Age, but Not Experience, Affects Courtship Gene Expression in Male Drosophila melanogaster

Mutation screens in model organisms have helped identify the foundation of many fundamental organismal phenotypes. An emerging question in evolutionary and behavioral biology is the extent to which these “developmental” genes contribute to the subtle individual variation that characterizes natural populations. A related question is whether individual differences arise from static differences in gene expression that arose during previous life stages, or whether they are due to dynamic regulation of expression during the life stage under investigation. Here, we address these questions using genes that have been discovered to control the development of normal courtship behavior in male Drosophila melanogaster. We examined whether these genes have static or dynamic expression in the heads of adult male flies of different ages and with different levels of social experience. We found that 16 genes of the 25 genes examined were statically expressed, and 9 genes were dynamically expressed with changes related to adult age. No genes exhibited rapid dynamic expression changes due to social experience or age*experience interaction. We therefore conclude that a majority of fly “courtship” genes are statically expressed, while a minority are regulated in adults with respect to age, but not with respect to relevant social experience. These results are consistent with those from a recent microarray analysis that found none of the canonical courtship genes changed expression in male flies after brief exposure to females.     

Autoimmune associated congenital heart block: integration of clinical and research clues in the management of the maternal / foetal dyad at risk

One of the strongest associations with autoantibodies directed to components of the SSA/Ro‐SSB/La ribonucleoprotein complex is the development of congenital heart block (CHB) in an offspring, an alarming prospect facing 2% of primigravid mothers with these reactivities. This risk is 10‐fold higher in women who have had a previously affected child with CHB. Anti‐Ro/La antibodies are necessary but insufficient to cause disease. In vitro and in vivo experiments suggest that the pathogenesis involves exaggerated apoptosis, macrophage/myfibroblast crosstalk, TGFβ expression and extensive fibrosis in the conducting system and in some cases surrounding myocardium. A disturbing observation is the rapidity of disease progression, with advanced heart block and life‐threatening cardiomyopathy observed <2 weeks from normal sinus rhythm. Once 3rd degree (complete) block is identified, reversal has never been achieved, despite dexamethasone. Current strategies include the evaluation of an early echocardiographic marker of injury, such as a prolonged PR interval and the use of IVIG as a preventative measure for pregnancies of mothers with previously affected children.     

Dietary intervention with vitamin D,calcium, and whey protein reduced fat mass and increased lean mass in rats

The aim of the current study was to determine the effects and the mechanisms of inclusion of dietary whey protein, high calcium, and high vitamin D intake with either a high-sucrose or high-fat base diets on body composition of rodents. Male Wistar rats were assigned to either no whey protein, suboptimal calcium (0.25%), and vitamin D (400 IU/kg) diet (LD), or a diet containing whey protein, high calcium (1.5%), and vitamin D (10 000 IU/kg) diet (HD), and either high-fat (40% of energy) or high-sucrose (60%) base diets for 13 weeks. Liver tissue homogenates were used to determine [¹⁴C]glucose and [¹⁴C]palmitate oxidation. mRNA expression of enzymes related to energy metabolism in liver, adipose, and muscle, as well as regulators of muscle mass and insulin receptor was assessed. The results demonstrated that there was reduced accumulation of body fat mass (P = .01) and greater lean mass (P = .03) for the HD- compared to LD-fed group regardless of the background diet. There were no consistent differences between the LD and HD groups across background diets in substrate oxidation and mRNA expression for enzymes measured that regulate energy metabolism, myostatin, or muscle vascular endothelial growth factor. However, there was an increase in insulin receptor mRNA expression in muscle in the HD compared to the LD groups. In conclusion, elevated whey protein, calcium, and vitamin D intake resulted in reduced accumulation of body fat mass and increased lean mass, with a commensurate increase in insulin receptor expression, regardless of the level of calories from fat or sucrose.     

Longitudinal analysis of retinal changes after branch retinal artery occlusion using optical coherence tomography.

BACKGROUND: Branch retinal artery occlusion (BRAO) causes inner retinal ischemia leading to permanent inner retinal dysfunction and visual field loss in affected retinal sectors. Optical coherence tomography (OCT) offers a novel way to evaluate in vivo retinal morphologic changes in BRAO in both acute and longitudinal phases. This case report describes OCT findings in BRAO at acute presentation and at follow-up, including the longitudinal evaluation of retinal and peripapillary retinal nerve fiber layer (RNFL) thickness. CASE REPORT: A 58-year-old white man with an acute branch retinal artery occlusion was examined by OCT at initial presentation and at 2, 4, and 8 months. At initial presentation, OCT line scan showed thickening and hyper-reflectivity of the inner retina with shadowing of photoreceptor and retinal pigment epithelial layers. At 2 months, hyper-reflectivity and thickening were reduced. At 4 months, the inner retina showed no hyper-reflectivity and was attenuated. Peripapillary RNFL thickness was reduced in corresponding sectors. Findings at the 8-month follow-up were unchanged from the 4-month visit. CONCLUSIONS: OCT provides useful information regarding the evolution of inner retinal attenuation in BRAO. Differential diagnosis of sectoral peripapillary RNFL thinning should include previous BRAO.     

Common variation in the BRCA1 gene and prostate cancer risk.

Rare inactivating mutations in the BRCA1 gene seem to play a limited role in prostate cancer. To our knowledge, however, no study has comprehensively assessed the role of other BRCA1 sequence variations (e.g., missense mutations) in prostate cancer. In a study of 817 men with and without prostate cancer from 323 familial and early-onset prostate cancer families, we used family-based association tests and conditional logistic regression to investigate the association between prostate cancer and single nucleotide polymorphisms (SNPs) tagging common haplotype variation in a 200-kb region surrounding (and including) the BRCA1 gene. We also used the Genotype-Identity-by-Descent Sharing Test to determine whether our most strongly associated SNP could account for prostate cancer linkage to chromosome 17q21 in a sample of 154 families from our previous genome-wide linkage study. The strongest evidence for prostate cancer association was for a glutamine-to-arginine substitution at codon 356 (Gln(356)Arg) in exon 11 of the BRCA1 gene. The minor (Arg) allele was preferentially transmitted to affected men (P = 0.005 for a dominant model), with an estimated odds ratio of 2.25 (95% confidence interval, 1.21-4.20). Notably, BRCA1 Gln(356)Arg is not in strong linkage disequilibrium with other BRCA1 coding SNPs or any known HapMap SNP on chromosome 17. In addition, Genotype-Identity-by-Descent Sharing Test results suggest that Gln(356)Arg accounts (in part) for our prior evidence of prostate cancer linkage to chromosome 17q21 (P = 0.022). Thus, we have identified a common, nonsynonymous substitution in the BRCA1 gene that is associated with and linked to prostate cancer.     

Cell line-dependent internalization pathways and intracellular trafficking determine transfection efficiency of nanoparticle vectors.

It has been suggested that cell physiology may affect the internalization pathways of non-viral vectors, leading to cell line-dependent transfection efficiency. To verify this hypothesis, fluorescently labeled alginate-chitosan nanoparticle complexes were used as non-viral vectors to transfect 293T, COS7, and CHO cells and to observe the cellular interactions and internalization mechanisms of the complexes in each cell line. 293T cells, which demonstrate the highest transfection efficiency, internalize complexes primarily through clathrin-mediated processes. COS7 cells also demonstrate some internalization of complexes through the clathrin-dependent pathway, explaining the moderate transfection exhibited. In contrast, CHO cells internalize complexes predominantly through caveolin-mediated pathways and are not transfected. Results suggest that following clathrin-mediated endocytosis, complexes are trafficked to the endo-lysosomal pathway, where the proton-sponge effect leads to their release into the cytosol. Contrarily, the absence of trafficking to this pathway following caveolin-mediated endocytosis results in vesicle-entrapped complexes that become transfection-incompetent. These results demonstrate that cell physiology is a critical factor in efficient transfection, and that trafficking to the endo-lysosomal pathway through specific internalization mechanisms is essential for transfection with alginate-chitosan nanoparticle complexes.