On the mechanism of inhibition of p27 degradation by 15-deoxy-Δ12,14-prostaglandin J 2 in lymphoblasts of Alzheimer’s disease patients

It has been proposed that neuroinflammation, among other factors, may trigger an aberrant neuronal cell cycle re-entry leading to neuronal death. Cell cycle disturbances are also detectable in peripheral cells from Alzheimer’s disease (AD) patients. We previously reported that the anti-inflammatory 15- deoxy-Δ^12,14-prostaglandin J ₂ (15d-PGJ ₂) increased the cellular content of the cyclin-dependent kinase inhibitor p27, in lymphoblasts from AD patients. This work aimed at elucidating the mechanisms of 15d-PGJ ₂-induced p27 accumulation. Phosphorylation, half-life, and the nucleo-cytoplasmic traffic of p27 protein were altered by 15d-PGJ2 by mechanisms dependent on PI3K/Akt activity. 15d-PGJ ₂ prevents the calmodulin-dependent Akt overactivation in AD lymphoblasts by blocking its binding to the 85-kDa regulatory subunit of PI3K. These effects of 15d-PGJ ₂ were not mimicked by 9,10-dihydro-15-deoxy-Δ^12,14- prostaglandin J ₂, suggesting that 15d-PGJ ₂ acts independently of peroxisome proliferator-activated receptor γ activation and that the α,β-unsaturated carbonyl group in the cyclopentenone ring of 15d-PGJ ₂ is a requisite for the observed effects. Received 14 July 2008; received after revision 2 September 2008; accepted 12 September 2008     

Common variants on 1p36 and 1q42 are associated with cutaneous basal cell carcinoma but not with melanoma or pigmentation traits

To search for new sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conducted a genome-wide SNP association study of 930 Icelanders with BCC and 33,117 controls. After analyzing 304,083 SNPs, we observed signals from loci at 1p36 and 1q42, and replicated these associations in additional sample sets from Iceland and Eastern Europe. Overall, the most significant signals were from rs7538876 on 1p36 (OR = 1.28, P = 4.4 x 10(-12)) and rs801114 on 1q42 (OR = 1.28, P = 5.9 x 10(-12)). The 1p36 locus contains the candidate genes PADI4, PADI6, RCC2 and ARHGEF10L, and the gene nearest to the 1q42 locus is the ras-homolog RHOU. Neither locus was associated with fair pigmentation traits that are known risk factors for BCC, and no risk was observed for melanoma. Approximately 1.6% of individuals of European ancestry are homozygous for both variants, and their estimated risk of BCC is 2.68 times that of noncarriers.     

基于SolidWorks 渐开线齿轮的三维辅助设计

探讨了基于SolidW orks的二次开发技术,研究如何利用V isual Basic程序语言在SolidW orks中强大的三维绘图功能进行计算机三维辅助设计;并以渐开线齿轮的设计与绘制为例,提出了通过程序计算后利用SolidW orks曲线连接阵列点构建封闭齿廓的方法。实践证明该方法为其它CAD二次开发平台绘画渐开线齿轮提供可借鉴之处。     

窖水中主要无机离子对光催化灭除大肠杆菌(E.coli)的影响研究

采用自主开发的N-TiO_2作为光催化剂,在流动相光催化反应装置中,对窖水中所含Ca~(2+)、Cl~-、CO_3~(2-)、HCO_3~-、SO_4~(2-)等主要无机离子对光催化剂灭除E.coli的影响,以及复配模拟窖水和实际窖水对光催化灭除E.coli的影响进行了实验研究,并分析了其影响机理。实验结果表明:Ca~(2+)、HCO_3~-对光催化灭除E.coli有抑制作用,CO_3~(2-)对光催化灭除E.coli有明显的促进作用,而SO_4~(2-)、Cl~-对光催化灭除E.coli无影响。在对实际窖水进行光催化灭除E.coli菌落总数的实验中,经60min反应,窖水中菌落总数和总大肠菌群均为零,达到国家饮用水卫生标准,说明自主开发的NTiO_2光催化剂在农村窖水深度处理灭除E.coli效果好,可推广应用。     

Retinoic acid regulates avian lung branching through a molecular network

Retinoic acid (RA) is of major importance during vertebrate embryonic development and its levels need to be strictly regulated otherwise congenital malformations will develop. Through the action of specific nuclear receptors, named RAR/RXR, RA regulates the expression of genes that eventually influence proliferation and tissue patterning. RA has been described as crucial for different stages of mammalian lung morphogenesis, and as part of a complex molecular network that contributes to precise organogenesis; nonetheless, nothing is known about its role in avian lung development. The current report characterizes, for the first time, the expression pattern of RA signaling members (stra6, raldh2, raldh3, cyp26a1, rarα, and rarβ) and potential RA downstream targets (sox2, sox9, meis1, meis2, tgfβ2, and id2) by in situ hybridization. In the attempt of unveiling the role of RA in chick lung branching, in vitro lung explants were performed. Supplementation studies revealed that RA stimulates lung branching in a dose-dependent manner. Moreover, the expression levels of cyp26a1, sox2, sox9, rarβ, meis2, hoxb5, tgfβ2, id2, fgf10, fgfr2, and shh were evaluated after RA treatment to disclose a putative molecular network underlying RA effect. In situ hybridization analysis showed that RA is able to alter cyp26a1, sox9, tgfβ2, and id2 spatial distribution; to increase rarβ, meis2, and hoxb5 expression levels; and has a very modest effect on sox2, fgf10, fgfr2, and shh expression levels. Overall, these findings support a role for RA in the proximal–distal patterning and branching morphogenesis of the avian lung and reveal intricate molecular interactions that ultimately orchestrate branching morphogenesis.     

On the Modelling and Forecasting of Multivariate Realized Volatility: Generalized Heterogeneous Autoregressive (GHAR) Model

Recent multivariate extensions of the popular heterogeneous autoregressive model (HAR) for realized volatility leave substantial information unmodelled in residuals. We propose to employ a system of seemingly unrelated regressions to model and forecast a realized covariance matrix to capture this information. We find that the newly proposed generalized heterogeneous autoregressive (GHAR) model outperforms competing approaches in terms of economic gains, providing better mean–variance trade‐off, while, in terms of statistical precision, GHAR is not substantially dominated by any other model. Our results provide a comprehensive comparison of the performance when realized covariance, subsampled realized covariance and multivariate realized kernel estimators are used. We study the contribution of the estimators across different sampling frequencies, and show that the multivariate realized kernel and subsampled realized covariance estimators deliver further gains compared to realized covariance estimated on a 5‐minute frequency. In order to show economic and statistical gains, a portfolio of various sizes is used. Copyright © 2016 John Wiley & Sons, Ltd.     

Microhabitat selection in the sand recluse spider (Sicarius thomisoides): the effect of rock size and temperature

In spiders, temperature is considered an important environmental variable for microhabitat selection. In this study, we evaluated the effect of temperature and rock size on the presence of the sand recluse spider Sicarius thomisoides and the degree of selectivity in different locations. This species is a large spider that lives under rocks in desert and semi-desert climates and is particularly active during the summer. In Chile, these spiders can be found at both coastal and inland locations under different thermal conditions, where usually the temperatures are lower near the coast. If large-scale climatic conditions are important for this species, they may be expected to select lower rock temperatures on the coast than at inland locations. In addition, we would expect that the spiders would choose larger rocks in inland compared to coast locations, which reduce the effect of high temperatures. We found that the probability of finding individuals of this species increased according to rock temperature and rock size in the field. Our results suggest that S. thomisoides prefers larger and warmer rocks to shelter under during the day, this selectivity being similar at both coastal and inland locations. Thus, this species tends to select rocks with the same thermal and structural conditions, independent of the climatic conditions.     

Increased migration of olfactory ensheathing cells secreting the Nogo receptor ectodomain over inhibitory substrates and lesioned spinal cord

Olfactory ensheathing cell (OEC) transplantation emerged some years ago as a promising therapeutic strategy to repair injured spinal cord. However, inhibitory molecules are present for long periods of time in lesioned spinal cord, inhibiting both OEC migration and axonal regrowth. Two families of these molecules, chondroitin sulphate proteoglycans (CSPG) and myelin-derived inhibitors (MAIs), are able to trigger inhibitory responses in lesioned axons. Mounting evidence suggests that OEC migration is inhibited by myelin. Here we demonstrate that OEC migration is largely inhibited by CSPGs and that inhibition can be overcome by the bacterial enzyme Chondroitinase ABC. In parallel, we have generated a stable OEC cell line overexpressing the Nogo receptor (NgR) ectodomain to reduce MAI-associated inhibition in vitro and in vivo. Results indicate that engineered cells migrate longer distances than unmodified OECs over myelin or oligodendrocyte-myelin glycoprotein (OMgp)-coated substrates. In addition, they also show improved migration in lesioned spinal cord. Our results provide new insights toward the improvement of the mechanisms of action and optimization of OEC-based cell therapy for spinal cord lesion.     

Year-round activity patterns in a hyperdiverse community of rainforest amphibians in Madagascar

Madagascar hosts a high diversity of amphibians estimated at over 500 species, nearly all of them endemic. Surprisingly few data are available on the activity cycles of this fauna, despite its importance for ecological, evolutionary and conservation research. Here we report the results of a year-round survey of amphibians along a transect bordering the Analamazaotra forest near Andasibe in central eastern Madagascar. During 120 transect walks evenly spaced through the year, a total of 2530 individuals of 40 species of anurans was observed. Abundance was higher during the warm/rainy season (December to April) and peaked in February. Of the five climatic predictors measured, only mean temperature and relative humidity showed high importance values, and multi-model averages indicate that these two variables have a strong effect on amphibian abundance along the transect. Species richness showed no evident peak during the study period and was best explained by a model including average temperature and rainfall. Canonical correspondence analysis indicates that Boophis sibilans, B. tephraeomystax, B. boehmei and Plethodontohyla notosticta were more frequently encountered along the transect on cold and humid days while Plethodontohyla mihanika, Gephyromantis boulengeri and Spinomantis aglavei were distinctly more abundant on cold and dry days, and Paradoxophyla palmata on warm and dry days. The results of our study flag a number of species as suitable candidates for future monitoring initiatives and suggest that a simple combination of visual and acoustic surveys can estimate amphibian activity with high sample sizes in Madagascar’s rainforests.