A phylo-functional core of gut microbiota in healthy young Chinese cohorts across lifestyles,geography and ethnicities

Structural profiling of healthy human gut microbiota across heterogeneous populations is necessary for benchmarking and characterizing the potential ecosystem services provided by particular gut symbionts for maintaining the health of their hosts. Here we performed a large structural survey of fecal microbiota in 314 healthy young adults, covering 20 rural and urban cohorts from 7 ethnic groups living in 9 provinces throughout China. Canonical analysis of unweighted UniFrac principal coordinates clustered the subjects mainly by their ethnicities/geography and less so by lifestyles. Nine predominant genera, all of which are known to contain short-chain fatty acid producers, co-occurred in all individuals and collectively represented nearly half of the total sequences. Interestingly, species-level compositional profiles within these nine genera still discriminated the subjects according to their ethnicities/geography and lifestyles. Therefore, a phylogenetically diverse core of gut microbiota at the genus level may be commonly shared by distinctive healthy populations as functionally indispensable ecosystem service providers for the hosts.     

Energy coding in neural network with inhibitory neurons

This paper aimed at assessing and comparing the effects of the inhibitory neurons in the neural network on the neural energy distribution, and the network activities in the absence of the inhibitory neurons to understand the nature of neural energy distribution and neural energy coding. Stimulus, synchronous oscillation has significant difference between neural networks with and without inhibitory neurons, and this difference can be quantitatively evaluated by the characteristic energy distribution. In addition, the synchronous oscillation difference of the neural activity can be quantitatively described by change of the energy distribution if the network parameters are gradually adjusted. Compared with traditional method of correlation coefficient analysis, the quantitative indicators based on nervous energy distribution characteristics are more effective in reflecting the dynamic features of the neural network activities. Meanwhile, this neural coding method from a global perspective of neural activity effectively avoids the current defects of neural encoding and decoding theory and enormous difficulties encountered. Our studies have shown that neural energy coding is a new coding theory with high efficiency and great potential.     

Global Analysis Reveals Families of Chemical Motifs Enriched for hERG Inhibitors

Promiscuous inhibition of the human ether-à-go-go-related gene (hERG) potassium channel by drugs poses a major risk for life threatening arrhythmia and costly drug withdrawals. Current knowledge of this phenomenon is derived from a limited number of known drugs and tool compounds. However, in a diverse, naïve chemical library, it remains unclear which and to what degree chemical motifs or scaffolds might be enriched for hERG inhibition. Here we report electrophysiology measurements of hERG inhibition and computational analyses of >300,000 diverse small molecules. We identify chemical ‘communities’ with high hERG liability, containing both canonical scaffolds and structurally distinctive molecules. These data enable the development of more effective classifiers to computationally assess hERG risk. The resultant predictive models now accurately classify naïve compound libraries for tendency of hERG inhibition. Together these results provide a more complete reference map of characteristic chemical motifs for hERG liability and advance a systematic approach to rank chemical collections for cardiotoxicity risk.     

Upper arm circumference development in Chinese children and adolescents: a pooled analysis

Background

Upper arm development in children is different in different ethnic groups. There have been few reports on upper arm circumference (UAC) at different stages of development in children and adolescents in China. The purpose of this study was to provide a reference for growth with weighted assessment of the overall level of development.

Methods

Using a pooled analysis, an authoritative journal database search and reports of UAC, we created a new database on developmental measures in children. In conducting a weighted analysis, we compared reference values for 0~60 months of development according to the World Health Organization (WHO) statistics considering gender and nationality and used Z values as interval values for the second sampling to obtain an exponential smooth curve to analyze the mean, standard deviation, and sites of attachment.

Results

Ten articles were included in the pooled analysis, and these articles included participants from different areas of China. The point of intersection with the WHO curve was 3.5 years with higher values at earlier ages and lower values at older ages. Boys curve was steeper after puberty. The curves in the studies had a merged line compatible. The Z values of exponential smoothing showed the curves were similar for body weight and had a right normal distribution.

Conclusions

The integrated index of UAC in Chinese children and adolescents indicated slightly variations with regions. Exponential curve smoothing was suitable for assessment at different developmental stages.     

Prevalence and Molecular Characterization of Glucose-6-Phosphate Dehydrogenase Deficiency at the China-Myanmar Border

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked hereditary disease that predisposes red blood cells to oxidative damage. G6PD deficiency is particularly prevalent in historically malaria-endemic areas. Use of primaquine for malaria treatment may result in severe hemolysis in G6PD deficient patients. In this study, we systematically evaluated the prevalence of G6PD deficiency in the Kachin (Jingpo) ethnic group along the China-Myanmar border and determined the underlying G6PD genotypes. We surveyed G6PD deficiency in 1770 adult individuals (671 males and 1099 females) of the Kachin ethnicity using a G6PD fluorescent spot test. The overall prevalence of G6PD deficiency in the study population was 29.6% (523/1770), among which 27.9% and 30.6% were males and females, respectively. From these G6PD deficient samples, 198 unrelated individuals (147 females and 51 males) were selected for genotyping at 11 known G6PD single nucleotide polymorphisms (SNPs) in Southeast Asia (ten in exons and one in intron 11) using a multiplex SNaPshot assay. Mutations with known association to a deficient phenotype were detected in 43.9% (87/198) of cases, intronic and synonymous mutations were detected alone in 34.8% (69/198) cases and no mutation were found in 21.2% (42/198) cases. Five non-synonymous mutations, Mahidol 487G>A, Kaiping 1388G>A, Canton 1376G>T, Chinese 4 392G>T, and Viangchan 871G>A were detected. Of the 87 cases with known deficient mutations, the Mahidol variant was the most common (89.7%; 78/87), followed by the Kaiping (8.0%; 7/87) and the Viangchan (2.2%; 2/87) variants. The Canton and Chinese 4 variants were found in 1.1% of these 87 cases. Among them, two females carried the Mahidol/Viangchan and Mahidol/Kaiping double mutations, respectively. Interestingly, the silent SNPs 1311C>T and IVS11nt93T>C both occurred in the same 95 subjects with frequencies at 56.4% and 23.5% in tested females and males, respectively (P<0.05). It is noteworthy that 24 subjects carrying the Mahidol mutation and two carrying the Kaiping mutation also carried the 1311C>T/IVS11nt93T>C SNPs. Further studies are needed to determine the enzyme levels of the G6PD deficient people and presence of additional G6PD mutations in the study population.     

cAMP/PKA Pathways and S56 Phosphorylation Are Involved in AA/PGE2-Induced Increases in rNaV1.4 Current

Arachidonic acid (AA) and its metabolites are important second messengers for ion channel modulation. The effects of extracellular application of AA and its non-metabolized analogue on muscle rNa_V1.4 Na⁺ current has been studied, but little is known about the effects of intracellular application of AA on this channel isoform. Here, we report that intracellular application of AA significantly augmented the rNa_V1.4 current peak without modulating the steady-state activation and inactivation properties of the rNa_V1.4 channel. These results differed from the effects of extracellular application of AA on rNa_V1.4 current. The effects of intracellular AA were mimicked by prostaglandin E₂ but not eicosatetraynoic acid (ETYA), the non-metabolized analogue of AA, and were eliminated by treatment with cyclooxygenase inhibitors, flufenamic acid, or indomethacin. AA/PGE₂-induced activation of rNa_V1.4 channels was mimicked by a cAMP analogue (db-cAMP) and eliminated by a PKA inhibitor, PKAi. Furthermore, inhibition of EP2 and EP4 (PGE₂ receptors) with AH6809 and AH23848 reduced the intracellular AA/PGE₂-induced increase of rNa_V1.4 current. Two mutated channels, rNa_V1.4S56A and rNa_V1.4T21A, were designed to investigate the role of predicted phosphorylation sites in the AA/PGE₂–mediated regulation of rNa_V1.4 currents. In rNa_V1.4S56A, the effects of intracellular db-cAMP, AA, and PGE₂ were significantly reduced. The results of the present study suggest that intracellular AA augments rNa_V1.4 current by PGE₂/EP receptor-mediated activation of the cAMP/PKA pathway, and that the S56 residue on the channel protein is important for this process.