Leptin modulates oocyte maturation by a central and a direct pathway in zebrafish.

Loss of LEPR function (LOF) in mammals leads to diverse phenotypes including morbid obesity and infertility while zebrafish show relatively minor phenotypes. This however allows the study of LEPR LOF in the absence of the detrimental effects of hyperglycemia or obesity. Here, we show evidence that leptin plays a role in the central as well as peripheral regulation of the hypothalamic-pituitary-gonadal (HPG) axis in zebrafish. Animals with a Lepr LOF show dysregulated pituitary HPG genes as well as evidence that oocytes mature slower and/or exhibit an increased rate of atresia. In culture, Lepr LOF attenuates the effect of 17α-20ß-dihydroxy-4 pregnen-3-one in promoting germinal vesicle breakdown (GVBD) and increases the rate of GVBD as well as attenuates the rate of oocyte atresia.

Enhanced Cortical Metabolic Activity in Females and Males of a Slow Progressing Mouse Model of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with selective degeneration of motor neurons in the central nervous system. The pathophysiology of ALS is not well understood. We have used 1H-[13C]-NMR spectroscopy together with an administration of [1,6-13C2]glucose and [2-13C]acetate in female and male SOD1G37R mice to assess neuronal and astroglial metabolic activity, respectively, in the central nervous system in ALS condition. The female (p = 0.0008) and male (p < 0.0001) SOD1G37R mice exhibited decreased forelimb strength when compared with wild-type mice. There was a reduction in N-acetylaspartylglutamate level, and elevation in myo-inositol in the spinal cord of female and male SOD1G37R mice. The transgenic male mice exhibited increased acetate oxidation in the spinal cord (p = 0.05) and cerebral cortex (p = 0.03), while females showed an increase in the spinal cord (p = 0.02) only. As acetate is transported and preferentially metabolized in the astrocytes, the finding of increased rate of acetate oxidation in the transgenic mice is suggestive of astrocytic involvement in the pathogenesis of ALS. The rates of glucose oxidation in glutamatergic (p = 0.0004) and GABAergic neurons (p = 0.0052) were increased in the cerebral cortex of male SOD1G37R mice when compared with the controls. The female mice showed an increase in glutamatergic (p = 0.039) neurometabolic activity only. The neurometabolic activity was unperturbed in the spinal cord of either sex. These data suggest differential changes in neurometabolic activity across the central nervous system in SOD1G37R mice.

Role of trim5α in the suppression of cross-species transmission and its defence against human immunodeficiency virus.

Acquired Immunodeficiency Syndrome (AIDS) was discovered 30 years ago and was followed by the identification and characterization of its causative agent, Human Immunodeficiency Virus (HIV). Increasing spread of retroviral infections has impelled science to understand the evolution of retroviruses from primates to humans. In the course of evolution, host cells have developed intracellular proteins to counteract the transforming viral defence system. Such inhibitory endogenous intracellular proteins are known as restriction factors. Tripartite motif protein isoform 5 alpha (TRIM5α), Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC), and Tetherin proteins are few important restriction factors that have been extensively studied. Several evidences have conveyed information regarding specific adaptations occurring in HIV-1 and its relatives to inhibit these host defenses; making the study more interesting. The characteristic potential of restriction factors to restrict the replication of retroviruses was enticing when studies were found that HIV-1 virus cannot infect nonhuman primate species. This review emphasizes on TRIM5α as a restriction factor and its significance in the evolution of retroviruses. It also accentuates the role of polymorphism within the regions of TRIM5α in both human and primate species that eventually affect the cross-species transmission of immunodeficiency viruses.