The Genetic Architecture of Adaptations to High Altitude in Ethiopia

Although hypoxia is a major stress on physiological processes, several human populations have survived for millennia at high altitudes, suggesting that they have adapted to hypoxic conditions. This hypothesis was recently corroborated by studies of Tibetan highlanders, which showed that polymorphisms in candidate genes show signatures of natural selection as well as well-replicated association signals for variation in hemoglobin levels. We extended genomic analysis to two Ethiopian ethnic groups: Amhara and Oromo. For each ethnic group, we sampled low and high altitude residents, thus allowing genetic and phenotypic comparisons across altitudes and across ethnic groups. Genome-wide SNP genotype data were collected in these samples by using Illumina arrays. We find that variants associated with hemoglobin variation among Tibetans or other variants at the same loci do not influence the trait in Ethiopians. However, in the Amhara, SNP rs10803083 is associated with hemoglobin levels at genome-wide levels of significance. No significant genotype association was observed for oxygen saturation levels in either ethnic group. Approaches based on allele frequency divergence did not detect outliers in candidate hypoxia genes, but the most differentiated variants between high- and lowlanders have a clear role in pathogen defense. Interestingly, a significant excess of allele frequency divergence was consistently detected for genes involved in cell cycle control and DNA damage and repair, thus pointing to new pathways for high altitude adaptations. Finally, a comparison of CpG methylation levels between high- and lowlanders found several significant signals at individual genes in the Oromo.     

Endocrine Control of Embryonic Diapause in the Australian Sharpnose Shark Rhizoprionodon taylori

The reproductive cycle of the Australian sharpnose shark, Rhizoprionodon taylori, includes a temporary suspension of development at the commencement of embryogenesis termed embryonic diapause. This study investigated levels of 17β-estradiol (E₂), testosterone (T) and progesterone (P₄) in plasma samples of mature wild female R. taylori captured throughout the reproductive cycle and correlated them with internal morphological changes. Levels of T were elevated through most of the embryonic diapause period, suggesting a role of this hormone in the maintenance of this condition. Increasing plasma T concentrations from late diapause to early active development were associated with a possible role of androgens in the termination of embryonic diapause. As in other elasmobranchs, a concomitant increase of E₂ with ovarian follicle size indicated a direct role of this hormone in regulating vitellogenesis, while a peak in P₄ suggested this hormone is associated with preovulation and ovulation. Additionally, significant correlations between photoperiod or water temperature and maximum follicular diameter and hepatosomatic index suggest that these abiotic factors may also play a role triggering and regulating the synchrony and timing of reproductive events.     

Connective Tissue Growth Factor (CTGF/CCN2) enhances lactogenic differentiation of mammary epithelial cells via integrin-mediated cell adhesion

Background  

Connective Tissue Growth Factor (CTGF/CCN2), a known matrix-associated protein, is required for the lactogenic differentiation of mouse mammary epithelial cells. An HC11 mammary epithelial cell line expressing CTGF/CCN2 was constructed to dissect the cellular responses to CTGF/CCN2 that contribute to this differentiation program.     

Biosynthesis of l-β-(methylenecyclopropyl)-alanine (hypoglycin) in Blighia sapida

Threonine and C₁ units from methionine contribute to form an intermediate in the biosynthesis of l-β-(methylenecyclopropyl)-alanine, the toxi     

Presence of Kynurenine Hydroxylase in Developing Rat Brain

Abstract: Kynurenine-3-hydroxylase, an enzyme that is part of the degradative pathway for tryptophan, was present in the cerebral cortex of neonatal rats and exhibited a K_m , for L-kynurenine close to that of the liver enzyme. This enzyme was enriched in mitochondrial fractions isolated from cerebral cortices of neonatal rats by Ficoll-sucrose gradient centrifugation, with some activity also present in synaptosomal fractions probably due to the mitochondrial content of synaptosomes since cytochrome c oxidase, another mitochondrial enzyme, had a similar distribution in the gradient. Kynurenine hydroxylase as well as monoamine oxidase, another mitochondrial enzyme, had increased specific activities in synaptosomal fractions isolated from 14-day-old rats compared to fractions from 8-day-old rats. Hypothyroidism, induced on the day of birth, resulted in increased activities of kynurenine hydroxylase and monoamine oxidase in synaptosomal fractions isolated from 14-day-old rats.