Whether novel risk variants of Alzheimer's disease (AD) identified through genome-wide association studies also influence magnetic resonance imaging-based intermediate phenotypes of AD in the general population is unclear. We studied association of 24 AD risk loci with intracranial volume, total brain volume, hippocampal volume (HV), white matter hyperintensity burden, and brain infarcts in a meta-analysis of genetic association studies from large population-based samples (N = 8175-11,550). In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (p = 0.0054) and CD33 (rs3865444) with smaller intracranial volume (p = 0.0058). In gene-based tests, there was associations of HLA-DRB1 with total brain volume (p = 0.0006) and BIN1 with HV (p = 0.00089). A weighted AD genetic risk score was associated with smaller HV (beta +/- SE = -0.047 +/- 0.013, p = 0.00041), even after excluding the APOE locus (p = 0.029). However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested). These results suggest that novel AD genetic risk variants may contribute to structural brain aging in nondemented older community persons. (C) 2015 Elsevier Inc. All rights reserved.

The aim of the present study is to test a hypothesis that 5-HT1A and 5-HT2C receptors in the amygdala play an important role in the regulation of anxiety behaviors. We examined alterations in anxiety-like behaviors after manipulation of the expression of 5-HT1A and 5-HT2C receptors in the amygdala using recombinant adenovirus approaches. Recombinant adenoviruses containing a 5-HT1A promoter-controlled 5-HT1A antisense sequence or a 5-HT2C promoter-controlled 5-HT2C sense sequence were injected into the amygdala. Elevated plus-maze (EPM) and open field tests were conducted to determine anxiety-like behavior and locomotor activity. Reductions in the expression of 5-HT1A receptors in the amygdala significantly attenuated the time spent in the open arms of EPM and time spent in the center of an open field. Reduction in the percent of time spent in the open arms of EPM is negatively correlated with the density of 5-HT1A receptors in the central amygdala. On the other hand, increased expression of 5-HT2C receptors reduced the time spent in the open arms of EPM and time spent in the center of an open field. The reductions in the time spent and distance traveled in the open arms of EPM were correlated to the density of 5-HT2C receptors in the basolateral nucleus of amygdala. These data suggest that amygdaloid 5-HT1A receptors produce anxiolytic and 5-HT2C receptors produce anxiogenic effects. Together, the present results demonstrate the important role of the amygdaloid 5-HT1A and 5-HT2C receptors in the regulation of anxiety-like behaviors. This article is part of a Special Issue entitled 'Anxiety and Depression'. (C) 2011 Elsevier Ltd. All rights reserved.

A new series of 2-(3'-indolyl)-N-arylthiazole-4-carboxamides 17a-p has been designed and synthesized. Initial reaction of readily available thioamides 15 with bromopyruvic acid under refluxing conditions produced different thiazole carboxylic acids 16 which upon coupling with arylamines by using EDCI.HCl and HOBt afforded diverse arylthiazole-4-carboxamides 17a-p in 78-87% yields. Antibacterial activity evaluation against Gram-positive and Gram-negative bacterial strains led to compounds 17i-k and 17o as potent and selectively (Gram-negative) antibacterial agents. The cytotoxicity of thiazole carboxamides 17a-p was also evaluated on a panel of human cancer cell lines. Among the tested derivatives, compounds 17i (IC50 = 8.64 mu M; HEK293T) and 17l (IC50 = 3.41 mu M; HeLa) were identified as the most potent analogues of the series. Preliminary mechanism of action studies of thiazole carboxamide 17i suggested that its cytotoxicity against HeLa cells involves the induction of cell death by apoptosis. (C) 2015 Elsevier Ltd. All rights reserved.

The gene for cyclin-dependent kinase inhibitor 1B (CDKN1B; also known as P27(KIP1) and P27) encodes a cyclin-dependent kinase inhibitor and controls ovarian development in mice. In p27-deficient (p27(-/-)) mice, the overactivated follicular pool in ovaries was largely depleted, causing premature ovarian failure. The goal of this research was to investigate whether there are nucleotide changes in the CDKN1B gene of Han Chinese women with premature ovarian failure, as compared with control volunteers using candidate gene sequencing. No novel variations were found in exons encoding for CDKN1B. So the mutations in CDKN1B are not common with premature ovarian failure in Han Chinese women. (C) 2010, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Premature ovarian failure (POF) is defined as a cessation of ovarian function in women before the age of 40 years. POU5F1 has a critical role in regulating pluripotency in embryonic development and POU5F1 transcription factor is down-regulated more than 30-fold in the POF candidate gene Nobox knockout ovaries. In order to identify the potential correlation between POU5F1 and the development of POF, the exon regions of POU5F1 were amplified and sequenced in 115 POF patients and 149 healthy controls. One non-synonymous variant of POU5F1 (c. C37A, p. Pro13Thr) was identified and confirmed in one of the POF patients. The substitution replacing a hydrophobic amino acid, proline, with a hydrophilic amino acid, threonine. As far as is known, the present study is the first to identify a potential association between POU5F1 and the development of POF. (C) 2011, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Tensile creep behaviors of a hot compressed Mg-4Y-2Nd-0.2Zn-0.5Zr alloy with aging (the AA sample) and without aging (the AS sample) are studied at 473, 493 and 523 K under a wide range of applied stresses. The creep mechanism of the AS sample is dislocation viscous gliding. For the AA sample, the creep mechanism is cross-slip during the early creep stage and dislocation climb and pyramidal slip during the late. Furthermore, the precipitates can be dissolved into the matrix and restarted during the subsequent creep stages. At 473 and 493 K, the AA sample has a better creep resistance than the AS sample, due to the hindering effect of the precipitates on dislocation movement. At 523 K and higher stress levels, the precipitates have limited hindering effect on dislocation movement in the AA sample while the kink bands continue to serve as the strengthening mechanism in the AS sample. The creep resistance of the AA sample becomes lower than that of the AS sample. It is recommended that the AA sample be used in the applications where their service temperature is lower than the pre-aging temperature while the AS sample be used where service temperature is higher than the pre-aging temperature.