Genetic variation in α1-antichymotrypsin and its association with Alzheimer's disease

Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by extracellular neuritic plaques and intracellular neurofibrillary tangles in brain parenchyma. Alpha-1-antichymotrypsin (ACT) is a component of plaque cores, can bind to Abeta, and has been proposed as a possible candidate gene for AD susceptibility. The genetic association between the ACT codon -17*A allele of the signal peptide polymorphism and AD has been shown in some, but not in all studies. One hypothesis is that the ACT codon -17*A allele is in linkage disequilibrium with unknown functional mutation(s) in the ACT gene. This study was undertaken to identify new mutation(s) in the ACT gene by PCR-SSCP-sequencing and, in conjunction with known mutations, to assess their role in affecting the risk of AD. A total of seven new point mutations were observed: 5'UTR(A-->G), Asp128Asn(G-->A), Ser250Ser(C-->T), Leu301Pro(T-->C), Thr324Thr(A-->G), G-->A in intron 4, and 3'UTR C-->A. Of these, mutations at codon 250, codon 324, intron 4 and 3'UTR showed a frequency of 1% or more. Of the known mutations, Thr-17Ala(A-->G), Lys76Lys(A-->G) and Leu241Leu(G-->A) occur at a polymorphic level. The ACT codon -17*A allele was associated with increased risk of AD (OR for AA vs TT: 1.71; 95% CI: 1.16-2.53; P=0.007), especially in the presence of the APOE*4 allele (OR for AA vs TT: 2.35; 95% CI: 1.13-4.85; P=0.02). The codon 241*A allele and the codon 250*T allele were associated with protective effects against AD (OR: 0.36; 95% CI: 0.13-0.86; P=0.02) (OR:0.39; 95% CI: 0.18-0.85; P=0.02). irrespective of the APOE*4 status. The codon 324*G allele was associated with a marginal protective effect (OR:0.57; 95% CI: 0.26-1.26; P=0.17). While the codon 241*A allele was in linkage disequilibrium with the codon -17*A allele, the codon 250*T and codon 324*G alleles were non-randomly associated with the codon -17*T allele. In contrast, the codon 76*G (OR:1.34; 95% CI: 0.92-1.95; P=0.13), codon 227*G (OR:3.96; 95% CI: 0.83-18.8; P=0.08) and intron 4*G (OR:1.47; 95% CI: 0.88-2.29; P=0.15) alleles were associated with a modest risk of AD, and all were in linkage disequilibrium with the codon -17*A allele. EH-based haplotype analysis showed that certain haplotypes are associated with either higher or lower risk of AD. Our data indicate that the ACT gene harbors several potentially important variable sites, which are associated with either an increased or decreased risk of AD. The non-random combination of risk and protective alleles may explain, in part, why the association studies regarding the ACT codon -17*A have been inconsistent, especially if the frequency of other ACT mutations varies between populations.     

Review on global change status and its impacts on the Tibetan Plateau environment

The Tibetan Plateau (TP) holds fundamental ecological and environmental significances to China and Asia. The TP also lies in the core zone of the belt and road initiative. To protect the TP environment, a comprehensive screening on current ecological research status is entailed. The teased out research gap can also be utilized as guidelines for the recently launched major research programs, i.e. the second TP scientific expedition and silk and belt road research plan. The findings showed that the TP has experienced significant temperature increase at a rate of 0.2°C per decade since 1960s. The most robust warming trend was found in the northern plateau. Precipitation also exhibited an increasing trend but with high spatial heterogeneity. Changing climates have caused a series of environmental consequences, including lake area changes, glacier shrinkage, permafrost degradation and exacerbated desertification. The rising temperature is the main reason behind the glaciers shrinkage, snow melting, permafrost degradation and lake area changes on the TP and neighboring regions. The projected loss of glacial area on the plateau is estimated to be around 43% by 2070 and 75% by the end of the century. Vegetation was responsive to the changed environments, varied climates and intensified human activities by changing phenology and productivity. Future global change study should be more oriented toward integrating various research methods and tools, and synthesizing diverse subjects of water, vegetation, atmosphere and soil.     

Ethnobotanical and ecological assessment of plant resources at District Dir,Tehsil Timergara,Khyber Pakhtunkhwa,Pakistan

Background

Ethnobotanical and ecological study of plants is very important in understanding the culture of a society and it provides a base for further study on scientific lines. This paper, the use of medicinal plants and their role in the treatment of different diseases have been duly observed and noted in Tehsil Timergara.

Whole genome sequencing of an ethnic Pathan (Pakhtun) from the north-west of Pakistan

Background

Pakistan covers a key geographic area in human history, being both part of the Indus River region that acted as one of the cradles of civilization and as a link between Western Eurasia and Eastern Asia. This region is inhabited by a number of distinct ethnic groups, the largest being the Punjabi, Pathan (Pakhtuns), Sindhi, and Baloch.

Results

We analyzed the first ethnic male Pathan genome by sequencing it to 29.7-fold coverage using the Illumina HiSeq2000 platform. A total of 3.8 million single nucleotide variations (SNVs) and 0.5 million small indels were identified by comparing with the human reference genome. Among the SNVs, 129,441 were novel, and 10,315 nonsynonymous SNVs were found in 5,344 genes. SNVs were annotated for health consequences and high risk diseases, as well as possible influences on drug efficacy. We confirmed that the Pathan genome presented here is representative of this ethnic group by comparing it to a panel of Central Asians from the HGDP-CEPH panels typed for ~650 k SNPs. The mtDNA (H2) and Y haplogroup (L1) of this individual were also typical of his geographic region of origin. Finally, we reconstruct the demographic history by PSMC, which highlights a recent increase in effective population size compatible with admixture between European and Asian lineages expected in this geographic region.

Conclusions

We present a whole-genome sequence and analyses of an ethnic Pathan from the north-west province of Pakistan. It is a useful resource to understand genetic variation and human migration across the whole Asian continent.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1290-1) contains supplementary material, which is available to authorized users.     

The change of blood Pb levels of basketball players after strenuous exercise

This study is related to the investigation of the Pb levels in blood of the 12 healthy University male basketball players before and after a strenuous training session by the use of square wave anodic stripping voltammetry. Although the results do not show acute lead intoxication it is obvious that blood lead levels show significant increase after training sessions. The average increase in blood lead levels is 297%. This increase is largely due to increased respiration rate during the training period.     

RNA challenges for computational chemists

Some experimental results for the thermodynamics of RNA folding cannot be explained by simple pairwise hydrogen-bonding models. Such effects include the stabilities of isoguanosine-isocytidine (iG-iC) base pairs and of various 2 x 2 nucleotide internal loops. Presumably, these results can be explained by base stacking effects, which can be partitioned into Coulombic and overlap effects. We review experimental measurements that provide benchmarks for testing the approximations and theories used for modeling nucleic acids. Quantitative agreement between experiment and theory will indicate understanding of the interactions determining RNA stability and structure.     

The impact of factor XIIIa V34L polymorphism on plasma factor XIII activity in the Chinese and Asian Indians from Singapore

Factor XIII (FXIII) is a plasma transglutaminase that is essential for normal haemostasis and fibrinolysis. A few polymorphic sites have been identified in the gene, one of them being a point mutation (V34L) in exon 2 of the FXIIIa subunit gene leading to an amino acid change of valine to leucine. We have examined the role of this polymorphism in relation to plasma FXIII activity in a total of 532 healthy individuals belonging to two ethnic groups in Singapore. The frequency of the L34 allele was significantly higher (P<0.001) among the Asian Indians (0.08) when compared with the Chinese (0.005). No significant difference in frequency of the L34 allele was observed between Asian Indian CAD patients and controls. The mean FXIII levels were significantly higher (P<0.0005) among the Asian Indians (148.4%±35.5) when compared with Chinese (111.2%±26.7). The L34 variant was associated with increased FXIII activity among Asian Indian females. This study shows that both racial and genetic components play a significant role in determining plasma FXIII activity. The effect of V34L polymorphism on FXIII activity in the Indian females is independent of the effects of the P564L and E651Q polymorphic sites in the FXIIIa gene.C.-K. Heng and S. Lal contributed equally to this work     

Impact of rapid urbanization on the floral diversity and agriculture land of district Dir,Pakistan

In the World urbanization is a serious problem especially in developing countries which creates serious environmental problems like climatic and ecological changes in the ecosystem. The present paper aims to explain urbanization that causes loss of agriculture lands, biodiversity, soil erosions and grazing in District Dir. Urbanization decreased species richness such as Salix alba and Populus alba in the last few years in the local area. Soil of local area was divided into three different zones and was tested for soil texture and mineral percentage. Zone I soil showed sandy loamy texture with a pH of 8.3, Nitrogen 0.012%, Phosphorus 5.0% and organic matter was 0.74 (ppm). Zone II soil was loamy sand in texture with pH 8.1, Nitrogen 0.011%, Phosphorus 6.2%, and organic matter was 0.24 (ppm) while Zone III soil texture was silty clay loam with a pH of 8.1, Nitrogen 0.032%, Phosphorus 11.3%, and organic matter was 0.60 (ppm). The current work concludes that urbanizations affect natural biodiversity and agriculture lands, and that soil erosion and watering-points trampled by livestock is one of the significant problems in district Dir, and that the main degrading factor is the overexploitation of vegetation for fuel-wood and livestock grazing.