Variations in genotype–phenotype correlations in phenylalanine hydroxylase deficiency in Chinese Han population

Background

The value of genotyping to predict variant phenotypes in patients with phenylalanine hydroxylase (Pah) deficiency is a matter of debate. However, there exists no comprehensive population relationship study focused on the Han Chinese.

Methods

We analyzed genotype–phenotype correlation for 186 different genotypes in 338 unrelated Chinese patients harboring 109 different Pah mutations. Two systems were used in this process. The first was a phenotype prediction system based on arbitrary values (AV) attributed to each mutation. The second was a pair-wise correlation analysis. The observed phenotype for AV analysis was the corresponding metabolic phenotype stratified according to the pretreatment phenylalanine (Phe) value.

Results

We found that the observed phenotype matched the predicted phenotype in 54.41% of 272 patients for whom AV information was available; the highest degree of concordance (61.83%) was found in patients with null/null genotypes, whereas the lowest “concordance rate” (32.69%) was observed for patients with expected mild-PKU phenotype. There are repeated inconsistencies for such mutations as R241C, R243Q, R261Q, V388M, V399V, R408Q, A434D and EX6-96A>G which are associated with variable phenotypes in patients with identical genotype. Significant correlations were disclosed between pretreatment Phe values and predicted residual activity (r = − 0.45643, P < 0.0001) or AV sum (r = − 0.59523, P < 0.0001).

Conclusion

Our study supports the notion that the Pah mutation genotype is the main determinant of metabolic phenotype in most patients in a particular population, and provided novel insights into the values that underpin the subsequent treatment and the prognosis of PKU in Chinese.     

The hMLH1 promoter polymorphisms and cancer susceptibility in Asian populations: A meta-analysis

Background

A variety of studies have evaluated the associations between polymorphisms in the promoter regions of the hMLH1 and cancer risk. However, the results remain inconclusive. To better understand the roles of the hMLH1 polymorphisms and cancer risk, we conducted a comprehensive meta-analysis to investigate the association between the hMLH1 − 93G/A and 1151T/A (Val384Asp) polymorphisms and cancer risk in Asian population.

Methods

We performed a meta-analysis by conducting searches of the published studies in Pub Med, CNKI, CBM, ISI web of knowledge and Google scholar search databases. Finally, 12 studies were included into our meta-analysis. Overall and subgroup analyses were performed. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the associations between hMLH1 polymorphisms and cancer risk. Statistical analysis was performed with Review Manager 5.0.

Results

Twelve studies addressing two hMLH1 polymorphisms were analyzed among a total of 4128 cancer cases and 4678 controls. For hMLH1 − 93G/A, there was no evidence that the hMLH1 − 93G/A polymorphism was significantly associated with an increased cancer risk (P > 0.05) in Asian populations (heterozygote comparison: OR = 0.89 [95% CI (0.75, 1.060)] P = 0.20; dominant model comparison: OR = 0.98 [95% CI (0.83, 1.15)] P = 0.79). In subgroup analysis based on cancer types and the sources of control, no associations were found in colorectal cancer, gastric cancer and “other cancers” under the any gene model except for lung cancer (recessive model comparison: OR = 1.69 [95% CI (1.30, 2.19)] P < 0.0001). For hMLH1 1151T/A, the polymorphism significantly associated with an increased cancer risk in Asians: OR = 1.88 [95% CI (1.49, 2.25)], P < 0.0001, and OR = 1.87 [95% CI (1.49, 2.25)], P < 0.0001.

Conclusions

Our investigations demonstrated that the hMLH1 − 93G/A polymorphism is not a candidate for susceptibility to overall cancers, and that the hMLH1 1151T/A polymorphism is significantly associated with higher cancer risk in Asian populations. Further studies with large sample size for hMLH1 should be conducted.     

Sex differences in the antecedents of animal use attitudes

Abstract

Sex differences in attitudes toward the use of animals have been reported in previous research. This study examines sex differences in the levels of, and the interrelations among, three potential antecedents of attitudes toward animal use: caring value orientation, pet care experience and attachment to pets. Path analysis showed that pet care experience, through attachment to pets, accounted for a significant portion of variance in animal use attitudes in both males and females. Caring value orientation was directly linked to animal use attitudes in females, but in males, caring value orientation affected attachment to pets, which in turn impacted on animal use attitudes. Results are discussed in terms of Gilligan's theory of socialization.     

BetaDock: Shape-Priority Docking Method Based on Beta-Complex

Abstract

This paper presents an approach and a software, BetaDock, to the docking problem by putting the priority on shape complementarity between a receptor and a ligand. The approach is based on the theory of the β-complex. Given the Voronoi diagram of the receptor whose topology is stored in the quasi-triangulation, the β-complex corresponding to water molecule is computed. Then, the boundary of the β-complex defines the β-shape which has the complete proximity information among all atoms on the receptor boundary. From the β-shape, we first compute pockets where the ligand may bind. Then, we quickly place the ligand within each pocket by solving the singular value decomposition problem and the assignment problem. Using the conformations of the ligands within the pockets as the initial solutions, we run the genetic algorithm to find the optimal solution for the docking problem. The performance of the proposed algorithm was verified through a benchmark test and showed that BetaDock is superior to a popular docking software AutoDock 4.     

Old‐male paternity advantage is a function of accumulating sperm and last‐male precedence in a butterfly

Old‐male mating advantage has been convincingly demonstrated in Bicyclus anynana butterflies. This intriguing pattern may be explained by two alternative hypotheses: (i) an increased aggressiveness and persistence of older males during courtship, being caused by the older males' low residual reproductive value; and (ii) an active preference of females towards older males what reflects a good genes hypothesis. Against this background, we here investigate postcopulatory sexual selection by double‐mating Bicyclus anynana females to older and younger males, thus allowing for sperm competition and cryptic mate choice, and by genotyping the resulting offspring. Virgin females were mated with a younger virgin (2–3 days old) and afterwards an older virgin male (12–13 days old) or vice versa. Older males had a higher paternity success than younger ones, but only when being the second (=last) mating partner, while paternity success was equal among older and younger males when older males were the first mating partner. Older males produced larger spermatophores with much higher numbers of fertile sperm than younger males. Thus, we found no evidence for cryptic female mate choice. Rather, the findings reported here seem to result from a combination of last‐male precedence and the number of sperm transferred upon mating, both increasing paternity success.     

光核桃遗传资源的经济价值评估与保护

本文将光核桃遗传资源的经济价值划分为直接利用价值、间接利用价值和潜在利用价值,采用市场价格法、旅行费用法、防护费用法及类比分析法等方法对光核桃遗传资源的经济价值进行估算,并提出该资源保护与管理建议。光核桃遗传资源经济价值的评估,将为具有潜在巨大经济价值的生物遗传资源管理提供价值评估方法,同时为维护国家利益、制订生物多样性保护与管理政策及建立生物遗传资源惠益分享制度提供技术支持。     

马尾松和苦槠林根际土壤矿化和根系分解CO2释放的温度敏感性

以中亚热带马尾松林和苦槠林为对象,原位收集根际和非根际土壤、树木不同生态功能的根系,开展15℃、25℃、35℃和45℃恒温培养模拟试验,采用密闭气室碱液吸收法测定53 d内CO2释放的动态变化.结果表明:两种森林类型不同温度下土壤矿化CO2释放速率的根际效应介于1.12 ～3.09,且培养前期高于培养后期;15℃下马尾松林和苦槠林差异不显著,25℃和35℃下前者低于后者,45℃下则相反.不同培养温度下两树种吸收根分解的CO2释放速率均高于过渡根和贮存根,且马尾松均低于苦槠.两种森林类型CO2释放的Q10值均为土壤(1.21 ～1.83)显著高于根系(0.96 ～1.36).两种森林类型土壤矿化CO2释放的Q10值差异不显著,而马尾松根系分解CO2释放的Q10值高于苦槠.推断全球变暖导致的土壤矿化CO2释放的增量将远远高于根系分解,且马尾松林高于苦槠林;地带性顶极群落应对气候变化的抵抗力强于先锋树种群落.     

南方红壤区3年生茶园土壤呼吸特征

为探讨南方红壤区茶园的土壤呼吸特征,采用LI-Cor8100开路式土壤碳通量测定系统观测3年生茶园系统的土壤呼吸速率,对茶园土壤呼吸速率的季节变化和在茶行尺度上的空间异质性进行了研究。结果表明,茶园土壤呼吸速率的月动态变化呈明显的单峰曲线特征,峰值出现在8月;茶园土壤呼吸速率的月动态变化与温度呈极显著相关(P<0.01),土壤10 cm的温度能够解释茶园不同观测区域土壤呼吸速率月动态变化的67.79%~88.52%;用指数方程计算的茶园不同观测区域土壤呼吸Q10值为1.58~1.86。在茶行尺度上,茶园土壤呼吸速率存在明显的空间异质性,土壤呼吸速率通常在距离茶树基部较近的位置较高;根系生物量能够解释茶园土壤呼吸速率在茶行尺度上空间变异的82.68%。因此,根系分布的空间差异是造成茶园土壤呼吸速率空间异质性的主要原因。     

Deriving metabolic engineering strategies from genome-scale modeling with flux ratio constraints

Optimized production of bio-based fuels and chemicals from microbial cell factories is a central goal of systems metabolic engineering. To achieve this goal, a new computational method of using flux balance analysis with flux ratios (FBrAtio) was further developed in this research and applied to five case studies to evaluate and design metabolic engineering strategies. The approach was implemented using publicly available genome-scale metabolic flux models. Synthetic pathways were added to these models along with flux ratio constraints by FBrAtio to achieve increased (i) cellulose production from Arabidopsis thaliana; (ii) isobutanol production from Saccharomyces cerevisiae; (iii) acetone production from Synechocystis sp. PCC6803; (iv) H₂ production from Escherichia coli MG1655; and (v) isopropanol, butanol, and ethanol (IBE) production from engineered Clostridium acetobutylicum. The FBrAtio approach was applied to each case to simulate a metabolic engineering strategy already implemented experimentally, and flux ratios were continually adjusted to find (i) the end-limit of increased production using the existing strategy, (ii) new potential strategies to increase production, and (iii) the impact of these metabolic engineering strategies on product yield and culture growth. The FBrAtio approach has the potential to design “fine-tuned” metabolic engineering strategies in silico that can be implemented directly with available genomic tools.     

Health assessment of freshwater fish species from Albasini Dam,outside a DDT-sprayed area in Limpopo province,South Africa: a preliminary study

During 2006 to 2008, the water, sediment and fish in Albasini Dam, used as a reference site outside a DDT-sprayed area, had been found to be as affected as those in the nearby DDT-sprayed area were. Accordingly, the aim of the current study, conducted in 2014, was to determine the health status of fish from Albasini Dam by means of a histology-based fish health assessment protocol. High levels of nitrates, as well as the organochlorine pesticides aldrin, dieldrin, chlordane and methoxychlor, were found in the water. Fish muscle tissue contained pesticides, including methoxychlor. A semi-quantitative histological assessment on Clarias gariepinus, Coptodon rendalli and Oreochromis mossambicus showed diverse histopathology in selected target organs, with the gills being most affected. Notably, the testis tissue of one C. rendalli was filled with eosinophilic liquid, characteristic of necrosis. Microscopic intersex was found in two of the nine O. mossambicus sampled. This is the second time that intersex as microscopic testicular oocytes has been reported in O. mossambicus in South Africa. This finding perhaps indicates that reproduction may be compromised and this will be investigated further. The presence of intersex and other histopathology in organs could be early warning signs of the declining water quality in this dam.