Cdc2, CDK6, Bcl-2 and Bax) were measured for mechanisms exploration. MIXPs with long-term low-dose exposure could cause male reproductive toxicity to the rats, including the decrease of both serum and testicular testosterone, and the constructional damage of testis. These effects were related to down-regulated steroidogenic proteins, arresting cell cycle progression and promoting apoptosis in rat testicular cells. The results indicate that MIXPs with long-term low-dose exposure may pose male reproductive toxicity in human. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. An integrative review of ethnic and cultural variation in socialization and children's self-regulation.

    PubMed

    LeCuyer, Elizabeth A; Zhang, Yi

    2015-04-01

    To examine the evidence for cross-cultural variation in socialization and children's normative self-regulation, based on a contextual-developmental perspective. Nurses and healthcare workers in multi-cultural societies must understand diversity in socializing influences (including parenting) and in children's behaviour. A contextual-developmental perspective implies that normative cultural and ethnic values will influence socializing processes and behaviour, which in turn will influence children's self-regulation. Integrative review. Studies were located using five major search engines from 1990-2011. Domains of a contextual-developmental perspective and a comprehensive definition of self-regulation assisted the generation of search terms. Selected studies compared at least two ethnic or cultural groups and addressed contextual-developmental domains: (1) culturally specific social values, beliefs, or attitudes; (2) socializing behaviours; and (3) children's normative self-regulation. Eleven studies about children's self-regulation were found to have data consistent with a contextual-developmental perspective. Studies used descriptive correlational or comparative designs with primarily convenience sampling; eight confirmed stated hypotheses, three were exploratory. Findings across studies evidenced coherent patterns of sociocultural influence on children's attention, compliance, delay of gratification, effortful control and executive function. A contextual-developmental perspective provided a useful perspective to examine normative differences in values, socializing behaviours and children's self-regulation. This perspective and these findings are expected to guide future research, to assist nurses and healthcare providers to understand diversity in parenting and children's behaviour. © 2014 John Wiley & Sons Ltd.

  5. Dopamine D1 Receptor Signaling in the Medial Preoptic Area Facilitates Experience-induced Enhancement of Mating Behavior in Male Rats

    PubMed Central

    McHenry, Jenna A.; Bell, Genevieve A.; Parrish, Bradley P.; Hull, Elaine M.

    2012-01-01

    The medial preoptic area (MPOA) is an integral site for male sexual behavior. Dopamine is released in the MPOA before and during copulation and facilitates male rat sexual behavior. Repeated sexual experience and noncopulatory exposures to an estrous female facilitate subsequent copulation. However, the neurobiological mechanisms that mediate such enhancement remain unclear. Here, we examined the role of dopamine D1 receptors in the MPOA in experience-induced enhancement of male sexual behavior in rats. In Experiment 1, microinjections of the D1 antagonist SCH-23390 into the MPOA before each of 7 daily 30-min noncopulatory exposures to a receptive female impaired copulation on a drug-free test on day 8, compared to vehicle-treated female-exposed animals. Copulatory performance in drug-treated animals was similar to vehicle-treated males that had not been pre-exposed to females. This effect was site specific. There were no group differences in locomotor activity in an open field on the copulation test day. In Experiment 2, a separate cohort of animals was used to examine phosphorylation of dopamine-and cAMP-regulated phosphoprotein (DARPP-32) in the MPOA of animals with acute and/or chronic sexual experience. DARPP-32 is a downstream marker of D1 receptor signaling and substrate of cAMP-dependent protein kinase (PKA). Western immunoblot analysis revealed that p-DARPP-32 expression was greatest in the MPOA of males that received both acute and chronic sexual experience, compared to all other mated conditions and naïve controls. These data suggest that D1 receptors in the MPOA contribute to experience-induced enhancement of male sexual behavior, perhaps through a PKA regulated mechanism. PMID:22708956

  6. Integrated evaluation of visually induced motion sickness in terms of autonomic nervous regulation.

    PubMed

    Kiryu, Tohru; Tada, Gen; Toyama, Hiroshi; Iijima, Atsuhiko

    2008-01-01

    To evaluate visually-induced motion sickness, we integrated subjective and objective responses in terms of autonomic nervous regulation. Twenty-seven subjects viewed a 2-min-long first-person-view video section five times (total 10 min) continuously. Measured biosignals, the RR interval, respiration, and blood pressure, were used to estimate the indices related to autonomic nervous activity (ANA). Then we determined the trigger points and some sensation sections based on the time-varying behavior of ANA-related indices. We found that there was a suitable combination of biosignals to present the symptoms of visually-induced motion sickness. Based on the suitable combination, integrating trigger points and subjective scores allowed us to represent the time-distribution of subjective responses during visual exposure, and helps us to understand what types of camera motions will cause visually-induced motion sickness.

  7. Advances and challenges in logical modeling of cell cycle regulation: perspective for multi-scale, integrative yeast cell models

    PubMed Central

    Todd, Robert G.; van der Zee, Lucas

    2016-01-01

    Abstract The eukaryotic cell cycle is robustly designed, with interacting molecules organized within a definite topology that ensures temporal precision of its phase transitions. Its underlying dynamics are regulated by molecular switches, for which remarkable insights have been provided by genetic and molecular biology efforts. In a number of cases, this information has been made predictive, through computational models. These models have allowed for the identification of novel molecular mechanisms, later validated experimentally. Logical modeling represents one of the youngest approaches to address cell cycle regulation. We summarize the advances that this type of modeling has achieved to reproduce and predict cell cycle dynamics. Furthermore, we present the challenge that this type of modeling is now ready to tackle: its integration with intracellular networks, and its formalisms, to understand crosstalks underlying systems level properties, ultimate aim of multi-scale models. Specifically, we discuss and illustrate how such an integration may be realized, by integrating a minimal logical model of the cell cycle with a metabolic network. PMID:27993914

  8. Integration of Social, Cultural, and Biomedical Strategies into an Existing Couple-Based Behavioral HIV/STI Prevention Intervention: Voices of Latino Male Couples.

    PubMed

    Martinez, Omar; Wu, Elwin; Levine, Ethan C; Muñoz-Laboy, Miguel; Fernandez, M Isabel; Bass, Sarah Bauerle; Moya, Eva M; Frasca, Timothy; Chavez-Baray, Silvia; Icard, Larry D; Ovejero, Hugo; Carballo-Diéguez, Alex; Rhodes, Scott D

    2016-01-01

    Successful HIV prevention and treatment requires evidence-based approaches that combine biomedical strategies with behavioral interventions that are socially and culturally appropriate for the population or community being prioritized. Although there has been a push for a combination approach, how best to integrate different strategies into existing behavioral HIV prevention interventions remains unclear. The need to develop effective combination approaches is of particular importance for men who have sex with men (MSM), who face a disproportionately high risk of HIV acquisition. We collaborated with Latino male couples and providers to adapt Connect 'n Unite, an evidence-based intervention for Black male couples, for Latino male couples. We conducted a series of three focus groups, each with two cohorts of couples, and one focus group with providers. A purposive stratified sample of 20 couples (N = 40, divided into two cohorts) and 10 providers provided insights into how to adapt and integrate social, cultural, and biomedical approaches in a couples-based HIV/AIDS behavioral intervention. The majority (N = 37) of the couple participants had no prior knowledge of the following new biomedical strategies: non-occupational post-exposure prophylaxis (nPEP); pre-exposure prophylaxis (PrEP); and HIV self-testing kits. After they were introduced to these biomedical interventions, all participants expressed a need for information and empowerment through knowledge and awareness of these interventions. In particular, participants suggested that we provide PrEP and HIV self-testing kits by the middle or end of the intervention. Providers suggested a need to address behavioral, social and structural issues, such as language barriers; and the promotion of client-centered approaches to increase access to, adaptation of, and adherence to biomedical strategies. Corroborating what couple participants suggested, providers agreed that biomedical strategies should be offered after

  9. The development, regulation and use of biopesticides for integrated pest management

    PubMed Central

    Chandler, David; Bailey, Alastair S.; Tatchell, G. Mark; Davidson, Gill; Greaves, Justin; Grant, Wyn P.

    2011-01-01

    Over the past 50 years, crop protection has relied heavily on synthetic chemical pesticides, but their availability is now declining as a result of new legislation and the evolution of resistance in pest populations. Therefore, alternative pest management tactics are needed. Biopesticides are pest management agents based on living micro-organisms or natural products. They have proven potential for pest management and they are being used across the world. However, they are regulated by systems designed originally for chemical pesticides that have created market entry barriers by imposing burdensome costs on the biopesticide industry. There are also significant technical barriers to making biopesticides more effective. In the European Union, a greater emphasis on Integrated Pest Management (IPM) as part of agricultural policy may lead to innovations in the way that biopesticides are regulated. There are also new opportunities for developing biopesticides in IPM by combining ecological science with post-genomics technologies. The new biopesticide products that will result from this research will bring with them new regulatory and economic challenges that must be addressed through joint working between social and natural scientists, policy makers and industry. PMID:21624919

  10. Social Control of Hypothalamus-Mediated Male Aggression.

    PubMed

    Yang, Taehong; Yang, Cindy F; Chizari, M Delara; Maheswaranathan, Niru; Burke, Kenneth J; Borius, Maxim; Inoue, Sayaka; Chiang, Michael C; Bender, Kevin J; Ganguli, Surya; Shah, Nirao M

    2017-08-16

    How environmental and physiological signals interact to influence neural circuits underlying developmentally programmed social interactions such as male territorial aggression is poorly understood. We have tested the influence of sensory cues, social context, and sex hormones on progesterone receptor (PR)-expressing neurons in the ventromedial hypothalamus (VMH) that are critical for male territorial aggression. We find that these neurons can drive aggressive displays in solitary males independent of pheromonal input, gonadal hormones, opponents, or social context. By contrast, these neurons cannot elicit aggression in socially housed males that intrude in another male's territory unless their pheromone-sensing is disabled. This modulation of aggression cannot be accounted for by linear integration of environmental and physiological signals. Together, our studies suggest that fundamentally non-linear computations enable social context to exert a dominant influence on developmentally hard-wired hypothalamus-mediated male territorial aggression. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. The splicing activator DAZAP1 integrates splicing control into MEK/Erk-regulated cell proliferation and migration

    NASA Astrophysics Data System (ADS)

    Choudhury, Rajarshi; Roy, Sreerupa Ghose; Tsai, Yihsuan S.; Tripathy, Ashutosh; Graves, Lee M.; Wang, Zefeng

    2014-01-01

    Alternative splicing of pre-messenger RNA (mRNA) is a critical stage of gene regulation in response to environmental stimuli. Here we show that DAZAP1, an RNA-binding protein involved in mammalian development and spermatogenesis, promotes inclusion of weak exons through specific recognition of diverse cis-elements. The carboxy-terminal proline-rich domain of DAZAP1 interacts with and neutralizes general splicing inhibitors, and is sufficient to activate splicing when recruited to pre-mRNA. This domain is phosphorylated by the MEK/Erk (extracellular signal-regulated protein kinase) pathway and this modification is essential for the splicing regulatory activity and the nuclear/cytoplasmic translocation of DAZAP1. Using mRNA-seq, we identify endogenous splicing events regulated by DAZAP1, many of which are involved in maintaining cell growth. Knockdown or over-expression of DAZAP1 causes a cell proliferation defect. Taken together, these studies reveal a molecular mechanism that integrates splicing control into MEK/Erk-regulated cell proliferation.

  12. Integrating postabortion care, menstrual regulation and family planning services in Bangladesh: a pre-post evaluation.

    PubMed

    Biswas, Kamal K; Pearson, Erin; Shahidullah, S M; Sultana, Sharmin; Chowdhury, Rezwana; Andersen, Kathryn L

    2017-03-11

    In Bangladesh, abortion is restricted except to save the life of a woman, but menstrual regulation is allowed to induce menstruation and return to non-pregnancy after a missed period. MR services are typically provided through the Directorate General of Family Planning, while postabortion care services for incomplete abortion are provided by facilities under the Directorate General of Health Services. The bifurcated health system results in reduced quality of care, particularly for postabortion care patients whose procedures are often performed using sub-optimal uterine evacuation technology and typically do not receive postabortion contraceptive services. This study evaluated the success of a pilot project that aimed to integrate menstrual regulation, postabortion care and family planning services across six Directorate General of Health Services and Directorate General of Family Planning facilities by training providers on woman-centered abortion care and adding family planning services at sites offering postabortion care. A pre-post evaluation was conducted in the six large intervention facilities. Structured client exit interviews were administered to all uterine evacuation clients presenting in the 2-week data collection period for each facility at baseline (n = 105; December 2011-January 2012) and endline (n = 107; February-March 2013). Primary outcomes included service integration indicators such as provision of menstrual regulation, postabortion care and family planning services in both facility types, and quality of care indicators such as provision of pain management, provider communication and women's satisfaction with the services received. Outcomes were compared between baseline and endline for Directorate General of Family Planning and Directorate General of Health Services facilities, and chi-square tests and t-tests were used to test for differences between baseline and endline. At the end of the project there was an increase in menstrual

  13. Developmental staging of male murine embryonic gonad by SAGE analysis

    PubMed Central

    Lee, Tin-Lap; Li, Yunmin; Alba, Diana; Vong, Queenie P.; Wu, Shao-Ming; Baxendale, Vanessa; Rennert, Owen M.; Lau, Yun-Fai Chris; Chan, Wai-Yee

    2012-01-01

    Despite the identification of key genes such as Sry integral to embryonic gonadal development, the genomic classification and identification of chromosomal activation of this process is still poorly understood. To better understand the genetic regulation of gonadal development, we performed Serial Analysis of Gene Expression (SAGE) to profile the genes and novel transcripts, and an average of 152,000 tags from male embryonic gonads at E10.5 (embryonic day 10.5), E11.5, E12.5, E13.5, E15.5 and E17.5 were analyzed. A total of 275,583 non-singleton tags that do not map to any annotated sequence were identified in the six gonad libraries, and 47,255 tags were mapped to 24,975 annotated sequences, among which 987 sequences were uncharacterized. Utilizing an unsupervised pattern identification technique, we established molecular staging of male gonadal development. Rather than providing a static descriptive analysis, we developed algorithms to cluster the SAGE data and assign SAGE tags to a corresponding chromosomal position; these data are displayed in chromosome graphic format. A prominent increase in global genomic activity from E10.5 to E17.5 was observed. Important chromosomal regions related to the developmental processes were identified and validated based on established mouse models with developmental disorders. These regions may represent markers for early diagnosis for disorders of male gonad development as well as potential treatment targets. PMID:19376482

  14. Building-to-Grid Integration through Commercial Building Portfolios Participating in Energy and Frequency Regulation Markets

    NASA Astrophysics Data System (ADS)

    Pavlak, Gregory S.

    Building energy use is a significant contributing factor to growing worldwide energy demands. In pursuit of a sustainable energy future, commercial building operations must be intelligently integrated with the electric system to increase efficiency and enable renewable generation. Toward this end, a model-based methodology was developed to estimate the capability of commercial buildings to participate in frequency regulation ancillary service markets. This methodology was integrated into a supervisory model predictive controller to optimize building operation in consideration of energy prices, demand charges, and ancillary service revenue. The supervisory control problem was extended to building portfolios to evaluate opportunities for synergistic effect among multiple, centrally-optimized buildings. Simulation studies performed showed that the multi-market optimization was able to determine appropriate opportunities for buildings to provide frequency regulation. Total savings were increased by up to thirteen percentage points, depending on the simulation case. Furthermore, optimizing buildings as a portfolio achieved up to seven additional percentage points of savings, depending on the case. Enhanced energy and cost savings opportunities were observed by taking the novel perspective of optimizing building portfolios in multiple grid markets, motivating future pursuits of advanced control paradigms that enable a more intelligent electric grid.

  15. Sexual experience increases oxytocin receptor gene expression and protein in the medial preoptic area of the male rat.

    PubMed

    Gil, Mario; Bhatt, Renu; Picotte, Katie B; Hull, Elaine M

    2013-09-01

    Oxytocin (OT) promotes social and reproductive behaviors in mammals, and OT deficits may be linked to disordered social behaviors like autism and severe anxiety. Male rat sexual behavior is an excellent model for OT regulation of behavior, as its pattern and neural substrates are well characterized. We previously reported that OT microinjected into the medial preoptic area (MPOA), a major integrative site for male sexual behavior, facilitates copulation in sexually experienced male rats, whereas intra-MPOA injection of an OT antagonist (OTA) inhibits copulation. In the present studies, copulation on the day of sacrifice stimulated OTR mRNA expression in the MPOA, irrespective of previous sexual experience, with the highest levels observed in first-time copulators. In addition, sexually experienced males had higher levels of OTR protein in the MPOA than sexually naïve males and first-time copulators. Finally, intra-MPOA injection of OT facilitated mating in sexually naive males. Others have reported a positive correlation between OT mRNA levels and male sexual behavior. Our studies show that OT in the MPOA facilitates mating in both sexually naive and experienced males, some of the behavioral effects of OT are mediated by the OTR, and sexual experience is associated with increased OTR expression in the MPOA. Taken together, these data suggest a reciprocal interaction between central OT and behavior, in which OT facilitates copulation and copulation stimulates the OT/OTR system in the brain. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Lesions that functionally disconnect the anterior and posterodorsal sub-regions of the medial amygdala eliminate opposite-sex odor preference in male Syrian hamsters (Mesocricetus auratus)

    PubMed Central

    Maras, Pamela M.; Petrulis, Aras

    2009-01-01

    In many rodent species, such as Syrian hamsters, reproductive behavior requires neural integration of chemosensory information and steroid hormone cues. The medial amygdala processes both of these signals through anatomically distinct sub-regions; the anterior region (MeA) receives substantial chemosensory input, but contains few steroid receptor-labeled neurons, whereas the posterodorsal region (MePD) receives less chemosensory input, but contains a dense population of steroid receptors. Importantly, these sub-regions have considerable reciprocal connections, and the goal of this experiment was therefore to determine whether interactions between MeA and MePD are required for male hamsters’ preference to investigate female over male odors. To functionally disconnect MeA and MePD, males received unilateral lesions of MeA and MePD within opposite brain hemispheres. Control males received either unilateral lesions of MeA and MePD within the same hemisphere or sham surgery. Odor preferences were measured using a 3-choice apparatus, which simultaneously presented female, male and clean odor stimuli; all tests were done under conditions that either prevented or allowed contact with the odor sources. Under non-contact conditions, males with asymmetrical lesions investigated female and male odors equally, whereas males in both control groups preferred to investigate female odors. Under contact conditions, all groups investigated female odors longer than male odors, although males with asymmetrical lesions displayed decreased investigation of female odors compared to sham males. These data suggest that MeA-MePD interactions are critical for processing primarily the volatile components of social odors and highlight the importance of input from the main olfactory system to these nuclei in the regulation of reproductive behavior. More broadly, these results support the role of the medial amygdala in integrating chemosensory and hormone information, a process that may

  17. Physiological regulation of magnocellular neurosecretory cell activity: Integration of intrinsic, local and afferent mechanisms

    PubMed Central

    Brown, Colin H.; Bains, Jaideep S.; Ludwig, Mike; Stern, Javier E.

    2013-01-01

    The hypothalamic supraoptic and paraventricular nucleus contain magnocellular neurosecretory cells (MNCs) that project to the posterior pituitary gland where they secrete either oxytocin or vasopressin (the anti-diuretic hormone) into the circulation. Oxytocin is important for delivery at birth and is essential for milk ejection during suckling. Vasopressin primarily promotes water reabsorption in the kidney to maintain body fluid balance, but also increases vasoconstriction. The profile of oxytocin and vasopressin secretion is principally determined by the pattern of action potentials initiated at the cell bodies. While it has long been known that the activity of MNCs depends upon afferent inputs that relay information on reproductive, osmotic and cardiovascular status, it has recently become clear that activity depends critically on local regulation by glial cells, as well as intrinsic regulation by the MNCs themselves. Here, we provide an overview of recent advances in our understanding of how intrinsic and local extrinsic mechanisms integrate with afferent inputs to generate appropriate physiological regulation of oxytocin and vasopressin MNC activity. PMID:23701531

  18. [Effects of an Integrated Internet Addiction Prevention Program on Elementary Students' Self-regulation and Internet Addiction].

    PubMed

    Mun, So Youn; Lee, Byoung Sook

    2015-04-01

    The purpose of this study was to develop an integrated internet addiction prevention program and test its effects on the self-regulation and internet addiction of elementary students who are at risk for internet addiction. A quasi-experimental study with a nonequivalent control group pretest-posttest design was used. Participants were assigned to the experimental group (n=28) or control group (n=28). Contents of the program developed in this study included provision of information about internet addiction, interventions for empowerment and methods of behavioral modification. A pre-test and two post-tests were done to identify the effects of the program and their continuity. Effects were testified using Repeated measures ANOVA, simple effect analysis, and Time Contrast. The self-regulation of the experimental group after the program was significantly higher than the control group. The score for internet addiction self-diagnosis and the internet use time in the experimental group were significantly lower than the control group. The effects of the integrated internet addiction prevention program for preventing internet addiction in elementary students at risk for internet addiction were validated.

  19. Peroxisome proliferator activated receptor alpha regulates a male-specific cytochrome P450 in mouse liver.

    PubMed

    Jeffery, Brett; Choudhury, Agharul I; Horley, Neill; Bruce, Mary; Tomlinson, Simon R; Roberts, Ruth A; Gray, Tim J B; Barrett, David A; Shaw, P Nicholas; Kendall, David; Bell, David R

    2004-09-15

    We set out to find if the strain-specific, male-specific hepatic expression of Cyp4a protein in mouse was due to expression of Cyp4a12 and to understand the genetic basis for reported differences in expression. 12-Lauric acid hydroxylase (LAH) activity was found to show higher levels in male ddY, but not C57Bl/6, mouse liver microsomes. The expression of Cyp4a12 mRNA was studied using RNAase protection assays in male and female liver and kidney of nine mouse strains. Cyp4a12 was found to be highly expressed in male liver and kidney, but at much lower levels in female liver and kidney, in all strains studied. Western blotting with an antibody specific for Cyp4a12 confirmed that Cyp4a12 was expressed in a male specific fashion in C57Bl/6 mouse liver. RNAase protection analysis for Cyp4a10 and 14 in ddY mice revealed that neither of these genes showed male-specific expression. To further investigate genetic factors that control male-specific Cyp4a12 expression, PPARalpha+/+ and -/- mice were studied, showing that total P450 and 12-LAH activity was male-specific in +/+, but not -/- mice. RNAase protection assays were used to confirm that Cyp4a12 was lower in -/- mice. However, the male-specific Slp and MUP-1 genes retained hepatic male-specific levels of expression in +/+ and -/- mice, showing that the decrease in Cyp4a12 was not a general effect on male-specific expression. Thus, PPARalpha has a specific effect on constitutive expression of Cyp4a12.

  20. DOCK8 regulates lymphocyte shape integrity for skin antiviral immunity

    PubMed Central

    Zhang, Qian; Dove, Christopher G.; Hor, Jyh Liang; Murdock, Heardley M.; Strauss-Albee, Dara M.; Garcia, Jordan A.; Mandl, Judith N.; Grodick, Rachael A.; Jing, Huie; Chandler-Brown, Devon B.; Lenardo, Timothy E.; Crawford, Greg; Matthews, Helen F.; Freeman, Alexandra F.; Cornall, Richard J.; Germain, Ronald N.

    2014-01-01

    DOCK8 mutations result in an inherited combined immunodeficiency characterized by increased susceptibility to skin and other infections. We show that when DOCK8-deficient T and NK cells migrate through confined spaces, they develop cell shape and nuclear deformation abnormalities that do not impair chemotaxis but contribute to a distinct form of catastrophic cell death we term cytothripsis. Such defects arise during lymphocyte migration in collagen-dense tissues when DOCK8, through CDC42 and p21-activated kinase (PAK), is unavailable to coordinate cytoskeletal structures. Cytothripsis of DOCK8-deficient cells prevents the generation of long-lived skin-resident memory CD8 T cells, which in turn impairs control of herpesvirus skin infections. Our results establish that DOCK8-regulated shape integrity of lymphocytes prevents cytothripsis and promotes antiviral immunity in the skin. PMID:25422492

  1. How does mindfulness modulate self-regulation in pre-adolescent children? An integrative neurocognitive review.

    PubMed

    Kaunhoven, Rebekah Jane; Dorjee, Dusana

    2017-03-01

    Pre-adolescence is a key developmental period in which complex intrinsic volitional methods of self-regulation are acquired as a result of rapid maturation within the brain networks underlying the self-regulatory processes of attention control and emotion regulation. Fostering adaptive self-regulation skills during this stage of development has strong implications for physical health, emotional and socio-economic outcomes during adulthood. There is a growing interest in mindfulness-based programmes for pre-adolescents with initial findings suggesting self-regulation improvements, however, neurodevelopmental studies on mindfulness with pre-adolescents are scarce. This analytical review outlines an integrative neuro-developmental approach, which combines self-report and behavioural assessments with event related brain potentials (ERPs) to provide a systemic multilevel understanding of the neurocognitive mechanisms of mindfulness in pre-adolescence. We specifically focus on the N2, error related negativity (ERN), error positivity (Pe), P3a, P3b and late positive potential (LPP) ERP components as indexes of mindfulness related modulations in non-volitional bottom-up self-regulatory processes (salience detection, stimulus driven orienting and mind wandering) and volitional top-down self-regulatory processes (endogenous orienting and executive attention). Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  2. An improved procedure for integrated behavioral z-scoring illustrated with modified Hole Board behavior of male inbred laboratory mice.

    PubMed

    Labots, M Maaike; Laarakker, M C Marijke; Schetters, D Dustin; Arndt, S S Saskia; van Lith, H A Hein

    2018-01-01

    Guilloux et al. introduced: integrated behavioral z-scoring, a method for behavioral phenotyping of mice. Using this method multiple ethological variables can be combined to show an overall description of a certain behavioral dimension or motivational system. However, a problem may occur when the control group used for the calculation has a standard deviation of zero or when no control group is present to act as a reference group. In order to solve these problems, an improved procedure is suggested: taking the pooled data as reference. For this purpose a behavioral study with male mice from three inbred strains was carried out. The integrated behavioral z-scoring methodology was applied, thereby taking five different reference group options. The outcome regarding statistical significance and practical importance was compared. Significant effects and effect sizes were influenced by the choice of the reference group. In some cases it was impossible to use a certain population and condition, because one or more behavioral variables in question had a standard deviation of zero. Based on the improved method, male mice from the three inbred strains differed regarding activity and anxiety. Taking the method described by Guilloux et al. as basis, the present procedure improved the generalizability to all types of experimental designs in animal behavioral research. To solve the aforementioned problems and to avoid getting the diagnosis of data manipulation, the pooled data (combining the data from all experimental groups in a study) as reference option is recommended. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. [Vocational Health Schools (ETSUS) in Brazil: regulation of the integration of teaching-service-administrative sustainability of ETSUS].

    PubMed

    Borges, Fabiano Tonaco; Garbin, Cléa Adas Saliba; Siqueira, Carlos Eduardo; Garbin, Artênio José Ísper; Rocha, Najara Barbosa da; Lolli, Luíz Fernando; Moimaz, Suzely Adas Saliba

    2012-04-01

    The scope of this study was to discuss the administrative sustainability of Brazil's Vocational Health Schools (ETSUS) based on the principle of teaching and service integration, which brings a new dimension to healthcare work as yet unregulated by Brazilian public administration. It was a qualitative study using case study methodology. The research involved a semi-structured questionnaire given to ETSUS managers addressing institutional, administrative, and work management aspects. The sample was composed of 6 ETSUS that belong to the Network of Vocational Health Schools (RET-SUS). The ETSUS showed centralized planning and management, and decentralized implementation of their core activities. The majority did not have administrative autonomy and relied heavily on funding from the federal government. According to ETSUS managers, the lack of regulation of teaching activities by civil servants weakens the management of ETSUS. The ETSUS have managerial problems related to teaching-service integration, which has to be regulated in order to guarantee the sustainability of these schools and avoid conflicts with Brazilian legislation.

  4. Integrating family planning and HIV services in western Kenya: the impact on HIV-infected patients' knowledge of family planning and male attitudes toward family planning.

    PubMed

    Onono, Maricianah; Guzé, Mary A; Grossman, Daniel; Steinfeld, Rachel; Bukusi, Elizabeth A; Shade, Starley; Cohen, Craig R; Newmann, Sara J

    2015-01-01

    Little information exists on the impact of integrating family planning (FP) services into HIV care and treatment on patients' familiarity with and attitudes toward FP. We conducted a cluster-randomized trial in 18 public HIV clinics with 12 randomized to integrated FP and HIV services and 6 to the standard referral-based system where patients are referred to an FP clinic. Serial cross-sectional surveys were done before (n = 488 women, 486 men) and after (n = 479 women, 481 men) the intervention to compare changes in familiarity with FP methods and attitudes toward FP between integrated and nonintegrated (NI) sites. We created an FP familiarity score based on the number of more effective FP methods patients could identify (score range: 0-6). Generalized estimating equations were used to control for clustering within sites. An increase in mean familiarity score between baseline (mean = 5.16) and post-intervention (mean = 5.46) occurred with an overall mean change of 0.26 (95% confidence intervals [CI] = 0.09, 0.45; p = 0.003) across all sites. At end line, there was no difference in increase of mean FP familiarity scores at intervention versus control sites (mean = 5.41 vs. 5.49, p = 0.94). We observed a relative decrease in the proportion of males agreeing that FP was "women's business" at integrated sites (baseline 42% to end line 30%; reduction of 12%) compared to males at NI sites (baseline 35% to end line 42%; increase of 7%; adjusted odds ration [aOR] = 0.43; 95% CI = 0.22, 0.85). Following FP-HIV integration, familiarity with FP methods increased but did not differ by study arm. Integration was associated with a decrease in negative attitudes toward FP among men.

  5. A Cholinergic-Regulated Circuit Coordinates the Maintenance and Bi-Stable States of a Sensory-Motor Behavior during Caenorhabditis elegans Male Copulation

    PubMed Central

    Liu, Yishi; LeBeouf, Brigitte; Guo, Xiaoyan; Correa, Paola A.; Gualberto, Daisy G.; Lints, Robyn; Garcia, L. Rene

    2011-01-01

    Penetration of a male copulatory organ into a suitable mate is a conserved and necessary behavioral step for most terrestrial matings; however, the detailed molecular and cellular mechanisms for this distinct social interaction have not been elucidated in any animal. During mating, the Caenorhabditis elegans male cloaca is maintained over the hermaphrodite's vulva as he attempts to insert his copulatory spicules. Rhythmic spicule thrusts cease when insertion is sensed. Circuit components consisting of sensory/motor neurons and sex muscles for these steps have been previously identified, but it was unclear how their outputs are integrated to generate a coordinated behavior pattern. Here, we show that cholinergic signaling between the cloacal sensory/motor neurons and the posterior sex muscles sustains genital contact between the sexes. Simultaneously, via gap junctions, signaling from these muscles is transmitted to the spicule muscles, thus coupling repeated spicule thrusts with vulval contact. To transit from rhythmic to sustained muscle contraction during penetration, the SPC sensory-motor neurons integrate the signal of spicule's position in the vulva with inputs from the hook and cloacal sensilla. The UNC-103 K+ channel maintains a high excitability threshold in the circuit, so that sustained spicule muscle contraction is not stimulated by fewer inputs. We demonstrate that coordination of sensory inputs and motor outputs used to initiate, maintain, self-monitor, and complete an innate behavior is accomplished via the coupling of a few circuit components. PMID:21423722

  6. Phenotypic integration mediated by hormones: associations among digit ratios, body size and testosterone during tadpole development.

    PubMed

    Lofeu, Leandro; Brandt, Renata; Kohlsdorf, Tiana

    2017-08-02

    Developmental associations often explain phenotypic integration. The intersected hormonal regulation of ontogenetic processes fosters predictions of steroid-mediated phenotypic integration among sexually dimorphic traits, a statement defied by associations between classical dimorphism predictors (e.g. body size) and traits that apparently lack sex-specific functions (e.g. ratios between the lengths of Digits II and IV - 2D:4D). Developmental bases of female-biased 2D:4D have been identified, but these remain unclear for taxa presenting male-biased 2D:4D (e.g. anura). Here we propose two alternative hypotheses to investigate evolution of male-biased 2D:4D associated with sexually dimorphic body size using Leptodactylus frogs: I)'hypothesis of sex-specific digit responses' - Digit IV would be reactive to testosterone but exhibit responses in the opposite direction of those observed in female-biased 2D:4D lineages, so that Digit IV turns shorter in males; II) 'hypothesis of identity of the dimorphic digit'- Digit II would be the dimorphic digit. We compiled the following databases using Leptodactylus frogs: 1) adults of two species from natural populations and 2) testosterone-treated L. fuscus at post-metamorphic stage. Studied traits seem monomorphic in L. fuscus; L. podicipinus exhibits male-biased 2D:4D. When present, 2D:4D dimorphism was male-biased and associated with dimorphic body size; sex differences resided on Digit II instead of IV, corroborating our 'hypothesis of identity of the dimorphic digit'. Developmental steroid roles were validated: testosterone-treated L. fuscus frogs were smaller and exhibited masculinized 2D:4D, and Digit II was the digit that responded to testosterone. We propose a model where evolution of sexual dimorphism in 2D:4D first originates from the advent, in a given digit, of increased tissue sensitivity to steroids. Phenotypic integration with other sexually dimorphic traits would then occur through multi-trait hormonal effects

  7. New frontiers in nonhormonal male contraception.

    PubMed

    Cheng, C Yan; Mruk, Dolores D

    2010-11-01

    The world's population is nearing 6.8 billion, and we are in need of a male contraceptive that is safe, effective, reversible and affordable. Hormonal approaches, which employ different formulations of testosterone administered in combination with other hormones, have shown considerable promise in clinical trials, and they are currently at the forefront of research and development. However, the long-term effects of using hormones throughout a male's reproductive life for contraception are unknown, and it may take decades before this information becomes available. Because of this, many investigators are aiming to bring a nonhormonal male contraceptive to the consumer market. Indeed, there are several distinct but feasible avenues in which fertility can be regulated without affecting the hypothalamus-pituitary-testis axis. In this review, we discuss several approaches for fertility control involving the testis that one day may lead to the development of a nonhormonal male contraceptive. Copyright © 2010 Elsevier Inc. All rights reserved.

  8. Groundwater regulation and integrated planning

    USGS Publications Warehouse

    Quevauviller, Philippe; Batelaan, Okke; Hunt, Randall J.

    2016-01-01

    The complex nature of groundwater and the diversity of uses and environmental interactions call for emerging groundwater problems to be addressed through integrated management and planning approaches. Planning requires different levels of integration dealing with: the hydrologic cycle (the physical process) including the temporal dimension; river basins and aquifers (spatial integration); socioeconomic considerations at regional, national and international levels; and scientific knowledge. The great natural variation in groundwater conditions obviously affects planning needs and options as well as perceptions from highly localised to regionally-based approaches. The scale at which planning is done therefore needs to be carefully evaluated against available policy choices and options in each particular setting. A solid planning approach is based on River Basin Management Planning (RBMP), which covers: (1) objectives that management planning are designed to address; (2) the way various types of measures fit into the overall management planning; and (3) the criteria against which the success or failure of specific strategies or interventions can be evaluated (e.g. compliance with environmental quality standards). A management planning framework is to be conceived as a “living” or iterated document that can be updated, refined and if necessary changed as information and experience are gained. This chapter discusses these aspects, providing an insight into European Union (EU), United States and Australia groundwater planning practices.

  9. Integration of human sleep-wake regulation and circadian rhythmicity

    NASA Technical Reports Server (NTRS)

    Dijk, Derk-Jan; Lockley, Steven W.

    2002-01-01

    The human sleep-wake cycle is generated by a circadian process, originating from the suprachiasmatic nuclei, in interaction with a separate oscillatory process: the sleep homeostat. The sleep-wake cycle is normally timed to occur at a specific phase relative to the external cycle of light-dark exposure. It is also timed at a specific phase relative to internal circadian rhythms, such as the pineal melatonin rhythm, the circadian sleep-wake propensity rhythm, and the rhythm of responsiveness of the circadian pacemaker to light. Variations in these internal and external phase relationships, such as those that occur in blindness, aging, morning and evening, and advanced and delayed sleep-phase syndrome, lead to sleep disruptions and complaints. Changes in ocular circadian photoreception, interindividual variation in the near-24-h intrinsic period of the circadian pacemaker, and sleep homeostasis can contribute to variations in external and internal phase. Recent findings on the physiological and molecular-genetic correlates of circadian sleep disorders suggest that the timing of the sleep-wake cycle and circadian rhythms is closely integrated but is, in part, regulated differentially.

  10. Integration of Social, Cultural, and Biomedical Strategies into an Existing Couple-Based Behavioral HIV/STI Prevention Intervention: Voices of Latino Male Couples

    PubMed Central

    Martinez, Omar; Wu, Elwin; Levine, Ethan C.; Muñoz-Laboy, Miguel; Fernandez, M. Isabel; Bass, Sarah Bauerle; Moya, Eva M.; Frasca, Timothy; Chavez-Baray, Silvia; Icard, Larry D.; Ovejero, Hugo; Carballo-Diéguez, Alex; Rhodes, Scott D.

    2016-01-01

    Introduction Successful HIV prevention and treatment requires evidence-based approaches that combine biomedical strategies with behavioral interventions that are socially and culturally appropriate for the population or community being prioritized. Although there has been a push for a combination approach, how best to integrate different strategies into existing behavioral HIV prevention interventions remains unclear. The need to develop effective combination approaches is of particular importance for men who have sex with men (MSM), who face a disproportionately high risk of HIV acquisition. Materials and Methods We collaborated with Latino male couples and providers to adapt Connect ‘n Unite, an evidence-based intervention for Black male couples, for Latino male couples. We conducted a series of three focus groups, each with two cohorts of couples, and one focus group with providers. A purposive stratified sample of 20 couples (N = 40, divided into two cohorts) and 10 providers provided insights into how to adapt and integrate social, cultural, and biomedical approaches in a couples-based HIV/AIDS behavioral intervention. Results The majority (N = 37) of the couple participants had no prior knowledge of the following new biomedical strategies: non-occupational post-exposure prophylaxis (nPEP); pre-exposure prophylaxis (PrEP); and HIV self-testing kits. After they were introduced to these biomedical interventions, all participants expressed a need for information and empowerment through knowledge and awareness of these interventions. In particular, participants suggested that we provide PrEP and HIV self-testing kits by the middle or end of the intervention. Providers suggested a need to address behavioral, social and structural issues, such as language barriers; and the promotion of client-centered approaches to increase access to, adaptation of, and adherence to biomedical strategies. Corroborating what couple participants suggested, providers agreed that

  11. Caenorhabditis elegans glutamylating enzymes function redundantly in male mating.

    PubMed

    Chawla, Daniel G; Shah, Ruchi V; Barth, Zachary K; Lee, Jessica D; Badecker, Katherine E; Naik, Anar; Brewster, Megan M; Salmon, Timothy P; Peel, Nina

    2016-09-15

    Microtubule glutamylation is an important modulator of microtubule function and has been implicated in the regulation of centriole stability, neuronal outgrowth and cilia motility. Glutamylation of the microtubules is catalyzed by a family of tubulin tyrosine ligase-like (TTLL) enzymes. Analysis of individual TTLL enzymes has led to an understanding of their specific functions, but how activities of the TTLL enzymes are coordinated to spatially and temporally regulate glutamylation remains relatively unexplored. We have undertaken an analysis of the glutamylating TTLL enzymes in C. elegans We find that although all five TTLL enzymes are expressed in the embryo and adult worm, loss of individual enzymes does not perturb microtubule function in embryonic cell divisions. Moreover, normal dye-filling, osmotic avoidance and male mating behavior indicate the presence of functional amphid cilia and male-specific neurons. A ttll-4(tm3310); ttll-11(tm4059); ttll-5(tm3360) triple mutant, however, shows reduced male mating efficiency due to a defect in the response step, suggesting that these three enzymes function redundantly, and that glutamylation is required for proper function of the male-specific neurons. © 2016. Published by The Company of Biologists Ltd.

  12. Uncovering Hidden Layers of Cell Cycle Regulation through Integrative Multi-omic Analysis

    PubMed Central

    Aviner, Ranen; Shenoy, Anjana; Elroy-Stein, Orna; Geiger, Tamar

    2015-01-01

    Studying the complex relationship between transcription, translation and protein degradation is essential to our understanding of biological processes in health and disease. The limited correlations observed between mRNA and protein abundance suggest pervasive regulation of post-transcriptional steps and support the importance of profiling mRNA levels in parallel to protein synthesis and degradation rates. In this work, we applied an integrative multi-omic approach to study gene expression along the mammalian cell cycle through side-by-side analysis of mRNA, translation and protein levels. Our analysis sheds new light on the significant contribution of both protein synthesis and degradation to the variance in protein expression. Furthermore, we find that translation regulation plays an important role at S-phase, while progression through mitosis is predominantly controlled by changes in either mRNA levels or protein stability. Specific molecular functions are found to be co-regulated and share similar patterns of mRNA, translation and protein expression along the cell cycle. Notably, these include genes and entire pathways not previously implicated in cell cycle progression, demonstrating the potential of this approach to identify novel regulatory mechanisms beyond those revealed by traditional expression profiling. Through this three-level analysis, we characterize different mechanisms of gene expression, discover new cycling gene products and highlight the importance and utility of combining datasets generated using different techniques that monitor distinct steps of gene expression. PMID:26439921

  13. Integrative Genomic Analysis Identifies Isoleucine and CodY as Regulators of Listeria monocytogenes Virulence

    PubMed Central

    Lobel, Lior; Sigal, Nadejda; Borovok, Ilya; Ruppin, Eytan; Herskovits, Anat A.

    2012-01-01

    Intracellular bacterial pathogens are metabolically adapted to grow within mammalian cells. While these adaptations are fundamental to the ability to cause disease, we know little about the relationship between the pathogen's metabolism and virulence. Here we used an integrative Metabolic Analysis Tool that combines transcriptome data with genome-scale metabolic models to define the metabolic requirements of Listeria monocytogenes during infection. Twelve metabolic pathways were identified as differentially active during L. monocytogenes growth in macrophage cells. Intracellular replication requires de novo synthesis of histidine, arginine, purine, and branch chain amino acids (BCAAs), as well as catabolism of L-rhamnose and glycerol. The importance of each metabolic pathway during infection was confirmed by generation of gene knockout mutants in the respective pathways. Next, we investigated the association of these metabolic requirements in the regulation of L. monocytogenes virulence. Here we show that limiting BCAA concentrations, primarily isoleucine, results in robust induction of the master virulence activator gene, prfA, and the PrfA-regulated genes. This response was specific and required the nutrient responsive regulator CodY, which is known to bind isoleucine. Further analysis demonstrated that CodY is involved in prfA regulation, playing a role in prfA activation under limiting conditions of BCAAs. This study evidences an additional regulatory mechanism underlying L. monocytogenes virulence, placing CodY at the crossroads of metabolism and virulence. PMID:22969433

  14. Integrated Proteomics and Metabolomics Suggests Symbiotic Metabolism and Multimodal Regulation in a Fungal-Endobacterial System: Symbiotic Metabolism and Multimodal Regulation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Zhou; Yao, Qiuming; Dearth, Stephen P.

    Many plant-associated fungi host endosymbiotic endobacteria with reduced genomes. While endobacteria play important roles in these tri-partite plant-fungal-endobacterial systems, the active physiology of fungal endobacteria has not been characterized extensively by systems biology approaches. Here in this paper, we use integrated proteomics and metabolomics to characterize the relationship between the endobacterium Mycoavidus sp. and the root-associated fungus Mortierella elongata. In nitrogen-poor media, M. elongata had decreased growth but hosted a large and growing endobacterial population. The active endobacterium likely extracted malate from the fungal host as the primary carbon substrate for energy production and biosynthesis of phospho-sugars, nucleobases, peptidoglycan, andmore » some amino acids. The endobacterium obtained nitrogen by importing a variety of nitrogen-containing compounds. Further, nitrogen limitation significantly perturbed the carbon and nitrogen flows in the fungal metabolic network. M. elongata regulated many pathways by concordant changes on enzyme abundances, post-translational modifications, reactant concentrations, and allosteric effectors. Lastly, such multimodal regulations may be a general mechanism for metabolic modulation.« less

  15. Integrated Proteomics and Metabolomics Suggests Symbiotic Metabolism and Multimodal Regulation in a Fungal-Endobacterial System: Symbiotic Metabolism and Multimodal Regulation

    DOE PAGES

    Li, Zhou; Yao, Qiuming; Dearth, Stephen P.; ...

    2016-11-21

    Many plant-associated fungi host endosymbiotic endobacteria with reduced genomes. While endobacteria play important roles in these tri-partite plant-fungal-endobacterial systems, the active physiology of fungal endobacteria has not been characterized extensively by systems biology approaches. Here in this paper, we use integrated proteomics and metabolomics to characterize the relationship between the endobacterium Mycoavidus sp. and the root-associated fungus Mortierella elongata. In nitrogen-poor media, M. elongata had decreased growth but hosted a large and growing endobacterial population. The active endobacterium likely extracted malate from the fungal host as the primary carbon substrate for energy production and biosynthesis of phospho-sugars, nucleobases, peptidoglycan, andmore » some amino acids. The endobacterium obtained nitrogen by importing a variety of nitrogen-containing compounds. Further, nitrogen limitation significantly perturbed the carbon and nitrogen flows in the fungal metabolic network. M. elongata regulated many pathways by concordant changes on enzyme abundances, post-translational modifications, reactant concentrations, and allosteric effectors. Lastly, such multimodal regulations may be a general mechanism for metabolic modulation.« less

  16. Strong contribution of immigration to local population regulation: evidence from a migratory passerine.

    PubMed

    Schaub, Michael; Jakober, Hans; Stauber, Wolfgang

    2013-08-01

    A mechanistic understanding of the dynamics of populations requires knowledge about the variation of the underlying demographic rates and about the reasons for their variability. In geographically open populations, immigration is often necessary to prevent declines, but little is known about whether immigration can contribute to its regulation. We studied the dynamics of a Red-backed Shrike population (Lanius collurio) over 36 years in Germany with a Bayesian integrated population model. We estimated mean and temporal variability of population sizes, productivity, apparent survival, and immigration. We assessed how strongly the demographic rates were correlated with population growth to understand the demographic reasons of population change and how strongly the demographic rates were correlated with population size to identify possible density-dependent mechanisms. The shrike population varied between 35 and 74 breeding pairs but did not show a significant trend in population size over time (growth rate 1.002 +/- 0.001 [mean +/- SD]). Apparent survival of females (juveniles 0.06 +/- 0.01; adults 0.37 +/- 0.03) was lower than that of males (juveniles 0.10 +/- 0.01; adults 0.44 +/- 0.02). Immigration rates were substantial and higher in females (0.56 +/- 0.02) than in males (0.43 +/- 0.02), and average productivity was 2.76 +/- 0.14. Without immigration, the Red-backed Shrike population would have declined strongly. Immigration was the strongest driver for the number of females while local recruitment was the most important driver for the number of males. Immigration of both sexes and productivity, but not local recruitment and survival, were subject to density dependence. Density-dependent productivity was not effectively regulating the local population but may have contributed to regulate shrike populations at larger spatial scales. These findings suggest that immigration is not only an important component to prevent a geographically open population from decline

  17. Effect of Integrated Approach of Yoga Therapy on Male Obesity and Psychological Parameters-A Randomised Controlled Trial

    PubMed Central

    Subramanya, Pailoor

    2016-01-01

    Introduction Obesity is a growing global epidemic and cause of non-communicable diseases. Yoga is one of the effective ways to reduce stress which is one of the causes of obesity. Aim To assess the effect of Integrated Approach of Yoga Therapy (IAYT) yoga module on adult male obesity in an urban setting. Materials and Methods RCT (Randomized Controlled Trial) was conducted for 14 weeks on obese male subjects with yoga and control groups. Total number of subjects were 72 and they were randomized into two groups (Yoga n=37, Control n=35). The subjects were from an urban setting of Mumbai and were doing yoga for the first time. Special yoga training of IAYT was given to yoga group for one and half hour for 5 days in a week for 14 weeks. The control group continued regular physical activities and no specific physical activity was given. The assessments were anthropometric parameters of weight, Body Mass Index (BMI), MAC (Mid Upper Arm Circumferences) of Left and Right Arm, Waist Circumference (WC), HC (Hip Circumference), WHR (Waist Hip Ratio), SKF(Skin Fold Thickness of Biceps, Triceps, Sub scapular, suprailiac and cumulative), Percentage body fat based on SKF and Psychological Questionnaires of Perceived Stress Scale (PSS) and AAQW (Acceptance and Action Questionnaire for Weight Related Difficulty). These were taken before and after intervention for both yoga and control groups. Within and between group analysis & correlation of differences from post to pre readings among the variables, were carried out using SPSS 21. Results The anthropometric and psychological parameters were improved in both the groups but changes were significant in yoga group. Conclusion Incorporating the IAYT for obese male in urban setting will be effective for obesity treatment and for reducing the obesity related problems. PMID:27891357

  18. New approaches to male non-hormonal contraception.

    PubMed

    Nya-Ngatchou, Jean-Jacques; Amory, John K

    2013-03-01

    A non-hormonal male contraceptive is a contraceptive that does not involve the administration of hormones or hormone blockers. This review will focus on the use of lonidamine derivatives and inhibitors of retinoic acid biosynthesis and function as approaches to male non-hormonal contraception. Two current lonidamine derivatives, adjudin and H2-gamendazole, are in development as male contraceptives. These potent anti-spermatogenic compounds impair the integrity of the apical ectoplasmic specialization, resulting in premature spermiation and infertility. Another approach to male contraceptive development is the inhibition of retinoic acid in the testes, as retinoic acid signaling is necessary for spermatogenesis. The administration of the retinoic acid receptor antagonist BMS-189453 reversibly inhibits spermatogenesis in mice. Similarly, oral dosing of WIN 18,446, which inhibits testicular retinoic acid biosynthesis, effectively contracepts rabbits. Hopefully, one of these approaches to non-hormonal male contraception will prove to be safe and effective in future clinical trials. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. New approaches to male non-hormonal contraception

    PubMed Central

    Nya-Ngatchou, Jean-Jacques; Amory, John K.

    2012-01-01

    A non-hormonal male contraceptive is a contraceptive that does not involve the administration of hormones or hormone blockers. This review will focus on the use of lonidamine derivatives and inhibitors of retinoic acid biosynthesis and function as approaches to male non-hormonal contraception. Two current lonidamine derivatives, Adjudin and H2-gamendazole, are in development as male contraceptives. These potent anti-spermatogenic compounds impair the integrity of the apical ectoplasmic specialization, resulting in premature spermiation and infertility. Another approach to male contraceptive development is the inhibition of retinoic acid in the testes, as retinoic acid signaling is necessary for spermatogenesis. The administration of the retinoic acid receptor antagonist BMS-189453 reversibly inhibits spermatogenesis in mice. Similarly, oral dosing of WIN 18,446, which inhibits testicular retinoic acid biosynthesis, effectively contracepts rabbits. Hopefully, one of these approaches to non-hormonal male contraception will prove to be safe and effective in future clinical trials. PMID:22995542

  20. Inhibition of Estradiol Synthesis Impairs Fear Extinction in Male Rats

    ERIC Educational Resources Information Center

    Graham, Bronwyn M.; Milad, Mohammed R.

    2014-01-01

    Emerging research has demonstrated that the sex hormone estradiol regulates fear extinction in female rodents and women. Estradiol may also regulate fear extinction in males, given its role in synaptic plasticity in both sexes. Here we report that inhibition of estradiol synthesis during extinction training, via the aromatase inhibitor fadrozole,…

  1. Sex determination in beetles: Production of all male progeny by Parental RNAi knockdown of transformer

    PubMed Central

    Shukla, Jayendra Nath; Palli, Subba Reddy

    2012-01-01

    Sex in insects is determined by a cascade of regulators ultimately controlling sex-specific splicing of a transcription factor, Doublesex (Dsx). We recently identified homolog of dsx in the red flour beetle, Tribolium castaneum (Tcdsx). Here, we report on the identification and characterization of a regulator of Tcdsx splicing in T. castaneum. Two male-specific and one female-specific isoforms of T. castaneum transformer (Tctra) were identified. RNA interference-aided knockdown of Tctra in pupa or adults caused a change in sex from females to males by diverting the splicing of Tcdsx pre-mRNA to male-specific isoform. All the pupa and adults developed from Tctra dsRNA injected final instar larvae showed male-specific sexually dimorphic structures. Tctra parental RNAi caused an elimination of females from the progeny resulting in production of all male progeny. Transformer parental RNAi could be used to produce all male population for use in pest control though sterile male release methods. PMID:22924109

  2. The splicing activator DAZAP1 integrates splicing control into MEK/Erk regulated cell proliferation and migration

    PubMed Central

    Choudhury, Rajarshi; Roy, Sreerupa Ghose; Tsai, Yihsuan S.; Tripathy, Ashutosh; Graves, Lee M.; Wang, Zefeng

    2014-01-01

    Alternative splicing of pre-mRNA is a critical stage of gene regulation in response to environmental stimuli. Here we show that DAZAP1, an RNA binding protein involved in mammalian development and spermatogenesis, promotes inclusion of weak exons through specific recognition of diverse cis-elements. The C-terminal proline-rich domain of DAZAP1 interacts with and neutralizes general splicing inhibitors, and is sufficient to activate splicing when recruited to pre-mRNA. This domain is phosphorylated by the MEK/Erk pathway and this modification is essential for the splicing regulatory activity and the nuclear/cytoplasmic translocation of DAZAP1. Using mRNA-seq we identify endogenous splicing events regulated by DAZAP1, many of which are involved in maintaining cell growth. Knockdown or over-expression of DAZAP1 causes a cell proliferation defect. Taken together, these studies reveal a molecular mechanism that integrates splicing control into MEK/Erk regulated cell proliferation. PMID:24452013

  3. LGR4 and its ligands, R-spondin 1 and R-spondin 3, regulate food intake in the hypothalamus of male rats.

    PubMed

    Li, Ji-Yao; Chai, Biaoxin; Zhang, Weizhen; Fritze, Danielle M; Zhang, Chao; Mulholland, Michael W

    2014-02-01

    The hypothalamus plays a key role in the regulation of feeding behavior. Several hypothalamic nuclei, including the arcuate nucleus (ARC), paraventricular nucleus, and ventromedial nucleus of the hypothalamus (VMH), are involved in energy homeostasis. Analysis of microarray data derived from ARC revealed that leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) is highly expressed. LGR4, LGR5, and LGR6 form a subfamily of closely related receptors. Recently, R-spondin (Rspo) family proteins were identified as ligands of the LGR4 subfamily. In the present study, we investigated the distribution and function of LGR4-LGR6 and Rspos (1-4) in the brain of male rat. In situ hybridization showed that LGR4 is expressed in the ARC, VMH, and median eminence of the hypothalamus. LGR4 colocalizes with neuropeptide Y, proopiomelanocortin, and brain-derived neurotrophic factor neurons. LGR5 is not detectable with in situ hybridization; LGR6 is only expressed in the epithelial lining of the lower portion of the third ventricle and median eminence. Rspo1 is expressed in the VMH and down-regulated with fasting. Rspo3 is expressed in the paraventricular nucleus and also down-regulated with fasting. Rspos 1 and 3 colocalize with the neuronal marker HuD, indicating that they are expressed by neurons. Injection of Rspo1 or Rspo3 into the third brain ventricle inhibited food intake. Rspo1 decreased neuropeptide Y and increased proopiomelanocortin expression in the ARC. Rspo1 and Rspo3 mRNA is up-regulated by insulin. These data indicate that Rspo1 and Rspo3 and their receptor LGR4 form novel circuits in the brain to regulate energy homeostasis.

  4. Integrating environmental management into food safety and food packaging in Malaysia: review of the food regulation 1985

    NASA Astrophysics Data System (ADS)

    Nordin, N. H.; Hara, H.; Kaida, N.

    2017-05-01

    Food safety is an important issue that is related to public safety to prevent the toxicity threats of the food. Management through legal approach has been used in Malaysia as one of the predominant approaches to manage the environment. In this regard, the Food Regulation 1985 has been one of the mechanisms of environmental management through legal approach in controlling the safety of packaged food in food packaging industry in Malaysia. The present study aims to analyse and to explain the implementation of the Food Regulation 1985 in controlling the safety of packaged food in Malaysia and to integrate the concept of environmental management into the food safety issue. Qualitative analysis on the regulation document revealed that there are two main themes, general and specific, while their seven sub themes are included harmful packages, safety packages, reuse packages, polyvinyl chloride (PVC), alcoholic bottle, toys, money and others and iron powder. The implementation of the Food Regulation 1985 in controlling the safety of packaged food should not be regarded solely for regulation purposes but should be further developed for a broader sense of food safety from overcoming the food poisoning.

  5. Novel Role for p110β PI 3-Kinase in Male Fertility through Regulation of Androgen Receptor Activity in Sertoli Cells

    PubMed Central

    Guillermet-Guibert, Julie; Smith, Lee B.; Halet, Guillaume; Whitehead, Maria A.; Pearce, Wayne; Rebourcet, Diane; León, Kelly; Crépieux, Pascale; Nock, Gemma; Strömstedt, Maria; Enerback, Malin; Chelala, Claude; Graupera, Mariona; Carroll, John; Cosulich, Sabina; Saunders, Philippa T. K.; Huhtaniemi, Ilpo; Vanhaesebroeck, Bart

    2015-01-01

    The organismal roles of the ubiquitously expressed class I PI3K isoform p110β remain largely unknown. Using a new kinase-dead knockin mouse model that mimics constitutive pharmacological inactivation of p110β, we document that full inactivation of p110β leads to embryonic lethality in a substantial fraction of mice. Interestingly, the homozygous p110β kinase-dead mice that survive into adulthood (maximum ~26% on a mixed genetic background) have no apparent phenotypes, other than subfertility in females and complete infertility in males. Systemic inhibition of p110β results in a highly specific blockade in the maturation of spermatogonia to spermatocytes. p110β was previously suggested to signal downstream of the c-kit tyrosine kinase receptor in germ cells to regulate their proliferation and survival. We now report that p110β also plays a germ cell-extrinsic role in the Sertoli cells (SCs) that support the developing sperm, with p110β inactivation dampening expression of the SC-specific Androgen Receptor (AR) target gene Rhox5, a homeobox gene critical for spermatogenesis. All extragonadal androgen-dependent functions remain unaffected by global p110β inactivation. In line with a crucial role for p110β in SCs, selective inactivation of p110β in these cells results in male infertility. Our study is the first documentation of the involvement of a signalling enzyme, PI3K, in the regulation of AR activity during spermatogenesis. This developmental pathway may become active in prostate cancer where p110β and AR have previously been reported to functionally interact. PMID:26132308

  6. Aurora Kinase B, a novel regulator of TERF1 binding and telomeric integrity

    PubMed Central

    Chan, Foong Lyn; Vinod, Benjamin; Novy, Karel; Schittenhelm, Ralf B.; Huang, Cheng; Udugama, Maheshi; Nunez-Iglesias, Juan; Lin, Jane I.; Hii, Linda; Chan, Julie; Pickett, Hilda A.; Daly, Roger J.

    2017-01-01

    Abstract AURKB (Aurora Kinase B) is a serine/threonine kinase better known for its role at the mitotic kinetochore during chromosome segregation. Here, we demonstrate that AURKB localizes to the telomeres in mouse embryonic stem cells, where it interacts with the essential telomere protein TERF1. Loss of AURKB function affects TERF1 telomere binding and results in aberrant telomere structure. In vitro kinase experiments successfully identified Serine 404 on TERF1 as a putative AURKB target site. Importantly, in vivo overexpression of S404-TERF1 mutants results in fragile telomere formation. These findings demonstrate that AURKB is an important regulator of telomere structural integrity. PMID:29040668

  7. Juvenile hormone-dopamine systems for the promotion of flight activity in males of the large carpenter bee Xylocopa appendiculata.

    PubMed

    Sasaki, Ken; Nagao, Takashi

    2013-12-01

    The reproductive roles of dopamine and dopamine regulation systems are known in social hymenopterans, but the knowledge on the regulation systems in solitary species is still needed. To test the possibility that juvenile hormone (JH) and brain dopamine interact to trigger territorial flight behavior in males of a solitary bee species, the effects on biogenic amines of JH analog treatments and behavioral assays with dopamine injections in males of the large carpenter bee Xylocopa appendiculata were quantified. Brain dopamine levels were significantly higher in methoprene-treated males than in control males 4 days after treatment, but were not significantly different after 7 days. Brain octopamine and serotonin levels did not differ between methoprene-treated and control males at 4 and 7 days after treatment. Injection of dopamine caused significantly higher locomotor activities and a shorter duration for flight initiation in experimental versus control males. These results suggest that brain dopamine can be regulated by JH and enhances flight activities in males. The JH-dopamine system in males of this solitary bee species is similar to that of males of the highly eusocial honeybee Apis mellifera.

  8. Juvenile hormone-dopamine systems for the promotion of flight activity in males of the large carpenter bee Xylocopa appendiculata

    NASA Astrophysics Data System (ADS)

    Sasaki, Ken; Nagao, Takashi

    2013-12-01

    The reproductive roles of dopamine and dopamine regulation systems are known in social hymenopterans, but the knowledge on the regulation systems in solitary species is still needed. To test the possibility that juvenile hormone (JH) and brain dopamine interact to trigger territorial flight behavior in males of a solitary bee species, the effects on biogenic amines of JH analog treatments and behavioral assays with dopamine injections in males of the large carpenter bee Xylocopa appendiculata were quantified. Brain dopamine levels were significantly higher in methoprene-treated males than in control males 4 days after treatment, but were not significantly different after 7 days. Brain octopamine and serotonin levels did not differ between methoprene-treated and control males at 4 and 7 days after treatment. Injection of dopamine caused significantly higher locomotor activities and a shorter duration for flight initiation in experimental versus control males. These results suggest that brain dopamine can be regulated by JH and enhances flight activities in males. The JH-dopamine system in males of this solitary bee species is similar to that of males of the highly eusocial honeybee Apis mellifera.

  9. Vitamin D metabolism, sex hormones, and male reproductive function.

    PubMed

    Blomberg Jensen, Martin

    2012-08-01

    The spectrum of vitamin D (VD)-mediated effects has expanded in recent years, and VD is now recognized as a versatile signaling molecule rather than being solely a regulator of bone health and calcium homeostasis. One of the recently identified target areas of VD is male reproductive function. The VD receptor (VDR) and the VD metabolizing enzyme expression studies documented the presence of this system in the testes, mature spermatozoa, and ejaculatory tract, suggesting that both systemic and local VD metabolism may influence male reproductive function. However, it is still debated which cell is the main VD target in the testis and to what extent VD is important for sex hormone production and function of spermatozoa. This review summarizes descriptive studies on testicular VD metabolism and spatial distribution of VDR and the VD metabolizing enzymes in the mammalian testes and discusses mechanistic and association studies conducted in animals and humans. The reviewed evidence suggests some effects of VD on estrogen and testosterone biosynthesis and implicates involvement of both systemic and local VD metabolism in the regulation of male fertility potential.

  10. New frontiers in nonhormonal male contraception

    PubMed Central

    Cheng, C. Yan; Mruk, Dolores D.

    2015-01-01

    The world’s population is nearing 6.8 billion, and we are in need of a male contraceptive that is safe, effective, reversible and affordable. Hormonal approaches, which employ different formulations of testosterone administered in combination with other hormones, have shown considerable promise in clinical trials, and they are currently at the forefront of research and development. However, the long-term effects of using hormones throughout a male’s reproductive life for contraception are unknown, and it may take decades before this information becomes available. Because of this, many investigators are aiming to bring a nonhormonal male contraceptive to the consumer market. Indeed, there are several distinct but feasible avenues in which fertility can be regulated without affecting the hypothalamus-pituitary-testis axis. In this review, we discuss several approaches for fertility control involving the testis that one day may lead to the development of a nonhormonal male contraceptive. PMID:20933122

  11. Mining disease genes using integrated protein-protein interaction and gene-gene co-regulation information.

    PubMed

    Li, Jin; Wang, Limei; Guo, Maozu; Zhang, Ruijie; Dai, Qiguo; Liu, Xiaoyan; Wang, Chunyu; Teng, Zhixia; Xuan, Ping; Zhang, Mingming

    2015-01-01

    In humans, despite the rapid increase in disease-associated gene discovery, a large proportion of disease-associated genes are still unknown. Many network-based approaches have been used to prioritize disease genes. Many networks, such as the protein-protein interaction (PPI), KEGG, and gene co-expression networks, have been used. Expression quantitative trait loci (eQTLs) have been successfully applied for the determination of genes associated with several diseases. In this study, we constructed an eQTL-based gene-gene co-regulation network (GGCRN) and used it to mine for disease genes. We adopted the random walk with restart (RWR) algorithm to mine for genes associated with Alzheimer disease. Compared to the Human Protein Reference Database (HPRD) PPI network alone, the integrated HPRD PPI and GGCRN networks provided faster convergence and revealed new disease-related genes. Therefore, using the RWR algorithm for integrated PPI and GGCRN is an effective method for disease-associated gene mining.

  12. Integral control of plant gravitropism through the interplay of hormone signaling and gene regulation.

    PubMed

    Rodrigo, Guillermo; Jaramillo, Alfonso; Blázquez, Miguel A

    2011-08-17

    The interplay between hormone signaling and gene regulatory networks is instrumental in promoting the development of living organisms. In particular, plants have evolved mechanisms to sense gravity and orient themselves accordingly. Here, we present a mathematical model that reproduces plant gravitropic responses based on known molecular genetic interactions for auxin signaling coupled with a physical description of plant reorientation. The model allows one to analyze the spatiotemporal dynamics of the system, triggered by an auxin gradient that induces differential growth of the plant with respect to the gravity vector. Our model predicts two important features with strong biological implications: 1), robustness of the regulatory circuit as a consequence of integral control; and 2), a higher degree of plasticity generated by the molecular interplay between two classes of hormones. Our model also predicts the ability of gibberellins to modulate the tropic response and supports the integration of the hormonal role at the level of gene regulation. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  13. RegulonDB version 9.0: high-level integration of gene regulation, coexpression, motif clustering and beyond

    PubMed Central

    Gama-Castro, Socorro; Salgado, Heladia; Santos-Zavaleta, Alberto; Ledezma-Tejeida, Daniela; Muñiz-Rascado, Luis; García-Sotelo, Jair Santiago; Alquicira-Hernández, Kevin; Martínez-Flores, Irma; Pannier, Lucia; Castro-Mondragón, Jaime Abraham; Medina-Rivera, Alejandra; Solano-Lira, Hilda; Bonavides-Martínez, César; Pérez-Rueda, Ernesto; Alquicira-Hernández, Shirley; Porrón-Sotelo, Liliana; López-Fuentes, Alejandra; Hernández-Koutoucheva, Anastasia; Moral-Chávez, Víctor Del; Rinaldi, Fabio; Collado-Vides, Julio

    2016-01-01

    RegulonDB (http://regulondb.ccg.unam.mx) is one of the most useful and important resources on bacterial gene regulation,as it integrates the scattered scientific knowledge of the best-characterized organism, Escherichia coli K-12, in a database that organizes large amounts of data. Its electronic format enables researchers to compare their results with the legacy of previous knowledge and supports bioinformatics tools and model building. Here, we summarize our progress with RegulonDB since our last Nucleic Acids Research publication describing RegulonDB, in 2013. In addition to maintaining curation up-to-date, we report a collection of 232 interactions with small RNAs affecting 192 genes, and the complete repertoire of 189 Elementary Genetic Sensory-Response units (GENSOR units), integrating the signal, regulatory interactions, and metabolic pathways they govern. These additions represent major progress to a higher level of understanding of regulated processes. We have updated the computationally predicted transcription factors, which total 304 (184 with experimental evidence and 120 from computational predictions); we updated our position-weight matrices and have included tools for clustering them in evolutionary families. We describe our semiautomatic strategy to accelerate curation, including datasets from high-throughput experiments, a novel coexpression distance to search for ‘neighborhood’ genes to known operons and regulons, and computational developments. PMID:26527724

  14. Negative regulation of ciliary length by ciliary male germ cell-associated kinase (Mak) is required for retinal photoreceptor survival.

    PubMed

    Omori, Yoshihiro; Chaya, Taro; Katoh, Kimiko; Kajimura, Naoko; Sato, Shigeru; Muraoka, Koichiro; Ueno, Shinji; Koyasu, Toshiyuki; Kondo, Mineo; Furukawa, Takahisa

    2010-12-28

    Cilia function as cell sensors in many organs, and their disorders are referred to as "ciliopathies." Although ciliary components and transport machinery have been well studied, regulatory mechanisms of ciliary formation and maintenance are poorly understood. Here we show that male germ cell-associated kinase (Mak) regulates retinal photoreceptor ciliary length and subcompartmentalization. Mak was localized both in the connecting cilia and outer-segment axonemes of photoreceptor cells. In the Mak-null retina, photoreceptors exhibit elongated cilia and progressive degeneration. We observed accumulation of intraflagellar transport 88 (IFT88) and IFT57, expansion of kinesin family member 3A (Kif3a), and acetylated α-tubulin signals in the Mak-null photoreceptor cilia. We found abnormal rhodopsin accumulation in the Mak-null photoreceptor cell bodies at postnatal day 14. In addition, overexpression of retinitis pigmentosa 1 (RP1), a microtubule-associated protein localized in outer-segment axonemes, induced ciliary elongation, and Mak coexpression rescued excessive ciliary elongation by RP1. The RP1 N-terminal portion induces ciliary elongation and increased intensity of acetylated α-tubulin labeling in the cells and is phosphorylated by Mak. These results suggest that Mak is essential for the regulation of ciliary length and is required for the long-term survival of photoreceptors.

  15. Negative regulation of ciliary length by ciliary male germ cell-associated kinase (Mak) is required for retinal photoreceptor survival

    PubMed Central

    Omori, Yoshihiro; Chaya, Taro; Katoh, Kimiko; Kajimura, Naoko; Sato, Shigeru; Muraoka, Koichiro; Ueno, Shinji; Koyasu, Toshiyuki; Kondo, Mineo; Furukawa, Takahisa

    2010-01-01

    Cilia function as cell sensors in many organs, and their disorders are referred to as “ciliopathies.” Although ciliary components and transport machinery have been well studied, regulatory mechanisms of ciliary formation and maintenance are poorly understood. Here we show that male germ cell-associated kinase (Mak) regulates retinal photoreceptor ciliary length and subcompartmentalization. Mak was localized both in the connecting cilia and outer-segment axonemes of photoreceptor cells. In the Mak-null retina, photoreceptors exhibit elongated cilia and progressive degeneration. We observed accumulation of intraflagellar transport 88 (IFT88) and IFT57, expansion of kinesin family member 3A (Kif3a), and acetylated α-tubulin signals in the Mak-null photoreceptor cilia. We found abnormal rhodopsin accumulation in the Mak-null photoreceptor cell bodies at postnatal day 14. In addition, overexpression of retinitis pigmentosa 1 (RP1), a microtubule-associated protein localized in outer-segment axonemes, induced ciliary elongation, and Mak coexpression rescued excessive ciliary elongation by RP1. The RP1 N-terminal portion induces ciliary elongation and increased intensity of acetylated α-tubulin labeling in the cells and is phosphorylated by Mak. These results suggest that Mak is essential for the regulation of ciliary length and is required for the long-term survival of photoreceptors. PMID:21148103

  16. LGR4 and Its Ligands, R-Spondin 1 and R-Spondin 3, Regulate Food Intake in the Hypothalamus of Male Rats

    PubMed Central

    Li, Ji-Yao; Chai, Biaoxin; Zhang, Weizhen; Fritze, Danielle M.; Zhang, Chao

    2014-01-01

    The hypothalamus plays a key role in the regulation of feeding behavior. Several hypothalamic nuclei, including the arcuate nucleus (ARC), paraventricular nucleus, and ventromedial nucleus of the hypothalamus (VMH), are involved in energy homeostasis. Analysis of microarray data derived from ARC revealed that leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) is highly expressed. LGR4, LGR5, and LGR6 form a subfamily of closely related receptors. Recently, R-spondin (Rspo) family proteins were identified as ligands of the LGR4 subfamily. In the present study, we investigated the distribution and function of LGR4–LGR6 and Rspos (1–4) in the brain of male rat. In situ hybridization showed that LGR4 is expressed in the ARC, VMH, and median eminence of the hypothalamus. LGR4 colocalizes with neuropeptide Y, proopiomelanocortin, and brain-derived neurotrophic factor neurons. LGR5 is not detectable with in situ hybridization; LGR6 is only expressed in the epithelial lining of the lower portion of the third ventricle and median eminence. Rspo1 is expressed in the VMH and down-regulated with fasting. Rspo3 is expressed in the paraventricular nucleus and also down-regulated with fasting. Rspos 1 and 3 colocalize with the neuronal marker HuD, indicating that they are expressed by neurons. Injection of Rspo1 or Rspo3 into the third brain ventricle inhibited food intake. Rspo1 decreased neuropeptide Y and increased proopiomelanocortin expression in the ARC. Rspo1 and Rspo3 mRNA is up-regulated by insulin. These data indicate that Rspo1 and Rspo3 and their receptor LGR4 form novel circuits in the brain to regulate energy homeostasis. PMID:24280058

  17. Social regulation of gonadotropin-releasing hormone.

    PubMed

    White, Stephanie A; Nguyen, Tuan; Fernald, Russell D

    2002-09-01

    Behavioral interactions among social animals can regulate both reproductive behavior and fertility. A prime example of socially regulated reproduction occurs in the cichlid fish Haplochromis burtoni, in which interactions between males dynamically regulate gonadal function throughout life. This plasticity is mediated by the brain, where neurons that contain the key reproductive regulatory peptide gonadotropin-releasing hormone (GnRH) change size reversibly depending on male social status. To understand how behavior controls the brain, we manipulated the social system of these fish, quantified their behavior and then assessed neural and physiological changes in the reproductive and stress axes. GnRH gene expression was assessed using molecular probes specific for the three GnRH forms in the brain of H. burtoni. We found that perception of social opportunity to increase status by a male leads to heightened aggressiveness, to increased expression of only one of the three GnRH forms and to increases in size of GnRH-containing neurons and of the gonads. The biological changes characteristic of social ascent happen faster than changes following social descent. Interestingly, behavioral changes show the reverse pattern: aggressive behaviors emerge more slowly in ascending animals than they disappear in descending animals. Although the gonads and GnRH neurons undergo similar changes in female H. burtoni, regulation occurs via endogenous rather than exogenous social signals. Our data show that recognition of social signals by males alters stress levels, which may contribute to the alteration in GnRH gene expression in particular neurons essential for the animal to perform in its new social status.

  18. Self-Monitoring Strategies as a Unique Predictor of Latino Male Student Achievement

    ERIC Educational Resources Information Center

    Covarrubias, Rebecca; Stone, Jeff

    2015-01-01

    We examined how self-monitoring (i.e., regulating one's behaviors; Snyder, 1987) relates to Latino male achievement. In Study 1, college students (N = 413) completed self-monitoring items and reported SAT math scores. As hypothesized, self-monitoring was positively correlated with achievement for Latino male students but was unrelated to…

  19. Mergeomics: a web server for identifying pathological pathways, networks, and key regulators via multidimensional data integration.

    PubMed

    Arneson, Douglas; Bhattacharya, Anindya; Shu, Le; Mäkinen, Ville-Petteri; Yang, Xia

    2016-09-09

    Human diseases are commonly the result of multidimensional changes at molecular, cellular, and systemic levels. Recent advances in genomic technologies have enabled an outpour of omics datasets that capture these changes. However, separate analyses of these various data only provide fragmented understanding and do not capture the holistic view of disease mechanisms. To meet the urgent needs for tools that effectively integrate multiple types of omics data to derive biological insights, we have developed Mergeomics, a computational pipeline that integrates multidimensional disease association data with functional genomics and molecular networks to retrieve biological pathways, gene networks, and central regulators critical for disease development. To make the Mergeomics pipeline available to a wider research community, we have implemented an online, user-friendly web server ( http://mergeomics. idre.ucla.edu/ ). The web server features a modular implementation of the Mergeomics pipeline with detailed tutorials. Additionally, it provides curated genomic resources including tissue-specific expression quantitative trait loci, ENCODE functional annotations, biological pathways, and molecular networks, and offers interactive visualization of analytical results. Multiple computational tools including Marker Dependency Filtering (MDF), Marker Set Enrichment Analysis (MSEA), Meta-MSEA, and Weighted Key Driver Analysis (wKDA) can be used separately or in flexible combinations. User-defined summary-level genomic association datasets (e.g., genetic, transcriptomic, epigenomic) related to a particular disease or phenotype can be uploaded and computed real-time to yield biologically interpretable results, which can be viewed online and downloaded for later use. Our Mergeomics web server offers researchers flexible and user-friendly tools to facilitate integration of multidimensional data into holistic views of disease mechanisms in the form of tissue-specific key regulators

  20. Suppression and restoration of male fertility using a transcription factor.

    PubMed

    Li, Song Feng; Iacuone, Sylvana; Parish, Roger W

    2007-03-01

    The Arabidopsis AtMYB103 gene codes for an R2R3 MYB domain protein whose expression is restricted to the tapetum of developing anthers and to trichomes. Down-regulation of expression using anti-sense leads to abnormal tapetum and pollen development, although seed setting still occurs (Higginson, T., Li, S.F. and Parish, R.W. (2003) AtMYB103 regulates tapetum and trichome development in Arabidopsis thaliana. Plant J. 35, 177-192). In this study, we show that blocking the function of the AtMYB103 gene, employing either an insertion mutant or an AtMYB103EAR chimeric repressor construct under the control of the AtMYB103 promoter, results in complete male sterility and failure to set seed. These plants exhibit similar abnormalities in tapetum and pollen development, with the tapetum becoming highly vacuolated at early stages and degenerating prematurely. No exine is deposited on to the pollen wall. The degeneration of pollen grains commences prior to pollen mitosis, the pollen collapsing and largely lacking cytoplasmic content. A restorer containing the AtMYB103 gene under the control of a stronger anther-specific promoter was introduced into pollen donor plants and crossed into the male sterile plants transgenic for the repressor. The male fertility of F1 plants was restored. The chimeric repressor and the restorer constitute a reversible male sterility system which could be adapted for hybrid seed production. This is the first reversible male sterility system targeting a transcription factor essential for pollen development. Strategies for generating inducible male sterility and maintainable male sterility for the production of hybrid crops are discussed.

  1. Genome-wide association study of sexual maturation in males and females highlights a role for body mass and menarche loci in male puberty

    PubMed Central

    Cousminer, Diana L.; Stergiakouli, Evangelia; Berry, Diane J.; Ang, Wei; Groen-Blokhuis, Maria M.; Körner, Antje; Siitonen, Niina; Ntalla, Ioanna; Marinelli, Marcella; Perry, John R.B.; Kettunen, Johannes; Jansen, Rick; Surakka, Ida; Timpson, Nicholas J.; Ring, Susan; Mcmahon, George; Power, Chris; Wang, Carol; Kähönen, Mika; Viikari, Jorma; Lehtimäki, Terho; Middeldorp, Christel M.; Hulshoff Pol, Hilleke E.; Neef, Madlen; Weise, Sebastian; Pahkala, Katja; Niinikoski, Harri; Zeggini, Eleftheria; Panoutsopoulou, Kalliope; Bustamante, Mariona; Penninx, Brenda W.J.H.; Murabito, Joanne; Torrent, Maties; Dedoussis, George V.; Kiess, Wieland; Boomsma, Dorret I.; Pennell, Craig E.; Raitakari, Olli T.; Hyppönen, Elina; Davey Smith, George; Ripatti, Samuli; McCarthy, Mark I.; Widén, Elisabeth

    2014-01-01

    Little is known about genes regulating male puberty. Further, while many identified pubertal timing variants associate with age at menarche, a late manifestation of puberty, and body mass, little is known about these variants' relationship to pubertal initiation or tempo. To address these questions, we performed genome-wide association meta-analysis in over 11 000 European samples with data on early pubertal traits, male genital and female breast development, measured by the Tanner scale. We report the first genome-wide significant locus for male sexual development upstream of myocardin-like 2 (MKL2) (P = 8.9 × 10−9), a menarche locus tagging a developmental pathway linking earlier puberty with reduced pubertal growth (P = 4.6 × 10−5) and short adult stature (p = 7.5 × 10−6) in both males and females. Furthermore, our results indicate that a proportion of menarche loci are important for pubertal initiation in both sexes. Consistent with epidemiological correlations between increased prepubertal body mass and earlier pubertal timing in girls, body mass index (BMI)-increasing alleles correlated with earlier breast development. In boys, some BMI-increasing alleles associated with earlier, and others with delayed, sexual development; these genetic results mimic the controversy in epidemiological studies, some of which show opposing correlations between prepubertal BMI and male puberty. Our results contribute to our understanding of the pubertal initiation program in both sexes and indicate that although mechanisms regulating pubertal onset in males and females may largely be shared, the relationship between body mass and pubertal timing in boys may be complex and requires further genetic studies. PMID:24770850

  2. Sleep and emotion regulation: An organizing, integrative review.

    PubMed

    Palmer, Cara A; Alfano, Candice A

    2017-02-01

    A growing body of research suggests that disrupted sleep is a robust risk and maintenance factor for a range of psychiatric conditions. One explanatory mechanism linking sleep and psychological health is emotion regulation. However, numerous components embedded within this construct create both conceptual and empirical challenges to the study of emotion regulation. These challenges are reflected in most sleep-emotion research by way of poor delineation of constructs and insufficient distinction among emotional processes. Most notably, a majority of research has focused on emotions generated as a consequence of inadequate sleep rather than underlying regulatory processes that may alter these experiences. The current review utilizes the process model of emotion regulation as an organizing framework for examining the impact of sleep upon various aspects of emotional experiences. Evidence is provided for maladaptive changes in emotion at multiple stages of the emotion generation and regulation process. We conclude with a call for experimental research designed to clearly explicate which points in the emotion regulation process appear most vulnerable to sleep loss as well as longitudinal studies to follow these processes in relation to the development of psychopathological conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. The regulation of cellular apoptosis by the ROS-triggered PERK/EIF2α/chop pathway plays a vital role in bisphenol A-induced male reproductive toxicity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yin, Li

    Bisphenol A (2,2-bis(4-hydroxyphenyl)propane, BPA) is ubiquitous in the environment, wildlife, and humans. Evidence from past studies suggests that BPA is associated with decreased semen quality. However, the molecular basis for the adverse effect of BPA on male reproductive toxicity remains unclear. We evaluated the effect of BPA on mouse spermatocytes GC-2 cells and adult mice, and we explored the potential mechanism of its action. The results showed that BPA inhibited cell proliferation and increased the apoptosis rate. The testes from BPA-treated mice showed fewer spermatogenic cells and sperm in the seminiferous tubules. In addition, BPA caused reactive oxygen species (ROS)more » accumulation. Previous study has verified that mitochondrion was the organelle affected by the BPA-triggered ROS accumulation. We found that BPA induced damage to the endoplasmic reticulum (ER) in addition to mitochondria, and most ER stress-related proteins were activated in cellular and animal models. Knocking down of the PERK/EIF2α/chop pathway, one of the ER stress pathways, partially recovered the BPA-induced cell apoptosis. In addition, an ROS scavenger attenuated the expression of the PERK/EIF2α/chop pathway-related proteins. Taken together, these data suggested that the ROS regulated PERK/EIF2α/chop pathway played a vital role in BPA-induced male reproductive toxicity. - Highlights: • BPA exposure caused the damage of the endoplasmic reticulum. • BPA exposure activated ER stress related proteins in male reproductive system. • ROS regulated PERK/EIF2α/chop pathway played a vital role in BPA-induced toxicity.« less

  4. Implications of Integrating Women into USMC Infantry

    DTIC Science & Technology

    2015-01-01

    well-defined, updated, and clearly communicated sexual harassment policies; and procedures to ensure that women receive equal training and...traditionally male groups depends on the culture of the group: Groups more hostile to women experience lower cohesion after gender integration than do...creates a hostile environment for women. A variety of efforts can mitigate whatever detrimental effects integration of women would have on male -dominated

  5. Male-mimicking females increase male-male interactions, and decrease male survival and condition in a female-polymorphic damselfly.

    PubMed

    Gering, Eben J

    2017-05-01

    Biologists are still discovering diverse and powerful ways sexual conflicts shape biodiversity. The present study examines how the proportion of females in a population that exhibit male mimicry, a mating resistance trait, influences conspecific males' behavior, condition, and survival. Like most female-polymorphic damselflies, Ischnura ramburii harbors both "andromorph" females, which closely resemble males, and sexually dimorphic "gynomorph" counterparts. There is evidence that male mimicry helps andromorphs evade detection and harassment, but males can also learn to target locally prevalent morph(s) via prior mate encounters. I hypothesized that the presence of male mimics could therefore predispose males to mate recognition errors, and thereby increase rates of costly male-male interactions. Consistent with this hypothesis, male-male interaction rates were highest in mesocosms containing more andromorph (vs. gynomorph) females. Males in andromorph-biased mesocosms also had lower final body mass and higher mortality than males assigned to gynomorph-majority treatments. Male survival and body mass were each negatively affected by mesocosm density, and mortality data revealed a marginally significant interaction between andromorph frequency and population density. These findings suggest that, under sufficiently crowded conditions, female mating resistance traits such as male mimicry could have pronounced indirect effects on male behavior, condition, and survival. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

  6. Hypothalamic roles of mTOR complex I: integration of nutrient and hormone signals to regulate energy homeostasis

    PubMed Central

    Xu, Yong; Liu, Feng

    2016-01-01

    Mammalian or mechanistic target of rapamycin (mTOR) senses nutrient, energy, and hormone signals to regulate metabolism and energy homeostasis. mTOR activity in the hypothalamus, which is associated with changes in energy status, plays a critical role in the regulation of food intake and body weight. mTOR integrates signals from a variety of “energy balancing” hormones such as leptin, insulin, and ghrelin, although its action varies in response to these distinct hormonal stimuli as well as across different neuronal populations. In this review, we summarize and highlight recent findings regarding the functional roles of mTOR complex 1 (mTORC1) in the hypothalamus specifically in its regulation of body weight, energy expenditure, and glucose/lipid homeostasis. Understanding the role and underlying mechanisms behind mTOR-related signaling in the brain will undoubtedly pave new avenues for future therapeutics and interventions that can combat obesity, insulin resistance, and diabetes. PMID:27166282

  7. Hypothalamic roles of mTOR complex I: integration of nutrient and hormone signals to regulate energy homeostasis.

    PubMed

    Hu, Fang; Xu, Yong; Liu, Feng

    2016-06-01

    Mammalian or mechanistic target of rapamycin (mTOR) senses nutrient, energy, and hormone signals to regulate metabolism and energy homeostasis. mTOR activity in the hypothalamus, which is associated with changes in energy status, plays a critical role in the regulation of food intake and body weight. mTOR integrates signals from a variety of "energy balancing" hormones such as leptin, insulin, and ghrelin, although its action varies in response to these distinct hormonal stimuli as well as across different neuronal populations. In this review, we summarize and highlight recent findings regarding the functional roles of mTOR complex 1 (mTORC1) in the hypothalamus specifically in its regulation of body weight, energy expenditure, and glucose/lipid homeostasis. Understanding the role and underlying mechanisms behind mTOR-related signaling in the brain will undoubtedly pave new avenues for future therapeutics and interventions that can combat obesity, insulin resistance, and diabetes. Copyright © 2016 the American Physiological Society.

  8. Two ATP Binding Cassette G Transporters, Rice ATP Binding Cassette G26 and ATP Binding Cassette G15, Collaboratively Regulate Rice Male Reproduction1[OPEN

    PubMed Central

    Zhao, Guochao; Shi, Jianxin; Liang, Wanqi; Xue, Feiyang; Luo, Qian; Zhu, Lu; Qu, Guorun; Chen, Mingjiao; Schreiber, Lukas; Zhang, Dabing

    2015-01-01

    Male reproduction in higher plants requires the support of various metabolites, including lipid molecules produced in the innermost anther wall layer (the tapetum), but how the molecules are allocated among different anther tissues remains largely unknown. Previously, rice (Oryza sativa) ATP binding cassette G15 (ABCG15) and its Arabidopsis (Arabidopsis thaliana) ortholog were shown to be required for pollen exine formation. Here, we report the significant role of OsABCG26 in regulating the development of anther cuticle and pollen exine together with OsABCG15 in rice. Cytological and chemical analyses indicate that osabcg26 shows reduced transport of lipidic molecules from tapetal cells for anther cuticle development. Supportively, the localization of OsABCG26 is on the plasma membrane of the anther wall layers. By contrast, OsABCG15 is polarly localized in tapetal plasma membrane facing anther locules. osabcg26 osabcg15 double mutant displays an almost complete absence of anther cuticle and pollen exine, similar to that of osabcg15 single mutant. Taken together, we propose that OsABCG26 and OsABCG15 collaboratively regulate rice male reproduction: OsABCG26 is mainly responsible for the transport of lipidic molecules from tapetal cells to anther wall layers, whereas OsABCG15 mainly is responsible for the export of lipidic molecules from the tapetal cells to anther locules for pollen exine development. PMID:26392263

  9. Homosexual Behavior Between Male Spider Monkeys (Ateles geoffroyi).

    PubMed

    Busia, Laura; Denice, Anthony R; Aureli, Filippo; Schaffner, Colleen M

    2018-05-01

    Homosexual behavior is defined as genital contact or genital manipulation between same-sex individuals. In nonhuman primates, it may regulate social relationships by serving as a means of reconciliation, tension alleviation, or alliance formation. Grappling is a rare and complex behavior, which most frequently occurs between same-sex individuals of the genus Ateles and can include mutual manipulation of the genitalia. Here we report three cases of penile-anal intromission during grappling between wild male spider monkeys living in the natural protected area of Otoch Ma'ax Yetel Kooh, Mexico. In all the observed cases, the same adult male was the actor. To our knowledge, this is the first report of penile-anal intromission between males in any New World primate species.

  10. Circumcision of male infants as a human rights violation.

    PubMed

    Svoboda, J Steven

    2013-07-01

    Every infant has a right to bodily integrity. Removing healthy tissue from an infant is only permissible if there is an immediate medical indication. In the case of infant male circumcision there is no evidence of an immediate need to perform the procedure. As a German court recently held, any benefit to circumcision can be obtained by delaying the procedure until the male is old enough to give his own fully informed consent. With the option of delaying circumcision providing all of the purported benefits, circumcising an infant is an unnecessary violation of his bodily integrity as well as an ethically invalid form of medical violence. Parental proxy 'consent' for newborn circumcision is invalid. Male circumcision also violates four core human rights documents-the Universal Declaration of Human Rights, the Convention on the Rights of the Child, the International Covenant on Civil and Political Rights, and the Convention Against Torture. Social norm theory predicts that once the circumcision rate falls below a critical value, the social norms that currently distort our perception of the practice will dissolve and rates will quickly fall.

  11. The Male-Specific Lethal-One (Msl-1) Gene of Drosophila Melanogaster Encodes a Novel Protein That Associates with the X Chromosome in Males

    PubMed Central

    Palmer, M. J.; Mergner, V. A.; Richman, R.; Manning, J. E.; Kuroda, M. I.; Lucchesi, J. C.

    1993-01-01

    male-specific lethal-one (msl-1) is one of four genes that are required for dosage compensation in Drosophila males. To determine the molecular basis of msl-1 regulation of dosage compensation, we have cloned the gene and characterized its products. The predicted msl-1 protein (MSL-1) has no significant similarity to proteins in the current data bases but contains an acidic N terminus characteristic of proteins involved in transcription and chromatin modeling. We present evidence that the msl-1 protein is associated with hundreds of sites along the length of the X chromosome in male, but not in female, nuclei. Our findings support the hypothesis that msl-1 plays a direct role in increasing the level of X-linked gene transcription in male nuclei. PMID:8325488

  12. Construction of a male sterility system for hybrid rice breeding and seed production using a nuclear male sterility gene

    PubMed Central

    Chang, Zhenyi; Chen, Zhufeng; Wang, Na; Xie, Gang; Lu, Jiawei; Yan, Wei; Zhou, Junli; Tang, Xiaoyan; Deng, Xing Wang

    2016-01-01

    The breeding and large-scale adoption of hybrid seeds is an important achievement in agriculture. Rice hybrid seed production uses cytoplasmic male sterile lines or photoperiod/thermo-sensitive genic male sterile lines (PTGMS) as female parent. Cytoplasmic male sterile lines are propagated via cross-pollination by corresponding maintainer lines, whereas PTGMS lines are propagated via self-pollination under environmental conditions restoring male fertility. Despite huge successes, both systems have their intrinsic drawbacks. Here, we constructed a rice male sterility system using a nuclear gene named Oryza sativa No Pollen 1 (OsNP1). OsNP1 encodes a putative glucose–methanol–choline oxidoreductase regulating tapetum degeneration and pollen exine formation; it is specifically expressed in the tapetum and miscrospores. The osnp1 mutant plant displays normal vegetative growth but complete male sterility insensitive to environmental conditions. OsNP1 was coupled with an α-amylase gene to devitalize transgenic pollen and the red fluorescence protein (DsRed) gene to mark transgenic seed and transformed into the osnp1 mutant. Self-pollination of the transgenic plant carrying a single hemizygous transgene produced nontransgenic male sterile and transgenic fertile seeds in 1:1 ratio that can be sorted out based on the red fluorescence coded by DsRed. Cross-pollination of the fertile transgenic plants to the nontransgenic male sterile plants propagated the male sterile seeds of high purity. The male sterile line was crossed with ∼1,200 individual rice germplasms available. Approximately 85% of the F1s outperformed their parents in per plant yield, and 10% out-yielded the best local cultivars, indicating that the technology is promising in hybrid rice breeding and production. PMID:27864513

  13. Construction of a male sterility system for hybrid rice breeding and seed production using a nuclear male sterility gene.

    PubMed

    Chang, Zhenyi; Chen, Zhufeng; Wang, Na; Xie, Gang; Lu, Jiawei; Yan, Wei; Zhou, Junli; Tang, Xiaoyan; Deng, Xing Wang

    2016-12-06

    The breeding and large-scale adoption of hybrid seeds is an important achievement in agriculture. Rice hybrid seed production uses cytoplasmic male sterile lines or photoperiod/thermo-sensitive genic male sterile lines (PTGMS) as female parent. Cytoplasmic male sterile lines are propagated via cross-pollination by corresponding maintainer lines, whereas PTGMS lines are propagated via self-pollination under environmental conditions restoring male fertility. Despite huge successes, both systems have their intrinsic drawbacks. Here, we constructed a rice male sterility system using a nuclear gene named Oryza sativa No Pollen 1 (OsNP1). OsNP1 encodes a putative glucose-methanol-choline oxidoreductase regulating tapetum degeneration and pollen exine formation; it is specifically expressed in the tapetum and miscrospores. The osnp1 mutant plant displays normal vegetative growth but complete male sterility insensitive to environmental conditions. OsNP1 was coupled with an α-amylase gene to devitalize transgenic pollen and the red fluorescence protein (DsRed) gene to mark transgenic seed and transformed into the osnp1 mutant. Self-pollination of the transgenic plant carrying a single hemizygous transgene produced nontransgenic male sterile and transgenic fertile seeds in 1:1 ratio that can be sorted out based on the red fluorescence coded by DsRed Cross-pollination of the fertile transgenic plants to the nontransgenic male sterile plants propagated the male sterile seeds of high purity. The male sterile line was crossed with ∼1,200 individual rice germplasms available. Approximately 85% of the F1s outperformed their parents in per plant yield, and 10% out-yielded the best local cultivars, indicating that the technology is promising in hybrid rice breeding and production.

  14. Urinary Retention, Incontinence, and Dysregulation of Muscarinic Receptors in Male Mice Lacking Mras.

    PubMed

    Ehrhardt, Annette; Wang, Bin; Yung, Andrew C; Wang, Yanni; Kozlowski, Piotr; van Breemen, Cornelis; Schrader, John W

    2015-01-01

    Here we show that male, but not female mice lacking expression of the GTPase M-Ras developed urinary retention with distention of the bladder that exacerbated with age but occurred in the absence of obvious anatomical outlet obstruction. There were changes in detrusor morphology in Mras-/- males: Smooth muscle tissue, which exhibited a compact organization in WT mice, appeared disorganized and became increasingly 'layered' with age in Mras-/- males, but was not fibrotic. Bladder tissue near the apex of bladders of Mras-/- males exhibited hypercontractility in response to the cholinergic agonist carbachol in in vitro, while responses in Mras-/- females were normal. In addition, spontaneous phasic contractions of detrusors from Mras-/- males were increased, and Mras-/- males exhibited urinary incontinence. We found that expression of the muscarinic M2 and M3 receptors that mediate the cholinergic contractile stimuli of the detrusor muscle was dysregulated in both Mras-/- males and females, although only males exhibited a urinary phenotype. Elevated expression of M2R in young males lacking M-Ras and failure to upregulate M3R with age resulted in significantly lower ratios of M3R/M2R expression that correlated with the bladder abnormalities. Our data suggests that M-Ras and M3R are functionally linked and that M-Ras is an important regulator of male bladder control in mice. Our observations also support the notion that bladder control is sexually dimorphic and is regulated through mechanisms that are largely independent of acetylcholine signaling in female mice.

  15. Urinary Retention, Incontinence, and Dysregulation of Muscarinic Receptors in Male Mice Lacking Mras

    PubMed Central

    Ehrhardt, Annette; Wang, Bin; Yung, Andrew C.; Wang, Yanni; Kozlowski, Piotr; van Breemen, Cornelis; Schrader, John W.

    2015-01-01

    Here we show that male, but not female mice lacking expression of the GTPase M-Ras developed urinary retention with distention of the bladder that exacerbated with age but occurred in the absence of obvious anatomical outlet obstruction. There were changes in detrusor morphology in Mras -/- males: Smooth muscle tissue, which exhibited a compact organization in WT mice, appeared disorganized and became increasingly ‘layered’ with age in Mras -/- males, but was not fibrotic. Bladder tissue near the apex of bladders of Mras -/- males exhibited hypercontractility in response to the cholinergic agonist carbachol in in vitro, while responses in Mras -/- females were normal. In addition, spontaneous phasic contractions of detrusors from Mras -/- males were increased, and Mras -/- males exhibited urinary incontinence. We found that expression of the muscarinic M2 and M3 receptors that mediate the cholinergic contractile stimuli of the detrusor muscle was dysregulated in both Mras -/- males and females, although only males exhibited a urinary phenotype. Elevated expression of M2R in young males lacking M-Ras and failure to upregulate M3R with age resulted in significantly lower ratios of M3R/M2R expression that correlated with the bladder abnormalities. Our data suggests that M-Ras and M3R are functionally linked and that M-Ras is an important regulator of male bladder control in mice. Our observations also support the notion that bladder control is sexually dimorphic and is regulated through mechanisms that are largely independent of acetylcholine signaling in female mice. PMID:26516777

  16. Personality and self-regulation: trait and information-processing perspectives.

    PubMed

    Hoyle, Rick H

    2006-12-01

    This article introduces the special issue of Journal of Personality on personality and self-regulation. The goal of the issue is to illustrate and inspire research that integrates personality and process-oriented accounts of self-regulation. The article begins by discussing the trait perspective on self-regulation--distinguishing between temperament and personality accounts--and the information-processing perspective. Three approaches to integrating these perspectives are then presented. These range from methodological approaches, in which constructs representing the two perspectives are examined in integrated statistical models, to conceptual approaches, in which the two perspectives are unified in a holistic theoretical model of self-regulation. The article concludes with an overview of the special issue contributions, which are organized in four sections: broad, integrative models of personality and self-regulation; models that examine the developmental origins of self-regulation and self-regulatory styles; focused programs of research that concern specific aspects or applications of self-regulation; and strategies for increasing the efficiency and effectiveness of self-regulation.

  17. RegulonDB version 9.0: high-level integration of gene regulation, coexpression, motif clustering and beyond.

    PubMed

    Gama-Castro, Socorro; Salgado, Heladia; Santos-Zavaleta, Alberto; Ledezma-Tejeida, Daniela; Muñiz-Rascado, Luis; García-Sotelo, Jair Santiago; Alquicira-Hernández, Kevin; Martínez-Flores, Irma; Pannier, Lucia; Castro-Mondragón, Jaime Abraham; Medina-Rivera, Alejandra; Solano-Lira, Hilda; Bonavides-Martínez, César; Pérez-Rueda, Ernesto; Alquicira-Hernández, Shirley; Porrón-Sotelo, Liliana; López-Fuentes, Alejandra; Hernández-Koutoucheva, Anastasia; Del Moral-Chávez, Víctor; Rinaldi, Fabio; Collado-Vides, Julio

    2016-01-04

    RegulonDB (http://regulondb.ccg.unam.mx) is one of the most useful and important resources on bacterial gene regulation,as it integrates the scattered scientific knowledge of the best-characterized organism, Escherichia coli K-12, in a database that organizes large amounts of data. Its electronic format enables researchers to compare their results with the legacy of previous knowledge and supports bioinformatics tools and model building. Here, we summarize our progress with RegulonDB since our last Nucleic Acids Research publication describing RegulonDB, in 2013. In addition to maintaining curation up-to-date, we report a collection of 232 interactions with small RNAs affecting 192 genes, and the complete repertoire of 189 Elementary Genetic Sensory-Response units (GENSOR units), integrating the signal, regulatory interactions, and metabolic pathways they govern. These additions represent major progress to a higher level of understanding of regulated processes. We have updated the computationally predicted transcription factors, which total 304 (184 with experimental evidence and 120 from computational predictions); we updated our position-weight matrices and have included tools for clustering them in evolutionary families. We describe our semiautomatic strategy to accelerate curation, including datasets from high-throughput experiments, a novel coexpression distance to search for 'neighborhood' genes to known operons and regulons, and computational developments. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. Starch as a major integrator in the regulation of plant growth

    PubMed Central

    Sulpice, Ronan; Pyl, Eva-Theresa; Ishihara, Hirofumi; Trenkamp, Sandra; Steinfath, Matthias; Witucka-Wall, Hanna; Gibon, Yves; Usadel, Björn; Poree, Fabien; Piques, Maria Conceição; Von Korff, Maria; Steinhauser, Marie Caroline; Keurentjes, Joost J. B.; Guenther, Manuela; Hoehne, Melanie; Selbig, Joachim; Fernie, Alisdair R.; Altmann, Thomas; Stitt, Mark

    2009-01-01

    Rising demand for food and bioenergy makes it imperative to breed for increased crop yield. Vegetative plant growth could be driven by resource acquisition or developmental programs. Metabolite profiling in 94 Arabidopsis accessions revealed that biomass correlates negatively with many metabolites, especially starch. Starch accumulates in the light and is degraded at night to provide a sustained supply of carbon for growth. Multivariate analysis revealed that starch is an integrator of the overall metabolic response. We hypothesized that this reflects variation in a regulatory network that balances growth with the carbon supply. Transcript profiling in 21 accessions revealed coordinated changes of transcripts of more than 70 carbon-regulated genes and identified 2 genes (myo-inositol-1-phosphate synthase, a Kelch-domain protein) whose transcripts correlate with biomass. The impact of allelic variation at these 2 loci was shown by association mapping, identifying them as candidate lead genes with the potential to increase biomass production. PMID:19506259

  19. Male tolerance and male-male bonds in a multilevel primate society.

    PubMed

    Patzelt, Annika; Kopp, Gisela H; Ndao, Ibrahima; Kalbitzer, Urs; Zinner, Dietmar; Fischer, Julia

    2014-10-14

    Male relationships in most species of mammals generally are characterized by intense intrasexual competition, with little bonding among unrelated individuals. In contrast, human societies are characterized by high levels of cooperation and strong bonds among both related and unrelated males. The emergence of cooperative male-male relationships has been linked to the multilevel structure of traditional human societies. Based on an analysis of the patterns of spatial and social interaction in combination with genetic relatedness data of wild Guinea baboons (Papio papio), we show that this species exhibits a multilevel social organization in which males maintain strong bonds and are highly tolerant of each other. Several "units" of males with their associated females form "parties," which team up as "gangs." Several gangs of the same "community" use the same home range. Males formed strong bonds predominantly within parties; however, these bonds were not correlated with genetic relatedness. Agonistic interactions were relatively rare and were restricted to a few dyads. Although the social organization of Guinea baboons resembles that of hamadryas baboons, we found stronger male-male affiliation and more elaborate greeting rituals among male Guinea baboons and less aggression toward females. Thus, the social relationships of male Guinea baboons differ markedly from those of other members of the genus, adding valuable comparative data to test hypotheses regarding social evolution. We suggest that this species constitutes an intriguing model to study the predictors and fitness benefits of male bonds, thus contributing to a better understanding of the evolution of this important facet of human social behavior.

  20. A Global Overview of Male Escort Websites.

    PubMed

    Kumar, Navin; Minichiello, Victor; Scott, John; Harrington, Taylor

    2017-01-01

    This article details a preliminary dataset of global male escort sites to give insight into the scale of the online market. We conducted a content analysis of 499 Web sites and also measured traffic to these sites. Our analysis examined the structural characteristics of escort services, geographical and regulatory contexts, and resilience of such services. Results suggest that most sites are independent and not affiliated to escort agencies, and the majority cater to male escorts soliciting male clients, with a number of sites for female clientele and couples. These Web sites are dispersed globally, with Asian, European, and South American countries the major hubs in the market and a small number of large multinational sites based in the United States and Europe figuring as a major presence in markets. Although still subject to high levels of regulation in many parts of the world, the data suggest that male escorting is becoming more visible in diverse cultural contexts as measured by the number of Web sites appearing in public spaces.

  1. The integrate model of emotion, thinking and self regulation: an application to the "paradox of aging".

    PubMed

    Williams, Leanne M; Gatt, Justine M; Hatch, Ainslie; Palmer, Donna M; Nagy, Marie; Rennie, Christopher; Cooper, Nicholas J; Morris, Charlotte; Grieve, Stuart; Dobson-Stone, Carol; Schofield, Peter; Clark, C Richard; Gordon, Evian; Arns, Martijn; Paul, Robert H

    2008-09-01

    This study was undertaken using the INTEGRATE Model of brain organization, which is based on a temporal continuum of emotion, thinking and self regulation. In this model, the key organizing principle of self adaption is the motivation to minimize danger and maximize reward. This principle drives brain organization across a temporal continuum spanning milliseconds to seconds, minutes and hours. The INTEGRATE Model comprises three distinct processes across this continuum. Emotion is defined by automatic action tendencies triggered by signals that are significant due to their relevance to minimizing danger-maximizing reward (such as abrupt, high contrast stimuli). Thinking represents cognitive functions and feelings that rely on brain and body feedback emerging from around 200 ms post-stimulus onwards. Self regulation is the modulation of emotion, thinking and feeling over time, according to more abstract adaptions to minimize danger-maximize reward. Here, we examined the impact of dispositional factors, age and genetic variation, on this temporal continuum. Brain Resource methodology provided a standardized platform for acquiring genetic, brain and behavioral data in the same 1000 healthy subjects. Results showed a "paradox" of declining function in the "thinking" time scale over the lifespan (6 to 80+ years), but a corresponding preservation or even increase in automatic functions of "emotion" and "self regulation". This paradox was paralleled by a greater loss of grey matter in cortical association areas (assessed using MRI) over age, but a relative preservation of subcortical grey matter. Genetic polymorphisms associated with both healthy function and susceptibility to disorder (including the BDNFVal(66)Met, COMTVal(158/108)Met, MAOA and DRD4 tandem repeat and 5HTT-LPR polymorphisms) made specific contributions to emotion, thinking and self regulatory functions, which also varied according to age.

  2. Synthesis and assessment of fertility-regulating potential of 2-(2''-chloroacetamidobenzyl)-3-(3'-indolyl) quinoline in adult rats as a male contraceptive agent.

    PubMed

    Bhowal, Sujit K; Lala, Sanchita; Hazra, Abhijit; Paira, Priyankar; Banerjee, Sukdeb; Mondal, Nirup B; Chakraborty, Smritinath

    2008-03-01

    The purpose of this study was to investigate the fertility-regulating potential of the compound 2-(2''-chloroacetamidobenzyl)-3-(3'-indolyl) quinoline in male rats. Rats of proven fertility were treated with the compound by oral gavage for 1 to 8 consecutive weeks. Functional fertility, testicular, epididymal and seminal vesicular weight, epididymal sperm count and spermatogenesis were quantitated. Reproductive hormones and some biochemical parameters were measured. Functional fertility was reduced significantly as revealed by a fall in fertility and pregnancy rate. The weight of the reproductive organs was reduced significantly. A reduction of sperm count and number of different types of testicular cells was observed. The treatment with the compound resulted in decline of testosterone and an increase of FSH hormone levels. The compound effectively reduced testicular protein, glycogen and epididymal glyceryl phosphorylcholine. Increase in testicular alkaline phosphatase and cholesterol was also observed. Fertility and other effects were regained gradually after cessation of treatment. The results revealed from the study indicate that the compound has reversible antifertility activity and can be explored as male contraceptive agent.

  3. Anti-Müllerian hormone may regulate the number of calbindin-positive neurons in the sexually dimorphic nucleus of the preoptic area of male mice

    PubMed Central

    2013-01-01

    Background The male brain is putatively organised early in development by testosterone, with the sexually dimorphic nucleus of the medial preoptic area (SDN) a main exemplifier of this. However, pubescent neurogenesis occurs in the rat SDN, and the immature testes secrete anti-Müllerian hormone (AMH) as well as testosterone. We have therefore re-examined the development of the murine SDN to determine whether it is influenced by AMH and/or whether the number of calbindin-positive (calbindin+ve) neurons in it changes after pre-pubescent development. Methods In mice, the SDN nucleus is defined by calbindin+ve neurons (CALB-SDN). The number and size of the neurons in the CALB-SDN of male and female AMH null mutant (Amh-/-) mice and their wild-type littermates (Amh+/+) were studied using stereological techniques. Groups of mice were examined immediately before the onset of puberty (20 days postnatal) and at adulthood (129–147 days old). Results The wild-type pre-pubertal male mice had 47% more calbindin+ve neurons in the CALB-SDN than their female wild-type littermates. This sex difference was entirely absent in Amh-/- mice. In adults, the extent of sexual dimorphism almost doubled due to a net reduction in the number and size of calbindin+ve neurons in females and a net increase in neuron number in males. These changes occurred to a similar extent in the Amh-/- and Amh+/+ mice. Consequently, the number of calbindin+ve neurons in Amh-/- adult male mice was intermediate between Amh+/+ males and Amh+/+ females. The sex difference in the size of the neurons was predominantly generated by a female-specific atrophy after 20 days, independent of AMH. Conclusions The establishment of dimorphic cell number in the CALB-SDN of mice is biphasic, with each phase being subject to different regulation. The second phase of dimorphism is not dependent on the first phase having occurred as it was present in the Amh-/- male mice that have female-like numbers of calbindin+ve neurons at

  4. Anti-Müllerian hormone may regulate the number of calbindin-positive neurons in the sexually dimorphic nucleus of the preoptic area of male mice.

    PubMed

    Wittmann, Walter; McLennan, Ian S

    2013-10-11

    The male brain is putatively organised early in development by testosterone, with the sexually dimorphic nucleus of the medial preoptic area (SDN) a main exemplifier of this. However, pubescent neurogenesis occurs in the rat SDN, and the immature testes secrete anti-Müllerian hormone (AMH) as well as testosterone. We have therefore re-examined the development of the murine SDN to determine whether it is influenced by AMH and/or whether the number of calbindin-positive (calbindin+ve) neurons in it changes after pre-pubescent development. In mice, the SDN nucleus is defined by calbindin+ve neurons (CALB-SDN). The number and size of the neurons in the CALB-SDN of male and female AMH null mutant (Amh-/-) mice and their wild-type littermates (Amh+/+) were studied using stereological techniques. Groups of mice were examined immediately before the onset of puberty (20 days postnatal) and at adulthood (129-147 days old). The wild-type pre-pubertal male mice had 47% more calbindin+ve neurons in the CALB-SDN than their female wild-type littermates. This sex difference was entirely absent in Amh-/- mice. In adults, the extent of sexual dimorphism almost doubled due to a net reduction in the number and size of calbindin+ve neurons in females and a net increase in neuron number in males. These changes occurred to a similar extent in the Amh-/- and Amh+/+ mice. Consequently, the number of calbindin+ve neurons in Amh-/- adult male mice was intermediate between Amh+/+ males and Amh+/+ females. The sex difference in the size of the neurons was predominantly generated by a female-specific atrophy after 20 days, independent of AMH. The establishment of dimorphic cell number in the CALB-SDN of mice is biphasic, with each phase being subject to different regulation. The second phase of dimorphism is not dependent on the first phase having occurred as it was present in the Amh-/- male mice that have female-like numbers of calbindin+ve neurons at 20 days. These observations extend

  5. Marijuana, phytocannabinoids, the endocannabinoid system, and male fertility.

    PubMed

    du Plessis, Stefan S; Agarwal, Ashok; Syriac, Arun

    2015-11-01

    Marijuana has the highest consumption rate among all of the illicit drugs used in the USA, and its popularity as both a recreational and medicinal drug is increasing especially among men of reproductive age. Male factor infertility is on the increase, and the exposure to the cannabinoid compounds released by marijuana could be a contributing cause. The endocannabinoid system (ECS) is deeply involved in the complex regulation of male reproduction through the endogenous release of endocannabinoids and binding to cannabinoid receptors. Disturbing the delicate balance of the ECS due to marijuana use can negatively impact reproductive potential. Various in vivo and in vitro studies have reported on the empirical role that marijuana plays in disrupting the hypothalamus-pituitary-gonadal axis, spermatogenesis, and sperm function such as motility, capacitation, and the acrosome reaction. In this review, we highlight the latest evidence regarding the effect of marijuana use on male fertility and also provide a detailed insight into the ECS and its significance in the male reproductive system.

  6. Fertility: purinergic receptors and the male contraceptive pill.

    PubMed

    Dunn, P M

    2000-04-20

    Knockout mice lacking the P2X(1) receptor appear normal, but fail to breed. Analysis of these mutant mice clearly shows that purinergic co-transmission has a physiological role in the was deferens. These findings also raise the possibility of developing non-hormonal ways of regulating male fertility.

  7. Lycopene and male infertility

    PubMed Central

    Durairajanayagam, Damayanthi; Agarwal, Ashok; Ong, Chloe; Prashast, Pallavi

    2014-01-01

    Excessive amounts of reactive oxygen species (ROS) cause a state of oxidative stress, which result in sperm membrane lipid peroxidation, DNA damage and apoptosis, leading to decreased sperm viability and motility. Elevated levels of ROS are a major cause of idiopathic male factor infertility, which is an increasingly common problem today. Lycopene, the most potent singlet oxygen quencher of all carotenoids, is a possible treatment option for male infertility because of its antioxidant properties. By reacting with and neutralizing free radicals, lycopene could reduce the incidence of oxidative stress and thus, lessen the damage that would otherwise be inflicted on spermatozoa. It is postulated that lycopene may have other beneficial effects via nonoxidative mechanisms in the testis, such as gap junction communication, modulation of gene expression, regulation of the cell cycle and immunoenhancement. Various lycopene supplementation studies conducted on both humans and animals have shown promising results in alleviating male infertility—lipid peroxidation and DNA damage were decreased, while sperm count and viability, and general immunity were increased. Improvement of these parameters indicates a reduction in oxidative stress, and thus the spermatozoa is less vulnerable to oxidative damage, which increases the chances of a normal sperm fertilizing the egg. Human trials have reported improvement in sperm parameters and pregnancy rates with supplementation of 4–8 mg of lycopene daily for 3–12 months. However, further detailed and extensive research is still required to determine the dosage and the usefulness of lycopene as a treatment for male infertility. PMID:24675655

  8. Activation of Extracellular Signal-Regulated Kinases (ERK 1/2) in the Locus Coeruleus Contributes to Pain-Related Anxiety in Arthritic Male Rats

    PubMed Central

    Borges, Gisela; Miguelez, Cristina; Neto, Fani; Mico, Juan Antonio; Ugedo, Luisa

    2017-01-01

    Abstract Background: There is increasing evidence suggesting that the Locus Coeruleus plays a role in pain-related anxiety. Indeed, we previously found that prolonged arthritis produces anxiety-like behavior in rats, along with enhanced expression of phosphorylated extracellular signal-regulated kinase 1/2 (a marker of plasticity) in the Locus Coeruleus. However, it is unknown how this effect correlates with the electrophysiological activity of Locus Coeruleus neurons or pain-related anxiety. Methods: Using the complete Freund’s adjuvant model of monoarthritis in male Sprague-Dawley rats, we studied the behavioral attributes of pain and anxiety as well as Locus Coeruleus electrophysiology in vivo 1 (MA1W) and 4 weeks (MA4W) after disease induction. Results: The manifestation of anxiety in MA4W was accompanied by dampened tonic Locus Coeruleus activity, which was coupled to an exacerbated evoked Locus Coeruleus response to noxious stimulation of the inflamed and healthy paw. When a mitogen-activating extracellular kinase inhibitor was administered to the contralateral Locus Coeruleus of MA4W, the phosphorylated extracellular signal-regulated kinase 1/2 levels in the Locus Coeruleus were restored and the exaggerated evoked response was blocked, reversing the anxiogenic-like behavior while pain hypersensitivity remained unaltered. Conclusion: As phosphorylated extracellular signal-regulated kinase 1/2 blockade in the Locus Coeruleus relieved anxiety and counteracted altered LC function, we propose that phosphorylated extracellular signal-regulated kinase 1/2 activation in the Locus Coeruleus plays a crucial role in pain-related anxiety. PMID:28158734

  9. Activation of Extracellular Signal-Regulated Kinases (ERK 1/2) in the Locus Coeruleus Contributes to Pain-Related Anxiety in Arthritic Male Rats.

    PubMed

    Borges, Gisela; Miguelez, Cristina; Neto, Fani; Mico, Juan Antonio; Ugedo, Luisa; Berrocoso, Esther

    2017-06-01

    There is increasing evidence suggesting that the Locus Coeruleus plays a role in pain-related anxiety. Indeed, we previously found that prolonged arthritis produces anxiety-like behavior in rats, along with enhanced expression of phosphorylated extracellular signal-regulated kinase 1/2 (a marker of plasticity) in the Locus Coeruleus. However, it is unknown how this effect correlates with the electrophysiological activity of Locus Coeruleus neurons or pain-related anxiety. Using the complete Freund's adjuvant model of monoarthritis in male Sprague-Dawley rats, we studied the behavioral attributes of pain and anxiety as well as Locus Coeruleus electrophysiology in vivo 1 (MA1W) and 4 weeks (MA4W) after disease induction. The manifestation of anxiety in MA4W was accompanied by dampened tonic Locus Coeruleus activity, which was coupled to an exacerbated evoked Locus Coeruleus response to noxious stimulation of the inflamed and healthy paw. When a mitogen-activating extracellular kinase inhibitor was administered to the contralateral Locus Coeruleus of MA4W, the phosphorylated extracellular signal-regulated kinase 1/2 levels in the Locus Coeruleus were restored and the exaggerated evoked response was blocked, reversing the anxiogenic-like behavior while pain hypersensitivity remained unaltered. As phosphorylated extracellular signal-regulated kinase 1/2 blockade in the Locus Coeruleus relieved anxiety and counteracted altered LC function, we propose that phosphorylated extracellular signal-regulated kinase 1/2 activation in the Locus Coeruleus plays a crucial role in pain-related anxiety. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  10. The Relationship between Student Self-Regulation Strategies and Increased Student Achievement: A Study on How the Explicit Integration of Self-Regulation Strategies Impacts Student Reading Achievement in the Elementary Classroom

    ERIC Educational Resources Information Center

    Egan, Patti A.

    2017-01-01

    Student ownership in learning is a topic that has become quite prevalent in recent years. While emphasis has grown on the importance of active student involvement in learning, integration of student self-regulation strategies is often absent in elementary classrooms. A paradigm shift that encourages active involvement of students in the learning…

  11. Sexual Selection on male cuticular hydrocarbons via male-male competition and female choice.

    PubMed

    Lane, S M; Dickinson, A W; Tregenza, T; House, C M

    2016-07-01

    Traditional views of sexual selection assumed that male-male competition and female mate choice work in harmony, selecting upon the same traits in the same direction. However, we now know that this is not always the case and that these two mechanisms often impose conflicting selection on male sexual traits. Cuticular hydrocarbons (CHCs) have been shown to be linked to both social dominance and male attractiveness in several insect species. However, although several studies have estimated the strength and form of sexual selection imposed on male CHCs by female mate choice, none have established whether these chemical traits are also subject to sexual selection via male-male competition. Using a multivariate selection analysis, we estimate and compare sexual selection exerted by male-male competition and female mate choice on male CHC composition in the broad-horned flour beetle Gnatocerus cornutus. We show that male-male competition exerts strong linear selection on both overall CHC abundance and body size in males, while female mate choice exerts a mixture of linear and nonlinear selection, targeting not just the overall amount of CHCs expressed but the relative abundance of specific hydrocarbons as well. We discuss the potential implications of this antagonistic selection with regard to male reproductive success. © 2016 The Authors. Journal of Evolutionary Biology published by John Wiley & Sons Ltd on behalf of European Society for Evolutionary Biology.

  12. A translational systems biology approach in both animals and humans identifies a functionally related module of accumbal genes involved in the regulation of reward processing and binge drinking in males.

    PubMed

    Stacey, David; Lourdusamy, Anbarasu; Ruggeri, Barbara; Maroteaux, Matthieu; Jia, Tianye; Cattrell, Anna; Nymberg, Charlotte; Banaschewski, Tobias; Bhattacharyya, Sohinee; Band, Hamid; Barker, Gareth; Bokde, Arun; Buchel, Christian; Carvalho, Fabiana; Conrod, Patricia; Desrivieres, Sylvane; Easton, Alanna; Fauth-Buehler, Mira; Fernandez-Medarde, Alberto; Flor, Herta; Frouin, Vincent; Gallinat, Jurgen; Garavanh, Hugh; Heinz, Andreas; Ittermann, Bernd; Lathrop, Mark; Lawrence, Claire; Loth, Eva; Mann, Karl; Martinot, Jean-Luc; Nees, Frauke; Paus, Tomas; Pausova, Zdenka; Rietschel, Marcella; Rotter, Andrea; Santos, Eugenio; Smolka, Michael; Sommer, Wolfgang; Mameli, Manuel; Spanagel, Rainer; Girault, Jean-Antoine; Mueller, Christian; Schumann, Gunter

    2016-04-01

    The mesolimbic dopamine system, composed primarily of dopaminergic neurons in the ventral tegmental area that project to striatal structures, is considered to be the key mediator of reinforcement-related mechanisms in the brain. Prompted by a genome-wide association meta-analysis implicating the Ras-specific guanine nucleotide-releasing factor 2 (RASGRF2) gene in the regulation of alcohol intake in men, we have recently shown that male Rasgrf2(-/-) mice exhibit reduced ethanol intake and preference accompanied by a perturbed mesolimbic dopamine system. We therefore propose that these mice represent a valid model to further elucidate the precise genes and mechanisms regulating mesolimbic dopamine functioning. Transcriptomic data from the nucleus accumbens (NAcc) of male Rasgrf2(-/-) mice and wild-type controls were analyzed by weighted gene coexpression network analysis (WGCNA). We performed follow-up genetic association tests in humans using a sample of male adolescents from the IMAGEN study characterized for binge drinking (n = 905) and ventral striatal activation during an fMRI reward task (n = 608). The WGCNA analyses using accumbal transcriptomic data revealed 37 distinct "modules," or functionally related groups of genes. Two of these modules were significantly associated with Rasgrf2 knockout status: M5 (p < 0.001) and M6 (p < 0.001). In follow-up translational analyses we found that human orthologues for the M5 module were significantly (p < 0.01) enriched with genetic association signals for binge drinking in male adolescents. Furthermore, the most significant locus, originating from the EH-domain containing 4 (EHD4) gene (p < 0.001), was also significantly associated with altered ventral striatal activity in male adolescents performing an fMRI reward task (pempirical < 0.001). It was not possible to determine the extent to which the M5 module was dysregulated in Rasgrf2(-/-) mice by perturbed mesolimbic dopamine signalling or by the loss of Rasgrf2

  13. Integrated mixed signal control IC for 500-kHz switching frequency buck regulator

    NASA Astrophysics Data System (ADS)

    Chen, Keng; Zhang, Hong

    2015-12-01

    The main purpose for this work is to study the challenges of designing a digital buck regulator using pipelined analog to digital converter (ADC). Although pipelined ADC can achieve high sampling speed, it will introduce additional phase lag to the buck circuit. Along with the latency brought by processing time of additional digital circuits, as well as the time delay associated with the switching frequency, the closed loop will be unstable; moreover, raw ADC outputs have low signal-to-noise ratio, which usually need back-end calibration. In order to compensate these phase lag and make control loop unconditional stable, as well as boost up signal-to-noise ratio of the ADC block with cost-efficient design, a finite impulse response filter followed by digital proportional-integral-derivative blocks were designed. All these digital function blocks were optimised with processing speed. In the system simulation, it can be found that this controller achieved output regulation within 10% of nominal 5 V output voltage under 1 A/µs load transient condition; moreover, with the soft-start method, there is no turn-on overshooting. The die size of this controller is controlled within 3 mm2 by using 180 nm CMOS technology.

  14. Measuring acculturation among male Arab immigrants in the United States: an exploratory study.

    PubMed

    Barry, Declan T

    2005-07-01

    Given the absence of empirical measures that assess acculturation patterns among male Arab immigrants, a new acculturation instrument was developed and evaluated. One hundred and fifteen adult male Arab immigrants were administered the Male Arab Acculturation Scale (MAAS), and psychometrically established measures of ethnic identity and self-esteem. Satisfactory reliability is reported for the two acculturation scales, separation/assimilation and integration/marginalization. Ethnic identity, self-construal, personal self-esteem, and collective self-esteem appear to be differentially associated with acculturation patterns among male Arab immigrants.

  15. Recent methodological advances in male hormonal contraception

    PubMed Central

    Liu, Peter Y.; Swerdloff, Ronald S.; Wang, Christina

    2010-01-01

    Landmark WHO-sponsored trials showed decades ago that male hormonal contraception (MHC) is an effective male-directed contraceptive approach. Considerable progress has been made particularly in the last 5 years, establishing for the first time the reversibility of MHC and its short-term safety. Methodological advances in recent years include: the pooling of information and individual-level integrated analysis; the first-time use of centralized semen analysis and fluorescence to detect low sperm concentrations; the establishment of sperm quality reference ranges in fertile men; the measurement of blood steroid concentrations by gas or chromatography/mass spectrometry; and the inclusion of placebo groups to delineate clearly possible adverse effects of androgens and progestins in men. We report integrated analyses of factors that are important in predicting suppression and recovery of spermatogenesis after MHC clinical trials for the past 15 years. These are the best data available and will provide guidance and reassurance for the larger scale Phase III specific regimen efficacy studies that will be required to bring MHC to the population (market). PMID:20933121

  16. Recent methodological advances in male hormonal contraception.

    PubMed

    Liu, Peter Y; Swerdloff, Ronald S; Wang, Christina

    2010-11-01

    Landmark WHO-sponsored trials showed decades ago that male hormonal contraception (MHC) is an effective male-directed contraceptive approach. Considerable progress has been made particularly in the last 5 years, establishing for the first time the reversibility of MHC and its short-term safety. Methodological advances in recent years include the pooling of information and individual-level integrated analysis; the first-time use of centralized semen analysis and fluorescence to detect low sperm concentrations; the establishment of sperm quality reference ranges in fertile men; the measurement of blood steroid concentrations by gas chromatography/mass spectrometry; and the inclusion of placebo groups to delineate clearly possible adverse effects of androgens and progestins in men. We report integrated analyses of factors that are important in predicting suppression and recovery of spermatogenesis after MHC clinical trials for the past 15 years. These are the best data available and will provide guidance and reassurance for the larger-scale Phase III specific regimen efficacy studies that will be required to bring MHC to the population (market). Copyright © 2010 Elsevier Inc. All rights reserved.

  17. Plasma kisspeptin levels in male cases with hypogonadism.

    PubMed

    Kotani, Masato; Katagiri, Fumihiko; Hirai, Tsuyoshi; Kagawa, Jiro

    2014-01-01

    The hypothalamic hormone kisspeptin (metastin) regulates human reproduction by modulating gonadotropin-releasing hormone (GnRH) secretion. Kisspeptin is detected in peripheral blood, although GnRH is not. In this study, we measured plasma kisspeptin levels in four male cases with hypogonadism and seven normal male controls using enzyme immunoassay (EIA) to elucidate the clinical implications of kisspeptin levels in male hypogonadism. The results showed a variety of plasma kisspeptin levels: 6.0 fmol/mL in a male with isolated hypogonadotropic hypogonadism (IHH), 43.2 fmol/mL in a male with Kallmann's syndrome, 40.7 fmol/mL in a male with azoospermia, 323.2 fmol/mL in a male with hypergonadotropic hypogonadism, and 12.3 ± 2.5 fmol/mL (mean ± SD) in seven normal controls. Except for the case with IHH, the plasma kisspetin levels were elevated in the three cases with Kallmann's syndrome, azoospermia, and hypergonadotropic hypogonadism. The reason why the three cases had high values was their lesions were downstream of the kisspeptin neuron in the hypothalamic-pituitary-gonadal axis, suggesting that elevated kisspeptin levels were implicated in hypothalamic kisspeptin secretion under decreased negative feedback of gonadal steroids. The result that the plasma kisspeptin levels were decreased by gonadotropin therapy in the case with Kallmann's syndrome supported this hypothesis. In conclusion, to measure plasma kisspeptin levels could be useful for better understanding of male hypogonadism.

  18. Two bHLH-type transcription factors, JA-ASSOCIATED MYC2-LIKE2 and JAM3, are transcriptional repressors and affect male fertility

    PubMed Central

    Nakata, Masaru; Ohme-Takagi, Masaru

    2013-01-01

    The jasmonate (JA) plant hormones regulate responses to biotic and abiotic stress and aspects of plant development, including male fertility in Arabidopsis thaliana. The bHLH-type transcription factor JA-ASSOCIATED MYC2-LIKE1 (JAM1) negatively regulates JA signaling and gain-of-function JAM1 transgenic plants have impaired JA-mediated male fertility. Here we report that JAM2 and JAM3, 2 bHLHs closely related to JAM1, also act as transcriptional repressors. Moreover, overexpression of JAM2 and JAM3 also results in reduced male fertility. These results suggest that JAM1, JAM2, and JAM3 act redundantly as negative regulators of JA-mediated male fertility. PMID:24056034

  19. Coffee and caffeine intake and male infertility: a systematic review.

    PubMed

    Ricci, Elena; Viganò, Paola; Cipriani, Sonia; Somigliana, Edgardo; Chiaffarino, Francesca; Bulfoni, Alessandro; Parazzini, Fabio

    2017-06-24

    Semen quality, a predictor of male fertility, has been suggested declining worldwide. Among other life style factors, male coffee/caffeine consumption was hypothesized to influence semen parameters, but also sperm DNA integrity. To summarize available evidence, we performed a systematic review of observational studies on the relation between coffee/caffeine intake and parameters of male fertility including sperm ploidy, sperm DNA integrity, semen quality and time to pregnancy. A systematic literature search was performed up to November 2016 (MEDLINE and EMBASE). We included all observational papers that reported the relation between male coffee/caffeine intake and reproductive outcomes: 1. semen parameters, 2. sperm DNA characteristics, 3. fecundability. All pertinent reports were retrieved and the relative reference lists were systematically searched in order to identify any potential additional studies that could be included. We retrieved 28 papers reporting observational information on coffee/caffeine intake and reproductive outcomes. Overall, they included 19,967 men. 1. Semen parameters did not seem affected by caffeine intake, at least caffeine from coffee, tea and cocoa drinks, in most studies. Conversely, other contributions suggested a negative effect of cola-containing beverages and caffeine-containing soft drinks on semen volume, count and concentration. 2. As regards sperm DNA defects, caffeine intake seemed associated with aneuploidy and DNA breaks, but not with other markers of DNA damage. 3. Finally, male coffee drinking was associated to prolonged time to pregnancy in some, but not all, studies. The literature suggests that caffeine intake, possibly through sperm DNA damage, may negatively affect male reproductive function. Evidence from epidemiological studies on semen parameters and fertility is however inconsistent and inconclusive. Well-designed studies with predefined criteria for semen analysis, subject selection, and life style habits

  20. Central dopamine D2 receptors regulate growth-hormone-dependent body growth and pheromone signaling to conspecific males.

    PubMed

    Noaín, Daniela; Pérez-Millán, M Inés; Bello, Estefanía P; Luque, Guillermina M; Casas Cordero, Rodrigo; Gelman, Diego M; Peper, Marcela; Tornadu, Isabel García; Low, Malcolm J; Becú-Villalobos, Damasia; Rubinstein, Marcelo

    2013-03-27

    Competition between adult males for limited resources such as food and receptive females is shaped by the male pattern of pituitary growth hormone (GH) secretion that determines body size and the production of urinary pheromones involved in male-to-male aggression. In the brain, dopamine (DA) provides incentive salience to stimuli that predict the availability of food and sexual partners. Although the importance of the GH axis and central DA neurotransmission in social dominance and fitness is clearly appreciated, the two systems have always been studied unconnectedly. Here we conducted a cell-specific genetic dissection study in conditional mutant mice that selectively lack DA D2 receptors (D2R) from pituitary lactotropes (lacDrd2KO) or neurons (neuroDrd2KO). Whereas lacDrd2KO mice developed a normal GH axis, neuroDrd2KO mice displayed fewer somatotropes; reduced hypothalamic Ghrh expression, pituitary GH content, and serum IGF-I levels; and exhibited reduced body size and weight. As a consequence of a GH axis deficit, neuroDrd2KO adult males excreted low levels of major urinary proteins and their urine failed to promote aggression and territorial behavior in control male challengers, in contrast to the urine taken from control adult males. These findings reveal that central D2Rs mediate a neuroendocrine-exocrine cascade that controls the maturation of the GH axis and downstream signals that are critical for fitness, social dominance, and competition between adult males.

  1. Processes regulating the initiation and postejaculatory resumption of copulatory behavior in male hamsters.

    PubMed

    Floody, Owen R

    2014-06-01

    Studies using factor analysis have helped describe the organization of copulatory behavior in male rodents. However, the focus of these studies on a few traditional measures may have limited their results. To test this possibility, 74 sexually-experienced male hamsters were observed as they copulated with stimulus females. The measures collected exceeded the conventional ones in number, variety and independence. The factor analysis of these data revealed a structure with seven factors collectively accounting for 80% of the variance. Most resembled the factors in previous reports, reinforcing the contributions that the processes suggested by these factors make to the organization of male behavior. But several other factors were more novel, possibly reflecting the use of measures that were novel or revised for greater independence. The most interesting of these were two factors focusing on early steps in the progression leading to ejaculation. Importantly, both incorporated measures from each of the three copulatory series that were observed. Past work suggests that independent processes control the times required to initiate copulation and later resume it after an ejaculation. In contrast, these results suggest the existence of two processes, each of which contributes to both the initiation and reinitiation of copulation. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Regulation of endothelial Fas expression as a mechanism of promotion of vascular integrity by mural cells in tumors.

    PubMed

    Kamei, Ryosuke; Tanaka, Hiroyoshi Y; Kawano, Takao; Morii, Chiharu; Tanaka, Sayaka; Nishihara, Hiroshi; Iwata, Caname; Kano, Mitsunobu R

    2017-05-01

    Angiogenesis is a multi-step process that culminates in vascular maturation whereby nascent vessels stabilize to become functional, and mural cells play an essential role in this process. Recent studies have shown that mural cells in tumors also promote and maintain vascular integrity, with wide-reaching clinical implications including the regulation of tumor growth, metastases, and drug delivery. Various regulatory signaling pathways have been hitherto implicated, but whether regulation of Fas-dependent apoptotic mechanisms is involved has not yet been fully investigated. We first compared endothelial FAS staining in human pancreatic ductal adenocarcinomas and colon carcinomas and show that the latter, characterized by lower mural cell coverage of tumor vasculature, demonstrated higher expression of FAS than the former. Next, in an in vitro coculture system of MS-1 and 10T1/2 cells as endothelial and mural cells respectively, we show that mural cells decreased endothelial Fas expression. Then, in an in vivo model in which C26 colon carcinoma cells were inoculated together with MS-1 cells alone or with the further addition of 10T1/2 cells, we demonstrate that mural cells prevented hemorrhage. Finally, knockdown of endothelial Fas sufficiently recapitulated the protection against hemorrhage seen with the addition of mural cells. These results together suggest that regulation of endothelial Fas signaling is involved in the promotion of vascular integrity by mural cells in tumors. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  3. HsfA2 Controls the Activity of Developmentally and Stress-Regulated Heat Stress Protection Mechanisms in Tomato Male Reproductive Tissues1[OPEN

    PubMed Central

    Simm, Stefan; Paupière, Marine Josephine; Theres, Klaus; Bovy, Arnaud; Schleiff, Enrico; Scharf, Klaus-Dieter

    2016-01-01

    Male reproductive tissues are more sensitive to heat stress (HS) compared to vegetative tissues, but the basis of this phenomenon is poorly understood. Heat stress transcription factors (Hsfs) regulate the transcriptional changes required for protection from HS. In tomato (Solanum lycopersicum), HsfA2 acts as coactivator of HsfA1a and is one of the major Hsfs accumulating in response to elevated temperatures. The contribution of HsfA2 in heat stress response (HSR) and thermotolerance was investigated in different tissues of transgenic tomato plants with suppressed HsfA2 levels (A2AS). Global transcriptome analysis and immunodetection of two major Hsps in vegetative and reproductive tissues showed that HsfA2 regulates subsets of HS-induced genes in a tissue-specific manner. Accumulation of HsfA2 by a moderate HS treatment enhances the capacity of seedlings to cope with a subsequent severe HS, suggesting an important role for HsfA2 in regulating acquired thermotolerance. In pollen, HsfA2 is an important coactivator of HsfA1a during HSR. HsfA2 suppression reduces the viability and germination rate of pollen that received the stress during the stages of meiosis and microspore formation but had no effect on more advanced stages. In general, pollen meiocytes and microspores are characterized by increased susceptibility to HS due to their lower capacity to induce a strong HSR. This sensitivity is partially mitigated by the developmentally regulated expression of HsfA2 and several HS-responsive genes mediated by HsfA1a under nonstress conditions. Thereby, HsfA2 is an important factor for the priming process that sustains pollen thermotolerance during microsporogenesis. PMID:26917685

  4. Adjustable suburethral sling (male remeex system) in the treatment of male stress urinary incontinence: a multicentric European study.

    PubMed

    Sousa-Escandón, Alejandro; Cabrera, Javier; Mantovani, Franco; Moretti, Marco; Ioanidis, Evangelos; Kondelidis, Nikolaos; Neymeyer, Joerg; Noguera, Rui

    2007-11-01

    To evaluate the effectiveness of a readjustable sling for the treatment of male stress urinary incontinence (SUI). Between October 2002 and August 2005, 51 male patients with mild to severe SUI were prospectively operated with the use of a readjustable sling (MRS) at seven different European hospitals: Spain (2), Italy (2), Greece (1), Germany (1), and Portugal (1). The origin of incontinence was radical prostatectomy in 43 cases, TUR in 4, and open prostatectomy in another 4. Duration of incontinence ranged from 1 to 10 yr with an average of 3.5 yr. All patients but 5 were regulated during the early postoperative period; 44 patients (including all 5 not regulated during the early period) required a second regulation under local anaesthesia between 1 to 4 mo after surgery, and 17 other patients required more than one delayed regulation. After that, 33 patients (64.7%) were considered cured (25 of them wore no pads at all, and 8 used small pads or sanitary napkins for security but normally remained dry); another 10 cases showed important improvement (19.6%); and only 8 patients remain unchanged (15.7%). The average follow-up time was 32 mo (range: 16-50). The mesh was removed in 1 case owing to urethral erosion and the varitensor in 2 cases owing to infection. There were five (9.8%) uneventful intraoperative bladder perforations at the postoperative period, and there were three mild perineal haematomas (5.9%). Most patients felt perineal discomfort or pain, which was easily treated with oral medications. The MRS((R)) allowed postoperative readjustment of the suburethral sling pressure at the immediate or midterm postoperative period, which allowed the achievement of good midterm results in almost 85% of patients without significant postoperative complications.

  5. Advancing Black Male Success: Understanding the Contributions of Urban Black Colleges and Universities

    ERIC Educational Resources Information Center

    Gasman, Marybeth; Nguyen, Thai-Huy; Commodore, Felecia

    2017-01-01

    To understand the context of urban Historically Black Colleges and Universities (HBCUs) and their role in educating Black males, we conducted a literature review examining the academic contributions of these institutions to Black males. To bolster the literature, we examined Integrated Postsecondary Education Data System data, determining a set of…

  6. Expression of Pleiotrophin in the Prostate is Androgen Regulated and it Functions as an Autocrine Regulator of Mesenchyme and Cancer Associated Fibroblasts and as a Paracrine Regulator of Epithelia

    PubMed Central

    Orr, Brigid; Vanpoucke, Griet; Grace, O Cathal; Smith, Lee; Anderson, Richard A; Riddick, Antony CP; Franco, Omar E; Hayward, Simon W; Thomson, Axel A

    2011-01-01

    BACKGROUND Androgens and paracrine signaling from mesenchyme/stroma regulate development and disease of the prostate, and gene profiling studies of inductive prostate mesenchyme have identified candidate molecules such as pleiotrophin (Ptn). METHODS Ptn transcripts and protein were localized by in situ and immunohistochemistry and Ptn mRNA was quantitated by Northern blot and qRT-PCR. Ptn function was examined by addition of hPTN protein to rat ventral prostate organ cultures, primary human fetal prostate fibroblasts, prostate cancer associated fibroblasts, and BPH1 epithelia. RESULTS During development, Ptn transcripts and protein were expressed in ventral mesenchymal pad (VMP) and prostatic mesenchyme. Ptn was localized to mesenchyme surrounding ductal epithelial tips undergoing branching morphogenesis, and was located on the surface of epithelia. hPTN protein stimulated branching morphogenesis and stromal and epithelial proliferation, when added to rat VP cultures, and also stimulated growth of fetal human prostate fibroblasts, prostate cancer associated fibroblasts, and BPH1 epithelia. PTN mRNA was enriched in patient-matched normal prostate fibroblasts versus prostate cancer associated fibroblasts. PTN also showed male enriched expression in fetal human male urethra versus female, and between wt male and ARKO male mice. Transcripts for PTN were upregulated by testosterone in fetal human prostate fibroblasts and organ cultures of female rat VMP. Ptn protein was increased by testosterone in organ cultures of female rat VMP and in rat male urethra compared to female. CONCLUSIONS Our data suggest that in the prostate Ptn functions as a regulator of both mesenchymal and epithelial proliferation, and that androgens regulate Ptn levels. Prostate 71:305–317, 2011. © 2010 Wiley-Liss, Inc. PMID:20812209

  7. Transactivation domain of p53 regulates DNA repair and integrity in human iPS cells.

    PubMed

    Kannappan, Ramaswamy; Mattapally, Saidulu; Wagle, Pooja A; Zhang, Jianyi

    2018-05-18

    The role of p53 transactivation domain (p53-TAD), a multifunctional and dynamic domain, on DNA repair and retaining DNA integrity in human iPS cells has never been studied. p53-TAD was knocked out in iPS cells using CRISPR/Cas9 and was confirmed by DNA sequencing. p53-TAD KO cells were characterized by: accelerated proliferation, decreased population doubling time, and unaltered Bcl2, BBC3, IGF1R, Bax and altered Mdm2, p21, and PIDD transcripts expression. In p53-TAD KO cells p53 regulated DNA repair proteins XPA, DNA polH and DDB2 expression were found to be reduced compared to p53-WT cells. Exposure to low dose of doxorubicin (Doxo) induced similar DNA damage and DNA damage response (DDR) measured by RAD50 and MRE11 expression, Checkpoint kinase 2 activation and γH2A.X recruitment at DNA strand breaks in both the cell groups indicating silencing p53-TAD do not affect DDR mechanism upstream of p53. Following removal of Doxo p53-WT hiPS cells underwent DNA repair, corrected their damaged DNA and restored DNA integrity. Conversely, p53-TAD KO hiPS cells did not undergo complete DNA repair and failed to restore DNA integrity. More importantly continuous culture of p53-TAD KO hiPS cells underwent G2/M cell cycle arrest and expressed cellular senescent marker p16 INK4a . Our data clearly shows that silencing transactivation domain of p53 did not affect DDR but affected the DNA repair process implying the crucial role of p53 transactivation domain in maintaining DNA integrity. Therefore, activating p53-TAD domain using small molecules may promote DNA repair and integrity of cells and prevent senescence.

  8. Epididymal genomics and the search for a male contraceptive.

    PubMed

    Turner, T T; Johnston, D S; Jelinsky, S A

    2006-05-16

    This report represents the joint efforts of three laboratories, one with a primary interest in understanding regulatory processes in the epididymal epithelium (TTT) and two with a primary interest in identifying and characterizing new contraceptive targets (DSJ and SAJ). We have developed a highly refined mouse epididymal transcriptome and have used it as a starting point for determining genes in the human epididymis, which may serve as targets for male contraceptives. Our database represents gene expression information for approximately 39,000 transcripts, of which over 17,000 are significantly expressed in at least one segment of the mouse epididymis. Over 2000 of these transcripts are up- or down-regulated by at least four-fold between at least two segments. In addition, human databases have been queried to determine expression of orthologs in the human epididymis and the specificity of their expression in the epididymis. Genes highly regulated in the human epididymis and showing high tissue specificity are potential targets for male contraceptives.

  9. Endoplasmic reticulum-plasma membrane contact sites integrate sterol and phospholipid regulation.

    PubMed

    Quon, Evan; Sere, Yves Y; Chauhan, Neha; Johansen, Jesper; Sullivan, David P; Dittman, Jeremy S; Rice, William J; Chan, Robin B; Di Paolo, Gilbert; Beh, Christopher T; Menon, Anant K

    2018-05-01

    in regulating ER-PM contact site formation. In sterol-depleted cells, levels of the yeast E-Syt tether Tcb3 were induced and ER-PM contact increased dramatically. These results support a model in which ER-PM contact sites provide a nexus for coordinating the complex interrelationship between sterols, sphingolipids, and phospholipids that maintain PM composition and integrity.

  10. Analysis of the meiotic transcriptome reveals the genes related to the regulation of pollen abortion in cytoplasmic male-sterile pepper (Capsicum annuum L.).

    PubMed

    Qiu, Yilan; Liao, Lijuan; Jin, Xiaorui; Mao, Dandan; Liu, Rushi

    2018-01-30

    CMS, which refers to the inability to generate functional pollen grains while still producing a normal gynoecium, has been widely used for pepper hybrid seed production. Pepper line 8214A is an excellent CMS line exhibiting 100% male sterility and superior economic characteristics. A TUNEL assay revealed the nuclear DNA is damaged in 8214A PMCs during meiosis. TEM images indicated that the 8214A PMCs exhibited asynchronous meiosis after prophase I, and some PMCs degraded prematurely with morphological features typical of PCD. Additionally, at the end of meiosis, the 8214A PMCs formed abnormal non-tetrahedral tetrads that degraded in situ. To identify the genes involved in the pollen abortion of line 8214A, the transcriptional profiles of the 8214A and the 8214B anthers (i.e., from the fertile maintainer line) during meiosis were analyzed using an RNA-seq approach. A total of 1355 genes were determined to be differentially expressed, including 424 and 931 up- and down- regulated genes, respectively, in the 8214A anthers during meiosis relative to the expression levels in the 8214B. The expression levels of ubiquitin ligase and cell cycle-related genes were apparently down-regulated, while the expression of methyltransferase genes was up-regulated in the 8214A anthers during meiosis, which likely contributed to the PCD of these PMCs during meiosis. Thus, our results may be useful for revealing the molecular mechanism regulating the pollen abortion of CMS pepper. Copyright © 2017. Published by Elsevier B.V.

  11. Integrated proteomics and metabolomics suggests symbiotic metabolism and multimodal regulation in a fungal-endobacterial system.

    PubMed

    Li, Zhou; Yao, Qiuming; Dearth, Stephen P; Entler, Matthew R; Castro Gonzalez, Hector F; Uehling, Jessie K; Vilgalys, Rytas J; Hurst, Gregory B; Campagna, Shawn R; Labbé, Jessy L; Pan, Chongle

    2017-03-01

    Many plant-associated fungi host endosymbiotic endobacteria with reduced genomes. While endobacteria play important roles in these tri-partite plant-fungal-endobacterial systems, the active physiology of fungal endobacteria has not been characterized extensively by systems biology approaches. Here, we use integrated proteomics and metabolomics to characterize the relationship between the endobacterium Mycoavidus sp. and the root-associated fungus Mortierella elongata. In nitrogen-poor media, M. elongata had decreased growth but hosted a large and growing endobacterial population. The active endobacterium likely extracted malate from the fungal host as the primary carbon substrate for energy production and biosynthesis of phospho-sugars, nucleobases, peptidoglycan and some amino acids. The endobacterium obtained nitrogen by importing a variety of nitrogen-containing compounds. Further, nitrogen limitation significantly perturbed the carbon and nitrogen flows in the fungal metabolic network. M. elongata regulated many pathways by concordant changes on enzyme abundances, post-translational modifications, reactant concentrations and allosteric effectors. Such multimodal regulations may be a general mechanism for metabolic modulation. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  12. The melanocortin system regulates body pigmentation and social behaviour in a colour polymorphic cichlid fish†

    PubMed Central

    Maguire, Sean M.; Harris, Rayna M.; Rodriguez, Agosto A.; DeAngelis, Ross S.; Flores, Stephanie A.; Hofmann, Hans A.

    2017-01-01

    The melanocortin system is a neuroendocrine system that regulates a range of physiological and behavioural processes. We examined the extent to which the melanocortin system simultaneously regulates colour and behaviour in the cichlid fish Astatotilapia burtoni. We found that yellow males are more aggressive than blue males, in line with previous studies. We then found that exogenous α-melanocyte-stimulating hormone (α-MSH) increases yellowness of the body and dispersal of xanthophore pigments in both morphs. However, α-MSH had a morph-specific effect on aggression, with only blue males showing an increase in the rate of aggression. Exogenous agouti signalling peptide (ASIP), a melanocortin antagonist, did not affect coloration but reduced the rate of aggression in both colour morphs. Blue males had higher cortisol levels than yellow males. Neural gene expression of melanocortin receptors (mcr) and ligands was not differentially regulated between colour morphs. In the skin, however, mc1r and pro-opiomelanocortin (pomc) β were upregulated in blue males, while asip 1 was upregulated in yellow males. The effects of α-MSH on behaviour and body coloration, combined with morph-specific regulation of the stress response and the melanocortin system, suggest that the melanocortin system contributes to the polymorphism in behaviour and coloration in A. burtoni. PMID:28356453

  13. Androgen responses to reproductive competition of males pursuing either fixed or plastic alternative reproductive tactics.

    PubMed

    von Kuerthy, Corinna; Ros, Albert F H; Taborsky, Michael

    2016-11-15

    Alternative reproductive tactics (ARTs), which can be plastic or fixed for life, may be characterized by distinct hormonal profiles. The relative plasticity hypothesis predicts flexible androgen regulation for adult males pursuing plastic tactics, but a less flexible regulation for males using a fixed tactic throughout life. Furthermore, androgen profiles may respond to changes in the social environment, as predicted by the social reciprocity models of hormone/behaviour interactions. The cichlid fish Lamprologus callipterus provides a rare opportunity to study the roles of androgens for male ARTs within a single species, because fixed and plastic ARTs coexist. We experimentally exposed males to competitors pursuing either the same or different tactics to test predictions of the relative plasticity and the social reciprocity models. Androgen profiles of different male types partly comply with predictions derived from the relative plasticity hypothesis: males of the plastic bourgeois/sneaker male trajectory showed different 11-ketotestosterone (11-KT) levels when pursuing either bourgeois or parasitic sneaker male behaviours. Surprisingly, males pursuing the fixed dwarf male tactic showed the highest free and conjugated 11-KT and testosterone (T) levels. Our experimental social challenges significantly affected the free 11-KT levels of bourgeois males, but the androgen responses did not differ between challenges involving different types of competitors. Furthermore, the free T-responses of the bourgeois males correlated with their aggressive behaviour exhibited against competitors. Our results provide new insights into the endocrine responsiveness of fixed and plastic ARTs, confirming and refuting some predictions of both the relative plasticity and the social reciprocity models. © 2016. Published by The Company of Biologists Ltd.

  14. Characterization of Reproductive Dormancy in Male Drosophila melanogaster

    PubMed Central

    Kubrak, Olga I.; Kučerová, Lucie; Theopold, Ulrich; Nylin, Sören; Nässel, Dick R.

    2016-01-01

    Insects are known to respond to seasonal and adverse environmental changes by entering dormancy, also known as diapause. In some insect species, including Drosophila melanogaster, dormancy occurs in the adult organism and postpones reproduction. This adult dormancy has been studied in female flies where it is characterized by arrested development of ovaries, altered nutrient stores, lowered metabolism, increased stress and immune resistance and drastically extended lifespan. Male dormancy, however, has not been investigated in D. melanogaster, and its physiology is poorly known in most insects. Here we show that unmated 3–6 h old male flies placed at low temperature (11°C) and short photoperiod (10 Light:14 Dark) enter a state of dormancy with arrested spermatogenesis and development of testes and male accessory glands. Over 3 weeks of diapause we see a dynamic increase in stored carbohydrates and an initial increase and then a decrease in lipids. We also note an up-regulated expression of genes involved in metabolism, stress responses and innate immunity. Interestingly, we found that male flies that entered reproductive dormancy do not attempt to mate females kept under non-diapause conditions (25°C, 12L:12D), and conversely non-diapausing males do not mate females in dormancy. In summary, our study shows that male D. melanogaster can enter reproductive dormancy. However, our data suggest that dormant male flies deplete stored nutrients faster than females, studied earlier, and that males take longer to recover reproductive capacity after reintroduction to non-diapause conditions. PMID:27932997

  15. Difficulties in emotion regulation and risky driving among Lithuanian drivers.

    PubMed

    Šeibokaitė, Laura; Endriulaitienė, Auksė; Sullman, Mark J M; Markšaitytė, Rasa; Žardeckaitė-Matulaitienė, Kristina

    2017-10-03

    Risky driving is a common cause of traffic accidents and injuries. However, there is no clear evidence of how difficulties in emotion regulation contribute to risky driving behavior, particularly in small post-Soviet countries. The present study aimed to investigate the relationship between difficulties in emotion regulation and self-reported risky driving behavior in a sample of Lithuanian drivers. A total of 246 nonprofessional Lithuanian drivers participated in a cross-sectional survey. Difficulties in emotion regulation were assessed using the Difficulties in Emotion Regulation Scale (DERS; Gratz and Roemer 2004), and risky driving behavior was assessed using the Manchester Driver Behaviour Questionnaire (DBQ; Lajunen et al. 2004). Males scored higher than females in aggressive violations and ordinary violations. Females scored higher for the nonacceptance of emotional responses, whereas males had more difficulties with emotional awareness than females. More difficulties in emotion regulation were positively correlated with driving errors, lapses, aggressive violations, and ordinary violations for both males and females. Structural equation modeling showed that difficulties in emotion regulation explained aggressive and ordinary violations more clearly than lapses and errors. When controlling for interactions among the distinct regulation difficulties, difficulties with impulse control and difficulties engaging in goal-directed behavior predicted risky driving. Furthermore, nonacceptance of emotional responses and limited access to emotion regulation strategies were related to less violations and more driving errors. Emotion regulation difficulties were associated with the self-reported risky driving behaviors of Lithuanian drivers. This provides useful hints for improving driver training programs in order to prevent traffic injuries.

  16. C-fos down-regulation inhibits testosterone-dependent male sexual behavior and the associated learning

    PubMed Central

    Niessen, Neville-Andrew; Balthazart, Jacques; Ball, Gregory F.; Charlier, Thierry D.

    2013-01-01

    Environmental stimulation results in an increased expression of transcription factors called immediate early genes (IEG) in specific neuronal populations. In male Japanese quail, copulation with a female increases the expression of the IEGs zenk and c-fos in the medial preoptic nucleus (POM), a key nucleus controlling male sexual behavior. The functional significance of this increased IEG expression that follows performance of copulatory behavior is unknown. We addressed this question by repeatedly quantifying the performance of appetitive (learned social proximity response) and consummatory (actual copulation) sexual behavior in castrated, testosterone-treated males that received daily intracerebroventricular injection of an antisense oligodeoxynucleotide targeting c-fos or control vehicle. Daily antisense injections significantly inhibited expression of copulatory behavior as well as acquisition of the learned social proximity response. A strong reduction of the proximity response was still observed in antisense-treated birds that copulated with a female, ruling out the indirect effect of the absence of interactions with females on the learning process. After a two-day interruption of behavioral testing but not of antisense injections, birds were submitted to a final copulatory test that confirmed the behavioral inhibition in antisense-injected birds. Brains were collected 90 min after the behavioral testing for quantification of c-fos immunoreactive cells. A significant reduction of the number of c-fos-positive cells in POM but not in other brain regions was observed following antisense injection. Together, data suggest that c-fos expression in POM modulates copulatory behavior and sexual learning in male quail. PMID:23895306

  17. Topography in the preoptic region: Differential regulation of appetitive and consummatory male sexual behaviors

    PubMed Central

    Balthazart, Jacques; Ball, Gregory F.

    2007-01-01

    Several studies have suggested dissociations between neural circuits underlying the expression of appetitive (i.e. sexual motivation) and consummatory components (i.e., copulatory behavior) of vertebrate male sexual behavior. The medial preoptic area (mPOA) clearly controls the expression of male copulation but, according to a number of experiments, is not necessarily implicated in the expression of appetitive sexual behavior. In rats for example, lesions to the mPOA eliminate male-typical copulatory behavior but have more subtle or no obvious effects on measures of sexual motivation. Rats with such lesions still pursue and attempt to mount females. They also acquire and perform learned instrumental responses to gain access to females. However, recent lesions studies and measures of the expression of the immediate early gene c-fos demonstrate that, in quail, sub-regions of the mPOA, in particular of its sexually dimorphic component the medial preoptic nucleus, can be specifically linked with either the expression of appetitive or consummatory sexual behavior. In particular more rostral regions can be linked to appetitive components while more caudal regions are involved in consummatory behavior. This functional sub-region variation is associated with neurochemical and hodological specializations (i.e. differences in chemical phenotype of the cells or in their connectivity), especially those related to the actions of androgens in relation to the activation of male sexual behavior, that are also present in rodents and other species. It could thus reflect general principles about POA organization and function in the vertebrate brain. PMID:17624413

  18. Joint-linkage mapping and GWAS reveal extensive genetic loci that regulate male inflorescence size in maize

    USDA-ARS?s Scientific Manuscript database

    Both insufficient and excessive male inflorescence size leads to a reduction in maize yield. Knowledge of the genetic architecture of male inflorescence is essential to achieve the optimum inflorescence size for maize breeding. In this study, we used approximately eight thousand inbreds, including b...

  19. Operational compatibility of 30-centimeter-diameter ion thruster with integrally regulated solar array power source

    NASA Technical Reports Server (NTRS)

    Gooder, S. T.

    1977-01-01

    System tests were performed in which Integrally Regulated Solar Arrays (IRSA's) were used to directly power the beam and accelerator loads of a 30-cm-diameter, electron bombardment, mercury ion thruster. The remaining thruster loads were supplied from conventional power-processing circuits. This combination of IRSA's and conventional circuits formed a hybrid power processor. Thruster performance was evaluated at 3/4- and 1-A beam currents with both the IRSA-hybrid and conventional power processors and was found to be identical for both systems. Power processing is significantly more efficient with the hybrid system. System dynamics and IRSA response to thruster arcs are also examined.

  20. How does male–male competition generate negative frequency-dependent selection and disruptive selection during speciation?

    PubMed Central

    Border, Shana E

    2018-01-01

    Abstract Natural selection has been shown to drive population differentiation and speciation. The role of sexual selection in this process is controversial; however, most of the work has centered on mate choice while the role of male–male competition in speciation is relatively understudied. Here, we outline how male–male competition can be a source of diversifying selection on male competitive phenotypes, and how this can contribute to the evolution of reproductive isolation. We highlight how negative frequency-dependent selection (advantage of rare phenotype arising from stronger male–male competition between similar male phenotypes compared with dissimilar male phenotypes) and disruptive selection (advantage of extreme phenotypes) drives the evolution of diversity in competitive traits such as weapon size, nuptial coloration, or aggressiveness. We underscore that male–male competition interacts with other life-history functions and that variable male competitive phenotypes may represent alternative adaptive options. In addition to competition for mates, aggressive interference competition for ecological resources can exert selection on competitor signals. We call for a better integration of male–male competition with ecological interference competition since both can influence the process of speciation via comparable but distinct mechanisms. Altogether, we present a more comprehensive framework for studying the role of male–male competition in speciation, and emphasize the need for better integration of insights gained from other fields studying the evolutionary, behavioral, and physiological consequences of agonistic interactions. PMID:29492042

  1. A PDF/NPF neuropeptide signaling circuitry of male Drosophila melanogaster controls rival-induced prolonged mating.

    PubMed

    Kim, Woo Jae; Jan, Lily Yeh; Jan, Yuh Nung

    2013-12-04

    A primary function of males for many species involves mating with females for reproduction. Drosophila melanogaster males respond to the presence of other males by prolonging mating duration to increase the chance of passing on their genes. To understand the basis of such complex behaviors, we examine the genetic network and neural circuits that regulate rival-induced Longer-Mating-Duration (LMD). Here, we identify a small subset of clock neurons in the male brain that regulate LMD via neuropeptide signaling. LMD requires the function of pigment-dispersing factor (PDF) in four s-LNv neurons and its receptor PDFR in two LNd neurons per hemisphere, as well as the function of neuropeptide F (NPF) in two neurons within the sexually dimorphic LNd region and its receptor NPFR1 in four s-LNv neurons per hemisphere. Moreover, rival exposure modifies the neuronal activities of a subset of clock neurons involved in neuropeptide signaling for LMD. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. A PDF/NPF neuropeptide signaling circuitry of male Drosophila melanogaster controls rival-induced prolonged mating

    PubMed Central

    Kim, Woo Jae; Jan, Lily Yeh; Jan, Yuh Nung

    2013-01-01

    SUMMARY A primary function of males for many species involves mating with females for reproduction. Drosophila melanogaster males respond to the presence of other males by prolonging mating duration to increase the chance of passing on their genes. To understand the basis of such complex behaviors, we examine the genetic network and neural circuits that regulate rival-induced longer mating duration (LMD). Here we identify a small subset of clock neurons in the male brain that regulate LMD via neuropeptide signaling. LMD requires the function of pigment-dispersing factor (PDF) in four s-LNv neurons and its receptor PDFR in two LNd neurons per hemisphere, as well as the function of neuropeptide F (NPF) in two neurons within the sexually dimorphic LNd region and its receptor NPFR1 in four s-LNv neurons per hemisphere. Moreover, rival exposure modifies the neuronal activities of a subset of clock neurons involved in neuropeptide signaling for LMD. PMID:24314729

  3. Understanding Transcription Factor Regulation by Integrating Gene Expression and DNase I Hypersensitive Sites.

    PubMed

    Wang, Guohua; Wang, Fang; Huang, Qian; Li, Yu; Liu, Yunlong; Wang, Yadong

    2015-01-01

    Transcription factors are proteins that bind to DNA sequences to regulate gene transcription. The transcription factor binding sites are short DNA sequences (5-20 bp long) specifically bound by one or more transcription factors. The identification of transcription factor binding sites and prediction of their function continue to be challenging problems in computational biology. In this study, by integrating the DNase I hypersensitive sites with known position weight matrices in the TRANSFAC database, the transcription factor binding sites in gene regulatory region are identified. Based on the global gene expression patterns in cervical cancer HeLaS3 cell and HelaS3-ifnα4h cell (interferon treatment on HeLaS3 cell for 4 hours), we present a model-based computational approach to predict a set of transcription factors that potentially cause such differential gene expression. Significantly, 6 out 10 predicted functional factors, including IRF, IRF-2, IRF-9, IRF-1 and IRF-3, ICSBP, belong to interferon regulatory factor family and upregulate the gene expression levels responding to the interferon treatment. Another factor, ISGF-3, is also a transcriptional activator induced by interferon alpha. Using the different transcription factor binding sites selected criteria, the prediction result of our model is consistent. Our model demonstrated the potential to computationally identify the functional transcription factors in gene regulation.

  4. Gun control and suicide: the impact of state firearm regulations in the United States, 1995-2004.

    PubMed

    Rodríguez Andrés, Antonio; Hempstead, Katherine

    2011-06-01

    To empirically assess the impact of firearm regulation on male suicides. A negative binomial regression model was applied by using a panel of state level data for the years 1995-2004. The model was used to identify the association between several firearm regulations and male suicide rates. Our empirical analysis suggest that firearms regulations which function to reduce overall gun availability have a significant deterrent effect on male suicide, while regulations that seek to prohibit high risk individuals from owning firearms have a lesser effect. Restricting access to lethal means has been identified as an effective approach to suicide prevention, and firearms regulations are one way to reduce gun availability. The analysis suggests that gun control measures such as permit and licensing requirements have a negative effect on suicide rates among males. Since there is considerable heterogeneity among states with regard to gun control, these results suggest that there are opportunities for many states to reduce suicide by expanding their firearms regulations. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  5. Gender and enterprise in fragile refugee settings: female empowerment amidst male emasculation-a challenge to local integration?

    PubMed

    Ritchie, Holly A

    2018-01-01

    This paper examines gender and enterprise in fragile refugee settings. Building on previous research in Afghanistan, it analyses refugee women's evolving economic lives and enterprise initiatives and related social dynamics in refugee communities. Case studies look specifically at two Islamic refugee contexts: Nairobi, Kenya (Somali refugees), and Irbid and Zarqa, Jordan (Syrian refugees). The discussion spotlights the precarious nature of refugee women's new practices and work norms under forced and strained circumstances, without a process of negotiation with male family members. In the case of longer-term refugees (Somalis), it describes new collective agency among refugee women, boosting support for new practices. The paper reflects on emerging gender roles and relations in such hostile conditions, particularly as men remain excluded and struggle for their own identity and authority. In addition, it draws attention to the gap relating to refugee men and policymaking, and highlights ways to address better their needs for refugee resilience, inclusion, and local integration. © 2018 The Author(s). Disasters © Overseas Development Institute, 2018.

  6. Expression of the nuclear gene TaF(A)d is under mitochondrial retrograde regulation in anthers of male sterile wheat plants with timopheevii cytoplasm.

    PubMed

    Xu, Pei; Yang, Yuwen; Zhang, Zhengzhi; Chen, Weihua; Zhang, Caiqin; Zhang, Lixia; Zou, Sixiang; Ma, Zhengqiang

    2008-01-01

    Alterations of mitochondrial-encoded subunits of the F(o)F(1)-ATP synthase are frequently associated with cytoplasmic male sterility (CMS) in plants; however, little is known about the relationship of the nuclear encoded subunits of this enzyme with CMS. In the present study, the full cDNA of the gene TaF(A)d that encodes the putative F(A)d subunit of the F(o)F(1)-ATP synthase was isolated from the wheat (Triticum aestivum) fertility restorer '2114' for timopheevii cytoplasm-based CMS. The deduced 238 amino acid polypeptide is highly similar to its counterparts in dicots and other monocots but has low homology to its mammalian equivalents. TaF(A)d is a single copy gene in wheat and maps to the short arm of the group 6 chromosomes. Transient expression of the TaF(A)d-GFP fusion in onion epidermal cells demonstrated TaF(A)d's mitochondrial location. TaF(A)d was expressed abundantly in stem, leaf, anther, and ovary tissues of 2114. Nevertheless, its expression was repressed in anthers of CMS plants with timopheevii cytoplasm. Genic male sterility did not affect its expression in anthers. The expression of the nuclear gene encoding the 20 kDa subunit of F(o) was down-regulated in a manner similar to TaF(A)d in the T-CMS anthers while that of genes encoding the 6 kDa subunit of F(o) and the gamma subunit of F(1) was unaffected. These observations implied that TaF(A)d is under mitochondrial retrograde regulation in the anthers of CMS plants with timopheevii cytoplasm.

  7. Corazonin Signaling Is Required in the Male for Sperm Transfer in the Oriental Fruit Fly Bactrocera dorsalis

    PubMed Central

    Hou, Qiu-Li; Chen, Er-Hu; Jiang, Hong-Bo; Yu, Shuai-Feng; Yang, Pei-Jin; Liu, Xiao-Qiang; Park, Yoonseong; Wang, Jin-Jun; Smagghe, Guy

    2018-01-01

    Corazonin (Crz) is a widely distributed neuropeptide (or neurohormone) in insects with diverse physiological functions. The present study aimed to reveal the functions of Crz and its receptor (CrzR) in the regulation of sexual behavior and fertility in male Bactrocera dorsalis. Tissue-specific expression analyses showed that the BdCrz transcript was most abundant in the central nervous system (CNS), and the BdCrzR transcript was most abundant in both the fat body and CNS. Immunochemical localization confirmed that three pairs of Crz-immunoreactive neurons are located in the dorsolateral protocerebrum region of male adult brain. Importantly, RNAi-mediated Crz knockdown lengthened mating duration in males, and knockdown of Crz or CrzR strongly decreased male fertility in the following 3 days, while the courtship behavior and mating efficiency were not affected. The reduced number of sperm in the reproductive organs of mated females indicated that Crz knockdown in males reduced sperm transfer. The findings of this study indicate that Crz contributes to the reproductive physiology of the oriental fruit fly B. dorsalis by regulating sperm transfer in male adults.

  8. Corazonin Signaling Is Required in the Male for Sperm Transfer in the Oriental Fruit Fly Bactrocera dorsalis.

    PubMed

    Hou, Qiu-Li; Chen, Er-Hu; Jiang, Hong-Bo; Yu, Shuai-Feng; Yang, Pei-Jin; Liu, Xiao-Qiang; Park, Yoonseong; Wang, Jin-Jun; Smagghe, Guy

    2018-01-01

    Corazonin (Crz) is a widely distributed neuropeptide (or neurohormone) in insects with diverse physiological functions. The present study aimed to reveal the functions of Crz and its receptor (CrzR) in the regulation of sexual behavior and fertility in male Bactrocera dorsalis . Tissue-specific expression analyses showed that the BdCrz transcript was most abundant in the central nervous system (CNS), and the BdCrzR transcript was most abundant in both the fat body and CNS. Immunochemical localization confirmed that three pairs of Crz-immunoreactive neurons are located in the dorsolateral protocerebrum region of male adult brain. Importantly, RNAi-mediated Crz knockdown lengthened mating duration in males, and knockdown of Crz or CrzR strongly decreased male fertility in the following 3 days, while the courtship behavior and mating efficiency were not affected. The reduced number of sperm in the reproductive organs of mated females indicated that Crz knockdown in males reduced sperm transfer. The findings of this study indicate that Crz contributes to the reproductive physiology of the oriental fruit fly B. dorsalis by regulating sperm transfer in male adults.

  9. Integration of multiple stimuli-sensing systems to regulate HrpS and type III secretion system in Erwinia amylovora.

    PubMed

    Lee, Jae Hoon; Zhao, Youfu

    2018-02-01

    The bacterial enhancer binding protein (bEBP) HrpS is essential for Erwinia amylovora virulence by activating the type III secretion system (T3SS). However, how the hrpS gene is regulated remains poorly understood in E. amylovora. In this study, 5' rapid amplification of cDNA ends and promoter deletion analyses showed that the hrpS gene contains two promoters driven by HrpX/HrpY and the Rcs phosphorelay system, respectively. Electrophoretic mobility shift and gene expression assays demonstrated that integration host factor IHF positively regulates hrpS expression through directly binding the hrpX promoter and positively regulating hrpX/hrpY expression. Moreover, hrpX expression was down-regulated in the relA/spoT ((p)ppGpp-deficient) mutant and the dksA mutant, but up-regulated when the wild-type strain was treated with serine hydroxamate, which induced (p)ppGpp-mediated stringent response. Furthermore, the csrA mutant showed significantly reduced transcripts of major hrpS activators, including the hrpX/hrpY, rcsA and rcsB genes, indicating that CsrA is required for full hrpS expression. On the other hand, the csrB mutant exhibited up-regulation of the rcsA and rcsB genes, and hrpS expression was largely diminished in the csrB/rcsB mutant, indicating that the Rcs system is mainly responsible for the increased hrpS expression in the csrB mutant. These findings suggest that E. amylovora recruits multiple stimuli-sensing systems, including HrpX/HrpY, the Rcs phosphorelay system and the Gac-Csr system, to regulate hrpS and T3SS gene expression.

  10. Heat stress affects male reproduction in a parasitoid wasp.

    PubMed

    Nguyen, Thanh Manh; Bressac, Christophe; Chevrier, Claude

    2013-03-01

    In insects, reproductive success and survival are affected by temperature. Reproduction is more sensitive than other physiological traits. While the effects of heat stress on females are well known, the effects on males are less clear. Hymenopteran parasitoids are valuable for studying the consequences of heat stress on male reproduction. In these species, through arrhenotoquous parthenogenesis, the sex ratio of the offspring is directly dependent on the sperm stock acquired by females during copulation. In the lab, heat temperature treatments (32-44°C) were applied for 3 days in the pupal stage of Anisopteromalus calandrae males, and development was completed at 30°C. Three different effects were observed depending on the temperature: mortality above 42°C, sterility of emerging males at 40°C, and sub-fertility at 38°C. This sub-fertility is characterized by a dramatic decrease in male sperm supplies, of up to 7% compared to control males. In the course of ageing, the sperm stock of sub-fertile males increases but never reaches the level of control males. Survival was significantly higher in control (30°C) males than those treated at 38°C. Male mating ability was similar whatever the treatment (control and 38°C), but females mated with 38°C-treated males stored 100 times less sperm on average than those mated with control males. The offspring sex ratio of females mated with 38°C-treated males was strongly male biased. The physiological mechanisms are as yet unknown. The relationship between temperature, sperm stock and sex ratio should be taken into account in the management of parasitoids for integrated pest management. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Slow stamen movement in a perennial herb decreases male-male and male-female interference.

    PubMed

    Wang, Lingyan; Bao, Yu; Wang, Hanxi; He, Chunguang; Wang, Ping; Sheng, Lianxi; Tang, Zhanhui

    2017-07-01

    Approximately 80 % of angiosperm species produce hermaphroditic flowers, which face the problem of male - male sexual interference (one or more anthers gets in the way of disseminating pollen from other anthers) or male - female sexual interference (the pistil interferes with disseminating pollen from the anthers by preventing the anther from touching a pollinator, or the anther prevents pollinator from depositing outcross pollen on the stigma). Slow stamen movement in hermaphrodite flowers has been interpreted as an adaptation for reducing male - male sexual interference. Using slow stamen movement in Lychnis cognata (Caryophyllaceae), this study presents new evidence that this phenomenon can reduce both male - male and male - female sexual interference. Ten stamens in L. cognata flowers vertically elongated their filaments in two batches and displayed similar patterns in pollen dispensing. More importantly, 10 stamens bend out of the floral centre by curving the filament also in 2 batches and pollen grains located at the flower centre displayed the highest viability. Thus, three stages of stamen movement can be identified, comprising two male stages (M1 and M2) and one female stage (F). We found that the main pollinator for L. cognata, Bhutanitis yulongensis (Papilionodae) generally preferred M1 flowers. Manipulation experiments show that vertical stamen movement enabled the anthers to dehisce at different times to prolong the presentation of pollen grains. Horizontal movement of the stamen decreased both male - male and male - female interference. However, vertical stamen movement had a minor role in increasing amount of pollen received by the stigma. This study provides the first direct experimental evidence of concurrent male - male and male - female interference in a flower. We suggest that the selection pressure to reduce such interference might be a strong force in floral evolution. We also propose that other selective pressure, including pollen

  12. An Integrative Genetics Approach to Identify Candidate Genes Regulating BMD: Combining Linkage, Gene Expression, and Association

    PubMed Central

    Farber, Charles R; van Nas, Atila; Ghazalpour, Anatole; Aten, Jason E; Doss, Sudheer; Sos, Brandon; Schadt, Eric E; Ingram-Drake, Leslie; Davis, Richard C; Horvath, Steve; Smith, Desmond J; Drake, Thomas A; Lusis, Aldons J

    2009-01-01

    Numerous quantitative trait loci (QTLs) affecting bone traits have been identified in the mouse; however, few of the underlying genes have been discovered. To improve the process of transitioning from QTL to gene, we describe an integrative genetics approach, which combines linkage analysis, expression QTL (eQTL) mapping, causality modeling, and genetic association in outbred mice. In C57BL/6J × C3H/HeJ (BXH) F2 mice, nine QTLs regulating femoral BMD were identified. To select candidate genes from within each QTL region, microarray gene expression profiles from individual F2 mice were used to identify 148 genes whose expression was correlated with BMD and regulated by local eQTLs. Many of the genes that were the most highly correlated with BMD have been previously shown to modulate bone mass or skeletal development. Candidates were further prioritized by determining whether their expression was predicted to underlie variation in BMD. Using network edge orienting (NEO), a causality modeling algorithm, 18 of the 148 candidates were predicted to be causally related to differences in BMD. To fine-map QTLs, markers in outbred MF1 mice were tested for association with BMD. Three chromosome 11 SNPs were identified that were associated with BMD within the Bmd11 QTL. Finally, our approach provides strong support for Wnt9a, Rasd1, or both underlying Bmd11. Integration of multiple genetic and genomic data sets can substantially improve the efficiency of QTL fine-mapping and candidate gene identification. PMID:18767929

  13. The moderator role of emotion regulation ability in the link between stress and well-being

    PubMed Central

    Extremera, Natalio; Rey, Lourdes

    2015-01-01

    This article examined the moderating role of a central core dimension of emotional intelligence—emotion-regulation ability—in the relationship between perceived stress and indicators of well-being (depression and subjective happiness) in a sample from a community adult population. The relationships for males and females on these dimensions were also compared. Results revealed that emotion-regulation abilities moderated both the association between perceived stress and depression/happiness for the total sample. However, a gender-specific analysis showed that the moderation effect was only significant for males. In short, when males reported a high level of perceived stress, those with high scores in regulating emotions reported higher scores in subjective happiness and lower depression symptoms than those with low regulating emotions. However, no interaction effect of regulating emotions and stress for predicting subjective happiness and depression was found for females. In developing stress management programmes for reducing depression and increasing well-being, these findings suggest that training in emotional regulation may be more beneficial for males than females. Our findings are discussed in terms of the need for future research to understand the different gender associations and to consider these differences in further intervention programmes. PMID:26579017

  14. A link between hypothyroidism, obesity and male reproduction.

    PubMed

    Aiceles, Veronica; da Fonte Ramos, Cristiane

    2016-01-01

    Hypothyroidism is a condition in which the serum levels of thyroid hormones are below that necessary to carry out physiological functions in the body. Hypothyroidism is related to obesity as an increase in body weight gain is seen in hypothyroid patients. Moreover, an inverse correlation between free thyroxine values and body mass index has been reported. Leptin, a polypeptide hormone produced by adipocytes, was originally thought to be an antiobesity hormone due its anorexic effects on hypothalamic appetite regulation. However, nowadays it is known that leptin conveys information about the nutritional status to the brain being considered a crucial endocrine factor for regulating several physiological processes including reproduction. Since the identification of thyroid hormone and leptin receptors on the testes, these hormones are being recognized as having important roles in male reproductive functions. A clear link exists among thyroid hormones, leptin and reproduction. Both hormones can negatively affect spermatogenesis and consequently may cause male infertility. The World Health Organization (WHO) estimates the overall prevalence of primary infertility ranging from 8 to 15%. The fact that 30% of couples' inability to conceive is related to a male factor and that the longer hypothyroidism persisted, the greater the damage to the testes, strongly suggest that more studies attempting to clarify both hormones actions directly in the testes need to be conducted specially in cases of congenital hypothyroidism. Therefore, the goal of this review is to highlight the relationship of such hormones in the reproductive system.

  15. Hormonal and molecular effects of restraint stress on formalin-induced pain-like behavior in male and female mice.

    PubMed

    Long, Caela C; Sadler, Katelyn E; Kolber, Benedict J

    2016-10-15

    The evolutionary advantages to the suppression of pain during a stressful event (stress-induced analgesia (SIA)) are obvious, yet the reasoning behind sex-differences in the expression of this pain reduction are not. The different ways in which males and females integrate physiological stress responses and descending pain inhibition are unclear. A potential supraspinal modulator of stress-induced analgesia is the central nucleus of the amygdala (CeA). This limbic brain region is involved in both the processing of stress and pain; the CeA is anatomically and molecularly linked to regions of the hypothalamic pituitary adrenal (HPA) axis and descending pain network. The CeA exhibits sex-based differences in response to stress and pain that may differentially induce SIA in males and females. Here, sex-based differences in behavioral and molecular indices of SIA were examined following noxious stimulation. Acute restraint stress in male and female mice was performed prior to intraplantar injections of formalin, a noxious inflammatory agent. Spontaneous pain-like behaviors were measured for 60min following formalin injection and mechanical hypersensitivity was evaluated 120 and 180min post-injection. Restraint stress altered formalin-induced spontaneous behaviors in male and female mice and formalin-induced mechanical hypersensitivity in male mice. To assess molecular indices of SIA, tissue samples from the CeA and blood samples were collected at the 180min time point. Restraint stress prevented formalin-induced increases in extracellular signal regulated kinase 2 (ERK2) phosphorylation in the male CeA, but no changes associated with pERK2 were seen with formalin or restraint in females. Sex differences were also seen in plasma corticosterone concentrations 180min post injection. These results demonstrate sex-based differences in behavioral, molecular, and hormonal indices of acute stress in mice that extend for 180min after stress and noxious stimulation. Copyright

  16. The Anaphase-Promoting Complex is a dual integrator that regulates both microRNA-mediated transcriptional regulation of Cyclin B1 and degradation of Cyclin B1 during Arabidopsis male gametophyte development

    USDA-ARS?s Scientific Manuscript database

    The anaphase-promoting complex/cyclosome (APC/C), an essential ubiquitin protein ligase, regulates mitotic progression and exit by enhancing degradation of cell cycle regulatory proteins, such as CYCB1;1, whose transcripts are upregulated by DUO POLLEN1 (DUO1). DUO1 is required for cell division in ...

  17. The Anaphase-Promoting Complex Is a Dual Integrator That Regulates Both MicroRNA-Mediated Transcriptional Regulation of Cyclin B1 and Degradation of Cyclin B1 during Arabidopsis Male Gametophyte Development

    USDA-ARS?s Scientific Manuscript database

    The anaphase-promoting complex/cyclosome (APC/C), an essential ubiquitin protein ligase, regulates mitotic progression and exit by enhancing degradation of cell cycle regulatory proteins, such as CYCB1;1, whose transcripts are upregulated by DUO POLLEN1 (DUO1). DUO1 is required for cell division in ...

  18. Sperm-specific ion channels: targets holding the most potential for male contraceptives in development.

    PubMed

    Zheng, Li-Ping; Wang, Hua-Feng; Li, Bao-Ming; Zeng, Xu-Hui

    2013-10-01

    There is a global need for an ideal method of male contraception. However, the development of male contraceptives has not been well successful. Research on sperm-specific ion channels, especially the recent advance obtained from electrophysiological studies, has emphasized the conception that those channels are targets with the most potential to develop non-hormonal male contraceptives. While summarizing the general options for male contraception, this review focuses on the properties and functions of sperm ion channels together with the attempts of utilizing these channels to develop male contraceptives. We believe that a deeper insight into the signaling and molecular mechanisms by which ion channels regulate sperm functions will pave the way for developing novel male-based contraceptives. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. A translational systems biology approach in both animals and humans identifies a functionally related module of accumbal genes involved in the regulation of reward processing and binge drinking in males

    PubMed Central

    Stacey, David; Lourdusamy, Anbarasu; Ruggeri, Barbara; Maroteaux, Matthieu; Jia, Tianye; Cattrell, Anna; Nymberg, Charlotte; Banaschewski, Tobias; Bhattacharyya, Sohinee; Band, Hamid; Barker, Gareth; Bokde, Arun; Buchel, Christian; Carvalho, Fabiana; Conrod, Patricia; Desrivieres, Sylvane; Easton, Alanna; Fauth-Buehler, Mira; Fernandez-Medarde, Alberto; Flor, Herta; Frouin, Vincent; Gallinat, Jurgen; Garavanh, Hugh; Heinz, Andreas; Ittermann, Bernd; Lathrop, Mark; Lawrence, Claire; Loth, Eva; Mann, Karl; Martinot, Jean-Luc; Nees, Frauke; Paus, Tomas; Pausova, Zdenka; Rietschel, Marcella; Rotter, Andrea; Santos, Eugenio; Smolka, Michael; Sommer, Wolfgang; Mameli, Manuel; Spanagel, Rainer; Girault, Jean-Antoine; Mueller, Christian; Schumann, Gunter

    2016-01-01

    Background The mesolimbic dopamine system, composed primarily of dopaminergic neurons in the ventral tegmental area that project to striatal structures, is considered to be the key mediator of reinforcement-related mechanisms in the brain. Prompted by a genome-wide association meta-analysis implicating the Ras-specific guanine nucleotide-releasing factor 2 (RASGRF2) gene in the regulation of alcohol intake in men, we have recently shown that male Rasgrf2−/− mice exhibit reduced ethanol intake and preference accompanied by a perturbed mesolimbic dopamine system. We therefore propose that these mice represent a valid model to further elucidate the precise genes and mechanisms regulating mesolimbic dopamine functioning. Methods Transcriptomic data from the nucleus accumbens (NAcc) of male Rasgrf2−/− mice and wild-type controls were analyzed by weighted gene coexpression network analysis (WGCNA). We performed follow-up genetic association tests in humans using a sample of male adolescents from the IMAGEN study characterized for binge drinking (n = 905) and ventral striatal activation during an fMRI reward task (n = 608). Results The WGCNA analyses using accumbal transcriptomic data revealed 37 distinct “modules,” or functionally related groups of genes. Two of these modules were significantly associated with Rasgrf2 knockout status: M5 (p < 0.001) and M6 (p < 0.001). In follow-up translational analyses we found that human orthologues for the M5 module were significantly (p < 0.01) enriched with genetic association signals for binge drinking in male adolescents. Furthermore, the most significant locus, originating from the EH-domain containing 4 (EHD4) gene (p < 0.001), was also significantly associated with altered ventral striatal activity in male adolescents performing an fMRI reward task (pempirical < 0.001). Limitations It was not possible to determine the extent to which the M5 module was dysregulated in Rasgrf2−/− mice by perturbed mesolimbic

  20. Myostatin signaling is up-regulated in female patients with advanced heart failure.

    PubMed

    Ishida, Junichi; Konishi, Masaaki; Saitoh, Masakazu; Anker, Markus; Anker, Stefan D; Springer, Jochen

    2017-07-01

    Myostatin, a negative regulator of skeletal muscle mass, is up-regulated in the myocardium of heart failure (HF) and increased myostatin is associated with weight loss in animal models with HF. Although there are disparities in pathophysiology and epidemiology between male and female patients with HF, it remains unclear whether there is gender difference in myostatin expression and whether it is associated with weight loss in HF patients. Heart tissue samples were collected from patients with advanced heart failure (n=31, female n=5) as well as healthy control donors (n=14, female n=6). Expression levels of myostatin and its related proteins in the heart were evaluated by western blotting analysis. Body mass index was significantly lower in female HF patients than in male counterparts (20.0±4.2 in female vs 25.2±3.8 in male, p=0.04). In female HF patients, both mature myostatin and pSmad2 were significantly up-regulated by 1.9 fold (p=0.05) and 2.5 fold (p<0.01) respectively compared to female donors, while expression of pSmad2 was increased by 2.8 times in male HF patients compared to male healthy subjects, but that of myostatin was not. There was no significant difference in protein expression related to myostatin signaling between male and female patients. In this study, myostatin and pSmad2 were significantly up-regulated in the failing heart of female patients, but not male patients, and female patients displayed lower body mass index. Enhanced myostatin signaling in female failing heart may causally contribute to pathogenesis of HF and cardiac cachexia. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Characterizing steroid hormone receptor chromatin binding landscapes in male and female breast cancer.

    PubMed

    Severson, Tesa M; Kim, Yongsoo; Joosten, Stacey E P; Schuurman, Karianne; van der Groep, Petra; Moelans, Cathy B; Ter Hoeve, Natalie D; Manson, Quirine F; Martens, John W; van Deurzen, Carolien H M; Barbe, Ellis; Hedenfalk, Ingrid; Bult, Peter; Smit, Vincent T H B M; Linn, Sabine C; van Diest, Paul J; Wessels, Lodewyk; Zwart, Wilbert

    2018-02-02

    Male breast cancer (MBC) is rare and poorly characterized. Like the female counterpart, most MBCs are hormonally driven, but relapse after hormonal treatment is also noted. The pan-hormonal action of steroid hormonal receptors, including estrogen receptor alpha (ERα), androgen receptor (AR), progesterone receptor (PR), and glucocorticoid receptor (GR) in this understudied tumor type remains wholly unexamined. This study reveals genomic cross-talk of steroid hormone receptor action and interplay in human tumors, here in the context of MBC, in relation to the female disease and patient outcome. Here we report the characterization of human breast tumors of both genders for cistromic make-up of hormonal regulation in human tumors, revealing genome-wide chromatin binding landscapes of ERα, AR, PR, GR, FOXA1, and GATA3 and enhancer-enriched histone mark H3K4me1. We integrate these data with transcriptomics to reveal gender-selective and genomic location-specific hormone receptor actions, which associate with survival in MBC patients.

  2. Nitric oxide signaling: systems integration of oxygen balance in defense of cell integrity.

    PubMed

    Gong, Li; Pitari, Giovanni M; Schulz, Stephanie; Waldman, Scott A

    2004-01-01

    Nitric oxide has emerged as a ubiquitous signaling molecule subserving diverse pathophysiologic processes, including cardiovascular homeostasis and its decompensation in atherogenesis. Recent insights into molecular mechanisms regulating nitric oxide generation and the rich diversity of mechanisms by which it propagates signals reveal the role of this simple gas as a principle mediator of systems integration of oxygen balance. The molecular lexicon by which nitric oxide propagates signals encompasses the elements of posttranslational modification of proteins by redox-based nitrosylation of transition metal centers and free thiols. Spatial and temporal precision and specificity of signal initiation, amplification, and propagation are orchestrated by dynamic assembly of supramolecular complexes coupling nitric oxide production to upstream and downstream components in specific subcellular compartments. The concept of local paracrine signaling by nitric oxide over subcellular distances for short durations has expanded to include endocrine-like effects over anatomic spatial and temporal scales. From these insights emerges a role for nitric oxide in integrating system responses controlling oxygen supply and demand to defend cell integrity in the face of ischemic challenge. In this context, nitric oxide coordinates the respiratory cycle to acquire and deliver oxygen to target tissues by regulating hemoglobin function and vascular smooth muscle contractility and matches energy supply and demand by down-regulating energy-requiring functions while shifting metabolism to optimize energy production. Insights into mechanisms regulating nitric oxide production and signaling and their integration into responses mediating homeostasis place into specific relief the role of those processes in pathophysiology. Indeed, endothelial dysfunction associated with altered production of nitric oxide regulating tissue integrity contributes to the pathogenesis underlying atherogenesis

  3. Multisensory regulation of maternal behavior and masculine sexual behavior: a revised view.

    PubMed

    Stern, J M

    1990-01-01

    Frank Beach's view of the multisensory regulation in Norway rats of copulation in males (12) and of pup retrieval in females (23) is critically analyzed and revised in terms of Lashley's influence, Beach's other work, and current neurobiological knowledge. Beach's view was that no single sensory stimulus is essential to elicit these behaviors, but that all relevant stimuli available summate in the neocortex; consequently, (a) sexual "arousal" is increased in males, leading to copulation, and (b) the "efficiency," or likelihood, of retrieval is increased in postpartum mothers. The revised view is based on a component analysis in which each of these behaviors consists of a chain of motoric responses elicited by somatosensory stimulation. Distal stimuli emanating from the female or pups induce proximity by provoking orientation, attention and arousal; the meaning of these stimuli is largely learned by conditioned associations during the initial executions of the behavior, although odors may have a prepotent influence for some individuals. Stimuli are integrated in a multisensory manner by both subcortical and neocortical mechanisms. Generalizations concerning the reproductive behavior of other mammalian species are suggested.

  4. Perinatal cocaine exposure inhibits the development of the male SDN.

    PubMed

    Maecker, H L

    1993-12-17

    The sexually dimorphic nucleus of the hypothalamus (SDN) is involved in sexual differentiation of the rat brain. Perinatal cocaine exposure was found to significantly reduce the volume of the male rat SDN (P < 0.001) while having no effect upon the volume of the female SDN. Pregnant dams and their pups were exposed to either saline, 7.5, 15, or 30 mg/kg of cocaine from gestational day 15 through postnatal day 10. Litter size, pup weight, male-female sex ratio, and gross birth defects were unaffected, but maternal weight gain was significantly reduced in cocaine-treated dams. These findings imply that males perinatally exposed to cocaine during their critical period of SDN differentiation may exhibit compromised coital capabilities as well as impaired gonadotropin regulation.

  5. Ventral Tegmental Area Dopamine Cell Activation during Male Rat Sexual Behavior Regulates Neuroplasticity and d-Amphetamine Cross-Sensitization following Sex Abstinence.

    PubMed

    Beloate, Lauren N; Omrani, Azar; Adan, Roger A; Webb, Ian C; Coolen, Lique M

    2016-09-21

    , followed by a period of abstinence from sexual behavior, causes increased reward for amphetamine in male rats. This study demonstrates that activation of ventral tegmental area dopamine neurons during sexual experience regulates cross-sensitization of amphetamine reward. Finally, ventral tegmental area dopamine cell activation is essential for experience-induced neural adaptations in the nucleus accumbens, prefrontal cortex, and ventral tegmental area. These findings demonstrate a role of mesolimbic dopamine in the interaction between natural and drug rewards, and identify mesolimbic dopamine as a key mediator of changes in vulnerability for drug use after loss of natural reward. Copyright © 2016 the authors 0270-6474/16/369949-13$15.00/0.

  6. Identification of octopaminergic neurons that modulate sleep suppression by male sex drive

    PubMed Central

    Machado, Daniel R; Afonso, Dinis JS; Kenny, Alexandra R; Öztürk-Çolak, Arzu; Moscato, Emilia H; Mainwaring, Benjamin; Kayser, Matthew; Koh, Kyunghee

    2017-01-01

    Molecular and circuit mechanisms for balancing competing drives are not well understood. While circadian and homeostatic mechanisms generally ensure sufficient sleep at night, other pressing needs can overcome sleep drive. Here, we demonstrate that the balance between sleep and sex drives determines whether male flies sleep or court, and identify a subset of octopaminergic neurons (MS1) that regulate sleep specifically in males. When MS1 neurons are activated, isolated males sleep less, and when MS1 neurons are silenced, the normal male sleep suppression in female presence is attenuated and mating behavior is impaired. MS1 neurons do not express the sexually dimorphic FRUITLESS (FRU) transcription factor, but form male-specific contacts with FRU-expressing neurons; calcium imaging experiments reveal bidirectional functional connectivity between MS1 and FRU neurons. We propose octopaminergic MS1 neurons interact with the FRU network to mediate sleep suppression by male sex drive. DOI: http://dx.doi.org/10.7554/eLife.23130.001 PMID:28510528

  7. Progesterone Impairs Social Recognition in Male Rats

    PubMed Central

    Auger, Catherine J.

    2012-01-01

    The influence of progesterone in the brain and on the behavior of females is fairly well understood. However, less is known about the effect of progesterone in the male system. In male rats, receptors for progesterone are present in virtually all vasopressin (AVP) immunoreactive cells in the bed nucleus of the stria terminalis (BST) and the medial amygdala (MeA). This colocalization functions to regulate AVP expression, as progesterone and/or progestin receptors (PR)s suppresses AVP expression in these same extrahypothalamic regions in the brain. These data suggest that progesterone may influence AVP-dependant behavior. While AVP is implicated in numerous behavioral and physiological functions in rodents, AVP appears essential for social recognition of conspecifics. Therefore, we examined the effects of progesterone on social recognition. We report that progesterone plays an important role in modulating social recognition in the male brain, as progesterone treatment lead to a significant impairment of social recognition in male rats. Moreover, progesterone appears to act on PRs to impair social recognition, as progesterone impairment of social recognition is blocked by a PR antagonist, RU-486. Social recognition is also impaired by a specific progestin agonist, R5020. Interestingly, we show that progesterone does not interfere with either general memory or olfactory processes, suggesting that progesterone seems critically important to social recognition memory. These data provide strong evidence that physiological levels of progesterone can have an important impact on social behavior in male rats. PMID:22366506

  8. Progesterone impairs social recognition in male rats.

    PubMed

    Bychowski, Meaghan E; Auger, Catherine J

    2012-04-01

    The influence of progesterone in the brain and on the behavior of females is fairly well understood. However, less is known about the effect of progesterone in the male system. In male rats, receptors for progesterone are present in virtually all vasopressin (AVP) immunoreactive cells in the bed nucleus of the stria terminalis (BST) and the medial amygdala (MeA). This colocalization functions to regulate AVP expression, as progesterone and/or progestin receptors (PR)s suppress AVP expression in these same extrahypothalamic regions in the brain. These data suggest that progesterone may influence AVP-dependent behavior. While AVP is implicated in numerous behavioral and physiological functions in rodents, AVP appears essential for social recognition of conspecifics. Therefore, we examined the effects of progesterone on social recognition. We report that progesterone plays an important role in modulating social recognition in the male brain, as progesterone treatment leads to a significant impairment of social recognition in male rats. Moreover, progesterone appears to act on PRs to impair social recognition, as progesterone impairment of social recognition is blocked by a PR antagonist, RU-486. Social recognition is also impaired by a specific progestin agonist, R5020. Interestingly, we show that progesterone does not interfere with either general memory or olfactory processes, suggesting that progesterone seems critically important to social recognition memory. These data provide strong evidence that physiological levels of progesterone can have an important impact on social behavior in male rats. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Macronutrient intake regulates sexual conflict in decorated crickets.

    PubMed

    Rapkin, J; Jensen, K; Lane, S M; House, C M; Sakaluk, S K; Hunt, J

    2016-02-01

    Sexual conflict results in a diversity of sex-specific adaptations, including chemical additions to ejaculates. Male decorated crickets (Gryllodes sigillatus) produce a gelatinous nuptial gift (the spermatophylax) that varies in size and free amino acid composition, which influences a female's willingness to fully consume this gift. Complete consumption of this gift maximizes sperm transfer through increased retention of the sperm-containing ampulla, but hinders post-copulatory mate choice. Here, we examine the effects of protein (P) and carbohydrate (C) intake on the weight and amino acid composition of the spermatophylax that describes its gustatory appeal to the female, as well as the ability of this gift to regulate sexual conflict via ampulla attachment time. Nutrient intake had similar effects on the expression of these traits with each maximized at a high intake of nutrients with a P : C ratio of 1 : 1.3. Under dietary choice, males actively regulated their nutrient intake but this regulation did not coincide with the peak of the nutritional landscape for any trait. Our results therefore demonstrate that a balanced intake of nutrients is central to regulating sexual conflict in G. sigillatus, but males are constrained from reaching the optima needed to bias the outcome of this conflict in their favour. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

  10. Integrative regulation of human brain blood flow

    PubMed Central

    Willie, Christopher K; Tzeng, Yu-Chieh; Fisher, Joseph A; Ainslie, Philip N

    2014-01-01

    Herein, we review mechanisms regulating cerebral blood flow (CBF), with specific focus on humans. We revisit important concepts from the older literature and describe the interaction of various mechanisms of cerebrovascular control. We amalgamate this broad scope of information into a brief review, rather than detailing any one mechanism or area of research. The relationship between regulatory mechanisms is emphasized, but the following three broad categories of control are explicated: (1) the effect of blood gases and neuronal metabolism on CBF; (2) buffering of CBF with changes in blood pressure, termed cerebral autoregulation; and (3) the role of the autonomic nervous system in CBF regulation. With respect to these control mechanisms, we provide evidence against several canonized paradigms of CBF control. Specifically, we corroborate the following four key theses: (1) that cerebral autoregulation does not maintain constant perfusion through a mean arterial pressure range of 60–150 mmHg; (2) that there is important stimulatory synergism and regulatory interdependence of arterial blood gases and blood pressure on CBF regulation; (3) that cerebral autoregulation and cerebrovascular sensitivity to changes in arterial blood gases are not modulated solely at the pial arterioles; and (4) that neurogenic control of the cerebral vasculature is an important player in autoregulatory function and, crucially, acts to buffer surges in perfusion pressure. Finally, we summarize the state of our knowledge with respect to these areas, outline important gaps in the literature and suggest avenues for future research. PMID:24396059

  11. Motivation, emotion regulation, and the latent structure of psychopathology: An integrative and convergent historical perspective.

    PubMed

    Beauchaine, Theodore P; Zisner, Aimee

    2017-09-01

    Motivational models of psychopathology have long been advanced by psychophysiologists, and have provided key insights into neurobiological mechanisms of a wide range of psychiatric disorders. These accounts emphasize individual differences in activity and reactivity of bottom-up, subcortical neural systems of approach and avoidance in affecting behavior. Largely independent literatures emphasize the roles of top-down, cortical deficits in emotion regulation and executive function in conferring vulnerability to psychopathology. To date however, few models effectively integrate functions performed by bottom-up emotion generation system with those performed by top-down emotion regulation systems in accounting for alternative expressions of psychopathology. In this article, we present such a model, and describe how it accommodates the well replicated bifactor structure of psychopathology. We describe how excessive approach motivation maps directly into externalizing liability, how excessive passive avoidance motivation maps directly into internalizing liability, and how emotion dysregulation and executive function map onto general liability. This approach is consistent with the Research Domain Criteria initiative, which assumes that a limited number of brain systems interact to confer vulnerability to many if not most forms of psychopathology. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. SRSF3 maintains transcriptome integrity in oocytes by regulation of alternative splicing and transposable elements.

    PubMed

    Do, Dang Vinh; Strauss, Bernhard; Cukuroglu, Engin; Macaulay, Iain; Wee, Keng Boon; Hu, Tim Xiaoming; Igor, Ruiz De Los Mozos; Lee, Caroline; Harrison, Andrew; Butler, Richard; Dietmann, Sabine; Jernej, Ule; Marioni, John; Smith, Christopher W J; Göke, Jonathan; Surani, M Azim

    2018-01-01

    The RNA-binding protein SRSF3 (also known as SRp20) has critical roles in the regulation of pre-mRNA splicing. Zygotic knockout of Srsf3 results in embryo arrest at the blastocyst stage. However, SRSF3 is also present in oocytes, suggesting that it might be critical as a maternally inherited factor. Here we identify SRSF3 as an essential regulator of alternative splicing and of transposable elements to maintain transcriptome integrity in mouse oocyte. Using 3D time-lapse confocal live imaging, we show that conditional deletion of Srsf3 in fully grown germinal vesicle oocytes substantially compromises the capacity of germinal vesicle breakdown (GVBD), and consequently entry into meiosis. By combining single cell RNA-seq, and oocyte micromanipulation with steric blocking antisense oligonucleotides and RNAse-H inducing gapmers, we found that the GVBD defect in mutant oocytes is due to both aberrant alternative splicing and derepression of B2 SINE transposable elements. Together, our study highlights how control of transcriptional identity of the maternal transcriptome by the RNA-binding protein SRSF3 is essential to the development of fertilized-competent oocytes.

  13. Genomic integration of ERRγ-HNF1β regulates renal bioenergetics and prevents chronic kidney disease.

    PubMed

    Zhao, Juanjuan; Lupino, Katherine; Wilkins, Benjamin J; Qiu, Chengxiang; Liu, Jian; Omura, Yasuhiro; Allred, Amanda L; McDonald, Caitlin; Susztak, Katalin; Barish, Grant D; Pei, Liming

    2018-05-22

    Mitochondrial dysfunction is increasingly recognized as a critical determinant of both hereditary and acquired kidney diseases. However, it remains poorly understood how mitochondrial metabolism is regulated to support normal kidney function and how its dysregulation contributes to kidney disease. Here, we show that the nuclear receptor estrogen-related receptor gamma (ERRγ) and hepatocyte nuclear factor 1 beta (HNF1β) link renal mitochondrial and reabsorptive functions through coordinated epigenomic programs. ERRγ directly regulates mitochondrial metabolism but cooperatively controls renal reabsorption via convergent binding with HNF1β. Deletion of ERRγ in renal epithelial cells (RECs), in which it is highly and specifically expressed, results in severe renal energetic and reabsorptive dysfunction and progressive renal failure that recapitulates phenotypes of animals and patients with HNF1β loss-of-function gene mutations. Moreover, ERRγ expression positively correlates with renal function and is decreased in patients with chronic kidney disease (CKD). REC-ERRγ KO mice share highly overlapping renal transcriptional signatures with human patients with CKD. Together these findings reveal a role for ERRγ in directing independent and HNF1β-integrated programs for energy production and use essential for normal renal function and the prevention of kidney disease.

  14. Histone modifications in the male germ line of Drosophila.

    PubMed

    Hennig, Wolfgang; Weyrich, Alexandra

    2013-02-22

    In the male germ line of Drosophila chromatin remains decondensed and highly transcribed during meiotic prophase until it is rapidly compacted. A large proportion of the cell cycle-regulated histone H3.1 is replaced by H3.3, a histone variant encoded outside the histone repeat cluster and not subject to cell cycle controlled expression. We investigated histone modification patterns in testes of D. melanogaster and D. hydei. In somatic cells of the testis envelope and in germ cells these modification patterns differ from those typically seen in eu- and heterochromatin of other somatic cells. During the meiotic prophase some modifications expected in active chromatin are not found or are found at low level. The absence of H4K16ac suggests that dosage compensation does not take place. Certain histone modifications correspond to either the cell cycle-regulated histone H3.1 or to the testis-specific variant H3.3. In spermatogonia we found H3K9 methylation in cytoplasmic histones, most likely corresponding to the H3.3 histone variant. Most histone modifications persist throughout the meiotic divisions. The majority of modifications persist until the early spermatid nuclei, and only a minority further persist until the final chromatin compaction stages before individualization of the spermatozoa. Histone modification patterns in the male germ line differ from expected patterns. They are consistent with an absence of dosage compensation of the X chromosome during the male meiotic prophase. The cell cycle-regulated histone variant H3.1 and H3.3, expressed throughout the cell cycle, also vary in their modification patterns. Postmeiotically, we observed a highly complex pattern of the histone modifications until late spermatid nuclear elongation stages. This may be in part due to postmeiotic transcription and in part to differential histone replacement during chromatin condensation.

  15. Photoperiodism of Male Offspring Production in the Water Flea Daphnia pulex.

    PubMed

    Toyota, Kenji; Sato, Tomomi; Tatarazako, Norihisa; Iguchi, Taisen

    2017-08-01

    Photoperiodism is a biological seasonal timing system utilized to regulate development and reproduction in organisms. The freshwater micro-crustacean Daphnia pulex displays environmental sex determination, the precise physiological mechanisms of which are largely unknown due to the lack of an experimental system to induce female or male offspring production by alterations of the rearing environment. We recently found that D. pulex, WTN6 strain, produces female or male offspring in response to long-day or short-day conditions, respectively. Taking advantage of this system, here we report the photoperiodic response curve for male offspring production, showing 12 hours as natural critical daylength (50% incidence of male-producing mothers), and that male offspring inducibility is highly sensitive to photoperiodic alterations. By using monochromatic light emitting diode (LED) devices, we found that the effective wavelength is red-light (627 nm), which stably induces male offspring production. This suggests that the red-light photoreceptor may be decisive in the primary step of sex determination process in this strain. Our findings provide the first insights into photoperiodism and red-light as key factors in triggering male offspring production in daphnids.

  16. Sharing Concerns: Interpersonal Worry Regulation in Romantic Couples

    PubMed Central

    2016-01-01

    Two dyadic studies investigated interpersonal worry regulation in heterosexual relationships. In Study 1, we video-recorded 40 romantic couples discussing shared concerns. Male partners’ worry positively predicted female partners’ interpersonal calming attempts, and negatively predicted female partners’ interpersonal alerting attempts (i.e., attempts to make their partners appreciate the seriousness of concerns). Video-cued recall data also indicated that changes in partner A’s worry over time positively predicted partner B’s motivation to reduce partner A’s worry, and that this effect was stronger when B was the female partner. Study 2 was a dyadic survey of 100 couples. Individual differences in partner A’s negative affect were positive predictors of partner B’s interpersonal calming, and individual differences in partner A’s expressive suppression were negative predictors of partner B’s interpersonal calming. Further, individual differences in male partners’ expressivity were significant positive predictors of female partners’ interpersonal calming, and individual differences in male partners’ reappraisal were significant positive predictors of female partners’ interpersonal alerting. These findings suggest that interpersonal worry regulation relates to partners’ expression and intrapersonal regulation of worry, but not equally for men and women. PMID:26882336

  17. Insulin-like growth factor (IGF)-like peptide and 20-hydroxyecdysone regulate the growth and development of the male genital disk through different mechanisms in the silkmoth, Bombyx mori.

    PubMed

    Fujinaga, Daiki; Kohmura, Yusuke; Okamoto, Naoki; Kataoka, Hiroshi; Mizoguchi, Akira

    2017-08-01

    It is well established that ecdysteroids play pivotal roles in the regulation of insect molting and metamorphosis. However, the mechanisms by which ecdysteroids regulate the growth and development of adult organs after pupation are poorly understood. Recently, we have identified insulin-like growth factor (IGF)-like peptides (IGFLPs), which are secreted after pupation under the control of 20-hydroxyecdysone (20E). In the silkmoth, Bombyx mori, massive amounts of Bombyx-IGFLP (BIGFLP) are present in the hemolymph during pupal-adult development, suggesting its importance in the regulation of adult tissue growth. Thus, we hypothesized that the growth and development of adult tissues including imaginal disks are regulated by the combined effects of BIGFLP and 20E. In this study, we investigated the growth-promoting effects of BIGFLP and 20E using the male genital disks of B. mori cultured ex vivo, and further analyzed the cell signaling pathways mediating hormone actions. We demonstrate that 20E induces the elongation of genital disks, that both hormones stimulate protein synthesis in an additive manner, and that BIGFLP and 20E exert their effects through the insulin/IGF signaling pathway and mitogen-activated protein kinase pathway, respectively. These results show that the growth and development of the genital disk are coordinately regulated by both BIGFLP and 20E. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Intrinsic and Extrinsic Factors That Influence Black Males to Attend Institutions of Higher Education

    ERIC Educational Resources Information Center

    Etheridge, Robert

    2013-01-01

    The purpose of this qualitative, narrative study was to explore the intrinsic and extrinsic factors that motivated Black males to attend institutions of higher education. The Self-determination theory and the Integrated Model for Educational Choice formed the theoretical framework for this study. Eight Black males who were between the ages of 18…

  19. The BCKDH Kinase and Phosphatase Integrate BCAA and Lipid Metabolism via Regulation of ATP-Citrate Lyase.

    PubMed

    White, Phillip J; McGarrah, Robert W; Grimsrud, Paul A; Tso, Shih-Chia; Yang, Wen-Hsuan; Haldeman, Jonathan M; Grenier-Larouche, Thomas; An, Jie; Lapworth, Amanda L; Astapova, Inna; Hannou, Sarah A; George, Tabitha; Arlotto, Michelle; Olson, Lyra B; Lai, Michelle; Zhang, Guo-Fang; Ilkayeva, Olga; Herman, Mark A; Wynn, R Max; Chuang, David T; Newgard, Christopher B

    2018-06-05

    Branched-chain amino acids (BCAA) are strongly associated with dysregulated glucose and lipid metabolism, but the underlying mechanisms are poorly understood. We report that inhibition of the kinase (BDK) or overexpression of the phosphatase (PPM1K) that regulates branched-chain ketoacid dehydrogenase (BCKDH), the committed step of BCAA catabolism, lowers circulating BCAA, reduces hepatic steatosis, and improves glucose tolerance in the absence of weight loss in Zucker fatty rats. Phosphoproteomics analysis identified ATP-citrate lyase (ACL) as an alternate substrate of BDK and PPM1K. Hepatic overexpression of BDK increased ACL phosphorylation and activated de novo lipogenesis. BDK and PPM1K transcript levels were increased and repressed, respectively, in response to fructose feeding or expression of the ChREBP-β transcription factor. These studies identify BDK and PPM1K as a ChREBP-regulated node that integrates BCAA and lipid metabolism. Moreover, manipulation of the BDK:PPM1K ratio relieves key metabolic disease phenotypes in a genetic model of severe obesity. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Male-male competition, female mate choice and their interaction: determining total sexual selection.

    PubMed

    Hunt, John; Breuker, Casper J; Sadowski, Jennifer A; Moore, Allen J

    2009-01-01

    Empirical studies of sexual selection typically focus on one of the two mechanisms of sexual selection without integrating these into a description of total sexual selection, or study total sexual selection without quantifying the contributions of all of the mechanisms of sexual selection. However, this can provide an incomplete or misleading view of how sexually selected traits evolve if the mechanisms of sexual selection are opposing or differ in form. Here, we take a two-fold approach to advocate a direction for future studies of sexual selection. We first show how a quantitative partitioning and examination of sexual selection mechanisms can inform by identifying illustrative studies that describe both male-male competition and female mate choice acting on the same trait. In our sample, the most common trait where this occurred was body size, and selection was typically linear. We found that male-male competition and female mate choice can be reinforcing or opposing, although the former is most common in the literature. The mechanisms of sexual selection can occur simultaneously or sequentially, and we found they were more likely to be opposing when the mechanisms operated sequentially. The degree and timing that these mechanisms interact have important implications for the operation of sexual selection and needs to be considered in designing studies. Our examples highlight where empirical data are needed. We especially lack standardized measures of the form and strength of selection imposed by each mechanism of sexual selection and how they combine to determine total sexual selection. Secondly, using quantitative genetic principles, we outline how the selection imposed by individual mechanisms can be measured and combined to estimate the total strength and form of sexual selection. We discuss the evolutionary consequences of combining the mechanisms of sexual selection and interpreting total sexual selection. We suggest how this approach may result in

  1. Effect of di(2-ethylhexyl) phthalate on the neuroendocrine regulation of reproduction in adult male rats and its relationship to anxiogenic behavior: Participation of GABAergic system.

    PubMed

    Carbone, S; Ponzo, O J; Gobetto, N; Samaniego, Y A; Reynoso, R; Moguilevsky, J A; Cutrera, R A

    2018-01-01

    The endocrine disruptor di-(2-ethylhexyl) phthalate (DEHP) is used in a variety of consumer products made with polyvinyl chloride and also in the manufacture of medical devices. DEHP disrupts reproductive tract development in an antiandrogenic manner and also may induce neurobehavioral changes. The aim of this study was to investigate the effects of chronic postnatal exposure to DEHP (30 mg/kg body weight/day, orally from birth to day 60) on the neuroendocrine regulation of the gonadal axis and its impact on the anxiety-like behavior in adult male rats, as well as the probable participation of the GABAergic system in these effects. DEHP produced a significant increase in plasmatic luteinizing hormone and follicle stimulating hormone, as well as significant testosterone decrease, accompanied with a decrease in hypothalamic gamma-aminobutyric acid (GABA) concentration. On the other hand, DEHP increased the anxiety-like behavior in the elevated plus maze test, evidenced by a significant decrease in the percentages of time spent in the open arms and the frequency in the open arm entries and a significant increase in the percentage of time spent in closed arms. Neuroendocrine and behavioral effects were reversed by GABA agonists, muscimol (2 mg/kg i.p. ) and baclofen (10 mg/kg i.p.). In conclusion, chronic DEHP postnatal exposure induced a disruption in the neuroendocrine regulation of the testicular axis in young adult male rats, and this effect was correlated with an anxiety-like behavior. Since GABA agonists reversed these effects, the results suggest that GABA could participate in the modulation of reproductive and behavioral DEHP effects.

  2. Juvenile hormone mediates developmental integration between exaggerated traits and supportive traits in the horned flour beetle Gnatocerus cornutus.

    PubMed

    Okada, Yasukazu; Gotoh, Hiroki; Miura, Toru; Miyatake, Takahisa; Okada, Kensuke

    2012-07-01

    Sexually selected exaggerated traits are often coupled with modifications in other nontarget traits. In insects with weapons, enlargements of nontarget characters that functionally support the weapon often occur (i.e. supportive traits). The support of sexual traits requires developmental coordination among functionally related multiple traits-an explicit example of morphological integration. The genetic theory predicts that developmental integration among different body modules, for which development is regulated via different sets of genes, is likely to be coordinated by pleiotropic factors. However, the developmental backgrounds of morphological integrations are largely unknown. We tested the hypothesis that the juvenile hormone (JH), as a pleiotropic factor, mediates the integration between exaggerated and supportive traits in an armed beetle Gnatocerus cornutus. During combat, males of this beetle use exaggerated mandibles to lift up their opponents with the supportive traits, that is, the head and prothoracic body parts. Application of methoprene, a JH analog (JHA), during the larval to prepupal period, induced the formation of large mandibles relative to the body sizes in males. Morphometric examination of nontarget traits elucidated an increase in the relative sizes of supportive traits, including the head and prothoracic body parts. In addition, reductions in the hind wing area and elytra length, which correspond to flight and reproductive abilities, were detected. Our findings are consistent with the genetic theory and support the idea that JH is a key pleiotropic factor that coordinates the developmental integration of exaggerated traits and supportive characters, as well as resource allocation trade-offs. © 2012 Wiley Periodicals, Inc.

  3. GPER Deficiency in Male Mice Results in Insulin Resistance, Dyslipidemia, and a Proinflammatory State

    PubMed Central

    Sharma, Geetanjali; Hu, Chelin; Brigman, Jonathan L.; Zhu, Gang; Hathaway, Helen J.

    2013-01-01

    Estrogen is an important regulator of metabolic syndrome, a collection of abnormalities including obesity, insulin resistance/glucose intolerance, hypertension, dyslipidemia, and inflammation, which together lead to increased risk of cardiovascular disease and diabetes. The role of the G protein-coupled estrogen receptor (GPER/GPR30), particularly in males, in these pathologies remains unclear. We therefore sought to determine whether loss of GPER contributes to aspects of metabolic syndrome in male mice. Although 6-month-old male and female GPER knockout (KO) mice displayed increased body weight compared with wild-type littermates, only female GPER KO mice exhibited glucose intolerance at this age. Weight gain in male GPER KO mice was associated with increases in both visceral and sc fat. GPER KO mice, however, exhibited no differences in food intake or locomotor activity. One-year-old male GPER KO mice displayed an abnormal lipid profile with higher cholesterol and triglyceride levels. Fasting blood glucose levels remained normal, whereas insulin levels were elevated. Although insulin resistance was evident in GPER KO male mice from 6 months onward, glucose intolerance was pronounced only at 18 months of age. Furthermore, by 2 years of age, a proinflammatory phenotype was evident, with increases in the proinflammatory and immunomodulatory cytokines IL-1β, IL-6, IL-12, TNFα, monocyte chemotactic protein-1, interferon γ-induced protein 10, and monokine induced by interferon gamma and a concomitant decrease in the adipose-specific cytokine adiponectin. In conclusion, our study demonstrates for the first time that in male mice, GPER regulates metabolic parameters associated with obesity and diabetes. PMID:23970785

  4. GPER deficiency in male mice results in insulin resistance, dyslipidemia, and a proinflammatory state.

    PubMed

    Sharma, Geetanjali; Hu, Chelin; Brigman, Jonathan L; Zhu, Gang; Hathaway, Helen J; Prossnitz, Eric R

    2013-11-01

    Estrogen is an important regulator of metabolic syndrome, a collection of abnormalities including obesity, insulin resistance/glucose intolerance, hypertension, dyslipidemia, and inflammation, which together lead to increased risk of cardiovascular disease and diabetes. The role of the G protein-coupled estrogen receptor (GPER/GPR30), particularly in males, in these pathologies remains unclear. We therefore sought to determine whether loss of GPER contributes to aspects of metabolic syndrome in male mice. Although 6-month-old male and female GPER knockout (KO) mice displayed increased body weight compared with wild-type littermates, only female GPER KO mice exhibited glucose intolerance at this age. Weight gain in male GPER KO mice was associated with increases in both visceral and sc fat. GPER KO mice, however, exhibited no differences in food intake or locomotor activity. One-year-old male GPER KO mice displayed an abnormal lipid profile with higher cholesterol and triglyceride levels. Fasting blood glucose levels remained normal, whereas insulin levels were elevated. Although insulin resistance was evident in GPER KO male mice from 6 months onward, glucose intolerance was pronounced only at 18 months of age. Furthermore, by 2 years of age, a proinflammatory phenotype was evident, with increases in the proinflammatory and immunomodulatory cytokines IL-1β, IL-6, IL-12, TNFα, monocyte chemotactic protein-1, interferon γ-induced protein 10, and monokine induced by interferon gamma and a concomitant decrease in the adipose-specific cytokine adiponectin. In conclusion, our study demonstrates for the first time that in male mice, GPER regulates metabolic parameters associated with obesity and diabetes.

  5. PPL2ab neurons restore sexual responses in aged Drosophila males through dopamine.

    PubMed

    Kuo, Shu-Yun; Wu, Chia-Lin; Hsieh, Min-Yen; Lin, Chen-Ta; Wen, Rong-Kun; Chen, Lien-Cheng; Chen, Yu-Hui; Yu, Yhu-Wei; Wang, Horng-Dar; Su, Yi-Ju; Lin, Chun-Ju; Yang, Cian-Yi; Guan, Hsien-Yu; Wang, Pei-Yu; Lan, Tsuo-Hung; Fu, Tsai-Feng

    2015-06-30

    Male sexual desire typically declines with ageing. However, our understanding of the neurobiological basis for this phenomenon is limited by our knowledge of the brain circuitry and neuronal pathways controlling male sexual desire. A number of studies across species suggest that dopamine (DA) affects sexual desire. Here we use genetic tools and behavioural assays to identify a novel subset of DA neurons that regulate age-associated male courtship activity in Drosophila. We find that increasing DA levels in a subset of cells in the PPL2ab neuronal cluster is necessary and sufficient for increased sustained courtship in both young and aged male flies. Our results indicate that preventing the age-related decline in DA levels in PPL2ab neurons alleviates diminished courtship behaviours in male Drosophila. These results may provide the foundation for deciphering the circuitry involved in sexual motivation in the male Drosophila brain.

  6. Mixed Impact of Firearms Restrictions on Fatal Firearm Injuries in Males: A National Observational Study

    PubMed Central

    Gjertsen, Finn; Leenaars, Antoon; Vollrath, Margarete E.

    2013-01-01

    Introduction: Public health organizations have recommended restricted access and safe storage practices as means to reduce firearm injuries and deaths. We aimed to assess the effect of four firearm restrictions on firearm deaths in Norway 1969–2009. Methods: All deaths due to firearm discharge were included (5,660 deaths, both sexes). The statistical analysis to assess impact of firearm legislations was restricted to males because of the sex disproportionality (94% were males). Results: A total of 89% of firearm deaths (both sexes) were classified as suicide, 8% as homicide, and 3% as unintentional (accident). During the past four decades, male accidental firearm death rates were reduced significantly by 90%. Male firearms suicide rates increased from 1969 to 1991 by 166%, and decreased by 62% from 1991 to 2009. Despite the great reduction in male accidental firearm deaths, we were unable to demonstrate effects of the laws. In contrast, we found that a 1990 regulation, requiring a police permit before acquiring a shotgun, had a beneficial impact on suicide in the total sample and in those aged 15–34 years. Male firearm homicides decreased post-2003 regulation regarding storing home guard weapons in private homes. Conclusions: Our findings suggest that two laws could have contributed to reduce male firearm mortality. It is, however, a challenge to measure the role of four firearm restrictions. The null findings are inconclusive, as they may reflect no true impact or study limitations. PMID:24380979

  7. Homosexual Fellatio: Erect Penis Licking between Male Bonin Flying Foxes Pteropus pselaphon.

    PubMed

    Sugita, Norimasa

    2016-01-01

    A recent focus of interest has been on the functional significance of genital licking (fellatio and cunnilingus) in relation to sexual selection in Pteropodid bats. In the present paper, a form of fellatio in wild Bonin flying foxes, Pteropus pselaphon, performed between adult males has been reported. During the mating season, adult flying foxes roost in same-sex groups, forming ball-shaped clusters which provide warmth. The female clusters may also contain a few males. Unassociated with allogrooming, same-sex genital licking occurred among males in the all male clusters. As such, male-male fellatio can be considered as homosexual behavior, two functional explanations could account for this behavior; the social bonding and the social tension regulation hypotheses suggested in a previous review. Given that neither the simpler alternative that in all male groups such fellatio may represent misdirected sexual behavior, nor the two previously proposed functional hypotheses were supported by the data, I propose another functional hypothesis. Homosexual fellatio in this species could help males solve inconsistent situations in the roost when there are conflicts between cooperative behavior for social thermoregulation and competition for mating.

  8. Homosexual Fellatio: Erect Penis Licking between Male Bonin Flying Foxes Pteropus pselaphon

    PubMed Central

    Sugita, Norimasa

    2016-01-01

    A recent focus of interest has been on the functional significance of genital licking (fellatio and cunnilingus) in relation to sexual selection in Pteropodid bats. In the present paper, a form of fellatio in wild Bonin flying foxes, Pteropus pselaphon, performed between adult males has been reported. During the mating season, adult flying foxes roost in same-sex groups, forming ball-shaped clusters which provide warmth. The female clusters may also contain a few males. Unassociated with allogrooming, same-sex genital licking occurred among males in the all male clusters. As such, male-male fellatio can be considered as homosexual behavior, two functional explanations could account for this behavior; the social bonding and the social tension regulation hypotheses suggested in a previous review. Given that neither the simpler alternative that in all male groups such fellatio may represent misdirected sexual behavior, nor the two previously proposed functional hypotheses were supported by the data, I propose another functional hypothesis. Homosexual fellatio in this species could help males solve inconsistent situations in the roost when there are conflicts between cooperative behavior for social thermoregulation and competition for mating. PMID:27824953

  9. The FACT Complex Promotes Avian Leukosis Virus DNA Integration.

    PubMed

    Winans, Shelby; Larue, Ross C; Abraham, Carly M; Shkriabai, Nikolozi; Skopp, Amelie; Winkler, Duane; Kvaratskhelia, Mamuka; Beemon, Karen L

    2017-04-01

    All retroviruses need to integrate a DNA copy of their genome into the host chromatin. Cellular proteins regulating and targeting lentiviral and gammaretroviral integration in infected cells have been discovered, but the factors that mediate alpharetroviral avian leukosis virus (ALV) integration are unknown. In this study, we have identified the FACT protein complex, which consists of SSRP1 and Spt16, as a principal cellular binding partner of ALV integrase (IN). Biochemical experiments with purified recombinant proteins show that SSRP1 and Spt16 are able to individually bind ALV IN, but only the FACT complex effectively stimulates ALV integration activity in vitro Likewise, in infected cells, the FACT complex promotes ALV integration activity, with proviral integration frequency varying directly with cellular expression levels of the FACT complex. An increase in 2-long-terminal-repeat (2-LTR) circles in the depleted FACT complex cell line indicates that this complex regulates the ALV life cycle at the level of integration. This regulation is shown to be specific to ALV, as disruption of the FACT complex did not inhibit either lentiviral or gammaretroviral integration in infected cells. IMPORTANCE The majority of human gene therapy approaches utilize HIV-1- or murine leukemia virus (MLV)-based vectors, which preferentially integrate near genes and regulatory regions; thus, insertional mutagenesis is a substantial risk. In contrast, ALV integrates more randomly throughout the genome, which decreases the risks of deleterious integration. Understanding how ALV integration is regulated could facilitate the development of ALV-based vectors for use in human gene therapy. Here we show that the FACT complex directly binds and regulates ALV integration efficiency in vitro and in infected cells. Copyright © 2017 American Society for Microbiology.

  10. Males collectively defend their one-male units against bachelor males in a multi-level primate society.

    PubMed

    Xiang, Zuo-Fu; Yang, Bang-He; Yu, Yang; Yao, Hui; Grueter, Cyril C; Garber, Paul A; Li, Ming

    2014-07-01

    Group-level male-male co-operation, which has been documented in several primate and non-primate societies, may be mutualistically advantageous to the participants when confronted with threats such as takeovers and cuckoldry by external males. Co-operation among members of distinct social units-while universal among humans-is extremely rare in non-human primates. We present the first observations of collective action or co-operation among males of different one-male units (OMU) in a multi-level society of Rhinopithecus roxellana. A total of 59 instances of male co-operation were recorded. Male co-operation included coordinated chasing, joint vigilance, and patrolling behavior directed at lone adult males trying to enter an OMU. Male co-operation was significantly more frequent during the mating season when the risk of incursions and extra-group paternity was higher. Paternity of infants born in the subsequent birth season and kin relationships among resident males were identified using microsatellite genotype. All infants were sired by OMU males, which we interpret as possible evidence for their success at thwarting mating attempts by satellite males. OMU males were principally unrelated suggesting that male co-operation is best understood in terms of the mutual direct benefits individuals obtain through collective action. Our findings lend support to the bachelor threat hypothesis in which the cooperative behavior of several individuals is more effective than the lone action of a single individual in providing mate defense. Our research has implications for understanding male bonding, higher-level collective action, and the evolution of social co-operation in human societies. © 2013 Wiley Periodicals, Inc.

  11. Gender Integration of a Traditionally Male Field: A Definition of the Occupation.

    DTIC Science & Technology

    1982-07-01

    National Meetings of Applied Anthropology, Denver , Colorado , March, 1980, _____________________ "The Introduction of Females into an All-Male Subculture...PerformanceEvlain Bartlett, Harold and Arthur Rosenblum. Policewomen Effectiveness ( Denver Colorado : Civil Service Comission and Denver Police...gender related qualities to those categories of persons believed to be deficient. While either approach addresses the legal issues, the second has been

  12. Wives' Relative Income Production and Household Male Dominance: Examining Violence among Asian American Enduring Couples

    ERIC Educational Resources Information Center

    Chung, Grace H.; Tucker, M. Belinda; Takeuchi, David

    2008-01-01

    This study integrates relative resource theory and cultural perspectives on husband-to-wife authority to examine male-to-female physical violence reported by Asian American wives in the National Latino and Asian American Survey. Findings indicated that the association between marital violence and male household dominance is complicated by women's…

  13. Control of male sexual behavior and sexual orientation in Drosophila by the fruitless gene.

    PubMed

    Ryner, L C; Goodwin, S F; Castrillon, D H; Anand, A; Villella, A; Baker, B S; Hall, J C; Taylor, B J; Wasserman, S A

    1996-12-13

    Sexual orientation and courtship behavior in Drosophila are regulated by fruitless (fru), the first gene in a branch of the sex-determination hierarchy functioning specifically in the central nervous system (CNS). The phenotypes of new fru mutants encompass nearly all aspects of male sexual behavior. Alternative splicing of fru transcripts produces sex-specific proteins belonging to the BTB-ZF family of transcriptional regulators. The sex-specific fru products are produced in only about 500 of the 10(5) neurons that comprise the CNS. The properties of neurons expressing these fru products suggest that fru specifies the fates or activities of neurons that carry out higher order control functions to elicit and coordinate the activities comprising male courtship behavior.

  14. Factors That Promote the Academic Success of African American Male Students in High School Math

    ERIC Educational Resources Information Center

    Allen, Tyrone J.

    2014-01-01

    Low performance of African American male students in high school math is an ongoing concern of Maryland's public schools. Because disproportionately large numbers of African American male students enroll in Algebra 2 in Grade 11, the use of early academic counseling to promote enrollment in Algebra 2 in Grade 9 and to increase self-regulation may…

  15. RIP1 maintains DNA integrity and cell proliferation by regulating PGC-1α-mediated mitochondrial oxidative phosphorylation and glycolysis.

    PubMed

    Chen, W; Wang, Q; Bai, L; Chen, W; Wang, X; Tellez, C S; Leng, S; Padilla, M T; Nyunoya, T; Belinsky, S A; Lin, Y

    2014-07-01

    Aerobic glycolysis or the Warburg effect contributes to cancer cell proliferation; however, how this glucose metabolism pathway is precisely regulated remains elusive. Here we show that receptor-interacting protein 1 (RIP1), a cell death and survival signaling factor, regulates mitochondrial oxidative phosphorylation and aerobic glycolysis. Loss of RIP1 in lung cancer cells suppressed peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) expression, impairing mitochondrial oxidative phosphorylation and accelerating glycolysis, resulting in spontaneous DNA damage and p53-mediated cell proliferation inhibition. Thus, although aerobic glycolysis within a certain range favors cancer cell proliferation, excessive glycolysis causes cytostasis. Our data suggest that maintenance of glycolysis by RIP1 is pivotal to cancer cell energy homeostasis and DNA integrity and may be exploited for use in anticancer therapy.

  16. Caenorhabditis elegans Pheromones Regulate Multiple Complex Behaviors

    PubMed Central

    Edison, Arthur S.

    2009-01-01

    Summary of recent advances A family of small molecules called ascarosides act as pheromones to control multiple behaviors in the nematode Caenorhabditis elegans. At picomolar concentrations, a synergistic mixture of at least three ascarosides produced by hermaphrodites causes male-specific attraction. At higher concentrations, the same ascarosides, perhaps in a different mixture, induce the developmentally arrested stage known as dauer. The production of ascarosides is strongly dependent on environmental conditions, although relatively little is known about the major variables and mechanisms of their regulation. Thus, male mating and dauer formation are linked through a common set of small molecules whose expression is sensitive to a given microenvironment, suggesting a model by which ascarosides regulate the overall life cycle of C. elegans. PMID:19665885

  17. Coping, Regulation, and Development during Childhood and Adolescence

    ERIC Educational Resources Information Center

    Compas, Bruce E.

    2009-01-01

    This chapter identifies four challenges to the study of the development of coping and regulation and outlines specific theoretical and empirical strategies for addressing them. The challenges are (1) to integrate work on coping and processes of emotion regulation, (2) to use the integration of research on neuro-biology and context to inform the…

  18. Integrating male sexual diversity into violence prevention efforts with men and boys: evidence from the Asia-Pacific Region.

    PubMed

    Miedema, Stephanie S; Yount, Kathryn M; Chirwa, Esnat; Dunkle, Kristin; Fulu, Emma

    2017-02-01

    Men's perpetration of gender-based violence remains a global public health issue. Violence prevention experts call for engagement of boys and men to change social norms around masculinity in order to prevent gender-based violence. Yet, men do not comprise a homogenous category. Drawing on probability estimates of men who report same-sex practices and preferences captured in a multi-country gender-based violence prevention survey in the Asia-Pacific region, we test the effects of sexuality-related factors on men's adverse life experiences. We find that sexual minority men face statistically higher risk of lifetime adversity related to gender-based violence, stemming from gender inequitable norms in society. Sexuality is thus a key axis of differentiation among men in the Asia-Pacific region, influencing health and wellbeing and reflecting men's differential engagement with dominant norms of masculinity. Integrating awareness of male sexual diversity into gender-based violence prevention interventions, particularly those that work with boys and men, and bridging violence prevention programming between sexual minority communities and women, are essential to tackle the root drivers of violence.

  19. Cell type-specific translational repression of Cyclin B during meiosis in males.

    PubMed

    Baker, Catherine Craig; Gim, Byung Soo; Fuller, Margaret T

    2015-10-01

    The unique cell cycle dynamics of meiosis are controlled by layers of regulation imposed on core mitotic cell cycle machinery components by the program of germ cell development. Although the mechanisms that regulate Cdk1/Cyclin B activity in meiosis in oocytes have been well studied, little is known about the trans-acting factors responsible for developmental control of these factors in male gametogenesis. During meiotic prophase in Drosophila males, transcript for the core cell cycle protein Cyclin B1 (CycB) is expressed in spermatocytes, but the protein does not accumulate in spermatocytes until just before the meiotic divisions. Here, we show that two interacting proteins, Rbp4 and Fest, expressed at the onset of spermatocyte differentiation under control of the developmental program of male gametogenesis, function to direct cell type- and stage-specific repression of translation of the core G2/M cell cycle component cycB during the specialized cell cycle of male meiosis. Binding of Fest to Rbp4 requires a 31-amino acid region within Rbp4. Rbp4 and Fest are required for translational repression of cycB in immature spermatocytes, with Rbp4 binding sequences in a cell type-specific shortened form of the cycB 3' UTR. Finally, we show that Fest is required for proper execution of meiosis I. © 2015. Published by The Company of Biologists Ltd.

  20. Males are overrepresented among life science researchers committing scientific misconduct.

    PubMed

    Fang, Ferric C; Bennett, Joan W; Casadevall, Arturo

    2013-01-22

    A review of the United States Office of Research Integrity annual reports identified 228 individuals who have committed misconduct, of which 94% involved fraud. Analysis of the data by career stage and gender revealed that misconduct occurred across the entire career spectrum from trainee to senior scientist and that two-thirds of the individuals found to have committed misconduct were male. This exceeds the overall proportion of males among life science trainees and faculty. These observations underscore the need for additional efforts to understand scientific misconduct and to ensure the responsible conduct of research. As many of humanity's greatest problems require scientific solutions, it is critical for the scientific enterprise to function optimally. Misconduct threatens the scientific enterprise by undermining trust in the validity of scientific findings. We have examined specific demographic characteristics of individuals found to have committed research misconduct in the life sciences. Our finding that misconduct occurs across all stages of career development suggests that attention to ethical aspects of the conduct of science should not be limited to those in training. The observation that males are overrepresented among those who commit misconduct implies a gender difference that needs to be better understood in any effort to promote research integrity.

  1. Males adjust their signalling behaviour according to experience of male signals and male-female signal duets.

    PubMed

    Rebar, D; Rodríguez, R L

    2016-04-01

    Sexual signals are conspicuous sources of information about neighbouring competitors, and species in which males and females signal during pair formation provide various sources of public information to which individuals can adjust their behaviour. We performed two experiments with a duetting vibrational insect, Enchenopa binotata treehoppers (Hemiptera: Membracidae), to ask whether males adjust their signalling behaviour according to (1a) their own experience of competitors' signals, (1b) how females adjust their mate preferences on the basis of their experience of male signals (described in prior work), and/or (2) their own experience of female response signals to competitors' signals. We presented males with synthetic male signals of different frequencies and combinations thereof for 2 weeks. We recorded males a day after their last signal exposure, finding that (1a) male signal rate increased in response to experience of attractive competitors, but that (1b) male signal frequency did not shift in a manner consistent with how females adjust their mate preferences in those experience treatments. Second, we presented males with different male-female duets for 2 weeks, finding that (2) male signal length increased from experience of female duets with attractive competitors. Males thus make two types of adjustment according to two sources of public information: one provided by experience of male signals and another by experience of female responses to male signals. Signalling plasticity can generate feedback loops between the adjustments that males and females make, and we discuss the potential consequences of such feedback loops for the evolution of communication systems. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

  2. The Escherichia coli Cpx envelope stress response regulates genes of diverse function that impact antibiotic resistance and membrane integrity.

    PubMed

    Raivio, Tracy L; Leblanc, Shannon K D; Price, Nancy L

    2013-06-01

    The Cpx envelope stress response mediates adaptation to stresses that cause envelope protein misfolding. Adaptation is partly conferred through increased expression of protein folding and degradation factors. The Cpx response also plays a conserved role in the regulation of virulence determinant expression and impacts antibiotic resistance. We sought to identify adaptive mechanisms that may be involved in these important functions by characterizing changes in the transcriptome of two different Escherichia coli strains when the Cpx response is induced. We show that, while there is considerable strain- and condition-specific variability in the Cpx response, the regulon is enriched for proteins and functions that are inner membrane associated under all conditions. Genes that were changed by Cpx pathway induction under all conditions were involved in a number of cellular functions and included several intergenic regions, suggesting that posttranscriptional regulation is important during Cpx-mediated adaptation. Some Cpx-regulated genes are centrally involved in energetics and play a role in antibiotic resistance. We show that a number of small, uncharacterized envelope proteins are Cpx regulated and at least two of these affect phenotypes associated with membrane integrity. Altogether, our work suggests new mechanisms of Cpx-mediated envelope stress adaptation and antibiotic resistance.

  3. Male contraception: another Holy Grail.

    PubMed

    Murdoch, Fern E; Goldberg, Erwin

    2014-01-15

    The idea that men should participate in family planning by playing an active role in contraception has become more acceptable in recent years. Up to the present the condom and vasectomy have been the main methods of male contraception. There have been and continue to be efforts to develop an acceptable hormonal contraceptive involving testosterone (T) suppression. However the off target affects, delivery of the analogs and the need for T replacement have proven difficult obstacles to this technology. Research into the development of non-hormonal contraception for men is progressing in several laboratories and this will be the subject of the present review. A number of promising targets for the male pill are being investigated. These involve disruption of spermatogenesis by compromising the integrity of the germinal epithelium, interfering with sperm production at the level of meiosis, attacking specific sperm proteins to disrupt fertilizing ability, or interfering with the assembly of seminal fluid components required by ejaculated sperm for acquisition of motility. Blocking contractility of the vas deferens smooth muscle vasculature to prevent ejaculation is a unique approach that prevents sperm from reaching the egg. We shall note the lack of interest by big pharma with most of the support for male contraception provided by the NIH. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Tomato Male sterile 1035 is essential for pollen development and meiosis in anthers

    PubMed Central

    Jeong, Hee-Jin; Kang, Jin-Ho; Zhao, Meiai; Kwon, Jin-Kyung; Choi, Hak-Soon; Bae, Jung Hwan; Lee, Hyun-ah; Joung, Young-Hee; Choi, Doil; Kang, Byoung-Cheorl

    2014-01-01

    Male fertility in flowering plants depends on proper cellular differentiation in anthers. Meiosis and tapetum development are particularly important processes in pollen production. In this study, we showed that the tomato male sterile (ms10 35) mutant of cultivated tomato (Solanum lycopersicum) exhibited dysfunctional meiosis and an abnormal tapetum during anther development, resulting in no pollen production. We demonstrated that Ms10 35 encodes a basic helix–loop–helix transcription factor that is specifically expressed in meiocyte and tapetal tissue from pre-meiotic to tetrad stages. Transgenic expression of the Ms10 35 gene from its native promoter complemented the male sterility of the ms10 35 mutant. In addition, RNA-sequencing-based transcriptome analysis revealed that Ms10 35 regulates 246 genes involved in anther development processes such as meiosis, tapetum development, cell-wall degradation, pollen wall formation, transport, and lipid metabolism. Our results indicate that Ms10 35 plays key roles in regulating both meiosis and programmed cell death of the tapetum during microsporogenesis. PMID:25262227

  5. Expression of the reproductive female-specific vitellogenin gene in endocrinologically induced male and intersex Cherax quadricarinatus crayfish.

    PubMed

    Shechter, Asaf; Aflalo, Eliahu D; Davis, Claytus; Sagi, Amir

    2005-07-01

    In oviparous females, the synthesis of the yolk precursor vitellogenin is an important step in ovarian maturation and oocyte development. In decapod Crustacea, including the red-claw crayfish (Cherax quadricarinatus), this reproductive process is regulated by inhibitory neurohormones secreted by the endocrine X-organ-sinus gland (XO-SG) complex. In males, the C. quadricarinatus vitellogenin gene (CqVg), although present, is not expressed under normal conditions. We show here that endocrine manipulation by removal of the XO-SG complex from male animals induced CqVg transcription. The CqVg gene was expressed differentially during the molt cycle in these induced males: no expression was seen in the intermolt stages, but expression was occasionally detected in the premolt stages and always detected in the early postmolt stages. Relative quantitation with a real-time reverse transcriptase-polymerase chain reaction showed that expression of CqVg in induced early postmolt males was an order of magnitude lower than that in reproductive females, a finding that was consistent with RNA in situ hybridization results. The SDS-PAGE of high-density lipoproteins from the hemolymph of endocrinologically induced early postmolt males did not show the typical vitellogenin-related polypeptide profile found in reproductive females. On the other hand, removal of the XO-SG complex from intersex individuals, which are chromosomally female but functionally male and possess an arrested female reproductive system, induced the expression, translation, and release of CqVg products into the hemolymph, as was the case for vitellogenic females. The expression of CqVg in endocrinologically manipulated molting males and intersex animals provides an inducible model for the investigation and understanding of the endocrine regulation of CqVg expression and translation in Crustacea as well as the relationship between the endocrine axes regulating molt and reproduction.

  6. Integrative modelling of pH-dependent enzyme activity and transcriptomic regulation of the acetone–butanol–ethanol fermentation of Clostridium acetobutylicum in continuous culture

    PubMed Central

    Millat, Thomas; Janssen, Holger; Bahl, Hubert; Fischer, Ralf-Jörg; Wolkenhauer, Olaf

    2013-01-01

    Summary In a continuous culture under phosphate limitation the metabolism of Clostridium acetobutylicum depends on the external pH level. By comparing seven steady-state conditions between pH 5.7 and pH 4.5 we show that the switch from acidogenesis to solventogenesis occurs between pH 5.3 and pH 5.0 with an intermediate state at pH 5.1. Here, an integrative study is presented investigating how a changing external pH level affects the clostridial acetone–butanol–ethanol (ABE) fermentation pathway. This is of particular interest as the biotechnological production of n-butanol as biofuel has recently returned into the focus of industrial applications. One prerequisite is the furthering of the knowledge of the factors determining the solvent production and their integrative regulations. We have mathematically analysed the influence of pH-dependent specific enzyme activities of branch points of the metabolism on the product formation. This kinetic regulation was compared with transcriptomic regulation regarding gene transcription and the proteomic profile. Furthermore, both regulatory mechanisms were combined yielding a detailed projection of their individual and joint effects on the product formation. The resulting model represents an important platform for future developments of industrial butanol production based on C. acetobutylicum. PMID:23332010

  7. Sensory Integration and Ego Development in a Schizophrenic Adolescent Male.

    ERIC Educational Resources Information Center

    Pettit, Karen A.

    1987-01-01

    A retrospective study compared hours spent by a schizophrenic adolescent in "time out" before and after initiation of treatment. The study evaluated the effects of sensory integrative treatment on the ability to handle anger and frustration. Results demonstrate the utility of statistical analysis versus visual comparison to validate effectiveness…

  8. [The male nurses' experiences of adaptation in clinical setting].

    PubMed

    Son, Haeng-Mi; Koh, Moon-Hee; Kim, Chun-Mi; Moon, Jin-Ha; Yi, Myung-Sun

    2003-02-01

    The purpose of this study was to identified the male nurses' encounter in adapting themselves in the hospital settings dominated by the female nurses in number. Data were collected through the in-depth interview of 16 male nurses and analysed through the grounded theory methodology. The behaviors of male nurses for job-adaptation can be summarized as a series of struggles to consolidate their own ground. They have made tremendous efforts to hold their own ground in the nursing profession composed of a large numbers of female nurses, while they have experienced many difficulties and problems as minorities. They have struggled to adapt themselves professionally through efforts such as; challenging the social and professional barriers, identifying the job identity, empowering themselves through self-development and dedication, expanding their influence among colleagues. In spite of these efforts, they had the perception that nursing is not a lifelong occupation for them. Thus, they had tendency to find outlets of change to occupations. A specific strategy is needed to provide an environment that is helpful for males in integrating into and adapting to the nursing profession.

  9. Effects of biomotor structures on performance of competitive gymnastics elements in elementary school male sixth-graders.

    PubMed

    Delas, Suncica; Zagorac, Nebojsa; Katić, Ratko

    2008-06-01

    In order to identify the biomotor systems that determine performance of competitive gymnastics elements in elementary school male sixth-graders, factor structures of morphological characteristics and basic motor abilities were determined first, followed by relations of the morphological-motor system factors obtained with a set of criterion variables evaluating specific motor skills in competitive gymnastics in 110 male children aged 12 years +/- 3 months. Factor analysis of 17 morphological measures produced three morphological factors: factor of mesoectoendomorphy (general morphological factor) and factor of pronounced endomorphy, i.e. excessive adipose tissue, along with low skeleton longitudinality. Factor analysis of 16 motor variables yielded four motor factors: factor of general motoricity; factor integrating leg flexibility and arm explosiveness; factor juxtaposing body flexibility and repetitive leg strength; and factor predominantly defining leg movement frequency. Three significant canonical correlations, i.e. linear combinations, explained the association between the set of six latent variables of the morphological and basic motor system, and five variables assessing the knowledge in competitive gymnastics. The first canonical linear combination was based on the favorable and predominant impact of the general motor factor (a system integrating leg explosiveness, whole body coordination, relative arm and trunk strength, and arm movement frequency), along with unfavorable effect of morphological factors on the gymnastics elements performance, squat vault and handstand in particular The relation of the second pair of canonical factors pointed to the effects of leg flexibility and arm explosiveness on the cartwheel and backward pullover mount performance, whereas the relation of the third pair of canonical factors showed a favorable impact of the general morphological factor and leg movement frequency regulator on the forward shoulderkip from increase

  10. Dynamic control of type I IFN signalling by an integrated network of negative regulators.

    PubMed

    Porritt, Rebecca A; Hertzog, Paul J

    2015-03-01

    Whereas type I interferons (IFNs) have critical roles in protection from pathogens, excessive IFN responses contribute to pathology in both acute and chronic settings, pointing to the importance of balancing activating signals with regulatory mechanisms that appropriately tune the response. Here we review evidence for an integrated network of negative regulators of IFN production and action, which function at all levels of the activating and effector signalling pathways. We propose that the aim of this extensive network is to limit tissue damage while enabling an IFN response that is temporally appropriate and of sufficient magnitude. Understanding the architecture and dynamics of this network, and how it differs in distinct tissues, will provide new insights into IFN biology and aid the design of more effective therapeutics. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  11. The Control of Male Fertility by Spermatozoan Ion Channels

    PubMed Central

    Lishko, Polina V.; Kirichok, Yuriy; Ren, Dejian; Navarro, Betsy; Chung, Jean-Ju

    2014-01-01

    Ion channels control the sperm ability to fertilize the egg by regulating sperm maturation in the female reproductive tract and by triggering key sperm physiological responses required for successful fertilization such as hyperactivated motility, chemotaxis, and the acrosome reaction. CatSper, a pH-regulated, calcium-selective ion channel, and KSper (Slo3) are core regulators of sperm tail calcium entry and sperm hyperactivated motility. Many other channels had been proposed as regulating sperm activity without direct measurements. With the development of the sperm patch-clamp technique, CatSper and KSper have been confirmed as the primary spermatozoan ion channels. In addition, the voltage-gated proton channel Hv1 has been identified in human sperm tail, and the P2X2 ion channel has been identified in the midpiece of mouse sperm. Mutations and deletions in sperm-specific ion channels affect male fertility in both mice and humans without affecting other physiological functions. The uniqueness of sperm ion channels makes them ideal pharmaceutical targets for contraception. In this review we discuss how ion channels regulate sperm physiology. PMID:22017176

  12. College Students' Achievement Goal Orientation and Motivational Regulations in Physical Activity Classes: A Test of Gender Invariance

    ERIC Educational Resources Information Center

    Su, Xiaoxia; McBride, Ron E.; Xiang, Ping

    2015-01-01

    The current study examined the measurement invariance across 361 male and female college students' 2 × 2 achievement goal orientation and motivational regulations. Participants completed questionnaires assessing their achievement goals and motivational regulations. Multigroup CFA analyses showed that male and female students' scores were fully…

  13. Reproductive inefficiency in male black-footed ferrets (Mustela nigripes).

    PubMed

    Wolf, K.N.; Wildt, D.E.; Vargas, A.; Marinari, P.E.; Ottinger, M.A.; Howard, J.G.

    2000-01-01

    The black-footed ferret (Mustela nigripes), once considered extinct, has benefited from captive breeding and subsequent reintroduction into native habitat. A high proportion of females (>90%) exhibit estrus in captivity during the spring breeding season. However, many males considered to be prime-breeding age (1-3 years old) fail to sire offspring. Breeding records in 1995 revealed that 40 of 73 males (55%) managed under the Black-Footed Ferret Species Survival Plan did not reproduce, despite being provided opportunity. The present study was conducted to determine the incidence and etiology of male reproductive failure in 1996 and 1997. In 1996, 38 of 69 (55%) 1- to 3-year-old males failed to sire offspring. Likewise, 35 of 60 (58%) males did not reproduce in 1997. Overall, 21% of adult males failed to sire young in three consecutive breeding seasons (1995-1997). Electroejaculate traits (ejaculate volume, sperm concentration, motility, morphology, and acrosomal integrity) from 29 proven breeder males were not different (P > 0.05) from those of 23 males that did not sire young (nonproven breeders). However, six categories of reproductive failure were identified for the 73 prime-breeding age, nonproven males: 1) underdeveloped testes (22%); 2) improper breeding position with the female (25%); 3) excessive aggression toward estrous females (9%); 4) copulation with no sperm detected at postcoital lavage (19%); 5) copulation with sperm in the vaginal lavage but no resulting pregnancy (18%); and 6) copulation with no vaginal lavage performed and no resulting pregnancy (7%). These data indicate that combined behavioral and physiologic factors, but not overall sperm quality, influence reproductive performance in male black-footed ferrets managed in captivity. Zoo Biol 19:517-528, 2000. Copyright 2000 Wiley-Liss, Inc.

  14. Corticosteroid receptor expression in a teleost fish that displays alternative male reproductive tactics.

    PubMed

    Arterbery, Adam S; Deitcher, David L; Bass, Andrew H

    2010-01-01

    Corticosteroid signaling mechanisms mediate a wide range of adaptive physiological responses, including those essential to reproduction. Here, we investigated the presence and relative abundance of corticosteroid receptors during the breeding season in the plainfin midshipman fish (Porichthys notatus), a species that has two male reproductive morphs. Only type I "singing" males acoustically court females and aggressively defend a nest site, whereas type II "sneaker" males steal fertilizations from nesting type I males. Cloning and sequencing first identified glucocorticoid (GR) and mineralocorticoid (MR) receptors in midshipman that exhibited high sequence identity with other vertebrate GRs and MRs. Absolute-quantitative real-time PCR then revealed higher levels of GR in the central nervous system (CNS) of type II males than type I males and females, while GR levels in the sound-producing, vocal muscle and the liver were higher in type I males than type II males and females. MR expression was also greater in the CNS of type II males than type I males or females, but the differences were more modest in magnitude. Lastly, plasma levels of cortisol, the main glucocorticoid in teleosts, were 2- to 3-fold greater in type II males compared to type I males. Together, the results suggest a link between corticosteroid regulation and physiological and behavioral variation in a teleost fish that displays male alternative reproductive tactics.

  15. Integrally regulated solar array demonstration using an Intel 8080 microprocessor

    NASA Technical Reports Server (NTRS)

    Petrik, E. J.

    1977-01-01

    A concept for regulating the voltage of a solar array by using a microprocessor to effect discrete voltage changes was demonstrated. Eight shorting switches were employed to regulate a simulated array at set-point voltages between 10,000 and 15,000 volts. The demonstration showed that the microprocessor easily regulated the solar array output voltage independently of whether or not the switched cell groups were binary sized in voltage. In addition, the microprocessor provided logic memory capability to perform additional tasks such as locating and insolating a faulty switch.

  16. Structural brain differences in emotional processing and regulation areas between male batterers and other criminals: A preliminary study.

    PubMed

    Verdejo-Román, Juan; Bueso-Izquierdo, Natalia; Daugherty, Julia C; Pérez-García, Miguel; Hidalgo-Ruzzante, Natalia

    2018-05-31

    Poor emotion processing is thought to influence violent behaviors among male batterers in abusive relationships. Nevertheless, little is known about the neural mechanisms of emotion processing in this population. With the objective of better understanding brain structure and its relation to emotion processing in male batterers, the present study compares the cortical grey matter thickness of male batterers to that of other criminals in brain areas related to emotion. Differences among these brain areas were also compared to an emotional perception task. An MRI study and an emotional perception assessment was conducted with 21 male batterers and 20 men convicted of crimes other than Intimate Partner Violence (IPV). Results demonstrated that batterers' had significantly thinner cortices in prefrontal (orbitofrontal), midline (anterior and posterior cingulate) and limbic (insula, parahipocampal) brain regions. The thickness of the dorsal posterior cingulate cortex in the batterer group correlated with scores on the emotional perception task. These findings shed light on a neuroscientific approach to analyzing violent behavior perpetrated by male batterers, leading to a better understanding of the underlying mechanisms involved in IPV.

  17. Cumulative-genetic plasticity, parenting and adolescent self-regulation.

    PubMed

    Belsky, Jay; Beaver, Kevin M

    2011-05-01

    The capacity to control or regulate one's emotions, cognitions and behavior is central to competent functioning, with limitations in these abilities associated with developmental problems. Parenting appears to influence such self-regulation. Here the differential-susceptibility hypothesis is tested that the more putative 'plasticity alleles' adolescents carry, the more positively and negatively influenced they will be by, respectively, supportive and unsupportive parenting. One thousand, five hundred and eighty-six (1586) adolescents (n = 754 males; n = 832 females) enrolled in the American Add Health project were scored in terms of how many of 5 putative 'plasticity alleles' they carried - the 10R allele of DAT1, the A1 allele of DRD2, the 7R allele of DRD4, the short allele of 5HTTLPR, and the 2R/3R alleles of MAOA. Then the effect of the resultant index (ranging from 0 to 5) of cumulative-genetic plasticity in moderating effects of parenting on adolescent self-regulation was evaluated. Consistent with differential susceptibility, the more plasticity alleles males (but not females) carried, the more and less self-regulation they manifested under, respectively, supportive and unsupportive parenting conditions. Adolescent males appear to vary for genetic reasons in their susceptibility to parenting vis-à-vis self-regulation, perhaps due to epistatic and/or epigenetic processes. G×E research may benefit from compositing candidate genes. To afford comparative evaluation of differential-susceptibility vs. diathesis-stress models of environmental action, future G×E work should focus on positive as well as negative environmental conditions and developmental outcomes. © 2010 The Authors. Journal of Child Psychology and Psychiatry © 2010 Association for Child and Adolescent Mental Health.

  18. BDNF–ERK–CREB signalling mediates the role of miR-132 in the regulation of the effects of oleanolic acid in male mice

    PubMed Central

    Yi, Li-Tao; Li, Jing; Liu, Bin-Bin; Luo, Liu; Liu, Qing; Geng, Di

    2014-01-01

    Background Although previous study has demonstrated that brain-derived neurotrophic factor (BDNF) is involved in the antidepressant-like effect of oleanolic acid, there is little information regarding the details of the molecular mechanism involved in this effect. Methods We used a chronic unpredictable mild stress (CUMS) model to test the antidepressant-like effect of oleanolic acid on depressant-like behaviour, miR-132 expression and synaptic protein expression in the male mouse hippocampus. Furthermore, we explored the possible signalling pathways associated with miR-132 expression that mediate the effect of oleanolic acid on neuronal proliferation. Results The results demonstrated that a 3-week treatment with oleanolic acid ameliorated CUMS-induced anhedonic and anxiogenic behaviours. Furthermore, we found that oleanolic acid led to the BDNF-related phosphorylation and activation of extracellular signal-regulated kinases (ERK) and cyclic adenosine monophosphate response element binding protein (CREB), which was associated with the upregulation of miR-132 and hippocampal neuronal proliferation. Moreover, experiments with an miR-132 antagomir revealed that targeting miR-132 led to inhibition of neuronal proliferation and the postsynaptic density protein 95, but did not affect presynaptic protein synapsin I. Limitations Several other stimuli can also induce CREB phosphorylation in the hippocampus. Thus, regulation of miR-132 may not be restricted to neurotrophic signalling. Conclusion Our results show that oleanolic acid induces the upregulation of miR-132, which serves as an important regulator of neurotrophic actions, mainly through the activation of the hippocampal BDNF–ERK–CREB signalling pathways. PMID:25079084

  19. Studies on the membrane integrity of human sperm treated with a new injectable male contraceptive.

    PubMed

    Chaudhury, K; Bhattacharyya, A K; Guha, S K

    2004-08-01

    The aim of this study was to evaluate the integrity of sperm surface characteristics in the presence of a new male contraceptive, RISUG [1 mg styrene maleic anhydride (SMA)/100 microl dimethylsulphoxide (DMSO) in 1 ml sperm solution]. Progressively motile human sperm were treated in vitro with RISUG. The cells were analysed for the release of 5'-nucleotidase (5'-NT) (a plasma membrane marker) using 3 mmol/l 5'-AMP and 3 mmol/l beta-glycerophosphate as substrates. Hyaluronidase (an acrosomal membrane marker) was analysed using hyaluronic acid as a substrate. The contents of free and total acrosin, and % proacrosin (all acrosome markers) were assayed using 0.5 mmol/l alpha-N-benzoyl-L-arginine ethylester (BAEE). RISUG caused almost complete disintegration of the plasma membrane leading to significant (P < 0.0001) release of 5'-NT into the surrounding media. Complete dissolution of the acrosome with concomitant vesiculation of the membrane system, as judged from the loss of hyaluronidase, was observed. Total acrosin content in the sperm was also reduced to almost 10%, and proacrosin dropped to 13.2% in the presence of RISUG in comparison to 90.2% in control (P < 0.0001), indicating dispersion of acrosomal contents. Under in vitro conditions, RISUG, at a concentration of 1 mg SMA dissolved in 100 microl of DMSO, caused significant damage to the acrosome and its contents, indicating loss of functional ability of sperm. Copyright 2004 European Society of Human Reproduction and Embryology

  20. Light Regulation of Swarming Motility in Pseudomonas syringae Integrates Signaling Pathways Mediated by a Bacteriophytochrome and a LOV Protein

    PubMed Central

    Wu, Liang; McGrane, Regina S.; Beattie, Gwyn A.

    2013-01-01

    ABSTRACT The biological and regulatory roles of photosensory proteins are poorly understood for nonphotosynthetic bacteria. The foliar bacterial pathogen Pseudomonas syringae has three photosensory protein-encoding genes that are predicted to encode the blue-light-sensing LOV (light, oxygen, or voltage) histidine kinase (LOV-HK) and two red/far-red-light-sensing bacteriophytochromes, BphP1 and BphP2. We provide evidence that LOV-HK and BphP1 form an integrated network that regulates swarming motility in response to multiple light wavelengths. The swarming motility of P. syringae B728a deletion mutants indicated that LOV-HK positively regulates swarming motility in response to blue light and BphP1 negatively regulates swarming motility in response to red and far-red light. BphP2 does not detectably regulate swarming motility. The histidine kinase activity of each LOV-HK and BphP1 is required for this regulation based on the loss of complementation upon mutation of residues key to their kinase activity. Surprisingly, mutants lacking both lov and bphP1 were similar in motility to a bphP1 single mutant in blue light, indicating that the loss of bphP1 is epistatic to the loss of lov and also that BphP1 unexpectedly responds to blue light. Moreover, whereas expression of bphP1 did not alter motility under blue light in a bphP1 mutant, it reduced motility in a mutant lacking lov and bphP1, demonstrating that LOV-HK positively regulates motility by suppressing negative regulation by BphP1. These results are the first to show cross talk between the LOV protein and phytochrome signaling pathways in bacteria, and the similarity of this regulatory network to that of photoreceptors in plants suggests a possible common ancestry. PMID:23760465

  1. Sex Steroid Actions in Male Bone

    PubMed Central

    Laurent, Michaël R.; Claessens, Frank; Gielen, Evelien; Lagerquist, Marie K.; Vandenput, Liesbeth; Börjesson, Anna E.; Ohlsson, Claes

    2014-01-01

    Sex steroids are chief regulators of gender differences in the skeleton, and male gender is one of the strongest protective factors against osteoporotic fractures. This advantage in bone strength relies mainly on greater cortical bone expansion during pubertal peak bone mass acquisition and superior skeletal maintenance during aging. During both these phases, estrogens acting via estrogen receptor-α in osteoblast lineage cells are crucial for male cortical and trabecular bone, as evident from conditional genetic mouse models, epidemiological studies, rare genetic conditions, genome-wide meta-analyses, and recent interventional trials. Genetic mouse models have also demonstrated a direct role for androgens independent of aromatization on trabecular bone via the androgen receptor in osteoblasts and osteocytes, although the target cell for their key effects on periosteal bone formation remains elusive. Low serum estradiol predicts incident fractures, but the highest risk occurs in men with additionally low T and high SHBG. Still, the possible clinical utility of serum sex steroids for fracture prediction is unknown. It is likely that sex steroid actions on male bone metabolism rely also on extraskeletal mechanisms and cross talk with other signaling pathways. We propose that estrogens influence fracture risk in aging men via direct effects on bone, whereas androgens exert an additional antifracture effect mainly via extraskeletal parameters such as muscle mass and propensity to fall. Given the demographic trends of increased longevity and consequent rise of osteoporosis, an increased understanding of how sex steroids influence male bone health remains a high research priority. PMID:25202834

  2. 34 CFR 425.4 - What regulations apply?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., DEPARTMENT OF EDUCATION DEMONSTRATION PROJECTS FOR THE INTEGRATION OF VOCATIONAL AND ACADEMIC LEARNING... Projects for the Integration of Vocational and Academic Learning Program: (a) The regulations in this part...

  3. 34 CFR 425.4 - What regulations apply?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., DEPARTMENT OF EDUCATION DEMONSTRATION PROJECTS FOR THE INTEGRATION OF VOCATIONAL AND ACADEMIC LEARNING... Projects for the Integration of Vocational and Academic Learning Program: (a) The regulations in this part...

  4. 34 CFR 425.4 - What regulations apply?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., DEPARTMENT OF EDUCATION DEMONSTRATION PROJECTS FOR THE INTEGRATION OF VOCATIONAL AND ACADEMIC LEARNING... Projects for the Integration of Vocational and Academic Learning Program: (a) The regulations in this part...

  5. Extensive cross-talk and global regulators identified from an analysis of the integrated transcriptional and signaling network in Escherichia coli.

    PubMed

    Antiqueira, Lucas; Janga, Sarath Chandra; Costa, Luciano da Fontoura

    2012-11-01

    To understand the regulatory dynamics of transcription factors (TFs) and their interplay with other cellular components we have integrated transcriptional, protein-protein and the allosteric or equivalent interactions which mediate the physiological activity of TFs in Escherichia coli. To study this integrated network we computed a set of network measurements followed by principal component analysis (PCA), investigated the correlations between network structure and dynamics, and carried out a procedure for motif detection. In particular, we show that outliers identified in the integrated network based on their network properties correspond to previously characterized global transcriptional regulators. Furthermore, outliers are highly and widely expressed across conditions, thus supporting their global nature in controlling many genes in the cell. Motifs revealed that TFs not only interact physically with each other but also obtain feedback from signals delivered by signaling proteins supporting the extensive cross-talk between different types of networks. Our analysis can lead to the development of a general framework for detecting and understanding global regulatory factors in regulatory networks and reinforces the importance of integrating multiple types of interactions in underpinning the interrelationships between them.

  6. Males Are Overrepresented among Life Science Researchers Committing Scientific Misconduct

    PubMed Central

    Fang, Ferric C.; Bennett, Joan W.; Casadevall, Arturo

    2013-01-01

    ABSTRACT A review of the United States Office of Research Integrity annual reports identified 228 individuals who have committed misconduct, of which 94% involved fraud. Analysis of the data by career stage and gender revealed that misconduct occurred across the entire career spectrum from trainee to senior scientist and that two-thirds of the individuals found to have committed misconduct were male. This exceeds the overall proportion of males among life science trainees and faculty. These observations underscore the need for additional efforts to understand scientific misconduct and to ensure the responsible conduct of research. PMID:23341553

  7. Sexual dimorphism of sleep regulated by juvenile hormone signaling in Drosophila

    PubMed Central

    Zhang, Enyan; Du, Juan; Liu, Suning; Price, Jeffrey

    2018-01-01

    Sexually dimorphic phenotypes are a universal phenomenon in animals. In the model animal fruit fly Drosophila, males and females exhibit long- and short-sleep phenotypes, respectively. However, the mechanism is still a mystery. In this study, we showed that juvenile hormone (JH) is involved in regulation of sexually dimorphic sleep in Drosophila, in which gain of JH function enlarges differences of the dimorphic sleep phenotype with higher sleep in males and lower sleep in females, while loss of JH function blurs these differences and results in feminization of male sleep and masculinization of female sleep. Further studies indicate that germ cell-expressed (GCE), one of the JH receptors, mediates the response in the JH pathway because the sexually dimorphic sleep phenotypes cannot be rescued by JH hormone in a gce deletion mutant. The JH-GCE regulated sleep dimorphism is generated through the sex differentiation-related genes -fruitless (fru) and doublesex (dsx) in males and sex-lethal (sxl), transformer (tra) and doublesex (dsx) in females. These are the “switch” genes that separately control the sleep pattern in males and females. Moreover, analysis of sleep deprivation and circadian behaviors showed that the sexually dimorphic sleep induced by JH signals is a change of sleep drive and independent of the circadian clock. Furthermore, we found that JH seems to also play an unanticipated role in antagonism of an aging-induced sleep decrease in male flies. Taken together, these results indicate that the JH signal pathway is critical for maintenance of sexually dimorphic sleep by regulating sex-relevant genes. PMID:29617359

  8. Pressure Regulator With Internal Ejector Circulation Pump, Flow and Pressure Measurement Porting, and Fuel Cell System Integration Options

    NASA Technical Reports Server (NTRS)

    Vasquez, Arturo

    2011-01-01

    An advanced reactant pressure regulator with an internal ejector reactant circulation pump has been developed to support NASA's future fuel cell power systems needs. These needs include reliable and safe operation in variable-gravity environments, and for exploration activities with both manned and un manned vehicles. This product was developed for use in Proton Exchange Membrane Fuel Cell (PEMFC) power plant reactant circulation systems, but the design could also be applied to other fuel cell system types, (e.g., solid-oxide or alkaline) or for other gas pressure regulation and circulation needs. The regulator design includes porting for measurement of flow and pressure at key points in the system, and also includes several fuel cell system integration options. NASA has recognized ejectors as a viable alternative to mechanical pumps for use in spacecraft fuel cell power systems. The ejector motive force is provided by a variable, high-pressure supply gas that travels through the ejector s jet nozzle, whereby the pressure energy of the fluid stream is converted to kinetic energy in the gas jet. The ejector can produce circulation-to-consumption-flow ratios that are relatively high (2-3 times), and this phenomenon can potentially (with proper consideration of the remainder of the fuel cell system s design) be used to provide completely for reactant pre-humidification and product water removal in a fuel cell system. Specifically, a custom pressure regulator has been developed that includes: (1) an ejector reactant circulation pump (with interchangeable jet nozzles and mixer sections, gas-tight sliding and static seals in required locations, and internal fluid porting for pressure-sensing at the regulator's control elements) and (2) internal fluid porting to allow for flow rate and system pressure measurements. The fluid porting also allows for inclusion of purge, relief, and vacuum-breaker check valves on the regulator assembly. In addition, this regulator could also

  9. An essential cell cycle regulation gene causes hybrid inviability in Drosophila

    PubMed Central

    Phadnis, Nitin; Baker, EmilyClare P.; Cooper, Jacob C.; Frizzell, Kimberly A.; Hsieh, Emily; de la Cruz, Aida Flor A.; Shendure, Jay; Kitzman, Jacob O.; Malik, Harmit S.

    2015-01-01

    Speciation, the process by which new biological species arise, involves the evolution of reproductive barriers such as hybrid sterility or inviability between populations. However, identifying hybrid incompatibility genes remains a key obstacle in understanding the molecular basis of reproductive isolation. We devised a genomic screen, which identified a cell cycle regulation gene as the cause of male inviability in hybrids between Drosophila melanogaster and D. simulans. Ablation of the D. simulans allele of this gene is sufficient to rescue the adult viability of hybrid males. This dominantly acting cell cycle regulator causes mitotic arrest and, thereby, inviability of male hybrid larvae. Our genomic method provides a facile means to accelerate the identification of hybrid incompatibility genes in other model and non-model systems. PMID:26680200

  10. Sperm competition games when males invest in paternal care.

    PubMed

    Requena, Gustavo S; Alonzo, Suzanne H

    2017-08-16

    Sperm competition games investigate how males partition limited resources between pre- and post-copulatory competition. Although extensive research has explored how various aspects of mating systems affect this allocation, male allocation between mating, fertilization and parental effort has not previously been considered. Yet, paternal care can be energetically expensive and males are generally predicted to adjust their parental effort in response to expected paternity. Here, we incorporate parental effort into sperm competition games, particularly exploring how the relationship between paternal care and offspring survival affects sperm competition and the relationship between paternity and paternal care. Our results support existing expectations that (i) fertilization effort should increase with female promiscuity and (ii) paternal care should increase with expected paternity. However, our analyses also reveal that the cost of male care can drive the strength of these patterns. When paternal behaviour is energetically costly, increased allocation to parental effort constrains allocation to fertilization effort. As paternal care becomes less costly, the association between paternity and paternal care weakens and may even be absent. By explicitly considering variation in sperm competition and the cost of male care, our model provides an integrative framework for predicting the interaction between paternal care and patterns of paternity. © 2017 The Author(s).

  11. Protein and carbohydrate intake influence sperm number and fertility in male cockroaches, but not sperm viability.

    PubMed

    Bunning, Harriet; Rapkin, James; Belcher, Laurence; Archer, C Ruth; Jensen, Kim; Hunt, John

    2015-03-07

    It is commonly assumed that because males produce many, tiny sperm, they are cheap to produce. Recent work, however, suggests that sperm production is not cost-free. If sperm are costly to produce, sperm number and/or viability should be influenced by diet, and this has been documented in numerous species. Yet few studies have examined the exact nutrients responsible for mediating these effects. Here, we quantify the effects of protein (P) and carbohydrate (C) intake on sperm number and viability in the cockroach Nauphoeta cinerea, as well as the consequences for male fertility. We found the intake of P and C influenced sperm number, being maximized at a high intake of diets with a P : C ratio of 1 : 2, but not sperm viability. The nutritional landscapes for male fertility and sperm number were closely aligned, suggesting that sperm number is the major determinant of male fertility in N. cinerea. Under dietary choice, males regulate nutrient intake at a P : C ratio of 1 : 4.95, which is midway between the ratios needed to maximize sperm production and pre-copulatory attractiveness in this species. This raises the possibility that males regulate nutrient intake to balance the trade-off between pre- and post-copulatory traits in this species. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  12. Integrating co-morbid depression and chronic physical disease management: identifying and resolving failures in self-regulation.

    PubMed

    Detweiler-Bedell, Jerusha B; Friedman, Michael A; Leventhal, Howard; Miller, Ivan W; Leventhal, Elaine A

    2008-12-01

    Research suggests that treatments for depression among individuals with chronic physical disease do not improve disease outcomes significantly, and chronic disease management programs do not necessarily improve mood. For individuals experiencing co-morbid depression and chronic physical disease, demands on the self-regulation system are compounded, leading to a rapid depletion of self-regulatory resources. Because disease and depression management are not integrated, patients lack the understanding needed to prioritize self-regulatory goals in a way that makes disease and depression management synergistic. A framework in which the management of co-morbidity is considered alongside the management of either condition alone offers benefits to researchers and practitioners and may help improve clinical outcomes.

  13. Integrating Co-Morbid Depression and Chronic Physical Disease Management: Identifying and Resolving Failures in Self-Regulation

    PubMed Central

    Detweiler-Bedell, Jerusha B.; Friedman, Michael A.; Leventhal, Howard; Miller, Ivan W.; Leventhal, Elaine A.

    2008-01-01

    Research suggests that treatments for depression among individuals with chronic physical disease do not improve disease outcomes significantly, and chronic disease management programs do not necessarily improve mood. For individuals experiencing co-morbid depression and chronic physical disease, demands on the self-regulation system are compounded, leading to a rapid depletion of self-regulatory resources. Because disease and depression management are not integrated, patients lack the understanding needed to prioritize self-regulatory goals in a way that makes disease and depression management synergistic. A framework in which the management of co-morbidity is considered alongside the management of either condition alone offers benefits to researchers and practitioners and may help improve clinical outcomes. PMID:18848740

  14. ERK Signaling in the Pituitary Is Required for Female But Not Male Fertility

    PubMed Central

    Bliss, Stuart P.; Miller, Andrew; Navratil, Amy M.; Xie, JianJun; McDonough, Sean P.; Fisher, Patricia J.; Landreth, Gary E.; Roberson, Mark S.

    2009-01-01

    Males and females require different patterns of pituitary gonadotropin secretion for fertility. The mechanisms underlying these gender-specific profiles of pituitary hormone production are unknown; however, they are fundamental to understanding the sexually dimorphic control of reproductive function at the molecular level. Several studies suggest that ERK1 and -2 are essential modulators of hypothalamic GnRH-mediated regulation of pituitary gonadotropin production and fertility. To test this hypothesis, we generated mice with a pituitary-specific depletion of ERK1 and 2 and examined a range of physiological parameters including fertility. We find that ERK signaling is required in females for ovulation and fertility, whereas male reproductive function is unaffected by this signaling deficiency. The effects of ERK pathway ablation on LH biosynthesis underlie this gender-specific phenotype, and the molecular mechanism involves a requirement for ERK-dependent up-regulation of the transcription factor Egr1, which is necessary for LHβ expression. Together, these findings represent a significant advance in elucidating the molecular basis of gender-specific regulation of the hypothalamic-pituitary-gonadal axis and sexually dimorphic control of fertility. PMID:19372235

  15. Does cultural integration explain a mental health advantage for adolescents?

    PubMed Central

    Bhui, Kamaldeep S; Lenguerrand, Erik; Maynard, Maria J; Stansfeld, Stephen A; Harding, Seeromanie

    2012-01-01

    Background A mental health advantage has been observed among adolescents in urban areas. This prospective study tests whether cultural integration measured by cross-cultural friendships explains a mental health advantage for adolescents. Methods A prospective cohort of adolescents was recruited from 51 secondary schools in 10 London boroughs. Cultural identity was assessed by friendship choices within and across ethnic groups. Cultural integration is one of four categories of cultural identity. Using gender-specific linear-mixed models we tested whether cultural integration explained a mental health advantage, and whether gender and age were influential. Demographic and other relevant factors, such as ethnic group, socio-economic status, family structure, parenting styles and perceived racism were also measured and entered into the models. Mental health was measured by the Strengths and Difficulties Questionnaire as a ‘total difficulties score’ and by classification as a ‘probable clinical case’. Results A total of 6643 pupils in first and second years of secondary school (ages 11–13 years) took part in the baseline survey (2003/04) and 4785 took part in the follow-up survey in 2005–06. Overall mental health improved with age, more so in male rather than female students. Cultural integration (friendships with own and other ethnic groups) was associated with the lowest levels of mental health problems especially among male students. This effect was sustained irrespective of age, ethnicity and other potential explanatory variables. There was a mental health advantage among specific ethnic groups: Black Caribbean and Black African male students (Nigerian/Ghanaian origin) and female Indian students. This was not fully explained by cultural integration, although cultural integration was independently associated with better mental health. Conclusions Cultural integration was associated with better mental health, independent of the mental health advantage

  16. Does cultural integration explain a mental health advantage for adolescents?

    PubMed

    Bhui, Kamaldeep S; Lenguerrand, Erik; Maynard, Maria J; Stansfeld, Stephen A; Harding, Seeromanie

    2012-06-01

    A mental health advantage has been observed among adolescents in urban areas. This prospective study tests whether cultural integration measured by cross-cultural friendships explains a mental health advantage for adolescents. A prospective cohort of adolescents was recruited from 51 secondary schools in 10 London boroughs. Cultural identity was assessed by friendship choices within and across ethnic groups. Cultural integration is one of four categories of cultural identity. Using gender-specific linear-mixed models we tested whether cultural integration explained a mental health advantage, and whether gender and age were influential. Demographic and other relevant factors, such as ethnic group, socio-economic status, family structure, parenting styles and perceived racism were also measured and entered into the models. Mental health was measured by the Strengths and Difficulties Questionnaire as a 'total difficulties score' and by classification as a 'probable clinical case'. A total of 6643 pupils in first and second years of secondary school (ages 11-13 years) took part in the baseline survey (2003/04) and 4785 took part in the follow-up survey in 2005-06. Overall mental health improved with age, more so in male rather than female students. Cultural integration (friendships with own and other ethnic groups) was associated with the lowest levels of mental health problems especially among male students. This effect was sustained irrespective of age, ethnicity and other potential explanatory variables. There was a mental health advantage among specific ethnic groups: Black Caribbean and Black African male students (Nigerian/Ghanaian origin) and female Indian students. This was not fully explained by cultural integration, although cultural integration was independently associated with better mental health. Cultural integration was associated with better mental health, independent of the mental health advantage found among specific ethnic groups: Black Caribbean and

  17. Information Integration and Communication in Plant Growth Regulation.

    PubMed

    Chaiwanon, Juthamas; Wang, Wenfei; Zhu, Jia-Ying; Oh, Eunkyoo; Wang, Zhi-Yong

    2016-03-10

    Plants are equipped with the capacity to respond to a large number of diverse signals, both internal ones and those emanating from the environment, that are critical to their survival and adaption as sessile organisms. These signals need to be integrated through highly structured intracellular networks to ensure coherent cellular responses, and in addition, spatiotemporal actions of hormones and peptides both orchestrate local cell differentiation and coordinate growth and physiology over long distances. Further, signal interactions and signaling outputs vary significantly with developmental context. This review discusses our current understanding of the integrated intracellular and intercellular signaling networks that control plant growth. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Information Integration and Communication in Plant Growth Regulation

    PubMed Central

    Chaiwanon, Juthamas; Wang, Wenfei; Zhu, Jia-Ying; Oh, Eunkyoo; Wang, Zhi-Yong

    2016-01-01

    Plants are equipped with the capacity to respond to a large number of diverse signals, both internal ones and those emanating from the environment, that are critical to their survival and adaption as sessile organisms. These signals need to be integrated through highly structured intracellular networks to ensure coherent cellular responses, and in addition, spatiotemporal actions of hormones and peptides both orchestrate local cell differentiation and coordinate growth and physiology over long distances. Further, signal interactions and signaling outputs vary significantly with developmental context. This review discusses our current understanding of the integrated intracellular and intercellular signaling networks that control plant growth. PMID:26967291

  19. Gender differences in myogenic regulation along the vascular tree of the gerbil cochlea.

    PubMed

    Reimann, Katrin; Krishnamoorthy, Gayathri; Wier, Withrow Gil; Wangemann, Philine

    2011-01-01

    Regulation of cochlear blood flow is critical for hearing due to its exquisite sensitivity to ischemia and oxidative stress. Many forms of hearing loss such as sensorineural hearing loss and presbyacusis may involve or be aggravated by blood flow disorders. Animal experiments and clinical outcomes further suggest that there is a gender preference in hearing loss, with males being more susceptible. Autoregulation of cochlear blood flow has been demonstrated in some animal models in vivo, suggesting that similar to the brain, blood vessels supplying the cochlea have the ability to control flow within normal limits, despite variations in systemic blood pressure. Here, we investigated myogenic regulation in the cochlear blood supply of the Mongolian gerbil, a widely used animal model in hearing research. The cochlear blood supply originates at the basilar artery, followed by the anterior inferior cerebellar artery, and inside the inner ear, by the spiral modiolar artery and the radiating arterioles that supply the capillary beds of the spiral ligament and stria vascularis. Arteries from male and female gerbils were isolated and pressurized using a concentric pipette system. Diameter changes in response to increasing luminal pressures were recorded by laser scanning microscopy. Our results show that cochlear vessels from male and female gerbils exhibit myogenic regulation but with important differences. Whereas in male gerbils, both spiral modiolar arteries and radiating arterioles exhibited pressure-dependent tone, in females, only radiating arterioles had this property. Male spiral modiolar arteries responded more to L-NNA than female spiral modiolar arteries, suggesting that NO-dependent mechanisms play a bigger role in the myogenic regulation of male than female gerbil cochlear vessels.

  20. Repeated use of the GnRH analogue deslorelin to down-regulate reproduction in male cheetahs (Acinonyx jubatus).

    PubMed

    Bertschinger, H J; Jago, M; Nöthling, J O; Human, A

    2006-10-01

    The GnRH analogue deslorelin, as a subcutaneous implant, was initially developed in Australia as an ovulation-inducing agent in mares. Its uses, for the suppression of reproduction in the domestic dog and cat and in other species, including humans, have been developed subsequently. Such implants have been used as a contraceptive modality in a variety of wild carnivores, both males and females. This paper describes the use of deslorelin implants as a contraceptive agent for cheetah males maintained in a semi-captive environment and housed in various camps together with females. Annually, male cheetahs were treated for 1 (n = 2), 2 (n = 7), 3 (n = 9), 4 (n = 3) or 5 (n = 1) consecutive years with an implant containing 4.7, 5.0 or 6.0 mg of deslorelin. On the first day of treatment and then on an annual basis, blood testosterone concentrations were analysed, testicular measurements were taken, appearance of penile spikes was determined, and semen was collected and evaluated. Pregnancy rates of mated or inseminated females were determined. A dose of 6 mg of deslorelin suppressed reproduction for at least 1 year, whereas with 4.7 and 5 mg of deslorelin, 3 of 17 males had a few non-motile spermatozoa in their ejaculates. All testosterone concentrations were basal at 1 year post-implant and no side effects were observed. We concluded that deslorelin implantation, at a dose of 6 mg, was a safe and reliable method of annual contraception in male cheetahs.

  1. Male mealworm beetles increase resting metabolic rate under terminal investment.

    PubMed

    Krams, I A; Krama, T; Moore, F R; Kivleniece, I; Kuusik, A; Freeberg, T M; Mänd, R; Rantala, M J; Daukšte, J; Mänd, M

    2014-03-01

    Harmful parasite infestation can cause energetically costly behavioural and immunological responses, with the potential to reduce host fitness and survival. It has been hypothesized that the energetic costs of infection cause resting metabolic rate (RMR) to increase. Furthermore, under terminal investment theory, individuals exposed to pathogens should allocate resources to current reproduction when life expectancy is reduced, instead of concentrating resources on an immune defence. In this study, we activated the immune system of Tenebrio molitor males via insertion of nylon monofilament, conducted female preference tests to estimate attractiveness of male odours and assessed RMR and mortality. We found that attractiveness of males coincided with significant down-regulation of their encapsulation response against a parasite-like intruder. Activation of the immune system increased RMR only in males with heightened odour attractiveness and that later suffered higher mortality rates. The results suggest a link between high RMR and mortality and support terminal investment theory in T. molitor. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  2. A MATHEMATICAL MODEL FOR THE KINETICS OF THE MALE REPRODUCTIVE ENDOCRINE SYSTEM

    EPA Science Inventory

    In this presentation a model for the hormonal regulation of the reproductive endocrine system in the adult male rat will be discussed. The model includes a description of the kinetics of the androgenic hormones testosterone and dihydrotestosterone, as well as the receptor-mediate...

  3. 48 CFR 970.5232-8 - Integrated accounting.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Integrated accounting. 970... for Management and Operating Contracts 970.5232-8 Integrated accounting. As prescribed in 970.3270(b)(2), insert the following clause: Integrated Accounting (DEC 2000) Integrated accounting procedures...

  4. Complex and extensive post-transcriptional regulation revealed by integrative proteomic and transcriptomic analysis of metabolite stress response in Clostridium acetobutylicum.

    PubMed

    Venkataramanan, Keerthi P; Min, Lie; Hou, Shuyu; Jones, Shawn W; Ralston, Matthew T; Lee, Kelvin H; Papoutsakis, E Terry

    2015-01-01

    Clostridium acetobutylicum is a model organism for both clostridial biology and solvent production. The organism is exposed to its own toxic metabolites butyrate and butanol, which trigger an adaptive stress response. Integrative analysis of proteomic and RNAseq data may provide novel insights into post-transcriptional regulation. The identified iTRAQ-based quantitative stress proteome is made up of 616 proteins with a 15 % genome coverage. The differentially expressed proteome correlated poorly with the corresponding differential RNAseq transcriptome. Up to 31 % of the differentially expressed proteins under stress displayed patterns opposite to those of the transcriptome, thus suggesting significant post-transcriptional regulation. The differential proteome of the translation machinery suggests that cells employ a different subset of ribosomal proteins under stress. Several highly upregulated proteins but with low mRNA levels possessed mRNAs with long 5'UTRs and strong RBS scores, thus supporting the argument that regulatory elements on the long 5'UTRs control their translation. For example, the oxidative stress response rubrerythrin was upregulated only at the protein level up to 40-fold without significant mRNA changes. We also identified many leaderless transcripts, several displaying different transcriptional start sites, thus suggesting mRNA-trimming mechanisms under stress. Downregulation of Rho and partner proteins pointed to changes in transcriptional elongation and termination under stress. The integrative proteomic-transcriptomic analysis demonstrated complex expression patterns of a large fraction of the proteome. Such patterns could not have been detected with one or the other omic analyses. Our analysis proposes the involvement of specific molecular mechanisms of post-transcriptional regulation to explain the observed complex stress response.

  5. Evidence for a hierarchical transcriptional circuit in Drosophila male germline involving testis-specific TAF and two gene-specific transcription factors, Mod and Acj6.

    PubMed

    Jiang, Mei; Gao, Zhengliang; Wang, Jian; Nurminsky, Dmitry I

    2018-01-01

    To analyze transcription factors involved in gene regulation by testis-specific TAF (tTAF), tTAF-dependent promoters were mapped and analyzed in silico. Core promoters show decreased AT content, paucity of classical promoter motifs, and enrichment with translation control element CAAAATTY. Scanning of putative regulatory regions for known position frequency matrices identified 19 transcription regulators possibly contributing to tTAF-driven gene expression. Decreased male fertility associated with mutation in one of the regulators, Acj6, indicates its involvement in male reproduction. Transcriptome study of testes from male mutants for tTAF, Acj6, and previously characterized tTAF-interacting factor Modulo implies the existence of a regulatory hierarchy of tTAF, Modulo and Acj6, in which Modulo and/or Acj6 regulate one-third of tTAF-dependent genes. © 2017 Federation of European Biochemical Societies.

  6. Hypokalemia decreases testosterone production in male mice by altering luteinizing hormone secretion.

    PubMed

    Sánchez-Capelo, A; Castells, M T; Cremades, A; Peñafiel, R

    1996-09-01

    Potassium deficiency produced by feeding mice a low potassium diet caused a marked decrease in plasma and testicular testosterone concentrations and a concomitant fall in the weight of seminal vesicles and in renal ornithine decarboxylase activity. All of these parameters were rapidly restored when potassium supply was normalized. Immunocytochemical analysis of gonadotropes and plasma LH values suggested that the pulsatile liberation of LH by the pituitary was impaired in the potassium-deficient male mice. Because the synthesis of testosterone in the potassium-deficient mice was stimulated by exogenous LH, hCG, or GnRH, one can conclude that alteration of the transcellular potassium gradient could affect the regulation of the hypothalamo-hypophyseal-testicular axis by affecting the pulsatile release of GnRH. Our results showing that the stimulation of LH secretion after castration was similar in control and potassium-deficient male mice suggest that a testicular factor(s) different from testosterone could be implicated in the abnormal regulation of LH secretion in potassium-deficient mice. We conclude that plasma potassium concentration is an important factor in the regulation of gonadotropin secretion and testicular functions.

  7. Initiative for standardization of reporting genetics of male infertility.

    PubMed

    Traven, Eva; Ogrinc, Ana; Kunej, Tanja

    2017-02-01

    The number of publications on research of male infertility is increasing. Technologies used in research of male infertility generate complex results and various types of data that need to be appropriately managed, arranged, and made available to other researchers for further use. In our previous study, we collected over 800 candidate loci for male fertility in seven mammalian species. However, the continuation of the work towards a comprehensive database of candidate genes associated with different types of idiopathic human male infertility is challenging due to fragmented information, obtained from a variety of technologies and various omics approaches. Results are published in different forms and usually need to be excavated from the text, which hinders the gathering of information. Standardized reporting of genetic anomalies as well as causative and risk factors of male infertility therefore presents an important issue. The aim of the study was to collect examples of diverse genomic loci published in association with human male infertility and to propose a standardized format for reporting genetic causes of male infertility. From the currently available data we have selected 75 studies reporting 186 representative genomic loci which have been proposed as genetic risk factors for male infertility. Based on collected and formatted data, we suggested a first step towards unification of reporting the genetics of male infertility in original and review studies. The proposed initiative consists of five relevant data types: 1) genetic locus, 2) race/ethnicity, number of participants (infertile/controls), 3) methodology, 4) phenotype (clinical data, disease ontology, and disease comorbidity), and 5) reference. The proposed form for standardized reporting presents a baseline for further optimization with additional genetic and clinical information. This data standardization initiative will enable faster multi-omics data integration, database development and sharing

  8. Polymorphism at the avpr1a locus in male prairie voles correlated with genetic but not social monogamy in field populations.

    PubMed

    Solomon, N G; Richmond, A R; Harding, P A; Fries, A; Jacquemin, S; Schaefer, R L; Lucia, K E; Keane, B

    2009-11-01

    Integrative studies of genetics, neurobiology and behaviour indicate that polymorphism in specific genes contributes to variation observed in some complex social behaviours. The neuropeptide arginine vasopressin plays an important role in the regulation of a variety of social behaviours, including social attachment of males to females, through its action on the vasopressin 1a receptor (V1aR). In socially monogamous prairie voles (Microtus ochrogaster), polymorphism in the length of microsatellite DNA within the regulatory region of the gene (avpr1a) encoding the V1aR predicts differences among males in neural expression of V1aRs and partner preference under laboratory conditions. However, understanding the extent to which V1aR mediates variation in prairie vole social and reproductive behaviour observed in nature requires investigating the consequences of avpr1a polymorphism and environmental influences under ecologically relevant conditions. We examined the relationship between avpr1a length polymorphism and monogamy among male prairie voles living in 0.1 ha enclosures during a time similar to their natural lifespan. We found no evidence that avpr1a genotype of males predicts variation in social monogamy measured in the field but some indices of social monogamy were affected by population density. Parentage data indicated that a male's avpr1a genotype significantly influenced the number of females with which he sired offspring and the total number of offspring sired. Total brain concentrations of V1aR mRNA were not associated with either male behaviour or avpr1a genotype. These data show that melding ecological field studies with neurogenetics can substantially augment our understanding of the effects of genes and environment on social behaviours.

  9. Thyroid hormones regulate anxiety in the male mouse.

    PubMed

    Buras, Alexander; Battle, Loxley; Landers, Evan; Nguyen, Tien; Vasudevan, Nandini

    2014-02-01

    Thyroid hormone levels are implicated in mood disorders in the adult human but the mechanisms remain unclear partly because, in rodent models, more attention has been paid to the consequences of perinatal hypo and hyperthyroidism. Thyroid hormones act via the thyroid hormone receptor (TR) α and β isoforms, both of which are expressed in the limbic system. TR's modulate gene expression via both unliganded and liganded actions. Though the thyroid hormone receptor (TR) knockouts and a transgenic TRα1 knock-in mouse have provided us valuable insight into behavioral phenotypes such as anxiety and depression, it is not clear if this is because of the loss of unliganded actions or liganded actions of the receptor or due to locomotor deficits. We used a hypothyroid mouse model and supplementation with tri-iodothyronine (T3) or thyroxine (T4) to investigate the consequences of dysthyroid hormone levels on behaviors that denote anxiety. Our data from the open field and the light-dark transition tests suggest that adult onset hypothyroidism in male mice produces a mild anxiogenic effect that is possibly due to unliganded receptor actions. T3 or T4 supplementation reverses this phenotype and euthyroid animals show anxiety that is intermediate between the hypothyroid and thyroid hormone supplemented groups. In addition, T3 but not T4 supplemented animals have lower spine density in the CA1 region of the hippocampus and in the central amygdala suggesting that T3-mediated rescue of the hypothyroid state might be due to lower neuronal excitability in the limbic circuit. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Identification and function of proteolysis regulators in seminal fluid.

    PubMed

    Laflamme, Brooke A; Wolfner, Mariana F

    2013-02-01

    Proteins in the seminal fluid of animals with internal fertilization effect numerous responses in mated females that impact both male and female fertility. Among these proteins is the highly represented class of proteolysis regulators (proteases and their inhibitors). Though proteolysis regulators have now been identified in the seminal fluid of all animals in which proteomic studies of the seminal fluid have been conducted (as well as several other species in which they have not), a unified understanding of the importance of proteolysis to male fertilization success and other reproductive processes has not yet been achieved. In this review, we provide an overview of the identification of proteolysis regulators in the seminal fluid of humans and Drosophila melanogaster, the two species with the most comprehensively known seminal fluid proteomes. We also highlight reports demonstrating the functional significance of specific proteolysis regulators in reproductive and post-mating processes. Finally, we make broad suggestions for the direction of future research into the roles of both active seminal fluid proteolysis regulators and their inactive homologs, another significant class of seminal fluid proteins. We hope that this review aids researchers in pursuing a coordinated study of the functional significance of proteolysis regulators in semen. Copyright © 2012 Wiley Periodicals, Inc.

  11. An integrated mechanism of pediatric pseudotumor cerebri syndrome: evidence of bioenergetic and hormonal regulation of cerebrospinal fluid dynamics

    PubMed Central

    Sheldon, Claire A.; Kwon, Young Joon; Liu, Grant T.; McCormack, Shana E.

    2015-01-01

    Pseudotumor cerebri syndrome (PTCS) is defined by the presence of elevated intracranial pressure (ICP) in the setting of normal brain parenchyma and cerebrospinal fluid (CSF). Headache, vision changes, and papilledema are common presenting features. Up to 10% of appropriately treated patients may experience permanent visual loss. The mechanism(s) underlying PTCS is unknown. PTCS occurs in association with a variety of conditions, including kidney disease, obesity, and adrenal insufficiency, suggesting endocrine and/or metabolic derangements may occur. Recent studies suggest that fluid and electrolyte balance in renal epithelia is regulated by a complex interaction of metabolic and hormonal factors; these cells share many of the same features as the choroid plexus cells in the central nervous system (CNS) responsible for regulation of CSF dynamics. Thus, we posit that similar factors may influence CSF dynamics in both types of fluid-sensitive tissues. Specifically, we hypothesize that, in patients with PTCS, mitochondrial metabolites (glutamate, succinate) and steroid hormones (cortisol, aldosterone) regulate CSF production and/or absorption. In this integrated mechanism review, we consider the clinical and molecular evidence for each metabolite and hormone in turn. We illustrate how related intracellular signaling cascades may converge in the choroid plexus, drawing on evidence from functionally similar tissues. PMID:25420176

  12. Profile of Metacognition of Mathematics Pre-Service Teachers in Understanding the Concept of Integral Calculus with Regard Gender Differences

    NASA Astrophysics Data System (ADS)

    Misu, L.; Budayasa, I. K.; Lukito, A.

    2018-01-01

    This research is to describe metacognition profile of female and male mathematics’ pre-service teachers in understanding the concept of integral calculus. The subjects of this study are one female and 1 male mathematics’ pre-service teachers who have studied integral calculus. This research type is an explorative study with the qualitative approach. The main data collection of this research was obtained by using Interview technique. In addition, there are supporting data which is the result of the written work of research subjects (SP) in understanding the question of integral calculus. The results of this study are as follows: There is a difference in metacognition profiles between male and female mathematics’ pre-service teachers in the understanding concept of integral calculus in the interpreting category, especially the definite integral concept. While in the category of exemplifying, there is no difference in metacognition profile between male and female mathematics’ pre-service teachers either the definite integral concept and the indefinite integral concept.

  13. Integrated regulatory network reveals novel candidate regulators in the development of negative energy balance in cattle.

    PubMed

    Mozduri, Z; Bakhtiarizadeh, M R; Salehi, A

    2018-06-01

    Negative energy balance (NEB) is an altered metabolic state in modern high-yielding dairy cows. This metabolic state occurs in the early postpartum period when energy demands for milk production and maintenance exceed that of energy intake. Negative energy balance or poor adaptation to this metabolic state has important effects on the liver and can lead to metabolic disorders and reduced fertility. The roles of regulatory factors, including transcription factors (TFs) and micro RNAs (miRNAs) have often been separately studied for evaluating of NEB. However, adaptive response to NEB is controlled by complex gene networks and still not fully understood. In this study, we aimed to discover the integrated gene regulatory networks involved in NEB development in liver tissue. We downloaded data sets including mRNA and miRNA expression profiles related to three and four cows with severe and moderate NEB, respectively. Our method integrated two independent types of information: module inference network by TFs, miRNAs and mRNA expression profiles (RNA-seq data) and computational target predictions. In total, 176 modules were predicted by using gene expression data and 64 miRNAs and 63 TFs were assigned to these modules. By using our integrated computational approach, we identified 13 TF-module and 19 miRNA-module interactions. Most of these modules were associated with liver metabolic processes as well as immune and stress responses, which might play crucial roles in NEB development. Literature survey results also showed that several regulators and gene targets have already been characterized as important factors in liver metabolic processes. These results provided novel insights into regulatory mechanisms at the TF and miRNA levels during NEB. In addition, the method described in this study seems to be applicable to construct integrated regulatory networks for different diseases or disorders.

  14. Trichostatin A (TSA) facilitates formation of partner preference in male prairie voles (Microtus ochrogaster).

    PubMed

    Duclot, F; Wang, H; Youssef, C; Liu, Y; Wang, Z; Kabbaj, M

    2016-05-01

    In the socially monogamous prairie voles (Microtus ochrogaster), the development of a social bonding is indicated by the formation of partner preference, which involves a variety of environmental and neurochemical factors and brain structures. In a most recent study in female prairie voles, we found that treatment with the histone deacetylase inhibitor trichostatin A (TSA) facilitates the formation of partner preference through up-regulation of oxytocin receptor (OTR) and vasopressin V1a receptor (V1aR) genes expression in the nucleus accumbens (NAcc). In the present study, we tested the hypothesis that TSA treatment also facilitates partner preference formation and alters OTR and V1aR genes expression in the NAcc in male prairie voles. We thus observed that central injection of TSA dose-dependently promoted the formation of partner preference in the absence of mating in male prairie voles. Interestingly, TSA treatment up-regulated OTR, but not V1aR, gene expression in the NAcc similarly as they were affected by mating - an essential process for naturally occurring partner preference. These data, together with others, not only indicate the involvement of epigenetic events but also the potential role of NAcc oxytocin in the regulation of partner preference in both male and female prairie voles. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Cellular signaling by fibroblast growth factors (FGFs) and their receptors (FGFRs) in male reproduction.

    PubMed

    Cotton, Leanne M; O'Bryan, Moira K; Hinton, Barry T

    2008-04-01

    The major function of the reproductive system is to ensure the survival of the species by passing on hereditary traits from one generation to the next. This is accomplished through the production of gametes and the generation of hormones that function in the maturation and regulation of the reproductive system. It is well established that normal development and function of the male reproductive system is mediated by endocrine and paracrine signaling pathways. Fibroblast growth factors (FGFs), their receptors (FGFRs), and signaling cascades have been implicated in a diverse range of cellular processes including: proliferation, apoptosis, cell survival, chemotaxis, cell adhesion, motility, and differentiation. The maintenance and regulation of correct FGF signaling is evident from human and mouse genetic studies which demonstrate that mutations leading to disruption of FGF signaling cause a variety of developmental disorders including dominant skeletal diseases, infertility, and cancer. Over the course of this review, we will provide evidence for differential expression of FGFs/FGFRs in the testis, male germ cells, the epididymis, the seminal vesicle, and the prostate. We will show that this signaling cascade has an important role in sperm development and maturation. Furthermore, we will demonstrate that FGF/FGFR signaling is essential for normal epididymal function and prostate development. To this end, we will provide evidence for the involvement of the FGF signaling system in the regulation and maintenance of the male reproductive system.

  16. Medico-Artistic Complicities on Swedish Stages: The Boys in the Band and the Regulation of Gay Male Representation in the Welfare State.

    PubMed

    Gindt, Dirk

    2016-01-01

    Seeking to understand the highly unfavorable conditions for the development of gay male theater in Sweden, this essay engages in a historical study of the national opening of Mart Crowley's The Boys in the Band at Malmö City Theatre in 1970. Propelled by a Foucauldian-inspired theoretical approach, it identifies the subtle, yet highly effective, measures of control that the, at the time, social democratic welfare state exercised over representations of homosexuality on stage. State representatives, who complied with the official political and medical doctrine that homosexuality was a mental illness and posed a potential threat to social stability, interfered at various levels of the production, including the rehearsal process and post-performance talks between cast members and audiences. This alliance between Swedish theaters and members of the medical, psychological, and sexological professions constituted a medico-artistic complicity that supervised and regulated early attempts of gay representation on stage.

  17. Hepatic Long Intergenic Noncoding RNAs: High Promoter Conservation and Dynamic, Sex-Dependent Transcriptional Regulation by Growth Hormone

    PubMed Central

    Melia, Tisha; Hao, Pengying; Yilmaz, Feyza

    2015-01-01

    Long intergenic noncoding RNAs (lincRNAs) are increasingly recognized as key chromatin regulators, yet few studies have characterized lincRNAs in a single tissue under diverse conditions. Here, we analyzed 45 mouse liver RNA sequencing (RNA-Seq) data sets collected under diverse conditions to systematically characterize 4,961 liver lincRNAs, 59% of them novel, with regard to gene structures, species conservation, chromatin accessibility, transcription factor binding, and epigenetic states. To investigate the potential for functionality, we focused on the responses of the liver lincRNAs to growth hormone stimulation, which imparts clinically relevant sex differences to hepatic metabolism and liver disease susceptibility. Sex-biased expression characterized 247 liver lincRNAs, with many being nuclear RNA enriched and regulated by growth hormone. The sex-biased lincRNA genes are enriched for nearby and correspondingly sex-biased accessible chromatin regions, as well as sex-biased binding sites for growth hormone-regulated transcriptional activators (STAT5, hepatocyte nuclear factor 6 [HNF6], FOXA1, and FOXA2) and transcriptional repressors (CUX2 and BCL6). Repression of female-specific lincRNAs in male liver, but not that of male-specific lincRNAs in female liver, was associated with enrichment of H3K27me3-associated inactive states and poised (bivalent) enhancer states. Strikingly, we found that liver-specific lincRNA gene promoters are more highly species conserved and have a significantly higher frequency of proximal binding by liver transcription factors than liver-specific protein-coding gene promoters. Orthologs for many liver lincRNAs were identified in one or more supraprimates, including two rat lincRNAs showing the same growth hormone-regulated, sex-biased expression as their mouse counterparts. This integrative analysis of liver lincRNA chromatin states, transcription factor occupancy, and growth hormone regulation provides novel insights into the

  18. Water level management of lakes connected to regulated rivers: An integrated modeling and analytical methodology

    NASA Astrophysics Data System (ADS)

    Hu, Tengfei; Mao, Jingqiao; Pan, Shunqi; Dai, Lingquan; Zhang, Peipei; Xu, Diandian; Dai, Huichao

    2018-07-01

    Reservoir operations significantly alter the hydrological regime of the downstream river and river-connected lake, which has far-reaching impacts on the lake ecosystem. To facilitate the management of lakes connected to regulated rivers, the following information must be provided: (1) the response of lake water levels to reservoir operation schedules in the near future and (2) the importance of different rivers in terms of affecting the water levels in different lake regions of interest. We develop an integrated modeling and analytical methodology for the water level management of such lakes. The data-driven method is used to model the lake level as it has the potential of producing quick and accurate predictions. A new genetic algorithm-based synchronized search is proposed to optimize input variable time lags and data-driven model parameters simultaneously. The methodology also involves the orthogonal design and range analysis for extracting the influence of an individual river from that of all the rivers. The integrated methodology is applied to the second largest freshwater lake in China, the Dongting Lake. The results show that: (1) the antecedent lake levels are of crucial importance for the current lake level prediction; (2) the selected river discharge time lags reflect the spatial heterogeneity of the rivers' impacts on lake level changes; (3) the predicted lake levels are in very good agreement with the observed data (RMSE ≤ 0.091 m; R2 ≥ 0.9986). This study demonstrates the practical potential of the integrated methodology, which can provide both the lake level responses to future dam releases and the relative contributions of different rivers to lake level changes.

  19. Sexual selection in true fruit flies (Diptera: Tephritidae): transcriptome and experimental evidences for phytochemicals increasing male competitive ability.

    PubMed

    Kumaran, Nagalingam; Prentis, Peter J; Mangalam, Kalimuthu P; Schutze, Mark K; Clarke, Anthony R

    2014-09-01

    In male tephritid fruit flies of the genus Bactrocera, feeding on secondary plant compounds (sensu lato male lures = methyl eugenol, raspberry ketone and zingerone) increases male mating success. Ingested male lures alter the male pheromonal blend, normally making it more attractive to females and this is considered the primary mechanism for the enhanced mating success. However, the male lures raspberry ketone and zingerone are known, across a diverse range of other organisms, to be involved in increasing energy metabolism. If this also occurs in Bactrocera, then this may represent an additional benefit to males as courtship is metabolically expensive and lure feeding may increase a fly's short-term energy. We tested this hypothesis by performing comparative RNA-seq analysis between zingerone-fed and unfed males of Bactrocera tryoni. We also carried out behavioural assays with zingerone- and cuelure-fed males to test whether they became more active. RNA-seq analysis revealed, in zingerone-fed flies, up-regulation of 3183 genes with homologues transcripts to those known to regulate intermale aggression, pheromone synthesis, mating and accessory gland proteins, along with significant enrichment of several energy metabolic pathways and gene ontology terms. Behavioural assays show significant increases in locomotor activity, weight reduction and successful mating after mounting; all direct/indirect measures of increased activity. These results suggest that feeding on lures leads to complex physiological changes, which result in more competitive males. These results do not negate the pheromone effect, but do strongly suggest that the phytochemical-induced sexual selection is governed by both female preference and male competitive mechanisms. © 2014 John Wiley & Sons Ltd.

  20. Data Integrity: History, Issues, and Remediation of Issues.

    PubMed

    Rattan, Anil K

    2018-01-01

    Data integrity is critical to regulatory compliance, and the fundamental reason for 21 CFR Part 11 published by the U.S. Food and Drug Administration (FDA). FDA published the first guideline in 1963, and since then FDA and European Union (EU) have published numerous guidelines on various topics related to data integrity for the pharmaceutical industry. Regulators wanted to make certain that industry capture accurate data during the drug development lifecycle and through commercialization-consider the number of warning letters issued lately by inspectors across the globe on data integrity. This article discusses the history of regulations put forward by various regulatory bodies, the term ALCOA Plus adopted by regulators, the impact of not following regulations, and some prevention methods by using some simple checklists, self-audit, and self-inspection techniques. FDA uses the acronym ALCOA to define its expectations of electronic data. ALCOA stands for Attributable, Legible, Contemporaneous, Original, and Accurate. ALCOA was further expanded to ALCOA Plus, and the Plus means Enduring, Available and Accessible, Complete, Consistent, Credible, and Corroborated. If we do not follow the regulations as written, then there is a huge risk. This article covers some of the risk aspects. To prevent data integrity, various solutions can be implemented such as a simple checklist for various systems, self-audit, and self-inspections. To do that we have to develop strategy, people, implement better business processes, and gain a better understanding of data lifecycle as well as technology. LAY ABSTRACT: If one does a Google search on "What is data integrity?" the first page will give the definition of data integrity, how to learn more about data integrity, the history of data integrity, risk management of data integrity, and at the top about various U.S. Food and Drug Administration (FDA) and European Union (EU) regulations. Data integrity is nothing but about accuracy of data

  1. Melatonin and male reproductive health: relevance of darkness and antioxidant properties.

    PubMed

    Rocha, C S; Rato, L; Martins, A D; Alves, M G; Oliveira, P F

    2015-01-01

    The pineal hormone melatonin controls several physiological functions that reach far beyond the regulation of the circadian rhythm. Moreover, it can be produced in extra-pineal organs such as reproductive organs. The role of melatonin in the mammalian seasonal and circadian rhythm is well known. Nevertheless, its overall effect in male reproductive physiology remains largely unknown. Melatonin is a very powerful endogenous antioxidant that can also be exogenously taken safely. Interestingly, its antioxidant properties have been consistently reported to improve the male reproductive dysfunctions associated with pathological conditions and also with the exposure to toxicants. Nevertheless, the exact molecular mechanisms by which melatonin exerts its action in the male reproductive system remain a matter of debate. Herein, we propose to present an up-to-date overview of the melatonin effects in the male reproductive health and debate future directions to disclose possible sites of melatonin action in male reproductive system. We will discuss not only the role of melatonin during darkness and sleep but also the importance of the antioxidant properties of this hormone to male fertility. Since melatonin readily crosses the physiological barriers, such as the blood-testis barrier, and has a very low toxicity, it appears as an excellent candidate in the prevention and/or treatment of the multiple male reproductive dysfunctions associated with various pathologies.

  2. Behavioral and physiological polymorphism in males of the austral lizard Liolaemus sarmientoi.

    PubMed

    Fernández, Jimena B; Bastiaans, Elizabeth; Medina, Marlin; Méndez De la Cruz, Fausto R; Sinervo, Barry R; Ibargüengoytía, Nora R

    2018-02-01

    Integrative behavioral studies show that the interplay between individual physiology and social behavior influences the ecology of the species, ultimately affecting individual fitness. Particularly in lizards, color polymorphism is associated with differential behaviors and reproductive strategies, which are evident in mature males during the mating season. Dominant males generally have greater endurance, higher body temperature, and larger bodies than submissive males, so they can acquire and defend larger territories and have greater access to females for mating. We studied whether the color morphs observed in males of one of the world's southernmost reptiles, Liolaemus sarmientoi, are related to behavioral variation during agonistic interactions, thermal physiology, morphology, and/or locomotor stamina. Liolaemus sarmientoi males exhibit three color morphs: red (RR), red-yellow (RY), and yellow (YY). These lizards exhibit subtle behavioral displays and we did not observe stamina differences among morphs. However, we found that RR males are more aggressive than YY males during agonistic encounters. In addition, greater body temperature change during trials, higher field body temperatures, and greater head sizes of RR males compared to RY or YY indicate that RR is a dominant morph, which may influence their ability to acquire and defend territory and tactics for achieving reproductive success.

  3. Deletion analysis of male sterility effects of t-haplotypes in the mouse.

    PubMed

    Bennett, D; Artzt, K

    1990-01-01

    We present data on the effects of three chromosome 17 deletions on transmission ratio distortion (TRD) and sterility of several t-haplotypes. All three deletions have similar effects on male TRD: that is, Tdel/tcomplete genotypes all transmit their t-haplotype in very high proportion. However, each deletion has different effects on sterility of heterozygous males, with TOr/t being fertile, Thp/t less fertile, and TOrl/t still less fertile. These data suggest that wild-type genes on chromosomes homologous to t-haplotypes can be important regulators of both TRD and fertility in males, and that the wild-type genes concerned with TRD and fertility are at least to some extent different. The data also provide a rough map of the positions of these genes.

  4. Differential effects of zinc exposure on male and female oysters (Crassostrea angulata) as revealed by label-free quantitative proteomics.

    PubMed

    Luo, Lianzhong; Zhang, Qinghong; Kong, Xue; Huang, Heqing; You, Weiwei; Ke, Caihuan

    2017-10-01

    Oysters accumulate Zn as an adaptation to Zn exposure; however, it is not known whether male and female oysters respond differently to Zn exposure. Proteomic and real-time polymerase chain reaction analyses were used to investigate differential responses of male and female oysters (Crassostrea angulata) to Zn exposure. After exposure to 50 μg L -1 or 500 μg L -1 Zn for 30 d, gonads of female oysters accumulated more Zn than those of males, and gonadal development was accelerated in females but was abnormal in males. Differentially expressed proteins after exposure to Zn were identified and shown to function in Zn transport, Ca transport, phosphate metabolism, energy metabolism, immune regulation, oxidative stress responses, gene expression regulation, and fat metabolism. Proteins with functions in Zn transportation and storage, and multifunctional proteins, such as hemicentin-1 and histidinol dehydrogenase, were expressed at significantly higher levels in the gonads of female than male oysters after Zn exposure. Environ Toxicol Chem 2017;36:2602-2613. © 2017 SETAC. © 2017 SETAC.

  5. THE DEVELOPMENT OF SEXUAL DIMORPHISM: STUDIES OF THE C. ELEGANS MALE

    PubMed Central

    Emmons, Scott W.

    2014-01-01

    Studies of the development of the C. elegans male have been carried out with the aim of understanding the basis of sexual dimorphism. Postembryonic development of the two C. elegans sexes differs extensively. Development along either the hermaphrodite or male pathway is specified initially by the X to autosome ratio. The regulatory events initiated by this ratio include a male-determining paracrine intercellular signal. Expression of this signal leads to different consequences in three regions of the body: the non-gonadal soma, the somatic parts of the gonad, and the germ line. In the non-gonadal soma, activity of the key Zn-finger transcription factor TRA 1 determines hermaphrodite development; in its absence, the male pathway is followed. Only a few genes directly regulated by TRA 1 are currently known, including members of the evolutionarily conserved, male-determining DM domain Zn-finger transcription factors. In the somatic parts of the gonad and germ line, absence of TRA 1 activity is not sufficient for full expression of the male pathway. Several additional transcription factors involved have been identified. In the germ line, regulatory genes for sperm development that act at the level of RNA in the cytoplasm play a prominent role. PMID:25262817

  6. Taste receptor polymorphisms and male infertility.

    PubMed

    Gentiluomo, M; Crifasi, L; Luddi, A; Locci, D; Barale, R; Piomboni, P; Campa, D

    2017-11-01

    Are polymorphisms of taste receptor genes associated with male infertility? This study has showed the associations between three single nucleotide polymorphisms (SNPs) in taste receptors genes (TASR) and male infertility. Recent studies showed the expression of taste receptors in the testis and in spermatozoa, suggesting their possible role in infertility. The vast genetic variability in taste genes results in a large degree of diversity in various human phenotypes. In this study, we genotyped 19 SNPs in 12 taste related genes in a total of 494 Caucasian male patients undergoing semen evaluation at the Centre of Couple Sterility of the Siena University Hospital. Consecutive patients were enrolled during infertility investigations from October 2014 to February 2016. Median age of the patients was 36 years (18-58) and 141 were smokers. Genotyping was performed using the allele-specific PCR. The statistical analysis was carried out using generalized linear model (GLM) to explore the association between age, smoking, the genetic polymorphisms and sperm parameters. We observed that the homozygous carriers of the (G) allele of the TAS2R14-rs3741843 polymorphism showed a decreased sperm progressive motility compared to heterozygotes and (A) homozygotes (P = 0.003). Moreover, the homozygous carriers of the (T) allele of the TAS2R3-rs11763979 SNP showed fewer normal acrosome compared with the heterozygous and the homozygous carriers of the (G) allele (P = 0.002). Multiple comparisons correction was applied and the Bonferroni-corrected critical P-value was = 0.003. The analysis is restricted to SNPs within genes and to men of Caucasian ancestry. In silico analyses strongly point towards a functional effect of the two SNPs: TAS2R14-rs3741843 regulates TAS2R43 expression, a gene that is involved in cilia motility and therefore could influences sperm mobility; the (T) allele of TAS2R3-rs11763979 increases the expression of the WEE2 antisense RNA one gene (WEE2-AS1). According

  7. Differential regulation of apoptosis in slow and fast twitch muscles of aged female F344BN rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rice, Kevin M.; Manne, Nandini D. P. K.; Gadde, Murali K.

    Age-related muscle atrophy is characterized by decreases in muscle mass and is thought be mediated, at least in part, by increases in myocyte apoptosis. Recent data has demonstrated that the degree of muscle loss with aging may differ between males and females while other work has suggested that apoptosis as indicated by DNA fragmentation may be regulated differently in fast- and slow-twitch muscles. Herein, we investigate how aging affects the regulation of muscle apoptosis in the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles of young (6-month), aged (26-month), and very aged (30-month) female Fischer 344/NNiaHSD × Brown Norway/BiNiamore » (F344BN) rats. Tissue sections were stained with hydroethidium for ROS and protein extract was subjected to immunoblotting for assessing apoptotic markers. Our data suggest that decreases in muscle mass were associated with increased DNA fragmentation (TUNEL positive) and increases in reactive oxygen species (ROS) as determined by hydroethidium staining in both the EDL and soleus. Similar to our previous work using aged male animals, we observed that the time course and magnitude of changes in Bax, Bcl-2, caspase-3, caspase-9, and cleavage of α-fodrin protein were regulated differently between muscles. As a result, These data suggest that aging in the female F344BN rat is associated with decreases in muscle mass, elevations in ROS level, increased muscle cell DNA fragmentation, and alterations in cell membrane integrity and that apoptotic mechanisms may differ between fiber types.« less

  8. Differential regulation of apoptosis in slow and fast twitch muscles of aged female F344BN rats

    DOE PAGES

    Rice, Kevin M.; Manne, Nandini D. P. K.; Gadde, Murali K.; ...

    2015-03-28

    Age-related muscle atrophy is characterized by decreases in muscle mass and is thought be mediated, at least in part, by increases in myocyte apoptosis. Recent data has demonstrated that the degree of muscle loss with aging may differ between males and females while other work has suggested that apoptosis as indicated by DNA fragmentation may be regulated differently in fast- and slow-twitch muscles. Herein, we investigate how aging affects the regulation of muscle apoptosis in the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles of young (6-month), aged (26-month), and very aged (30-month) female Fischer 344/NNiaHSD × Brown Norway/BiNiamore » (F344BN) rats. Tissue sections were stained with hydroethidium for ROS and protein extract was subjected to immunoblotting for assessing apoptotic markers. Our data suggest that decreases in muscle mass were associated with increased DNA fragmentation (TUNEL positive) and increases in reactive oxygen species (ROS) as determined by hydroethidium staining in both the EDL and soleus. Similar to our previous work using aged male animals, we observed that the time course and magnitude of changes in Bax, Bcl-2, caspase-3, caspase-9, and cleavage of α-fodrin protein were regulated differently between muscles. As a result, These data suggest that aging in the female F344BN rat is associated with decreases in muscle mass, elevations in ROS level, increased muscle cell DNA fragmentation, and alterations in cell membrane integrity and that apoptotic mechanisms may differ between fiber types.« less

  9. Female contact modulates male aggression via a sexually dimorphic GABAergic circuit in Drosophila

    PubMed Central

    Yuan, Quan; Song, Yuanquan; Yang, Chung-Hui; Jan, Lily Yeh; Jan, Yuh Nung

    2014-01-01

    Intraspecific male-male aggression, important for sexual selection, is regulated by environment, experience and internal states through largely undefined molecular and cellular mechanisms. To understand the basic neural pathway underlying the modulation of this innate behavior, we established a behavioral paradigm in Drosophila melanogaster and investigated the relationship between sexual experience and aggression. In the presence of mating partners, adult male flies exhibited elevated levels of aggression, which was largely suppressed by prior exposure to females via a sexually dimorphic neural mechanism. The suppression involved the ability of male flies to detect females by contact chemosensation through the pheromone-sensing ion channel, ppk29, and was mediated by male specific GABAergic neurons acting upon GABA-a receptor RDL in target cells. Silencing or activation of this circuit led to dis-inhibition or elimination of sex-related aggression, respectively. We propose that the GABAergic inhibition represents a critical cellular mechanism that enables prior experience to modulate aggression. PMID:24241395

  10. Chinmo prevents transformer alternative splicing to maintain male sex identity.

    PubMed

    Grmai, Lydia; Hudry, Bruno; Miguel-Aliaga, Irene; Bach, Erika A

    2018-02-01

    Reproduction in sexually dimorphic animals relies on successful gamete production, executed by the germline and aided by somatic support cells. Somatic sex identity in Drosophila is instructed by sex-specific isoforms of the DMRT1 ortholog Doublesex (Dsx). Female-specific expression of Sex-lethal (Sxl) causes alternative splicing of transformer (tra) to the female isoform traF. In turn, TraF alternatively splices dsx to the female isoform dsxF. Loss of the transcriptional repressor Chinmo in male somatic stem cells (CySCs) of the testis causes them to "feminize", resembling female somatic stem cells in the ovary. This somatic sex transformation causes a collapse of germline differentiation and male infertility. We demonstrate this feminization occurs by transcriptional and post-transcriptional regulation of traF. We find that chinmo-deficient CySCs upregulate tra mRNA as well as transcripts encoding tra-splice factors Virilizer (Vir) and Female lethal (2)d (Fl(2)d). traF splicing in chinmo-deficient CySCs leads to the production of DsxF at the expense of the male isoform DsxM, and both TraF and DsxF are required for CySC sex transformation. Surprisingly, CySC feminization upon loss of chinmo does not require Sxl but does require Vir and Fl(2)d. Consistent with this, we show that both Vir and Fl(2)d are required for tra alternative splicing in the female somatic gonad. Our work reveals the need for transcriptional regulation of tra in adult male stem cells and highlights a previously unobserved Sxl-independent mechanism of traF production in vivo. In sum, transcriptional control of the sex determination hierarchy by Chinmo is critical for sex maintenance in sexually dimorphic tissues and is vital in the preservation of fertility.

  11. Chinmo prevents transformer alternative splicing to maintain male sex identity

    PubMed Central

    Hudry, Bruno; Miguel-Aliaga, Irene

    2018-01-01

    Reproduction in sexually dimorphic animals relies on successful gamete production, executed by the germline and aided by somatic support cells. Somatic sex identity in Drosophila is instructed by sex-specific isoforms of the DMRT1 ortholog Doublesex (Dsx). Female-specific expression of Sex-lethal (Sxl) causes alternative splicing of transformer (tra) to the female isoform traF. In turn, TraF alternatively splices dsx to the female isoform dsxF. Loss of the transcriptional repressor Chinmo in male somatic stem cells (CySCs) of the testis causes them to “feminize”, resembling female somatic stem cells in the ovary. This somatic sex transformation causes a collapse of germline differentiation and male infertility. We demonstrate this feminization occurs by transcriptional and post-transcriptional regulation of traF. We find that chinmo-deficient CySCs upregulate tra mRNA as well as transcripts encoding tra-splice factors Virilizer (Vir) and Female lethal (2)d (Fl(2)d). traF splicing in chinmo-deficient CySCs leads to the production of DsxF at the expense of the male isoform DsxM, and both TraF and DsxF are required for CySC sex transformation. Surprisingly, CySC feminization upon loss of chinmo does not require Sxl but does require Vir and Fl(2)d. Consistent with this, we show that both Vir and Fl(2)d are required for tra alternative splicing in the female somatic gonad. Our work reveals the need for transcriptional regulation of tra in adult male stem cells and highlights a previously unobserved Sxl-independent mechanism of traF production in vivo. In sum, transcriptional control of the sex determination hierarchy by Chinmo is critical for sex maintenance in sexually dimorphic tissues and is vital in the preservation of fertility. PMID:29389999

  12. Integrative screening approach identifies regulators of polyploidization and targets for acute megakaryocytic leukemia

    PubMed Central

    Wen, Qiang; Goldenson, Benjamin; Silver, Serena J.; Schenone, Monica; Dancik, Vladimir; Huang, Zan; Wang, Ling-Zhi; Lewis, Timothy; An, W. Frank; Li, Xiaoyu; Bray, Mark-Anthony; Thiollier, Clarisse; Diebold, Lauren; Gilles, Laure; Vokes, Martha S.; Moore, Christopher B.; Bliss-Moreau, Meghan; VerPlank, Lynn; Tolliday, Nicola J.; Mishra, Rama; Vemula, Sasidhar; Shi, Jianjian; Wei, Lei; Kapur, Reuben; Lopez, Cécile K.; Gerby, Bastien; Ballerini, Paola; Pflumio, Francoise; Gilliland, D. Gary; Goldberg, Liat; Birger, Yehudit; Izraeli, Shai; Gamis, Alan S.; Smith, Franklin O.; Woods, William G.; Taub, Jeffrey; Scherer, Christina A.; Bradner, James; Goh, Boon-Cher; Mercher, Thomas; Carpenter, Anne E.; Gould, Robert J.; Clemons, Paul A.; Carr, Steven A.; Root, David E.; Schreiber, Stuart L.; Stern, Andrew M.; Crispino, John D.

    2012-01-01

    Summary The mechanism by which cells decide to skip mitosis to become polyploid is largely undefined. Here we used a high-content image-based screen to identify small-molecule probes that induce polyploidization of megakaryocytic leukemia cells and serve as perturbagens to help understand this process. We found that dimethylfasudil (diMF, H-1152P) selectively increased polyploidization, mature cell-surface marker expression, and apoptosis of malignant megakaryocytes. A broadly applicable, highly integrated target identification approach employing proteomic and shRNA screening revealed that a major target of diMF is Aurora A kinase (AURKA), which has not been studied extensively in megakaryocytes. Moreover, we discovered that MLN8237 (Alisertib), a selective inhibitor of AURKA, induced polyploidization and expression of mature megakaryocyte markers in AMKL blasts and displayed potent anti-AMKL activity in vivo. This research provides the rationale to support clinical trials of MLN8237 and other inducers of polyploidization in AMKL. Finally, we have identified five networks of kinases that regulate the switch to polyploidy. PMID:22863010

  13. Opuntia humifusa Supplementation Increased Bone Density by Regulating Parathyroid Hormone and Osteocalcin in Male Growing Rats

    PubMed Central

    Kang, Junyong; Park, Jinho; Choi, Seong Hee; Igawa, Shoji; Song, Youngju

    2012-01-01

    We investigated the effect of Opuntia humifusa (O. humifusa) supplementation on bone density and related hormone secretion in growing male rats. Sixteen six-week-old male Sprague-Dawley rats were randomly divided into two groups; control diet group (CG, n = 8), and experimental diet group (EG, n = 8). The rats in the CG were given a control diet and those in the EG were given 5% O. humifusa added to the control diet for eight weeks. The serum OC level of the EG was significantly higher than that of the CG, and the serum parathyroid hormone (PTH) level of EG was significantly lower than that of the CG. In addition, the femoral and tibial BMD of the EG were significantly higher values than those of the CG, and the tibial BMC of the EG was significantly higher than that of the CG. These results suggest that O. humifusa supplementation has a positive effect on bone density by suppressing PTH and increasing the OC level in growing male rats. PMID:22837661

  14. The Sex Differences in Regulating Unpleasant Emotion by Expressive Suppression: Extraversion Matters

    PubMed Central

    Cai, Ayan; Lou, Yixue; Long, Quanshan; Yuan, Jiajin

    2016-01-01

    Males are known for more suppression of emotional displays than females. However, when the emotion regulation effect of expressive suppression is greater in males, and how this sex difference varies with emotion display-related personality (e.g., extraversion), are undetermined. Event-related potentials were recorded while male and female participants different in extraversion were required to attend to or suppress emotional expression to negative pictures. Sex and extraversion did not modulate self-reported emotional experience. However, late positive potential (LPP) amplitudes showed an extraversion-moderated sex difference in the 2000–3000 ms and the 3000–4000 ms time epochs. LPP amplitudes were decreased during suppression versus viewing conditions in ambivert males, while this effect was absent in ambivert females. However, the LPP amplitudes of extraverts were similar for suppression and viewing conditions, irrespective of sex and timing. Regardless of early, middle, or late time windows, LPP amplitudes were positively related to self-reported emotion. These results suggest a male advantage for using expressive suppression for emotion regulation in non-extraverted, ambivert individuals. PMID:27458408

  15. The Sex Differences in Regulating Unpleasant Emotion by Expressive Suppression: Extraversion Matters.

    PubMed

    Cai, Ayan; Lou, Yixue; Long, Quanshan; Yuan, Jiajin

    2016-01-01

    Males are known for more suppression of emotional displays than females. However, when the emotion regulation effect of expressive suppression is greater in males, and how this sex difference varies with emotion display-related personality (e.g., extraversion), are undetermined. Event-related potentials were recorded while male and female participants different in extraversion were required to attend to or suppress emotional expression to negative pictures. Sex and extraversion did not modulate self-reported emotional experience. However, late positive potential (LPP) amplitudes showed an extraversion-moderated sex difference in the 2000-3000 ms and the 3000-4000 ms time epochs. LPP amplitudes were decreased during suppression versus viewing conditions in ambivert males, while this effect was absent in ambivert females. However, the LPP amplitudes of extraverts were similar for suppression and viewing conditions, irrespective of sex and timing. Regardless of early, middle, or late time windows, LPP amplitudes were positively related to self-reported emotion. These results suggest a male advantage for using expressive suppression for emotion regulation in non-extraverted, ambivert individuals.

  16. Explicit and Implicit Emotion Regulation: A Dual-Process Framework

    PubMed Central

    Gyurak, Anett; Gross, James J.; Etkin, Amit

    2012-01-01

    It is widely acknowledged that emotions can be regulated in an astonishing variety of ways. Most research to date has focused on explicit (effortful) forms of emotion regulation. However, there is growing research interest in implicit (automatic) forms of emotion regulation. To organize emerging findings, we present a dual-process framework that integrates explicit and implicit forms of emotion regulation, and argue that both forms of regulation are necessary for well-being. In the first section of this review, we provide a broad overview of the construct of emotion regulation, with an emphasis on explicit and implicit processes. In the second section, we focus on explicit emotion regulation, considering both neural mechanisms that are associated with these processes and their experiential and physiological consequences. In the third section, we turn to several forms of implicit emotion regulation, and integrate the burgeoning literature in this area. We conclude by outlining open questions and areas for future research. PMID:21432682

  17. Master Regulators of Oncogenic KRAS Response in Pancreatic Cancer: An Integrative Network Biology Analysis

    PubMed Central

    2017-01-01

    Background KRAS is the most frequently mutated gene in pancreatic ductal adenocarcinoma (PDAC), but the mechanisms underlying the transcriptional response to oncogenic KRAS are still not fully understood. We aimed to uncover transcription factors that regulate the transcriptional response of oncogenic KRAS in pancreatic cancer and to understand their clinical relevance. Methods and Findings We applied a well-established network biology approach (master regulator analysis) to combine a transcriptional signature for oncogenic KRAS derived from a murine isogenic cell line with a coexpression network derived by integrating 560 human pancreatic cancer cases across seven studies. The datasets included the ICGC cohort (n = 242), the TCGA cohort (n = 178), and five smaller studies (n = 17, 25, 26, 36, and 36). 55 transcription factors were coexpressed with a significant number of genes in the transcriptional signature (gene set enrichment analysis [GSEA] p < 0.01). Community detection in the coexpression network identified 27 of the 55 transcription factors contributing to three major biological processes: Notch pathway, down-regulated Hedgehog/Wnt pathway, and cell cycle. The activities of these processes define three distinct subtypes of PDAC, which demonstrate differences in survival and mutational load as well as stromal and immune cell composition. The Hedgehog subgroup showed worst survival (hazard ratio 1.73, 95% CI 1.1 to 2.72, coxPH test p = 0.018) and the Notch subgroup the best (hazard ratio 0.62, 95% CI 0.42 to 0.93, coxPH test p = 0.019). The cell cycle subtype showed highest mutational burden (ANOVA p < 0.01) and the smallest amount of stromal admixture (ANOVA p < 2.2e–16). This study is limited by the information provided in published datasets, not all of which provide mutational profiles, survival data, or the specifics of treatment history. Conclusions Our results characterize the regulatory mechanisms underlying the transcriptional response to oncogenic

  18. High-glucose diets have sex-specific effects on aging in C. elegans: toxic to hermaphrodites but beneficial to males.

    PubMed

    Liggett, Marjorie R; Hoy, Michael J; Mastroianni, Michael; Mondoux, Michelle A

    2015-06-01

    Diet and sex are important determinants of lifespan. In humans, high sugar diets, obesity, and type 2 diabetes correlate with decreased lifespan, and females generally live longer than males. The nematode Caenorhabditis elegans is a classical model for aging studies, and has also proven useful for characterizing the response to high-glucose diets. However, studies on male animals are lacking. We found a surprising dichotomy: glucose regulates lifespan and aging in a sex-specific manner, with beneficial effects on males compared to toxic effects on hermaphrodites. High-glucose diet resulted in greater mobility with age for males, along with a modest increase in median lifespan. In contrast, high-glucose diets decrease both lifespan and mobility for hermaphrodites. Understanding sex-specific responses to high-glucose diets will be important for determining which evolutionarily conserved glucose-responsive pathways that regulate aging are "universal" and which are likely to be cell-type or sex-specific.

  19. Highly tissue specific expression of Sphinx supports its male courtship related role in Drosophila melanogaster.

    PubMed

    Chen, Ying; Dai, Hongzheng; Chen, Sidi; Zhang, Luoying; Long, Manyuan

    2011-04-26

    Sphinx is a lineage-specific non-coding RNA gene involved in regulating courtship behavior in Drosophila melanogaster. The 5' flanking region of the gene is conserved across Drosophila species, with the proximal 300 bp being conserved out to D. virilis and a further 600 bp region being conserved amongst the melanogaster subgroup (D. melanogaster, D. simulans, D. sechellia, D. yakuba, and D. erecta). Using a green fluorescence protein transformation system, we demonstrated that a 253 bp region of the highly conserved segment was sufficient to drive sphinx expression in male accessory gland. GFP signals were also observed in brain, wing hairs and leg bristles. An additional ∼800 bp upstream region was able to enhance expression specifically in proboscis, suggesting the existence of enhancer elements. Using anti-GFP staining, we identified putative sphinx expression signal in the brain antennal lobe and inner antennocerebral tract, suggesting that sphinx might be involved in olfactory neuron mediated regulation of male courtship behavior. Whole genome expression profiling of the sphinx knockout mutation identified significant up-regulated gene categories related to accessory gland protein function and odor perception, suggesting sphinx might be a negative regulator of its target genes.

  20. Highly Tissue Specific Expression of Sphinx Supports Its Male Courtship Related Role in Drosophila melanogaster

    PubMed Central

    Chen, Sidi; Zhang, Luoying; Long, Manyuan

    2011-01-01

    Sphinx is a lineage-specific non-coding RNA gene involved in regulating courtship behavior in Drosophila melanogaster. The 5′ flanking region of the gene is conserved across Drosophila species, with the proximal 300 bp being conserved out to D. virilis and a further 600 bp region being conserved amongst the melanogaster subgroup (D. melanogaster, D. simulans, D. sechellia, D. yakuba, and D. erecta). Using a green fluorescence protein transformation system, we demonstrated that a 253 bp region of the highly conserved segment was sufficient to drive sphinx expression in male accessory gland. GFP signals were also observed in brain, wing hairs and leg bristles. An additional ∼800 bp upstream region was able to enhance expression specifically in proboscis, suggesting the existence of enhancer elements. Using anti-GFP staining, we identified putative sphinx expression signal in the brain antennal lobe and inner antennocerebral tract, suggesting that sphinx might be involved in olfactory neuron mediated regulation of male courtship behavior. Whole genome expression profiling of the sphinx knockout mutation identified significant up-regulated gene categories related to accessory gland protein function and odor perception, suggesting sphinx might be a negative regulator of its target genes. PMID:21541324

  1. Meiotic recombination counteracts male-biased mutation (male-driven evolution).

    PubMed

    Mawaribuchi, Shuuji; Ito, Michihiko; Ogata, Mitsuaki; Oota, Hiroki; Katsumura, Takafumi; Takamatsu, Nobuhiko; Miura, Ikuo

    2016-01-27

    Meiotic recombination is believed to produce greater genetic variation despite the fact that deoxyribonucleic acid (DNA)-replication errors are a major source of mutations. In some vertebrates, mutation rates are higher in males than in females, which developed the theory of male-driven evolution (male-biased mutation). However, there is little molecular evidence regarding the relationships between meiotic recombination and male-biased mutation. Here we tested the theory using the frog Rana rugosa, which has both XX/XY- and ZZ/ZW-type sex-determining systems within the species. The male-to-female mutation-rate ratio (α) was calculated from homologous sequences on the X/Y or Z/W sex chromosomes, which supported male-driven evolution. Surprisingly, each α value was notably higher in the XX/XY-type group than in the ZZ/ZW-type group, although α should have similar values within a species. Interestingly, meiotic recombination between homologous chromosomes did not occur except at terminal regions in males of this species. Then, by subdividing α into two new factors, a replication-based male-to-female mutation-rate ratio (β) and a meiotic recombination-based XX-to-XY/ZZ-to-ZW mutation-rate ratio (γ), we constructed a formula describing the relationship among a nucleotide-substitution rate and the two factors, β and γ. Intriguingly, the β- and γ-values were larger and smaller than 1, respectively, indicating that meiotic recombination might reduce male-biased mutations. © 2016 The Author(s).

  2. 48 CFR 1334.202 - Integrated baseline reviews.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... CATEGORIES OF CONTRACTING MAJOR SYSTEM ACQUISITION Earned Value Management System 1334.202 Integrated baseline reviews. An Integrated Baseline Review shall be conducted when an Earned Value Management System... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Integrated baseline...

  3. 48 CFR 1334.202 - Integrated baseline reviews.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... CATEGORIES OF CONTRACTING MAJOR SYSTEM ACQUISITION Earned Value Management System 1334.202 Integrated baseline reviews. An Integrated Baseline Review shall be conducted when an Earned Value Management System... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Integrated baseline...

  4. 48 CFR 1334.202 - Integrated baseline reviews.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... CATEGORIES OF CONTRACTING MAJOR SYSTEM ACQUISITION Earned Value Management System 1334.202 Integrated baseline reviews. An Integrated Baseline Review shall be conducted when an Earned Value Management System... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Integrated baseline...

  5. 48 CFR 1334.202 - Integrated baseline reviews.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... CATEGORIES OF CONTRACTING MAJOR SYSTEM ACQUISITION Earned Value Management System 1334.202 Integrated baseline reviews. An Integrated Baseline Review shall be conducted when an Earned Value Management System... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Integrated baseline...

  6. 48 CFR 1334.202 - Integrated baseline reviews.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... CATEGORIES OF CONTRACTING MAJOR SYSTEM ACQUISITION Earned Value Management System 1334.202 Integrated baseline reviews. An Integrated Baseline Review shall be conducted when an Earned Value Management System... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Integrated baseline...

  7. Spiroplasma infection causes either early or late male killing in Drosophila, depending on maternal host age

    NASA Astrophysics Data System (ADS)

    Kageyama, Daisuke; Anbutsu, Hisashi; Shimada, Masakazu; Fukatsu, Takema

    2007-04-01

    Symbiont-induced male-killing phenotypes have been found in a variety of insects. Conventionally, these phenotypes have been divided into two categories according to the timing of action: early male killing at embryonic stages and late male killing at late larval stages. In Drosophila species, endosymbiotic bacteria of the genus Spiroplasma have been known to cause early male killing. Here, we report that a spiroplasma strain normally causing early male killing also induces late male killing depending on the maternal host age: male-specific mortality of larvae and pupae was more frequently observed in the offspring of young females. As the lowest spiroplasma density and occasional male production were also associated with newly emerged females, we proposed the density-dependent hypothesis for the expression of early and late male-killing phenotypes. Our finding suggested that (1) early and late male-killing phenotypes can be caused by the same symbiont and probably by the same mechanism; (2) late male killing may occur as an attenuated expression of early male killing; (3) expression of early and late male-killing phenotypes may be dependent on the symbiont density, and thus, could potentially be affected by the host immunity and regulation; and (4) early male killing and late male killing could be alternative strategies adopted by microbial reproductive manipulators.

  8. MEDIATOR25 Acts as an Integrative Hub for the Regulation of Jasmonate-Responsive Gene Expression in Arabidopsis1[C][W

    PubMed Central

    Çevik, Volkan; Kidd, Brendan N.; Zhang, Peijun; Hill, Claire; Kiddle, Steve; Denby, Katherine J.; Holub, Eric B.; Cahill, David M.; Manners, John M.; Schenk, Peer M.; Beynon, Jim; Kazan, Kemal

    2012-01-01

    The PHYTOCHROME AND FLOWERING TIME1 gene encoding the MEDIATOR25 (MED25) subunit of the eukaryotic Mediator complex is a positive regulator of jasmonate (JA)-responsive gene expression in Arabidopsis (Arabidopsis thaliana). Based on the function of the Mediator complex as a bridge between DNA-bound transcriptional activators and the RNA polymerase II complex, MED25 has been hypothesized to function in association with transcriptional regulators of the JA pathway. However, it is currently not known mechanistically how MED25 functions to regulate JA-responsive gene expression. In this study, we show that MED25 physically interacts with several key transcriptional regulators of the JA signaling pathway, including the APETALA2 (AP2)/ETHYLENE RESPONSE FACTOR (ERF) transcription factors OCTADECANOID-RESPONSIVE ARABIDOPSIS AP2/ERF59 and ERF1 as well as the master regulator MYC2. Physical interaction detected between MED25 and four group IX AP2/ERF transcription factors was shown to require the activator interaction domain of MED25 as well as the recently discovered Conserved Motif IX-1/EDLL transcription activation motif of MED25-interacting AP2/ERFs. Using transcriptional activation experiments, we also show that OCTADECANOID-RESPONSIVE ARABIDOPSIS AP2/ERF59- and ERF1-dependent activation of PLANT DEFENSIN1.2 as well as MYC2-dependent activation of VEGETATIVE STORAGE PROTEIN1 requires a functional MED25. In addition, MED25 is required for MYC2-dependent repression of pathogen defense genes. These results suggest an important role for MED25 as an integrative hub within the Mediator complex during the regulation of JA-associated gene expression. PMID:22822211

  9. Laccase-13 Regulates Seed Setting Rate by Affecting Hydrogen Peroxide Dynamics and Mitochondrial Integrity in Rice.

    PubMed

    Yu, Yang; Li, Quan-Feng; Zhang, Jin-Ping; Zhang, Fan; Zhou, Yan-Fei; Feng, Yan-Zhao; Chen, Yue-Qin; Zhang, Yu-Chan

    2017-01-01

    Seed setting rate is one of the most important components of rice grain yield. To date, only several genes regulating setting rate have been identified in plant. In this study, we showed that laccase-13 ( OsLAC13 ), a member of laccase family genes which are known for their roles in modulating phenylpropanoid pathway and secondary lignification in cell wall, exerts a regulatory function in rice seed setting rate. OsLAC13 expressed in anthers and promotes hydrogen peroxide production both in vitro and in the filaments and anther connectives. Knock-out of OsLAC13 showed significantly increased seed setting rate, while overexpression of this gene exhibited induced mitochondrial damage and suppressed sugar transportation in anthers, which in turn affected seed setting rate. OsLAC13 also induced H 2 O 2 production and mitochondrial damage in the root tip cells which caused the lethal phenotype. We also showed that high abundant of OsmiR397, the suppressor of OsLAC13 mRNA, increased the seed setting rate of rice plants, and restrains H 2 O 2 accumulation in roots during oxidative stress. Our results suggested a novel regulatory role of OsLAC13 gene in regulating seed setting rate by affecting H 2 O 2 dynamics and mitochondrial integrity in rice.

  10. High-Fat Diet During Mouse Pregnancy and Lactation Targets GIP-Regulated Metabolic Pathways in Adult Male Offspring.

    PubMed

    Kruse, Michael; Keyhani-Nejad, Farnaz; Isken, Frank; Nitz, Barbara; Kretschmer, Anja; Reischl, Eva; de las Heras Gala, Tonia; Osterhoff, Martin A; Grallert, Harald; Pfeiffer, Andreas F H

    2016-03-01

    Maternal obesity is a worldwide problem associated with increased risk of metabolic diseases in the offspring. Genetic deletion of the gastric inhibitory polypeptide (GIP) receptor (GIPR) prevents high-fat diet (HFD)-induced obesity in mice due to specific changes in energy and fat cell metabolism. We investigated whether GIP-associated pathways may be targeted by fetal programming and mimicked the situation by exposing pregnant mice to control or HFD during pregnancy (intrauterine [IU]) and lactation (L). Male wild-type (WT) and Gipr(-/-) offspring received control chow until 25 weeks of age followed by 20 weeks of HFD. Gipr(-/-) offspring of mice exposed to HFD during IU/L became insulin resistant and obese and exhibited increased adipose tissue inflammation and decreased peripheral tissue substrate utilization after being reintroduced to HFD, similar to WT mice on regular chow during IU/L. They showed decreased hypothalamic insulin sensitivity compared with Gipr(-/-) mice on control diet during IU/L. DNA methylation analysis revealed increased methylation of CpG dinucleotides and differential transcription factor binding of promoter regions of genes involved in lipid oxidation in the muscle of Gipr(-/-) offspring on HFD during IU/L, which were inversely correlated with gene expression levels. Our data identify GIP-regulated metabolic pathways that are targeted by fetal programming. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  11. Calcium Influx and Male Fertility in the Context of the Sperm Proteome: An Update

    PubMed Central

    Rahman, Md Saidur; Kwon, Woo-Sung; Pang, Myung-Geol

    2014-01-01

    Freshly ejaculated spermatozoa are incapable or poorly capable of fertilizing an oocyte. The fertilization aptness of spermatozoa depends on the appropriate and time-dependent acquisition of hyperactivation, chemotaxis, capacitation, and the acrosome reaction, where calcium (Ca2+) is extensively involved in almost every step. A literature review showed that several ion channel proteins are likely responsible for regulation of the Ca2+ uptake in spermatozoa. Therefore, manipulation of the functions of channel proteins is closely related to Ca2+ influx, ultimately affecting male fertility. Recently, it has been shown that, together with different physiological stimuli, protein-protein interaction also modifies the Ca2+ influx mechanism in spermatozoa. Modern proteomic analyses have identified several sperm proteins, and, therefore, these findings might provide further insight into understanding the Ca2+ influx, protein functions, and regulation of fertility. The objective of this review was to synthesize the published findings on the Ca2+ influx mechanism in mammalian spermatozoa and its implications for the regulation of male fertility in the context of sperm proteins. Finally, Pathway Studio (9.0) was used to catalog the sperm proteins that regulate the Ca2+ influx signaling by using the information available from the PubMed database following a MedScan Reader (5.0) search. PMID:24877140

  12. Experimental increase of testosterone increases boldness and decreases anxiety in male African striped mouse helpers.

    PubMed

    Raynaud, Julien; Schradin, Carsten

    2014-04-22

    Males of many species can adjust their behaviors to environmental conditions by changing reproductive tactics. Testosterone surges in adult breeding males typically inhibit the expression of paternal care while facilitating the expression of aggression during environmental changes. Similarly, in non-breeding philopatric males of cooperatively breeding species, up-regulation of testosterone may inhibit alloparental care while facilitating dispersal, i.e. males might become bolder and more explorative. We tested this hypothesis in philopatric male African striped mice, Rhabdomys pumilio. Striped mouse males can either remain in their natal groups providing alloparental care or they can disperse seeking mating opportunities. Compared to philopatric males, dispersed males typically show higher testosterone levels and lower corticosterone levels, and more aggression toward pups and same sex conspecifics. We experimentally increased the testosterone levels of the philopatric males kept in their family groups when pups were present. Testosterone-treated males did not differ significantly from control males in alloparental care and in aggression toward same-sex conspecifics. Compared to the control males, testosterone treated males were bolder, more active, and less anxious; they also showed lower corticosterone levels. The philopatric males were sensitive to our testosterone treatment for dispersal- and anxiety-like behavior but insensitive for social behaviors. Our results suggest a role of testosterone in dispersal. Copyright © 2014. Published by Elsevier Inc.

  13. Mlc Is a Transcriptional Activator with a Key Role in Integrating Cyclic AMP Receptor Protein and Integration Host Factor Regulation of Leukotoxin RNA Synthesis in Aggregatibacter actinomycetemcomitans

    PubMed Central

    Childress, Catherine; Feuerbacher, Leigh A.; Phillips, Linda; Burgum, Alex

    2013-01-01

    Aggregatibacter actinomycetemcomitans, a periodontal pathogen, synthesizes leukotoxin (LtxA), a protein that helps the bacterium evade the host immune response. Transcription of the ltxA operon is induced during anaerobic growth. The cyclic AMP (cAMP) receptor protein (CRP) indirectly increases ltxA expression, but the intermediary regulator is unknown. Integration host factor (IHF) binds to and represses the leukotoxin promoter, but neither CRP nor IHF is responsible for the anaerobic induction of ltxA RNA synthesis. Thus, we have undertaken studies to identify other regulators of leukotoxin transcription and to demonstrate how these proteins work together to modulate leukotoxin synthesis. First, analyses of ltxA RNA expression from defined leukotoxin promoter mutations in the chromosome identify positions −69 to −35 as the key control region and indicate that an activator protein modulates leukotoxin transcription. We show that Mlc, which is a repressor in Escherichia coli, functions as a direct transcriptional activator in A. actinomycetemcomitans; an mlc deletion mutant reduces leukotoxin RNA synthesis, and recombinant Mlc protein binds specifically at the −68 to −40 region of the leukotoxin promoter. Furthermore, we show that CRP activates ltxA expression indirectly by increasing the levels of Mlc. Analyses of Δmlc, Δihf, and Δihf Δmlc strains demonstrate that Mlc can increase RNA polymerase (RNAP) activity directly and that IHF represses ltxA RNA synthesis mainly by blocking Mlc binding. Finally, a Δihf Δmlc mutant still induces ltxA during anaerobic growth, indicating that there are additional factors involved in leukotoxin transcriptional regulation. A model for the coordinated regulation of leukotoxin transcription is presented. PMID:23475968

  14. A discourse analysis of male sexuality in the magazine Intimacy

    PubMed Central

    2015-01-01

    Abstract Background The World Health Organization's publication, Developing sexual health programmes, states that the media is an important source of information about sexuality. Although the media can promote awareness of sexual health issues, it also acts as a vehicle for defining and regulating sex norms. In other words, the standards of ‘normal’ sex are in part defined by the media. Accordingly, it has become imperative to analyse the media's construction of sexual norms in order to reveal how they are related to specific ideological views. For the purposes of this study, the focus will be limited to analysing the South African publication Intimacy. Aim The study aims to reveal how the sex advice articles written in Intimacy for women in regard to their male partner's sexuality reflect patriarchal and phallocentric ideologies. Method A discourse analysis of the sex advice articles in the magazine Intimacy was conducted. It was informed by feminist theories of sexuality that seek to examine the ways in which texts are associated with male-centred versions of sexual pleasure. Results The discourse analysis identified a number of key themes regarding male sexuality. These include: (1) biological accounts of male sexuality; (2) phallocentric scripting of the sex act; and (3) the melodramatic penis. Conclusion Constructions of male sexuality require the inclusion of alternative modes of male erotic pleasure. This requires texts that encourage men to explore and also to experiment with pleasurable feelings associated with non-genital erogenous zones of the body. PMID:26245621

  15. A discourse analysis of male sexuality in the magazine Intimacy.

    PubMed

    du Plessis, Rory

    2015-03-19

    The World Health Organization's publication, Developing sexual health programmes, states that the media is an important source of information about sexuality. Although the media can promote awareness of sexual health issues, it also acts as a vehicle for defining and regulating sex norms. In other words, the standards of 'normal' sex are in part defined by the media. Accordingly, it has become imperative to analyse the media's construction of sexual norms in order to reveal how they are related to specific ideological views. For the purposes of this study, the focus will be limited to analysing the South African publication Intimacy. The study aims to reveal how the sex advice articles written in Intimacy for women in regard to their male partner's sexuality reflect patriarchal and phallocentric ideologies. A discourse analysis of the sex advice articles in the magazine Intimacy was conducted. It was informed by feminist theories of sexuality that seek to examine the ways in which texts are associated with male-centred versions of sexual pleasure. The discourse analysis identified a number of key themes regarding male sexuality. These include: (1) biological accounts of male sexuality; (2) phallocentric scripting of the sex act; and (3) the melodramatic penis. Constructions of male sexuality require the inclusion of alternative modes of male erotic pleasure. This requires texts that encourage men to explore and also to experiment with pleasurable feelings associated with non-genital erogenous zones of the body.

  16. Severe XIST hypomethylation clearly distinguishes (SRY+) 46,XX-maleness from Klinefelter syndrome.

    PubMed

    Poplinski, Andreas; Wieacker, Peter; Kliesch, Sabine; Gromoll, Jörg

    2010-01-01

    46,XX-maleness affects 1 in 20 000 live male newborns resulting in infertility and hypergonadotrophic hypogonadism. Although the phenotypes of XX-males have been well described, the molecular nature of the X chromosomes remains elusive. We assessed the X inactivation status by DNA methylation analysis of four informative loci and compared those to Klinefelter syndrome (KS) and Turner syndrome. Patient cohort consisted of ten sex-determining region of the Y (SRY+) XX-males, two (SRY-) XX-males, ten 47,XXY Klinefelter men, six 45,X Turner females and ten male and female control individuals each. Methylation analysis was carried out by bisulphite sequencing of DNA from peripheral blood lymphocytes analysing X-inactive-specific transcript (XIST), phosphoglycerate kinase 1 (PGK1), ferritin, heavy peptide-like 17 (FTHL17) and short stature homeobox (SHOX). XIST methylation was 18% in (SRY+) XX-males, and thus they were severely hypomethylated compared to (SRY-) XX-males (48%; P<0.01), Klinefelter men (44%; P<0.01) and female controls (47%; P<0.01). Turner females and male controls displayed a high degree of XIST methylation of 98 and 94% respectively. Methylation of PGK1, undergoing X inactivation, was not significantly reduced in (SRY+) XX-males compared to female controls in spite of severe XIST hypomethylation (51 vs 69%; P>0.05). FTHL17, escaping X inactivation, but undergoing cell-type-specific inactivation was similarly methylated in XX-males (89%), KS patients (87%) and female controls (90%). SHOX, an X inactivation escapee located in the pseudoautosomal region, displays similarly low degrees of methylation for XX-males (7%), KS patients (7%) and female controls (9%). XIST hypomethylation clearly distinguishes (SRY+) XX-males from Klinefelter men. It does not, however, impair appropriate epigenetic regulation of representative X-linked loci.

  17. An essential cell cycle regulation gene causes hybrid inviability in Drosophila.

    PubMed

    Phadnis, Nitin; Baker, EmilyClare P; Cooper, Jacob C; Frizzell, Kimberly A; Hsieh, Emily; de la Cruz, Aida Flor A; Shendure, Jay; Kitzman, Jacob O; Malik, Harmit S

    2015-12-18

    Speciation, the process by which new biological species arise, involves the evolution of reproductive barriers, such as hybrid sterility or inviability between populations. However, identifying hybrid incompatibility genes remains a key obstacle in understanding the molecular basis of reproductive isolation. We devised a genomic screen, which identified a cell cycle-regulation gene as the cause of male inviability in hybrids resulting from a cross between Drosophila melanogaster and D. simulans. Ablation of the D. simulans allele of this gene is sufficient to rescue the adult viability of hybrid males. This dominantly acting cell cycle regulator causes mitotic arrest and, thereby, inviability of male hybrid larvae. Our genomic method provides a facile means to accelerate the identification of hybrid incompatibility genes in other model and nonmodel systems. Copyright © 2015, American Association for the Advancement of Science.

  18. Comparative transcriptome analysis reveals carbohydrate and lipid metabolism blocks in Brassica napus L. male sterility induced by the chemical hybridization agent monosulfuron ester sodium.

    PubMed

    Li, Zhanjie; Cheng, Yufeng; Cui, Jianmin; Zhang, Peipei; Zhao, Huixian; Hu, Shengwu

    2015-03-17

    Chemical hybridization agents (CHAs) are often used to induce male sterility for the production of hybrid seeds. We previously discovered that monosulfuron ester sodium (MES), an acetolactate synthase (ALS) inhibitor of the herbicide sulfonylurea family, can induce rapeseed (Brassica napus L.) male sterility at approximately 1% concentration required for its herbicidal activity. To find some clues to the mechanism of MES inducing male sterility, the ultrastructural cytology observations, comparative transcriptome analysis, and physiological analysis on carbohydrate content were carried out in leaves and anthers at different developmental stages between the MES-treated and mock-treated rapeseed plants. Cytological analysis revealed that the plastid ultrastructure was abnormal in pollen mother cells and tapetal cells in male sterility anthers induced by MES treatment, with less material accumulation in it. However, starch granules were observed in chloroplastids of the epidermis cells in male sterility anthers. Comparative transcriptome analysis identified 1501 differentially expressed transcripts (DETs) in leaves and anthers at different developmental stages, most of these DETs being localized in plastid and mitochondrion. Transcripts involved in metabolism, especially in carbohydrate and lipid metabolism, and cellular transport were differentially expressed. Pathway visualization showed that the tightly regulated gene network for metabolism was reprogrammed to respond to MES treatment. The results of cytological observation and transcriptome analysis in the MES-treated rapeseed plants were mirrored by carbohydrate content analysis. MES treatment led to decrease in soluble sugars content in leaves and early stage buds, but increase in soluble sugars content and decrease in starch content in middle stage buds. Our integrative results suggested that carbohydrate and lipid metabolism were influenced by CHA-MES treatment during rapeseed anther development, which might

  19. Cellular Signaling by Fibroblast Growth Factors (FGFs) and Their Receptors (FGFRs) in Male Reproduction

    PubMed Central

    Cotton, Leanne M.; O’Bryan, Moira K.; Hinton, Barry T.

    2008-01-01

    The major function of the reproductive system is to ensure the survival of the species by passing on hereditary traits from one generation to the next. This is accomplished through the production of gametes and the generation of hormones that function in the maturation and regulation of the reproductive system. It is well established that normal development and function of the male reproductive system is mediated by endocrine and paracrine signaling pathways. Fibroblast growth factors (FGFs), their receptors (FGFRs), and signaling cascades have been implicated in a diverse range of cellular processes including: proliferation, apoptosis, cell survival, chemotaxis, cell adhesion, motility, and differentiation. The maintenance and regulation of correct FGF signaling is evident from human and mouse genetic studies which demonstrate that mutations leading to disruption of FGF signaling cause a variety of developmental disorders including dominant skeletal diseases, infertility, and cancer. Over the course of this review, we will provide evidence for differential expression of FGFs/FGFRs in the testis, male germ cells, the epididymis, the seminal vesicle, and the prostate. We will show that this signaling cascade has an important role in sperm development and maturation. Furthermore, we will demonstrate that FGF/FGFR signaling is essential for normal epididymal function and prostate development. To this end, we will provide evidence for the involvement of the FGF signaling system in the regulation and maintenance of the male reproductive system. PMID:18216218

  20. Male risk taking, female odors, and the role of estrogen receptors.

    PubMed

    Kavaliers, Martin; Clipperton-Allen, Amy; Cragg, Cheryl L; Gustafsson, Jan-Åke; Korach, Kenneth S; Muglia, Louis; Choleris, Elena

    2012-12-05

    Male risk-taking and decision making are affected by sex-related cues, with men making riskier choices and decisions after exposure to either women or stimuli associated with women. In non-human species females and, or their cues can also increase male risk taking. Under the ecologically relevant condition of predation threat, brief exposure of male mice to the odors of a sexually receptive novel female reduces the avoidance of, and aversive responses to, a predator. We briefly review evidence showing that estrogen receptors (ERs), ERα and ERβ, are associated with the mediation of these risk taking responses. We show that ERs influence the production of the female odors that affect male risk taking, with the odors of wild type (ERαWT, ERβWT), oxytocin (OT) wildtype (OTWT), gene-deleted 'knock-out' ERβ (ERβKO), but not ERαKO or oxytocin (OT) OTKO or ovariectomized (OVX) female mice reducing the avoidance responses of male mice to cat odor. We further show that administration of specific ERα and ERβ agonists to OVX females results in their odors increasing male risk taking and boldness towards a predator. We also review evidence that ERs are involved in the mediation of the responses of males to female cues, with ERα being associated with the sexual and both ERβ and ERα with the sexual and social mechanisms underlying the effects of female cues on male risk taking. The implications and relations of these findings with rodents to ERs and the regulation of human risk taking are briefly considered. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Male risk taking, female odors, and the role of estrogen receptors

    PubMed Central

    Kavaliers, Martin; Clipperton-Allen, Amy; Cragg, Cheryl L.; Gustafsson, Jan-Åke; Korach, Kenneth S.; Muglia, Louis; Choleris, Elena

    2016-01-01

    Male risk-taking and decision making are affected by sex-related cues, with men making riskier choices and decisions after exposure to either women or stimuli associated with women. In non-human species females and, or their cues can also increase male risk taking. Under the ecologically relevant condition of predation threat, brief exposure of male mice to the odors of a sexually receptive novel female reduces the avoidance of, and aversive responses to, a predator. We briefly review evidence showing that estrogen receptors (ERs), ERα and ERβ, are associated with the mediation of these risk taking responses. We show that ERs influence the production of the female odors that affect male risk taking, with the odors of wild type (ERαWT, ERβWT), oxytocin (OT) wildtype (OTWT), gene-deleted ‘knock-out’ ERβ (ERβKO), but not ERαKO or oxytocin (OT) OTKO or ovariectomized (OVX) female mice reducing the avoidance responses of male mice to cat odor. We further show that administration of specific ERα and ERβ agonists to OVX females results in their odors increasing male risk taking and boldness towards a predator. We also review evidence that ERs are involved in the mediation of the responses of males to female cues, with ERα being associated with the sexual and both ERβ and ERα with the sexual and social mechanisms underlying the effects of female cues on male risk taking. The implications and relations of these findings with rodents to ERs and the regulation of human risk taking are briefly considered. PMID:22472459

  2. Interpersonal emotion regulation.

    PubMed

    Zaki, Jamil; Williams, W Craig

    2013-10-01

    Contemporary emotion regulation research emphasizes intrapersonal processes such as cognitive reappraisal and expressive suppression, but people experiencing affect commonly choose not to go it alone. Instead, individuals often turn to others for help in shaping their affective lives. How and under what circumstances does such interpersonal regulation modulate emotional experience? Although scientists have examined allied phenomena such as social sharing, empathy, social support, and prosocial behavior for decades, there have been surprisingly few attempts to integrate these data into a single conceptual framework of interpersonal regulation. Here we propose such a framework. We first map a "space" differentiating classes of interpersonal regulation according to whether an individual uses an interpersonal regulatory episode to alter their own or another person's emotion. We then identify 2 types of processes--response-dependent and response-independent--that could support interpersonal regulation. This framework classifies an array of processes through which interpersonal contact fulfills regulatory goals. More broadly, it organizes diffuse, heretofore independent data on "pieces" of interpersonal regulation, and identifies growth points for this young and exciting research domain.

  3. Emotion-Related Regulation: Sharpening the Definition

    ERIC Educational Resources Information Center

    Eisenberg, Nancy; Spinrad, Tracy L.

    2004-01-01

    Cole, Martin, and Dennis (this issue) considered many important conceptual and methodological issues in their discussion of emotion regulation. Although it may be necessary to develop an integrated definition of the construct of emotion regulation, the definition provided in the Cole et al. article is too encompassing. It is important to…

  4. A Developmentally Regulated Chaperone Complex for the Endoplasmic Reticulum of Male Haploid Germ Cells

    PubMed Central

    van Lith, Marcel; Karala, Anna-Riikka; Bown, Dave; Gatehouse, John A.; Ruddock, Lloyd W.; Saunders, Philippa T.K.

    2007-01-01

    Glycoprotein folding is mediated by lectin-like chaperones and protein disulfide isomerases (PDIs) in the endoplasmic reticulum. Calnexin and the PDI homologue ERp57 work together to help fold nascent polypeptides with glycans located toward the N-terminus of a protein, whereas PDI and BiP may engage proteins that lack glycans or have sugars toward the C-terminus. In this study, we show that the PDI homologue PDILT is expressed exclusively in postmeiotic male germ cells, in contrast to the ubiquitous expression of many other PDI family members in the testis. PDILT is induced during puberty and represents the first example of a PDI family member under developmental control. We find that PDILT is not active as an oxido-reductase, but interacts with the model peptide Δ-somatostatin and nonnative bovine pancreatic trypsin inhibitor in vitro, indicative of chaperone activity. In vivo, PDILT forms a tissue-specific chaperone complex with the calnexin homologue calmegin. The identification of a redox-inactive chaperone partnership defines a new system of testis-specific protein folding with implications for male fertility. PMID:17507649

  5. Optogenetic Stimulation of Arcuate Nucleus Kiss1 Neurons Reveals a Steroid-Dependent Glutamatergic Input to POMC and AgRP Neurons in Male Mice

    PubMed Central

    Nestor, Casey C; Qiu, Jian; Padilla, Stephanie L.; Zhang, Chunguang; Bosch, Martha A.; Fan, Wei; Aicher, Sue A.; Palmiter, Richard D.

    2016-01-01

    Kisspeptin (Kiss1) neurons are essential for reproduction, but their role in the control of energy balance and other homeostatic functions remains unclear. Proopiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons, located in the arcuate nucleus (ARC) of the hypothalamus, integrate numerous excitatory and inhibitory inputs to ultimately regulate energy homeostasis. Given that POMC and AgRP neurons are contacted by Kiss1 neurons in the ARC (Kiss1ARC) and they express androgen receptors, Kiss1ARC neurons may mediate the orexigenic action of testosterone via POMC and/or AgRP neurons. Quantitative PCR analysis of pooled Kiss1ARC neurons revealed that mRNA levels for Kiss1 and vesicular glutamate transporter 2 were higher in castrated male mice compared with gonad-intact males. Single-cell RT-PCR analysis of yellow fluorescent protein (YFP) ARC neurons harvested from males injected with AAV1-EF1α-DIO-ChR2:YFP revealed that 100% and 88% expressed mRNAs for Kiss1 and vesicular glutamate transporter 2, respectively. Whole-cell, voltage-clamp recordings from nonfluorescent postsynaptic ARC neurons showed that low frequency photo-stimulation (0.5 Hz) of Kiss1-ChR2:YFP neurons elicited a fast glutamatergic inward current in POMC and AgRP neurons. Paired-pulse, photo-stimulation revealed paired-pulse depression, which is indicative of greater glutamate release, in the castrated male mice compared with gonad-intact male mice. Group I and group II metabotropic glutamate receptor agonists depolarized and hyperpolarized POMC and AgRP neurons, respectively, which was mimicked by high frequency photo-stimulation (20 Hz) of Kiss1ARC neurons. Therefore, POMC and AgRP neurons receive direct steroid- and frequency-dependent glutamatergic synaptic input from Kiss1ARC neurons in male mice, which may be a critical pathway for Kiss1 neurons to help coordinate energy homeostasis and reproduction. PMID:27093227

  6. Characteristics of Female Solo and Female Co-Offenders and Male Solo Sexual Offenders Against Children.

    PubMed

    Williams, Rebecca; Gillespie, Steven M; Elliott, Ian A; Eldridge, Hilary J

    2017-09-01

    Studies have highlighted differences in the victim choice, offender, and offense characteristics of female and male sexual offenders. However, little is known about how solo and co-offending females differ from solo male sexual offenders. We compared the characteristics of 20 solo and 20 co-offending females (co-offended with a male and/or female accomplice), and 40 male sexual offenders against children. We found that solo female offenders showed the most evidence of personal problems, including depression and sexual dissatisfaction. Compared with male offenders, female co-offenders showed poorer self-management, but better sexual self-regulation. Male offenders had a greater history of offending and showed more evidence of sexual abuse supportive cognitions relative to both solo and co-offending females. These results are consistent with the need for a gender-specific approach to working with sexual offenders and may have implications for understanding the often complex treatment needs of these clients.

  7. The impact of environmental stress on male reproductive development in plants: biological processes and molecular mechanisms

    PubMed Central

    de Storme, Nico; Geelen, Danny

    2014-01-01

    In plants, male reproductive development is extremely sensitive to adverse climatic environments and (a)biotic stress. Upon exposure to stress, male gametophytic organs often show morphological, structural and metabolic alterations that typically lead to meiotic defects or premature spore abortion and male reproductive sterility. Depending on the type of stress involved (e.g. heat, cold, drought) and the duration of stress exposure, the underlying cellular defect is highly variable and either involves cytoskeletal alterations, tapetal irregularities, altered sugar utilization, aberrations in auxin metabolism, accumulation of reactive oxygen species (ROS; oxidative stress) or the ectopic induction of programmed cell death (PCD). In this review, we present the critically stress-sensitive stages of male sporogenesis (meiosis) and male gametogenesis (microspore development), and discuss the corresponding biological processes involved and the resulting alterations in male reproduction. In addition, this review also provides insights into the molecular and/or hormonal regulation of the environmental stress sensitivity of male reproduction and outlines putative interaction(s) between the different processes involved. PMID:23731015

  8. Title IX: Parity of Coaches' Salaries for Male and Female Athletic Teams.

    ERIC Educational Resources Information Center

    National Education Association, Washington, DC.

    A study by the National Education Association (NEA) of the existing literature, teacher opinion polls, federal legislation and regulations, state salary schedules, and collective bargaining agreements revealed important information concerning the differences in salaries in the late 1970s for coaches of male and female athletic teams in the public…

  9. Optimizing a Male Reproductive Aging Mouse Model by d-Galactose Injection

    PubMed Central

    Liao, Chun-Hou; Chen, Bing-Huei; Chiang, Han-Sun; Chen, Chiu-Wei; Chen, Mei-Feng; Ke, Chih-Chun; Wang, Ya-Yun; Lin, Wei-Ning; Wang, Chi-Chung; Lin, Ying-Hung

    2016-01-01

    The d-galactose (d-gal)-injected animal model, which is typically established by administering consecutive subcutaneous d-gal injections to animals for approximately six or eight weeks, has been frequently used for aging research. In addition, this animal model has been demonstrated to accelerate aging in the brain, kidneys, liver and blood cells. However, studies on aging in male reproductive organs that have used this animal model remain few. Therefore, the current study aimed to optimize a model of male reproductive aging by administering d-gal injections to male mice and to determine the possible mechanism expediting senescence processes during spermatogenesis. In this study, C57Bl/6 mice were randomized into five groups (each containing 8–10 mice according to the daily intraperitoneal injection of vehicle control or 100 or 200 mg/kg dosages of d-gal for a period of six or eight weeks). First, mice subjected to d-gal injections for six or eight weeks demonstrated considerably decreased superoxide dismutase activity in the serum and testis lysates compared to those in the control group. The lipid peroxidation in testis also increased in the d-gal-injected groups. Furthermore, the d-gal-injected groups exhibited a decreased ratio of testis weight/body weight and sperm count compared to the control group. The percentages of both immotile sperm and abnormal sperm increased considerably in the d-gal-injected groups compared to those of the control group. To determine the genes influenced by the d-gal injection during murine spermatogenesis, a c-DNA microarray was conducted to compare testicular RNA samples between the treated groups and the control group. The d-gal-injected groups exhibited RNA transcripts of nine spermatogenesis-related genes (Cycl2, Hk1, Pltp, Utp3, Cabyr, Zpbp2, Speer2, Csnka2ip and Katnb1) that were up- or down-regulated by at least two-fold compared to the control group. Several of these genes are critical for forming sperm-head morphologies

  10. A mitochondrial DNA hypomorph of cytochrome oxidase specifically impairs male fertility in Drosophila melanogaster

    PubMed Central

    Patel, Maulik R; Miriyala, Ganesh K; Littleton, Aimee J; Yang, Heiko; Trinh, Kien; Young, Janet M; Kennedy, Scott R; Yamashita, Yukiko M; Pallanck, Leo J; Malik, Harmit S

    2016-01-01

    Due to their strict maternal inheritance in most animals and plants, mitochondrial genomes are predicted to accumulate mutations that are beneficial or neutral in females but harmful in males. Although a few male-harming mtDNA mutations have been identified, consistent with this ‘Mother’s Curse’, their effect on females has been largely unexplored. Here, we identify COIIG177S, a mtDNA hypomorph of cytochrome oxidase II, which specifically impairs male fertility due to defects in sperm development and function without impairing other male or female functions. COIIG177S represents one of the clearest examples of a ‘male-harming’ mtDNA mutation in animals and suggest that the hypomorphic mtDNA mutations like COIIG177S might specifically impair male gametogenesis. Intriguingly, some D. melanogaster nuclear genetic backgrounds can fully rescue COIIG177S -associated sterility, consistent with previously proposed models that nuclear genomes can regulate the phenotypic manifestation of mtDNA mutations. DOI: http://dx.doi.org/10.7554/eLife.16923.001 PMID:27481326

  11. Hypoxia alters testicular functions of marine medaka through microRNAs regulation.

    PubMed

    Tse, Anna Chung-Kwan; Li, Jing-Woei; Wang, Simon Yuan; Chan, Ting-Fung; Lai, Keng Po; Wu, Rudolf Shiu-Sun

    2016-11-01

    Hypoxia is a global environmental concern and poses a significant threat to aquatic ecosystems, including the sustainability of natural fish populations. The deleterious effects of hypoxia on fish reproductive fitness, as mediated by disruption of sex hormones and gene expression along the Brain-Pituitary-Gonad axis, have been well documented. Recently, we further demonstrated that the observed disruption of steroidogenesis in the ovary of marine medaka Oryzias melastigma is mediated through microRNAs (miRNAs). More importantly, we reported the transgenerational epigenetic effect of hypoxia on the male reproductive impairment of marine medaka. This study attempts to elucidate the function of miRNAs and its potential role in the transgenerational effect of hypoxia in the male medaka testis, using small RNA sequencing. A total of 558 miRNAs were found in the testis, of which 9 were significant upregulated and 5 were downregulated by hypoxia. Bioinformatics analysis further revealed that among the 2885 genes targeted by the hypoxia-responsive miRNAs, many are closely related to stress response, cell cycle, epigenetic modification, sugar metabolism and cell motion. Furthermore, the integrated analysis of transcriptome data and the result of target gene prediction demonstrated 108 genes and 65 genes were concordantly upregulated and downregulated, respectively. In which, euchromatic histone-lysine N-methyltransferase 2, the epigenetic regulator of transgenerational reproductive impairment caused by hypoxia, is found to be targeted by miR-125-5p. The present findings not only reveal that miRNAs are crucial downstream mediators of hypoxic stress in fish male gonad, but also shed light on the underlying epigenetic mechanism for the reproductive impairments of hypoxia on male fish, including the observed transgenerational effects. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Male sexuality.

    PubMed

    Ginsberg, Terrie B

    2010-05-01

    It should be recognized that sexuality in the aging male is of such import that a complete sexual history must be performed. By taking a complete sexual history, facts can be obtained that will allow for appropriate focus relating to a holistic evaluation and will enable us to dispel antiquated sexual myths pertaining to the aging male. If initiated by the history taker, questions concerning sexuality may be discussed more comfortably by the patient. Erectile dysfunction, male sexual response cycle, testosterone, sexually transmitted diseases, human immunodeficiency virus, long-term illness, along with religion and culture are explored in this article with the aim of improving one's knowledge base, self reflection, and awareness of the importance of male sexuality. A complete understanding and appreciation of the aging male's medical history, surgical history, social history, and emotional history as well as his sexual, cultural, and religious concepts will allow the health care provider to better analyze information, and to recommend and provide appropriate advice and treatment to the aging male patient. Copyright 2010 Elsevier Inc. All rights reserved.

  13. Thyroid hormone actions on male reproductive system of teleost fish.

    PubMed

    Tovo-Neto, Aldo; da Silva Rodrigues, Maira; Habibi, Hamid R; Nóbrega, Rafael Henrique

    2018-04-17

    Thyroid hormones (THs) play important roles in the regulation of many biological processes of vertebrates, such as growth, metabolism, morphogenesis and reproduction. An increasing number of studies have been focused on the involvement of THs in the male reproductive system of vertebrates, in particular of fish. Therefore, this mini-review aims to summarize the main findings on THs role in male reproductive system of fish, focusing on sex differentiation, testicular development and spermatogenesis. The existing data in the literature have demonstrated that THs exert their roles at the different levels of the hypothalamic-pituitary-gonadal (HPG) axis. In general a positive correlation has been shown between THs and fish reproductive status; where THs are associated with testicular development, growth and maturation. Recently, the molecular mechanisms underlying the role of THs in spermatogenesis have been unraveled in zebrafish testis. THs promote germ cell proliferation and differentiation by increasing a stimulatory growth factor of spermatogenesis produced by Sertoli cells. In addition, THs enhanced the gonadotropin-induced androgen release in zebrafish testis. Next to their functions in the adult testis, THs are involved in the gonadal sex differentiation through modulating sex-related gene expression, and testicular development via regulation of Sertoli cell proliferation. In conclusion, this mini-review showed that THs modulate the male reproductive system during the different life stages of fish. The physiological and molecular mechanisms showed a link between the thyroid and reproduction, suggesting a possibly co-evolution and interdependence of these two systems. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Suppressing male spermatogenesis-associated protein 5-like gene expression reduces vitellogenin gene expression and fecundity in Nilaparvata lugens Stål

    USDA-ARS?s Scientific Manuscript database

    In our previous study with the brown planthopper (BPH), Nilaparvata lugens, triazophos (tzp, organophosphate) treatments led to substantial up-regulation of a male spermatogenesis-associated protein 5-like gene (NlSPATA5) compared to untreated controls. Mating with tzp-treated males significantly in...

  15. Lin28a regulates germ cell pool size and fertility

    PubMed Central

    Shinoda, Gen; de Soysa, T. Yvanka; Seligson, Marc T.; Yabuuchi, Akiko; Fujiwara, Yuko; Huang, Pei Yi; Hagan, John P.; Gregory, Richard I.; Moss, Eric G.; Daley, George Q.

    2013-01-01

    Overexpression of LIN28A is associated with human germ cell tumors and promotes primordial germ cell (PGC) development from embryonic stem cells in vitro and in chimeric mice. Knockdown of Lin28a inhibits PGC development in vitro, but how constitutional Lin28a deficiency affects the mammalian reproductive system in vivo remains unknown. Here, we generated Lin28a knockout (KO) mice and found that Lin28a deficiency compromises the size of the germ cell pool in both males and females by affecting PGC proliferation during embryogenesis. Interestingly however, in Lin28a KO males the germ cell pool partially recovers during postnatal expansion, while fertility remains impaired in both males and females mated to wild type mice. Embryonic overexpression of let-7, a microRNA negatively regulated by Lin28a, reduces the germ cell pool, corroborating the role of the Lin28a/let-7 axis in regulating the germ lineage. PMID:23378032

  16. Stimulation of the medial amygdala enhances medial preoptic dopamine release: implications for male rat sexual behavior.

    PubMed

    Dominguez, J M; Hull, E M

    2001-11-02

    Increased dopamine (DA) in the medial preoptic area (MPOA) facilitates male sexual behavior. A major source of innervation to the MPOA is the medial amygdala (MeA). We now report that chemical stimulation of the MeA enhanced levels of extracellular MPOA DA in anesthetized male rats. These results suggest that DA activity in the MPOA can be regulated by input from the MeA to the MPOA.

  17. Sex steroid hormones matter for learning and memory: estrogenic regulation of hippocampal function in male and female rodents

    PubMed Central

    Kim, Jaekyoon; Tuscher, Jennifer J.; Fortress, Ashley M.

    2015-01-01

    Ample evidence has demonstrated that sex steroid hormones, such as the potent estrogen 17β-estradiol (E2), affect hippocampal morphology, plasticity, and memory in male and female rodents. Yet relatively few investigators who work with male subjects consider the effects of these hormones on learning and memory. This review describes the effects of E2 on hippocampal spinogenesis, neurogenesis, physiology, and memory, with particular attention paid to the effects of E2 in male rodents. The estrogen receptors, cell-signaling pathways, and epigenetic processes necessary for E2 to enhance memory in female rodents are also discussed in detail. Finally, practical considerations for working with female rodents are described for those investigators thinking of adding females to their experimental designs. PMID:26286657

  18. How Song Experience Affects Female Mate-Choice, Male Song, and Monoaminergic Activity in the Auditory Telencephalon in Lincoln's Sparrows.

    PubMed

    Sockman, Keith W; Lyons, Susan M

    2017-10-01

    A sexual signal can indicate not only the signaler's attractiveness as a potential mate but also the signaler's competitiveness relative to rivals. As the attractiveness or competitiveness of the prevailing signaling environment increases, individuals prospecting for mates should change their choice threshold, whereas competing individuals should shift resources toward elevating their own competitiveness. Previous studies show that experimental elevations of song competition increase male competitive behavior in Lincoln's sparrows (Melospiza lincolnii) and European starlings (Sturnus vulgaris). Through a series of experimental manipulations using laboratory-housed Lincoln's sparrows, we have also discovered that females change the strength of their song preferences depending on the attractiveness of the song environment to which they have recently been exposed; compared to a less-attractive environment, a highly-attractive environment elevates the threshold for releasing phonotaxis behavior toward male song. These behavioral adjustments are associated with changes in forebrain monoaminergic activity that are triggered by experimental manipulations of the quality of the song environment. Findings from these studies suggest possible neural mechanisms for the regulation of adaptive behavioral plasticity associated with dynamic sexual signaling environments. © The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  19. Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders.

    PubMed

    Codina-Solà, Marta; Rodríguez-Santiago, Benjamín; Homs, Aïda; Santoyo, Javier; Rigau, Maria; Aznar-Laín, Gemma; Del Campo, Miguel; Gener, Blanca; Gabau, Elisabeth; Botella, María Pilar; Gutiérrez-Arumí, Armand; Antiñolo, Guillermo; Pérez-Jurado, Luis Alberto; Cuscó, Ivon

    2015-01-01

    Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders with high heritability. Recent findings support a highly heterogeneous and complex genetic etiology including rare de novo and inherited mutations or chromosomal rearrangements as well as double or multiple hits. We performed whole-exome sequencing (WES) and blood cell transcriptome by RNAseq in a subset of male patients with idiopathic ASD (n = 36) in order to identify causative genes, transcriptomic alterations, and susceptibility variants. We detected likely monogenic causes in seven cases: five de novo (SCN2A, MED13L, KCNV1, CUL3, and PTEN) and two inherited X-linked variants (MAOA and CDKL5). Transcriptomic analyses allowed the identification of intronic causative mutations missed by the usual filtering of WES and revealed functional consequences of some rare mutations. These included aberrant transcripts (PTEN, POLR3C), deregulated expression in 1.7% of mutated genes (that is, SEMA6B, MECP2, ANK3, CREBBP), allele-specific expression (FUS, MTOR, TAF1C), and non-sense-mediated decay (RIT1, ALG9). The analysis of rare inherited variants showed enrichment in relevant pathways such as the PI3K-Akt signaling and the axon guidance. Integrative analysis of WES and blood RNAseq data has proven to be an efficient strategy to identify likely monogenic forms of ASD (19% in our cohort), as well as additional rare inherited mutations that can contribute to ASD risk in a multifactorial manner. Blood transcriptomic data, besides validating 88% of expressed variants, allowed the identification of missed intronic mutations and revealed functional correlations of genetic variants, including changes in splicing, expression levels, and allelic expression.

  20. A novel mitochondrial orf147 causes cytoplasmic male sterility in pigeonpea by modulating aberrant anther dehiscence.

    PubMed

    Bhatnagar-Mathur, Pooja; Gupta, Ranadheer; Reddy, Palakolanu Sudhakar; Reddy, Bommineni Pradeep; Reddy, Dumbala Srinivas; Sameerkumar, C V; Saxena, Rachit Kumar; Sharma, Kiran K

    2018-05-01

    A novel open reading frame (ORF) identified and cloned from the A4 cytoplasm of Cajanus cajanifolius induced partial to complete male sterility when introduced into Arabidopsis and tobacco. Pigeonpea (Cajanus cajan L. Millsp.) is the only legume known to have commercial hybrid seed technology based on cytoplasmic male sterility (CMS). We identified a novel ORF (orf147) from the A4 cytoplasm of C. cajanifolius that was created via rearrangements in the CMS line and co-transcribes with the known and unknown sequences. The bi/poly-cistronic transcripts cause gain-of-function variants in the mitochondrial genome of CMS pigeonpea lines having distinct processing mechanisms and transcription start sites. In presence of orf147, significant repression of Escherichia coli growth indicated its toxicity to the host cells and induced partial to complete male sterility in transgenic progenies of Arabidopsis thaliana and Nicotiana tabacum where phenotype co-segregated with the transgene. The male sterile plants showed aberrant floral development and reduced lignin content in the anthers. Gene expression studies in male sterile pigeonpea, Arabidopsis and tobacco plants confirmed down-regulation of several anther biogenesis genes and key genes involved in monolignol biosynthesis, indicative of regulation of retrograde signaling. Besides providing evidence for the involvement of orf147 in pigeonpea CMS, this study provides valuable insights into its function. Cytotoxicity and aberrant programmed cell death induced by orf147 could be important for mechanism underlying male sterility that offers opportunities for possible translation for these findings for exploiting hybrid vigor in other recalcitrant crops as well.