Receipt of Seminal Fluid Proteins Causes Reduction of Male Investment in a Simultaneous Hermaphrodite

Nakadera Y, Swart E M, Hoffer J NA, den Boon O, Ellers J, Koene J M. Receipt of Seminal Fluid Proteins Causes Reduction of Male Investment in a Simultaneous Hermaphrodite. Current Biology. 2014;24(8):859-862

Selective Glucocorticoid Receptor Modulation Prevents and Reverses Nonalcoholic Fatty Liver Disease in Male Mice

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Global invasion genetics of two parasitic copepods infecting marine bivalves

Invasive species, and especially invasive parasites, represent excellent models to study ecological and evolutionary mechanisms in the wild. To understand these processes, it is crucial to obtain more knowledge on the native range, invasion routes and invasion history of invasive parasites. We investigated the consecutive invasions of two parasitic copepods (Mytilicola intestinalis and Mytilicola orientalis) by combining an extensive literature survey covering the reported putative native regions and the present-day invaded regions with a global phylogeography of both species. The population genetic analyses based on partial COI sequences revealed significant population differentiation for M. orientalis within the native region in Japan, while introduced populations in North America and Europe could not be distinguished from the native ones. Thus, M. orientalis' invasion history resembles the genetic structure and recent spread of its principal host, the Pacific oyster, Crassostrea gigas, while M. intestinalis lacks population genetic structure and has an overall low genetic diversity. Therefore, the native origin of M. intestinalis remains unclear. With this study, we demonstrate that even highly related and biologically similar invasive species can differ in their invasion genetics. From this, we conclude that extrapolating invasion genetics dynamics from related invasive taxa may not always be possible

Association of a Haplotype in the NR3C2 Gene, Encoding the Mineralocorticoid Receptor, With Chronic Central Serous Chorioretinopathy

IMPORTANCE Chronic central serous chorioretinopathy (cCSC) is a chorioretinal disease with unknown disease etiology. The glucocorticoid receptor and the mineralocorticoid receptor, 2 glucocorticoid-binding receptors, might be involved in the pathogenesis of cCSC. OBJECTIVE To assess the association of functional variants and haplotypes in the glucocorticoid receptor (NR3C1) and mineralocorticoid receptor (NR3C2) genes with cCSC. DESIGN, SETTING, AND PARTICIPANTS In this case-control genetic association study, 336 patients with cCSC and 1314 unaffected controls, collected at 3 university medical centers from September 1, 2009, to May 1, 2016, underwent KASP genotyping for selected variants in NR3C1 (rs56149945, rs41423247, and rs6198) and NR3C2 (rs2070951 and rs5522). MAIN OUTCOMES AND MEASURES Genetic associations of 3 NR3C1 variants and 2 NR3C2 variants with cCSC. RESULTS Among the 336 patients (274 men and 62 women; mean [ SD] age, 52 [10] years), after correction for multiple testing, rs2070951 in the NR3C2 gene was significantly associated with cCSC (odds ratio, 1.29; 95% CI, 1.08-1.53; P = .004). Moreover, the GA haplotype of single-nucleotide polymorphisms rs2070951 and rs5522 in NR3C2 conferred risk for cCSC (odds ratio, 1.39; 95% CI, 1.15-1.68; P = .004), whereas the CA haplotype decreased risk for cCSC (odds ratio, 0.72; 95% CI, 0.60-0.87; P < .001). Three known variants in NR3C1 that alter the activity of the glucocorticoid receptor (rs56149945, rs41423247, and rs6198) were not associated with cCSC. CONCLUSIONS AND RELEVANCE In this study, the variant rs2070951 and the GA haplotype in NR3C2 were associated with an increased risk for cCSC. Results of this genetic study support a possible role for the mineralocorticoid receptor in the pathogenesis of cCSC. Since these haplotypes have previously been associated with perceived stress, this study provides a clue to bridging clinical risk factors for cCSC to underlying genetic associations

Receipt of Seminal Fluid Proteins Causes Reduction of Male Investment in a Simultaneous Hermaphrodite

SummaryMating partners often have conflicting interests when copulating [1–3]. One of the major agents affecting female mating partners is seminal fluid, transferred along with sperm. The role of seminal fluid proteins (SFPs) in reproductive success is well studied in separate-sexed animals [4, 5] but is much less so in simultaneous hermaphrodites [6]. The latter potentially have a unique target to exploit for the sperm donor’s own benefit: the male function of their mating partners [7, 8]. Here we show that, in the great pond snail Lymnaea stagnalis, receipt of specific SFPs reduces both sperm transfer and paternity success in a subsequent insemination event. Lowering investment in the mating partner’s male function constitutes a novel role for SFPs. This demonstrates for the first time that hermaphrodites alter their mates’ male as well as female reproductive output [6]. Although it remains to be tested whether this represents mate manipulation or an adaptive response of recipients [9], our findings identify male investment as a new target for postcopulatory sexual selection [10]

Selective Glucocorticoid Receptor Modulation Prevents and Reverses Nonalcoholic Fatty Liver Disease in Male Mice

Medication for nonalcoholic fatty liver disease (NAFLD) is an unmet need. Glucocorticoid (GC) stress hormones drive fat metabolism in the liver, but both full blockade and full stimulation of GC signaling aggravate NAFLD pathology. We investigated the efficacy of selective glucocorticoid receptor (GR) modulator CORT118335, which recapitulates only a subset of GC actions, in reducing liver lipid accumulation in mice. Male C57BL/6J mice received a low-fat diet or high-fat diet mixed with vehicle or CORT118335. Livers were analyzed histologically and for genome-wide mRNA expression. Functionally, hepatic long-chain fatty acid (LCFA) composition was determined by gas chromatography. We determined very-low-density lipoprotein (VLDL) production by treatment with a lipoprotein lipase inhibitor after which blood was collected to isolate radiolabeled VLDL particles and apoB proteins. CORT118335 strongly prevented and reversed hepatic lipid accumulation. Liver transcriptome analysis showed increased expression of GR target genes involved in VLDL production. Accordingly, CORT118335 led to increased lipidation of VLDL particles, mimicking physiological GC action. Independent pathway analysis revealed that CORT118335 lacked induction of GC-responsive genes involved in cholesterol synthesis and LCFA uptake, which was indeed reflected in unaltered hepatic LCFA uptake in vivo. Our data thus reveal that the robust hepatic lipid-lowering effect of CORT118335 is due to a unique combination of GR-dependent stimulation of lipid (VLDL) efflux from the liver, with a lack of stimulation of GR-dependent hepatic fatty acid uptake. Our findings firmly demonstrate the potential use of CORT118335 in the treatment of NAFLD and underscore the potential of selective GR modulation in metabolic disease