Gender-specific association of MSA2756G with hypertension in patients attending a health facility in Ningxia Province, China

Purpose: To investigate the distribution of methionine synthase A2756G (MSA2756G) in the hypertensive patients in northwest Chinese population.Methods: A total of 378 unrelated hypertensive patients attending Ningxia Peoples Hospital, Ningxia Province, China, were recruited for this study. We analyzed genotype by amplication - created restriction sites (ACRS) and polymerase chain reaction - restrict fragment length polymorphism (PCR - RFLP) in hypertensive patients, and inspected the relation of the genotype with hypertension by χ2 and t test.Results: The frequency of G allele was 10.25 % in the control group and 14.04 % in hypertension group; it was not statistically different (p > 0.05). In the male group, the frequency of allele G was 11.50 % in control group, and 8.79 % in hypertension group. There was no significant difference between control and hypertension groups (p > 0.05). In the female group, the frequency of allele G was 9.00 %, in control and 19.54 % in hypertension group (p < 0.05), while in the hypertension group, allele G was 8.79 % in males which is significantly lower (p < 0.05) than in females (19.54 %) .Conclusion: Allele G of MSA2756G is a risk factor for hypertension in female in this Chinese population of this study.Keywords: Hypertension, Methionine synthase, Polymorphism, Gender, Amplification-created restriction sites, Allele G, MSA2756

Tyrosine phosphorylation of HPK1 by activated Src promotes ischemic brain injury in rat hippocampal CA1 region

AbstractHematopoietic progenitor kinase 1 (HPK1) is a hematopoietic cell-restricted member of the Ste20 serine/threonine kinase super family. We recently reported that HPK1 is involved in c-Jun NH2-terminal kinase (JNK) signaling pathway by sequential activation of MLK3–MKK7–JNK3 after cerebral ischemia. Here, we used 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo [3,4-d] pyrimidine (PP2) and MK801 to investigate the events upstream of HPK1 in ischemic brain injury. Immunoprecipitation and immunoblot results showed that PP2 and MK801 significantly decreased the activation of Src, HPK1, MLK3, JNK3 and c-Jun, respectively, during ischemia/reperfusion. Histology and TUNEL staining showed PP2 or MK801 protects against neuron death after brain ischemia. We speculate that this unique signaling pathway through the tyrosine phosphorylation of HPK1 promotes ischemic brain injury by activated Src via N-methyl-d-aspartate receptor and, ultimately, the activation of the MLK3–MKK7–JNK3 pathway after cerebral ischemia

Analysis of the EGFR gene mutation in patients with nonsmall cell lung cancer in a Chinese population

Purpose: To investigate the epidermal growth factor receptor (EGFR) gene mutations and analyze their clinical significance in patients with non-small cell lung cancer (NSCLC) in Hubei province of China.Methods: A total of 138 paraffin embedded tissues were taken from patients with NSCLC who were treated at Hubei Hospital from January 2014 to June 2015. The tissue DNA was extracted and EGFR mutation was evaluated by polymerase chain reaction (PCR) sequencing analysis of exons 18, 19, 20, and 21.Results: The overall mutation rate of EGFR gene was 30.43 % (42/138) in 138 NSCLC patients. The mutation rates of EGFR gene at exon 18, 19, 20, 21 were 0 %（0/138), 13.8 %（19/138), 0.7 % (1/138) and 15.9 % (22/138), respectively. The mutation rate of EGFR gene was higher in female patients than that in males (62.2 % (28/45) vs 15.1 % (14/93), p < 0.01), and higher in non-smoking patients than in smoking ones (p < 0.05), but had no correlation with age in NSCLC patients (p > 0.05). EGFR mutation frequency in adenocarcinoma was higher than that in squamous cell carcinoma: 33.9 % (41/121) vs. 5.9 % (1/17, p < 0.05).Conclusion: EGFR mutations in NSCLC patients mainly exist in exons 19 and 21, and the mutation rate of exon 21 is higher than that of exon 19, which is more commonly found in female, adenocarcinoma and non-smoking patients.Keywords: Non-small cell lung cancer, Epidermal growth factor receptor (EGFR), Targeted therapy, Sequencin

Shearing and Mixing Performance of Ultrahigh-Molecular-Weight Hydrolyzed Polyacrylamide (HPAM) Solution in a Helixes Static Mixer

Static mixers have been widely used to dilute high viscosity, high-molecular-weight polymer mother liquor for polymer flooding, in which the mixing performance plays a critical role. In this work, a novel mixing configuration, named as Helixes static mixer, was proposed to reduce high viscosity degradation rate of polyacrylamide solution resulting from mechanical shear during mixing process. Computational fluid dynamics simulations along with experiments were performed to investigate the mixing process. Several criteria such as the intensity of segregation, mixing distance, pressure loss, and shear strain rate were used to evaluate the mixing and shear performance of static mixers. Compared to the SMX and Kenics static mixer, a longer mixing distance is needed for the Helixes static mixer to achieve an ideal mixture. A lower shear strain rate along with less viscosity degradation rate is obtained in flow field of Helixes static mixer. The spiral-lead and helical directions of mixing elements were optimized to improve mixing performance. Experimental results are in good agreement with the numerical simulations on the intensity of segregation. The viscosity degradation rate of HPAM solution which flows through Helixes static mixer is lower than that of SMX and Kenics static mixers

The neutral theory and natural selection in the HLA region

Based on available DNA sequence data in the HLA region of 4 Mb, we review the degree of polymorphism at 39 loci of which most are involved in the immune system. The extent of nucleotide differences per silent site differs greatly from locus to locus. It is exceptionally high at classical MHC loci, intermediate at six MHC-related pseudogenes as well as at some loci in class I and II regions, and low in the class III region. Different exons of individual MHC loci show also different degrees of silent polymorphism; high in the exons encoding for the peptide binding region (PBR) and low in the exons encoding for trans-membranes and cytoplasmic tails. The degree of polymorphism within MHC allelic lineages is not much smaller than that between allelic lineages, contrary to the expectation where intra-allelic sequence exchanges are restricted. The observation that many allelic lineages at the HLA-DRB1 locus are combinations of distinct motifs in the beta pleated sheet and alpha helix of PBR indicates that sequence exchanges occur even within exon 2. Semi-quantitative analysis is presented about the rate of sequence exchanges between selected and linked neutral regions, although more sequence information is necessary to make definite conclusions. The extraordinary MHC polymorphism is viewed from the dual function of MHC molecules that controls the acquired immune system

Application of a rank-based genetic association test to age-at-onset data from the Collaborative Study on the Genetics of Alcoholism study

Association studies of quantitative traits have often relied on methods in which a normal distribution of the trait is assumed. However, quantitative phenotypes from complex human diseases are often censored, highly skewed, or contaminated with outlying values. We recently developed a rank-based association method that takes into account censoring and makes no distributional assumptions about the trait. In this study, we applied our new method to age-at-onset data on ALDX1 and ALDX2. Both traits are highly skewed (skewness > 1.9) and often censored. We performed a whole genome association study of age at onset of the ALDX1 trait using Illumina single-nucleotide polymorphisms. Only slightly more than 5% of markers were significant. However, we identified two regions on chromosomes 14 and 15, which each have at least four significant markers clustering together. These two regions may harbor genes that regulate age at onset of ALDX1 and ALDX2. Future fine mapping of these two regions with densely spaced markers is warranted

mGluR5 antagonism inhibits cocaine reinforcement and relapse by elevation of extracellular glutamate in the nucleus accumbens via a CB1 receptor mechanism.

Metabotropic glutamate receptor 5 (mGluR5) antagonism inhibits cocaine self-administration and reinstatement of drug-seeking behavior. However, the cellular and molecular mechanisms underlying this action are poorly understood. Here we report a presynaptic glutamate/cannabinoid mechanism that may underlie this action. Systemic or intra-nucleus accumbens (NAc) administration of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) dose-dependently reduced cocaine (and sucrose) self-administration and cocaine-induced reinstatement of drug-seeking behavior. The reduction in cocaine-taking and cocaine-seeking was associated with a reduction in cocaine-enhanced extracellular glutamate, but not cocaine-enhanced extracellular dopamine (DA) in the NAc. MPEP alone, when administered systemically or locally into the NAc, elevated extracellular glutamate, but not DA. Similarly, the cannabinoid CB1 receptor antagonist, rimonabant, elevated NAc glutamate, not DA. mGluR5s were found mainly in striatal medium-spiny neurons, not in astrocytes, and MPEP-enhanced extracellular glutamate was blocked by a NAc CB1 receptor antagonist or N-type Ca++ channel blocker, suggesting that a retrograde endocannabinoid-signaling mechanism underlies MPEP-induced glutamate release. This interpretation was further supported by our findings that genetic deletion of CB1 receptors in CB1-knockout mice blocked both MPEP-enhanced extracellular glutamate and MPEP-induced reductions in cocaine self-administration. Together, these results indicate that the therapeutic anti-cocaine effects of mGluR5 antagonists are mediated by elevation of extracellular glutamate in the NAc via an endocannabinoid-CB1 receptor disinhibition mechanism