21 research outputs found

    Myocyte Enhancer Factor 2 and Class II Histone Deacetylases Control a Gender-Specific Pathway of Cardioprotection Mediated by the Estrogen Receptor

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    Gender differences in cardiovascular disease have long been recognized and attributed to beneficial cardiovascular actions of estrogen. Class II histone deacetylases (HDACs) act as key modulators of heart disease by repressing the activity of the myocyte enhancer factor (MEF)2 transcription factor, which promotes pathological cardiac remodeling in response to stress. Although it is proposed that HDACs additionally influence nuclear receptor signaling, the effect of class II HDACs on gender differences in cardiovascular disease remains unstudied

    Mutant screen reveals the Piccolo's control over depression and brain-gonad crosstalk

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    Successful sexual reproduction involves a highly complex, genetically encoded interplay between animal physiology and behavior. Here we developed a screen to identify genes essential for rat reproduction based on an unbiased methodology involving mutagenesis via the Sleeping Beauty transposon. As expected, our screen identified genes where reproductive failure was connected to gametogenesis (Btrc, Pan3, Spaca6, Ube2k) and embryogenesis (Alk3, Exoc6b, Slc1a3, Tmx4, Zmynd8). In addition, our screen identified Atg13 (longevity) Dlg1 and Pclo (neuronal disorders), previously not associated with reproduction. Dominant Pclo traits caused epileptiform activity and affected genes supporting GABAergic synaptic transmission (Gabra6, Gabrg3), and animals exhibited a compromised crosstalk between the brain and gonads via disturbed GnRH signaling. Recessive Pclo traits disrupted conspecific recognition required for courtship/mating and were mapped to allelic markers for major depressive disorder (Grm5, Htr2a, Sorcs3, Negr1, Drd2). Thus, Pclo-deficiency in rats link neural networks controlling sexual motivation to Pclo variants that have been associated with human neurological disorders

    Systematic bias in estimates of reproductive potential of an Atlantic cod (Gadus morhua) stock: implications for stock–recruit theory and management

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    Stock–recruit relationships that use spawning stock biomass (SSB) to represent reproductive potential assume that the proportion of SSB composed of females and the relative fecundity (number of eggs produced per unit mass) are both constant over time. To test these two assumptions, female-only spawner biomass (FSB) and total egg production (TEP) were estimated for the Northeast Arctic stock of Atlantic cod (Gadus morhua) over a 56-year time period. The proportion of females (FSB/SSB) varied between 24% and 68%, and the variation was systematic with length such that SSB became more female-biased as the mean length of spawners increased. Relative fecundity of the stock (TEP/SSB) varied between 115 and 355 eggs·g–1 and was significantly, positively correlated with mean length of spawners. Both FSB and TEP gave a different interpretation of the recruitment response to reductions in stock size (overcompensatory) compared with that obtained using SSB (either compensatory or depensatory). There was no difference between SSB and FSB in the assessment of stock status; however, in recent years (1980–2001) TEP fell below the threshold level at which recruitment becomes impaired more frequently than did SSB. This suggests that using SSB as a measure of stock reproductive potential could lead to overly optimistic assessments of stock status
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