Meta-analysis supports association of a functional SNP (rs1801133) in the MTHFR gene with Parkinson's disease

The MTHFR is a candidate risk gene for Parkinson's disease (PD), and a functional SNP (rs1801133) in the coding region of this gene has been investigated for the associations with the illness extensively among worldwide populations, but overall the results were inconsistent. Here, to assess the relationship between rs1801133 and risk of PD in general populations, we conducted a systematic meta-analysis by combining all available case–control samples in European and Asian populations, with a total of 1820 PD cases and 7530 healthy controls, and the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for rs1801133 and PD were calculated using the Mantel–Haenszel method with a fixed-effect model. Overall, rs1801133 was significantly associated with the risk of PD (allelic model, pooled OR = 1.212 for T allele, 95% CI = 1.097–1.340, p-value = 0.0002). When stratifying for ethnicity, significant association was also observed in European (allelic model, pooled OR = 1.187 for T allele, 95% CI = 1.058–1.332, p-value = 0.004) and Asian samples (allelic model, pooled OR = 1.293 for T allele, 95% CI = 1.058–1.580, p-value = 0.012) respectively. In addition, rs1801133 was also significantly associated with MTHFR mRNA expression in both CEU (European, p-value = 0.0149) and CHB (Chinese, p-value = 0.0178) HapMap populations. Collectively, our meta-analysis suggests that rs1801133 is significantly associated with susceptibility to PD in European and Asian populations, and MTHFR is likely an authentic risk gene for PD.     

Differences in circadian patterns between rural and urban populations: An epidemiological study in countryside

The physiological pattern of the sleep–wake cycle is influenced by external synchronizing agents such as light and social patterns, creating variations in each individual’s preferred active and sleep periods. Because of the demands of a 24-h working society, it may be imperative for many people to adapt their sleep patterns (physiologically) to their daily activities. Therefore, we analyzed the difference in sleep patterns and chronobiological parameters between an essentially rural farming and urban small-town populations. We studied 5942 subjects (women, 67.1%, N?=?3985; mean age, 44.3?±?13.1 years), from which the chronotype, circadian sleep pattern, and period of light exposure were collected using the Munich Chronotype Questionnaire (MCTQ). A structured questionnaire was also made for collection of social and demographic information. Compared with the urban population (N?=?3427, 57.7%), the rural population (N?=?2515, 42.3%) presented a more predominantly early sleep pattern, as determined by the mid-sleep phase (rural: 2.26?±?1.16; urban: 3.15?±?1.55; t-test, p?<?0.001). We also found less social jetlag (rural: 0.32; urban: 0.55; Mann–Whitney U test, p?<?0.001) and higher light-exposure (rural: 9.55?±?2.31; urban: 8.46?±?2.85; t test, p?<?0.001) in the rural population. Additionally, the rural population presented a higher prevalence of psychiatric disorders (rural: 156, 6.20%; urban: 165, 4.80%; Chi-square, p?<?0.05), and a lower prevalence of metabolic diseases (rural: 143, 5.70%; urban: 225, 6.60%; Chi-square, p?<?0.05). The significant difference in sleep parameters, chronotype, and light exposure between groups remained after multivariate regression analysis (r^2?=?0.41, F?=?297.19, p?<?0.001, β?=?1.208). In this study, there was a significant difference between the rural and urban populations in natural light exposure and sleeping patterns. Because of agricultural work schedules, rural populations spend considerable time outside that is an obligation related to work schedules. Our results emphasize the idea that latitude may not be the main factor influencing individual circadian habits. Rather, circadian physiology adapts to differences in exposure to light (natural and artificial) as well as social and work schedules.     

Liquid chromatography tandem mass spectrometry in study of the pharmacokinetics of six steroidal saponins in rats

A rapid, simple and sensitive high-performance liquid chromatography tandem mass spectrometry method was developed and validated for simultaneous determination of six main steroidal saponins in Paris polyphylla in rat plasma. Ginsenoside Rg3 was selected as the internal standard (IS). Plasma samples were pretreated with protein precipitation, and the separation was achieved on a reverse phase Agilent poroshell120 EC-C18 column using a gradient mobile phase system of acetonitrile–water containing 0.1% formic acid. The triple quadruple mass spectrometer was set in negative electrospray ionization mode and multiple reaction monitoring (MRM) was used for six steroidal saponins quantification. The precursors to produce ion transitions monitored for polyphyllin I, polyphyllin II, polyphyllin VI, polyphyllin VII, dioscin, gracillin and IS were m/z 899.5 > 853.4, 1059.5 > 1013.5, 783.4 > 737.4, 1075.5 > 1029.5, 913.5 > 867.4, 929.5 > 883.4 and 819.5 > 783.4, respectively. The intra- and inter-day precisions (RSD%) were less than 13% and the average extraction recoveries ranged from 85% to 97.0% for each analyte. Six steroidal saponins were proved to be stable during sample storage, preparation and analytical procedures. The established method was employed for simultaneous quantification and successfully used for the first time for the pharmacokinetics evaluation of the six main compounds after intragastric administration of P. polyphylla extract in Sprague–Dawley rats.     

Segregation in the African wintering ranges of English and Swiss Swallow Hirundo rustica populations: a stable isotope study

Capsule Stable isotope analysis of Swallow feathers, grown in Africa, revealed significant differences between populations breeding in Switzerland and England.

Aims To investigate the extent to which Swallow populations breeding in Switzerland and England are separated on their African wintering grounds.

Methods Swallows were caught at breeding colonies, biometric measurements were taken and feathers, grown in Africa, were collected. Feathers were combusted in a Carlo Erba C/N/S analyser and the δ¹³C and δ¹⁵N signatures were measured using a mass spectrometer.

Results The δ¹³C signatures of Swiss birds were significantly more depleted than those of birds from England. The δ¹⁵N signatures did not differ between the two populations.

Conclusion Birds from Switzerland and England probably winter in geographically distinct parts of Africa. The Swiss birds probably feed on prey that are more reliant on C₃ vegetation, from woodlands, than the prey of English birds, which are more reliant on C₄ vegetation, from grasslands.     

Genotype Imputation Reference Panel Selection Using Maximal Phylogenetic Diversity

The recent dramatic cost reduction of next-generation sequencing technology enables investigators to assess most variants in the human genome to identify risk variants for complex diseases. However, sequencing large samples remains very expensive. For a study sample with existing genotype data, such as array data from genome-wide association studies, a cost-effective approach is to sequence a subset of the study sample and then to impute the rest of the study sample, using the sequenced subset as a reference panel. The use of such an internal reference panel identifies population-specific variants and avoids the problem of a substantial mismatch in ancestry background between the study population and the reference population. To efficiently select an internal panel, we introduce an idea of phylogenetic diversity from mathematical phylogenetics and comparative genomics. We propose the “most diverse reference panel”, defined as the subset with the maximal “phylogenetic diversity”, thereby incorporating individuals that span a diverse range of genotypes within the sample. Using data both from simulations and from the 1000 Genomes Project, we show that the most diverse reference panel can substantially improve the imputation accuracy compared to randomly selected reference panels, especially for the imputation of rare variants. The improvement in imputation accuracy holds across different marker densities, reference panel sizes, and lengths for the imputed segments. We thus propose a novel strategy for planning sequencing studies on samples with existing genotype data.     

Discovery of highly potent and selective D4 ligands by interactive SAR study

A series of thienylmethylphenylpiperazins was synthesized and tested for affinity towards the five subtypes of dopaminergic receptors. Compound 5f showed more than 1000 folds selectivity to D4 receptors; analogue 5e showed the highest affinity to D4 receptors with K_i 3.9 nM. An interactive SAR approach was adopted and lead to compound 14a with K_i (D4) as low as 0.03 nM. Molecular docking studies showed a potential, first to report arene cation interaction between the D4 unique residue Arg-186 and the ligands’ arene moiety, explaining the importance of having a strong negative electrostatic potential at this area of the compound structure.     

Some New Aryl-5′-fluoro-2′-meth-oxyphenyl Ketones and Their Thiosemicarbazones as Possible Fungicides

Feeding studies on rice genetically modified with soybean glycinin were performed on rats for four weeks. The rats were divided into three groups, each being fed on (I) only a commercial diet, (II) this diet plus control rice and (III) this diet plus rice genetically modified with glycinin. The rats were fed with 10 g/kg-weight of rice every day by oral administration. During the test period, the rats in every group grew well without marked differences in appearance, food intake, body weight, or cumulative body weight gain. There were also no significant differences in the blood count, blood composition or internal organ weights among the rats. Necropsy at the end of the experiment indicated neither pathological symptoms nor histopathological abnormalities in the liver and kidney. Judging from these results, the rice genetically modified with glycinin is considered to have been essentially the same in nutritional and biochemical characteristics as the control rice.     

The Protein Encoded by NCgl1221 in Corynebacterium glutamicum Functions as a Mechanosensitive Channel

The function of the NCgl1221-encoded protein of Corynebacterium glutamicum was analyzed using Bacillus subtilis as host because a method for preparing the giant provacuole required for electrophysiological studies has been established. Expression of NCgl1221 in a strain deficient in mscL and ykuT, both of which encode mechanosensitive channels, resulted in an 8.9-fold higher cell survival rate upon osmotic downshock than the control. Electrophysiological investigation showed that the giant provacuole prepared from this strain, expressing NCgl1221, exhibited significantly higher pressure-dependent conductance than the control. These findings show that the NCgl1221-encoded protein functions as a mechanosensitive channel.     

Temperature-related sex allocation shifts in a recovering keystone species,Pinus palustris

Summary

In the light of all that has been discovered about the mechanism of evolution it has become tempting to follow Darwin's lead and to “see no limit to this power“. Yet a careful examination of situations in which evolution is known to be occurring in some species, shows complete absence of evolution in others. This not because these species have not had the opportunity; in many situations there may even be uncolonised bare space.

The explanation must lie in the supply of appropriate variation. A tacit assumption of evolution by natural selection is that the necessary variation is always available. Yet there is no a priori justification for this. Evidence from populations in nature, particularly of species which are potential colonists of old metal mine workings and similar metal contaminated habitats, shows that the species that successfully colonise these habitats, by the evolution of metal tolerant populations, possess within their normal populations the necessary variation. But those species which fail to colonise these habitats, despite the opportunity, do not possess this variation. This applies also at the level of the population, in the replicated evolutionary situations occurring under electricity pylons.

Such evidence, together with arguments from theory, suggests that the failures of evolution have been as important as its successes in moulding the living world as we see it today, and that the reasons for failure must be sought at the molecular level in limitations to the origin of new variation.