Deficits of cortical nicotinic acetylcholine receptors (nAChRs) have been observed in Alzheimer's disease (AD) by receptor binding assays. Little is known about the receptor subunit specificity influenced by AD, and it might be of importance for therapeutic strategies. In the present study, the protein levels of nAChR ␣3, ␣4, ␣7, and ␤2 subunits were investigated using western blot analysis on postmortem brains of patients with AD and age-matched controls. The results showed that in human postmortem brain samples, bands with molecular masses of 52, 42, and 50 kDa were detected by anti-␣4, anti-␣7, and anti-␤2 antibodies, respectively. When anti-␣3 antibody was used, one major band of 49 kDa and two minor bands of 70 and 38 kDa were detected. In AD patients, as compared with age-matched controls, the ␣4 subunit was reduced significantly by ϳ35 and 47% in the hippocampus and temporal cortex, respectively. A significant reduction of 25% in the ␣3 subunit was also observed in the hippocampus and a 29% reduction in the temporal cortex. For the ␣7 subunit, the protein level was reduced significantly by 36% in the hippocampus of AD patients, but no significant change was detected in the temporal cortex. In neither the hippocampus nor the temporal cortex was a significant difference observed in the ␤2 subunit between AD patients and controls. These results reveal brain region-specific changes in the protein levels of the nAChR ␣3, ␣4, and ␣7 subunits in AD. Key Words: Alzheimer's disease-Neuronal nicotinic acetylcholine receptor-Postmortem brain-Western blot.

Yak domestication represents an important episode in the early human occupation of the high-altitude Qinghai-Tibet Plateau (QTP). The precise timing of domestication is debated and little is known about the underlying genetic changes that occurred during the process. Here we investigate genome variation of wild and domestic yaks. We detect signals of selection in 209 genes of domestic yaks, several of which relate to behaviour and tameness. We date yak domestication to 7,300 years before present (yr BP), most likely by nomadic people, and an estimated sixfold increase in yak population size by 3,600 yr BP. These dates coincide with two early human population expansions on the QTP during the early-Neolithic age and the late-Holocene, respectively. Our findings add to an understanding of yak domestication and its importance in the early human occupation of the QTP.

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BackgroundCopy number variation (CNV) represents an important source of genetic divergence that can produce drastic phenotypic differences and may therefore be subject to selection during domestication and environmental adaptation. To investigate the evolutionary dynamics of CNV in the yak genome, we used a read depth approach to detect CNV based on genome resequencing data from 14 wild and 65 domestic yaks and determined CNV regions related to domestication and adaptations to high-altitude.ResultsWe identified 2,634 CNV regions (CNVRs) comprising a total of 153 megabases (5.7 % of the yak genome) and 3,879 overlapping annotated genes. Comparison between domestic and wild yak populations identified 121 potentially selected CNVRs, harboring genes related to neuronal development, reproduction, nutrition and energy metabolism. In addition, we found 85 CNVRs that are significantly different between domestic yak living in high- and low-altitude areas, including three genes related to hypoxia response and six related to immune defense. This analysis shows that genic CNVs may play an important role in phenotypic changes during yak domestication and adaptation to life at high-altitude.ConclusionsWe present the first refined CNV map for yak along with comprehensive genomic analysis of yak CNV. Our results provide new insights into the genetic basis of yak domestication and adaptation to living in a high-altitude environment, as well as a valuable genetic resource that will facilitate future CNV association studies of important traits in yak and other bovid species.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2702-6) contains supplementary material, which is available to authorized users.

BackgroundOrganisms living at high altitudes must overcome three major environmental challenges: hypoxia, cold, and intense UV radiation. The molecular mechanisms that enable these challenges to be overcome have mainly been studied in endothermic organisms; relatively little attention has been paid to poikilothermic species. Here, we present deep transcriptome sequencing in two closely related lizards, the high altitude-dwelling Phrynocephalus erythrurus and the lowland-dwelling P. putjatia, to identify candidate genes under positive selection and to explore the convergent evolutionary adaptation of poikilothermic animals to high altitude life.ResultsMore than 70 million sequence reads were generated for each species via Illumina sequencing. De novo assembly produced 56,845 and 63,140 transcripts for P. erythrurus and P. putjatia, respectively. P. erythrurus had higher Ka/Ks ratios than P. putjatia, implying an accelerated evolutionary rate in the high altitude lizard lineage. 206 gene ontology (GO) categories with accelerated evolutionary rates and 43 candidate positively selected genes were detected along the P. erythrurus lineage. Some of these GO categories have functions associated with responses to hypoxia, energy metabolism and responses to UV damage. We also found that the high-altitude ranid frog R. kukunoris had higher Ka/Ks ratios than the closely related low-altitude frog R. chensinensis, and that the functional categories with accelerated evolutionary rates in R. kukunoris overlapped extensively with those detected along the P. erythrurus lineage.ConclusionsThe mechanisms of high altitude adaptation in P. erythrurus were tentatively inferred. By comparing two pairs of low- and high-altitude poikilothermic species, we found that similar functional categories had undergone positive selection in high altitude-dwelling Phrynocephalus and Rana lineages, indicating that similar mechanisms of adaptation to high altitude might have evolved in both genera. Our findings provide important guidance for future functional studies on high altitude adaptation in poikilothermic animals.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-015-0371-8) contains supplementary material, which is available to authorized users.

Abstract:We investigated the effects of RNA interference-mediated silencing of the c-myc gene on celluar proliferation and apoptosis in human colon cancer HT-29 cells in vitro and in vivo. A small interfering RNA (siRNA) targeting c-myc was designed, the DNA template was synthesized, and the siRNA was obtained by in vitro transcription. After siRNA transfection into HT-29 and human neuroblastoma IMR-32 cells with Lipofectamine 2000 TM , the proliferation of the HT-29 and IMR-32 cells was assessed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) colorimetry, and Hoechst 33258 staining was used to observe cell apoptosis. Following gene transfer to HT-29 cells, the expression of c-myc mRNA was examined via reverse transcription polymerase chain reaction, and the level of the protein via Western blot assay. Growth curves were constructed and in vivo experiments were performed on nude mice to assess the effects of c-myc silencing on tumor growth. The c-myc expression in the tumor tissue was measured by reverse transcription polymerase chain reaction and subsequently by immunohistochemistry. Our paper demonstrates that the delivery of siRNA directed against c-myc not only efficiently down-regulated the expression of c-myc, inhibited the proliferation of HT-29 cells and induced apoptosis in vitro, but also suppressed the growth of colon cancer cells in vivo.

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