However, it is not well understood how selection on the phenotype

However, it is not well understood how selection on the phenotype determines fitness. In accordance with Fisher’s fundamental theorem, fitness should have no or very little genetic variance, whereas empirical data suggest that is not the case. To bridge these knowledge gaps, we follow Fisher’s geometrical model and assume that fitness is determined by multivariate stabilizing selection toward an optimum that may vary among generations. We assume random mating, free recombination, additive genes, and uncorrelated stabilizing selection and mutational effects on traits. In a constant environment, we find that genetic variance in fitness under

mutation-selection balance is a U-shaped function of the number of traits (i.e., AZD8186 of the so-called organismal complexity). Because the variance can be high if the organism is of either low or high complexity, this suggests that complexity has little direct costs. Under a temporally varying

optimum, genetic variance increases relative to a constant optimum BYL719 in vitro and increasingly so when the mutation rate is small. Therefore, mutation and changing environment together can maintain high genetic variance. These results therefore lend support to Fisher’s geometric model of a fitness landscape.”
“Two unusual cases of anterior urethral valves (AUV) without diverticulae are presented. The first case is a male child born with prenatal diagnosis of bilateral hydronephrosis. On cystoscopy, iris-like diaphragm valves were encountered about 3mm distal to the skeletal sphincter. In the second case, an 18-month-old male child was investigated for recurrent febrile urinary tract infections and obstructed urinary symptoms. Cystoscopy confirmed the presence of slit-like valves 5mm distal to the PFTα inhibitor skeletal sphincter. Fulguration of the AUVs was performed in both cases. It may be worthwhile to review all cases of anterior urethral obstruction collectively and re-categorize them appropriately

to include the unusual AUVs without diverticulum in that classification.”
“Bacterial infections are a common and serious complication of type 2 diabetes (T2D). The prevalence of melioidosis, an emerging tropical infection caused by the Gram-negative bacterium Burkholderia pseudomallei, is increased in people with T2D. This is the first study to compare murine models of T2D and melioidosis. Susceptibility and disease progression following infection with B. pseudomallei were compared in our diet-induced polygenic mouse model and a leptin receptor-deficient monogenic model of T2D. The metabolic profile of mice with diet-induced diabetes, including body weight, blood glucose, cholesterol, triglycerides, insulin resistance, and baseline levels of inflammation, closely resembled that of clinical T2D. Following subcutaneous infection with B.

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