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111.
Genetic variation in α1-antichymotrypsin and its association with Alzheimer's disease 总被引:4,自引:0,他引:4
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. 相似文献
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113.
Aamir Latif Sana Ilyas Yangjian Zhang Yuqin Xin Lin Zhou Quan Zhou 《Journal of Plant Ecology》2019,12(6):917
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. 相似文献
114.
Muhammad Shuaib Sajjad Ahmed Kashif Ali Muhammad Ilyas Firasat Hussain Zara Urooj Syed Sadaqat Shah Tanweer Kumar Muzammil Shah Ikramullah Khan Fida Hussain 《农业工程》2019,39(1):109-115
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.Methods
The survey was carried out from September 2014 to October 2016. During this survey, a total of 16 trips with 4 in each season were carried out to collect data. A total of 115 respondents were interviewed through questionnaires regarding the available medicinal plants; most of the respondents were 65 to 80?years old. The obtained ethnobotanical data was then analyzed by Frequency Citation (FC), Relative Frequency Citation index (RFC), and Use Value index (UV) to find the most common plants species used for various diseases.Results
The local community of the study area, 59 plant species belonging to 39 genera, 28 families for different medicinal purposes. During the survey 38 species were herbs, 6 shrubs, and 15 trees. Leaf and whole plants were most frequently used parts in making of medicine while 30% of the whole plant was used in the ethnobotanical uses. A total of 46 plants showed important value in the ethnomedicinal purpose, in which the highest number of species (11) were used for chest problem particularly in a cough, as laxatives (4) and in asthma (5 species), 14 species were used as fuel which is also an important feature of the plants. Soil analysis of five collection area is studied.Conclusion
The current result of RFC and UV shows that medicinal flora needs to be pharmacologically and phytochemically investigated to prove their efficacy. The documentation of medicinal knowledge is important to preserve this precious old knowledge before it is lost forever, due to technological and environmental changes in the world. 相似文献115.
Muhammad Ilyas Jong-Soo Kim Jesse Cooper Young-Ah Shin Hak-Min Kim Yun Sung Cho Seungwoo Hwang Hyunho Kim Jaewoo Moon Oksung Chung JeHoon Jun Achal Rastogi Sanghoon Song Junsu Ko Andrea Manica Ziaur Rahman Tayyab Husnain Jong Bhak 《BMC genomics》2015,16(1)
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. 相似文献116.
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. 相似文献
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118.
Manuel A. Castro Kristine F. Parson Ilyas Beg Mason C. Wilkinson Kamila Nurmakova Iliana Levesque Markus W. Voehler Michael S. Wolfe Brandon T. Ruotolo Charles R. Sanders 《The Journal of biological chemistry》2022,298(4)
This work reports substrate-selective inhibition of a protease with broad substrate specificity based on direct binding of a small-molecule inhibitor to the substrate. The target for these studies was γ-secretase protease, which cleaves dozens of different single-span membrane protein substrates, including both the C99 domain of the human amyloid precursor protein and the Notch receptor. Substrate-specific inhibition of C99 cleavage is desirable to reduce production of the amyloid-β polypeptide without inhibiting Notch cleavage, a major source of toxicity associated with broad specificity γ-secretase inhibitors. In order to identify a C99-selective inhibitors of the human γ-secretase, we conducted an NMR-based screen of FDA-approved drugs against C99 in model membranes. From this screen, we identified the small-molecule verteporfin with these properties. We observed that verteporfin formed a direct 1:1 complex with C99, with a KD of 15–47 μM (depending on the membrane mimetic used), and that it did not bind the transmembrane domain of the Notch-1 receptor. Biochemical assays showed that direct binding of verteporfin to C99 inhibits γ-secretase cleavage of C99 with IC50 values in the range of 15–164 μM, while Notch-1 cleavage was inhibited only at higher concentrations, and likely via a mechanism that does not involve binding to Notch-1. This work documents a robust NMR-based approach to discovery of small-molecule binders to single-span membrane proteins and confirmed that it is possible to inhibit γ-secretase in a substrate-specific manner. 相似文献
119.
Ilyas Potamitis 《PloS one》2014,9(5)
There is a rich literature on automatic species identification of a specific target taxon as regards various vocalizing animals. Research usually is restricted to specific species – in most cases a single one. It is only very recently that the number of monitored species has started to increase for certain habitats involving birds. Automatic acoustic monitoring has not yet been proven to be generic enough to scale to other taxa and habitats than the ones described in the original research. Although attracting much attention, the acoustic monitoring procedure is neither well established yet nor universally adopted as a biodiversity monitoring tool. Recently, the multi-instance multi-label framework on bird vocalizations has been introduced to face the obstacle of simultaneously vocalizing birds of different species. We build on this framework to integrate novel, image-based heterogeneous features designed to capture different aspects of the spectrum. We applied our approach to a taxon-rich habitat that included 78 birds, 8 insect species and 1 amphibian. This dataset constituted the Multi-label Bird Species Classification Challenge-NIPS 2013 where the proposed approach achieved an average accuracy of 91.25% on unseen data. 相似文献
120.
Zoumpoulakis P Camoutsis Ch Pairas G Soković M Glamočlija J Potamitis C Pitsas A 《Bioorganic & medicinal chemistry》2012,20(4):1569-1583