GABRB2 Haplotype Association with Heroin Dependence in Chinese Population

Substance dependence is a frequently observed comorbid disorder in schizophrenia, but little is known about genetic factors possibly shared between the two psychotic disorders. GABRB2, a schizophrenia candidate gene coding for GABA_A receptor β₂ subunit, is examined for possible association with heroin dependence in Han Chinese population. Four single nucleotide polymorphisms (SNPs) in GABRB2, namely rs6556547 (S1), rs1816071 (S3), rs18016072 (S5), and rs187269 (S29), previously associated with schizophrenia, were examined for their association with heroin dependence. Two additional SNPs, rs10051667 (S31) and rs967771 (S32), previously associated with alcohol dependence and bipolar disorder respectively, were also analyzed. The six SNPs were genotyped by direct sequencing of PCR amplicons of target regions for 564 heroin dependent individuals and 498 controls of Han Chinese origin. Interestingly, it was found that recombination between the haplotypes of all-derived-allele (H1; OR = 1.00) and all-ancestral-allele (H2; OR = 0.74) at S5-S29 junction generated two recombinants H3 (OR = 8.51) and H4 (OR = 5.58), both conferring high susceptibility to heroin dependence. Additional recombination between H2 and H3 haplotypes at S1-S3 junction resulted in a risk-conferring haplotype H5 (OR = 1.94x10⁹). In contrast, recombination between H1 and H2 haplotypes at S3-S5 junction rescued the risk-conferring effect of recombination at S5-S29 junction, giving rise to the protective haplotype H6 (OR = 0.68). Risk-conferring effects of S1-S3 and S5-S29 crossovers and protective effects of S3-S5 crossover were seen in both pure heroin dependent and multiple substance dependence subgroups. In conclusion, significant association was found with haplotypes of the S1-S29 segment in GABRB2 for heroin dependence in Han Chinese population. Local recombination was an important determining factor for switching haplotypes between risk-conferring and protective statuses. The present study provide evidence for the schizophrenia candidate gene GABRB2 to play a role in heroin dependence, but replication of these findings is required.     

Kidney Function,Endothelial Activation and Atherosclerosis in Black and White Africans with Rheumatoid Arthritis

Objective

To determine whether kidney function independently relates to endothelial activation and ultrasound determined carotid atherosclerosis in black and white Africans with rheumatoid arthritis (RA).

Methods

We calculated the Jelliffe, 5 Cockcroft-Gault equations, Salazar-Corcoran, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (EGFR) equations in 233 (112 black) RA patients.

Results

The CKD-EPI eGFR was <90 ml/min/1.73m² in 49.1% and 30.6% of black and white patients, respectively (odds ratio (95% confidence interval) = 2.19 (1.28–3.75), p = 0.004). EGFRs were overall consistently associated with monocyte chemoattractant protein-1 and angiopoietin 2 concentrations in white patients, and with carotid intima-media thickness and plaque in black participants. Amongst black patients, plaque prevalence was 36.7% and the area under the curve (AUC) of the receiver operating characteristic (ROC) curve was not associated with plaque presence for the MDRD equation (p = 0.3), whereas the respective relationship was significant or borderline significant (p = 0.003 to 0.08) and of similar extent (p>0.1 for comparisons of AUC (SE)) for the other 8 equations. Based on optimal eGFR cutoff values with sensitivities and specificities ranging from 42 to 60% and 70 to 91% respectively, as determined in ROC curve analysis, a low eGFR increased the odds ratio for plaque 2.2 to 4.0 fold.

Conclusion

Reduced kidney function is independently associated with atherosclerosis and endothelial activation in black and white Africans with RA, respectively. CKD is highly prevalent in black Africans with RA. Apart from the MDRD, eGFR equations are useful in predicting carotid plaque presence, a coronary heart disease equivalent, amongst black African RA patients.     

Switching from bone marrow-derived neurons to epithelial cells through dedifferentiation and translineage redifferentiation

While the ability of stem cells to switch lineages has been suggested, the route(s) through which this may happen is unclear. To date, the best characterized adult stem cell population considered to possess transdifferentiation capacity is BM-MSCs (bone marrow mesenchymal stem cells). We investigated whether BM-MSCs that had terminally differentiated into the neural or epithelial lineage could be induced to transdifferentiate into the other phenotype in vitro. Our results reveal that neuronal phenotypic cells derived from adult rat bone marrow cells can be switched to epithelial phenotypic cells, or vice versa, by culture manipulation allowing the differentiated cells to go through, first, dedifferentiation and then redifferentiation to another phenotype. Direct transdifferentiation from differentiated neuronal or epithelial phenotype to the other differentiated phenotype cannot be observed even when appropriate culture conditions are provided. Thus, dedifferentiation appears to be a prerequisite for changing fate and differentiating into a different lineage from a differentiated cell population.     

Epigallocatechin gallate up-regulation of miR-16 and induction of apoptosis in human cancer cells

Epigallocatechin gallate (EGCG) is a major type of green tea polyphenols and is known to have cancer prevention effect. MicroRNAs (miRNAs) are 19 to 25 nucleotides and are believed to be important in gene regulation. In the present study, the influence of EGCG on the expressions of miRNAs in human cancer cells was investigated as this has not yet been reported. By miRNA microarray analysis, EGCG treatment was found to modify the expressions of some of the miRNAs in human hepatocellular carcinoma HepG2 cells, 13 were up-regulated and 48 were down-regulated. miR-16 is one of the miRNAs up-regulated by EGCG and one of its target genes is confirmed to be the anti-apoptotic protein Bcl-2. EGCG treatment induced apoptosis and down-regulated Bcl-2 in HepG2 cells. Transfection with anti-miR-16 inhibitor suppressed miR-16 expression and counteracted the EGCG effects on Bcl-2 down-regulation and also induction of apoptosis in cells. Results from the present study confirm the role of miR-16 in mediating the apoptotic effect of EGCG and also support the importance of miRNAs in the regulation of the biological activity of EGCG.     

Microsatellite primers for Halophila ovalis and cross-amplification in H. minor (Hydrocharitaceae)

?Premise of the study: Polymorphic microsatellite primers were developed in the seagrass Halophila ovalis to investigate genetic variation. ?Methods and Results: Ten polymorphic microsatellite loci were developed in Halophila ovalis. The number of alleles per locus ranged from 2 to 12 across 80 H. ovalis individuals. These loci were successfully amplified in H. minor, and four were monomorphic across 30 individuals. ?Conclusions: These results from four H. ovalis populations and one H. minor population show the broad utility of microsatellite loci in future studies of population genetics. Four distinct alleles were present in H. minor but absent in H. ovalis, indicating potential divergence between them.     

Cryopreservation of mammalian embryos: Advancement of putting life on hold

Rodent transgenesis and human‐assisted reproductive programs involve multistep handling of preimplantation embryos. The efficacy of production and quality of results from conventionally scheduled programs are limited by temporal constraints other than the quality and quantities of embryos per se. The emergence of vitrification, a water ice‐free cryopreservation technique, as a reliable way to arrest further growth of preimplantation embryos, provides an option to eliminate the time constraint. In this article, current and potential applications of cryopreservation to facilitate laboratory animal experiments, colony management, and human‐assisted reproductive programs are reviewed. Carrier devices developed for vitrification in the last two decades are compared with an emphasis on their physical properties that infer cooling rate of samples and sterility assurance. Biological impacts of improved cryopreservation on preimplantation embryos are also discussed. Birth Defects Research (Part C) 90:163–175, 2010. © 2010 Wiley‐Liss, Inc.     

Establishment and characterization of a cell line from embryos of the Indianmeal moth,Plodia interpunctella

A cell line, UMN-PIE-1181, initiated in November, 1981, from embryos of a malathion-resistant strain of Indianmeal moth, Plodia interpunctella, was in the 83rd passage on January 28, 1985. The line consists of single, small, fibroblastlike cells that are polyploid with chromosome numbers ranging from 56 to 180. Growth rate is dependent on seeding density, there being no growth at or below seeding densities of $\text{2 ×}\text{10}{}^5\text{5}\text{,}\text{ml}$; optimum growth requires a fetal bovine serum concentration of at least 5%. Twenty-nine isozymes were examined. Five enzymes from the cell lines resolved well and subsequently were compared to enzymes extracted from 4-day-old embryos and other life stages of the insects. Phosphomannose isomerase, malic enzyme, malate dehydrogenase, phosphoglucose isomerase, and glucose-6-phosphate dehydrogenase in extracts from the cultured cells and from the insects had identical patterns. Two bands for glutamate-oxalacetate transaminase, present in the cell line, were not observed in the tissue extracts. Furthermore, lactate dehydrogenase from the cultured cells appeared as four bands but was not detectable in any of the samples run from the various life stages of the insects.