Mitochondrial targeting adaptation of the hominoid-specific glutamate dehydrogenase driven by positive Darwinian selection

Many new gene copies emerged by gene duplication in hominoids, but little is known with respect to their functional evolution. Glutamate dehydrogenase (GLUD) is an enzyme central to the glutamate and energy metabolism of the cell. In addition to the single, GLUD-encoding gene present in all mammals (GLUD1), humans and apes acquired a second GLUD gene (GLUD2) through retroduplication of GLUD1, which codes for an enzyme with unique, potentially brain-adapted properties. Here we show that whereas the GLUD1 parental protein localizes to mitochondria and the cytoplasm, GLUD2 is specifically targeted to mitochondria. Using evolutionary analysis and resurrected ancestral protein variants, we demonstrate that the enhanced mitochondrial targeting specificity of GLUD2 is due to a single positively selected glutamic acid-to-lysine substitution, which was fixed in the N-terminal mitochondrial targeting sequence (MTS) of GLUD2 soon after the duplication event in the hominoid ancestor ~18–25 million years ago. This MTS substitution arose in parallel with two crucial adaptive amino acid changes in the enzyme and likely contributed to the functional adaptation of GLUD2 to the glutamate metabolism of the hominoid brain and other tissues. We suggest that rapid, selectively driven subcellular adaptation, as exemplified by GLUD2, represents a common route underlying the emergence of new gene functions

Essential Hypertension Is Associated With Changes in Gut Microbial Metabolic Pathways A Multisite Analysis of Ambulatory Blood Pressure

Recent evidence supports a role for the gut microbiota in hypertension, but whether ambulatory blood pressure is associated with gut microbiota and their metabolites remains unclear. We characterized the function of the gut microbiota, their metabolites and receptors in untreated human hypertensive participants in Australian metropolitan and regional areas. Ambulatory blood pressure, fecal microbiome predicted from 16S rRNA gene sequencing, plasma and fecal metabolites called short-chain fatty acid, and expression of their receptors were analyzed in 70 untreated and otherwise healthy participants from metropolitan and regional communities. Most normotensives were female (66%) compared with hypertensives (35%, P<0.01), but there was no difference in age between the groups (59.2±7.7 versus 60.3±6.6 years old). Based on machine learning multivariate covariance analyses of de-noised amplicon sequence variant prevalence data, we determined that there were no significant differences in predicted gut microbiome α- and β-diversity metrics between normotensives versus essential or masked hypertensives. However, select taxa were specific to these groups, notably Acidaminococcus spp., Eubacterium fissicatena, and Muribaculaceae were higher, while Ruminococcus and Eubacterium eligens were lower in hypertensives. Importantly, normotensive and essential hypertensive cohorts could be differentiated based on gut microbiome gene pathways and metabolites. Specifically, hypertensive participants exhibited higher plasma acetate and butyrate, but their immune cells expressed reduced levels of short-chain fatty acid-activated GPR43 (G-protein coupled receptor 43). In conclusion, gut microbial diversity did not change in essential hypertension, but we observed a significant shift in microbial gene pathways. Hypertensive subjects had lower levels of GPR43, putatively blunting their response to blood pressure-lowering metabolites

Genetic diversity of Brazilian isolates of feline immunodeficiency virus

We isolated Feline immunodeficiency virus (FIV) from three adult domestic cats, originating from two open shelters in Brazil. Viruses were isolated from PBMC following co-cultivation with the feline T-lymphoblastoid cell line MYA-1. All amplified env gene products were cloned directly into pGL8MYA. The nucleic acid sequences of seven clones were determined and then compared with those of previously described isolates. The sequences of all of the Brazilian virus clones were distinct and phylogenetic analysis revealed that all belong to subtype B. Three variants isolated from one cat and two variants were isolated from each of the two other cats, indicating that intrahost diversity has the potential to pose problems for the treatment and diagnosis of FIV infection

Bisphenol-S removal via photoelectro-fenton/H2O2 process using Co-porphyrin/Printex L6 gas diffusion electrode

The present work reports the development and application of gas diffusion electrode (GDE) based on carbon Printex L6 modified with 5% Co-Porphyrin/CPL6 for the removal of Bisphenol S (BPS) in wastewater using different electrochemical advanced oxidation processes (EAOPs). The application of the modified GDE led to the in-situ generation of 333 mg L−1 of H2O2 in only 90 min; this represents an increase of 88% in H2O2 generation in relation to the unmodified GDE. The process involving bisphenol S degradation fitted well into a pseudo-first order kinetic reaction for all the treatment techniques evaluated; the treatment techniques investigated recorded an increase in kinetic rate constant in the following order: anodic oxidation (0.004 min−1) < UV-C (0.006 min−1) < H2O2 (0.008 min−1) < H2O2/UV-C (0.016 min−1) < electro-Fenton (0.063 min−1) < photo electro-Fenton (0.154 min−1). The photo electro-Fenton (PEF) process exhibited the best degradation efficiency; BPS was completely removed after only 30 min of treatment and 78% mineralization was recorded after 360 min of treatment. The remaining organic matter under the PEF treatment process corresponded to short-chain carboxylic acids; this confirms the efficiency of the process applied for BPS decontamination. The results obtained show that the proposed treatment mechanism can be successfully combined with cheaper biological treatments for a total remediation of wastes.El presente trabajo reporta el desarrollo y aplicación de un electrodo de difusión de gas (GDE) a base de carbón Printex L6 modificado con 5% de Co-Porfirina/CPL6 para la remoción de Bisfenol S (BPS) en aguas residuales utilizando diferentes procesos electroquímicos de oxidación avanzada (EAOPs). La aplicación del GDE modificado condujo a la generación in situ de 333 mg L −1 de H 2 O 2 en sólo 90 min; esto representa un aumento del 88% en H 2 O 2generación en relación con el GDE no modificado. El proceso de degradación del bisfenol S encajaba bien en una reacción cinética de pseudo primer orden para todas las técnicas de tratamiento evaluadas; las técnicas de tratamiento investigadas registraron un aumento en la constante de velocidad cinética en el siguiente orden: oxidación anódica (0,004 min - 1 ) < UV-C (0,006 min- 1 ) < H 2 O 2 (0,008 min- 1 ) < H 2 O 2 /UV-C (0,016 min −1 ) < electro-Fenton (0,063 min −1 ) < fotoelectro-Fenton (0,154 min −1). El proceso fotoelectro-Fenton (PEF) exhibió la mejor eficiencia de degradación; El BPS se eliminó por completo después de solo 30 minutos de tratamiento y se registró un 78% de mineralización después de 360 ​​minutos de tratamiento. La materia orgánica remanente bajo el proceso de tratamiento con PEF correspondió a ácidos carboxílicos de cadena corta; esto confirma la eficiencia del proceso aplicado para la descontaminación de BPS. Los resultados obtenidos muestran que el mecanismo de tratamiento propuesto puede combinarse con éxito con tratamientos biológicos más económicos para una remediación total de los residuos

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations

WSB1 and IL21R Genetic Variants Are Involved in Th2 Immune Responses to Ascaris lumbricoides.

Genetic and epigenetic factors are considered to be critical for host-parasite interactions. There are limited data on the role of such factors during human infections with Ascaris lumbricoides. Here, we describe the potential role of genetic factors as determinants of the Th2 immune response to A. lumbricoides in Brazilian children. Stool samples were collected from the children to detect A. lumbricoides by microscopy and peripheral blood leukocytes (PBLs) were cultured in whole blood cultures for detection of cytokines (IL-5, IL-10, and IL-13) in vitro. Levels of anti-A. lumbricoides IgE and IgG4 were measured in plasma. DNA was extracted from PBLs and genotyped using Illumina 2.5 Human Omni Beadchip. Candidate genes associated with A. lumbricoides responses were identified and SNVs in these selected genes associated with the Th2 immune response to A. lumbricoides. Haplotype, gene expression, and epigenetic analyses were done to identify potential associations with Th2 immune responses. GWAS on samples from 1,189 children identified WSB1 as a candidate gene, and IL-21R was selected as a biologically relevant linked gene for further analysis. Variants in WSB1 and IL21R were associated with markers of Th2 immune responses: increased A. lumbricoides-specific IgE and IL-5/IL-13 by PBLs from infected compared to uninfected individuals. In infected children, WSB1 but not IL21R gene expression was suppressed and increased methylation was observed in the WSB1 promoter region. This is the first study to show an association between genetic variants in WSB1 and IL21R and Th2 immune responses during A. lumbricoides infections in children. WSB1/IL21R pathways could provide a potential target for the treatment of Th2-mediated diseases