An association between − 866G/A polymorphism in the promoter of UCP2 and obesity: A meta-analysis

− 866G/A polymorphism in the promoter of UCP2 gene has been reported to be associated with obesity, but the results remain inconclusive. To assess the relation of UCP2 − 866G/A polymorphism and obesity susceptibility, a meta-analysis was performed. PubMed, ISI, Wanfang database, VIP and CBM were searched to identify relevant studies up to July 31, 2012. Odds ratios (OR) and 95% confidence interval (95% CI) were pooled using fixed or random effect models. Subgroup analysis was performed by ethnicity (categorized as Asian and European). Heterogeneity and publication bias evaluation were performed to validate the credibility. Meta-regression and the ‘leave one out’ sensitive analysis were used to explore the potential sources of between-study heterogeneity. 14 studies were included in this meta-analysis. After exclusion of articles that deviated from the HWE in controls, and were the key contributors to between-study heterogeneity, the meta-analysis showed a significant association of the A allele with reduced risk of obesity in overall analysis and in European in the dominant, codominant and additional models. In Asian, no significant association was found between the − 866G/A in UCP2 gene and obesity susceptibility. The meta-analysis suggested that UCP2 − 866G/A polymorphism was associated with obesity. The A allele may be an important protective factor for obesity in European, but not in Asian. Further studies are needed to elucidate the relationship.     

Antigen binding and stability properties of non-covalently linked anti-CD22 single-chain Fv dimers

By varying linker length and domain orientation three multivalent derivatives of a monovalent anti-CD22 single-chain fragment variable (scFv) antibody were generated. Shortening the linker of the V(H)-V(L) oriented scFv to 5 or 0 residues resulted in the formation of diabodies or a mixture of tetramers and trimers, respectively. Unexpectedly, a V(L)-0-V(H) scFv assembled to homogenous dimers, remained substantially more stable than the V(H)-5-V(L) diabody when incubated in human serum at 37 degrees C, and retained its dimeric state when concentrated up to 4 mg/ml. These properties suggest the V(L)-0-V(H) scFv could become an attractive vehicle for the selective delivery of multiple effector molecules to CD22(+) tumor cells.     

Application of the equilibrium concept to the development of agaric fruit-bodies, with special reference to their straight downward growth in light from below

Equilibrium, a concept of dynamics, is found to be applicable to the phototropic and gravitropic growth in agaric fruit-bodies. The fruit-bodies exposed to light from below grow straight downward without bending upward, and those exposed to light from obliquely below grow first downward and then upward by negative gravitropism. The fruit-bodies exposed to light from above grow upward. Fruit-bodies growing straight downward or upward do not change the direction of growth; they are in ‘equilibria’. The straight downward growth can be regarded as an ‘unstable equilibrium’ having a higher potential, and the straight upward growth as a ‘stable equilibrium’ having a lower potential. The change in the direction of growth can be explained by the change in the potential; the upward bending in fruit-bodies that have grown obliquely downward can be regarded as a ‘transition’ from the unstable equilibrium to the stable one.     

陕西汉族人群12号染色体上7个STR基因座的遗传多态性分析

分析了中国汉族人群中12号染色体上7个短串联重复序列（short tandem repeat,STR）基因座的多态性。 采用荧光标记基因扫描对12号染色体上D12S1718、D12S1675、D12S358、D12S367、D12S1638、D12S1646和D12S1682基因座在80名陕西咸阳、榆林汉族人中的遗传多态性进行分析。结果在中国汉族人群中, D12S1718、D12S1675、D12S358、D12S367、D12S1638、D12S1646和D12S1682基因座分别检出7、10、8、8、6、9和11个等位基因,10、17、18、18、14、18和26个基因型,杂合度分别为44.28％、66.10％、78.89％、77.89％、73.69％、74.55％和82.39％。表明这7个STR基因座在中国人群中有较好的多态性,其基因型分布均符合Hard－Weinberg平衡（P>0.05）。     

Spatial genetic patterns generated by two admixing genetic lineages: a simulation study

Two formerly geographically separated lineages of the zebra mussel Dreissena polymorpha had been given the opportunity to mix extensively across the newly built German Main–Danube canal. We had monitored this admixture of mussel lineages and had described spatial patterns in different genetic measures [Müller et al. 2001 (Heredity, 86: 103); 2002 (Proc. R. Soc. Lond., 269: 1139)]. Here, we present an individual-based model to assess the potential of spatial genetic patterns of detecting and quantifying admixture of mussel lineages. Genetic measures studied are (1) allele frequencies, (2) deviations from Hardy–Weinberg expectations of loci (deficit of heterozygotes, HWD) and (3) linkage disequilibria between unlinked loci (LD). For allele frequencies, we observed a cline over the zone of admixture in all simulations of mixing mussel lineages suggesting that these are appropriate for verification of their mixture. The point of the first contact between lineages was always detectable from their intermediate allele frequencies. LD and HWD were only spatially informative for diagnostic loci or loci with very strong differences in allele frequencies of lineages. For such loci, the probability of disequilibria was highest where lineages had met and decreased towards both sources of lineages Main and Danube. The overall probability of detecting any disequilibrium was higher for LD than for HWD and increased with an increasing rate of genetic interchange. Our simulation results are corroborated by our zebra mussel data and studies from literature. They are applicable to any case of two known linearly mixing genetic lineages.     

Association between the CYP1A1 T3801C polymorphism and risk of cancer: Evidence from 268 case–control studies

T3801C is a common polymorphism in CYP1A1, showing differences in its biological functions. Case–control studies have been performed to elucidate the role of T3801C in cancer, although the results are conflicting and heterogeneous. Hence, we performed a meta-analysis to investigate the association between cancer susceptibility and T3801C (55,963 cases and 76,631 controls from 268 studies) polymorphism in different inheritance models. We used odds ratios with 95% confidence intervals to assess the strength of the association. Overall, significantly increased cancer risk was observed in any genetic model (dominant model: odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.09–1.19; recessive model: OR = 1.23, 95% CI = 1.12–1.34; CC vs. TT: OR = 1.31, 95% CI = 1.19–1.45; TC vs. TT: OR = 1.12, 95% CI = 1.07–1.18; additive model: OR = 1.14, 95% CI = 1.09–1.19) when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, the elevated risk remained for subgroups of cervical cancer, head and neck cancer, hepatocellular cancer, leukemia, lung cancer, prostate cancer and breast cancer. In addition, significantly decreased colorectal cancer risk was also observed. In summary, this meta-analysis suggests that the participation of CYP1A1 T3801C is a genetic susceptibility for some cancer types. Moreover, our work also points out the importance of new studies for T3801C association in some cancer types, such as gallbladder cancer, Asians of acute myeloid leukemia, and thyroid cancer, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the CYP1A1 T3801C polymorphism in cancer development.     

Testing island biogeography theory with visitation rates of birds to British islands

Aim We consider three hypotheses – MacArthur and Wilson’s island biogeography theory (IBT), Lack’s habitat diversity idea and the ‘target effect’– that explain the pattern of decreased species richness on small and distant islands. Location We evaluate these hypotheses using a detailed dataset on the occurrence and abundance of terrestrial birds on nine islands off the coast of Britain and the Republic of Ireland. Methods  Unlike previous studies, we compile data on species that visit the islands, rather than just those that breed on them. We divided the species into five mutually exclusive categories based upon their migratory status and where they regularly breed: British residents, summer visitors to Britain, winter visitors to Britain, and vagrants from Europe or beyond Europe. For each species group on each island we calculated the average number of species visiting each year. We then regressed the average number of species against island area and distance to the mainland (all variables were log‐transformed). We also compared the average number of species visiting each island with the average number of species breeding on each island. Results  Average number of visiting British residents decreased significantly with increasing island distance, but showed no relationship with island area. There was no significant relationship between island area or island distance and average number of summer or winter visitors. European and non‐European vagrants likewise showed no relationship between numbers of species visiting and island distance. However, the relationship between island area and number of visiting species was significant for both these categories; as island area increases so too does the number of visiting species. Main conclusions  As predicted by IBT, there were fewer visiting species on more distant islands. There were substantially more visitors to each island than breeding species, supporting Lack’s argument that lower bird richness is not a result of varying immigration rates (as predicted by IBT) but rather a result of some other island property, e.g. fewer resources. Birds make a decision to either leave an island or stay and breed. The target effect was also clearly demonstrated by the increase in European and non‐European breeders with increasing island size.     

A comparative analysis of the equilibrium dynamics of a designed protein inferred from NMR,X‐ray,and computations

A detailed analysis of high‐resolution structural data and computationally predicted dynamics was carried out for a designed sugar‐binding protein. The mean‐square deviations in the positions of residues derived from nuclear magnetic resonance (NMR) models and those inferred from X‐ray crystallographic B‐factors for two different crystal forms were compared with the predictions based on the Gaussian Network Model (GNM) and the results from molecular dynamics (MD) simulations. GNM systematically yielded a higher correlation than MD, with experimental data, suggesting that the lack of atomistic details in the coarse‐grained GNM is more than compensated for by the mathematically exact evaluation of fluctuations using the native contacts topology. Evidence is provided that particular loop motions are curtailed by intermolecular contacts in the crystal environment causing a discrepancy between theory and experiments. Interestingly, the information conveyed by X‐ray crystallography becomes more consistent with NMR models and computational predictions when ensembles of X‐ray models are considered. Less precise (broadly distributed) ensembles indeed appear to describe the accessible conformational space under native state conditions better than B‐factors. Our results highlight the importance of using multiple conformations obtained by alternative experimental methods, and analyzing results from both coarse‐grained models and atomic simulations, for accurate assessment of motions accessible to proteins under native state conditions. Proteins 2009. © 2009 Wiley‐Liss, Inc.