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Sample records for integration regulating male

  1. Sensory Integration Regulating Male Courtship Behavior in Drosophila

    PubMed Central

    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. PMID:19214231

  2. RFX1 maintains testis cord integrity by regulating the expression of Itga6 in male mouse embryos.

    PubMed

    Wang, Bo; Qi, Tao; Chen, Shi-Qin; Ye, Lei; Huang, Zhan-Sen; Li, Hao

    2016-07-01

    Formation and maintenance of testis cords during embryogenesis are essential for establishing testicular structure and function in adults. At least five genes (Wt1, Dhh, Sox8/Sox9, and Dax1) appear to be required for the maintenance of testis cord integrity in mice. Here, we report that RFX1 is specifically expressed in fetal Sertoli cells. Mouse embryos conditionally deficient in Rfx1 (Rfx1(flox/flox) , Amh-Cre) possessed disrupted testis cords, as the basal lamina lining was fragmented or completely absent in some areas of the testes. Spermatogenesis was blocked, leading to complete infertility. Expression of integrin alpha-6 was significantly decreased in Rfx1-deficient testes compared to control testes; indeed, luciferase and chromatin immunoprecipitation assays indicated that RFX1 directly activates transcription of Itga6 (the gene coding for integrin alpha-6). Taken together, RFX1 transcriptionally targets Itga6 in Sertoli cells, thereby, helping maintain the integrity of the basal lamina during testis cord development. Mol. Reprod. Dev. 83: 606-614, 2016. © 2016 Wiley Periodicals, Inc. PMID:27228460

  3. 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

  4. Magnetoreception Regulates Male Courtship Activity in Drosophila

    PubMed Central

    Wu, Chia-Lin; Fu, Tsai-Feng; Chiang, Meng-Hsuan; Chang, Yu-Wei; Her, Jim-Long; Wu, Tony

    2016-01-01

    The possible neurological and biophysical effects of magnetic fields on animals is an area of active study. Here, we report that courtship activity of male Drosophila increases in a magnetic field and that this effect is regulated by the blue light-dependent photoreceptor cryptochrome (CRY). Naïve male flies exhibited significantly increased courtship activities when they were exposed to a ≥ 20-Gauss static magnetic field, compared with their behavior in the natural environment (0 Gauss). CRY-deficient flies, cryb and crym, did not show an increased courtship index in a magnetic field. RNAi-mediated knockdown of cry in cry-GAL4-positive neurons disrupted the increased male courtship activity in a magnetic field. Genetically expressing cry under the control of cry-GAL4 in the CRY-deficient flies restored the increase in male courtship index that occurred in a magnetic field. Interestingly, artificially activating cry-GAL4-expressing neurons, which include large ventral lateral neurons and small ventral lateral neurons, via expression of thermosensitive cation channel dTrpA1, also increased the male courtship index. This enhancement was abolished by the addition of the cry-GAL80 transgene. Our results highlight the phenomenon of increased male courtship activity caused by a magnetic field through CRY-dependent magnetic sensation in CRY expression neurons in Drosophila. PMID:27195955

  5. 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

  6. 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

  7. 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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  8. 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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  9. 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…

  10. Regulation of Isoprenoid Pheromone Biosynthesis in Bumblebee Males.

    PubMed

    Prchalová, Darina; Buček, Aleš; Brabcová, Jana; Žáček, Petr; Kindl, Jiří; Valterová, Irena; Pichová, Iva

    2016-02-01

    Males of the closely related species Bombus terrestris and Bombus lucorum attract conspecific females by completely different marking pheromones. MP of B. terrestris and B. lucorum pheromones contain mainly isoprenoid (ISP) compounds and fatty acid derivatives, respectively. Here, we studied the regulation of ISP biosynthesis in both bumblebees. RNA-seq and qRT-PCR analyses indicated that acetoacetyl-CoA thiolase (AACT), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), and farnesyl diphosphate synthase (FPPS) transcripts are abundant in the B. terrestris labial gland. Maximal abundance of these transcripts correlated well with AACT enzymatic activity detected in the LG extracts. In contrast, transcript abundances of AACT, HMGR, and FPPS in B. lucorum were low, and AACT activity was not detected in LGs. These results suggest that transcriptional regulation plays a key role in the control of ISP biosynthetic gene expression and ISP pheromone biosynthesis in bumblebee males. PMID:26632352

  11. Implications of leptin in neuroendocrine regulation of male reproduction.

    PubMed

    Landry, David; Cloutier, Frank; Martin, Luc J

    2013-03-01

    Obesity is a major health problem contributing to increased subfertility in males, as well as increased morbidity for diseases related to a decline in testosterone production with aging. Leptin is a hormone produced by adipose tissue whose production increases with the amount of body fat. Several studies have supported a relationship between increased leptin production and regulation of reproductive function. Indeed, leptin acts at all levels of the hypothalamus-pituitary-gonadal (HPG) axis in males. However, most of the obese individuals become insensitive to increased endogenous leptin production and develop a functional leptin resistance. This deregulation of leptin signaling might result in abnormal endocrine and reproductive functions. Altered leptin dynamics may contribute to male infertility in different ways, leading to hypogonadism. These include leptin resistance or leptin insufficiency at the hypothalamus and leptin modulation of testicular physiology. In this review, we address the mechanisms of action of leptin at different levels of the HPG axis. Moreover, the influences of leptin on steroidogenesis and spermatogenesis, as well as seasonal variations of leptin's action on male reproduction are discussed. PMID:23522066

  12. 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. PMID:25566097

  13. 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

  14. Juvenile hormone regulates extreme mandible growth in male stag beetles.

    PubMed

    Gotoh, Hiroki; Cornette, Richard; Koshikawa, Shigeyuki; Okada, Yasukazu; Lavine, Laura Corley; Emlen, Douglas J; Miura, Toru

    2011-01-01

    The morphological diversity of insects is one of the most striking phenomena in biology. Evolutionary modifications to the relative sizes of body parts, including the evolution of traits with exaggerated proportions, are responsible for a vast range of body forms. Remarkable examples of an insect trait with exaggerated proportions are the mandibular weapons of stag beetles. Male stag beetles possess extremely enlarged mandibles which they use in combat with rival males over females. As with other sexually selected traits, stag beetle mandibles vary widely in size among males, and this variable growth results from differential larval nutrition. However, the mechanisms responsible for coupling nutrition with growth of stag beetle mandibles (or indeed any insect structure) remain largely unknown. Here, we demonstrate that during the development of male stag beetles (Cyclommatus metallifer), juvenile hormone (JH) titers are correlated with the extreme growth of an exaggerated weapon of sexual selection. We then investigate the putative role of JH in the development of the nutritionally-dependent, phenotypically plastic mandibles, by increasing hemolymph titers of JH with application of the JH analog fenoxycarb during larval and prepupal developmental periods. Increased JH signaling during the early prepupal period increased the proportional size of body parts, and this was especially pronounced in male mandibles, enhancing the exaggerated size of this trait. The direction of this response is consistent with the measured JH titers during this same period. Combined, our results support a role for JH in the nutrition-dependent regulation of extreme mandible growth in this species. In addition, they illuminate mechanisms underlying the evolution of trait proportion, the most salient feature of the evolutionary diversification of the insects. PMID:21731659

  15. The PSI-U1 snRNP interaction regulates male mating behavior in Drosophila.

    PubMed

    Wang, Qingqing; Taliaferro, J Matthew; Klibaite, Ugne; Hilgers, Valérie; Shaevitz, Joshua W; Rio, Donald C

    2016-05-10

    Alternative pre-mRNA splicing (AS) is a critical regulatory mechanism that operates extensively in the nervous system to produce diverse protein isoforms. Fruitless AS isoforms have been shown to influence male courtship behavior, but the underlying mechanisms are unknown. Using genome-wide approaches and quantitative behavioral assays, we show that the P-element somatic inhibitor (PSI) and its interaction with the U1 small nuclear ribonucleoprotein complex (snRNP) control male courtship behavior. PSI mutants lacking the U1 snRNP-interacting domain (PSIΔAB mutant) exhibit extended but futile mating attempts. The PSIΔAB mutant results in significant changes in the AS patterns of ∼1,200 genes in the Drosophila brain, many of which have been implicated in the regulation of male courtship behavior. PSI directly regulates the AS of at least one-third of these transcripts, suggesting that PSI-U1 snRNP interactions coordinate the behavioral network underlying courtship behavior. Importantly, one of these direct targets is fruitless, the master regulator of courtship. Thus, PSI imposes a specific mode of regulatory control within the neuronal circuit controlling courtship, even though it is broadly expressed in the fly nervous system. This study reinforces the importance of AS in the control of gene activity in neurons and integrated neuronal circuits, and provides a surprising link between a pleiotropic pre-mRNA splicing pathway and the precise control of successful male mating behavior. PMID:27114556

  16. Disrupting Immune Regulation Incurs Transient Costs in Male Reproductive Function

    PubMed Central

    Belloni, Virginia; Sorci, Gabriele; Paccagnini, Eugenio; Guerreiro, Romain; Bellenger, Jérôme; Faivre, Bruno

    2014-01-01

    Background Immune protection against pathogenic organisms has been shown to incur costs. Previous studies investigating the cost of immunity have mostly focused on the metabolic requirements of immune maintenance and activation. In addition to these metabolic costs, the immune system can induce damage to the host if the immune response is mis-targeted or over-expressed. Given its non-specific nature, an over-expressed inflammatory response is often associated with substantial damage for the host. Here, we investigated the cost of an over-expressed inflammatory response in the reproductive function of male mice. Methodology/Principal Findings We experimentally blocked the receptors of an anti-inflammatory cytokine (IL-10) in male mice exposed to a mild inflammatory challenge, with each treatment having an appropriate control group. The experiment was conducted on two age classes, young (3 month old) and old (15 month old) mice, to assess any age-related difference in the cost of a disrupted immune regulation. We found that the concomitant exposure to an inflammatory insult and the blockade of IL-10 induced a reduction in testis mass, compared to the three other groups. The frequency of abnormal sperm morphology was also higher in the group of mice exposed to the inflammatory challenge but did not depend on the blockade of the IL-10. Conclusions Our results provide evidence that immune regulation confers protection against the risk of inflammation-induced infertility during infection. They also suggest that disruption of the effectors involved in the regulation of the inflammatory response can have serious fitness consequences even under mild inflammatory insult and benign environmental conditions. PMID:24400103

  17. 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. PMID:26712234

  18. Male and female synchrony and the regulation of mating in flowering plants.

    PubMed Central

    Herrero, M

    2003-01-01

    Successful mating clearly requires synchronous development of the male and female sexual organs. Evidence is accumulating that this synchrony of development also persists after pollination, with both pollen and pistil following complex, but highly integrated developmental pathways. The timing of the male-female interaction is crucial for the pistil, which, far from being a mature passive structure, is engaged in a continuing programme of development: only being receptive to the advances of the pollen for a relatively short window of time. This developmental programme is most conspicuous in the ovary, and this review focuses on the interaction between the male and female tissues in this structure. The review first considers pollen tube development in the ovary, concentrating of the mechanisms by which its growth is modulated at various control points associated with structures within the ovary. Second, alterations to this 'normal' developmental programme are reviewed and considered in the context of a breakdown of developmental synchrony. Finally, the consequences of male-female developmental synchrony and asynchrony are explored. Clearly, a synchronous male-female relationship leads to a successful fertilization. However, lack of synchrony also occurs, and could emerge as a powerful tool to investigate the regulation of mating. PMID:12831467

  19. 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

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

    PubMed Central

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

    2016-01-01

    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. PMID:27585557

  1. 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

    2016-01-01

    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. PMID:27585557

  2. Social Regulation of Male Reproductive Plasticity in an African Cichlid Fish

    PubMed Central

    Maruska, Karen P.; Fernald, Russell D.

    2013-01-01

    Social interactions with the outcome of a position in a dominance hierarchy can have profound effects on reproductive behavior and physiology, requiring animals to integrate environmental information with their internal physiological state; but how is salient information from the animal’s dynamic social environment transformed into adaptive behavioral, physiological, and molecular-level changes? The African cichlid fish, Astatotilapia burtoni, is ideally suited to understand socially controlled reproductive plasticity because activity of the male reproductive (brain–pituitary–gonad) axis is tightly linked to social status. Males form hierarchies in which a small percentage of brightly colored dominant individuals have an active reproductive axis, defend territories, and spawn with females, while the remaining males are subordinate, drably colored, do not hold a territory, and have a suppressed reproductive system with minimal opportunities for spawning. These social phenotypes are plastic and quickly reversible, meaning that individual males may switch between dominant and subordinate status multiple times within a lifetime. Here, we review the rapid and remarkable plasticity that occurs along the entire reproductive axis when males rise in social rank, a transition that has important implications for the operational sex ratio of the population. When males rise in rank, transformations occur in the brain, pituitary, circulation, and testes over short time-scales (minutes to days). Changes are evident in overt behavior, as well as modifications at the physiological, cellular, and molecular levels that regulate reproductive capacity. Widespread changes triggered by a switch in rank highlight the significance of external social information in shaping internal physiology and reproductive competence. PMID:23613320

  3. Septal regulation of male sexual behavior in rats.

    PubMed

    Gogate, M G; Brid, S V; Wingkar, K C; Kantak, N M

    1995-06-01

    Involvement of septal nuclei in modulation of male sexual behavior in rats was investigated. Sexually active Wistar male rats were assigned to intact, sham, lateral septal nuclei lesioned (LSL), and medial septal nuclei lesioned (MSL) groups. All male rats were tested for sexual behavior in an arena in the presence of a sexually receptive female. Intromission and ejaculation latencies were increased, and mount, intromission, and ejaculation frequencies were decreased in the LSL group compared to the intact group. In contrast, mount and intromission latencies were decreased, and pursuit and mount frequencies were increased in the MSL group compared to the intact group. The results indicate that medial septal nuclei may inhibit and lateral septal nuclei may facilitate male sexual behavior in rats. PMID:7652045

  4. Tight hormonal phenotypic integration ensures honesty of the electric signal of male and female Brachyhypopomus gauderio.

    PubMed

    Gavassa, Sat; Silva, Ana C; Stoddard, Philip K

    2011-09-01

    Hormones mediate sexually selected traits including advertisement signals. Hormonal co-regulation links the signal to other hormonally-mediated traits such that the tighter the integration, the more reliable the signal is as a predictor of those other traits. Androgen administration increases the duration of the communication signal pulse in both sexes of the electric fish Brachyhypopomus gauderio. To determine whether the duration of the signal pulse could function as an honest indicator of androgen levels and other androgen-mediated traits, we measured the variation in sex steroids, signal pulse duration, and sexual development throughout the breeding season of B. gauderio in marshes in Uruguay. Although the sexes had different hormone titres and signal characteristics, in both sexes circulating levels of the androgens testosterone (T) and 11-ketotestosterone (11-KT) were strongly related to signal pulse duration. Consequently, signal pulse duration can serve as an honest indicator of circulating androgens in males and females alike. Additionally, through phenotypic integration, signal pulse duration also predicts other sexual traits directly related to androgen production: gonad size in males and estradiol (E2) levels in females. Our findings show that tight hormonal phenotypic integration between advertisement signal and other sex steroid-mediated traits renders the advertisement signal an honest indicator of a suite of reproductive traits. PMID:21802421

  5. The effects of diabetes on male fertility and epigenetic regulation during spermatogenesis.

    PubMed

    Ding, Guo-Lian; Liu, Ye; Liu, Miao-E; Pan, Jie-Xue; Guo, Meng-Xi; Sheng, Jian-Zhong; Huang, He-Feng

    2015-01-01

    The effects of diabetes mellitus include long-term damages, dysfunctions, and failures of various organs. An important complication of diabetes is the disturbance in the male reproductive system. Glucose metabolism is an important event in spermatogenesis. Moreover, glucose metabolism is also important for maintaining basic cell activity, as well as specific functions, such as motility and fertilization ability in mature sperm. Diabetic disease and experimentally induced diabetes both demonstrated that either type 1 diabetes or type 2 diabetes could have detrimental effects on male fertility, especially on sperm quality, such as sperm motility, sperm DNA integrity, and ingredients of seminal plasma. Epigenetic modifications are essential during spermatogenesis. The epigenetic regulation represents chromatin modifications including DNA methylation, histone modifications, remodeling of nucleosomes and the higher-order chromatin reorganization and noncoding RNAs. If spermatogenesis is affected during the critical developmental window, embryonic gonadal development, and germline differentiation, environmentally-induced epigenetic modifications may become permanent in the germ line epigenome and have a potential impact on subsequent generations through epigenetic transgenerational inheritance. Diabetes may influence the epigenetic modification during sperm spermatogenesis and that these epigenetic dysregulation may be inherited through the male germ line and passed onto more than one generation, which in turn may increase the risk of diabetes in offspring. PMID:25814158

  6. The effects of diabetes on male fertility and epigenetic regulation during spermatogenesis

    PubMed Central

    Ding, Guo-Lian; Liu, Ye; Liu, Miao-E; Pan, Jie-Xue; Guo, Meng-Xi; Sheng, Jian-Zhong; Huang, He-Feng

    2015-01-01

    The effects of diabetes mellitus include long-term damages, dysfunctions, and failures of various organs. An important complication of diabetes is the disturbance in the male reproductive system. Glucose metabolism is an important event in spermatogenesis. Moreover, glucose metabolism is also important for maintaining basic cell activity, as well as specific functions, such as motility and fertilization ability in mature sperm. Diabetic disease and experimentally induced diabetes both demonstrated that either type 1 diabetes or type 2 diabetes could have detrimental effects on male fertility, especially on sperm quality, such as sperm motility, sperm DNA integrity, and ingredients of seminal plasma. Epigenetic modifications are essential during spermatogenesis. The epigenetic regulation represents chromatin modifications including DNA methylation, histone modifications, remodeling of nucleosomes and the higher-order chromatin reorganization and noncoding RNAs. If spermatogenesis is affected during the critical developmental window, embryonic gonadal development, and germline differentiation, environmentally-induced epigenetic modifications may become permanent in the germ line epigenome and have a potential impact on subsequent generations through epigenetic transgenerational inheritance. Diabetes may influence the epigenetic modification during sperm spermatogenesis and that these epigenetic dysregulation may be inherited through the male germ line and passed onto more than one generation, which in turn may increase the risk of diabetes in offspring. PMID:25814158

  7. Integrating Membrane Transport with Male Gametophyte Development and Function through Transcriptomics1[W

    PubMed Central

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

    2006-01-01

    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∷β-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. PMID:16607029

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

    SciTech Connect

    Bock KW; D Honys; JM. Ward; S Padmanaban; EP Nawrocki; KD Hirschi; D Twell; H Sze

    2006-01-01

    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. About 1269 genes encoding classified transporters were collected from the 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.

  9. Regulation of the malic enzyme gene malE by the transcriptional regulator MalR in Corynebacterium glutamicum.

    PubMed

    Krause, Jens P; Polen, Tino; Youn, Jung-Won; Emer, Denise; Eikmanns, Bernhard J; Wendisch, Volker F

    2012-06-15

    Corynebacterium glutamicum is a Gram-positive nonpathogenic bacterium that is used for the biotechnological production of amino acids. Here, we investigated the transcriptional control of the malE gene encoding malic enzyme (MalE) in C. glutamicum ATCC 13032, which is known to involve the nitrogen regulator AmtR. Gel shift experiments using purified regulators RamA and RamB revealed binding of these regulators to the malE promoter. In DNA-affinity purification experiments a hitherto uncharacterized transcriptional regulator belonging to the MarR family was found to bind to malE promoter DNA and was designated as MalR. C. glutamicum cells overexpressing malR showed reduced MalE activities in LB medium or in minimal media with acetate, glucose, pyruvate or citrate. Deletion of malR positively affected MalE activities during growth in LB medium and minimal media with pyruvate, glucose or the TCA cycle dicarboxylates l-malate, succinate and fumarate. Transcriptional fusion analysis revealed elevated malE promoter activity in the malR deletion mutant during growth in pyruvate minimal medium suggesting that MalR acts as a repressor of malE. Purified MalR bound malE promoter DNA in gel shift experiments. Two MalR binding sites were identified in the malE promoter by mutational analysis. Thus, MalR contributes to the complex transcriptional control of malE which also involves RamA, RamB and AmtR. PMID:22261175

  10. FET proteins regulate lifespan and neuronal integrity

    PubMed Central

    Therrien, Martine; Rouleau, Guy A.; Dion, Patrick A.; Parker, J. Alex

    2016-01-01

    The FET protein family includes FUS, EWS and TAF15 proteins, all of which have been linked to amyotrophic lateral sclerosis, a fatal neurodegenerative disease affecting motor neurons. Here, we show that a reduction of FET proteins in the nematode Caenorhabditis elegans causes synaptic dysfunction accompanied by impaired motor phenotypes. FET proteins are also involved in the regulation of lifespan and stress resistance, acting partially through the insulin/IGF-signalling pathway. We propose that FET proteins are involved in the maintenance of lifespan, cellular stress resistance and neuronal integrity. PMID:27117089

  11. Regulation of Anopheles gambiae male accessory gland genes influences postmating response in female.

    PubMed

    Dottorini, Tania; Persampieri, Tania; Palladino, Pietro; Baker, Dean A; Spaccapelo, Roberta; Senin, Nicola; Crisanti, Andrea

    2013-01-01

    In Drosophila, the accessory gland proteins (Acps) secreted from the male accessory glands (MAGs) and transferred along with sperm into the female reproductive tract have been implicated in triggering postmating behavioral changes, including refractoriness to subsequent mating and propensity to egg laying. Recently, Acps have been found also in Anopheles, suggesting similar functions. Understanding the mechanisms underlying transcriptional regulation of Acps and their functional role in modulating Anopheles postmating behavior may lead to the identification of novel vector control strategies to reduce mosquito populations. We identified heat-shock factor (HSF) binding sites within the Acp promoters of male Anopheles gambiae and discovered three distinct Hsf isoforms; one being significantly up-regulated in the MAGs after mating. Through genome-wide transcription analysis of Hsf-silenced males, we observed significant down-regulation in 50% of the Acp genes if compared to control males treated with a construct directed against an unrelated bacterial sequence. Treated males retained normal life span and reproductive behavior compared to control males. However, mated wild-type females showed a ∼46% reduction of egg deposition rate and a ∼23% reduction of hatching rate (∼58% combined reduction of progeny). Our results highlight an unsuspected role of HSF in regulating Acp transcription in A. gambiae and provide evidence that Acp down-regulation in males leads a significant reduction of progeny, thus opening new avenues toward the development of novel vector control strategies. PMID:22997226

  12. GermlncRNA: a unique catalogue of long non-coding RNAs and associated regulations in male germ cell development.

    PubMed

    Luk, Alfred Chun-Shui; Gao, Huayan; Xiao, Sizhe; Liao, Jinyue; Wang, Daxi; Tu, Jiajie; Rennert, Owen M; Chan, Wai-Yee; Lee, Tin-Lap

    2015-01-01

    Spermatogenic failure is a major cause of male infertility, which affects millions of couples worldwide. Recent discovery of long non-coding RNAs (lncRNAs) as critical regulators in normal and disease development provides new clues for delineating the molecular regulation in male germ cell development. However, few functional lncRNAs have been characterized to date. A major limitation in studying lncRNA in male germ cell development is the absence of germ cell-specific lncRNA annotation. Current lncRNA annotations are assembled by transcriptome data from heterogeneous tissue sources; specific germ cell transcript information of various developmental stages is therefore under-represented, which may lead to biased prediction or fail to identity important germ cell-specific lncRNAs. GermlncRNA provides the first comprehensive web-based and open-access lncRNA catalogue for three key male germ cell stages, including type A spermatogonia, pachytene spermatocytes and round spermatids. This information has been developed by integrating male germ transcriptome resources derived from RNA-Seq, tiling microarray and GermSAGE. Characterizations on lncRNA-associated regulatory features, potential coding gene and microRNA targets are also provided. Search results from GermlncRNA can be exported to Galaxy for downstream analysis or downloaded locally. Taken together, GermlncRNA offers a new avenue to better understand the role of lncRNAs and associated targets during spermatogenesis. Database URL: http://germlncrna.cbiit.cuhk.edu.hk/ PMID:25982314

  13. GermlncRNA: a unique catalogue of long non-coding RNAs and associated regulations in male germ cell development

    PubMed Central

    Luk, Alfred Chun-Shui; Gao, Huayan; Xiao, Sizhe; Liao, Jinyue; Wang, Daxi; Tu, Jiajie; Rennert, Owen M.; Chan, Wai-Yee; Lee, Tin-Lap

    2015-01-01

    Spermatogenic failure is a major cause of male infertility, which affects millions of couples worldwide. Recent discovery of long non-coding RNAs (lncRNAs) as critical regulators in normal and disease development provides new clues for delineating the molecular regulation in male germ cell development. However, few functional lncRNAs have been characterized to date. A major limitation in studying lncRNA in male germ cell development is the absence of germ cell-specific lncRNA annotation. Current lncRNA annotations are assembled by transcriptome data from heterogeneous tissue sources; specific germ cell transcript information of various developmental stages is therefore under-represented, which may lead to biased prediction or fail to identity important germ cell-specific lncRNAs. GermlncRNA provides the first comprehensive web-based and open-access lncRNA catalogue for three key male germ cell stages, including type A spermatogonia, pachytene spermatocytes and round spermatids. This information has been developed by integrating male germ transcriptome resources derived from RNA-Seq, tiling microarray and GermSAGE. Characterizations on lncRNA-associated regulatory features, potential coding gene and microRNA targets are also provided. Search results from GermlncRNA can be exported to Galaxy for downstream analysis or downloaded locally. Taken together, GermlncRNA offers a new avenue to better understand the role of lncRNAs and associated targets during spermatogenesis. Database URL: http://germlncrna.cbiit.cuhk.edu.hk/ PMID:25982314

  14. Testosterone regulates the density of dendritic spines in the male preoptic area.

    PubMed

    Garelick, Timothy; Swann, Jennifer

    2014-03-01

    Male-typical behavior is dependent on testosterone. Castrated males gradually stop mating and engaging in sexual behaviors. Castrates treated with testosterone regain motivation and sex behaviors over time. Although this effect is well characterized, the specific mechanisms by which testosterone treatment recovers sexual behaviors remain unknown. The medial preoptic area (MPOA) is a likely site for testosterone's action on copulation. The integrity of the area is essential for the expression of male sex behavior; and the MPOA is densely populated with receptors for gonadal steroids. Moreover testosterone appears to regulate synaptic efficacy in the MPOA. Exposure to sexually relevant stimuli stimulates the MPOA but only in the presence of circulating testosterone. Sites afferent to the area respond to similar exposure independent of the hormonal milieu suggesting that testosterone mediates communication between the MPOA and its afferents. The protracted time course suggests that the effects of steroidal manipulation are mediated by structural changes. The present experiment evaluated this hypothesis by comparing dendritic spine density among Syrian hamsters that were castrated, castrated and treated with testosterone, or were left gonadally intact. Brains were sectioned and stained using the rapid Golgi stain protocol (FD Neurotechnologies, Baltimore), and the spine density, dendrite length, and the number of branches were compared among groups. Intact and testosterone replaced animals had more spines and greater spine density but did not differ in dendrite length and branching from castrated animals. These results suggest that existing dendrites increase the number of spines available for synapse formation but do not extend their dendrites in response to testosterone treatment. PMID:24492023

  15. PECAM-1: regulator of endothelial junctional integrity.

    PubMed

    Privratsky, Jamie R; Newman, Peter J

    2014-03-01

    PECAM-1 (also known as CD31) is a cellular adhesion and signaling receptor comprising six extracellular immunoglobulin (Ig)-like homology domains, a short transmembrane domain and a 118 amino acid cytoplasmic domain that becomes serine and tyrosine phosphorylated upon cellular activation. PECAM-1 expression is restricted to blood and vascular cells. In circulating platelets and leukocytes, PECAM-1 functions largely as an inhibitory receptor that, via regulated sequential phosphorylation of its cytoplasmic domain, limits cellular activation responses. PECAM-1 is also highly expressed at endothelial cell intercellular junctions, where it functions as a mechanosensor, as a regulator of leukocyte trafficking and in the maintenance of endothelial cell junctional integrity. In this review, we will describe (1) the functional domains of PECAM-1 and how they contribute to its barrier-enhancing properties, (2) how the physical properties of PECAM-1 influence its subcellular localization and its ability to influence endothelial cell barrier function, (3) various stimuli that initiate PECAM-1 signaling and/or function at the endothelial junction and (4) cross-talk of PECAM-1 with other junctional molecules, which can influence endothelial cell function. PMID:24435645

  16. Male gonadal function in coeliac disease: III. Pituitary regulation.

    PubMed

    Farthing, M J; Rees, L H; Dawson, A M

    1983-12-01

    Pituitary regulation of gonadal function was investigated in 39 consecutive men with treated and untreated coeliac disease and in an intestinal disease control group of 19 men with Crohn's disease of similar age and general nutritional status. Basal serum FSH concentration was increased in 10 of the coeliacs (26%) compared to only two of 19 men with Crohn's disease (11%). This abnormality was observed with equal frequency in both treated and untreated coeliacs, and was not associated with oligospermia. Serum LH concentration was increased in eight of 15 untreated coeliacs (53%) with sub-total villous atrophy, an abnormality which unlike the elevation of serum FSH, appears to return towards normal after gluten withdrawal. Serum LH was high in coeliacs despite marked elevation of the free testosterone index. Exaggerated responses of FSH and LH to LHRH were found in 89% and 45% respectively, of coeliacs with sub-total villous atrophy. However, exaggerated responses of LH alone were found more frequently in coeliacs than in men with Crohn's disease (P less than 0.02) and unlike the exaggerated FSH responses, LH responses were closely related to jejunal morphology. Exaggerated responses of FSH and LH in coeliacs were commonly found when basal gonadotrophin concentrations were normal. The occurrence of exaggerated gonadotrophin responses could not be related to plasma concentration of testosterone, dihydrotestosterone, oestradiol or the free testosterone index. Serum prolactin was modestly raised in 25% of untreated and partially treated coeliacs and in the same proportion of men with Crohn's disease. Elevated serum prolactin concentrations never exceeded 809 mU/l and were not associated with impotence or infertility. This study provides further evidence that in men with coeliac disease there is a derangement of pituitary regulation of gonadal function. This would seem to be part of a wider disturbance of central regulatory mechanisms of endocrine function in coeliac

  17. 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

  18. Genetic Isolation of Hypothalamic Neurons that Regulate Context-Specific Male Social Behavior.

    PubMed

    Soden, Marta E; Miller, Samara M; Burgeno, Lauren M; Phillips, Paul E M; Hnasko, Thomas S; Zweifel, Larry S

    2016-07-12

    Nearly all animals engage in a complex assortment of social behaviors that are essential for the survival of the species. In mammals, these behaviors are regulated by sub-nuclei within the hypothalamus, but the specific cell types within these nuclei responsible for coordinating behavior in distinct contexts are only beginning to be resolved. Here, we identify a population of neurons in the ventral premammillary nucleus of the hypothalamus (PMV) that are strongly activated in male intruder mice in response to a larger resident male but that are not responsive to females. Using a combination of molecular and genetic approaches, we demonstrate that these PMV neurons regulate intruder-specific male social behavior and social novelty recognition in a manner dependent on synaptic release of the excitatory neurotransmitter glutamate. These data provide direct evidence for a unique population of neurons that regulate social behaviors in specific contexts. PMID:27346361

  19. 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

  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. Epigenetic regulation of the RHOX homeobox gene cluster and its association with human male infertility

    PubMed Central

    Richardson, Marcy E.; Bleiziffer, Andreas; Tüttelmann, Frank; Gromoll, Jörg; Wilkinson, Miles F.

    2014-01-01

    The X-linked RHOX cluster encodes a set of homeobox genes that are selectively expressed in the reproductive tract. Members of the RHOX cluster regulate target genes important for spermatogenesis promote male fertility in mice. Studies show that demethylating agents strongly upregulate the expression of mouse Rhox genes, suggesting that they are regulated by DNA methylation. However, whether this extends to human RHOX genes, whether DNA methylation directly regulates RHOX gene transcription and how this relates to human male infertility are unknown. To address these issues, we first defined the promoter regions of human RHOX genes and performed gain- and loss-of-function experiments to determine whether human RHOX gene transcription is regulated by DNA methylation. Our results indicated that DNA methylation is necessary and sufficient to silence human RHOX gene expression. To determine whether RHOX cluster methylation associates with male infertility, we evaluated the methylation status of RHOX genes in sperm from a large cohort of infertility patients. Linear regression analysis revealed a strong association between RHOX gene cluster hypermethylation and three independent types of semen abnormalities. Hypermethylation was restricted specifically to the RHOX cluster; we did not observe it in genes immediately adjacent to it on the X chromosome. Our results strongly suggest that human RHOX homeobox genes are under an epigenetic control mechanism that is aberrantly regulated in infertility patients. We propose that hypermethylation of the RHOX gene cluster serves as a marker for idiopathic infertility and that it is a candidate to exert a causal role in male infertility. PMID:23943794

  2. Evaluation of an integrated approach to safeguards regulations. Volume 1

    SciTech Connect

    Al-Ayat, R.A.; Judd, B.R.; McCord, R.K.

    1981-03-01

    This study investigates advantages and disadvantages of an integrated approach to safeguards regulation. We define integrated safeguards regulation as a single, performance-oriented rule governing the performance of both the physical protection (PP) and material control and accounting (MC and A) systems at licensed nuclear fuel-cycle facilities. The study produced a systematic framework for NRC to evaluate the advantages and disadvantages of an integrated approach. Within this framework, we consider the effects of integration on NRC, on licensed facilities and on the public. We present several specific examples of how integrated safeguards could be implemented at licensed facilities. Some of these examples are analyzed quantitatively using the Aggregated Systems Model (ASM) to show how safeguards performance could improve with integrated safeguards. The ASM uses an integrated approach to safeguards evaluation by ''giving credit'' for the contribution of both PP and MC and A performance in achieving safeguards goals. 12 refs., 11 figs.

  3. Prenatal nicotine exposure alters postnatal cardiorespiratory integration in young male but not female rats

    PubMed Central

    Boychuk, Carie R.; Hayward, Linda F.

    2011-01-01

    The present study tested the hypothesis that prenatal nicotine exposure (PNE) induces sex specific alternations in indices of cardiorespiratory coupling during early development. Rat pups exposed to either nicotine (6mg/kg/day) or saline (control) in utero were chronically instrumented with ECG electrodes for measurement of heart rate (HR) and respiratory frequency (RF) was monitored by whole body plethysmography on postnatal days (P)13, P16 and P26. PNE had no identifiable effect on resting respiratory frequency (RF) in either sex. There was however a strong trend (p=0.057) for resting HR to be elevated by PNE in male offspring only. Alternatively, the HR response to hypoxia (10% O2), was significantly blunted at P13 but significantly elevated at P26 s in the absence of any significant change in RF in PNE males only. Indicators of respiratory sinus arrhythmia (RSA) were also significantly reduced in P26 PNE males. No significant effects of PNE on HR, RF or RSA were identified in female offspring at any age. Our results demonstrate that PNE induces very specific changes in cardiorespiratory integration at select postnatal ages and these changes are more prominent in males. Additionally, alternations in cardiorespiratory integration appear to persist into later development in males only, potentially increasing the risk for cardiovascular diseases such as hypertension later in life. PMID:21945005

  4. INTEGRATED CONTROL OF COMBINED SEWER REGULATORS USING WEATHER RADAR

    EPA Science Inventory

    Integrated operation was simulated of ten dynamic combined sewer regulators on a Montreal interceptor. Detailed review of digital recording weather radar capabilities indicated that it is potentially the best rainfall estimation means for accomplishing the runoff prediction that ...

  5. 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

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

    PubMed

    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

  7. HIV-Positive Men's Experiences with Integrated Family Planning and HIV Services in Western Kenya: Integration Fosters Male Involvement

    PubMed Central

    Baum, Sarah; Grossman, Daniel; Steinfeld, Rachel; Onono, Maricianah; Cohen, Craig; Bukusi, Elizabeth; Newmann, Sara

    2014-01-01

    Abstract A growing body of evidence indicates that integrating family planning (FP) services into HIV care is effective at improving contraceptive uptake among HIV-positive women in resource-poor settings, yet little research has examined HIV-positive men's experiences with such integration. We conducted in-depth interviews with 21 HIV-positive men seeking care at HIV clinics in Nyanza, Kenya. All clinics were intervention sites for a FP/HIV service integration cluster-randomized trial. Grounded theory was used to code and analyze the data. Our findings highlight men's motivations for FP, reasons why men prefer obtaining their FP services, which include education, counseling, and commodities, at HIV care clinics, and specific ways in which integrated FP/HIV services fostered male inclusion in FP decision-making. In conclusion, men appear invested in FP and their inclusion in FP decision-making may bolster both female and male agency. Men's positive attitudes towards FP being provided at HIV care clinics supports the programmatic push towards integrated delivery models for FP and HIV services. PMID:24927494

  8. HIV-positive men's experiences with integrated family planning and HIV services in western Kenya: integration fosters male involvement.

    PubMed

    Patel, Rena; Baum, Sarah; Grossman, Daniel; Steinfeld, Rachel; Onono, Maricianah; Cohen, Craig; Bukusi, Elizabeth; Newmann, Sara

    2014-08-01

    A growing body of evidence indicates that integrating family planning (FP) services into HIV care is effective at improving contraceptive uptake among HIV-positive women in resource-poor settings, yet little research has examined HIV-positive men's experiences with such integration. We conducted in-depth interviews with 21 HIV-positive men seeking care at HIV clinics in Nyanza, Kenya. All clinics were intervention sites for a FP/HIV service integration cluster-randomized trial. Grounded theory was used to code and analyze the data. Our findings highlight men's motivations for FP, reasons why men prefer obtaining their FP services, which include education, counseling, and commodities, at HIV care clinics, and specific ways in which integrated FP/HIV services fostered male inclusion in FP decision-making. In conclusion, men appear invested in FP and their inclusion in FP decision-making may bolster both female and male agency. Men's positive attitudes towards FP being provided at HIV care clinics supports the programmatic push towards integrated delivery models for FP and HIV services. PMID:24927494

  9. Understanding the Relationships among Racial Identity, Self-Efficacy, Institutional Integration and Academic Achievement of Black Males Attending Research Universities

    ERIC Educational Resources Information Center

    Reid, Karl W.

    2013-01-01

    This study asserts that African American males with higher grade point averages (GPAs) in college are also academically and socially integrated into campus and hold racial identity attitudes and self-efficacy beliefs that facilitate their level of institutional integration. The statistical study of 190 African American males attending five…

  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. Integrative regulation of human brain blood flow.

    PubMed

    Willie, Christopher K; Tzeng, Yu-Chieh; Fisher, Joseph A; Ainslie, Philip N

    2014-03-01

    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

  12. 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

  13. 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

  14. SCML2 Establishes the Male Germline Epigenome through Regulation of Histone H2A Ubiquitination

    PubMed Central

    Hasegawa, Kazuteru; Sin, Ho-Su; Maezawa, So; Broering, Tyler J.; Kartashov, Andrey V.; Alavattam, Kris G.; Ichijima, Yosuke; Zhang, Fan; Bacon, W. Clark; Greis, Kenneth D.; Andreassen, Paul R.; Barski, Artem; Namekawa, Satoshi H.

    2015-01-01

    SUMMARY Gametogenesis is dependent on the expression of germline-specific genes. However, it remains unknown how the germline epigenome is distinctly established from that of somatic lineages. Here we show that genes commonly expressed in somatic lineages and spermatogenesis-progenitor cells undergo repression in a genome-wide manner in late stages of the male germline and identify underlying mechanisms. SCML2, a germline-specific subunit of a Polycomb repressive complex 1 (PRC1), establishes the unique epigenome of the male germline through two distinct antithetical mechanisms. SCML2 works with PRC1 and promotes RNF2-dependent ubiquitination of H2A, thereby marking somatic/progenitor genes on autosomes for repression. Paradoxically, SCML2 also prevents RNF2-dependent ubiquitination of H2A on sex chromosomes during meiosis, thereby enabling unique epigenetic programming of sex chromosomes for male reproduction. Our results reveal divergent mechanisms involving a shared regulator by which the male germline epigenome is distinguished from that of the soma and progenitor cells. PMID:25703348

  15. Androgen Inhibits Abdominal Fat Accumulation and Negatively Regulates the PCK1 Gene in Male Chickens

    PubMed Central

    Shao, Yonggang; Li, Junying; Ling, Yao; Teng, Kedao; Li, Hongwei; Wu, Changxin

    2013-01-01

    Capons are male chickens whose testes have been surgically incised. Capons show a significant increase in fat accumulation compared to intact male chickens. However, while caponization leads to a significant reduction in androgen levels in roosters, little is known about the molecular mechanisms through which androgen status affects lipogenesis in avian species. Therefore, investigation of the influence of androgens on fat accumulation in the chicken will provide insights into this process. In this study, Affymetrix microarray technology was used to analyze the gene expression profiles of livers from capons and intact male chickens because the liver is the major site of lipogenesis in avian species. Through gene ontology, we found that genes involved in hepatic lipogenic biosynthesis were the most highly enriched. Interestingly, among the upregulated genes, the cytosolic form of the phosphoenolpyruvate carboxykinase (PCK1) gene showed the greatest fold change. Additionally, in conjunction with quantitative real-time PCR data, our results suggested that androgen status negatively regulated the PCK1 gene in male chickens. PMID:23544081

  16. Doublesex Regulates the Connectivity of a Neural Circuit Controlling Drosophila Male Courtship Song.

    PubMed

    Shirangi, Troy R; Wong, Allan M; Truman, James W; Stern, David L

    2016-06-20

    It is unclear how regulatory genes establish neural circuits that compose sex-specific behaviors. The Drosophila melanogaster male courtship song provides a powerful model to study this problem. Courting males vibrate a wing to sing bouts of pulses and hums, called pulse and sine song, respectively. We report the discovery of male-specific thoracic interneurons-the TN1A neurons-that are required specifically for sine song. The TN1A neurons can drive the activity of a sex-non-specific wing motoneuron, hg1, which is also required for sine song. The male-specific connection between the TN1A neurons and the hg1 motoneuron is regulated by the sexual differentiation gene doublesex. We find that doublesex is required in the TN1A neurons during development to increase the density of the TN1A arbors that interact with dendrites of the hg1 motoneuron. Our findings demonstrate how a sexual differentiation gene can build a sex-specific circuit motif by modulating neuronal arborization. PMID:27326931

  17. Cystic fibrosis transmembrane conductance regulator protein expression in the male excretory duct system during development.

    PubMed

    Marcorelles, Pascale; Gillet, Danièle; Friocourt, Gaëlle; Ledé, Françoise; Samaison, Laura; Huguen, Geneviève; Ferec, Claude

    2012-03-01

    Sterility due to bilateral destruction in utero or in early infancy resulting in congenital absence of the vas deferens is the rule in male patients with cystic fibrosis. To understand the developmental pattern of this anomaly, the microscopic morphology of the male excretory system was analyzed during development and the expression of the cystic fibrosis transmembrane conductance regulator protein was explored by immunohistochemistry. We observed that cystic fibrosis fetuses had no excretory ducts agenesis or obstruction until 22 weeks of gestation. However, a focal inflammatory pattern and mucinous plugs in the oldest cystic fibrosis case suggested a disruptive mechanism. Immunolabeling of cytoplasmic epithelial cystic fibrosis transmembrane conductance regulator protein was demonstrated in all cystic fibrosis and control cases with a similar pattern of expression of the protein between age-matched controls and cystic fibrosis cases. At midgestation, an apical intensification appeared in both cystic fibrosis and control cases and was stable during the remainder of fetal life. No gradient of intensity could be detected between the different segments of the excretory tract. These findings are different from those reported in adults. The absence of any morphologic anomaly until 22 weeks of gestation, the focal destruction of the epithelial structures during the second trimester, and the chronological pattern of expression of cystic fibrosis transmembrane conductance regulator are of interest for a better understanding of the pathophysiology of this disease. PMID:21840567

  18. Regulation of Caenorhabditis elegans Male Mate Searching Behavior by the Nuclear Receptor DAF-12

    PubMed Central

    Kleemann, Gunnar; Jia, Lingyun; Emmons, Scott W.

    2008-01-01

    Coordination of animal behavior with reproductive status is often achieved through elaboration of hormones by the gonad. In the nematode Caenorhabditis elegans, adult males explore their environment to locate mates. Mate searching is regulated by presence of mates, nutritional status, and a signal from the gonad. Here we show that the gonadal signal acts via the nuclear receptor DAF-12, a protein known to regulate several C. elegans life-history traits. DAF-12 has both activational and organizational functions to stimulate exploratory behavior and acts downstream of the gonadal signal, outside of the gonad. DAF-12 acts upstream of sensory input from mating partners and physiological signals indicating nutritional status. Mate searching was rescued in germ-line ablated animals, but not if both germ line and somatic gonad were ablated, by a precursor of the DAF-12 ligand, dafachronic acid (DA). The results are interpreted to suggest that the germ line produces a DA precursor that is converted to DA outside of the germ line, possibly in the somatic gonad. As it does in other pathways in which it functions, in regulation of male mate searching behavior DAF-12 acts at a choice point between alternatives favoring reproduction (mate searching) vs. survival (remaining on food). PMID:18854588

  19. Characterization and steroidal regulation of gonadotropin beta subunits in the male leopard frog, Rana pipiens.

    PubMed

    Zhang, Lihong; Kessler, Ann E; Tsai, Pei-San

    2007-01-01

    In ranid frogs, the secretion of gonadotropins (GtHs), luteinizing hormone (LH), and follicle-stimulating hormone (FSH), is potently regulated by gonadal steroids. To better understand the gonadal regulation of GtHs at the molecular level, we elucidated the full-length cDNA sequences of LH and FSH beta subunits from the leopard frog, Rana pipiens. The cDNAs for LHbeta and FSHbeta were 1084 and 667 bp in size excluding the poly (A) tail, and encoded proteins of 138 and 127 amino acids, respectively. Using reverse-transcription polymerase chain reaction (RT-PCR), the messages for LHbeta and FSHbeta were found in the pituitary, but not in the brain, heart, kidney, or the liver. Semi-quantitative RT-PCR revealed a significant elevation of FSHbeta, but not LHbeta, in mature male R. pipiens 21 days after gonadectomy (GDX). 17beta-estradiol implant for 21 days in GDX male frogs significantly suppressed the levels of both LHbeta and FSHbeta transcripts, whereas 5alpha-dihydrotestosterone implant suppressed only the latter. Together, these results laid the groundwork for investigating gonadal regulation of GtHbeta subunits in a ranid frog. Importantly, these data also revealed differential feedback effects of an androgen and an estrogen upon GtHbeta expression. PMID:16920113

  20. Specific regulation of male rat liver cytosolic estrogen receptor by the modulator of the glucocorticoid receptor.

    PubMed

    Celiker, M Y; Haas, A; Saunders, D; Litwack, G

    1993-08-31

    Modulator is a novel low-molecular-weight organic compound that regulates activities of glucocorticoid and mineralocorticoid receptors as well as protein kinase C. In this study we show that male rat liver cytosolic estrogen receptor activation is inhibited by modulator in a dose-dependent manner. Fifty percent inhibition is obtained with 1 unit/ml modulator purified from bovine liver which is within the physiological concentration for modulator. However, sheep uterine cytosolic estrogen and androgen receptors are insensitive to regulation by modulator. Exogenous sodium molybdate treatment inhibits activation of all of these receptors of liver or uterus origin in an identical manner, further differentiating the effects of modulator and the molybdate anion. PMID:8363596

  1. 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

  2. The Lombard effect in male ultrasonic frogs: Regulating antiphonal signal frequency and amplitude in noise.

    PubMed

    Shen, Jun-Xian; Xu, Zhi-Min

    2016-01-01

    Acoustic communication in noisy environments presents a significant challenge for vocal animals because noise can interfere with animal acoustic signals by decreasing signal-to-noise ratios and masking signals. Birds and mammals increase call intensity or frequency as noise levels increase, but it is unclear to what extend this behavior is shared by frogs. Concave-eared torrent frogs (Odorrana tormota) have evolved the capacity to produce various calls containing ultrasonic harmonics and to communicate beside noisy streams. However, it is largely unclear how frogs regulate vocalization in response to increasing noise levels. We exposed male frogs to various levels of noise with playback of conspecific female courtship calls and recorded antiphonal signals and spontaneous short calls. Males were capable of rapidly adjusting fundamental frequency and amplitude of antiphonal signals as noise levels increased. The increment in fundamental frequency and amplitude was approximately 0.5 kHz and 3 dB with every 10 dB increase in noise level, indicating the presence of noise-dependent signal characteristics. Males showed the noise-tolerant adaption in response to female calls in noise level from 40 to 90 dB SPL. The results suggest that the noise-dependent signal characteristics in O. tormota have evolved as a strategy to cope with varying torrent noise. PMID:27345957

  3. Low dose 4-MBC effect on neuroendocrine regulation of reproductive axis in adult male rats.

    PubMed

    Carou, Maria E; Ponzo, Osvaldo J; Cardozo Gutierrez, Romina P; Szwarcfarb, Berta; Deguiz, Maria L; Reynoso, Roxana; Carbone, Silvia; Moguilevsky, Jaime A; Scacchi, Pablo

    2008-09-01

    4-Methylbenzylidene camphor (4-MBC) is an ultraviolet absorbent. The objective of this paper was to evaluate the effect of 4-MBC low-dose exposure on the neuroendocrine reproductive regulation in male rats. Wistar male adult rats were injected sc. with 4-MBC during 5 days with a dose of 2 and 10mg/kg or during 2 days with a dose of 2 and 20mg/kg. In all rats serum prolactin, LH and FSH concentration were assayed. The hypothalamus of rats injected during 2 days were also dissected to study GnRH release. Rats that received 2 and 10mg/kg of 4-MBC during 5 days showed a decrease in the LH and FSH serum concentration. In rats injected during 2 days, serum LH decreased with 2 and 20mg/kg and FSH decreased with 2mg/kg of 4-MBC. In vitro hypothalamic GnRH release also decreased in these animals. These results show that low doses of 4-MBC inhibit the reproductive axis in adult male rats. PMID:21783915

  4. The Lombard effect in male ultrasonic frogs: Regulating antiphonal signal frequency and amplitude in noise

    PubMed Central

    Shen, Jun-Xian; Xu, Zhi-Min

    2016-01-01

    Acoustic communication in noisy environments presents a significant challenge for vocal animals because noise can interfere with animal acoustic signals by decreasing signal-to-noise ratios and masking signals. Birds and mammals increase call intensity or frequency as noise levels increase, but it is unclear to what extend this behavior is shared by frogs. Concave-eared torrent frogs (Odorrana tormota) have evolved the capacity to produce various calls containing ultrasonic harmonics and to communicate beside noisy streams. However, it is largely unclear how frogs regulate vocalization in response to increasing noise levels. We exposed male frogs to various levels of noise with playback of conspecific female courtship calls and recorded antiphonal signals and spontaneous short calls. Males were capable of rapidly adjusting fundamental frequency and amplitude of antiphonal signals as noise levels increased. The increment in fundamental frequency and amplitude was approximately 0.5 kHz and 3 dB with every 10 dB increase in noise level, indicating the presence of noise-dependent signal characteristics. Males showed the noise-tolerant adaption in response to female calls in noise level from 40 to 90 dB SPL. The results suggest that the noise-dependent signal characteristics in O. tormota have evolved as a strategy to cope with varying torrent noise. PMID:27345957

  5. 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

  6. 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. PMID:26710087

  7. Subacute toxicity assessment of diflubenzuron, an insect growth regulator, in adult male rats.

    PubMed

    de Barros, Aline Lima; Cavalheiro, Gabriela Finoto; de Souza, Alexsandra Vila Maior; Traesel, Giseli Karenina; Anselmo-Franci, Janete A; Kassuya, Cândida Aparecida Leite; Arena, Arielle Cristina

    2016-04-01

    Diflubenzuron (DFB), an insecticide and acaricide insect growth regulator, can be used in agriculture against insect predators and in public health programs, to control insects and vectors, mainly Aedes aegypti larvae. Due to the lack of toxicological assessments of this compound, the objective of the present study was to evaluate the toxicological effects of subacute exposure to the DFB insecticide in adult male rats. Adult male rats were exposed (gavage) to 0, 2, 4, or 8 mg/kg of DFB for 28 days. No clinical signs of toxicity were observed in the DFB-treated animals of the experimental groups. However, there was an increase in serum levels of alanine aminotransferase in the group that received 8 mg/kg/DFB/day and urea at doses of 4 and 8 mg/kg/DFB/day, without altering other biochemical or hematological parameters. The subacute exposure to the lowest dose of DFB caused significant decrease in testis weight, daily sperm production, and in number of sperm in the epididymis in relation to the control group. However, no alterations were observed in the sperm morphology, testicular, epididymis, liver and kidney histology, or testosterone levels. These findings unveiled the hazardous effects of DFB on male reproduction after the subacute exposure and special attention should be addressed to the effects of low doses of this pesticide. PMID:25266294

  8. Regulation of male fertility by the bone-derived hormone osteocalcin

    PubMed Central

    KARSENTY, Gerard; OURY, Franck

    2013-01-01

    Traditionally, bone has been viewed as a relatively static tissue only fulfilling mechanical and scaffolding function. In the past decade however, this classical view of the bone has considerably evolved towards a more complex picture. It is now clear that the skeleton is not only a recipient for hormonal input but it is also an endocrine organ itself. Through the secretion of an osteoblast-derived molecule, osteocalcin, the skeleton regulates glucose homeostasis and male reproductive functions. When undercarboxylated, osteocalcin acts following its binding to a G-coupled receptor, GPRC6A, on pancreatic β cells to increase insulin secretion, on muscle and white adipose tissue to promote glucose homeostasis and on Leydig cells of the testis to favor testosterone biosynthesis. More recently, it was also shown that osteocalcin acts via a pancreas-bone-testis axis that regulates, independently of and in parallel to the hypothalamus-pituitary-testis axis, male reproductive functions by promoting testosterone biosynthesis. Lastly, in trying to expand the biological relevance of osteocalcin from mouse to human, it was shown that GPRC6A is a potential new susceptibility locus for primary testicular failure in humans. Altogether, these results shed new light on the importance of the endocrine role of the skeleton and also provide credence to the search for additional endocrine functions of this organ. PMID:24145129

  9. Are separable aromatase systems involved in hormonal regulation of the male brain

    SciTech Connect

    Hutchison, J.B.; Schumacher, M.; Steimer, T.; Gahr, M. )

    1990-07-01

    In vitro study of testosterone (T) metabolism shows that formation of estradiol-17 beta (E2) is regionally specific within the preoptic area (POA) of the male ring dove. The POA is known to be involved in the formation of E2 required for specific components of male sexual behavior. Two sub-areas of high aromatase activity, anterior (aPOA) and posterior preoptic (pPOA) areas, have been identified. Aromatase activity is higher in aPOA than in pPOA. The aromatase activity within the aPOA is also more sensitive to the inductive effects of low circulating T, derived from subcutaneous silastic implants, than the enzyme activity in pPOA. Kinetic analysis of preoptic fractions indicates that a similar high-affinity enzyme occurs in both areas (apparent Km less than 14 nM), but the Vmax of aPOA enzyme activity is higher than pPOA. Cells containing estrogen receptors (ER) are localized in areas of high aromatase activity. There is overlap between immunostained cells in the aPOA and in samples containing inducible aromatase activity measured in vitro. Within the aPOA there is a higher density of ER cells in the nucleus preopticus medialis. The pPOA area also contains ER, notably in the nucleus interstitialis, but at a lower density. We conclude that the hormonal regulation of the male preoptic-anterior hypothalamic region, which is a target for the behavioral action of T, involves at least two inducible aromatase systems with associated estrogen receptor cells.

  10. Regulation of the corpora allata in male larvae of the cockroach Diploptera punctata

    SciTech Connect

    Paulson, C.R.

    1986-01-01

    The regulation of corpora allata was studied in final instar males of Diploptera punctata. The glands were manipulated in vivo and removed to determine the effect by in vitro radiochemical assay for juvenile hormone synthesis. Corpora allata were also treated with putative regulatory factors in vitro. During the final stadium the corpora allata were inhibited both by nerves and by humoral factors. Neural inhibition was shown by an increase in juvenile hormone synthesis following denervation of the corpora allata. This operation elicited an extra larval instar. Humoral inhibition was shown by the decline in juvenile hormone synthesis of adult female corpora allata following transplantation into final instar larval hosts, and conversely the increase in juvenile hormone synthesis by larval corpora allata following implantation into adult females. Humoral inhibition was prevented by decapitation of larvae prior to the head critical period for molting and restored by implantation of a larval brain, showing that the brain is the source of this inhibition.

  11. Sox8 is a critical regulator of adult Sertoli cell function and male fertility.

    PubMed

    O'Bryan, Moira K; Takada, Shuji; Kennedy, Claire L; Scott, Greg; Harada, Shun-ichi; Ray, Manas K; Dai, Qunsheng; Wilhelm, Dagmar; de Kretser, David M; Eddy, E Mitch; Koopman, Peter; Mishina, Yuji

    2008-04-15

    Sox8 encodes a high-mobility group transcription factor that is widely expressed during development. Sox8, -9 and -10 form group E of the Sox gene family which has been implicated in several human developmental disorders. In contrast to other SoxE genes, the role of Sox8 is unclear and Sox8 mouse mutants reportedly showed only idiopathic weight loss and reduced bone density. The careful analysis of our Sox8 null mice, however, revealed a progressive male infertility phenotype. Sox8 null males only sporadically produced litters of reduced size at young ages. We have shown that SOX8 protein is a product of adult Sertoli cells and its elimination results in an age-dependent deregulation of spermatogenesis, characterized by sloughing of spermatocytes and round spermatids, spermiation failure and a progressive disorganization of the spermatogenic cycle, which resulted in the inappropriate placement and juxtaposition of germ cell types within the epithelium. Those sperm that did enter the epididymides displayed abnormal motility. These data show that SOX8 is a critical regulator of adult Sertoli cell function and is required for both its cytoarchitectural and paracrine interactions with germ cells. PMID:18342849

  12. Integrator complex and transcription regulation: Recent findings and pathophysiology.

    PubMed

    Rienzo, Monica; Casamassimi, Amelia

    2016-10-01

    In the last decade, a novel molecular complex has been added to the RNA polymerase II-mediated transcription machinery as one of the major components. This multiprotein complex, named Integrator, plays a pivotal role in the regulation of most RNA Polymerase II-dependent genes. This complex consists of at least 14 different subunits. However, studies investigating its structure and composition are still lacking. Although it was originally discovered as a complex implicated in the 3'-end formation of noncoding small nuclear RNAs, recent studies indicate additional roles for Integrator in transcription regulation, for example during transcription pause-release and elongation of polymerase, in the biogenesis of transcripts derived from enhancers, as well as in DNA and RNA metabolism for some of its components. Noteworthy, several subunits have been emerging to play roles during development and differentiation; more importantly, their alterations are likely to be involved in several human pathologies, including cancer and lung diseases. PMID:27427483

  13. Regulation of Sclerostin Production in Human Male Osteocytes by Androgens: Experimental and Clinical Evidence.

    PubMed

    Di Nisio, Andrea; De Toni, Luca; Speltra, Elena; Rocca, Maria Santa; Taglialavoro, Giuseppe; Ferlin, Alberto; Foresta, Carlo

    2015-12-01

    In this study we aimed to elucidate a possible role of T in the regulation of sclerostin, a glycoprotein secreted by osteocytes known to regulate bone mass. To this end, we evaluated the effect of T stimulation on sclerostin production and gene expression in human cultured osteocytes. In addition, we evaluated serum sclerostin levels in a cohort of 20 hypogonadal male patients, compared with 20 age-matched eugonadal controls. Stimulation with DHT decreased sclerostin expression in cultured osteocytes in a time- and dose-dependent manner. Confirming a direct androgen receptor-mediated effect on sclerostin production, flutamide coincubation and silencing of androgen receptor gene in osteocytes abolished the DHT effects. In addition, hypogonadal patients showed higher serum sclerostin levels with respect to controls (145.87 ± 50.83 pg/mL vs 84.02 ± 32.15 pg/mL; P < .001) and in both probands and controls, serum T levels were negatively correlated with sclerostin (R = -0.664, P = 0.007, and R = -0.447, P = .045, respectively). Finally, multiple stepwise regression analysis showed that T represented the only independent predictor of sclerostin levels. In conclusion, by showing a direct correlation between T and sclerostin, both in vivo and in vitro, this study adds further support to the emerging clinical and experimental studies focusing on sclerostin as a therapeutic target for osteoporosis treatment. PMID:26393301

  14. 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

  15. Ephrin-A5 regulates inter-male aggression in mice.

    PubMed

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

    2015-06-01

    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

  16. Transcriptional regulation of glutamic acid decarboxylase in the male mouse amygdala by dietary phyto-oestrogens.

    PubMed

    Sandhu, K V; Yanagawa, Y; Stork, O

    2015-04-01

    Phyto-oestrogens are biologically active components of many human and laboratory animal diets. In the present study, we investigated, in adult male mice with C57BL/6 genetic background, the effects of a reduced phyto-oestrogens intake on anxiety-related behaviour and associated gene expression in the amygdala. After 6 weeks on a low-phyto-oestrogen diet (< 20 μg/g cumulative phyto-oestrogen content), animals showed reduced centre exploration in an open-field task compared to their littermates on a soybean-based standard diet (300 μg/g). Freezing behaviour in an auditory fear memory task, in contrast, was not affected. We hypothesised that this mildly increased anxiety may involve changes in the function of GABAergic local circuit neurones in the amygdala. Using GAD67(+/GFP) mice, we could demonstrate reduced transcription of the GAD67 gene in the lateral and basolateral amygdala under the low-phyto-oestrogen diet. Analysis of mRNA levels in microdissected samples confirmed this regulation and demonstrated concomitant changes in expression of the second glutamic acid decarboxylase (GAD) isoform, GAD65, as well as the anxiolytic neuropeptide Y. These molecular and behavioural alterations occurred without apparent changes in circulating oestrogens or testosterone levels. Our data suggest that expression regulation of interneurone-specific gene products in the amygdala may provide a mechanism for the control of anxiety-related behaviour through dietary phyto-oestrogens. PMID:25650988

  17. Nutrition regulation of male accessory gland growth and maturation in Tribolium castaneum.

    PubMed

    Xu, Jingjing; Anciro, Ashlee L; Palli, Subba Reddy

    2015-01-01

    Insulin/IGF-1 signaling (IIS) pathway is known to control growth, development and reproduction. Insulin-like peptide mediated body size plasticity in Drosophila melanogaster has been reported. Here, our studies showed that IIS pathway and nutrition regulate growth and maturation of the male accessory gland (MAG) in the red flour beetle, Tribolium castaneum. The size of MAG increased from day 1 to day 5 post-adult emergence (PAE). This increase in the size of MAG is contributed by an increase in cell size, but not cell number. The growth of MAG was impaired after double-stranded RNA (dsRNA)-mediated knockdown in the expression of genes coding for ILP3, InR, Chico, PI3k, AKT, and GATA1 involved in IIS pathway. Interestingly, starvation showed similar effects on the growth and maturation of MAG. The phenotypes observed in animals where IIS signaling pathway genes were knocked down are similar to the phenotypes observed after starving beetles for 5 days PAE. These data suggest that nutrition signals working through IIS pathway regulate maturation of MAG by promoting the growth of MAG cells. PMID:26035685

  18. How can flexibility be integrated into coexistence regulations? A review.

    PubMed

    Devos, Yann; Dillen, Koen; Demont, Matty

    2014-02-01

    Member states in the European Union (EU) implemented both ex ante coexistence regulations and ex post liability schemes to ensure that genetically modified (GM) and non-GM crops can be cultivated side by side without excluding any agricultural option. Although proportionate coexistence is best achieved if regulated in a flexible manner, most implemented coexistence regulations merely rely on rigid measures. Flexible coexistence regulations, however, would reduce the regulatory burden on certain agricultural options and avoid jeopardizing economic incentives for coexistence. Flexibility can be integrated at: (i) the regulatory level by relaxing the rigidity of coexistence measures in ex ante regulations, yet without offsetting incentives to implement coexistence measures; (ii) the farm level by recommending the use of pollen barriers instead of large and fixed isolation distances; and (iii) the national/regional level by allowing diversified coexistence measures, which are adapted to the heterogeneity of farming in the EU. Owing to difficulties of implementation, the adoption of flexible and proportionate coexistence regulations will inevitably entail challenges. PMID:23965758

  19. 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

  20. Acute regulation of plasma insulin-like peptide 3 concentrations by luteinizing hormone in male goats.

    PubMed

    Hannan, M A; Kawate, N; Fukami, Y; Pathirana, I N; Büllesbach, E E; Inaba, T; Tamada, H

    2016-08-01

    Recently, it was reported that in bulls secretion of insulin-like peptide 3 (INSL3) in blood occurred in a pulsatile manner and was acutely regulated by LH. In the present study, the acute regulation of plasma INSL3 and its temporal relationships with LH and testosterone were examined in six sexually matured male goats using the following experimental design. (1) After stimulating LH release by administering a GnRH analogue, blood levels of LH, INSL3, and testosterone were monitored at 15-minute intervals for 2 hours followed by hourly intervals up to 8 hours. (2) After activation of the LH receptor by hCG blood levels of INSL3 and testosterone were determine at 15-minute intervals for 2 hours, followed by hourly intervals up to 8 hours, daily intervals up to Day 8, and finally on Day 12. (3) The release of LH, INSL3, and testosterone in normal physiology was established at 15-minute intervals for an 8-hour session. Concentrations of LH, INSL3, and testosterone in plasma were measured by enzyme-immunoassays. After GnRH treatment, mean plasma concentrations of all three hormones increased (P < 0.05) dramatically from 30 minutes and remained high until 120 minutes (LH), 75 minutes (INSL3), and 4 hours (testosterone) after treatment. After hCG treatment, mean plasma INSL3 concentrations increased (P < 0.05) from 30 minutes and remained elevated until the end of sampling on Day 12. An increase (P < 0.05) in mean plasma testosterone concentrations occurred from 15 minutes and remained high until Day 6. The mean increase (maximum per pretreatment concentration) of INSL3 concentrations after administration of GnRH and hCG was lower (P < 0.01) than that of testosterone. The secretory pattern of LH, INSL3, and testosterone in the general circulation was pulsatile with a frequency of 5.5 ± 0.6, 4.7 ± 0.5, and 2.2 ± 0.5, respectively, during the 8-hour period. Twenty out of 28 (71%) of these INSL3 pulses peaked within 1 hour after a peak of an LH

  1. Identification of nuclear receptors involved in regulation of male reproduction in the red flour beetle, Tribolium castaneum.

    PubMed

    Xu, Jingjing; Raman, Chandrasekar; Zhu, Fang; Tan, Anjiang; Palli, Subba R

    2012-05-01

    Nineteen canonical and two Knirps-like family nuclear receptors (NRs) were identified in the genome of Tribolium castaneum. The current study was conducted to identify NRs involved in regulation of male reproduction. RNA interference (RNAi)-aided knockdown in the expression of genes coding for all 21 NRs showed that reduction in the levels of 11 NRs (E75, E78, FTZ-F1, HR38, HR4, Knirps-like, HNF4, Tailless, HR51, Dsf and HR39) in the male beetles caused more than 50% reduction in the eggs laid by the female beetles mated with RNAi male beetles. Among these 11 NRs that are required for male reproduction, knockdown in the expression of genes coding for E78 and HR39 in the male beetles resulted in a reduction in the number of sperm produced and transferred to the female when compared to the sperms produced and transferred by the control male beetles injected with bacterial malE dsRNA. In contrast, knockdown in the expression of genes coding for E75 and HR38 caused a reduction in the size of male accessory glands (MAG), the amount of protein produced by the MAG and the expression of genes coding for accessory gland proteins. These data suggest that NRs such as E78 and HR39 regulate sperm production and their transfer to the females and the other NRs such as E75 and HR38 regulate the development of MAG and the production of accessory gland proteins. PMID:22402169

  2. 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

  3. Whole-animal genome-wide RNAi screen identifies networks regulating male germline stem cells in Drosophila.

    PubMed

    Liu, Ying; Ge, Qinglan; Chan, Brian; Liu, Hanhan; Singh, Shree Ram; Manley, Jacob; Lee, Jae; Weideman, Ann Marie; Hou, Gerald; Hou, Steven X

    2016-01-01

    Stem cells are regulated both intrinsically and externally, including by signals from the local environment and distant organs. To identify genes and pathways that regulate stem-cell fates in the whole organism, we perform a genome-wide transgenic RNAi screen through ubiquitous gene knockdowns, focusing on regulators of adult Drosophila testis germline stem cells (GSCs). Here we identify 530 genes that regulate GSC maintenance and differentiation. Of these, we further knock down 113 selected genes using cell-type-specific Gal4s and find that more than half were external regulators, that is, from the local microenvironment or more distal sources. Some genes, for example, versatile (vers), encoding a heterochromatin protein, regulates GSC fates differentially in different cell types and through multiple pathways. We also find that mitosis/cytokinesis proteins are especially important for male GSC maintenance. Our findings provide valuable insights and resources for studying stem cell regulation at the organismal level. PMID:27484291

  4. Whole-animal genome-wide RNAi screen identifies networks regulating male germline stem cells in Drosophila

    PubMed Central

    Liu, Ying; Ge, Qinglan; Chan, Brian; Liu, Hanhan; Singh, Shree Ram; Manley, Jacob; Lee, Jae; Weideman, Ann Marie; Hou, Gerald; Hou, Steven X.

    2016-01-01

    Stem cells are regulated both intrinsically and externally, including by signals from the local environment and distant organs. To identify genes and pathways that regulate stem-cell fates in the whole organism, we perform a genome-wide transgenic RNAi screen through ubiquitous gene knockdowns, focusing on regulators of adult Drosophila testis germline stem cells (GSCs). Here we identify 530 genes that regulate GSC maintenance and differentiation. Of these, we further knock down 113 selected genes using cell-type-specific Gal4s and find that more than half were external regulators, that is, from the local microenvironment or more distal sources. Some genes, for example, versatile (vers), encoding a heterochromatin protein, regulates GSC fates differentially in different cell types and through multiple pathways. We also find that mitosis/cytokinesis proteins are especially important for male GSC maintenance. Our findings provide valuable insights and resources for studying stem cell regulation at the organismal level. PMID:27484291

  5. Signal integration by Ca2+ regulates intestinal stem cell activity

    PubMed Central

    Deng, Hansong; Gerencser, Akos A.; Jasper, Heinrich

    2015-01-01

    Summary Somatic stem cells (SCs) maintain tissue homeostasis by dynamically adjusting proliferation and differentiation in response to stress and metabolic cues. Here, we identify Ca2+ signaling as a central regulator of intestinal SC (ISC) activity in Drosophila. We find that dietary L-glutamate stimulates ISC division and gut growth. The metabotropic glutamate receptor (mGluR) is required in ISCs for this response and for an associated modulation of cytosolic Ca2+ oscillations that results in sustained high cytosolic Ca2+ concentrations. High cytosolic Ca2+ induces ISC proliferation by regulating Calcineurin and CREB - regulated transcriptional co-activator (CRTC). In response to a wide range of dietary and stress stimuli, ISCs reversibly transition between Ca2+ oscillation states that represent poised or activated modes of proliferation, respectively. We propose that the dynamic regulation of intracellular Ca2+ levels allows effective integration of diverse mitogenic signals in ISCs to tailor their proliferative activity to the needs of the tissue. PMID:26633624

  6. Circuit-level input integration in bacterial gene regulation.

    PubMed

    Espinar, Lorena; Dies, Marta; Cagatay, Tolga; Süel, Gürol M; Garcia-Ojalvo, Jordi

    2013-04-23

    Gene regulatory circuits can receive multiple simultaneous inputs, which can enter the system through different locations. It is thus necessary to establish how these genetic circuits integrate multiple inputs as a function of their relative entry points. Here, we use the dynamic circuit regulating competence for DNA uptake in Bacillus subtilis as a model system to investigate this issue. Specifically, we map the response of single cells in vivo to a combination of (i) a chemical signal controlling the constitutive expression of key competence genes, and (ii) a genetic perturbation in the form of copy number variation of one of these genes, which mimics the level of stress signals sensed by the bacteria. Quantitative time-lapse fluorescence microscopy shows that a variety of dynamical behaviors can be reached by the combination of the two inputs. Additionally, the integration depends strongly on the relative locations where the two perturbations enter the circuit. Specifically, when the two inputs act upon different circuit elements, their integration generates novel dynamical behavior, whereas inputs affecting the same element do not. An in silico bidimensional bifurcation analysis of a mathematical model of the circuit offers good quantitative agreement with the experimental observations, and sheds light on the dynamical mechanisms leading to the different integrated responses exhibited by the gene regulatory circuit. PMID:23572583

  7. Photoperiod regulates growth of male accessory glands through juvenile hormone signaling in the linden bug, Pyrrhocoris apterus.

    PubMed

    Urbanová, Veronika; Bazalová, Olga; Vaněčková, Hanka; Dolezel, David

    2016-03-01

    Adult reproductive diapause is characterized by lower behavioral activity, ceased reproduction and absence of juvenile hormone (JH). The role of JH receptor Methoprene-tolerant (Met) in female reproduction is well established; however, its function in male reproductive development and behavior is unclear. In the bean bug, Riptortus pedestris, circadian genes are essential for mediating photoperiodically-dependent growth of the male accessory glands (MAGs). The present study explores the role of circadian genes and JH receptor in male diapause in the linden bug, Pyrrhocoris apterus. These data indicate that circadian factors Clock, Cycle and Cry2 are responsible for photoperiod measurement, whereas Met and its partner protein Taiman participate in JH reception. Surprisingly, knockdown of the JH receptor neither lowered locomotor activity nor reduced mating behavior of males. These data suggest existence of a parallel, JH-independent or JH-upstream photoperiodic regulation of reproductive behavior. PMID:26826599

  8. 77 FR 52739 - Federal Acquisition Regulation; Information Collection; Integrity of Unit Prices

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-30

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

  9. Dgcr8 and Dicer are essential for sex chromosome integrity during meiosis in males

    PubMed Central

    Modzelewski, Andrew J.; Hilz, Stephanie; Crate, Elizabeth A.; Schweidenback, Caterina T. H.; Fogarty, Elizabeth A.; Grenier, Jennifer K.; Freire, Raimundo; Cohen, Paula E.; Grimson, Andrew

    2015-01-01

    ABSTRACT Small RNAs play crucial roles in regulating gene expression during mammalian meiosis. To investigate the function of microRNAs (miRNAs) and small interfering RNAs (siRNAs) during meiosis in males, we generated germ-cell-specific conditional deletions of Dgcr8 and Dicer in mice. Analysis of spermatocytes from both conditional knockout lines revealed that there were frequent chromosomal fusions during meiosis, always involving one or both sex chromosomes. RNA sequencing indicates upregulation of Atm in spermatocytes from miRNA-deficient mice, and immunofluorescence imaging demonstrates an increased abundance of activated ATM kinase and mislocalization of phosphorylated MDC1, an ATM phosphorylation substrate. The Atm 3′UTR contains many potential microRNA target sites, and, notably, target sites for several miRNAs depleted in both conditional knockout mice were highly effective at promoting repression. RNF8, a telomere-associated protein whose localization is controlled by the MDC1–ATM kinase cascade, normally associates with the sex chromosomes during pachytene, but in both conditional knockouts redistributed to the autosomes. Taken together, these results suggest that Atm dysregulation in microRNA-deficient germ lines contributes to the redistribution of proteins involved in chromosomal stability from the sex chromosomes to the autosomes, resulting in sex chromosome fusions during meiotic prophase I. PMID:25934699

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

    PubMed

    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

  11. 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

  12. DOCK8 regulates lymphocyte shape integrity for skin antiviral immunity.

    PubMed

    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; Mueller, Scott N; Su, Helen C

    2014-12-15

    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

  13. Testosterone regulates androgen receptor immunoreactivity in the copulatory, but not courtship, neuromuscular system in adult male green anoles.

    PubMed

    Holmes, M M; Wade, J

    2005-09-01

    Androgens regulate the expression of male reproductive behaviour in diverse vertebrate species, often acting on androgen receptors (AR) to induce structural or functional changes in the nervous system and periphery. Male green anoles possess two sexually dimorphic neuromuscular systems, one controlling throat fan (dewlap) extension, which occurs during courtship, and the other mediating copulatory organ function. Although androgens are required for behavioural activation in both systems, testosterone has differential effects on the neuromuscular morphology. It increases the size of copulatory muscle fibres during the breeding season, but significant effects on dewlap muscle fibre size and motoneurone soma size in either system have not been detected. Corresponding to the lack of testosterone-induced morphological effects in the courtship system, relatively low levels of AR are expressed in the associated motoneurones. The present experiment had two goals, aiming to determine whether: (i) the other courtship and copulatory neuromuscular tissues express AR and (ii) testosterone and/or seasonal environmental changes regulate AR expression. The percentage of AR+ nuclei was evaluated in both the breeding and nonbreeding seasons in gonadally intact adult males (Experiment 1) and in castrated males treated with either testosterone or vehicle (Experiment 2). AR was extensively expressed in the dewlap and copulatory muscles, and in a high percentage of the copulatory motoneurones, but immunoreactivity did not vary across season. Testosterone increased the percentage of AR+ nuclei in the copulatory muscles of both breeding and nonbreeding males but not in the dewlap muscle or copulatory motoneurones. Finally, the target structures for both systems (cartilages and hemipenes) expressed AR in all animals. Therefore, the effects of testosterone on AR immunoreactivity suggest that up-regulation of the receptors may be important for morphological change. However, because all

  14. GONADAL STEROIDS REGULATED THE EXPRESSION OF GLIAL FIBRILLARY ACIDIC PROTEIN IN THE ADULT MALE RAT HIPPOCAMPUS

    EPA Science Inventory

    This study demonstrates that gonadal steroids (estradiol, testosterone, dihydrotestosterone) can inhibit the expression of glial fibrillary acidic protein and it MRNA in the adult male rat brain. esticular hormones may influence the activity of astrocytes in the intact and lesion...

  15. Integration of the transcriptional networks regulating limb morphogenesis.

    PubMed

    Rabinowitz, Adam H; Vokes, Steven A

    2012-08-15

    The developing limb is one of the best described vertebrate systems for understanding how coordinated gene expression during embryogenesis leads to the structures present in the mature organism. This knowledge, derived from decades of research, is largely based upon gain- and loss-of-function experiments. These studies have provided limited information about how the key signaling pathways interact with each other and the downstream effectors of these pathways. We summarize our current understanding of known genetic interactions in the context of three temporally defined gene regulatory networks. These networks crystallize our current knowledge, depicting a dynamic process involving multiple feedback loops between the ectoderm and mesoderm. At the same time, they highlight the fact that many essential processes are still largely undescribed. Much of the dynamic transcriptional activity occurring during development is regulated by distal cis-regulatory elements. Modern genomic tools have provided new approaches for studying the function of cis-regulatory elements and we discuss the results of these studies in regard to understanding limb development. Ultimately, these genomic techniques will allow scientists to understand how multiple signaling pathways are integrated in space and time to drive gene expression and regulate the formation of the limb. PMID:22683377

  16. HABP2 is a Novel Regulator of Vascular Integrity

    PubMed Central

    Mambetsariev, N.; Mirzapoiazova, T.; Mambetsariev, B.; Sammani, S.; Lennon, F.E.; Garcia, J.G.N.; Singleton, P.A.

    2010-01-01

    Objective We evaluated the role of the extracellular serine protease, Hyaluronic Acid Binding Protein 2 (HABP2), in vascular barrier regulation. Methods and Results Using immunoblot and immunohistochemical analysis, we observed that lipopolysaccharide (LPS)-induces HABP2 expression in murine lung endothelium in vivo and in human pulmonary microvascular endothelial cell (HPMVEC) in vitro. High molecular weight hyaluronan (HMW-HA, ~1 million Da) decreased HABP2 protein expression in HPMVEC and decreased purified HABP2 enzymatic activity whereas low MW HA (LMW-HA, ~2,500 Da) increased these activities. The effects of LMW-HA on HABP2 activity, but not HMW-HA, were inhibited with a peptide of the polyanion binding domain (PABD) of HABP2. Silencing (siRNA) HABP2 expression augmented HMW-HA-induced EC barrier enhancement and inhibited LPS and LMW-HA-mediated EC barrier disruption, results which were reversed with overexpression of HABP2. Silencing PAR receptors 1 and 3, RhoA or ROCK expression attenuated LPS, LMW-HA and HABP2-mediated EC barrier disruption. Utilizing murine models of acute lung injury, we observed that LPS- and ventilator-induced pulmonary vascular hyper-permeability were significantly reduced with vascular silencing (siRNA) of HABP2. Conclusions HABP2 negatively regulates vascular integrity via activation of PAR receptor/RhoA/ROCK signaling and represents a potentially useful therapeutic target for syndromes of increased vascular permeability. PMID:20042707

  17. Weight gain and inflammation regulate aromatase expression in male adipose tissue, as evidenced by reporter gene activity.

    PubMed

    Polari, L; Yatkin, E; Martínez Chacón, M G; Ahotupa, M; Smeds, A; Strauss, L; Zhang, F; Poutanen, M; Saarinen, N; Mäkelä, S I

    2015-09-01

    Obesity and white adipose tissue (WAT) inflammation are associated with enhanced aromatization in women, but little is known about the regulation of aromatase (CYP19A1) gene expression in male WAT. We investigated the impact of weight gain and WAT inflammation on the regulation of CYP19A1 in males, by utilizing the hARO-Luc aromatase reporter mouse model containing a >100-kb 5'-region of the human CYP19A1 gene. We show that hARO-Luc reporter activity is enhanced in WAT of mice with increased adiposity and inflammation. Dexamethasone and TNFα, as well as forskolin and phorbol 12-myristate 13-acetate, upregulate hARO-Luc activity, suggesting the involvement of promoters I.4 and I.3/II. Furthermore, we show that diet enriched with antioxidative plant polyphenols attenuates WAT inflammation and hARO-Luc activity in obese males. In conclusion, our data suggest that obesity-associated WAT inflammation leads to increased peripheral CYP19A1 expression in males, and that polyphenol-enriched diet may have the potential to attenuate excessive aromatization in WAT of obese men. PMID:26054748

  18. Integrating membrane transport with male gametophyte development and function through transcriptomics(1)[W

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 Ca(2+), H(+), and K(+) are critical for pollen ...

  19. Central oxytocin regulates social familiarity and scent marking behavior that involves amicable odor signals between male mice.

    PubMed

    Arakawa, Hiroyuki; Blanchard, D Caroline; Blanchard, Robert J

    2015-07-01

    The effect of oxytocin on social behavior and odor communication was investigated in male C57BL/6J mice. In three-male colonies, in visible burrow systems, icv oxytocin (OT) infusion before colony formation substantially increased huddling together over the initial 8 h of grouping, accompanied by decreased expression of a number of social approaches associated with conspecific aggression and defense. OT antagonist infusion had little impact on expression of social approaches but decreased time engaging in social components including huddle over the initial 8 h. These results demonstrate a linkage of social familiarity to OT availability in the brain. In a scent marking paradigm central infusion of OT reduced territorial marking towards male conspecifics, and this in turn reduced the scent marking of untreated stimulus males to OT-infused subjects. Infusion of an OT antagonist into stimulus mice who were confronted with OT-infused subjects prevented the reduction/suppression of scent marking that was normally seen following exposure of social odors released from OT-injected mice. Odor of pair-housed mice also induced a suppression of territorial scent marking in odor recipients, but OT antagonist administration into pair-housed mice blocked this suppressive effect of odor cue. These results indicate that central OT modulates release as well as detection of amicable signals facilitating/maintaining familiar relationships and suppressing territorial behavior between male mice. Overall, these findings suggest that OT plays a significant role in regulating social familiarity via changing qualities of conspecific odor cues. PMID:26066721

  20. G9a-mediated histone methylation regulates cadmium-induced male fertility damage in pubertal mice.

    PubMed

    Li, Min; Liu, Chuan; Yang, Lingling; Zhang, Lei; Chen, Chunhai; He, Mindi; Lu, Yonghui; Feng, Wei; Pi, Huifeng; Zhang, Yanwen; Zhong, Min; Yu, Zhengping; Zhou, Zhou

    2016-06-11

    Increasing evidence suggests that cadmium (Cd) is associated with male fertility damage. However, the effects of histone modification on Cd-induced male fertility damage remain obscure. This study aims to evaluate the roles of histone methylation mediated by euchromatin histone methyltransferase (EHMT2/G9a) in regulating Cd-induced male fertility damage. We exposed 4-week-old male C57BL/6J mice to Cd by intraperitoneal injection at 2mg/kg for 1, 3 and 5days. Our data showed that Cd exposure decreased the numbers of impregnated females and litter sizes, which was concomitant with sperm count reduction, histological changes in the cauda epididymal ducts and seminiferous epithelium, and testicular cell apoptosis as evaluated by terminal dUTP nick-end labeling (TUNEL) assay and immunoblotting with increased levels of cleaved caspase 3, PARP and Bax and a decreased level of Bcl-2. Cd-induced male fertility damage was accompanied by enhanced G9a activity followed by increased histone H3 lysine 9 monomethylation (H3K9me1) and dimethylation (H3K9me2) in testes. Furthermore, inhibition of G9a by BIX-01294 normalized H3K9me1 and H3K9me2 to basal levels and prevented Cd-induced male fertility damage and testicular cell apoptosis. Our present study revealed that G9a-mediated histone methylation plays a critical role in Cd-induced male fertility damage and testicular cell apoptosis. PMID:27060504

  1. Self-Regulated Learning and Executive Function: Exploring the Relationships in a Sample of Adolescent Males

    ERIC Educational Resources Information Center

    Effeney, Gerard; Carroll, Annemaree; Bahr, Nan

    2013-01-01

    This study investigated relationships between SRL and EF in a sample of 254 school-aged adolescent males. Two hypotheses were tested: that self-reported measures of SRL and EF are closely related and that as different aspects of EF mature during adolescence, the corresponding components of SRL should also improve, leading to an age-related…

  2. 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.

  3. 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

  4. The Arabidopsis transcription factor IIB-related protein BRP4 is involved in the regulation of mitotic cell-cycle progression during male gametogenesis

    PubMed Central

    Hu, Yuxin

    2014-01-01

    Male gametogenesis in angiosperms involves two rounds of mitosis that are essential for the generation of two sperm cells to achieve double fertilization, a distinct event in the sexual reproduction of flowering plants. Precise regulation of mitosis during male gametogenesis is critically important for the establishment of the male germline. However, the molecular mechanisms underlying mitotic division during male gametophyte development have not been characterized fully. Here, we report that the Arabidopsis transcription initiation factor TFIIB-related protein BRP4 is involved in the regulation of mitotic cell-cycle progression during male gametogenesis. BRP4 was expressed predominately in developing male gametophytes. Knockdown expression of BRP4 by a native promoter-driven RNA interference construct in Arabidopsis resulted in arrest of the mitotic progression of male gametophytes, leading to a defect in pollen development. Moreover, we showed that the level of expression of a gene encoding a subunit of the origin recognition complex, ORC6, was decreased in BRP4 knockdown plants, and that the ORC6 knockdown transgenic plants phenocopied the male gametophyte defect observed in BRP4 knockdown plants, suggesting that ORC6 acts downstream of BRP4 to mediate male mitotic progression. Taken together, our results reveal that BRP4 plays an important role in the regulation of mitotic cell-cycle progression during male gametogenesis. PMID:24723406

  5. Transcriptomic Profiling Reveals Complex Molecular Regulation in Cotton Genic Male Sterile Mutant Yu98-8A

    PubMed Central

    Xie, Deyi; Sun, Li; Xu, Zhenzhen; Zhu, Wei; Yang, Lirong; Zhao, Yuanming; Lv, Shuping; Tang, Zhongjie; Nie, Lihong; Li, Wu; Hou, Jianan; Duan, Zhengzheng; Yu, Yuebo; Yang, Xiaojie

    2015-01-01

    Although cotton genic male sterility (GMS) plays an important role in the utilization of hybrid vigor, its precise molecular mechanism remains unclear. To characterize the molecular events of pollen abortion, transcriptome analysis, combined with histological observations, was conducted in the cotton GMS line, Yu98-8A. A total of 2,412 genes were identified as significant differentially expressed genes (DEGs) before and during the critical pollen abortion stages. Bioinformatics and biochemical analysis showed that the DEGs mainly associated with sugars and starch metabolism, oxidative phosphorylation, and plant endogenous hormones play a critical and complicated role in pollen abortion. These findings extend a better understanding of the molecular events involved in the regulation of pollen abortion in genic male sterile cotton, which may provide a foundation for further research studies on cotton heterosis breeding. PMID:26382878

  6. Boule-like genes regulate male and female gametogenesis in the flatworm Macrostomum lignano.

    PubMed

    Kuales, Georg; De Mulder, Katrien; Glashauser, Jade; Salvenmoser, Willi; Takashima, Shigeo; Hartenstein, Volker; Berezikov, Eugene; Salzburger, Walter; Ladurner, Peter

    2011-09-01

    Members of the DAZ (Deleted in AZoospermia) gene family are important players in the process of gametogenesis and their dysregulation accounts for 10% of human male infertility. Boule, the ancestor of the family, is mainly involved in male meiosis in most organisms. With the exception of Drosophila and C. elegans, nothing is known on the function of boule in non-vertebrate animals. In the present study, we report on three boule orthologues in the flatworm Macrostomum lignano. We demonstrate that macbol1 and macbol2 are expressed in testes whilst macbol3 is expressed in ovaries and developing eggs. Macbol1 RNAi blocked spermatocyte differentiation whereas macbol2 showed no effect upon RNAi treatment. Macbol3 RNAi resulted in aberrant egg maturation and led to female sterility. We further demonstrated the evolutionary functional conservation of macbol1 by introducing this gene into Drosophila bol(1) mutants. Macbol1 was able to rescue the progression of fly meiotic divisions. In summary, our findings provide evidence for an involvement of boule genes in male and female gamete development in one organism. Furthermore, boule gene function is shown here for the first time in a lophotrochozoan. Our results point to a more diverse functional assignment of boule genes. Therefore, a better understanding of boule function in flatworms can help to elucidate the molecular mechanisms of and concomitant infertility in higher organisms including humans. PMID:21740899

  7. Boule-like genes regulate male and female gametogenesis in the flatworm Macrostomum lignano

    PubMed Central

    Kuales, Georg; De Mulder, Katrien; Glashauser, Jade; Salvenmoser, Willi; Takashima, Shigeo; Hartenstein, Volker; Berezikov, Eugene; Salzburger, Walter; Ladurner, Peter

    2011-01-01

    Members of the DAZ (Deleted in AZoospermia) gene family are important players in the process of gametogenesis and their dysregulation accounts for 10% of human male infertility. Boule, the ancestor of the family, is mainly involved in male meiosis in most organisms. With the exception of Drosophila and C. elegans, nothing is known on the function of boule in non-vertebrate animals. In the present study, we report on three boule orthologues in the flatworm Macrostomum lignano. We demonstrate that macbol1 and macbol2 are expressed in testes whilst macbol3 is expressed in ovaries and developing eggs. Macbol1 RNAi blocked spermatocyte differentiation whereas macbol2 showed no effect upon RNAi treatment. Macbol3 RNAi resulted in aberrant egg maturation and led to female sterility. We further demonstrated the evolutionary functional conservation of macbol1 by introducing this gene into Drosophila bol1 mutants. Macbol1 was able to rescue the progression of fly meiotic divisions. In summary, our findings provide evidence for an involvement of boule genes in male and female gamete development in one organism. Furthermore, boule gene function is shown here for the first time in a lophotrochozoan. Our results point to a more diverse functional assignment of boule genes. Therefore, a better understanding of boule function in flatworms can help to elucidate the molecular mechanisms of and concomitant infertility in higher organisms including humans. PMID:21740899

  8. Inositol 1,4,5-Trisphosphate Signaling Regulates Mating Behavior in Caenorhabditis elegans MalesD⃞

    PubMed Central

    Gower, Nicholas J. D.; Walker, Denise S.; Baylis, Howard A.

    2005-01-01

    Complex behavior requires the coordinated action of the nervous system and nonneuronal targets. Male mating in Caenorhabditis elegans consists of a series of defined behavioral steps that lead to the physiological outcomes required for successful impregnation. We demonstrate that signaling mediated by inositol 1,4,5-trisphosphate (IP3) is required at several points during mating. Disruption of IP3 receptor (itr-1) function results in dramatic loss of male fertility, due to defects in turning behavior (during vulva location), spicule insertion and sperm transfer. To elucidate the signaling pathways responsible, we knocked down the six C. elegans genes encoding phospholipase C (PLC) family members. egl-8, which encodes PLC-β, functions in spicule insertion and sperm transfer. itr-1 and egl-8 are widely expressed in the male reproductive system. An itr-1 gain-of-function mutation rescues infertility caused by egl-8 RNA interference, indicating that egl-8 and itr-1 function together as central components of the signaling events controlling sperm transfer. PMID:15958491

  9. The Drosophila splicing regulator sex-lethal directly inhibits translation of male-specific-lethal 2 mRNA.

    PubMed Central

    Gebauer, F; Merendino, L; Hentze, M W; Valcárcel, J

    1998-01-01

    Male-specific expression of the protein male-specific-lethal 2 (MSL-2) controls dosage compensation in Drosophila. msl-2 gene expression is inhibited in females by Sex-lethal (SXL), an RNA binding protein known to regulate pre-mRNA splicing. An intron present at the 5' untranslated region (UTR) of msl-2 mRNA contains putative SXL binding sites and is retained in female flies. Here we show that SXL plays a dual role in the inhibition of msl-2 expression. Cotransfection of Drosophila Schneider cells with an SXL expression vector and a reporter containing the 5' UTR of msl-2 mRNA resulted in retention of the 5' UTR intron and efficient accumulation of the unspliced mRNA in the cytoplasm, where its translation was blocked by SXL, but not by the intron per se. Both splicing and translation inhibition by SXL were recapitulated in vitro and found to be dependent upon SXL binding to high-affinity sites within the intron, showing that SXL directly regulates these events. Our data reveal a coordinated mechanism for the regulation of msl-2 expression by the same regulatory factor: SXL enforces intron retention in the nucleus and subsequent translation inhibition in the cytoplasm. PMID:9570314

  10. Diversifying sunflower germplasm by integration and mapping of a novel male fertility restoration gene

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The combination of a single cytoplasmic male-sterile (CMS) PET-1, originating from wild Helianthus petiolaris subsp. petiolaris Nutt., and the corresponding fertility restoration gene Rf1, has been used for commercial sunflower hybrid seed production worldwide since the early 1970s. A new CMS line 5...

  11. Improving sterile male performance in support of programmes integrating the sterile insect technique against fruit flies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Sterile Insect Technique (SIT) is being applied against fruit fly pests in many areas of the world. Currently, factories have the capacity to produce several billion sterile male insects per week and to make them available for, irradiatiation and shipment to their destinations, where the emergin...

  12. Analysis of integral controls in linear quadratic regulator design

    NASA Technical Reports Server (NTRS)

    Slater, G. L.

    1979-01-01

    The application of linear optimal control to the design of systems with integral control action on specified outputs is considered. Using integral terms in a quadratic performance index, an asymptotic analysis is used to determine the effect of variable quadratic weights on the eigenvalues and eigenvectors of the closed loop system. It is shown that for small integral terms the placement of integrator poles and gain calculation can be effectively decoupled from placement of the primary system eigenvalues. This technique is applied to the design of integral controls for a STOL aircraft outer loop guidance system.

  13. [The role of testosterone in regulating the aggressive behavior of male laboratory mice of different strains].

    PubMed

    Diuzhikova, N A

    1994-01-01

    The influence of testosterone on aggressive behaviour, on urinal pheromonal activity, on weight of the preputial gland, seminal vesicles and coagulating glands of male mouse CBA, C57BL/6 and hybrids CBAB6F1 was studied. The interstrain differences in reactivity to testosterone in aggressive behaviour tests and in seminal vesicles and coagulating gland weight were found. The urinal pheromonal characteristics were not changed by testosterone influence. No significant correlations between the aggressive behaviour parameters, urinal pheromonal activity, testosterone plasma levels and reactivity to its action were discovered. PMID:7941714

  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. CLOCK and BMAL1 Regulate Muscle Insulin Sensitivity via SIRT1 in Male Mice.

    PubMed

    Liu, Jun; Zhou, Ben; Yan, Menghong; Huang, Rui; Wang, Yuangao; He, Zhishui; Yang, Yonggang; Dai, Changgui; Wang, Yiqian; Zhang, Fang; Zhai, Qiwei

    2016-06-01

    Circadian misalignment induces insulin resistance in both human and animal models, and skeletal muscle is the largest organ response to insulin. However, how circadian clock regulates muscle insulin sensitivity and the underlying molecular mechanisms are still largely unknown. Here we show circadian locomotor output cycles kaput (CLOCK) and brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein (BMAL)-1, two core circadian transcription factors, are down-regulated in insulin-resistant C2C12 myotubes and mouse skeletal muscle. Furthermore, insulin signaling is attenuated in the skeletal muscle of Clock(Δ19/Δ19) mice, and knockdown of CLOCK or BMAL1 by small interfering RNAs induces insulin resistance in C2C12 myotubes. Consistently, ectopic expression of CLOCK and BMAL1 improves insulin sensitivity in C2C12 myotubes. Moreover, CLOCK and BMAL1 regulate the expression of sirtuin 1 (SIRT1), an important regulator of insulin sensitivity, in C2C12 myotubes and mouse skeletal muscle, and two E-box elements in Sirt1 promoter are responsible for its CLOCK- and BMAL1-dependent transcription in muscle cells. Further studies show that CLOCK and BMAL1 regulate muscle insulin sensitivity through SIRT1. In addition, we find that BMAL1 and SIRT1 are decreased in the muscle of mice maintained in constant darkness, and resveratrol supplementation activates SIRT1 and improves insulin sensitivity. All these data demonstrate that CLOCK and BMAL1 regulate muscle insulin sensitivity via SIRT1, and activation of SIRT1 might be a potential valuable strategy to attenuate muscle insulin resistance related to circadian misalignment. PMID:27035655

  16. The Magea gene cluster regulates male germ cell apoptosis without affecting the fertility in mice.

    PubMed

    Hou, Siyuan; Xian, Li; Shi, Peiliang; Li, Chaojun; Lin, Zhaoyu; Gao, Xiang

    2016-01-01

    While apoptosis is essential for male germ cell development, improper activation of apoptosis in the testis can affect spermatogenesis and cause reproduction defects. Members of the MAGE-A (melanoma antigen family A) gene family are frequently clustered in mammalian genomes and are exclusively expressed in the testes of normal animals but abnormally activated in a wide variety of cancers. We investigated the potential roles of these genes in spermatogenesis by generating a mouse model with a 210-kb genomic deletion encompassing six members of the Magea gene cluster (Magea1, Magea2, Magea3, Magea5, Magea6 and Magea8). Male mice carrying the deletion displayed smaller testes from 2 months old with a marked increase in apoptotic germ cells in the first wave of spermatogenesis. Furthermore, we found that Magea genes prevented stress-induced spermatogenic apoptosis after N-ethyl-N-nitrosourea (ENU) treatment during the adult stage. Mechanistically, deletion of the Magea gene cluster resulted in a dramatic increase in apoptotic germ cells, predominantly spermatocytes, with activation of p53 and induction of Bax in the testes. These observations demonstrate that the Magea genes are crucial in maintaining normal testicular size and protecting germ cells from excessive apoptosis under genotoxic stress. PMID:27226137

  17. The Magea gene cluster regulates male germ cell apoptosis without affecting the fertility in mice

    PubMed Central

    Hou, Siyuan; Xian, Li; Shi, Peiliang; Li, Chaojun; Lin, Zhaoyu; Gao, Xiang

    2016-01-01

    While apoptosis is essential for male germ cell development, improper activation of apoptosis in the testis can affect spermatogenesis and cause reproduction defects. Members of the MAGE-A (melanoma antigen family A) gene family are frequently clustered in mammalian genomes and are exclusively expressed in the testes of normal animals but abnormally activated in a wide variety of cancers. We investigated the potential roles of these genes in spermatogenesis by generating a mouse model with a 210-kb genomic deletion encompassing six members of the Magea gene cluster (Magea1, Magea2, Magea3, Magea5, Magea6 and Magea8). Male mice carrying the deletion displayed smaller testes from 2 months old with a marked increase in apoptotic germ cells in the first wave of spermatogenesis. Furthermore, we found that Magea genes prevented stress-induced spermatogenic apoptosis after N-ethyl-N-nitrosourea (ENU) treatment during the adult stage. Mechanistically, deletion of the Magea gene cluster resulted in a dramatic increase in apoptotic germ cells, predominantly spermatocytes, with activation of p53 and induction of Bax in the testes. These observations demonstrate that the Magea genes are crucial in maintaining normal testicular size and protecting germ cells from excessive apoptosis under genotoxic stress. PMID:27226137

  18. The Levels of Male Gametic Mitochondrial DNA Are Highly Regulated in Angiosperms with Regard to Mitochondrial Inheritance[W

    PubMed Central

    Wang, Dan-Yang; Zhang, Quan; Liu, Yang; Lin, Zhi-Fu; Zhang, Shao-Xiang; Sun, Meng-Xiang; Sodmergen

    2010-01-01

    The mechanisms that regulate mitochondrial inheritance are not yet clear, even though it is 100 years since the first description of non-Mendelian genetics. Here, we quantified the copy numbers of mitochondrial DNA (mtDNA) in the gametic cells of angiosperm species. We demonstrate that each egg cell from Arabidopsis thaliana, Antirrhinum majus, and Nicotiana tabacum possesses 59.0, 42.7, and 73.0 copies of mtDNA on average, respectively. These values are equivalent to those in Arabidopsis mesophyll cells, at 61.7 copies per cell. On the other hand, sperm or generative cells from Arabidopsis, A. majus, and N. tabacum possess minor amounts of mtDNA, at 0.083, 0.47, and 1 copy on average, respectively. We further reveal a 50-fold degradation of mtDNA during pollen development in A. majus. In contrast, markedly high levels of mtDNA are found in the male gametic cells of Cucumis melo and Pelargonium zonale (1296.3 and 256.7 copies, respectively). Our results provide direct evidence for mitochondrial genomic insufficiency in the eggs and somatic cells and indicate that a male gamete of an angiosperm may possess mtDNA at concentrations as high as 21-fold (C. melo) or as low as 0.1% (Arabidopsis) of the levels in somatic cells. These observations reveal the existence of a strong regulatory system for the male gametic mtDNA levels in angiosperms with regard to mitochondrial inheritance. PMID:20605854

  19. 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. PMID:27235738

  20. The potential immune modulatory effect of chronic bisphenol A exposure on gene regulation in male medaka (Oryzias latipes) liver.

    PubMed

    Qiu, Wenhui; Shen, Yang; Pan, Chenyuan; Liu, Shuai; Wu, Minghong; Yang, Ming; Wang, Ke-Jian

    2016-08-01

    Bisphenol A (BPA) is a well-known estrogenic endocrine disrupting chemical (EDC) ubiquitously present in various environmental media. The present study aims to identify the responsive genes in male fish chronically exposed to low concentrations of BPA at the transcription level. We screened genes from a suppression subtractive hybridization library constructed from male medaka (Oryzias latipes) livers after 60-d exposure to 10μg/L BPA under the condition at which changes of hepatic antioxidant parameters have been previously reported. The identified genes were predicted to be involved in multiple biological processes including antioxidant physiology, endocrine system, detoxification, notably associated with the immune response processes. With real time PCR analysis, the immune-associated genes including hepcidin-like precursor, complement component and factors, MHC class I, alpha-2-macroglobulin and novel immune-type receptor 6 isoform were significantly up-regulated in a nonmonotonic dose response pattern in livers upon exposure to different concentrations of BPA (0.1, 1, 10, 100, 1000μg/L). Our results demonstrated a negative impact on gene regulation in fish chronically exposed to relatively low and environmentally relevant concentrations of BPA, and suggested the potential immune modulatory effect of chronic EDC exposure on fish. The immunotoxicity of BPA and other EDCs should be much concerned for the health of human beings and other vertebrates exposed to it. PMID:27104808

  1. ADVANCES IN INTEGRATING INSECT GROWTH REGULATORS INTO STORAGE PEST MANAGEMENT

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Insect growth regulators (IGRs) are insecticides that mimic insect-produced hormones that regulate the developmental process. They generally have little or no mammalian toxicity, and are considered reduced-risk insecticides that are often exempt from tolerance requirements of regulatory agencies. Al...

  2. Androgens regulate sex differences in signaling but are not associated with male variation in morphology in the weakly electric fish Parapteronotus hasemani.

    PubMed

    Petzold, Jacquelyn M; Smith, G Troy

    2016-02-01

    Sexually dimorphic signaling is widespread among animals and can act as an honest indicator of mate quality. Additionally, differences in signaling and morphology within a sex can be associated with different strategies for acquiring mates. Weakly electric fish communicate via self-generated electrical fields that transmit information about sex, reproductive state, and social status. The weakly electric knifefish Parapteronotus hasemani exhibits sexual dimorphism in body size as well as substantial within-male variation in body size and jaw length. We asked whether P. hasemani exhibits hormonally mediated sexual dimorphism in electrocommunication behavior. We also asked whether males with short versus long jaws differed significantly from each other in morphology, behavior, hormone levels, or reproductive maturity. Males produced longer chirps than females, but other signal parameters (electric organ discharge frequency; chirp rate and frequency modulation) were sexually monomorphic. Pharmacologically blocking androgen receptors in males reduced chirp duration, suggesting that this sexually dimorphic trait is regulated at least in part by the activational effects of androgens. Males sorted into two distinct morphological categories but did not differ in circulating 11-ketotestosterone or testosterone. Short-jawed males and long-jawed males also did not differ in any aspects of signaling. Thus, chirping and high levels of 11-ketotestosterone were reliably associated with reproductively active males but do not necessarily indicate male type or quality. This contrasts with other alternative male morph systems in which males that differ in morphology also differ in androgen profiles and signaling behavior. PMID:26518663

  3. 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.

  4. ROCK1 in AgRP Neurons Regulates Energy Expenditure and Locomotor Activity in Male Mice

    PubMed Central

    Huang, Hu; Lee, Seung Hwan; Ye, Chianping; Lima, Ines S.; Oh, Byung-Chul; Lowell, Bradford B.; Zabolotny, Janice M.

    2013-01-01

    Normal leptin signaling is essential for the maintenance of body weight homeostasis. Proopiomelanocortin- and agouti-related peptide (AgRP)-producing neurons play critical roles in regulating energy metabolism. Our recent work demonstrates that deletion of Rho-kinase 1 (ROCK1) in the AgRP neurons of mice increased body weight and adiposity. Here, we report that selective loss of ROCK1 in AgRP neurons caused a significant decrease in energy expenditure and locomotor activity of mice. These effects were independent of any change in food intake. Furthermore, AgRP neuron-specific ROCK1-deficient mice displayed central leptin resistance, as evidenced by impaired Signal Transducer and Activator of Transcription 3 activation in response to leptin administration. Leptin's ability to hyperpolarize and decrease firing rate of AgRP neurons was also abolished in the absence of ROCK1. Moreover, diet-induced and genetic forms of obesity resulted in reduced ROCK1 activity in murine arcuate nucleus. Of note, high-fat diet also impaired leptin-stimulated ROCK1 activity in arcuate nucleus, suggesting that a defect in hypothalamic ROCK1 activity may contribute to the pathogenesis of central leptin resistance in obesity. Together, these data demonstrate that ROCK1 activation in hypothalamic AgRP neurons is required for the homeostatic regulation of energy expenditure and adiposity. These results further support previous work identifying ROCK1 as a key regulator of energy balance and suggest that targeting ROCK1 in the hypothalamus may lead to development of antiobesity therapeutics. PMID:23885017

  5. Altered somatotroph feedback regulation improves metabolic efficiency and limits adipose deposition in male mice.

    PubMed

    Romero, Christopher J; Wolfe, Andrew; Law, Yi Ying; Costelloe, ChenChen Z; Miller, Ryan; Wondisford, Fredric; Radovick, Sally

    2016-04-01

    Several transgenic mouse models with disruption in the growth hormone (GH) axis support the role of GH in augmenting metabolic homeostasis. Specifically, interest has focused on GH's lipolytic properties and ability to affect adipose deposition. Furthermore, both GH and insulin growth factor 1 (IGF-1) may also play a direct or indirect role in adipose development. The somatotroph insulin-like growth factor-1 receptor knockout (SIGFRKO) mouse with only a modest increase in serum GH and IGF-1 demonstrates less adipose tissue than controls. In order to characterize the metabolic phenotype of SIGFRKO mice, histologic analysis of fat depots confirmed a smaller average diameter of adipocytes in the SIGFRKO mice compared to controls. These changes were accompanied by an increase in lipolytic gene expression in fat depots. Indirect calorimetry performed on 6-8week old male mice and again at 25weeks of age demonstrated that SIGFRKO mice, at both ages, had a higher VO2 and increased energy expenditure when compared with controls. The calculated respiratory exchange ratio (RER) was lower in the younger SIGFRKO mice compared to controls. No differences in food consumption or in either ambulatory or total activity were seen between SIGFRKO and control mice in either age group. These studies highlight the role of GH in adipose deposition and its influence on the expression of lipolytic genes resulting in an altered metabolic state, thus providing a mechanism for the decrease in weight gain seen in the SIGFRKO mouse model. PMID:26975547

  6. The feedback regulation of pituitary GTH-II secretion in male African catfish (Clarias gariepinus): Participation of 11-ketotestosterone.

    PubMed

    Schulz, R W; Paczoska-Eliasiewicz, H; Satijn, D G; Goos, H J

    1993-07-01

    11-ketotestosterone (OT) is a typical androgen of male teleost fish, but information on the question if it is involved in the feedback regulation of pituitary gonadotropin II (GTH-II) secretion is controversial. We have therefore studied the effects of OT on gonadotropin releasing-hormone (GnRH) stimulated GTH-II secretion in male African catfish Clarias gariepinus). In vivo experiments were carried out with intact and castrated fish. OT plasma levels were increased by implantation of silastic capsules containing 11-ketoandrostenedione (OA) which is converted to OT in both intact and castrated fish. When intact males received OA- or blank-capsules, treatment with salmon gonadotropin releasing-hormone analogue (Des-Gly(10)-D-Arg(6)-sGnRH-NEt; 0.2 μg sGnRHa/kg body weight) elevated the plasma GTH-11 levels in both groups. However, the levels were about 2 times higher in blank- than in OA-implanted fish. When castrated fish received either blank-or OA-capsules, sGnRHa treatment led to plasma GTH levels significantly higher than in sham-operated fish. However, there was no difference between the blank- or OA-implanted castrates, though OA implantation led to a restoration of OT plasma levels. This suggests that replacement ofOT is insufficient to reverse castration-induced effects. In vitro experiments were carried out with pituitary tissue fragments using a static culture system. The tissue remained sensitive to sGnRHa (5 × 10(-9)M) for 4 days after the beginning of incubation. Preincubation of pituitary tissue for 24 hours with 25 ng OT/ml medium (80 nM) completely abolished the stimulatory effect of sGnRHa on GTH-II secretion. Tritiated OT was not metabolized by pituitary tissue during 6 hours of incubation. We conclude that 11-ketotestosterone, a quantitatively prominent and non-aromatizeable circulating androgen participates, at least in part by direct action on the pituitary, in the negative feedback regulation of GnRH-stimulated GTH-II secretion in male

  7. Heparan sulfate regulates the number and centrosome positioning of Drosophila male germline stem cells

    PubMed Central

    Levings, Daniel C.; Arashiro, Takeshi; Nakato, Hiroshi

    2016-01-01

    Stem cell division is tightly controlled via secreted signaling factors and cell adhesion molecules provided from local niche structures. Molecular mechanisms by which each niche component regulates stem cell behaviors remain to be elucidated. Here we show that heparan sulfate (HS), a class of glycosaminoglycan chains, regulates the number and asymmetric division of germline stem cells (GSCs) in the Drosophila testis. We found that GSC number is sensitive to the levels of 6-O sulfate groups on HS. Loss of 6-O sulfation also disrupted normal positioning of centrosomes, a process required for asymmetric division of GSCs. Blocking HS sulfation specifically in the niche, termed the hub, led to increased GSC numbers and mispositioning of centrosomes. The same treatment also perturbed the enrichment of Apc2, a component of the centrosome-anchoring machinery, at the hub–GSC interface. This perturbation of the centrosome-anchoring process ultimately led to an increase in the rate of spindle misorientation and symmetric GSC division. This study shows that specific HS modifications provide a novel regulatory mechanism for stem cell asymmetric division. The results also suggest that HS-mediated niche signaling acts upstream of GSC division orientation control. PMID:26792837

  8. Dynamics of the Transcriptome during Human Spermatogenesis: Predicting the Potential Key Genes Regulating Male Gametes Generation

    PubMed Central

    Zhu, Zijue; Li, Chong; Yang, Shi; Tian, Ruhui; Wang, Junlong; Yuan, Qingqing; Dong, Hui; He, Zuping; Wang, Shengyue; Li, Zheng

    2016-01-01

    Many infertile men are the victims of spermatogenesis disorder. However, conventional clinical test could not provide efficient information on the causes of spermatogenesis disorder and guide the doctor how to treat it. More effective diagnosis and treating methods could be developed if the key genes that regulate spermatogenesis were determined. Many works have been done on animal models, while there are few works on human beings due to the limited sample resources. In current work, testis tissues were obtained from 27 patients with obstructive azoospermia via surgery. The combination of Fluorescence Activated Cell Sorting and Magnetic Activated Cell Sorting was chosen as the efficient method to sort typical germ cells during spermatogenesis. RNA Sequencing was carried out to screen the change of transcriptomic profile of the germ cells during spermatogenesis. Differential expressed genes were clustered according to their expression patterns. Gene Ontology annotation, pathway analysis, and Gene Set Enrichment Analysis were carried out on genes with specific expression patterns and the potential key genes such as HOXs, JUN, SP1, and TCF3 which were involved in the regulation of spermatogenesis, with the potential value serve as molecular tools for clinical purpose, were predicted. PMID:26753906

  9. Dynamics of the Transcriptome during Human Spermatogenesis: Predicting the Potential Key Genes Regulating Male Gametes Generation.

    PubMed

    Zhu, Zijue; Li, Chong; Yang, Shi; Tian, Ruhui; Wang, Junlong; Yuan, Qingqing; Dong, Hui; He, Zuping; Wang, Shengyue; Li, Zheng

    2016-01-01

    Many infertile men are the victims of spermatogenesis disorder. However, conventional clinical test could not provide efficient information on the causes of spermatogenesis disorder and guide the doctor how to treat it. More effective diagnosis and treating methods could be developed if the key genes that regulate spermatogenesis were determined. Many works have been done on animal models, while there are few works on human beings due to the limited sample resources. In current work, testis tissues were obtained from 27 patients with obstructive azoospermia via surgery. The combination of Fluorescence Activated Cell Sorting and Magnetic Activated Cell Sorting was chosen as the efficient method to sort typical germ cells during spermatogenesis. RNA Sequencing was carried out to screen the change of transcriptomic profile of the germ cells during spermatogenesis. Differential expressed genes were clustered according to their expression patterns. Gene Ontology annotation, pathway analysis, and Gene Set Enrichment Analysis were carried out on genes with specific expression patterns and the potential key genes such as HOXs, JUN, SP1, and TCF3 which were involved in the regulation of spermatogenesis, with the potential value serve as molecular tools for clinical purpose, were predicted. PMID:26753906

  10. Up-Regulation of microRNA-210 is Associated with Spermatogenesis by Targeting IGF2 in Male Infertility

    PubMed Central

    Tang, Dongdong; Huang, Yuanyuan; Liu, Weiqun; Zhang, Xiansheng

    2016-01-01

    Background MicroRNAs (miRNAs) play pivotal roles in spermatogenesis. MicroRNA-210 (miR-210) expression was up-regulated in the testes of sterile men with non-obstructive azoospermia (NOA). However, the underlying mechanisms of miR-210 involved in the spermatogenesis in patients with NOA are unknown. Material/Methods Expression of miR-210 and insulin-like growth factor II (IGF2) in the testes of NOA cases (only including maturation arrest and hypospermatogenesis) were detected in this study. We carried out in vitro experiments to determine if IGF2 was directly targeted by miR-210 in NT2 cells. Results Compared with obstructive azoospermia (OA) as normal control, our results suggest that miR-210 was significantly up-regulated in testis of patients with NOA (P<0.05), and IGF2 was down-regulated, but without a significant difference. The results also indicated that IGF2 was directly targeted by miR-210 in NT2 cells. Conclusions The results showed that miR-210 was involved in spermatogenesis by targeting IGF2 in male infertility. PMID:27535712

  11. Weight loss by calorie restriction versus bariatric surgery differentially regulates the HPA axis in male rats

    PubMed Central

    Grayson, Bernadette E.; Hakala-Finch, Andrew P.; Kekulawala, Melani; Laub, Holly; Egan, Ann E.; Ressler, Ilana B.; Woods, Stephen C.; Herman, James P.; Seeley, Randy J.; Benoit, Stephen C.; Ulrich-Lai, Yvonne M.

    2015-01-01

    Behavioral modifications for the treatment of obesity, including caloric restriction, have notoriously low long-term success rates relative to bariatric weight-loss surgery. The reasons for the difference in sustained weight loss are not clear. One possibility is that caloric restriction alone activates the stress-responsive hypothalamo-pituitary-adrenocortical (HPA) axis, undermining the long-term maintenance of weight loss, and that this is abrogated after bariatric surgery. Accordingly, we compared the HPA response to weight loss in 5 groups of male rats: (1) high-fat diet-induced obese (DIO) rats treated with Roux-en-Y gastric bypass surgery (RYGB, n=7), (2) DIO rats treated with vertical sleeve gastrectomy (VSG, n=11), (3) DIO rats given sham surgery and subsequently restricted to the food intake of the VSG/RYGB groups (Pair-fed, n=11), (4) ad libitum-fed DIO rats given sham surgery (Obese, n=11) and (5) ad libitum chow-fed rats given sham surgery (Lean, n=12). Compared to Lean controls, food-restricted rats exhibited elevated morning (nadir) non-stress plasma corticosterone concentrations and increased hypothalamic corticotropin releasing hormone and vasopressin mRNA expression, indicative of basal HPA activation. This was largely prevented when weight loss was achieved by bariatric surgery. DIO increased HPA activation by acute (novel environment) stress and this was diminished by bariatric surgery-, but not pair-feeding-, induced weight loss. These results suggest that the HPA axis is differentially affected by weight loss from caloric restriction versus bariatric surgery, and this may contribute to the differing long-term effectiveness of these two weight-loss approaches. PMID:25238021

  12. Diversifying Sunflower Germplasm by Integration and Mapping of a Novel Male Fertility Restoration Gene

    PubMed Central

    Liu, Zhao; Wang, Dexing; Feng, Jiuhuan; Seiler, Gerald J.; Cai, Xiwen; Jan, Chao-Chien

    2013-01-01

    The combination of a single cytoplasmic male-sterile (CMS) PET-1 and the corresponding fertility restoration (Rf) gene Rf1 is used for commercial hybrid sunflower (Helianthus annuus L., 2n = 34) seed production worldwide. A new CMS line 514A was recently developed with H. tuberosus cytoplasm. However, 33 maintainers and restorers for CMS PET-1 and 20 additional tester lines failed to restore the fertility of CMS 514A. Here, we report the discovery, characterization, and molecular mapping of a novel Rf gene for CMS 514A derived from an amphiploid (Amp H. angustifolius/P 21, 2n = 68). Progeny analysis of the male-fertile (MF) plants (2n = 35) suggested that this gene, designated Rf6, was located on a single alien chromosome. Genomic in situ hybridization (GISH) indicated that Rf6 was on a chromosome with a small segment translocation on the long arm in the MF progenies (2n = 34). Rf6 was mapped to linkage group (LG) 3 of the sunflower SSR map. Eight markers were identified to be linked to this gene, covering a distance of 10.8 cM. Two markers, ORS13 and ORS1114, were only 1.6 cM away from the gene. Severe segregation distortions were observed for both the fertility trait and the linked marker loci, suggesting the possibility of a low frequency of recombination or gamete selection in this region. This study discovered a new CMS/Rf gene system derived from wild species and provided significant insight into the genetic basis of this system. This will diversify the germplasm for sunflower breeding and facilitate understanding of the interaction between the cytoplasm and nuclear genes. PMID:23307903

  13. Localized RhoA GTPase activity regulates dynamics of endothelial monolayer integrity

    PubMed Central

    Szulcek, Robert; Beckers, Cora M.L.; Hodzic, Jasmina; de Wit, Jelle; Chen, Zhenlong; Grob, Tim; Musters, Rene J.P.; Minshall, Richard D.; van Hinsbergh, Victor W.M.; van Nieuw Amerongen, Geerten P.

    2013-01-01

    Aims Endothelial cells (ECs) control vascular permeability by forming a monolayer that is sealed by extracellular junctions. Various mediators modulate the endothelial barrier by acting on junctional protein complexes and the therewith connected F-actin cytoskeleton. Different Rho GTPases participate in this modulation, but their mechanisms are still partly resolved. Here, we aimed to elucidate whether the opening and closure of the endothelial barrier are associated with distinct localized RhoA activities at the subcellular level. Methods and results Live fluorescence resonance energy transfer (FRET) microscopy revealed spatially distinct RhoA activities associated with different aspects of the regulation of endothelial monolayer integrity. Unstimulated ECs were characterized by hotspots of RhoA activity at their periphery. Thrombin receptor activation in the femoral vein of male wistar rats and in cultured ECs enhanced RhoA activity at membrane protrusions, followed by a more sustained RhoA activity associated with cytoplasmic F-actin filaments, where prolonged RhoA activity coincided with cellular contractility. Unexpectedly, thrombin-induced peripheral RhoA hotspots were not spatially correlated to the formation of large inter-endothelial gaps. Rather, spontaneous RhoA activity at membrane protrusions coincided with the closure of inter-endothelial gaps. Electrical impedance measurements showed that RhoA signalling is essential for this protrusive activity and maintenance of barrier restoration. Conclusion Spontaneous RhoA activity at membrane protrusions is spatially associated with closure, but not formation of inter-endothelial gaps, whereas RhoA activity at distant contractile filaments contributes to thrombin-induced disruption of junctional integrity. Thus, these data indicate that distinct RhoA activities are associated with disruption and re-annealing of endothelial junctions. PMID:23536606

  14. Prostatic acid phosphatase is the main acid phosphatase with 5'-ectonucleotidase activity in the male mouse saliva and regulates salivation.

    PubMed

    Araujo, César L; Quintero, Ileana B; Kipar, Anja; Herrala, Annakaisa M; Pulkka, Anitta E; Saarinen, Lilli; Hautaniemi, Sampsa; Vihko, Pirkko

    2014-06-01

    We have previously shown that in addition to the well-known secreted isoform of prostatic acid phosphatase (sPAP), a transmembrane isoform exists (TMPAP) that interacts with snapin (a SNARE-associated protein) and regulates the endo-/exocytic pathways. We have also shown that PAP has 5'-ectonucleotidase and thiamine monophosphatase activity and elicits antinociceptive effects in mouse models of chronic inflammatory and neuropathic pain. Therefore, to determine the physiological role of PAP in a typical exocrine organ, we studied the submandibular salivary gland (SMG) of PAP(-/-) and wild-type C57BL/6J mice by microarray analyses, microRNA sequencing, activity tests, immunohistochemistry, and biochemical and physiological analyses of saliva. We show that PAP is the main acid phosphatase in the wild-type male mouse saliva, accounting for 50% of the total acid phosphatase activity, and that it is expressed only in the granular convoluted tubules of the SMGs, where it is the only 5'-ectonucleotidase. The lack of PAP in male PAP(-/-) mice was associated with a significant increase in the salivation volume under secretagogue stimulation, overexpression of genes related to cell proliferation (Mki67, Aurkb, Birc5) and immune response (Irf7, Cxcl9, Ccl3, Fpr2), and upregulation of miR-146a in SMGs. An increased and sustained acinar cell proliferation was detected without signs of glandular hyperplasia. Our results indicate that in PAP(-/-) mice, SMG homeostasis is maintained by an innate immune response. Additionally, we suggest that in male mice, PAP via its 5'-ectonucleotidase activity and production of adenosine can elicit analgesic effects when animals lick their wounds. PMID:24717577

  15. Fasting induced kisspeptin signaling suppression is regulated by glutamate mediated cues in adult male rhesus macaque (Macaca mulatta).

    PubMed

    Shamas, Shazia; Khan, Saeed-Ul-Hassan; Khan, Muhammad Yousaf; Shabbir, Nadia; Zubair, Hira; Shafqat, Saira; Wahab, Fazal; Shahab, Muhammad

    2015-08-01

    Kisspeptin signaling is suppressed by short term fasting. It has been reported that hypothalamic Kiss1 and Kiss1r mRNA expression decreased after 48h of fasting in male rhesus monkey. But the mechanism involved in the reduction of kisspeptin signaling after 48h of fasting is unknown. Recent studies have suggested the role of afferent excitatory and inhibitory pathways in the regulation of kisspeptin neurons. Therefore, this study was designed to observe the changes in the glutamate and GABA signaling during fed and 48h fasting states by performing immunofluorescence to examine the interaction of kisspeptin neurons with NR1 subunit of NMDA receptors and by performing SYBR green qRT-PCR to measure and quantify the levels of Kiss1, Kiss1r, NR1 and GAD67 mRNA in the POA and MBH of adult male rhesus macaque (Macaca mulatta) during 48h of fasting (n=2) and fed ad libitum (n=2). Plasma testosterone (p<0.05) and blood glucose levels were significantly (p<0.001) decreased after short term fasting. Our results clearly showed that expression of hypothalamic Kiss1, Kiss1r and NR1 mRNA was significantly (p<0.05) reduced in adult male rhesus monkeys which were fasted for 48h as compared to those which were fed ad libitum. There was no clear difference in the GAD67 mRNA contents between the two groups. Number of kisspeptin neurons and the interactions of kisspeptin neurons with NR1 were significantly (p<0.05) reduced after 48h fasting. These observations suggest that decreased kisspeptin signaling during fasting may occur due to reduction in glutamatergic inputs to kisspeptin neurons. Our results also suggest that fasting induced suppression of kisspeptin signaling is not mediated through GABAergic neurons. PMID:26138506

  16. Withdrawal of dietary phytoestrogens in adult male rats affects hypothalamic regulation of food intake, induces obesity and alters glucose metabolism.

    PubMed

    Andreoli, María Florencia; Stoker, Cora; Rossetti, María Florencia; Alzamendi, Ana; Castrogiovanni, Daniel; Luque, Enrique H; Ramos, Jorge Guillermo

    2015-02-01

    The absence of phytoestrogens in the diet during pregnancy has been reported to result in obesity later in adulthood. We investigated whether phytoestrogen withdrawal in adult life could alter the hypothalamic signals that regulate food intake and affect body weight and glucose homeostasis. Male Wistar rats fed from conception to adulthood with a high phytoestrogen diet were submitted to phytoestrogen withdrawal by feeding a low phytoestrogen diet, or a high phytoestrogen-high fat diet. Withdrawal of dietary phytoestrogens increased body weight, adiposity and energy intake through an orexigenic hypothalamic response characterized by upregulation of AGRP and downregulation of POMC. This was associated with elevated leptin and T4, reduced TSH, testosterone and estradiol, and diminished hypothalamic ERα expression, concomitant with alterations in glucose tolerance. Removing dietary phytoestrogens caused manifestations of obesity and diabetes that were more pronounced than those induced by the high phytoestrogen-high fat diet intake. PMID:25486512

  17. Adaptive Regulation of Testis Gene Expression and Control of Male Fertility by the Drosophila Harpin RNA Pathway

    PubMed Central

    Wen, Jiayu; Duan, Hong; Bejarano, Fernando; Okamura, Katsutomo; Fabian, Lacramioara; Brill, Julie A.; Bortolamiol-Becet, Diane; Martin, Raquel; Ruby, J. Graham; Lai, Eric C.

    2014-01-01

    SUMMARY Although endogenous siRNAs (endo-siRNAs) have been described in many species, still little is known about their endogenous utility. Here, we show that Drosophila hairpin RNAs (hpRNAs) generate an endo-siRNA class with predominant expression in testes. Although hpRNAs are universally recently evolved, we identify highly complementary protein-coding targets for all hpRNAs. Importantly, we find broad evidence for evolutionary divergences that preferentially maintain compensatory pairing between hpRNAs and targets, serving as first evidence for adaptive selection for siRNA-mediated target regulation in metazoans. We demonstrate organismal impact of hpRNA activity, since knockout of hpRNA1 derepresses its target ATP synthase-β in testes and compromises spermatogenesis and male fertility. Moreover, we reveal surprising male-specific impact of RNAi factors on germ cell development and fertility, consistent with testis-directed function of the hpRNA pathway. Finally, the collected hpRNA loci chronicle an evolutionary timeline that reflects their origins from prospective target genes, mirroring a strategy described for plant miRNAs. PMID:25544562

  18. Androgen regulation of adrenocorticotropin and corticosterone secretion in the male rat following novelty and foot shock stressors.

    PubMed

    Handa, R J; Nunley, K M; Lorens, S A; Louie, J P; McGivern, R F; Bollnow, M R

    1994-01-01

    To examine mechanisms responsible for sex differences in hypothalamo-pituitary-adrenal (HPA) axis responsiveness to stress, we studied the role of androgens in the regulation of the adrenocorticotropin (ACTH) and corticosterone (CORT) responses to foot shock and novelty stressors in gonadectomized (GDX) or intact male F344 rats. Foot shock or exposure to a novel open field increased plasma ACTH and CORT, which was significantly greater in GDX vs. intacts. Testosterone (T) or dihydrotestosterone propionate (DHT) treatment of GDX animals returned poststress levels of ACTH and CORT to intact levels. Estrogen treatment of GDX males further increased poststress CORT secretion above GDX levels. There was no difference in the ACTH response of anterior pituitaries from intact, GDX, and GDX+DHT animals to CRF using an in vitro perifusion system. There were no differences in beta max or binding affinity of type I or II CORT receptors in the hypothalamus or hippocampus of intact, GDX, or GDX+DHT groups. These data demonstrate an effect of GDX on hormonal indices of stress. The increased response in GDX rats appears to be due to the release from androgen receptor mediated inhibition of the HPA axis. This inhibition by androgen is not due to changes in anterior pituitary sensitivity to CRH, nor to changes in type I or type II corticosteroid receptor concentrations. PMID:8140154

  19. Deficits in coordinated motor behavior and in nigrostriatal dopaminergic system ameliorated and VMAT2 expression up-regulated in aged male rats by administration of testosterone propionate.

    PubMed

    Wang, Li; Kang, Yunxiao; Zhang, Guoliang; Zhang, Yingbo; Cui, Rui; Yan, Wensheng; Tan, Huibing; Li, Shuangcheng; Wu, Baiyila; Cui, Huixian; Shi, Geming

    2016-06-01

    The effects of testosterone propionate (TP) supplements on the coordinated motor behavior and nigrostriatal dopaminergic (NSDA) system were analyzed in aged male rats. The present study showed the coordinated motor behavioral deficits, the reduced activity of NSDA system and the decreased expression of vesicular monoamine transporter 2 (VMAT2) in 24month-old male rats. Long term TP treatment improved the motor coordination dysfunction with aging. Increased tyrosine hydroxylase and dopamine transporter, as well as dopamine and its metabolites were found in the NSDA system of TP-treated 24month-old male rats, indicative of the amelioratory effects of TP supplements on NSDA system of aged male rats. The enhancement of dopaminergic (DAergic) activity of NSDA system by TP supplements might underlie the amelioration of the coordinated motor dysfunction in aged male rats. TP supplements up-regulated VMAT2 expression in NSDA system of aged male rats. Up-regulation of VMAT2 expression in aged male rats following chronic TP treatment might be involved in the maintenance of DAergic function of NSDA system in aged male rats. PMID:26956479

  20. 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. PMID:26967291

  1. Bile acid-FXRα pathways regulate male sexual maturation in mice.

    PubMed

    Baptissart, Marine; Martinot, Emmanuelle; Vega, Aurélie; Sédes, Lauriane; Rouaisnel, Betty; de Haze, Angélique; Baron, Silvère; Schoonjans, Kristina; Caira, Françoise; Volle, David H

    2016-04-12

    The bile acid receptor Farnesol-X-Receptor alpha (FRXα) is a member of the nuclear receptor superfamily. FRXα is expressed in the interstitial compartment of the adult testes, which contain the Leydig cells. In adult, short term treatment (12 hours) with FRXα agonist inhibits the expression of steroidogenic genes via the induction of the Small heterodimer partner (SHP). However the consequences of FRXα activation on testicular pathophysiology have never been evaluated. We demonstrate here that mice fed a diet supplemented with bile acid during pubertal age show increased incidence of infertility. This is associated with altered differentiation and increase apoptosis of germ cells due to lower testosterone levels. At the molecular level, next to the repression of basal steroidogenesis via the induction expression of Shp and Dax-1, two repressors of steroidogenesis, the main action of the BA-FRXα signaling is through lowering the Leydig cell sensitivity to the hypothalamo-pituitary axis, the main regulator of testicular endocrine function. In conclusion, BA-FRXα signaling is a critical actor during sexual maturation. PMID:26848619

  2. Bile acid-FXRα pathways regulate male sexual maturation in mice

    PubMed Central

    Vega, Aurélie; Sédes, Lauriane; Rouaisnel, Betty; de Haze, Angélique; Baron, Silvère; Schoonjans, Kristina; Caira, Françoise; Volle, David H.

    2016-01-01

    The bile acid receptor Farnesol-X-Receptor alpha (FRXα) is a member of the nuclear receptor superfamily. FRXα is expressed in the interstitial compartment of the adult testes, which contain the Leydig cells. In adult, short term treatment (12 hours) with FRXα agonist inhibits the expression of steroidogenic genes via the induction of the Small heterodimer partner (SHP). However the consequences of FRXα activation on testicular pathophysiology have never been evaluated. We demonstrate here that mice fed a diet supplemented with bile acid during pubertal age show increased incidence of infertility. This is associated with altered differentiation and increase apoptosis of germ cells due to lower testosterone levels. At the molecular level, next to the repression of basal steroidogenesis via the induction expression of Shp and Dax-1, two repressors of steroidogenesis, the main action of the BA-FRXα signaling is through lowering the Leydig cell sensitivity to the hypothalamo-pituitary axis, the main regulator of testicular endocrine function. In conclusion, BA-FRXα signaling is a critical actor during sexual maturation. PMID:26848619

  3. Altered immunity in male patients with alcoholic liver disease: evidence for defective immune regulation.

    PubMed

    Smith, W I; Van Thiel, D H; Whiteside, T; Janoson, B; Magovern, J; Puet, T; Rabin, B S

    1980-04-01

    We sought evidence for altered immunity in patients with alcoholic liver disease, and we correlated the observed immunologic abnormalities with the extent of histologically proven liver disease. Total circulating lymphocytes and the absolute number of T lymphocytes were decreased in alcoholics (p less than 0.01) compared to controls. Immunoglobulins G and A were elevated significantly (p less than 0.05) in alcoholic patients with hepatic fibrosis or cirrhosis compared to controls and alcoholics without liver histopathology. In alcoholics with fibrosis or cirrhosis at time of admission, IgE levels were also elevated (p less than 0.01) but decreased 50% during hospitalization. Forty-eight percent of the patients with alcoholic liver disease had antibodies to small bowel epithelium, and 33% had antibodies to fibroblast cytoplasm. In addition, we found that alcoholics immunized with polyvalent pneumococcal polysaccharide responded with significantly elevated (p less than 0.025) antibody titers compared to hospitalized controls. In aggregate, these findings in patients with alcoholic liver disease are consistent with a defect in immune regulation. PMID:6990823

  4. Cystic fibrosis transmembrane conductance regulator (CFTR) gene abnormalities in Indian males with congenital bilateral absence of vas deferens & renal anomalies

    PubMed Central

    Gajbhiye, Rahul; Kadam, Kaushiki; Khole, Aalok; Gaikwad, Avinash; Kadam, Seema; Shah, Rupin; Kumaraswamy, Rangaswamy; Khole, Vrinda

    2016-01-01

    Background & objectives: The role of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in congenital bilateral absence of vas deferens and unilateral renal agenesis (CBAVD-URA) has been controversial. Here, we report the cases of five Indian males with CBAVD-URA. The objective was to evaluate the presence or absence of CFTR gene mutations and variants in CBAVD-URA. The female partners of these males were also screened for cystic fibrosis (CF) carrier status. Methods: Direct DNA sequencing of CFTR gene was carried out in five Indian infertile males having CBAVD-URA. Female partners (n=5) and healthy controls (n=32) were also screened. Results: Three potential regulatory CFTR gene variants (c.1540A>G, c.2694T>G and c.4521G>A) were detected along with IVS8-5T mutation in three infertile males with CBAVD-URA. Five novel CFTR gene variants (c.621+91A>G, c.2752+106A>T, c.2751+85_88delTA, c.3120+529InsC and c.4375-69C>T), four potential regulatory CFTR gene variants (M470V, T854T, P1290P, Q1463Q) and seven previously reported CFTR gene variants (c.196+12T>C, c.875+40A>G, c.3041-71G>C, c.3271+42A>T, c.3272-93T>C, c.3500-140A>C and c.3601-65C>A) were detected in infertile men having CBAVD and renal anomalies Interpretation & conclusions: Based on our findings, we speculate that CBAVD-URA may also be attributed to CFTR gene mutations and can be considered as CFTR-related disorder (CFTR-RD). The CFTR gene mutation screening may be offered to CBAVD-URA men and their female partners undergoing ICSI. Further studies need to be done in a large sample to confirm the findings. PMID:27488005

  5. 78 FR 39638 - U.S. Integrated Ocean Observing System; Regulations To Certify and Integrate Regional...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-02

    ... National Oceanic and Atmospheric Administration 15 CFR Part 997 RIN 0648-BC18 U.S. Integrated Ocean.... Integrated Ocean Observing System Program Office (IOOS), National Oceanic and Atmospheric Administration (NOAA), Commerce. ACTION: Notice of proposed rulemaking. SUMMARY: The U.S. Integrated Ocean...

  6. Regional specific regulation of steroid receptor coactivator-1 immunoreactivity by orchidectomy in the brain of adult male mice.

    PubMed

    Bian, Chen; Zhang, Kaiyuan; Zhao, Yangang; Guo, Qiang; Cai, Wenqin; Zhang, Jiqiang

    2014-10-01

    Androgens including testosterone and dihydrotestosterone play important roles on brain structure and function, either directly through androgen receptor or indirectly through estrogen receptors, which need coactivators for their transcription activation. Steroid receptor coactivator-1 (SRC-1) has been shown to be multifunctional potentials in the brain, but how it is regulated by androgens in the brain remains unclear. In this study, we explored the effect of orchidectomy (ORX) on the expression of SRC-1 in the adult male mice using nickel-intensified immunohistochemistry. The results showed that ORX induced dramatic decrease of SRC-1 immunoreactivity in the olfactory tubercle, piriform cortex, ventral pallidum, most parts of the septal area, hippocampus, substantia nigra (compact part), pontine nuclei and nucleus of the trapezoid body (p<0.01). Significant decrease of SRC-1 was noticed in the dorsal and lateral septal nucleus, medial preoptical area, dorsomedial and ventromedial hypothalamic nucleus and superior paraolivary nucleus (p<0.05). Whereas in other regions examined, levels of SRC-1 immunoreactivity were not obviously changed by ORX (p>0.05). The above results demonstrated ORX downregulation of SRC-1 in specific regions that have been involved in sense of smell, learning and memory, cognition, neuroendocrine, reproduction and motor control, indicating that SRC-1 play pivotal role in the mediating circulating androgenic regulation on these important brain functions. It also indicates that SRC-1 may serve as a novel target for the central disorders caused by the age-related decrease of circulating androgens. PMID:24945110

  7. 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. PMID:27197225

  8. 75 FR 14059 - Federal Acquisition Regulation; FAR Case 2008-027, Federal Awardee Performance and Integrity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-23

    ...The Civilian Agency Acquisition Council and the Defense Acquisition Regulations Council (Councils) are issuing a final rule amending the Federal Acquisition Regulation (FAR) to implement the Federal Awardee Performance and Integrity Information System (FAPIIS), as required by section 872 of the Duncan Hunter National Defense Authorization Act for Fiscal Year 2009. FAPIIS is designed to improve......

  9. 75 FR 41097 - Homeland Security Acquisition Regulation; Lead System Integrators [HSAR Case 2009-003

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-15

    ... Acquisition Regulation; Lead System Integrators AGENCY: Office of the Chief Procurement Officer, DHS. ACTION... lead system integrators in the acquisition of DHS major systems if they have direct financial interests... 6 U.S.C. 396; hereinafter ``Section 396''), limits firms that can serve as lead system...

  10. 77 FR 67804 - Federal Acquisition Regulation; Submission for OMB Review; Integrity of Unit Prices

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-14

    ... collection requirement concerning Integrity of Unit Prices. A notice was published in the Federal Register at 77 FR 52739, on August 30, 2012. No comments were received. Public comments are particularly invited... Regulation; Submission for OMB Review; Integrity of Unit Prices AGENCY: Department of Defense (DOD),...

  11. Ecdysone signaling opposes epidermal growth factor signaling in regulating cyst differentiation in the male gonad of Drosophila melanogaster.

    PubMed

    Qian, Yue; Dominado, Nicole; Zoller, Richard; Ng, Chun; Kudyba, Karl; Siddall, Nicole A; Hime, Gary R; Schulz, Cordula

    2014-10-15

    The development of stem cell daughters into the differentiated state normally requires a cascade of proliferation and differentiation steps that are typically regulated by external signals. The germline cells of most animals, in specific, are associated with somatic support cells and depend on them for normal development. In the male gonad of Drosophila melanogaster, germline cells are completely enclosed by cytoplasmic extensions of somatic cyst cells, and these cysts form a functional unit. Signaling from the germline to the cyst cells via the Epidermal Growth Factor Receptor (EGFR) is required for germline enclosure and has been proposed to provide a temporal signature promoting early steps of differentiation. A temperature-sensitive allele of the EGFR ligand Spitz (Spi) provides a powerful tool for probing the function of the EGRF pathway in this context and for identifying other pathways regulating cyst differentiation via genetic interaction studies. Using this tool, we show that signaling via the Ecdysone Receptor (EcR), a known regulator of developmental timing during larval and pupal development, opposes EGF signaling in testes. In spi mutant animals, reducing either Ecdysone synthesis or the expression of Ecdysone signal transducers or targets in the cyst cells resulted in a rescue of cyst formation and cyst differentiation. Despite of this striking effect in the spi mutant background and the expression of EcR signaling components within the cyst cells, activity of the EcR pathway appears to be dispensable in a wildtype background. We propose that EcR signaling modulates the effects of EGFR signaling by promoting an undifferentiated state in early stage cyst cells. PMID:25169192

  12. Cistrome: an integrative platform for transcriptional regulation studies

    PubMed Central

    2011-01-01

    The increasing volume of ChIP-chip and ChIP-seq data being generated creates a challenge for standard, integrative and reproducible bioinformatics data analysis platforms. We developed a web-based application called Cistrome, based on the Galaxy open source framework. In addition to the standard Galaxy functions, Cistrome has 29 ChIP-chip- and ChIP-seq-specific tools in three major categories, from preliminary peak calling and correlation analyses to downstream genome feature association, gene expression analyses, and motif discovery. Cistrome is available at http://cistrome.org/ap/. PMID:21859476

  13. Regulation of mitotic spindle orientation: an integrated view.

    PubMed

    di Pietro, Florencia; Echard, Arnaud; Morin, Xavier

    2016-08-01

    Mitotic spindle orientation is essential for cell fate decisions, epithelial maintenance, and tissue morphogenesis. In most animal cell types, the dynein motor complex is anchored at the cell cortex and exerts pulling forces on astral microtubules to position the spindle. Early studies identified the evolutionarily conserved Gαi/LGN/NuMA complex as a key regulator that polarizes cortical force generators. In recent years, a combination of genetics, biochemistry, modeling, and live imaging has contributed to decipher the mechanisms of spindle orientation. Here, we highlight the dynamic nature of the assembly of this complex and discuss the molecular regulation of its localization. Remarkably, a number of LGN-independent mechanisms were described recently, whereas NuMA remains central in most pathways involved in recruiting force generators at the cell cortex. We also describe the emerging role of the actin cortex in spindle orientation and discuss how dynamic astral microtubule formation is involved. We further give an overview on instructive external signals that control spindle orientation in tissues. Finally, we discuss the influence of cell geometry and mechanical forces on spindle orientation. PMID:27432284

  14. Integration of Shh and Wnt Signaling Pathways Regulating Hematopoiesis.

    PubMed

    Zhou, Zhigang; Wan, Liping; Wang, Chun; Zhou, Kun

    2015-12-01

    To investigate the spatial and temporal programmed expression of Shh and Wnt members during key stages of definitive hematopoiesis and the possible mechanism of Shh and Wnt signaling pathways regulating the proliferation of hematopoietic progenitor cells (HPCs). Spatial and temporal programmed gene expression of Shh and Wnt signaling during hematopoiesis corresponded with c-kit(+)lin(-) HPCs proliferation. C-kit(+)Lin(-) populations derived from aorta-gonad-mesonephros (AGM) of Balb/c mice at E10.5 with increased expression of Shh and Wnt3a demonstrated a greater potential for proliferation. Additionally, supplementation with soluble Shh N-terminal peptide promoted the proliferation of c-kit(+)Lin(-) populations by activating the Wnt signaling pathway, an effect which was inhibited by blocking Shh signaling. A specific inhibitor of wnt signaling was capable of inhibiting Shh-induced proliferation in a similar manner to shh inhibitor. Our results provide valuable information on Shh and Wnt signaling involved in hematopoiesis and highlight the importance of interaction of Shh and Wnt signaling in regulating HPCs proliferation. PMID:26378473

  15. The Mediating Role of Self-Regulation Between Intrafamilial Violence and Mental Health Adjustment in Incarcerated Male Adolescents

    PubMed Central

    Perkins, Suzanne C.; Cortina, Kai S.; Smith-Darden, Joanne; Graham-Bermann, Sandra

    2014-01-01

    Background This paper investigates the relation between history of intrafamilial violence and self-regulatory capacity, cognitive processing and mental health adjustment in incarcerated adolescents. Adolescents were incarcerated at the time of the study for various violent offenses, ranging from persistent delinquency to sexual assault (n = 115). A model is proposed that posits that self-regulation, cognitive ability and cognitive processing are integral to the relation between intrafamilial violence and mental health function. The primary hypothesis of the study tests this mediation model. The relations between mental health, cognitive processing, self-regulation and intrafamilial violence are also examined. Methods The study was conducted during two sessions at a juvenile facility in the Midwest using survey measures, academic and intelligence testing and cognitive tasks. Results Youth were between the ages of 13 and 20. Approximately 70% were previously diagnosed with a disability. Significant Pearson’s correlations were found between seven out of eight mental health subscales of the Youth Self-Report (YSR) and intrafamilial violence history. Structural equation modeling was used to examine the role of cognitive processing in the association between intrafamilial violence and mental health function. Non-verbal or performance deficits, a significant difference between verbal skills and non-verbal skills, were related to intrafamilial violence. Self-regulation partially mediated the relation between intrafamilial violence and mental health function. Conclusions Self-regulation ability may be compromised by intrafamilial violence and be a precursor to both internalizing and externalizing mental health problem in incarcerated youth. Educational, clinical and research implications are discussed. PMID:22080578

  16. NUCLEAR-MEDIATED MITOCHONDRIAL GENE REGULATION AND MALE FERTILITY IN HIGHER PLANTS: LIGHT AT THE END OF THE TUNNEL?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The exploitation of hybrid vigor in plants usually capitalizes on cytoplasmic male sterility (CMS), a maternally inherited trait characterized by the absence of functional pollen. Hybrids of many plants are produced using CMS, wherein a male-sterile line is grown adjacent to a selected male-fertile...

  17. 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. PMID:26564248

  18. TAK1 regulates Paneth cell integrity partly through blocking necroptosis

    PubMed Central

    Simmons, A N; Kajino-Sakamoto, R; Ninomiya-Tsuji, J

    2016-01-01

    Paneth cells reside at the base of crypts of the small intestine and secrete antimicrobial factors to control gut microbiota. Paneth cell loss is observed in the chronically inflamed intestine, which is often associated with increased reactive oxygen species (ROS). However, the relationship between Paneth cell loss and ROS is not yet clear. Intestinal epithelial-specific deletion of a protein kinase Tak1 depletes Paneth cells and highly upregulates ROS in the mouse model. We found that depletion of gut bacteria or myeloid differentiation factor 88 (Myd88), a mediator of bacteria-derived cell signaling, reduced ROS but did not block Paneth cell loss, suggesting that gut bacteria are the cause of ROS accumulation but bacteria-induced ROS are not the cause of Paneth cell loss. In contrast, deletion of the necroptotic cell death signaling intermediate, receptor-interacting protein kinase 3 (Ripk3), partially blocked Paneth cell loss. Thus, Tak1 deletion causes Paneth cell loss in part through necroptotic cell death. These results suggest that TAK1 participates in intestinal integrity through separately modulating bacteria-derived ROS and RIPK3-dependent Paneth cell loss. PMID:27077812

  19. 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. PMID:26631738

  20. Integrin β1 regulates leiomyoma cytoskeletal integrity and growth

    PubMed Central

    Malik, Minnie; Segars, James; Catherino, William H.

    2014-01-01

    Uterine leiomyomas are characterized by an excessive extracellular matrix, increased mechanical stress, and increased active RhoA. Previously, we observed that mechanical signaling was attenuated in leiomyoma, but the mechanisms responsible remain unclear. Integrins, especially integrin β1, are transmembrane adhesion receptors that couple extracellular matrix stresses to the intracellular cytoskeleton to influence cell proliferation and differentiation. Here we characterized integrin and laminin to signaling in leiomyoma cells. We observed a 2.25 ± 0.32 fold increased expression of integrin β1 in leiomyoma cells, compared to myometrial cells. Antibody-mediated inhibition of integrin β1 led to significant growth inhibition in leiomyoma cells and a loss of cytoskeletal integrity. Specifically, polymerization of actin filaments and formation of focal adhesions were reduced by inhibition of integrin p1. Inhibition of integrin β1 in leiomyoma cells led to 0.81 ± 0.02 fold decrease in active RhoA, and resembled levels found in serum-starved cells. Likewise, inhibition of integrin β1 was accompanied by a decrease in phospho-ERK. Compared to myometrial cells, leiomyoma cells demonstrated increased expression of integrin α6 subunit to laminin receptor (1.91 ± 0.11 fold), and increased expression of laminin 5α (1.52±0.02), laminin 5β (3.06±0.92), and laminin 5γ (1.66 ± 0.06). Of note, leiomyoma cells grown on laminin matrix appear to realign themselves. Taken together, the findings reveal that the attenuated mechanical signaling in leiomyoma cells is accompanied by an increased expression and a dependence on integrin β1 signaling in leiomyoma cells, compared to myometrial cells. PMID:23023061

  1. 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)...

  2. Combined melatonin and exendin-4 therapy preserves renal ultrastructural integrity after ischemia-reperfusion injury in the male rat.

    PubMed

    Yip, Hon-Kan; Yang, Chih-Chao; Chen, Kuan-Hung; Huang, Tien-Hung; Chen, Yi-Ling; Zhen, Yen-Yi; Sung, Pei-Hsun; Chiang, Hsin-Ju; Sheu, Jiunn-Jye; Chang, Chia-Lo; Chen, Chih-Hung; Chang, Hsueh-Wen; Chen, Yen-Ta

    2015-11-01

    We tested whether combined melatonin (Mel) and exendin-4 (Ex4) treatment can better preserve glomerular structural integrity after ischemia-reperfusion (IR) injury compared with either alone. Adult male Sprague Dawley rats (n = 50) were equally divided into sham control (SC), IR, IR-Ex4 (10 μg/kg subcutaneously 30 min after reperfusion and daily for 5 days), IR-Mel (20 mg/kg intraperitoneally at 30 min postreperfusion and 50 mg/kg at 6 and 18 hr), and IR-Ex4-Mel were euthanized at day 14. Serum creatinine level and urine protein-to-creatinine ratio at days 3 and 14 were highest in IR group and lowest in SC, significantly higher in IR-Ex4 and IR-Mel groups than in IR-Ex4-Mel group (all P < 0.001) without significant difference between IR-Ex4 and IR-Mel groups. Changes in podocyte injury score (PIS) and kidney injury score were highest in IR group and lowest in SC, significantly higher in IR-Ex4 and IR-Mel groups than in IR-Ex4-Mel, and significantly higher in IR-Mel group than in IR-Ex4 group (all P < 0.001). Immunohistochemical microscopic findings of the expressions of FSP-1 and WT-1 (two glomerular damage indicators) and KIM-1 and snail (two renal tubular-damaged indicators) showed an identical pattern, whereas the expressions of ZO-1, p-cadherin, podocin, dystroglycan, fibronectin, and synaptopodin (six indices of glomerular integrity) demonstrated an opposite pattern compared to that of PIS among five groups (all P < 0.001). Protein expressions of inflammatory (TNF-α/NF-κB/MMP-9) and oxidative stress (NOX-1, NOX-2, oxidized protein) biomarkers exhibited an identical pattern to that of PIS among five groups (all P < 0.001). Combined melatonin-exednin-4 therapy further protected glomerulus from IR injury. PMID:26309060

  3. Multiple-Family Group Intervention for Incarcerated Male Adolescents Who Sexually Offend and Their Families: Change in Maladaptive Emotion Regulation Predicts Adaptive Change in Adolescent Behaviors.

    PubMed

    Keiley, Margaret K; Zaremba-Morgan, Ali; Datubo-Brown, Christiana; Pyle, Raven; Cox, Milira

    2015-07-01

    The multiple-family group intervention is an effective, yet affordable, 8-week treatment that is conducted in a juvenile correctional institution in Alabama with adolescents who sexually offend and their families. Data from 115 incarcerated male adolescents and their male and female caregivers collected at pre-, post-, and 1-year follow-up were used to determine that problem behaviors (internalizing, externalizing) decreased over pre- and posttest and the significant decreases in maladaptive emotion regulation predicted those changes. Adolescent-reported anxiety over abandonment and attachment dependence on parents increased significantly; these changes were predicted by decreases in maladaptive emotion regulation. Linear growth models were also fit over the 3 time points and indicate decreases in adolescent problem behavior and maladaptive emotion regulation. PMID:24809985

  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. PIF4 Integrates Multiple Environmental and Hormonal Signals for Plant Growth Regulation in Arabidopsis.

    PubMed

    Choi, Hyunmo; Oh, Eunkyoo

    2016-08-31

    As sessile organisms, plants must be able to adapt to the environment. Plants respond to the environment by adjusting their growth and development, which is mediated by sophisticated signaling networks that integrate multiple environmental and endogenous signals. Recently, increasing evidence has shown that a bHLH transcription factor PIF4 plays a major role in the multiple signal integration for plant growth regulation. PIF4 is a positive regulator in cell elongation and its activity is regulated by various environmental signals, including light and temperature, and hormonal signals, including auxin, gibberellic acid and brassinosteroid, both transcriptionally and post-translationally. Moreover, recent studies have shown that the circadian clock and metabolic status regulate endogenous PIF4 level. The PIF4 transcription factor cooperatively regulates the target genes involved in cell elongation with hormone-regulated transcription factors. Therefore, PIF4 is a key integrator of multiple signaling pathways, which optimizes growth in the environment. This review will discuss our current understanding of the PIF4-mediated signaling networks that control plant growth. PMID:27432188

  6. PIF4 Integrates Multiple Environmental and Hormonal Signals for Plant Growth Regulation in Arabidopsis

    PubMed Central

    Choi, Hyunmo; Oh, Eunkyoo

    2016-01-01

    As sessile organisms, plants must be able to adapt to the environment. Plants respond to the environment by adjusting their growth and development, which is mediated by sophisticated signaling networks that integrate multiple environmental and endogenous signals. Recently, increasing evidence has shown that a bHLH transcription factor PIF4 plays a major role in the multiple signal integration for plant growth regulation. PIF4 is a positive regulator in cell elongation and its activity is regulated by various environmental signals, including light and temperature, and hormonal signals, including auxin, gibberellic acid and brassinosteroid, both transcriptionally and post-translationally. Moreover, recent studies have shown that the circadian clock and metabolic status regulate endogenous PIF4 level. The PIF4 transcription factor cooperatively regulates the target genes involved in cell elongation with hormone-regulated transcription factors. Therefore, PIF4 is a key integrator of multiple signaling pathways, which optimizes growth in the environment. This review will discuss our current understanding of the PIF4-mediated signaling networks that control plant growth. PMID:27432188

  7. Mechanisms regulating male sexual behavior in the rat: role of 3 alpha- and 3 beta-androstanediols.

    PubMed

    Morali, G; Oropeza, M V; Lemus, A E; Perez-Palacios, G

    1994-09-01

    To assess whether naturally occurring 5 alpha-androstanediols (5 alpha-androstane-3 alpha, 17 beta-diol and 5 alpha-androstane-3 beta, 17 beta-diol) play a role in the regulation of male sexual behavior in the rat, their capability to restore copulatory behavior in castrated animals was evaluated. Androstanediols were chronically administered either alone or in combination with 5 alpha-dihydrotestosterone (DHT) or with estradiol-17 beta (E2). Animals treated with testosterone (T), DHT, E2, and vehicle, either alone or in different combinations, served as controls. The occurrence of mounting, intromission, and ejaculation as well as detailed parameters of copulatory behavior were recorded twice per week for 3 weeks. At the end of treatments, the weights of sex accessory organs were also recorded. When 3 beta, 5 alpha-androstanediol (3 beta-diol; 500 micrograms/day) was administered in combination with DHT (300 micrograms/day), full copulatory behavior was restored in all subjects in a manner similar to that obtained with E2 plus DHT or T plus DHT combinations, thus indicating an estrogen-like behavioral effect of 3 beta-diol. Administration of 3 alpha, 5 alpha-androstanediol (3 alpha-diol; 500 micrograms/day) combined with DHT also restored sexual behavior, though to a lesser extent. When 3 alpha-diol (500 micrograms/day) was simultaneously administered with E2 (5 micrograms/day), the copulatory behavior of castrated animals was fully restored in a fashion similar to that observed after administration of DHT plus E2 and T plus E2 combinations, indicating a potent androgen-like effect of 3 alpha-diol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7803627

  8. 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. PMID:23536095

  9. 75 FR 3178 - Defense Federal Acquisition Regulation Supplement; Lead System Integrators

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-20

    ... an interim rule at 73 FR 1823 on January 10, 2008, to implement Section 807 of the National ] Defense... 74 FR 34268 on July 15, 2009, is adopted as a final rule without change. BILLING CODE 5001-08-P ... Acquisition Regulation Supplement; Lead System Integrators AGENCY: Department of Defense (DoD). ACTION:...

  10. Near-Perfect Synaptic Integration by Nav1.7 in Hypothalamic Neurons Regulates Body Weight.

    PubMed

    Branco, Tiago; Tozer, Adam; Magnus, Christopher J; Sugino, Ken; Tanaka, Shinsuke; Lee, Albert K; Wood, John N; Sternson, Scott M

    2016-06-16

    Neurons are well suited for computations on millisecond timescales, but some neuronal circuits set behavioral states over long time periods, such as those involved in energy homeostasis. We found that multiple types of hypothalamic neurons, including those that oppositely regulate body weight, are specialized as near-perfect synaptic integrators that summate inputs over extended timescales. Excitatory postsynaptic potentials (EPSPs) are greatly prolonged, outlasting the neuronal membrane time-constant up to 10-fold. This is due to the voltage-gated sodium channel Nav1.7 (Scn9a), previously associated with pain-sensation but not synaptic integration. Scn9a deletion in AGRP, POMC, or paraventricular hypothalamic neurons reduced EPSP duration, synaptic integration, and altered body weight in mice. In vivo whole-cell recordings in the hypothalamus confirmed near-perfect synaptic integration. These experiments show that integration of synaptic inputs over time by Nav1.7 is critical for body weight regulation and reveal a mechanism for synaptic control of circuits regulating long term homeostatic functions. PMID:27315482

  11. Food, stress, and circulating testosterone: Cue integration by the testes, not the brain, in male zebra finches (Taeniopygia guttata).

    PubMed

    Lynn, Sharon E; Perfito, Nicole; Guardado, Daisy; Bentley, George E

    2015-05-01

    Food abundance is closely associated with reproductive readiness in vertebrates. Food scarcity can activate the hypothalamo-pituitary-adrenal axis, decrease sex steroid secretion, and dampen reproductive behavior. However, the mechanisms underlying these transient effects are unclear. Gonadotropin inhibitory hormone (GnIH), a neuropeptide present in the brain and gonads, is also influenced by glucocorticoids and fasting in some species. We investigated whether fasting stress activated the GnIH system in zebra finches (Taeniopygia guttata), with the potential for downstream effects on reproductive physiology and behavior. We fasted or fed males ad libitum for 10h. Fasting increased corticosterone and decreased testosterone in circulation. To assess whether the decrease in testosterone was mediated by changes in the hypothalamus and/or the gonads, we (1) quantified GnRH- and GnIH-positive neurons in the hypothalamus, (2) assessed hypothalamic gene expression for GnRH and GnIH, and (3) examined gene expression for proteins involved in testosterone synthesis in fasted and control birds. No measure of hypothalamic neuropeptides was related to treatment or circulating steroids. However, birds with higher corticosterone had higher testicular GnIH expression and lower testosterone. StAR and LHR expression were lower in the testes of fasted birds than controls. Thus, the decrease in testosterone was not likely mediated by hypothalamic GnIH, but rather by direct actions of fasting and/or corticosterone on the testes, indicating that the testes can integrate and respond to cues of stress directly. Such local inhibition of testosterone synthesis may allow for rapid and reversible changes in physiology and behavior when conditions are inappropriate for breeding. PMID:25849310

  12. 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

  13. Male Osteoporosis

    PubMed Central

    Drake, Matthew T.; Khosla, Sundeep

    2013-01-01

    Synopsis Osteoporosis is now recognized as a major threat to health in aging men. Morbidity and mortality, particularly following hip fracture, are substantial. Whereas trabecular bone loss starts in early adulthood, loss of cortical bone only appears to occur from mid-life onwards. Declining bioavailable estradiol levels play an integral role in male age-associated bone loss. Both pharmacologic and supportive care interventions are important for optimal care in men at increased fracture risk. PMID:22877433

  14. Regulation of the seasonal leptin and leptin receptor expression profile during early sexual maturation and feed restriction in male Atlantic salmon, Salmo salar L., parr.

    PubMed

    Trombley, Susanne; Mustafa, Arshi; Schmitz, Monika

    2014-08-01

    In mammals, leptin acts as an adiposity signal and is a crucial link between nutritional status and the reproductive axis. So far the link between leptin and energy balance during sexual maturation in teleosts has been poorly investigated. In this study, seasonal gene expression changes in two leptin genes (lepa1 and lepa2) and the leptin receptor were investigated during early sexual maturation in male Atlantic salmon parr under fully fed (control) and feed restricted conditions from April through September. Both Atlantic salmon lepa1 and lepa2 in the liver and lepr in the brain were significantly down-regulated in non-maturing control males in early spring, coinciding with the start of the growth and fat accumulation. In maturing control males, hepatic leptin expression increased during mid-spermatogenesis and lepa1 and lepa2 mRNA levels were up-regulated by 7.7 and 49 times respectively during final maturation. For the first time in a fish species, a significant up-regulation of lepr expression was observed in the testis throughout mid to late spermatogenesis. Feed restriction decreased the incidence of sexual maturation by 53% and highly up-regulated both leptin genes in the liver and the leptin receptor in the pituitary. This study shows that hepatic lepa1 and lepa2 expression and lepr expression in the testis is affected by early sexual maturation in male Atlantic salmon parr. Fast growth and high fat stores are associated with low leptin levels while feed restriction has a stimulatory effect on hepatic leptin and leptin receptor gene expression in the pituitary, suggesting a role for leptin other than that as an adiposity signal. PMID:24818969

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

    PubMed Central

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

    2015-01-01

    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. PMID:26620795

  16. FoxO1 Plays an Important Role in Regulating β-Cell Compensation for Insulin Resistance in Male Mice.

    PubMed

    Zhang, Ting; Kim, Dae Hyun; Xiao, Xiangwei; Lee, Sojin; Gong, Zhenwei; Muzumdar, Radhika; Calabuig-Navarro, Virtu; Yamauchi, Jun; Harashima, Hideyoshi; Wang, Rennian; Bottino, Rita; Alvarez-Perez, Juan Carlos; Garcia-Ocaña, Adolfo; Gittes, George; Dong, H Henry

    2016-03-01

    β-Cell compensation is an essential mechanism by which β-cells increase insulin secretion for overcoming insulin resistance to maintain euglycemia in obesity. Failure of β-cells to compensate for insulin resistance contributes to insulin insufficiency and overt diabetes. To understand the mechanism of β-cell compensation, we characterized the role of forkhead box O1 (FoxO1) in β-cell compensation in mice under physiological and pathological conditions. FoxO1 is a key transcription factor that serves as a nutrient sensor for integrating insulin signaling to cell metabolism, growth, and proliferation. We showed that FoxO1 improved β-cell compensation via 3 distinct mechanisms by increasing β-cell mass, enhancing β-cell glucose sensing, and augmenting β-cell antioxidative function. These effects accounted for increased glucose-stimulated insulin secretion and enhanced glucose tolerance in β-cell-specific FoxO1-transgenic mice. When fed a high-fat diet, β-cell-specific FoxO1-transgenic mice were protected from developing fat-induced glucose disorder. This effect was attributable to increased β-cell mass and function. Furthermore, we showed that FoxO1 activity was up-regulated in islets, correlating with the induction of physiological β-cell compensation in high-fat-induced obese C57BL/6J mice. These data characterize FoxO1 as a pivotal factor for orchestrating physiological adaptation of β-cell mass and function to overnutrition and obesity. PMID:26727107

  17. 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 examininggroup-based emotion regulationthat 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. PMID:25870386

  18. 10 CFR 905.10 - Who must comply with the integrated resource planning and reporting regulations in this subpart?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 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... planning and reporting regulations in this subpart? (a) Integrated resource plans (IRP) and...

  19. 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... planning and reporting regulations in this subpart? (a) Integrated resource plans (IRP) and...

  20. NODAL secreted by male germ cells regulates the proliferation and function of human Sertoli cells from obstructive azoospermia and nonobstructive azoospermia patients.

    PubMed

    Tian, Ru-Hui; Yang, Shi; Zhu, Zi-Jue; Wang, Jun-Long; Liu, Yun; Yao, Chencheng; Ma, Meng; Guo, Ying; Yuan, Qingqing; Hai, Yanan; Huang, Yi-Ran; He, Zuping; Li, Zheng

    2015-01-01

    This study was designed to explore the regulatory effects of male germ cell secreting factor NODAL on Sertoli cell fate decisions from obstructive azoospermia (OA) and nonobstructive azoospermia (NOA) patients. Human Sertoli cells and male germ cells were isolated using two-step enzymatic digestion and SATPUT from testes of azoospermia patients. Expression of NODAL and its multiple receptors in human Sertoli cells and male germ cells were characterized by reverse transcription-polymerase chain reaction (RT-PCR) and immunochemistry. Human recombinant NODAL and its receptor inhibitor SB431542 were employed to probe their effect on the proliferation of Sertoli cells using the CCK-8 assay. Quantitative PCR and Western blots were utilized to assess the expression of Sertoli cell functional genes and proteins. NODAL was found to be expressed in male germ cells but not in Sertoli cells, whereas its receptors ALK4, ALK7, and ACTR-IIB were detected in Sertoli cells and germ cells, suggesting that NODAL plays a regulatory role in Sertoli cells and germ cells via a paracrine and autocrine pathway, respectively. Human recombinant NODAL could promote the proliferation of human Sertoli cells. The expression of cell cycle regulators, including CYCLIN A, CYCLIN D1 and CYCLIN E, was not remarkably affected by NODAL signaling. NODAL enhanced the expression of essential growth factors, including GDNF, SCF, and BMP4, whereas SB431542 decreased their levels. There was not homogeneity of genes changes by NODAL treatment in Sertoli cells from OA and Sertoli cell-only syndrome (SCO) patients. Collectively, this study demonstrates that NODAL produced by human male germ cells regulates proliferation and numerous gene expression of Sertoli cells. PMID:26289399

  1. Research integrity in greater China: surveying regulations, perceptions and knowledge of research integrity from a Hong Kong perspective.

    PubMed

    Jordan, Sara R; Gray, Phillip W

    2013-12-01

    In their 2010 article 'Research Integrity in China: Problems and Prospects', Zeng and Resnik challenge others to engage in empirical research on research integrity in China. Here we respond to that call in three ways: first, we provide updates to their analysis of regulations and allegations of scientific misconduct; second, we report on two surveys conducted in Hong Kong that provide empirical backing to describe ways in which problems and prospects that Zeng and Resnik identify are being explored; and third, we continue the discussion started by Zeng and Resnik, pointing to ways in which China's high-profile participation in international academic research presents concerns about research integrity. According to our research, based upon searches of both English and Chinese language literature and policies, and two surveys conducted in Hong Kong, academic faculty and research post-graduate students in Hong Kong are aware of and have a positive attitude towards responsible conduct of research. Although Hong Kong is but one small part of China, we present this research as a response to concerns Zeng and Resnik introduce and as a call for a continued conversation. PMID:22994886

  2. 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

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

    PubMed

    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

  4. Astrocytic laminin regulates pericyte differentiation and maintains blood brain barrier integrity

    NASA Astrophysics Data System (ADS)

    Yao, Yao; Chen, Zu-Lin; Norris, Erin H.; Strickland, Sidney

    2014-03-01

    Blood brain barrier (BBB) breakdown is not only a consequence of but also contributes to many neurological disorders, including stroke and Alzheimer’s disease. How the basement membrane (BM) contributes to the normal functioning of the BBB remains elusive. Here we use conditional knockout mice and an acute adenovirus-mediated knockdown model to show that lack of astrocytic laminin, a brain-specific BM component, induces BBB breakdown. Using functional blocking antibody and RNAi, we further demonstrate that astrocytic laminin, by binding to integrin α2 receptor, prevents pericyte differentiation from the BBB-stabilizing resting stage to the BBB-disrupting contractile stage, and thus maintains the integrity of BBB. Additionally, loss of astrocytic laminin decreases aquaporin-4 (AQP4) and tight junction protein expression. Altogether, we report a critical role for astrocytic laminin in BBB regulation and pericyte differentiation. These results indicate that astrocytic laminin maintains the integrity of BBB through, at least in part, regulation of pericyte differentiation.

  5. NF-κB and epigenetic mechanisms as integrative regulators of brain resilience to anoxic stress.

    PubMed

    Sarnico, Ilenia; Branca, Caterina; Lanzillotta, Annamaria; Porrini, Vanessa; Benarese, Marina; Spano, Pier Franco; Pizzi, Marina

    2012-10-01

    Brain cells display an amazing ability to respond to several different types of environmental stimuli and integrate this response physiologically. Some of these responses can outlive the original stimulus by days, weeks or even longer. Long-lasting changes in both physiological and pathological conditions occurring in response to external stimuli are almost always mediated by changes in gene expression. To effect these changes, cells have developed an impressive repertoire of signaling systems designed to modulate the activity of numerous transcription factors and epigenetic mechanisms affecting the chromatin structure. Since its initial characterization in the nervous system, NF-κB has shown to respond to multiple signals and elicit pleiotropic activities suggesting that it may play a pivotal role in integration of different types of information within the brain. Ample evidence demonstrates that NF-κB factors are engaged in and necessary for neuronal development and synaptic plasticity, but they also regulate brain response to environmental noxae. By focusing on the complexity of NF-κB transcriptional activity in neuronal cell death, it emerged that the composition of NF-κB active dimers finely tunes the neuronal vulnerability to brain ischemia. Even though we are only beginning to understand the contribution of distinct NF-κB family members to the regulation of gene transcription in the brain, an additional level of regulation of NF-κB activity has emerged as operated by the epigenetic mechanisms modulating histone acetylation. We will discuss NF-κB and epigenetic mechanisms as integrative regulators of brain resilience to anoxic stress and useful drug targets for restoration of brain function. This article is part of a Special Issue entitled: Brain Integration. PMID:22575713

  6. Soy protein diet alters expression of hepatic genes regulating fatty acid and thyroid hormone metabolism in the male rat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We determined effects of soy protein (SPI) and the isoflavone genistein (GEN) on mRNA expression of key lipid metabolism and thyroid hormone system genes in young adult, male Sprague-Dawley rats. SPI-fed rats had less retroperitoneal fat and less hepato-steatosis than casein (CAS, control protein)-...

  7. 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.

  8. PGC-1α Integrates Insulin Signaling, Mitochondrial Regulation, and Bioenergetic Function in Skeletal Muscle*S⃞

    PubMed Central

    Pagel-Langenickel, Ines; Bao, Jianjun; Joseph, Joshua J.; Schwartz, Daniel R.; Mantell, Benjamin S.; Xu, Xiuli; Raghavachari, Nalini; Sack, Michael N.

    2008-01-01

    The pathophysiology underlying mitochondrial dysfunction in insulin-resistant skeletal muscle is incompletely characterized. To further delineate this we investigated the interaction between insulin signaling, mitochondrial regulation, and function in C2C12 myotubes and in skeletal muscle. In myotubes elevated insulin and glucose disrupt insulin signaling, mitochondrial biogenesis, and mitochondrial bioenergetics. The insulin-sensitizing thiazolidinedione pioglitazone restores these perturbations in parallel with induction of the mitochondrial biogenesis regulator PGC-1α. Overexpression of PGC-1α rescues insulin signaling and mitochondrial bioenergetics, and its silencing concordantly disrupts insulin signaling and mitochondrial bioenergetics. In primary skeletal myoblasts pioglitazone also up-regulates PGC-1α expression and restores the insulin-resistant mitochondrial bioenergetic profile. In parallel, pioglitazone up-regulates PGC-1α in db/db mouse skeletal muscle. Interestingly, the small interfering RNA knockdown of the insulin receptor in C2C12 myotubes down-regulates PGC-1α and attenuates mitochondrial bioenergetics. Concordantly, mitochondrial bioenergetics are blunted in insulin receptor knock-out mouse-derived skeletal myoblasts. Taken together these data demonstrate that elevated glucose and insulin impairs and pioglitazone restores skeletal myotube insulin signaling, mitochondrial regulation, and bioenergetics. Pioglitazone functions in part via the induction of PGC-1α. Moreover, PGC-1α is identified as a bidirectional regulatory link integrating insulin-signaling and mitochondrial homeostasis in skeletal muscle. PMID:18579525

  9. An Integrative Approach for the Large-scale Identification of Human Genome Kinases Regulating Cancer Metastasis

    PubMed Central

    Zhang, Hanshuo; Wu, Pu-Yen; Ma, Ming; Ye, Yanzheng; Hao, Yang; Yang, Junyu; Yin, Shenyi; Sun, Changhong; Phan, John H.; Wang, May D.; Xi, Jianzhong Jeff

    2016-01-01

    Kinases regulate the majority of biological processes and become one of important groups of drug targets. To identify more kinases being potential for cancer therapy, we developed an integrative approach for the large-scale screen of functional genes capable of regulating the main traits of cancer metastasis, including cell migration as well as invasion. We first employed self-assembled cell microarray (SAMcell) to screen functional genes that regulate cancer cell migration using a siRNA library targeting 710 human genome kinase genes. We identified 81 genes capable of significantly regulating cancer cell migration. Following with invasion assays and bio-informatics analysis, we discovered that 16 genes with differentially expression in cancer samples can regulate both cell migration and invasion, among which 10 genes have been well known to play critical roles in the cancer development. The remaining 6 genes were experimentally validated to have the capacities of regulating the metastasis-related traits, including cell proliferation, apoptosis and anoikis activities besides cell motility. Together, these findings provide a new insight into the therapeutic use of human kinases. PMID:23751374

  10. Down-regulation of OsSPX1 caused semi-male sterility, resulting in reduction of grain yield in rice.

    PubMed

    Zhang, Kang; Song, Qian; Wei, Qiang; Wang, Chunchao; Zhang, Liwei; Xu, Wenying; Su, Zhen

    2016-08-01

    OsSPX1, a rice SPX domain gene, involved in the phosphate (Pi)-sensing mechanism plays an essential role in the Pi-signalling network through interaction with OsPHR2. In this study, we focused on the potential function of OsSPX1 during rice reproductive phase. Based on investigation of OsSPX1 antisense and sense transgenic rice lines in the paddy fields, we discovered that the down-regulation of OsSPX1 caused reduction of seed-setting rate and filled grain number. Through examination of anthers and pollens of the transgenic and wild-type plants by microscopy, we found that the antisense of OsSPX1 gene led to semi-male sterility, with lacking of mature pollen grains and phenotypes with a disordered surface of anthers and pollens. We further conducted rice whole-genome GeneChip analysis to elucidate the possible molecular mechanism underlying why the down-regulation of OsSPX1 caused deficiencies in anthers and pollens and lower seed-setting rate in rice. The down-regulation of OsSPX1 significantly affected expression of genes involved in carbohydrate metabolism and sugar transport, anther development, cell cycle, etc. These genes may be related to pollen fertility and male gametophyte development. Our study demonstrated that down-regulation of OsSPX1 disrupted rice normal anther and pollen development by affecting carbohydrate metabolism and sugar transport, leading to semi-male sterility, and ultimately resulted in low seed-setting rate and grain yield. PMID:26806409

  11. 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. PMID:27064123

  12. 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. PMID:26772997

  13. Regulation of the ndh gene of Escherichia coli by integration host factor and a novel regulator, Arr.

    PubMed

    Green, J; Anjum, M F; Guest, J R

    1997-09-01

    The ndh gene of Escherichia coli encodes the non-proton-translocating NADH dehydrogenase II. Expression of the ndh gene is subject to a complex network of regulatory controls at the transcriptional level. Under anaerobic conditions ndh is repressed by the regulator of fumarate and nitrate reduction (FNR). However, in the absence of FNR, ndh expression is activated by the amino acid response regulator (Arr) during anaerobic growth in rich medium. Expression of the ndh gene varies during the growth cycle in response to the intracellular concentration of the heat-stable DNA-binding protein, Fis. In this work two additional heat-stable proteins, integration host factor (IHF) and the histone-like protein HU were found to interact with the ndh promoter. IHF was shown to bind at three sites centred at +26, -17 and -58 in the ndh promoter (Kd = 10(-8) M), to prevent open-complex formation and to repress ndh transcription in vitro. Studies with an ndh-lacZ fusion confirmed that IHF represses ndh expression in vivo. Two putative binding sites for Arr, which overlap the two FNR boxes in the ndh promoter, were identified. Studies with the FNR-activated and amino-acid-inducible asparaginase II gene (ansB) showed that IHF and a component of the Arr-containing fraction (but not HU) interact with the corresponding ansB promoter. PMID:9308170

  14. 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

  15. Epidermal growth factor receptor plays a role in the regulation of liver and plasma lipid levels in adult male mice

    PubMed Central

    Zhang, Xiuqi; Garcia, Oscar A.; Wang, Rebecca F.; Stevenson, Mary C.; Threadgill, David W.; Russell, William E.

    2014-01-01

    Dsk5 mice have a gain of function in the epidermal growth factor receptor (EGFR), caused by a point mutation in the kinase domain. We analyzed the effect of this mutation on liver size, histology, and composition. We found that the livers of 12-wk-old male Dsk5 heterozygotes (+/Dsk5) were 62% heavier compared with those of wild-type controls (+/+). The livers of the +/Dsk5 mice compared with +/+ mice had larger hepatocytes with prominent, polyploid nuclei and showed modestly increased cell proliferation indices in both hepatocytes and nonparenchymal cells. An analysis of total protein, DNA, and RNA (expressed relative to liver weight) revealed no differences between the mutant and wild-type mice. However, the livers of the +/Dsk5 mice had more cholesterol but less phospholipid and fatty acid. Circulating cholesterol levels were twice as high in adult male +/Dsk5 mice but not in postweaned young male or female mice. The elevated total plasma cholesterol resulted mainly from an increase in low-density lipoprotein (LDL). The +/Dsk5 adult mouse liver expressed markedly reduced protein levels of LDL receptor, no change in proprotein convertase subtilisin/kexin type 9, and a markedly increased fatty acid synthase and 3-hydroxy-3-methyl-glutaryl-CoA reductase. Increased expression of transcription factors associated with enhanced cholesterol synthesis was also observed. Together, these findings suggest that the EGFR may play a regulatory role in hepatocyte proliferation and lipid metabolism in adult male mice, explaining why elevated levels of EGF or EGF-like peptides have been positively correlated to increased cholesterol levels in human studies. PMID:24407590

  16. 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

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

    PubMed

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

    2016-07-01

    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

  18. 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

  19. Basal regulation of HPA and dopamine systems is altered differentially in males and females by prenatal alcohol exposure and chronic variable stress

    PubMed Central

    Uban, Kristina A.; Comeau, Wendy; Ellis, Linda A.; Galea, Liisa A. M.; Weinberg, Joanne

    2013-01-01

    Effects of prenatal alcohol exposure (PAE) on central nervous system function include an increased prevalence of mental health problems, including substance use disorders (SUD). The hypothalamic-pituitary-adrenal (HPA) and dopamine systems have overlapping neurocircuitries and are both implicated in SUD. PAE alters both HPA and dopaminergic activity and regulation, resulting in increased HPA tone and an overall reduction in tonic dopamine activity. However, effects of PAE on the interaction between HPA and dopamine (DA) systems have not been investigated. The present study examined PAE effects on basal regulation of central stress and dopamine systems in key brain regions where these systems intersect. Adult Sprague-Dawley male and female offspring from prenatal alcohol-exposed (PAE), pairfed (PF), and ad libitum-fed control (C) groups were subjected to chronic variable stress (CVS) or remained as a no stress (non-CVS) control group. Corticotropin releasing hormone (CRH) mRNA, as well as glucocorticoid and DA receptor (DA-R) expression were measured under basal conditions 24 hours following the end of CVS. We show, for the first time, that regulation of basal HPA and DA systems, and likely, HPA-DA interactions, are altered differentially in males and females by PAE and CVS. PAE augmented the typical attenuation in weight gain during CVS in males and caused increased weight loss in females. Increased basal corticosterone levels in control, but not PAE, females suggest that PAE alters the profile of basal hormone secretion throughout CVS. CVS downregulated basal CRH mRNA in the prefrontal cortex and throughout the bed nucleus of the stria terminalis (BNST) in PAE females but only in the posterior BNST of control females. PAE males and females exposed to CVS exhibited more widespread upregulation of basal mineralocorticoid receptor (MR) mRNA throughout the hippocampus, and an attenuated decrease in DA-R expression throughout the nucleus accumbens and striatum compared

  20. An integrated approach to male-factor subfertility: bridging the gap between fertility specialists trained in urology and gynaecology.

    PubMed

    Hughes, Edward G; Grantmyre, John; Zini, Armand

    2015-03-01

    Subfertile men and women are usually cared for by different clinicians, namely urologists and gynaecologists. While these doctors share each other's goals, they may not always appreciate the content or implications of their opposite number's clinical decisions; to some degree they may practice in "silos." We address this problem by reviewing the effectiveness of medical treatments for male factor subfertility in the context of female factors. The effectiveness of treatments for couples with male factor subfertility, other than IVF with ICSI, appears modest. However, data from randomized controlled trials suggest benefits from some treatments: clomiphene and tamoxifen for the male (common odds ratio for pregnancy [COR] 2.42; 95% CI 1.47 to 3.94), antioxidants (COR 4.18; 95% CI 2.65 to 6.59) and surgical management of a clinical varicocele (COR 2.39; 95% CI 1.56 to 3.66). Nevertheless, close attention to female age and the duration of subfertility help to avoid lost opportunity through delays in treatment when IVF with ICSI is indicated. Making treatment decisions squarely in the context of the couple's overall prognosis is key for optimal outcomes. Future trials of male fertility treatments should focus on pregnancy as the primary outcome, rather than less important surrogates such as sperm quality. PMID:26001873

  1. The Integration of Genetic Propensities into Social-Control Models of Delinquency and Violence among Male Youths

    ERIC Educational Resources Information Center

    Guo, Guang; Roettger, Michael E.; Cai, Tianji

    2008-01-01

    This study, drawing on approximately 1,100 males from the National Longitudinal Study of Adolescent Health, demonstrates the importance of genetics, and genetic-environmental interactions, for understanding adolescent delinquency and violence. Our analyses show that three genetic polymorphisms--specifically, the 30-bp promoter-region variable…

  2. 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. PMID:25634244

  3. MAR-mediated integration of plasmid vectors for in vivo gene transfer and regulation

    PubMed Central

    2013-01-01

    Background The in vivo transfer of naked plasmid DNA into organs such as muscles is commonly used to assess the expression of prophylactic or therapeutic genes in animal disease models. Results In this study, we devised vectors allowing a tight regulation of transgene expression in mice from such non-viral vectors using a doxycycline-controlled network of activator and repressor proteins. Using these vectors, we demonstrate proper physiological response as consequence of the induced expression of two therapeutically relevant proteins, namely erythropoietin and utrophin. Kinetic studies showed that the induction of transgene expression was only transient, unless epigenetic regulatory elements termed Matrix Attachment Regions, or MAR, were inserted upstream of the regulated promoters. Using episomal plasmid rescue and quantitative PCR assays, we observed that similar amounts of plasmids remained in muscles after electrotransfer with or without MAR elements, but that a significant portion had integrated into the muscle fiber chromosomes. Interestingly, the MAR elements were found to promote plasmid genomic integration but to oppose silencing effects in vivo, thereby mediating long-term expression. Conclusions This study thus elucidates some of the determinants of transient or sustained expression from the use of non-viral regulated vectors in vivo. PMID:24295286

  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. 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

  6. 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

  7. 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.

  8. 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

  9. 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

  10. Plasminogen Activator Inhibitor-1 Controls Vascular Integrity by Regulating VE-Cadherin Trafficking

    PubMed Central

    Daniel, Anna E.; Timmerman, Ilse; Kovacevic, Igor; Hordijk, Peter L.; Adriaanse, Luc; Paatero, Ilkka; Belting, Heinz-Georg; van Buul, Jaap D.

    2015-01-01

    Background Plasminogen activator inhibitor-1 (PAI-1), a serine protease inhibitor, is expressed and secreted by endothelial cells. Patients with PAI-1 deficiency show a mild to moderate bleeding diathesis, which has been exclusively ascribed to the function of PAI-1 in down-regulating fibrinolysis. We tested the hypothesis that PAI-1 function plays a direct role in controlling vascular integrity and permeability by keeping endothelial cell-cell junctions intact. Methodology/Principal Findings We utilized PAI-039, a specific small molecule inhibitor of PAI-1, to investigate the role of PAI-1 in protecting endothelial integrity. In vivo inhibition of PAI-1 resulted in vascular leakage from intersegmental vessels and in the hindbrain of zebrafish embryos. In addition PAI-1 inhibition in human umbilical vein endothelial cell (HUVEC) monolayers leads to a marked decrease of transendothelial resistance and disrupted endothelial junctions. The total level of the endothelial junction regulator VE-cadherin was reduced, whereas surface VE-cadherin expression was unaltered. Moreover, PAI-1 inhibition reduced the shedding of VE-cadherin. Finally, we detected an accumulation of VE-cadherin at the Golgi apparatus. Conclusions/Significance Our findings indicate that PAI-1 function is important for the maintenance of endothelial monolayer and vascular integrity by controlling VE-cadherin trafficking to and from the plasma membrane. Our data further suggest that therapies using PAI-1 antagonists like PAI-039 ought to be used with caution to avoid disruption of the vessel wall. PMID:26714278

  11. Joint-linkage mapping and GWAS reveal extensive genetic loci that regulate male inflorescence size in maize.

    PubMed

    Wu, Xun; Li, Yongxiang; Shi, Yunsu; Song, Yanchun; Zhang, Dengfeng; Li, Chunhui; Buckler, Edward S; Li, Yu; Zhang, Zhiwu; Wang, Tianyu

    2016-07-01

    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 both linkage populations and association populations, to dissect the genetic architecture of male inflorescence. The linkage populations include 25 families developed in the U.S. and 11 families developed in China. Each family contains approximately 200 recombinant inbred lines (RILs). The association populations include approximately 1000 diverse lines from the U.S. and China. All inbreds were genotyped by either sequencing or microarray. Inflorescence size was measured as the tassel primary branch number (TBN) and tassel length (TL). A total of 125 quantitative trait loci (QTLs) were identified (63 for TBN, 62 for TL) through linkage analyses. In addition, 965 quantitative trait nucleotides (QTNs) were identified through genomewide study (GWAS) at a bootstrap posterior probability (BPP) above a 5% threshold. These QTLs/QTNs include 24 known genes that were cloned using mutants, for example Ramosa3 (ra3), Thick tassel dwarf1 (td1), tasselseed2 (ts2), liguleless2 (lg2), ramosa1 (ra1), barren stalk1 (ba1), branch silkless1 (bd1) and tasselseed6 (ts6). The newly identified genes encode a zinc transporter (e.g. GRMZM5G838098 and GRMZM2G047762), the adapt in terminal region protein (e.g. GRMZM5G885628), O-methyl-transferase (e.g. GRMZM2G147491), helix-loop-helix (HLH) DNA-binding proteins (e.g. GRMZM2G414252 and GRMZM2G042895) and an SBP-box protein (e.g. GRMZM2G058588). These results provide extensive genetic information to dissect the genetic architecture of inflorescence size for the improvement of maize yield. PMID:26801971

  12. Adenosinergic regulation of binge-like ethanol drinking and associated locomotor effects in male C57BL/6J mice

    PubMed Central

    Fritz, Brandon M; Boehm, Stephen L

    2015-01-01

    We recently observed that the addition of caffeine (a nonselective adenosine receptor antagonist) to a 20% ethanol solution significantly altered the intoxication profile of male C57BL/6J (B6) mice induced by voluntary binge-like consumption in the ‘Drinking-in-the-Dark’ (DID) paradigm. In the current study, the roles of A1 and A2A adenosine receptor subtypes, specifically, in binge-like ethanol consumption and associated locomotor effects were explored. Adult male B6 mice (PND 60-70) were allowed to consume 20% ethanol (v/v) or 2% sucrose (w/v) for 6 days via DID. On day 7, mice received a systemic administration (i.p.) of the A1 antagonist DPCPX (1, 3, 6 mg/kg), the A2A antagonist MSX-3 (1, 2, 4 mg/kg), or vehicle immediately prior to fluid access in DID. Antagonism of the A1 receptor via DPCPX was found to dose-dependently decrease binge-like ethanol intake and associated blood ethanol concentrations (p’s < 0.05), although no effect was observed on sucrose intake. Antagonism of A2A had no effect on ethanol or sucrose consumption, however, MSX-3 elicited robust locomotor stimulation in mice consuming either solution (p’s < 0.05). Together, these findings suggest unique roles for the A1 and A2A adenosine receptor subtypes in binge-like ethanol intake and its associated locomotor effects. PMID:26033424

  13. Dose-dependent regulation of steroid receptor coactivator-1 and steroid receptors by testosterone propionate in the hippocampus of adult male mice.

    PubMed

    Qiu, Linli; Zhao, Yangang; Guo, Qiang; Zhang, Yuanyuan; He, Li; Li, Wei; Zhang, Jiqiang

    2016-02-01

    Androgens have been proposed to play important roles in the regulation of hippocampus function either directly, through the androgen receptor (AR), or indirectly, through estrogen receptors (ERs), after aromatization into estradiol. Steroid receptor coactivator-1 (SRC-1) is present in the hippocampus of several species, and its expression is regulated by development and aging, as well as by orchidectomy and aromatase inhibitor letrozole administration, while ovariectomy only transiently downregulated hippocampal SRC-1. However, whether the expression of hippocampal SRC-1 can be directly regulated by testosterone, the principal male sex hormone, remains unclear. In the present study, we investigated the expression of hippocampal SRC-1 after orchidectomy and testosterone treatment using immunohistochemistry and Western blot analysis. We found that while hippocampal SRC-1 was significantly downregulated by orchidectomy (ORX), its expression was rescued by treatment with testosterone in a dose-dependent manner. Furthermore, we noticed that the decreased expression of hippocampal AR, ERs and the synaptic proteins GluR-1 and PSD-95 induced by ORX was also rescued by testosterone treatment in a dose-dependent manner. However, we found that hippocampal membrane estrogen receptor GPR30 and dendritic spine marker spinophilin were not altered by ORX or testosterone treatment. Together, the above results provided the first direct evidence for the androgenic regulation on hippocampal SRC-1, indicating that SRC-1 may be a direct target of androgenic regulation on the hippocampus. Furthermore, because AR and ERs can be differentially regulated by testosterone, and the transcriptional activity requires the involvement of local SRC-1, and considering the complicated regulatory pathway of each individual receptor, the converged hub regulator SRC-1 of these nuclear receptor networks is worthy of further investigation. PMID:26607693

  14. Regulation of active genome integrity and expression by Rad26p

    PubMed Central

    Malik, Shivani; Bhaumik, Sukesh R

    2014-01-01

    Rad26p is a SWI/SNF-like ATPase in yeast, and is conserved among eukaryotes. Both Rad26p and its human homolog CSB (Cockayne syndrome group B) are involved in regulation of chromatin structure, transcription and DNA repair.  Thus, mutations or malfunctions of these proteins have significant effects on cellular functions. Mutations in CSB are associated with Cockayne syndrome (CS) that is characterized by heterogeneous pathologies such as mental and physical retardation, sun sensitivity, premature aging, muscular and skeletal abnormalities, and progressive decline in neurological and cognitive functions. Therefore, many research groups focused their studies to understand the mechanisms of Rad26p/CSB functions to illuminate the molecular bases of CS. These studies have provided significant functional and mechanistic insights of Rad26p/CSB in regulation of gene expression and genome integrity as described here. PMID:25484185

  15. Evaluation of phase change materials for thermal regulation enhancement of building integrated photovoltaics

    SciTech Connect

    Hasan, A.; Norton, B.; McCormack, S.J.; Huang, M.J.

    2010-09-15

    Regulating the temperature of building integrated photovoltaics (BIPV) using phase change materials (PCMs) reduces the loss of temperature dependent photovoltaic (PV) efficiency. Five PCMs were selected for evaluation all with melting temperatures {proportional_to}25 {+-} 4 C and heat of fusion between 140 and 213 kJ/kg. Experiments were conducted at three insolation intensities to evaluate the performance of each PCM in four different PV/PCM systems. The effect on thermal regulation of PV was determined by changing the (i) mass of PCM and (ii) thermal conductivities of the PCM and PV/PCM system. A maximum temperature reduction of 18 C was achieved for 30 min while 10 C temperature reduction was maintained for 5 h at -1000 W/m{sup 2} insolation. (author)

  16. Active regulation of receptor ratios controls integration of quorum-sensing signals in Vibrio harveyi

    PubMed Central

    Teng, Shu-Wen; Schaffer, Jessica N; Tu, Kimberly C; Mehta, Pankaj; Lu, Wenyun; Ong, N P; Bassler, Bonnie L; Wingreen, Ned S

    2011-01-01

    Quorum sensing is a chemical signaling mechanism used by bacteria to communicate and orchestrate group behaviors. Multiple feedback loops exist in the quorum-sensing circuit of the model bacterium Vibrio harveyi. Using fluorescence microscopy of individual cells, we assayed the activity of the quorum-sensing circuit, with a focus on defining the functions of the feedback loops. We quantitatively investigated the signaling input–output relation both in cells with all feedback loops present as well as in mutants with specific feedback loops disrupted. We found that one of the feedback loops regulates receptor ratios to control the integration of multiple signals. Together, the feedback loops affect the input–output dynamic range of signal transmission and the noise in the output. We conclude that V. harveyi employs multiple feedback loops to simultaneously control quorum-sensing signal integration and to ensure signal transmission fidelity. PMID:21613980

  17. Impact of 4-methylbenzylidene-camphor (4-MBC) during embryonic and fetal development in the neuroendocrine regulation of testicular axis in prepubertal and peripubertal male rats.

    PubMed

    Carou, M E; Szwarcfarb, B; Deguiz, M L; Reynoso, R; Carbone, S; Moguilevsky, J A; Scacchi, P; Ponzo, O J

    2009-10-01

    4-Methylbenzylidene-camphor (4-MBC), an UV-B ray filter, belongs to the endocrine disrupters involved with alterations in the reproductive axis. Our target was to study the effect of 4-MBC on the neuroendocrine parameters that regulate reproduction in prepubertal and peripubertal male rats, which received this disrupter during embryonic and fetal development. 4-MBC was administered (sc) to female rats since pregnancy onset in doses of 20, 100 and 500 mg/kg/day. The litters were sacrificed at 15 or 30 days old to determine testicular weight, gonadotropin and prolactin serum levels and also GnRH and amino acids release from the hypothalamus. The exposure to 20 mg/kg/day only increased the LH serum levels in 30-day-old males. Doses of 100 and 500 mg/kg/day caused a decrease in testicular weight and in LH, GnRH and glutamate levels, in prepubertal rats (15-day-old specimens), and an increase in, gonadotropin (LH and FSH) con-centration and aspartate levels in peripubertal rats (30-day-old specimens), without changes in testicular weight. Prolactinaemia remained unaltered in all groups. Results obtained show that the administration of high doses of 4-MBC during embryonic and fetal stage inhibits the testicular axis in male rats during the prepubertal stage and stimulates it during peripubertad stage. On the other hand in the case of low doses no significant effects were observed. PMID:19885997

  18. Signal integration by Ca(2+) regulates intestinal stem-cell activity.

    PubMed

    Deng, Hansong; Gerencser, Akos A; Jasper, Heinrich

    2015-12-10

    Somatic stem cells maintain tissue homeostasis by dynamically adjusting proliferation and differentiation in response to stress and metabolic cues. Here we identify Ca(2+) signalling as a central regulator of intestinal stem cell (ISC) activity in Drosophila. We show that dietary L-glutamate stimulates ISC division and gut growth. The metabotropic glutamate receptor (mGluR) is required in ISCs for this response, and for an associated modulation of cytosolic Ca(2+) oscillations that results in sustained high cytosolic Ca(2+) concentrations. High cytosolic Ca(2+) concentrations induce ISC proliferation by regulating Calcineurin and CREB-regulated transcriptional co-activator (Crtc). In response to a wide range of dietary and stress stimuli, ISCs reversibly transition between Ca(2+) oscillation states that represent poised or activated modes of proliferation, respectively. We propose that the dynamic regulation of intracellular Ca(2+) levels allows effective integration of diverse mitogenic signals in ISCs to adapt their proliferative activity to the needs of the tissue. PMID:26633624

  19. Integrative Analysis of Transcriptomic and Epigenomic Data to Reveal Regulation Patterns for BMD Variation

    PubMed Central

    Zhang, Ji-Gang; Tan, Li-Jun; Xu, Chao; He, Hao; Tian, Qing; Zhou, Yu; Qiu, Chuan; Chen, Xiang-Ding; Deng, Hong-Wen

    2015-01-01

    Integration of multiple profiling data and construction of functional gene networks may provide additional insights into the molecular mechanisms of complex diseases. Osteoporosis is a worldwide public health problem, but the complex gene-gene interactions, post-transcriptional modifications and regulation of functional networks are still unclear. To gain a comprehensive understanding of osteoporosis etiology, transcriptome gene expression microarray, epigenomic miRNA microarray and methylome sequencing were performed simultaneously in 5 high hip BMD (Bone Mineral Density) subjects and 5 low hip BMD subjects. SPIA (Signaling Pathway Impact Analysis) and PCST (Prize Collecting Steiner Tree) algorithm were used to perform pathway-enrichment analysis and construct the interaction networks. Through integrating the transcriptomic and epigenomic data, firstly we identified 3 genes (FAM50A, ZNF473 and TMEM55B) and one miRNA (hsa-mir-4291) which showed the consistent association evidence from both gene expression and methylation data; secondly in network analysis we identified an interaction network module with 12 genes and 11 miRNAs including AKT1, STAT3, STAT5A, FLT3, hsa-mir-141 and hsa-mir-34a which have been associated with BMD in previous studies. This module revealed the crosstalk among miRNAs, mRNAs and DNA methylation and showed four potential regulatory patterns of gene expression to influence the BMD status. In conclusion, the integration of multiple layers of omics can yield in-depth results than analysis of individual omics data respectively. Integrative analysis from transcriptomics and epigenomic data improves our ability to identify causal genetic factors, and more importantly uncover functional regulation pattern of multi-omics for osteoporosis etiology. PMID:26390436

  20. Investigation of the malE Promoter and MalR, a Positive Regulator of the Maltose Regulon, for an Improved Expression System in Sulfolobus acidocaldarius

    PubMed Central

    Wagner, Michaela; Wagner, Alexander; Ma, Xiaoqing; Kort, Julia Christin; Ghosh, Abhrajyoti; Rauch, Bernadette; Siebers, Bettina

    2014-01-01

    In this study, the regulator MalR (Saci_1161) of the TrmB family from Sulfolobus acidocaldarius was identified and was shown to be involved in transcriptional control of the maltose regulon (Saci_1660 to Saci_1666), including the ABC transporter (malEFGK), α-amylase (amyA), and α-glycosidase (malA). The ΔmalR deletion mutant exhibited a significantly decreased growth rate on maltose and dextrin but not on sucrose. The expression of the genes organized in the maltose regulon was induced only in the presence of MalR and maltose in the growth medium, indicating that MalR, in contrast to its TrmB and TrmB-like homologues, is an activator of the maltose gene cluster. Electrophoretic mobility shift assays revealed that the binding of MalR to malE was independent of sugars. Here we report the identification of the archaeal maltose regulator protein MalR, which acts as an activator and controls the expression of genes involved in maltose transport and metabolic conversion in S. acidocaldarius, and its use for improvement of the S. acidocaldarius expression system under the control of an optimized maltose binding protein (malE) promoter by promoter mutagenesis. PMID:24271181

  1. 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

  2. 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

  3. Dehydroepiandrosterone and 7-oxo-dehydroepiandrosterone in male reproductive health: Implications of differential regulation of human Sertoli cells metabolic profile.

    PubMed

    Dias, Tânia R; Alves, Marco G; Almeida, Susana P; Silva, Joaquina; Barros, Alberto; Sousa, Mário; Silva, Branca M; Silvestre, Samuel M; Oliveira, Pedro F

    2015-11-01

    Dehydroepiandrosterone (DHEA) is a precursor of androgen synthesis whose action is partially exerted through its metabolites. 7-Oxo-dehydroepiandrosterone (7-oxo-DHEA) is a common DHEA metabolite, non-convertible to androgens, which constitutes a promising therapeutic strategy for multiple conditions. Sertoli cells (SCs) are responsible for the support of spermatogenesis, having unique metabolic characteristics strongly modulated by androgens. Consequently, disruptions in androgen synthesis compromise SCs function and hence male fertility. We aimed to evaluate the effects of DHEA and 7-oxo-DHEA in human SCs (hSCs) metabolism and oxidative profile. To do so, hSCs were exposed to increasing concentrations of DHEA and 7-oxo-DHEA (0.025, 1 and 50 μM) that revealed to be non-cytotoxic in these experimental conditions. We measured hSCs metabolites consumption/production by (1)H NMR, the protein expression levels of key players of the glycolytic pathway by Western blot as well as the levels of carbonyl groups, nitration and lipid peroxidation by Slot blot. The obtained data demonstrated that 7-oxo-DHEA is a more potent metabolic modulator than DHEA since it increased hSCs glycolytic flux. DHEA seem to redirect hSCs metabolism to the Krebs cycle, while 7-oxo-DHEA has some inhibitory effect in this path. The highest 7-oxo-DHEA concentrations (1 and 50 μM) also increased lactate production, which is of extreme relevance for the successful progression of spermatogenesis in vivo. None of these steroids altered the intracellular oxidative profile of hSCs, illustrating that, at the concentrations used they do not have pro- nor antioxidant actions in hSCs. Our study represents a further step in the establishment of safe doses of DHEA and 7-oxo-DHEA to hSCs, supporting its possible use in hormonal and non-hormonal therapies against male reproductive problems. PMID:26134425

  4. Developmentally regulated expression of APG-1, a member of heat shock protein 110 family in murine male germ cells.

    PubMed

    Kaneko, Y; Kimura, T; Nishiyama, H; Noda, Y; Fujita, J

    1997-04-01

    Apg-1 encodes a heat shock protein belonging to the heat shock protein 110 family, and is inducible by a 32 degrees C to 39 degrees C heat shock. Northern blot analysis of the testis from immature and adult mice, and of the purified germ cells revealed the quantitative change of the apg-1 transcripts during germ cell development. By in situ hybridization histochemistry the expressions of the apg-1 transcripts were detected in germ cells at specific stages of development including spermatocytes and spermatids. Although heat-induction of the apg-1 transcripts was observed in W/Wv mutant testis lacking germ cells, it was not detected in wild-type testis nor in the purified germ cells. Thus, the apg-1 expression is not heat-regulated but developmentally regulated in germ cells, suggesting that APG-1 plays a role in normal development of germ cells. PMID:9144406

  5. Emotion Regulation in Adolescent Males with Attention-Deficit Hyperactivity Disorder: Testing the Effects of Comorbid Conduct Disorder

    PubMed Central

    Northover, Clare; Thapar, Anita; Langley, Kate; van Goozen, Stephanie

    2015-01-01

    Although attention-deficit hyperactivity disorder (ADHD) has been linked to emotion dysregulation, few studies have experimentally investigated this whilst controlling for the effects of comorbid conduct disorder (CD). Economic decision-making games that assess how individuals respond to offers varying in fairness have been used to study emotion regulation. The present study compared adolescent boys with ADHD (n = 90), ADHD + CD (n = 94) and typical controls (n = 47) on the Ultimatum Game and examined the contribution of ADHD and CD symptom scores and callous and unemotional traits to acceptance levels of unfair offers. There were no significant differences in acceptance rates of fair and highly unfair offers between groups, and only boys with ADHD did not significantly differ from the controls. However, the subgroup of boys with ADHD and additional high levels of aggressive CD symptoms rejected significantly more ambiguous (i.e., moderately unfair) offers than any other subgroup, suggesting impaired emotion regulation in those with ADHD and aggressive CD. Correlations within the CD group showed that the rejection rate to moderately unfair offers was predicted by aggressive CD symptom severity, but not callous and unemotional traits. These findings highlight the fact that ADHD is a heterogeneous condition from an emotion regulation point of view. PMID:26371048

  6. Extracellular Vesicles from Caveolin-Enriched Microdomains Regulate Hyaluronan-Mediated Sustained Vascular Integrity

    PubMed Central

    Mirzapoiazova, Tamara; Lennon, Frances E.; Mambetsariev, Bolot; Allen, Michael; Riehm, Jacob; Poroyko, Valeriy A.; Singleton, Patrick A.

    2015-01-01

    Defects in vascular integrity are an initiating factor in several disease processes. We have previously reported that high molecular weight hyaluronan (HMW-HA), a major glycosaminoglycan in the body, promotes rapid signal transduction in human pulmonary microvascular endothelial cells (HPMVEC) leading to barrier enhancement. In contrast, low molecular weight hyaluronan (LMW-HA), produced in disease states by hyaluronidases and reactive oxygen species (ROS), induces HPMVEC barrier disruption. However, the mechanism(s) of sustained barrier regulation by HA are poorly defined. Our results indicate that long-term (6–24 hours) exposure of HMW-HA induced release of a novel type of extracellular vesicle from HLMVEC called enlargeosomes (characterized by AHNAK expression) while LMW-HA long-term exposure promoted release of exosomes (characterized by CD9, CD63, and CD81 expression). These effects were blocked by inhibiting caveolin-enriched microdomain (CEM) formation. Further, inhibiting enlargeosome release by annexin II siRNA attenuated the sustained barrier enhancing effects of HMW-HA. Finally, exposure of isolated enlargeosomes to HPMVEC monolayers generated barrier enhancement while exosomes led to barrier disruption. Taken together, these results suggest that differential release of extracellular vesicles from CEM modulate the sustained HPMVEC barrier regulation by HMW-HA and LMW-HA. HMW-HA-induced specialized enlargeosomes can be a potential therapeutic strategy for diseases involving impaired vascular integrity. PMID:26447809

  7. Environmental conditions and transcriptional regulation in Escherichia coli: a physiological integrative approach.

    PubMed

    Martínez-Antonio, Agustino; Salgado, Heladia; Gama-Castro, Socorro; Gutiérrez-Ríos, Rosa María; Jiménez-Jacinto, Verónica; Collado-Vides, Julio

    2003-12-30

    Bacteria develop a number of devices for sensing, responding, and adapting to different environmental conditions. Understanding within a genomic perspective how the transcriptional machinery of bacteria is modulated, as a response for changing conditions, is a major challenge for biologists. Knowledge of which genes are turned on or turned off under specific conditions is essential for our understanding of cell behavior. In this study we describe how the information pertaining to gene expression and associated growth conditions (even with very little knowledge of the associated regulatory mechanisms) is gathered from the literature and incorporated into RegulonDB, a database on transcriptional regulation and operon organization in E. coli. The link between growth conditions, signal transduction, and transcriptional regulation is modeled in the database in a simple format that highlights biological relevant information. As far as we know, there is no other database that explicitly clarifies the effect of environmental conditions on gene transcription. We discuss how this knowledge constitutes a benchmark that will impact future research aimed at integration of regulatory responses in the cell; for instance, analysis of microarrays, predicting culture behavior in biotechnological processes, and comprehension of dynamics of regulatory networks. This integrated knowledge will contribute to the future goal of modeling the behavior of E. coli as an entire cell. The RegulonDB database can be accessed on the web at the URL: http://www.cifn.unam.mx/Computational_Biology/regulondb/. PMID:14708114

  8. 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.

  9. KChIP-Like Auxiliary Subunits of Kv4 Channels Regulate Excitability of Muscle Cells and Control Male Turning Behavior during Mating in Caenorhabditis elegans

    PubMed Central

    Chen, Xin; Ruan, Mei-Yu

    2015-01-01

    Voltage-gated Kv4 channels control the excitability of neurons and cardiac myocytes by conducting rapidly activating-inactivating currents. The function of Kv4 channels is profoundly modulated by K+ channel interacting protein (KChIP) soluble auxiliary subunits. However, the in vivo mechanism of the modulation is not fully understood. Here, we identified three C. elegans KChIP-like (ceKChIP) proteins, NCS-4, NCS-5, and NCS-7. All three ceKChIPs alter electrical characteristics of SHL-1, a C. elegans Kv4 channel ortholog, currents by slowing down inactivation kinetics and shifting voltage dependence of activation to more hyperpolarizing potentials. Native SHL-1 current is completely abolished in cultured myocytes of Triple KO worms in which all three ceKChIP genes are deleted. Reexpression of NCS-4 partially restored expression of functional SHL-1 channels, whereas NCS-4(efm), a NCS-4 mutant with impaired Ca2+-binding ability, only enhanced expression of SHL-1 proteins, but failed to transport them from the Golgi apparatus to the cell membrane in body wall muscles of Triple KO worms. Moreover, translational reporter revealed that NCS-4 assembles with SHL-1 K+ channels in male diagonal muscles. Deletion of either ncs-4 or shl-1 significantly impairs male turning, a behavior controlled by diagonal muscles during mating. The phenotype of the ncs-4 null mutant could be rescued by reexpression of NCS-4, but not NCS-4(efm), further emphasizing the importance of Ca2+ binding to ceKChIPs in regulating native SHL-1 channel function. Together, these data reveal an evolutionarily conserved mechanism underlying the regulation of Kv4 channels by KChIPs and unravel critical roles of ceKChIPs in regulating muscle cell excitability and animal behavior in C. elegans. PMID:25653349

  10. Restoring ecological integrity in highly regulated rivers: the role of baseline data and analytical references.

    PubMed

    Downs, Peter W; Singer, Maia S; Orr, Bruce K; Diggory, Zooey E; Church, Tamara C; Stella, J C

    2011-10-01

    The goal of restoring ecological integrity in rivers is frequently accompanied by an assumption that a comparative reference reach can be identified to represent minimally impaired conditions. However, in many regulated rivers, no credible historical, morphological or process-based reference reach exists. Resilient restoration designs should instead be framed around naturalization, using multiple analytical references derived from empirically-calibrated field- and model-based techniques to develop an integrated ecological reference condition. This requires baseline data which are rarely collected despite increasing evidence for systematic deficiencies in restoration practice. We illustrate the utility of baseline data collection in restoration planning for the highly fragmented and regulated lower Merced River, California, USA. The restoration design was developed using various baseline data surveys, monitoring, and modeling within an adaptive management framework. Baseline data assisted in transforming conceptual models of ecosystem function into specific restoration challenges, defining analytical references of the expected relationships among ecological parameters required for restoration, and specifying performance criteria for post-project monitoring and evaluation. In this way the study is an example of process-based morphological restoration designed to prompt recovery of ecosystem processes and resilience. For the Merced River, we illustrate that project-specific baseline data collection is a necessary precursor in developing performance-based restoration designs and addressing scale-related uncertainties, such as whether periodic gravel augmentation will sustain bed recovery and whether piecemeal efforts will improve ecological integrity. Given the numerous impediments to full, historical, restoration in many river systems, it seems apparent that projects of naturalization are a critical step in reducing the deleterious impacts of fragmented rivers

  11. Restoring Ecological Integrity in Highly Regulated Rivers: The Role of Baseline Data and Analytical References

    NASA Astrophysics Data System (ADS)

    Downs, Peter W.; Singer, Maia S.; Orr, Bruce K.; Diggory, Zooey E.; Church, Tamara C.

    2011-10-01

    The goal of restoring ecological integrity in rivers is frequently accompanied by an assumption that a comparative reference reach can be identified to represent minimally impaired conditions. However, in many regulated rivers, no credible historical, morphological or process-based reference reach exists. Resilient restoration designs should instead be framed around naturalization, using multiple analytical references derived from empirically-calibrated field- and model-based techniques to develop an integrated ecological reference condition. This requires baseline data which are rarely collected despite increasing evidence for systematic deficiencies in restoration practice. We illustrate the utility of baseline data collection in restoration planning for the highly fragmented and regulated lower Merced River, California, USA. The restoration design was developed using various baseline data surveys, monitoring, and modeling within an adaptive management framework. Baseline data assisted in transforming conceptual models of ecosystem function into specific restoration challenges, defining analytical references of the expected relationships among ecological parameters required for restoration, and specifying performance criteria for post-project monitoring and evaluation. In this way the study is an example of process-based morphological restoration designed to prompt recovery of ecosystem processes and resilience. For the Merced River, we illustrate that project-specific baseline data collection is a necessary precursor in developing performance-based restoration designs and addressing scale-related uncertainties, such as whether periodic gravel augmentation will sustain bed recovery and whether piecemeal efforts will improve ecological integrity. Given the numerous impediments to full, historical, restoration in many river systems, it seems apparent that projects of naturalization are a critical step in reducing the deleterious impacts of fragmented rivers

  12. Molecular determinants and feedback circuits regulating type 2 CRH receptor signal integration.

    PubMed

    Markovic, Danijela; Punn, Anu; Lehnert, Hendrik; Grammatopoulos, Dimitris K

    2011-05-01

    In most target tissues, the adenylyl cyclase/cAMP/PKA, the extracellular signal regulated kinase and the protein kinase B/Akt are the main pathways employed by the type 2 corticotropin-releasing hormone receptor to mediate the biological actions of urocortins (Ucns) and CRH. To decipher the molecular determinants of CRH-R2 signaling, we studied the signaling pathways in HEK293 cells overexpressing recombinant human CRH-R2β receptors. Use of specific kinase inhibitors showed that the CRH-R2β cognate agonist, Ucn 2, activated extracellular signal regulated kinase in a phosphoinositide 3-kinase and cyclic adenosine monophosphate/PKA-dependent manner with contribution from Epac activation. Ucn 2 also induced PKA-dependent association between AKAP250 and CRH-R2β that appeared to be necessary for extracellular signal regulated kinase activation. PKB/Akt activation was also mediated via pertussis toxin-sensitive G-proteins and PI3-K activation but did not require cAMP/PKA, Epac or protein kinase C for optimal activation. Potential feedback mechanisms that target the CRH-R2β itself and modulate receptor trafficking and endocytosis were also investigated. Indeed, our results suggested that inhibition of either PKA or extracellular signal regulated kinase pathway accelerates CRH-R2β endocytosis. Furthermore, Ucn 2-activated extracellular signal regulated kinase appeared to target β-arrestin1 and modulate, through phosphorylation at Ser412, β-arrestin1 translocation to the plasma membrane and CRH-R2β internalization kinetics. Loss of this "negative feedback" mechanism through inhibition of the extracellular signal regulated kinase activity resulted in significant attenuation of Ucn 2-induced cAMP response, whereas Akt phosphorylation was not affected by altered receptor endocytosis. These findings reveal a complex interplay between the signaling molecules that allow "fine-tuning" of CRH-R2β functional responses and regulate signal integration. This article is part of

  13. Altered regulation of luteinizing hormone secretion in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated male rats

    SciTech Connect

    Bookstaff, R.C.

    1989-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) severely decreases plasma androgen concentrations, yet plasma luteinizing hormone (LH) concentrations remain unchanged. The mechanism by which TCDD prevents the expected compensatory increase in plasma LH was investigated. No effect on the plasma disappearance rate of LH or on pituitary capacity to synthesize or secrete LH was detected. Rather, TCDD altered the regulation of LH secretion by substantially increasing the potency of both androgens and estrogens as feedback inhibitors of LH secretion. The mechanism by which TCDD alters androgen-regulated LH secretion was further investigated. Seven days after dosing, TCDD decreased plasma testosterone concentrations but prevented the expected compensatory increases in pituitary gonadotropin-releasing hormone (GnRH) receptor number, pituitary responsiveness to GnRH, and plasma LH concentrations as seen in similarly hypoandrogenic vehicle dosed rats. Furthermore, the TCDD dose-response relationships for preventing the compensatory increases in pituitary GnRH receptor number and plasma LH concentration were similar. However, in the absence of gonadal steroids (7 days after castration) TCDD did not affect the compensatory increases in pituitary GnRH receptor number, pituitary responsiveness to GnRH, or plasma LH concentration. All of these parameters increased substantially relative to intact TCDD treated rats, and to levels virtually identical to those seen in castrated control rats. Treatment of castrated rats with testosterone restored the ability of TCDD to prevent these compensatory increases. Taken together, these results demonstrate that the presence of androgens is required for TCDD to alter the regulation of pituitary GnRH receptors.

  14. Positive feedback regulation between adiponectin and T-cadherin impacts adiponectin levels in tissue and plasma of male mice.

    PubMed

    Matsuda, Keisuke; Fujishima, Yuya; Maeda, Norikazu; Mori, Takuya; Hirata, Ayumu; Sekimoto, Ryohei; Tsushima, Yu; Masuda, Shigeki; Yamaoka, Masaya; Inoue, Kana; Nishizawa, Hitoshi; Kita, Shunbun; Ranscht, Barbara; Funahashi, Tohru; Shimomura, Iichiro

    2015-03-01

    Adiponectin (Adipo), a multimeric adipocyte-secreted protein abundant in the circulation, is implicated in cardiovascular protective functions. Recent work documented that Adipo locally associates with responsive tissues through interactions with T-cadherin (Tcad), an atypical, glycosylphosphatidylinositol (GPI)-anchored cadherin cell surface glycoprotein. Mice deficient for Tcad lack tissue-associated Adipo, accumulate Adipo in the circulation, and mimic the Adipo knockout (KO) cardiovascular phenotype. In reverse, Tcad protein is visibly reduced from cardiac tissue in Adipo-KO mice, suggesting interdependent regulation of the 2 proteins. Here, we evaluate the effect of Adipo on Tcad protein expression. Adipo and Tcad proteins were colocalized in aorta, heart, and skeletal muscle. Adipo positively regulated levels of Tcad protein in vivo and in endothelial cell (EC) cultures. In Tcad-KO mice, binding of endogenous and exogenously administered Adipo to cardiovascular tissues was dramatically reduced. Consistently, knockdown of Tcad in cultured murine vascular ECs significantly diminished Adipo binding. In search for a possible mechanism, we found that enzymatic cleavage of Tcad with phosphatidylinositol-specific phospholipase C increases plasma Adipo while decreasing tissue-bound levels. Similarly, pretreatment of cultured ECs with serum containing Adipo attenuated phosphatidylinositol-specific phospholipase C-mediated Tcad cleavage. In vivo administration of adenovirus producing Adipo suppressed plasma levels of GPI phospholipase D, the endogenous cleavage enzyme for GPI-anchored proteins. In conclusion, our data show that both circulating and tissue-bound Adipo levels are dependent on Tcad and, in reverse, regulate tissue Tcad levels through a positive feedback loop that operates by suppressing phospholipase-mediated Tcad release from the cell surface. PMID:25514086

  15. Regulation of Translocator Protein 18 kDa (TSPO) Expression in Rat and Human Male Germ Cells.

    PubMed

    Manku, Gurpreet; Culty, Martine

    2016-01-01

    Translocator protein 18 kDa (TSPO) is a high affinity cholesterol- and drug-binding protein highly expressed in steroidogenic cells, such as Leydig cells, where it plays a role in cholesterol mitochondrial transport. We have previously shown that TSPO is expressed in postnatal day 3 rat gonocytes, precursors of spermatogonial stem cells. Gonocytes undergo regulated phases of proliferation and migration, followed by retinoic acid (RA)-induced differentiation. Understanding these processes is important since their disruption may lead to the formation of carcinoma in situ, a precursor of testicular germ cell tumors (TGCTs). Previously, we showed that TSPO ligands do not regulate gonocyte proliferation. In the present study, we found that TSPO expression is downregulated in differentiating gonocytes. Similarly, in F9 embryonal carcinoma cells, a mouse TGCT cell line with embryonic stem cell properties, there is a significant decrease in TSPO expression during RA-induced differentiation. Silencing TSPO expression in gonocytes increased the stimulatory effect of RA on the expression of the differentiation marker Stra8, suggesting that TSPO exerts a repressive role on differentiation. Furthermore, in normal human testes, TSPO was located not only in Leydig cells, but also in discrete spermatogenic phases such as the forming acrosome of round spermatids. By contrast, seminomas, the most common type of TGCT, presented high levels of TSPO mRNA. TSPO protein was expressed in the cytoplasmic compartment of seminoma cells, identified by their nuclear expression of the transcription factors OCT4 and AP2G. Thus, TSPO appears to be tightly regulated during germ cell differentiation, and to be deregulated in seminomas, suggesting a role in germ cell development and pathology. PMID:27608010

  16. A chromatin modifier integrates insulin/IGF-1 signalling and dietary restriction to regulate longevity.

    PubMed

    Singh, Anupama; Kumar, Neeraj; Matai, Latika; Jain, Vaibhav; Garg, Amit; Mukhopadhyay, Arnab

    2016-08-01

    Insulin/IGF-1-like signalling (IIS) and dietary restriction (DR) are the two major modulatory pathways controlling longevity across species. Here, we show that both pathways license a common chromatin modifier, ZFP-1/AF10. The downstream transcription factors of the IIS and select DR pathways, DAF-16/FOXO or PHA-4/FOXA, respectively, both transcriptionally regulate the expression of zfp-1. ZFP-1, in turn, negatively regulates the expression of DAF-16/FOXO and PHA-4/FOXA target genes, apparently forming feed-forward loops that control the amplitude as well as the duration of gene expression. We show that ZFP-1 mediates this regulation by negatively influencing the recruitment of DAF-16/FOXO and PHA-4/FOXA to their target promoters. Consequently, zfp-1 is required for the enhanced longevity observed during DR and on knockdown of IIS. Our data reveal how two distinct sensor pathways control an overlapping set of genes, using different downstream transcription factors, integrating potentially diverse and temporally distinct nutritional situations. PMID:27039057

  17. 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. PMID:27086086

  18. 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

  19. Integrating Theory and Research: The Development of a Research-Based Treatment Program for Juvenile Male Sex Offenders

    ERIC Educational Resources Information Center

    Calley, Nancy G.

    2007-01-01

    A research-based treatment model designed to effectively address identified factors related to juvenile sexual offending behaviors is presented. Current research, theory, and national standards related to juvenile sexual offending are each explored with the treatment model reflecting an integration of these 3 components. The use of counseling…

  20. Soy Isoflavones Regulate Lipid Metabolism through an AKT/mTORC1 Pathway in Diet-Induced Obesity (DIO) Male Rats.

    PubMed

    Huang, Chao; Pang, Dejiang; Luo, Qihui; Chen, Xiaolin; Gao, Qi; Shi, Liangqin; Liu, Wentao; Zou, Yuanfeng; Li, Lixia; Chen, Zhengli

    2016-01-01

    The pandemic tendency of obesity and its strong association with serious co-morbidities have elicited interest in the underlying mechanisms of these pathologies. Lipid homeostasis, closely involved in obesity, has been reported to be regulated by multiple pathways. mTORC1 is emerging as a critical regulator of lipid metabolism. Here, we describe that the consumption of soy isoflavones, with a structural similarity to that of estradiol, could mitigate obesity through an AKT/mTORC1 pathway. Fed with soy isoflavones, the diet-induced obesity (DIO) male rats exhibited decreased body weight, accompanied with suppressed lipogenesis and adipogenesis, as well as enhanced lipolysis and β‑oxidation. The phosphorylation of AKT and S6 were decreased after soy isoflavone treatment in vivo and in vitro, suggesting an inhibition effect of soy isoflavones on mTORC1 activity. Our study reveals a potential mechanism of soy isoflavones regulating lipid homeostasis, which will be important for obesity treatment. PMID:27153053

  1. Cytoplasmic protein binding to highly conserved sequences in the 3' untranslated region of mouse protamine 2 mRNA, a translationally regulated transcript of male germ cells.

    PubMed

    Kwon, Y K; Hecht, N B

    1991-05-01

    The expression of the protamines, the predominant nuclear proteins of mammalian spermatozoa, is regulated translationally during male germ-cell development. The 3' untranslated region (UTR) of protamine 1 mRNA has been reported to control its time of translation. To understand the mechanisms controlling translation of the protamine mRNAs, we have sought to identify cis elements of the 3' UTR of protamine 2 mRNA that are recognized by cytoplasmic factors. From gel retardation assays, two sequence elements are shown to form specific RNA-protein complexes. Protein binding sites of the two complexes were determined by RNase T1 mapping, by blocking the putative binding sites with antisense oligonucleotides, and by competition assays. The sequences of these elements, located between nucleotides + 537 and + 572 in protamine 2 mRNA, are highly conserved among postmeiotic translationally regulated nuclear proteins of the mammalian testis. Two closely linked protein binding sites were detected. UV-crosslinking studies revealed that a protein of about 18 kDa binds to one of the conserved sequences. These data demonstrate specific protein binding to a highly conserved 3' UTR of translationally regulated testicular mRNA. PMID:2023906

  2. Weight loss by calorie restriction versus bariatric surgery differentially regulates the hypothalamo-pituitary-adrenocortical axis in male rats.

    PubMed

    Grayson, Bernadette E; Hakala-Finch, Andrew P; Kekulawala, Melani; Laub, Holly; Egan, Ann E; Ressler, Ilana B; Woods, Stephen C; Herman, James P; Seeley, Randy J; Benoit, Stephen C; Ulrich-Lai, Yvonne M

    2014-12-01

    Behavioral modifications for the treatment of obesity, including caloric restriction, have notoriously low long-term success rates relative to bariatric weight-loss surgery. The reasons for the difference in sustained weight loss are not clear. One possibility is that caloric restriction alone activates the stress-responsive hypothalamo-pituitary-adrenocortical (HPA) axis, undermining the long-term maintenance of weight loss, and that this is abrogated after bariatric surgery. Accordingly, we compared the HPA response to weight loss in five groups of male rats: (1) high-fat diet-induced obese (DIO) rats treated with Roux-en-Y gastric bypass surgery (RYGB, n = 7), (2) DIO rats treated with vertical sleeve gastrectomy (VSG, n = 11), (3) DIO rats given sham surgery and subsequently restricted to the food intake of the VSG/RYGB groups (Pair-fed, n = 11), (4) ad libitum-fed DIO rats given sham surgery (Obese, n = 11) and (5) ad libitum chow-fed rats given sham surgery (Lean, n = 12). Compared with Lean controls, food-restricted rats exhibited elevated morning (nadir) non-stress plasma corticosterone concentration and increased hypothalamic corticotropin-releasing hormone and vasopressin mRNA expression, indicative of basal HPA activation. This was largely prevented when weight loss was achieved by bariatric surgery. DIO increased HPA activation by acute (novel environment) stress and this was diminished by bariatric surgery-, but not pair-feeding-, induced weight loss. These results indicate that the HPA axis is differentially affected by weight loss from caloric restriction versus bariatric surgery, and this may contribute to the differing long-term effectiveness of these two weight-loss approaches. PMID:25238021

  3. 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

  4. Expression and regulation of neuromedin B in pituitary corticotrophs of male melanocortin 2 receptor-deficient mice.

    PubMed

    Kameda, Hiraku; Miyoshi, Hideaki; Shimizu, Chikara; Nagai, So; Nakamura, Akinobu; Kondo, Takuma; Chida, Dai; Atsumi, Tatsuya

    2014-07-01

    The hypothalamic-pituitary-adrenal (HPA) axis is a major part of the neuroendocrine system that controls responses to stress, and has an important function in the regulation of various body processes. We previously created a mouse line deficient in the melanocortin 2 receptor (MC2R). MC2R-deficient mice (MC2R(-/-) mice) have high adrenocorticotropic hormone (ACTH) levels because of undetectable corticosterone levels. Increased neuromedin B (NMB) expression was recently reported in the pituitary gland of adrenalectomized mice, a model for acute adrenal insufficiency. To investigate gene expression in the pituitary gland under chronic adrenal deficiency, we examined the pituitary gland of MC2R(-/-) mice, a model of chronic adrenal insufficiency. To understand the molecular background of pituitary cells under chronic adrenal deficiency, we first performed DNA microarray analyses using the pituitary glands of the MC2R(-/-) mice. The DNA microarray analysis and real-time polymerase chain reaction showed that NMB expression was higher in the MC2R(-/-) than in the wild-type (WT) mice. We detected NMB expression in the MC2R(-/-) pituitary corticotrophs by immunohistochemistry using the specific antibodies for ACTH and NMB. In addition, the plasma NMB concentration was significantly higher in the MC2R(-/-) mice than in the WT mice. Subcutaneous implantation of a sustained-release corticosterone pellet decreased the expression of NMB mRNA as well as pituitary proopiomelanocortin mRNA. In isolated anterior pituitary cells, NMB mRNA expression was increased by the administration of corticotropin-releasing hormone (CRH) and was suppressed by dexamethasone treatment. In this study, we first demonstrate NMB expression in corticotrophs and its regulation by CRH and glucocorticoids. Furthermore, corticotrophs seemed to secrete NMB into the systemic circulation. PMID:24742195

  5. Runx1 Regulates Myeloid Precursor Differentiation Into Osteoclasts Without Affecting Differentiation Into Antigen Presenting or Phagocytic Cells in Both Males and Females.

    PubMed

    Paglia, David N; Yang, Xiaochuan; Kalinowski, Judith; Jastrzebski, Sandra; Drissi, Hicham; Lorenzo, Joseph

    2016-08-01

    Runt-related transcription factor 1 (Runx1), a master regulator of hematopoiesis, is expressed in preosteoclasts. Previously we evaluated the bone phenotype of CD11b-Cre Runx1(fl/fl) mice and demonstrated enhanced osteoclasts and decreased bone mass in males. However, an assessment of the effects of Runx1 deletion in female osteoclast precursors was impossible with this model. Moreover, the role of Runx1 in myeloid cell differentiation into other lineages is unknown. Therefore, we generated LysM-Cre Runx1(fl/fl) mice, which delete Runx1 equally (∼80% deletion) in myeloid precursor cells from both sexes and examined the capacity of these cells to differentiate into osteoclasts and phagocytic and antigen-presenting cells. Both female and male LysM-Cre Runx1(fl/fl) mice had decreased trabecular bone mass (72% decrease in bone volume fraction) and increased osteoclast number (2-3 times) (P < .05) without alteration of osteoblast histomorphometric indices. We also demonstrated that loss of Runx1 in pluripotential myeloid precursors with LysM-Cre did not alter the number of myeloid precursor cells in bone marrow or their ability to differentiate into phagocytizing or antigen-presenting cells. This study demonstrates that abrogation of Runx1 in multipotential myeloid precursor cells significantly and specifically enhanced the ability of receptor activator of nuclear factor-κB ligand to stimulate osteoclast formation and fusion in female and male mice without affecting other myeloid cell fates. In turn, increased osteoclast activity in LysM-Cre Runx1(fl/fl) mice likely contributed to a decrease in bone mass. These dramatic effects were not due to increased osteoclast precursors in the deleted mutants and argue that inhibition of Runx1 in multipotential myeloid precursor cells is important for osteoclast formation and function. PMID:27267711

  6. Sexual attractiveness of male chemicals and vocalizations in mice

    PubMed Central

    Asaba, Akari; Hattori, Tatsuya; Mogi, Kazutaka; Kikusui, Takefumi

    2014-01-01

    Male-female interaction is important for finding a suitable mating partner and for ensuring reproductive success. Male sexual signals such as pheromones transmit information and social and sexual status to females, and exert powerful effects on the mate preference and reproductive biology of females. Likewise, male vocalizations are attractive to females and enhance reproductive function in many animals. Interestingly, females' preference for male pheromones and vocalizations is associated with their genetic background, to avoid inbreeding. Moreover, based on acoustic cues, olfactory signals have significant effects on mate choice in mice, suggesting mate choice involves multisensory integration. In this review, we synopsize the effects of both olfactory and auditory cues on female behavior and neuroendocrine functions. We also discuss how these male signals are integrated and processed in the brain to regulate behavior and reproductive function. PMID:25140125

  7. 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

    2016-05-01

    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. PMID:26565769

  8. 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. PMID:25725583

  9. The integrative role of orexin/hypocretin neurons in nociceptive perception and analgesic regulation.

    PubMed

    Inutsuka, Ayumu; Yamashita, Akira; Chowdhury, Srikanta; Nakai, Junichi; Ohkura, Masamichi; Taguchi, Toru; Yamanaka, Akihiro

    2016-01-01

    The level of wakefulness is one of the major factors affecting nociception and pain. Stress-induced analgesia supports an animal's survival via prompt defensive responses against predators or competitors. Previous studies have shown the pharmacological effects of orexin peptides on analgesia. However, orexin neurons contain not only orexin but also other co-transmitters such as dynorphin, neurotensin and glutamate. Thus, the physiological importance of orexin neuronal activity in nociception is unknown. Here we show that adult-stage selective ablation of orexin neurons enhances pain-related behaviors, while pharmacogenetic activation of orexin neurons induces analgesia. Additionally, we found correlative activation of orexin neurons during nociception using fiber photometry recordings of orexin neurons in conscious animals. These findings suggest an integrative role for orexin neurons in nociceptive perception and pain regulation. PMID:27385517

  10. Fitness Profiling Links Topoisomerase II Regulation of Centromeric Integrity to Doxorubicin Resistance in Fission Yeast

    PubMed Central

    Nguyen, Thi Thuy Trang; Lim, Julia Sze Lynn; Tang, Richard Ming Yi; Zhang, Louxin; Chen, Ee Sin

    2015-01-01

    Doxorubicin, a chemotherapeutic agent, inhibits the religation step of topoisomerase II (Top2). However, the downstream ramifications of this action are unknown. Here we performed epistasis analyses of top2 with 63 genes representing doxorubicin resistance (DXR) genes in fission yeast and revealed a subset that synergistically collaborate with Top2 to confer DXR. Our findings show that the chromatin-regulating RSC and SAGA complexes act with Top2 in a cluster that is functionally distinct from the Ino80 complex. In various DXR mutants, doxorubicin hypersensitivity was unexpectedly suppressed by a concomitant top2 mutation. Several DXR proteins showed centromeric localization, and their disruption resulted in centromeric defects and chromosome missegregation. An additional top2 mutation could restore centromeric chromatin integrity, suggesting a counterbalance between Top2 and these DXR factors in conferring doxorubicin resistance. Overall, this molecular basis for mitotic catastrophe associated with doxorubicin treatment will help to facilitate drug combinatorial usage in doxorubicin-related chemotherapeutic regimens. PMID:25669599