Admixture Mapping of 15,280 African Americans Identifies Obesity Susceptibility Loci on Chromosomes 5 and X

The prevalence of obesity (body mass index (BMI) ≥30 kg/m2) is higher in African Americans than in European Americans, even after adjustment for socioeconomic factors, suggesting that genetic factors may explain some of the difference. To identify genetic loci influencing BMI, we carried out a pooled analysis of genome-wide admixture mapping scans in 15,280 African Americans from 14 epidemiologic studies. Samples were genotyped at a median of 1,411 ancestry-informative markers. After adjusting for age, sex, and study, BMI was analyzed both as a dichotomized (top 20% versus bottom 20%) and a continuous trait. We found that a higher percentage of European ancestry was significantly correlated with lower BMI (ρ = −0.042, P = 1.6×10−7). In the dichotomized analysis, we detected two loci on chromosome X as associated with increased African ancestry: the first at Xq25 (locus-specific LOD = 5.94; genome-wide score = 3.22; case-control Z = −3.94); and the second at Xq13.1 (locus-specific LOD = 2.22; case-control Z = −4.62). Quantitative analysis identified a third locus at 5q13.3 where higher BMI was highly significantly associated with greater European ancestry (locus-specific LOD = 6.27; genome-wide score = 3.46). Further mapping studies with dense sets of markers will be necessary to identify the alleles in these regions of chromosomes X and 5 that may be associated with variation in BMI

Premature recruitment of oocyte pool and increased mTOR activity in Fmr1 knockout mice and reversal of phenotype with rapamycin

Abstract While mutations in the fragile X mental retardation-1 (FMR1) gene are associated with varying reproductive outcomes in females, the effects of a complete lack of FMR1 expression are not known. Here, we studied the ovarian and reproductive phenotypes in an Fmr1 knockout (KO) mouse model and the role of mammalian target of rapamycin (mTOR) signaling. Breeding, histologic and mTOR signaling data were obtained at multiple time points in KO and wild type (WT) mice fed a control or rapamycin (mTOR inhibitor) diet. KO mice showed an earlier decline in ovarian reserve than WT mice with an increased proportion of activated follicles. mTOR and phosphorylated S6 kinase (p-S6K) levels, a measure of downstream mTOR signaling, were elevated in the KO ovaries. Rapamycin blocked these effects in KO mice, and increased the primordial follicle pool and age of last litter in WT mice. Our data demonstrates an early decline in reproductive capacity in Fmr1 KO mice and proposes that premature recruitment of the primordial pool via altered mTOR signaling may be the mechanism. Reversal of phenotypes and protein levels in rapamycin-treated KO mice, as well as increased reproductive lifespan of rapamycin-fed WT mice, suggest the mTOR pathway as a potential therapeutic target

A multifunction and bidirectional valve-less rectification micropump based on bifurcation geometry

In this paper, we introduce a novel valve-less rectification micropump based on bifurcation geometry. Three micropumps based on three different bifurcation configurations were designed, fabricated and experimentally investigated. These designs demonstrate the potentials of developing bidirectional micropumps and multifunction microfluidic devices (combined functions of micro pumping and mixing). Polydimethylsiloxane (PDMS) was employed to fabricate the micropumps. Circular piezoelectric transducers (PZT) were used as flow actuators. Detailed fabrication procedures are illustrated. The micropumps were tested against two ranges of actuator frequencies. The first test was conducted in a frequency range between 0 and 100 Hz with small increments of 5 Hz, while the second test was conducted in a frequency range between 0 and 300 Hz with increments of 50 Hz. Ethanol was used as the working fluid in all experiments. A new dimensionless parameter was introduced to evaluate the efficiency of valve-less rectification micropumps and determine the optimum operational frequency. The flow rate and maximum back pressure were measured. Results of experiments confirmed and demonstrated the feasibility of valve-less rectification micropumps based on bifurcation geometry at a low frequency range. Additionally, results showed the potentials of multifunctional, bidirectional, and self-priming micropumps