Human metabolic individuality in biomedical and pharmaceutical research

Genome-wide association studies (GWAS) have identified many risk loci for complex diseases, but effect sizes are typically small and information on the underlying biological processes is often lacking. Associations with metabolic traits as functional intermediates can overcome these problems and potentially inform individualized therapy. Here we report a comprehensive analysis of genotype-dependent metabolic phenotypes using a GWAS with non-targeted metabolomics. We identified 37 genetic loci associated with blood metabolite concentrations, of which 25 show effect sizes that are unusually high for GWAS and account for 10-60% differences in metabolite levels per allele copy. Our associations provide new functional insights for many disease-related associations that have been reported in previous studies, including those for cardiovascular and kidney disorders, type 2 diabetes, cancer, gout, venous thromboembolism and Crohn's disease. The study advances our knowledge of the genetic basis of metabolic individuality in humans and generates many new hypotheses for biomedical and pharmaceutical research.     

A Pluto-like radius and a high albedo for the dwarf planet Eris from an occultation

The dwarf planet Eris is a trans-Neptunian object with an orbital eccentricity of 0.44, an inclination of 44 degrees and a surface composition very similar to that of Pluto. It resides at present at 95.7 astronomical units (1?AU is the Earth-Sun distance) from Earth, near its aphelion and more than three times farther than Pluto. Owing to this great distance, measuring its size or detecting a putative atmosphere is difficult. Here we report the observation of a multi-chord stellar occultation by Eris on 6 November 2010 UT. The event is consistent with a spherical shape for Eris, with radius 1,163?±?6?kilometres, density 2.52?±?0.05 grams per cm(3) and a high visible geometric albedo, Pv = 0.96(+0.09)(-0.04). No nitrogen, argon or methane atmospheres are detected with surface pressure larger than ～1?nanobar, about 10,000 times more tenuous than Pluto's present atmosphere. As Pluto's radius is estimated to be between 1,150 and 1,200 kilometres, Eris appears as a Pluto twin, with a bright surface possibly caused by a collapsed atmosphere, owing to its cold environment. We anticipate that this atmosphere may periodically sublimate as Eris approaches its perihelion, at 37.8 astronomical units from the Sun.     

Role of sulphuric acid, ammonia and galactic cosmic rays in atmospheric aerosol nucleation

Atmospheric aerosols exert an important influence on climate through their effects on stratiform cloud albedo and lifetime and the invigoration of convective storms. Model calculations suggest that almost half of the global cloud condensation nuclei in the atmospheric boundary layer may originate from the nucleation of aerosols from trace condensable vapours, although the sensitivity of the number of cloud condensation nuclei to changes of nucleation rate may be small. Despite extensive research, fundamental questions remain about the nucleation rate of sulphuric acid particles and the mechanisms responsible, including the roles of galactic cosmic rays and other chemical species such as ammonia. Here we present the first results from the CLOUD experiment at CERN. We find that atmospherically relevant ammonia mixing ratios of 100 parts per trillion by volume, or less, increase the nucleation rate of sulphuric acid particles more than 100-1,000-fold. Time-resolved molecular measurements reveal that nucleation proceeds by a base-stabilization mechanism involving the stepwise accretion of ammonia molecules. Ions increase the nucleation rate by an additional factor of between two and more than ten at ground-level galactic-cosmic-ray intensities, provided that the nucleation rate lies below the limiting ion-pair production rate. We find that ion-induced binary nucleation of H(2)SO(4)-H(2)O can occur in the mid-troposphere but is negligible in the boundary layer. However, even with the large enhancements in rate due to ammonia and ions, atmospheric concentrations of ammonia and sulphuric acid are insufficient to account for observed boundary-layer nucleation.     

马铃薯交联-羧甲基淀粉的结构与性能

以马铃薯淀粉为原料,环氧氯丙烷为交联剂,制备交联-羧甲基淀粉(CCMS).对比了CCMS与马铃薯原淀粉、交联淀粉(CS)、羧甲基淀粉(CMS)和羧甲基纤维素(CMC)的性质,结果表明CCMS糊液具有良好的抗老化能力、热稳定性、酸碱稳定性及抗剪切稳定性.采用傅里叶变换红外光谱(FT-IR)、环境扫描电镜(ESEM)和X射...     

“Without Ub I am nothing”: NEMO as a multifunctional player in ubiquitin-mediated control of NF-κB activation

Ubiquitination has emerged over the years as the most sophisticated way to modify proteins to affect their fate and function. In particular, it has been reported to be instrumental in regulating several steps of the NF-κB signalling pathway which controls inflammation, immunity, adhesion and cell survival. Integrating ubiquitination into NF-κB activation requires the regulatory subunit of IKK, NEMO, which not only displays affinity for polyubiquitin chains, but is also posttranslationally modified by a complex set of reactions involving ubiquitin. Here, we examine how studies of the NEMO/ubiquitin relationship have provided novel insights into the IKK activation process and have uncovered molecular mechanisms that should represent in the future attractive targets for specifically modulating NF-κB function.     

Sperm viability in the reproductive tract of females in a population of Sceloporus mucronatus exhibiting asynchronous reproduction

Asynchronous reproduction is a common phenomenon in high-elevation populations of lizards from Central México. Sperm storage in the reproductive tract of females is the mechanism for making oocyte fertilization possible. Our study addresses questions related to functional oviductal sperm storage of females mating on different dates throughout the reproductive season. A population of Sceloporus mucronatus with copulation in the summer and ovulation in the fall was chosen for this experiment. Eleven females that copulated in the field during June and 13 females that copulated in captivity during August were maintained in the laboratory until parturition. The number of pregnant females and the litter sizes produced in each experimental group were indicative of the viability of the stored sperm. Sperm stored in the reproductive tract of females were able to fertilize eggs after 4 months. No significant differences were found in the number of pregnant females between the 2 experimental groups nor in the litter sizes that they produced. We found that the amount of time sperm were held in the female reproductive tract (ca. 3 months) had no effect on the capacity of sperm to fertilize eggs. Histological examination of 8 oviducts collected before the mating season eliminated the possibility of sperm storage from one year to the next. In this system, sperm retention could have evolved as a response mechanism to deal with the asynchrony between sexes in the reproductive cycles. However, we cannot rule out alternative hypotheses.