Development of maizeSNP3072, a high-throughput compatible SNP array, for DNA fingerprinting identification of Chinese maize varieties.

Science.gov (United States)

Tian, Hong-Li; Wang, Feng-Ge; Zhao, Jiu-Ran; Yi, Hong-Mei; Wang, Lu; Wang, Rui; Yang, Yang; Song, Wei

2015-01-01

Single nucleotide polymorphisms (SNPs) are abundant and evenly distributed throughout the maize ( Zea mays L.) genome. SNPs have several advantages over simple sequence repeats, such as ease of data comparison and integration, high-throughput processing of loci, and identification of associated phenotypes. SNPs are thus ideal for DNA fingerprinting, genetic diversity analysis, and marker-assisted breeding. Here, we developed a high-throughput and compatible SNP array, maizeSNP3072, containing 3072 SNPs developed from the maizeSNP50 array. To improve genotyping efficiency, a high-quality cluster file, maizeSNP3072_GT.egt, was constructed. All 3072 SNP loci were localized within different genes, where they were distributed in exons (43 %), promoters (21 %), 3' untranslated regions (UTRs; 22 %), 5' UTRs (9 %), and introns (5 %). The average genotyping failure rate using these SNPs was only 6 %, or 3 % using the cluster file to call genotypes. The genotype consistency of repeat sample analysis on Illumina GoldenGate versus Infinium platforms exceeded 96.4 %. The minor allele frequency (MAF) of the SNPs averaged 0.37 based on data from 309 inbred lines. The 3072 SNPs were highly effective for distinguishing among 276 examined hybrids. Comparative analysis using Chinese varieties revealed that the 3072SNP array showed a better marker success rate and higher average MAF values, evaluation scores, and variety-distinguishing efficiency than the maizeSNP50K array. The maizeSNP3072 array thus can be successfully used in DNA fingerprinting identification of Chinese maize varieties and shows potential as a useful tool for germplasm resource evaluation and molecular marker-assisted breeding.

Inhibition of PTP1B Restores IRS1-Mediated Hepatic Insulin Signaling in IRS2-Deficient Mice

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González-Rodríguez, Águeda; Gutierrez, Jose A. Mas; Sanz-González, Silvia; Ros, Manuel; Burks, Deborah J.; Valverde, Ángela M.

2010-01-01

OBJECTIVE Mice with complete deletion of insulin receptor substrate 2 (IRS2) develop hyperglycemia, impaired hepatic insulin signaling, and elevated gluconeogenesis, whereas mice deficient for protein tyrosine phosphatase (PTP)1B display an opposing hepatic phenotype characterized by increased sensitivity to insulin. To define the relationship between these two signaling pathways in the regulation of liver metabolism, we used genetic and pharmacological approaches to study the effects of inhibiting PTP1B on hepatic insulin signaling and expression of gluconeogenic enzymes in IRS2−/− mice. RESEARCH DESIGN AND METHODS We analyzed glucose homeostasis and insulin signaling in liver and isolated hepatocytes from IRS2−/− and IRS2−/−/PTP1B−/− mice. Additionally, hepatic insulin signaling was assessed in control and IRS2−/− mice treated with resveratrol, an antioxidant present in red wine. RESULTS In livers of hyperglycemic IRS2−/− mice, the expression levels of PTP1B and its association with the insulin receptor (IR) were increased. The absence of PTP1B in the double-mutant mice restored hepatic IRS1-mediated phosphatidylinositol (PI) 3-kinase/Akt/Foxo1 signaling. Moreover, resveratrol treatment of hyperglycemic IRS2−/− mice decreased hepatic PTP1B mRNA and inhibited PTP1B activity, thereby restoring IRS1-mediated PI 3-kinase/Akt/Foxo1 signaling and peripheral insulin sensitivity. CONCLUSIONS By regulating the phosphorylation state of IR, PTB1B determines sensitivity to insulin in liver and exerts a unique role in the interplay between IRS1 and IRS2 in the modulation of hepatic insulin action. PMID:20028942

Meta-analysis diagnostic accuracy of SNP-based pathogenicity detection tools: a case of UTG1A1 gene mutations.

Science.gov (United States)

Galehdari, Hamid; Saki, Najmaldin; Mohammadi-Asl, Javad; Rahim, Fakher

2013-01-01

Crigler-Najjar syndrome (CNS) type I and type II are usually inherited as autosomal recessive conditions that result from mutations in the UGT1A1 gene. The main objective of the present review is to summarize results of all available evidence on the accuracy of SNP-based pathogenicity detection tools compared to published clinical result for the prediction of in nsSNPs that leads to disease using prediction performance method. A comprehensive search was performed to find all mutations related to CNS. Database searches included dbSNP, SNPdbe, HGMD, Swissvar, ensemble, and OMIM. All the mutation related to CNS was extracted. The pathogenicity prediction was done using SNP-based pathogenicity detection tools include SIFT, PHD-SNP, PolyPhen2, fathmm, Provean, and Mutpred. Overall, 59 different SNPs related to missense mutations in the UGT1A1 gene, were reviewed. Comparing the diagnostic OR, PolyPhen2 and Mutpred have the highest detection 4.983 (95% CI: 1.24 - 20.02) in both, following by SIFT (diagnostic OR: 3.25, 95% CI: 1.07 - 9.83). The highest MCC of SNP-based pathogenicity detection tools, was belong to SIFT (34.19%) followed by Provean, PolyPhen2, and Mutpred (29.99%, 29.89%, and 29.89%, respectively). Hence the highest SNP-based pathogenicity detection tools ACC, was fit to SIFT (62.71%) followed by PolyPhen2, and Mutpred (61.02%, in both). Our results suggest that some of the well-established SNP-based pathogenicity detection tools can appropriately reflect the role of a disease-associated SNP in both local and global structures.

The IRS-1 signaling system.

Science.gov (United States)

Myers, M G; Sun, X J; White, M F

1994-07-01

Insulin-receptor substrate 1 (IRS-1) is a principal substrate of the receptor tyrosine kinase for insulin and insulin-like growth factor 1, and a substrate for a tyrosine kinase activated by interleukin 4. IRS-1 undergoes multisite tyrosine phosphorylation and mediates downstream signals by 'docking' various proteins that contain Src homology 2 domains. IRS-1 appears to be a unique molecule; however, 4PS, a protein found mainly in hemopoietic cells, may represent another member of this family.

IR technology for enhanced force protection by AIM

Science.gov (United States)

Breiter, R.; Ihle, T.; Rode, W.; Wendler, J.; Rühlich, I.; Haiml, M.; Ziegler, J.

2008-04-01

In all recent missions our forces are faced with various types of asymmetric threads like snipers, IEDs, RPGs or MANPADS. 2 nd and 3 rd Gen IR technology is a backbone of modern force protection by providing situational awareness and accurate target engagement at day/night. 3 rd Gen sensors are developed for thread warning capabilities by use of spectral or spatial information. The progress on a dual-color IR module is discussed in a separate paper [1]. A 1024x256 SWIR array with flexure bearing compressor and pulse tube cold finger provides > 50,000h lifetime for space or airborne hyperspectral imaging in pushbroom geometry with 256 spectral channels for improved change detection and remote sensing of IEDs or chemical agents. Similar concepts are pursued in the LWIR with either spectroscopic imaging or a system of LWIR FPA combined with a cooled tunable Laser to do spectroscopy with stimulated absorption of specific wavelengths. AIM introduced the RangIR sight to match the requirements of sniper teams, AGLs and weapon stations, extending the outstanding optronic performance of the fielded HuntIR with position data of a target by a laser range finder (LRF), a 3 axis digital magnetic compass (DMC) and a ballistic computer for accurate engagement of remote targets. A version with flexure bearing cooler with >30,000h life time is being developed for continuous operation in e.g. gunfire detection systems. This paper gives an overview of AIM's technologies for enhanced force protection.

Distinct signalling properties of insulin receptor substrate (IRS)-1 and IRS-2 in mediating insulin/IGF-1 action.

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Rabiee, Atefeh; Krüger, Marcus; Ardenkjær-Larsen, Jacob; Kahn, C Ronald; Emanuelli, Brice

2018-07-01

Insulin/IGF-1 action is driven by a complex and highly integrated signalling network. Loss-of-function studies indicate that the major insulin/IGF-1 receptor substrate (IRS) proteins, IRS-1 and IRS-2, mediate different biological functions in vitro and in vivo, suggesting specific signalling properties despite their high degree of homology. To identify mechanisms contributing to the differential signalling properties of IRS-1 and IRS-2 in the mediation of insulin/IGF-1 action, we performed comprehensive mass spectrometry (MS)-based phosphoproteomic profiling of brown preadipocytes from wild type, IRS-1 -/- and IRS-2 -/- mice in the basal and IGF-1-stimulated states. We applied stable isotope labeling by amino acids in cell culture (SILAC) for the accurate quantitation of changes in protein phosphorylation. We found ~10% of the 6262 unique phosphorylation sites detected to be regulated by IGF-1. These regulated sites included previously reported substrates of the insulin/IGF-1 signalling pathway, as well as novel substrates including Nuclear Factor I X and Semaphorin-4B. In silico prediction suggests the protein kinase B (PKB), protein kinase C (PKC), and cyclin-dependent kinase (CDK) as the main mediators of these phosphorylation events. Importantly, we found preferential phosphorylation patterns depending on the presence of either IRS-1 or IRS-2, which was associated with specific sets of kinases involved in signal transduction downstream of these substrates such as PDHK1, MAPK3, and PKD1 for IRS-1, and PIN1 and PKC beta for IRS-2. Overall, by generating a comprehensive phosphoproteomic profile from brown preadipocyte cells in response to IGF-1 stimulation, we reveal both common and distinct insulin/IGF-1 signalling events mediated by specific IRS proteins. Copyright © 2018 Elsevier Inc. All rights reserved.

Distinct signalling properties of insulin receptor substrate (IRS)-1 and IRS-2 in mediating insulin/IGF-1 action

DEFF Research Database (Denmark)

Rabiee, Atefeh; Krüger, Marcus; Ardenkjær-Larsen, Jacob

2018-01-01

Insulin/IGF-1 action is driven by a complex and highly integrated signalling network. Loss-of-function studies indicate that the major insulin/IGF-1 receptor substrate (IRS) proteins, IRS-1 and IRS-2, mediate different biological functions in vitro and in vivo, suggesting specific signalling...... properties despite their high degree of homology. To identify mechanisms contributing to the differential signalling properties of IRS-1 and IRS-2 in the mediation of insulin/IGF-1 action, we performed comprehensive mass spectrometry (MS)-based phosphoproteomic profiling of brown preadipocytes from wild type......, IRS-1-/-and IRS-2-/-mice in the basal and IGF-1-stimulated states. We applied stable isotope labeling by amino acids in cell culture (SILAC) for the accurate quantitation of changes in protein phosphorylation. We found ~10% of the 6262 unique phosphorylation sites detected to be regulated by IGF-1...

Genetic variation in candidate obesity genes ADRB2, ADRB3, GHRL, HSD11B1, IRS1, IRS2, and SHC1 and risk for breast cancer in the Cancer Prevention Study II.

Science.gov (United States)

Feigelson, Heather Spencer; Teras, Lauren R; Diver, W Ryan; Tang, Weining; Patel, Alpa V; Stevens, Victoria L; Calle, Eugenia E; Thun, Michael J; Bouzyk, Mark

2008-01-01

Obesity has consistently been associated with postmenopausal breast cancer risk. Proteins that are secreted by adipose tissue or are involved in regulating body mass may play a role in breast tumor development. We conducted a nested case-control study among postmenopausal women from the American Cancer Society Cancer Prevention Study II Nutrition Cohort to determine whether genes associated with obesity increase risk for breast cancer. Tagging single nucleotide polymorphisms (SNPs) were selected to capture common variation across seven candidate genes that encode adipose-related proteins: ADRB2, ADRB3, GHRL, HSD11B1, IRS1, IRS2, and SHC1. Thirty-nine SNPs were genotyped in 648 cases and 659 controls. Logistic regression models were used to examine the association between each tagging SNP and risk for breast cancer while adjusting for matching factors and potential confounders. We also examined whether these SNPs were associated with measures of adult adiposity. Two out of five tagging SNPs in HSD11B1 were associated with breast cancer (rs11807619, P = 0.006; rs932335, P = 0.0001). rs11807619 and rs932335 were highly correlated (r2 = 0.74) and, when modeled as a haplotype, only haplotypes containing the rs932335 C allele were associated with breast cancer. The rs932335 C allele was associated with a nearly twofold increased risk for breast cancer (odds ratio = 1.83, 95% confidence interval = 1.01-3.33 for C/C versus G/G). Three of the 11 SNPs for IRS2 were associated with breast cancer (rs4773082, P = 0.007; rs2289046, P = 0.016; rs754204, P = 0.03). When these three SNPs were examined as a haplotype, only the haplotype that included the G allele of rs2289046 was associated with breast cancer (odds ratio = 0.76, 95% confidence interval = 0.63-0.92 for TGC versus CAT). IRS2 rs2289046, rs754204, and rs12584136 were also associated with adult weight gain but only among cases. None of the other SNPs in any gene investigated were associated with breast cancer or

GenMAPP 2: new features and resources for pathway analysis

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Dahlquist Kam D

2007-06-01

Full Text Available Abstract Background Microarray technologies have evolved rapidly, enabling biologists to quantify genome-wide levels of gene expression, alternative splicing, and sequence variations for a variety of species. Analyzing and displaying these data present a significant challenge. Pathway-based approaches for analyzing microarray data have proven useful for presenting data and for generating testable hypotheses. Results To address the growing needs of the microarray community we have released version 2 of Gene Map Annotator and Pathway Profiler (GenMAPP, a new GenMAPP database schema, and integrated resources for pathway analysis. We have redesigned the GenMAPP database to support multiple gene annotations and species as well as custom species database creation for a potentially unlimited number of species. We have expanded our pathway resources by utilizing homology information to translate pathway content between species and extending existing pathways with data derived from conserved protein interactions and coexpression. We have implemented a new mode of data visualization to support analysis of complex data, including time-course, single nucleotide polymorphism (SNP, and splicing. GenMAPP version 2 also offers innovative ways to display and share data by incorporating HTML export of analyses for entire sets of pathways as organized web pages. Conclusion GenMAPP version 2 provides a means to rapidly interrogate complex experimental data for pathway-level changes in a diverse range of organisms.

GenToS: Use of Orthologous Gene Information to Prioritize Signals from Human GWAS.

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Anselm S Hoppmann

Full Text Available Genome-wide association studies (GWAS evaluate associations between genetic variants and a trait or disease of interest free of prior biological hypotheses. GWAS require stringent correction for multiple testing, with genome-wide significance typically defined as association p-value <5*10-8. This study presents a new tool that uses external information about genes to prioritize SNP associations (GenToS. For a given list of candidate genes, GenToS calculates an appropriate statistical significance threshold and then searches for trait-associated variants in summary statistics from human GWAS. It thereby allows for identifying trait-associated genetic variants that do not meet genome-wide significance. The program additionally tests for enrichment of significant candidate gene associations in the human GWAS data compared to the number expected by chance. As proof of principle, this report used external information from a comprehensive resource of genetically manipulated and systematically phenotyped mice. Based on selected murine phenotypes for which human GWAS data for corresponding traits were publicly available, several candidate gene input lists were derived. Using GenToS for the investigation of candidate genes underlying murine skeletal phenotypes in data from a large human discovery GWAS meta-analysis of bone mineral density resulted in the identification of significantly associated variants in 29 genes. Index variants in 28 of these loci were subsequently replicated in an independent GWAS replication step, highlighting that they are true positive associations. One signal, COL11A1, has not been discovered through GWAS so far and represents a novel human candidate gene for altered bone mineral density. The number of observed genes that contained significant SNP associations in human GWAS based on murine candidate gene input lists was much greater than the number expected by chance across several complex human traits (enrichment p-value as

FT-IR Spectroscopic study on the 4-(3-Cyclohexen-1-yl)pyridine metal (II) tetracyanonickelate complex

International Nuclear Information System (INIS)

Parlak, C.

2005-01-01

New Hofmann type complex in the form of M(4-Chpy) 2 Ni(CN) 4 (where 4-Chpy=4-(3- Cyclohexen-1-yl)pyridine and M = Ni) was prepared in powder form and its infrared spectra is reported in the range of 4000-400 cm - 1. The spectral findings suggest that this compound is similar in structure to the Hofmann type complexes and its structure consists of polymeric layers | M-Ni(CN) 4 |∞ with the 4-(3-Cyclohexen-1-yl)pyridine molecule bound to the metal atom (M)

Traffic Generator (TrafficGen) Version 1.4.2: Users Guide

Science.gov (United States)

2016-06-01

the network with Transmission Control Protocol and User Datagram Protocol Internet Protocol traffic. Each node generating network traffic in an...TrafficGen Graphical User Interface (GUI) 3 3.1 Anatomy of the User Interface 3 3.2 Scenario Configuration and MGEN Files 4 4. Working with...for public release; distribution is unlimited. vi List of Figures Fig. 1 TrafficGen user interface

A SNP-Based Molecular Barcode for Characterization of Common Wheat.

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LiFeng Gao

Full Text Available Wheat is grown as a staple crop worldwide. It is important to develop an effective genotyping tool for this cereal grain both to identify germplasm diversity and to protect the rights of breeders. Single-nucleotide polymorphism (SNP genotyping provides a means for developing a practical, rapid, inexpensive and high-throughput assay. Here, we investigated SNPs as robust markers of genetic variation for typing wheat cultivars. We identified SNPs from an array of 9000 across a collection of 429 well-known wheat cultivars grown in China, of which 43 SNP markers with high minor allele frequency and variations discriminated the selected wheat varieties and their wild ancestors. This SNP-based barcode will allow for the rapid and precise identification of wheat germplasm resources and newly released varieties and will further assist in the wheat breeding program.

Computational modelling of Ti50Pt50-xMx shape memory alloys (M: Ni, Ir or Pd and x = 6.25-43.75 at.%)

CSIR Research Space (South Africa)

Modiba, Rosinah M

2017-09-01

Full Text Available The ab initio density functional theory approach was employed to study the effect of Ni, Ir or Pd addition to the TiPt shape memory alloy. The supercell approach in VASP was used to substitute Pt with 6.25, 18.75, 25.00, 31.25 and 43.75 at.% Ni, Ir...

SNP Arrays

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Jari Louhelainen

2016-10-01

Full Text Available The papers published in this Special Issue “SNP arrays” (Single Nucleotide Polymorphism Arrays focus on several perspectives associated with arrays of this type. The range of papers vary from a case report to reviews, thereby targeting wider audiences working in this field. The research focus of SNP arrays is often human cancers but this Issue expands that focus to include areas such as rare conditions, animal breeding and bioinformatics tools. Given the limited scope, the spectrum of papers is nothing short of remarkable and even from a technical point of view these papers will contribute to the field at a general level. Three of the papers published in this Special Issue focus on the use of various SNP array approaches in the analysis of three different cancer types. Two of the papers concentrate on two very different rare conditions, applying the SNP arrays slightly differently. Finally, two other papers evaluate the use of the SNP arrays in the context of genetic analysis of livestock. The findings reported in these papers help to close gaps in the current literature and also to give guidelines for future applications of SNP arrays.

SNP-SNP interactions in breast cancer susceptibility

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Wang Yuanyuan

2006-05-01

Full Text Available Abstract Background Breast cancer predisposition genes identified to date (e.g., BRCA1 and BRCA2 are responsible for less than 5% of all breast cancer cases. Many studies have shown that the cancer risks associated with individual commonly occurring single nucleotide polymorphisms (SNPs are incremental. However, polygenic models suggest that multiple commonly occurring low to modestly penetrant SNPs of cancer related genes might have a greater effect on a disease when considered in combination. Methods In an attempt to identify the breast cancer risk conferred by SNP interactions, we have studied 19 SNPs from genes involved in major cancer related pathways. All SNPs were genotyped by TaqMan 5'nuclease assay. The association between the case-control status and each individual SNP, measured by the odds ratio and its corresponding 95% confidence interval, was estimated using unconditional logistic regression models. At the second stage, two-way interactions were investigated using multivariate logistic models. The robustness of the interactions, which were observed among SNPs with stronger functional evidence, was assessed using a bootstrap approach, and correction for multiple testing based on the false discovery rate (FDR principle. Results None of these SNPs contributed to breast cancer risk individually. However, we have demonstrated evidence for gene-gene (SNP-SNP interaction among these SNPs, which were associated with increased breast cancer risk. Our study suggests cross talk between the SNPs of the DNA repair and immune system (XPD-[Lys751Gln] and IL10-[G(-1082A], cell cycle and estrogen metabolism (CCND1-[Pro241Pro] and COMT-[Met108/158Val], cell cycle and DNA repair (BARD1-[Pro24Ser] and XPD-[Lys751Gln], and within carcinogen metabolism (GSTP1-[Ile105Val] and COMT-[Met108/158Val] pathways. Conclusion The importance of these pathways and their communication in breast cancer predisposition has been emphasized previously, but their

SNP-SNP interactions in breast cancer susceptibility

International Nuclear Information System (INIS)

Onay, Venüs Ümmiye; Ozcelik, Hilmi; Briollais, Laurent; Knight, Julia A; Shi, Ellen; Wang, Yuanyuan; Wells, Sean; Li, Hong; Rajendram, Isaac; Andrulis, Irene L

2006-01-01

Breast cancer predisposition genes identified to date (e.g., BRCA1 and BRCA2) are responsible for less than 5% of all breast cancer cases. Many studies have shown that the cancer risks associated with individual commonly occurring single nucleotide polymorphisms (SNPs) are incremental. However, polygenic models suggest that multiple commonly occurring low to modestly penetrant SNPs of cancer related genes might have a greater effect on a disease when considered in combination. In an attempt to identify the breast cancer risk conferred by SNP interactions, we have studied 19 SNPs from genes involved in major cancer related pathways. All SNPs were genotyped by TaqMan 5'nuclease assay. The association between the case-control status and each individual SNP, measured by the odds ratio and its corresponding 95% confidence interval, was estimated using unconditional logistic regression models. At the second stage, two-way interactions were investigated using multivariate logistic models. The robustness of the interactions, which were observed among SNPs with stronger functional evidence, was assessed using a bootstrap approach, and correction for multiple testing based on the false discovery rate (FDR) principle. None of these SNPs contributed to breast cancer risk individually. However, we have demonstrated evidence for gene-gene (SNP-SNP) interaction among these SNPs, which were associated with increased breast cancer risk. Our study suggests cross talk between the SNPs of the DNA repair and immune system (XPD-[Lys751Gln] and IL10-[G(-1082)A]), cell cycle and estrogen metabolism (CCND1-[Pro241Pro] and COMT-[Met108/158Val]), cell cycle and DNA repair (BARD1-[Pro24Ser] and XPD-[Lys751Gln]), and within carcinogen metabolism (GSTP1-[Ile105Val] and COMT-[Met108/158Val]) pathways. The importance of these pathways and their communication in breast cancer predisposition has been emphasized previously, but their biological interactions through SNPs have not been described

Dosimetric and radiobiological comparison of TG-43 and Monte Carlo calculations in 192Ir breast brachytherapy applications.

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Peppa, V; Pappas, E P; Karaiskos, P; Major, T; Polgár, C; Papagiannis, P

2016-10-01

To investigate the clinical significance of introducing model based dose calculation algorithms (MBDCAs) as an alternative to TG-43 in 192 Ir interstitial breast brachytherapy. A 57 patient cohort was used in a retrospective comparison between TG-43 based dosimetry data exported from a treatment planning system and Monte Carlo (MC) dosimetry performed using MCNP v. 6.1 with plan and anatomy information in DICOM-RT format. Comparison was performed for the target, ipsilateral lung, heart, skin, breast and ribs, using dose distributions, dose-volume histograms (DVH) and plan quality indices clinically used for plan evaluation, as well as radiobiological parameters. TG-43 overestimation of target DVH parameters is statistically significant but small (less than 2% for the target coverage indices and 4% for homogeneity indices, on average). Significant dose differences (>5%) were observed close to the skin and at relatively large distances from the implant leading to a TG-43 dose overestimation for the organs at risk. These differences correspond to low dose regions (<50% of the prescribed dose), being less than 2% of the prescribed dose. Detected dosimetric differences did not induce clinically significant differences in calculated tumor control probabilities (mean absolute difference <0.2%) and normal tissue complication probabilities. While TG-43 shows a statistically significant overestimation of most indices used for plan evaluation, differences are small and therefore not clinically significant. Improved MBDCA dosimetry could be important for re-irradiation, technique inter-comparison and/or the assessment of secondary cancer induction risk, where accurate dosimetry in the whole patient anatomy is of the essence. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Analytical and statistical consideration on the use of the ISAG-ICAR-SNP bovine panel for parentage control, using the Illumina BeadChip technology: example on the German Holstein population.

Science.gov (United States)

Schütz, Ekkehard; Brenig, Bertram

2015-02-05

Parentage control is moving from short tandem repeats- to single nucleotide polymorphism (SNP) systems. For SNP-based parentage control in cattle, the ISAG-ICAR Committee proposes a set of 100/200 SNPs but quality criteria are lacking. Regarding German Holstein-Friesian cattle with only a limited number of evaluated individuals, the exclusion probability is not well-defined. We propose a statistical procedure for excluding single SNPs from parentage control, based on case-by-case evaluation of the GenCall score, to minimize parentage exclusion, based on miscalled genotypes. Exclusion power of the ISAG-ICAR SNPs used for the German Holstein-Friesian population was adjusted based on the results of more than 25,000 individuals. Experimental data were derived from routine genomic selection analyses of the German Holstein-Friesian population using the Illumina BovineSNP50 v2 BeadChip (20,000 individuals) or the EuroG10K variant (7000 individuals). Averages and standard deviations of GenCall scores for the 200 SNPs of the ISAG-ICAR recommended panel were calculated and used to calculate the downward Z-value. Based on minor allelic frequencies in the Holstein-Friesian population, one minus exclusion probability was equal to 1.4×10⁻¹⁰ and 7.2×10⁻²⁶, with one and two parents, respectively. Two monomorphic SNPs from the 100-SNP ISAG-ICAR core-panel did not contribute. Simulation of 10,000 parentage control combinations, using the GenCall score data from both BeadChips, showed that with a Z-value greater than 3.66 only about 2.5% parentages were excluded, based on the ISAG-ICAR recommendations (core-panel: ≥ 90 SNPs for one, ≥ 85 SNPs for two parents). When applied to real data from 1750 single parentage assessments, the optimal threshold was determined to be Z = 5.0, with only 34 censored cases and reduction to four (0.2%) doubtful parentages. About 70 parentage exclusions due to weak genotype calls were avoided, whereas true exclusions (n = 34) were

Crystal Structure of a Eukaryotic GEN1 Resolving Enzyme Bound to DNA

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Yijin Liu

2015-12-01

Full Text Available We present the crystal structure of the junction-resolving enzyme GEN1 bound to DNA at 2.5 Å resolution. The structure of the GEN1 protein reveals it to have an elaborated FEN-XPG family fold that is modified for its role in four-way junction resolution. The functional unit in the crystal is a monomer of active GEN1 bound to the product of resolution cleavage, with an extensive DNA binding interface for both helical arms. Within the crystal lattice, a GEN1 dimer interface juxtaposes two products, whereby they can be reconnected into a four-way junction, the structure of which agrees with that determined in solution. The reconnection requires some opening of the DNA structure at the center, in agreement with permanganate probing and 2-aminopurine fluorescence. The structure shows that a relaxation of the DNA structure accompanies cleavage, suggesting how second-strand cleavage is accelerated to ensure productive resolution of the junction.

Influence of the MDM2 single nucleotide polymorphism SNP309 on tumour development in BRCA1 mutation carriers

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Johnson Peter W

2006-03-01

Full Text Available Abstract Background The MDM2 gene encodes a negative regulator of the p53 tumour suppressor protein. A single nucleotide polymorphism (SNP in the MDM2 promoter (a T to G exchange at nucleotide 309 has been reported to produce accelerated tumour formation in individuals with inherited p53 mutations. We have investigated the effect of the MDM2 SNP309 on clinical outcome in a cohort of patients with germline mutations of BRCA1. Methods Genomic DNA was obtained for 102 healthy controls and 116 patients with established pathogenic mutations of BRCA1 and Pyrosequencing technology™ was used to determine the genotype at the MDM2 SNP309 locus. Results The polymorphism was present in 52.9% of the controls (G/T in 37.3% and G/G in 15.6% and 58.6% of the BRCA1 mutation carriers (47.4% G/T and 11.2% G/G. Incidence of malignancy in female BRCA1 carriers was not significantly higher in SNP309 carriers than in wildtype (T/T individuals (72.7% vs. 75.6%, p = 1.00. Mean age of diagnosis of first breast cancer was 41.2 years in the SNP309 G/G genotype carriers, 38.6 years in those with the SNP309 G/T genotype and 39.0 years in wildtype subjects (p = 0.80. Conclusion We found no evidence that the MDM2 SNP309 accelerates tumour development in carriers of known pathogenic germline mutations of BRCA1.

PENURUNAN KADAR AFLATOKSIN B1 PADA SARI KEDELAI OLEH SEL HIDUP DAN SEL MATI Lactobacillus acidophilus SNP-2 [Reduction of Aflatoxin B1 in Soymilk by Viable and Heat-killed Lactobacillus acidophilus SNP-2

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Tyas Utami1*

2012-06-01

Full Text Available Aflatoxins are carcinogenic mycotoxins that commonly contaminate foods and feed. There are many different forms of aflatoxin and its metabolites. Of these, aflatoxin B1 (AFB1 is the most prevalent and toxic. Lactobacillus acidophilus SNP-2 has previously been shown to remove AFB1 from liquid solution of phosphate saline buffer. However, the ability of lactic acid bacteria to reduce AFB1 content in soymilk has not been studied yet. The objective of this study was to investigate the ability of viable and heat-killed cells of L. acidophilus SNP-2 to reduce AFB1 in soymilk and fermented soymilk. Soymilk contaminated with Aspergillus flavus was inoculated with culture of L. acidophilus SNP-2, and incubated at 37C for 12 hours. Fermented soymilk, then, was heat sterilized and stored at cool room (4°C. Heat-killed cells were introduced to soy milk and then kept at cool room for 3 days. During soymilk fermentation, there was reduction of AFB1 content in soymilk related to the growth of lactic acid bacteria and the reduction of pH. The initial concentration of AFB1 in the soymilk was 4.9 ppb. Lactobacillus acidophilus SNP-2 reduced 67.58% of AFB1 in the soymilk after 12 hoursof fermentation. In cool environment, the binding of AFB1 to heat-killed cell after soymilk fermentation was relatively more stable than that of soymilk without fermentation.

SNP-RFLPing 2: an updated and integrated PCR-RFLP tool for SNP genotyping

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Chang Hsueh-Wei

2010-04-01

Full Text Available Abstract Background PCR-restriction fragment length polymorphism (RFLP assay is a cost-effective method for SNP genotyping and mutation detection, but the manual mining for restriction enzyme sites is challenging and cumbersome. Three years after we constructed SNP-RFLPing, a freely accessible database and analysis tool for restriction enzyme mining of SNPs, significant improvements over the 2006 version have been made and incorporated into the latest version, SNP-RFLPing 2. Results The primary aim of SNP-RFLPing 2 is to provide comprehensive PCR-RFLP information with multiple functionality about SNPs, such as SNP retrieval to multiple species, different polymorphism types (bi-allelic, tri-allelic, tetra-allelic or indels, gene-centric searching, HapMap tagSNPs, gene ontology-based searching, miRNAs, and SNP500Cancer. The RFLP restriction enzymes and the corresponding PCR primers for the natural and mutagenic types of each SNP are simultaneously analyzed. All the RFLP restriction enzyme prices are also provided to aid selection. Furthermore, the previously encountered updating problems for most SNP related databases are resolved by an on-line retrieval system. Conclusions The user interfaces for functional SNP analyses have been substantially improved and integrated. SNP-RFLPing 2 offers a new and user-friendly interface for RFLP genotyping that can be used in association studies and is freely available at http://bio.kuas.edu.tw/snp-rflping2.

SNP-RFLPing 2: an updated and integrated PCR-RFLP tool for SNP genotyping.

Science.gov (United States)

Chang, Hsueh-Wei; Cheng, Yu-Huei; Chuang, Li-Yeh; Yang, Cheng-Hong

2010-04-08

PCR-restriction fragment length polymorphism (RFLP) assay is a cost-effective method for SNP genotyping and mutation detection, but the manual mining for restriction enzyme sites is challenging and cumbersome. Three years after we constructed SNP-RFLPing, a freely accessible database and analysis tool for restriction enzyme mining of SNPs, significant improvements over the 2006 version have been made and incorporated into the latest version, SNP-RFLPing 2. The primary aim of SNP-RFLPing 2 is to provide comprehensive PCR-RFLP information with multiple functionality about SNPs, such as SNP retrieval to multiple species, different polymorphism types (bi-allelic, tri-allelic, tetra-allelic or indels), gene-centric searching, HapMap tagSNPs, gene ontology-based searching, miRNAs, and SNP500Cancer. The RFLP restriction enzymes and the corresponding PCR primers for the natural and mutagenic types of each SNP are simultaneously analyzed. All the RFLP restriction enzyme prices are also provided to aid selection. Furthermore, the previously encountered updating problems for most SNP related databases are resolved by an on-line retrieval system. The user interfaces for functional SNP analyses have been substantially improved and integrated. SNP-RFLPing 2 offers a new and user-friendly interface for RFLP genotyping that can be used in association studies and is freely available at http://bio.kuas.edu.tw/snp-rflping2.

Association of the TPO gene in Colombian families with type 1 diabetes Asociación del gen TPO en familias colombianas con la diabetes tipo 1

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Federico Uribe Londoño

2009-11-01

informada. Se encontró que un haplotipo en el gen TPO está asociado con la enfermedad. Tal haplotipo se caracteriza por los alelos G y A en los SNP rs4927611 y rs732609, respectivamente. Nuestros resultados sugieren una posible participación causal del

gen TPO en la T1D. Para verificarlos, se está recolectando una muestra de similar tamaño en la misma población colombiana.

Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function.

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Dana B Hancock

Full Text Available Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV(1, and its ratio to forced vital capacity (FEV(1/FVC. Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA of single nucleotide polymorphism (SNP and SNP-by-smoking (ever-smoking or pack-years associations on FEV(1 and FEV(1/FVC across 19 studies (total N = 50,047. We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P(JMA = 5.00×10(-11, HLA-DQB1 and HLA-DQA2 (smallest P(JMA = 4.35×10(-9, and KCNJ2 and SOX9 (smallest P(JMA = 1.28×10(-8 were associated with FEV(1/FVC or FEV(1 in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.

An Improved Opposition-Based Learning Particle Swarm Optimization for the Detection of SNP-SNP Interactions

Science.gov (United States)

Shang, Junliang; Sun, Yan; Li, Shengjun; Liu, Jin-Xing; Zheng, Chun-Hou; Zhang, Junying

2015-01-01

SNP-SNP interactions have been receiving increasing attention in understanding the mechanism underlying susceptibility to complex diseases. Though many works have been done for the detection of SNP-SNP interactions, the algorithmic development is still ongoing. In this study, an improved opposition-based learning particle swarm optimization (IOBLPSO) is proposed for the detection of SNP-SNP interactions. Highlights of IOBLPSO are the introduction of three strategies, namely, opposition-based learning, dynamic inertia weight, and a postprocedure. Opposition-based learning not only enhances the global explorative ability, but also avoids premature convergence. Dynamic inertia weight allows particles to cover a wider search space when the considered SNP is likely to be a random one and converges on promising regions of the search space while capturing a highly suspected SNP. The postprocedure is used to carry out a deep search in highly suspected SNP sets. Experiments of IOBLPSO are performed on both simulation data sets and a real data set of age-related macular degeneration, results of which demonstrate that IOBLPSO is promising in detecting SNP-SNP interactions. IOBLPSO might be an alternative to existing methods for detecting SNP-SNP interactions. PMID:26236727

Isomeric cross sections of neutron induced reactions on Ge and Ir isotopes

International Nuclear Information System (INIS)

Vlastou, R.; Papadopoulos, C.T.; Kokkoris, M.; Perdikakis, G.; Galanopoulos, S.; Patronis, N.; Serris, M.; Perdikakis, G.; Harissopulos, S.; Demetriou, P.

2008-01-01

The 72 Ge(n,α) 69m Zn, 74 Ge(n,α) 71m Zn, 76 Ge(n,2n) 75g+m Ge and 191 Ir(n,2n) 190 Ir g+m1 and 191 Ir(n,2n) 190 Ir m2 reaction cross sections were measured from 9.6 to 11.4 MeV relative to the 27 Al(n,α) 24 Na reference reaction via the activation method. The quasi-monoenergetic neutron beams were produced via the 2 H(d,n) 3 He reaction at the 5 MV VdG Tandem T11/25 accelerator of NCSR 'Demokritos'. Statistical model calculations using the codes STAPRE-F and EMPIRE (version 2.19) and taking into account pre-equilibrium emission were performed on the data measured in this work as well as on data reported in literature. (authors)

SNP interaction pattern identifier (SIPI)

DEFF Research Database (Denmark)

Lin, Hui Yi; Chen, Dung Tsa; Huang, Po Yu

2017-01-01

Motivation: Testing SNP-SNP interactions is considered as a key for overcoming bottlenecks of genetic association studies. However, related statistical methods for testing SNP-SNP interactions are underdeveloped. Results: We propose the SNP Interaction Pattern Identifier (SIPI), which tests 45...

SNP Data Quality Control in a National Beef and Dairy Cattle System and Highly Accurate SNP Based Parentage Verification and Identification

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Matthew C. McClure

2018-03-01

Full Text Available A major use of genetic data is parentage verification and identification as inaccurate pedigrees negatively affect genetic gain. Since 2012 the international standard for single nucleotide polymorphism (SNP verification in Bos taurus cattle has been the ISAG SNP panels. While these ISAG panels provide an increased level of parentage accuracy over microsatellite markers (MS, they can validate the wrong parent at ≤1% misconcordance rate levels, indicating that more SNP are needed if a more accurate pedigree is required. With rapidly increasing numbers of cattle being genotyped in Ireland that represent 61 B. taurus breeds from a wide range of farm types: beef/dairy, AI/pedigree/commercial, purebred/crossbred, and large to small herd size the Irish Cattle Breeding Federation (ICBF analyzed different SNP densities to determine that at a minimum ≥500 SNP are needed to consistently predict only one set of parents at a ≤1% misconcordance rate. For parentage validation and prediction ICBF uses 800 SNP (ICBF800 selected based on SNP clustering quality, ISAG200 inclusion, call rate (CR, and minor allele frequency (MAF in the Irish cattle population. Large datasets require sample and SNP quality control (QC. Most publications only deal with SNP QC via CR, MAF, parent-progeny conflicts, and Hardy-Weinberg deviation, but not sample QC. We report here parentage, SNP QC, and a genomic sample QC pipelines to deal with the unique challenges of >1 million genotypes from a national herd such as SNP genotype errors from mis-tagging of animals, lab errors, farm errors, and multiple other issues that can arise. We divide the pipeline into two parts: a Genotype QC and an Animal QC pipeline. The Genotype QC identifies samples with low call rate, missing or mixed genotype classes (no BB genotype or ABTG alleles present, and low genotype frequencies. The Animal QC handles situations where the genotype might not belong to the listed individual by identifying: >1 non

CFSAN SNP Pipeline: an automated method for constructing SNP matrices from next-generation sequence data

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Steve Davis

2015-08-01

Full Text Available The analysis of next-generation sequence (NGS data is often a fragmented step-wise process. For example, multiple pieces of software are typically needed to map NGS reads, extract variant sites, and construct a DNA sequence matrix containing only single nucleotide polymorphisms (i.e., a SNP matrix for a set of individuals. The management and chaining of these software pieces and their outputs can often be a cumbersome and difficult task. Here, we present CFSAN SNP Pipeline, which combines into a single package the mapping of NGS reads to a reference genome with Bowtie2, processing of those mapping (BAM files using SAMtools, identification of variant sites using VarScan, and production of a SNP matrix using custom Python scripts. We also introduce a Python package (CFSAN SNP Mutator that when given a reference genome will generate variants of known position against which we validate our pipeline. We created 1,000 simulated Salmonella enterica sp. enterica Serovar Agona genomes at 100× and 20× coverage, each containing 500 SNPs, 20 single-base insertions and 20 single-base deletions. For the 100× dataset, the CFSAN SNP Pipeline recovered 98.9% of the introduced SNPs and had a false positive rate of 1.04 × 10−6; for the 20× dataset 98.8% of SNPs were recovered and the false positive rate was 8.34 × 10−7. Based on these results, CFSAN SNP Pipeline is a robust and accurate tool that it is among the first to combine into a single executable the myriad steps required to produce a SNP matrix from NGS data. Such a tool is useful to those working in an applied setting (e.g., food safety traceback investigations as well as for those interested in evolutionary questions.

Analysis of SNP rs16754 of WT1 gene in a series of de novo acute myeloid leukemia patients.

Science.gov (United States)

Luna, Irene; Such, Esperanza; Cervera, Jose; Barragán, Eva; Jiménez-Velasco, Antonio; Dolz, Sandra; Ibáñez, Mariam; Gómez-Seguí, Inés; López-Pavía, María; Llop, Marta; Fuster, Óscar; Oltra, Silvestre; Moscardó, Federico; Martínez-Cuadrón, David; Senent, M Leonor; Gascón, Adriana; Montesinos, Pau; Martín, Guillermo; Bolufer, Pascual; Sanz, Miguel A

2012-12-01

The single nucleotide polymorphism (SNP) rs16754 of the WT1 gene has been previously described as a possible prognostic marker in normal karyotype acute myeloid leukemia (AML) patients. Nevertheless, the findings in this field are not always reproducible in different series. One hundred and seventy-five adult de novo AML patients were screened with two different methods for the detection of SNP rs16754: high-resolution melting (HRM) and FRET hybridization probes. Direct sequencing was used to validate both techniques. The SNP was detected in 52 out of 175 patients (30 %), both by HRM and hybridization probes. Direct sequencing confirmed that every positive sample in the screening methods had a variation in the DNA sequence. Patients with the wild-type genotype (WT1(AA)) for the SNP rs16754 were significantly younger than those with the heterozygous WT1(AG) genotype. No other difference was observed for baseline characteristic or outcome between patients with or without the SNP. Both techniques are equally reliable and reproducible as screening methods for the detection of the SNP rs16754, allowing for the selection of those samples that will need to be sequenced. We were unable to confirm the suggested favorable outcome of SNP rs16754 in de novo AML.

A Novel Role of Human Holliday Junction Resolvase GEN1 in the Maintenance of Centrosome Integrity

DEFF Research Database (Denmark)

Gao, M.; Danielsen, Jannie Michaela Rendtlew; Wei, L.-Z.

2012-01-01

but not catalytic activity of GEN1 is required for preventing centrosome hyper-amplification, formation of multiple mitotic spindles, and multi-nucleation. Our findings provide novel insight into the biological functions of GEN1 by uncovering an important role of GEN1 in the regulation of centrosome integrity....

Association between SNP and haplotypes in PPARGCl and adiponectin genes and bone mineral density in Chinese nuclear families

Institute of Scientific and Technical Information of China (English)

Zhen-lin ZHANG; Jin-wei HE; Yue-juan QIN; Yun-qiu HU; Miao LI; Yu-juan LIU; Hao ZHANG; Wei-wei HU

2007-01-01

Aim: To assess the contribution of single nucleotide polymorphisms (SNP) and haplotypes in the peroxisome proliferator-activated receptor-γ co-activator-1(PPARGC1) and adiponectin genes to normal bone mineral density (BMD) variation in healthy Chinese women and men. Methods: We performed population-based (ANOVA) and family-based (quantitative trait locus transmission disequi-librium test) association studies of PPARGC1 and adiponectin genes. SNP in the 2 genes were genotyped. BMD was measured using dual-energy X-ray absorptiometry in the lumbar spine and hip in 401 nuclear families with a total of1260 subjects, including 458 premenopausal women, 20-40 years of age; 401 post-menopausal women (mothers), 43-74 years of age; and 401 men (fathers), 49-76years of age. Results: Significant within-family association was found between the Thr394Thr polymorphism in the PPGAGC1 gene and peak BMD in the femoral neck (P=0.026). Subsequent permutations were in agreement with this significant within-family association result (P=0.016), but Thr394Thr SNP only accounted for0.7% of the variation in femoral neck peak BMD. However, no significant within-family association was detected between each SNP in the adiponect in gene and peak BMD. Although no significant association was found between BMD and SNP in the PPARGC1 and adiponectin genes in both men and postmenopausal women, haplotype 2 (T-T) in the adiponect in gene was associated with lumbar spine BMD in postmenopausal women (P=0.019). Conclusion: Our findings sug-gest that Thr394Thr SNP in the PPARGC1 gene was associated with peak BMD in the femoral neck in Chinese women. Confirmation of our results is needed in other populations and with more functional markers within and flanking the PPARGC1 or adiponectin genes region.

Novel cross-talk between IGF-IR and DDR1 regulates IGF-IR trafficking, signaling and biological responses

Science.gov (United States)

Sacco, Antonella; Morcavallo, Alaide; Vella, Veronica; Voci, Concetta; Spatuzza, Michela; Xu, Shi-Qiong; Iozzo, Renato V.; Vigneri, Riccardo; Morrione, Andrea; Belfiore, Antonino

2015-01-01

The insulin-like growth factor-I receptor (IGF-IR), plays a key role in regulating mammalian development and growth, and is frequently deregulated in cancer contributing to tumor initiation and progression. Discoidin domain receptor 1 (DDR1), a collagen receptor tyrosine-kinase, is as well frequently overexpressed in cancer and implicated in cancer progression. Thus, we investigated whether a functional cross-talk between the IGF-IR and DDR1 exists and plays any role in cancer progression. Using human breast cancer cells we found that DDR1 constitutively associated with the IGF-IR. However, this interaction was enhanced by IGF-I stimulation, which promoted rapid DDR1 tyrosine-phosphorylation and co-internalization with the IGF-IR. Significantly, DDR1 was critical for IGF-IR endocytosis and trafficking into early endosomes, IGF-IR protein expression and IGF-I intracellular signaling and biological effects, including cell proliferation, migration and colony formation. These biological responses were inhibited by DDR1 silencing and enhanced by DDR1 overexpression. Experiments in mouse fibroblasts co-transfected with the human IGF-IR and DDR1 gave similar results and indicated that, in the absence of IGF-IR, collagen-dependent phosphorylation of DDR1 is impaired. These results demonstrate a critical role of DDR1 in the regulation of IGF-IR action, and identify DDR1 as a novel important target for breast cancers that overexpress IGF-IR. PMID:25840417

Compensatory insulin receptor (IR) activation on inhibition of insulin-like growth factor-1 receptor (IGF-1R): rationale for cotargeting IGF-1R and IR in cancer.

Science.gov (United States)

Buck, Elizabeth; Gokhale, Prafulla C; Koujak, Susan; Brown, Eric; Eyzaguirre, Alexandra; Tao, Nianjun; Rosenfeld-Franklin, Maryland; Lerner, Lorena; Chiu, M Isabel; Wild, Robert; Epstein, David; Pachter, Jonathan A; Miglarese, Mark R

2010-10-01

Insulin-like growth factor-1 receptor (IGF-1R) is a receptor tyrosine kinase (RTK) and critical activator of the phosphatidylinositol 3-kinase-AKT pathway. IGF-1R is required for oncogenic transformation and tumorigenesis. These observations have spurred anticancer drug discovery and development efforts for both biological and small-molecule IGF-1R inhibitors. The ability for one RTK to compensate for another to maintain tumor cell viability is emerging as a common resistance mechanism to antitumor agents targeting individual RTKs. As IGF-1R is structurally and functionally related to the insulin receptor (IR), we asked whether IR is tumorigenic and whether IR-AKT signaling contributes to resistance to IGF-1R inhibition. Both IGF-1R and IR(A) are tumorigenic in a mouse mammary tumor model. In human tumor cells coexpressing IGF-1R and IR, bidirectional cross talk was observed following either knockdown of IR expression or treatment with a selective anti-IGF-1R antibody, MAB391. MAB391 treatment resulted in a compensatory increase in phospho-IR, which was associated with resistance to inhibition of IRS1 and AKT. In contrast, treatment with OSI-906, a small-molecule dual inhibitor of IGF-1R/IR, resulted in enhanced reduction in phospho-IRS1/phospho-AKT relative to MAB391. Insulin or IGF-2 activated the IR-AKT pathway and decreased sensitivity to MAB391 but not to OSI-906. In tumor cells with an autocrine IGF-2 loop, both OSI-906 and an anti-IGF-2 antibody reduced phospho-IR/phospho-AKT, whereas MAB391 was ineffective. Finally, OSI-906 showed superior efficacy compared with MAB391 in human tumor xenograft models in which both IGF-1R and IR were phosphorylated. Collectively, these data indicate that cotargeting IGF-1R and IR may provide superior antitumor efficacy compared with targeting IGF-1R alone.

ANALISIS SEKUEN GEN GLUTATION PEROKSIDASE (GPX1 SEBAGAI DETEKSI STRES OKSIDATIF AKIBAT INFEKSI MYCOBACTERIUM TUBERCULOSIS

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Ari Yuniastuti

2013-02-01

Full Text Available Glutation merupakan antioksidan yang berperan dalam fungsi imun, dan diekspresikan secara genetik oleh urutan gen yang membentuk protein enzim Glutation Peroxidase (GPx1. Bila ekspresi gen berubah maka terjadi perubahan fungsi glutation dan kerentanan terhadap stress oksidatif. Metode yang digunakan adalah Kasus-kontrol. Sampel yang digunakan adalah sampel darah. Kelompok kasus adalah sampel darah pasien tuberkulosis paru sedangkan kelompok kontrol adalah sampel darah orang sehat. Pemeriksaan gen Glutation peroxidase (GPx1 menggunakan metode Polymerase Chain Reaction (PCR untuk melihat pita DNA pada pasien tuberkulosis par serta elektroforesis produk PCR-RFLP gen GPx1 kelompok sampel tuberkulosis. Hasil penelitian menunjukkan bahwa tidak terdapat hubungan yang bermakna antara polimorfisme gen GPx1 (p=0,365 pasein tuberkulois dengan individu sehat, sehingga tidak dapat digunakan sebagai alat deteksi kerentanan terhadap stress oksidatif pada pasien tuberkulosis. Perlu penelitian lanjutan yang menggunakan sampel lebih besar dan populasi etnik yang berbeda.

Las variantes genéticas asociadas con niveles de hemoglobina fetal señalan diversos orígenes étnicos en pacientes colombianos con anemia falciforme

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Cristian Fong

2015-09-01

Full Text Available Introducción. La hemoglobina fetal es un importante factor modulador de la gravedad de la anemia falciforme, cuya expresión está muy condicionada por el factor genético. Los loci asociados con el incremento de la hemoglobina fetal pueden presentar frecuencias alélicas específicas para cada población. Objetivo. Investigar la presencia y el efecto de las variantes genéticas rs11886868, rs9399137, rs4895441 y rs7482144 asociadas con la persistencia de hemoglobina fetal, en 60 pacientes colombianos con anemia falciforme. Materiales y métodos. Se hizo la genotipificación de los polimorfismos de nucleótido simple (Single Nucleotide Polymorphisms, SNP mediante la técnica de polimorfismos de longitud de fragmentos de restricción (Restriction Fragment Length Polymorphisms, RFLP y el procedimiento TaqMan. La hemoglobina fetal (HbF se cuantificó utilizando la técnica de desnaturalización alcalina de la oxihemoglobina. Las frecuencias genotípicas se compararon con las reportadas en poblaciones de referencia global. Resultados. Se observaron variantes genéticas ya reportadas para aumento de HbF en los cuatro SNP. La asociación genética entre los SNP y el incremento de la HbF no alcanzó significancia estadística. La frecuencia de estos alelos reflejó la siguiente composición específica en esta muestra de pacientes colombianos: una gran prevalencia de rs7482144-‘A’, lo que indica que el origen de la mutación para la anemia falciforme es África occidental, y una gran frecuencia de rs4895441-‘G’ y rs11886868-‘C’, lo que denota la influencia significativa del origen genético amerindio. Conclusión. Los resultados evidenciaron que la población con anemia falciforme de Colombia no tiene un único origen genético, sino que existen dos (africano y amerindio. Esta situación genética única ofrece la oportunidad de llevar a cabo un estudio más amplio de estos loci a nivel molecular. Se espera que el estudio de pacientes

Genome-wide association study identifies single-nucleotide polymorphism in KCNB1 associated with left ventricular mass in humans: The HyperGEN Study

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Kraemer Rachel

2009-05-01

Full Text Available Abstract Background We conducted a genome-wide association study (GWAS and validation study for left ventricular (LV mass in the Family Blood Pressure Program – HyperGEN population. LV mass is a sensitive predictor of cardiovascular mortality and morbidity in all genders, races, and ages. Polymorphisms of candidate genes in diverse pathways have been associated with LV mass. However, subsequent studies have often failed to replicate these associations. Genome-wide association studies have unprecedented power to identify potential genes with modest effects on left LV mass. We describe here a GWAS for LV mass in Caucasians using the Affymetrix GeneChip Human Mapping 100 k Set. Cases (N = 101 and controls (N = 101 were selected from extreme tails of the LV mass index distribution from 906 individuals in the HyperGEN study. Eleven of 12 promising (Q Results Despite the relatively small sample, we identified 12 promising SNPs in the GWAS. Eleven SNPs were successfully genotyped in the validation study of 704 Caucasians and 1467 African Americans; 5 SNPs on chromosomes 5, 12, and 20 were significantly (P ≤ 0.05 associated with LV mass after correction for multiple testing. One SNP (rs756529 is intragenic within KCNB1, which is dephosphorylated by calcineurin, a previously reported candidate gene for LV hypertrophy within this population. Conclusion These findings suggest KCNB1 may be involved in the development of LV hypertrophy in humans.

SH2-B promotes insulin receptor substrate 1 (IRS1)- and IRS2-mediated activation of the phosphatidylinositol 3-kinase pathway in response to leptin.

Science.gov (United States)

Duan, Chaojun; Li, Minghua; Rui, Liangyou

2004-10-15

Leptin regulates energy homeostasis primarily by binding and activating its long form receptor (LRb). Deficiency of either leptin or LRb causes morbid obesity. Leptin stimulates LRb-associated JAK2, thus initiating multiple pathways including the Stat3 and phosphatidylinositol (PI) 3-kinase pathways that mediate leptin biological actions. Here we report that SH2-B, a JAK2-interacting protein, promotes activation of the PI 3-kinase pathway by recruiting insulin receptor substrate 1 (IRS1) and IRS2 in response to leptin. SH2-B directly bound, via its PH and SH2 domain, to both IRS1 and IRS2 both in vitro and in intact cells and mediated formation of a JAK2/SH2-B/IRS1 or IRS2 tertiary complex. Consequently, SH2-B dramatically enhanced leptin-stimulated tyrosine phosphorylation of IRS1 and IRS2 in HEK293 cells stably expressing LRb, thus promoting association of IRS1 and IRS2 with the p85 regulatory subunit of PI 3-kinase and phosphorylation and activation of Akt. SH2-B mutants with lower affinity for IRS1 and IRS2 exhibited reduced ability to promote association of JAK2 with IRS1, tyrosine phosphorylation of IRS1, and association of IRS1 with p85 in response to leptin. Moreover, deletion of the SH2-B gene impaired leptin-stimulated tyrosine phosphorylation of endogenous IRS1 in mouse embryonic fibroblasts (MEF), which was reversed by reintroduction of SH2-B. Similarly, SH2-B promoted growth hormone-stimulated tyrosine phosphorylation of IRS1 in both HEK293 and MEF cells. Our data suggest that SH2-B is a novel mediator of the PI 3-kinase pathway in response to leptin or other hormones and cytokines that activate JAK2.

Divergência genética entre genótipos de frangos tipo caipira

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R. C. Veloso

2015-10-01

Full Text Available RESUMOObjetivou-se com este trabalho verificar a divergência genética entre sete genótipos de frangos tipo caipira da linhagem Redbro utilizando as características de desempenho por meio de técnicas de análise multivariada. Foram utilizados 840 pintos de um dia, machos, distribuídos em delineamento inteiramente ao acaso, dos seguintes genótipos: Caboclo, Carijó, Colorpak, Gigante Negro, Pesadão Vermelho, Pescoço Pelado e Tricolor. Após a consistência dos dados, foram avaliadas as seguintes variáveis: ganho em peso médio diário, consumo de ração médio diário e conversão alimentar, para os períodos: 1 a 28, 1 a 56, 1 a 70 e 1 a 84 dias de idade; peso corporal ao nascimento, aos 28, 56, 70 e aos 84 dias de idade. O desempenho dos genótipos foi avaliado por meio da análise de variância multivariada e da função discriminante linear de Fisher, usando os testes do maior autovalor de Roy e da união-interseção de Roy para as comparações múltiplas. O estudo da divergência genética foi feito por meio da análise por variáveis canônicas e pelo método de otimização de Tocher. Os genótipos Caboclo e Gigante Negro apresentaram médias canônicas diferentes dos demais genótipos. As duas primeiras variáveis canônicas explicaram 97,41% da variação entre os genótipos. A divergência genética entre os genótipos avaliados permitiu a formação de quatro grupos com os seguintes genótipos: grupo 1 - Colorpak; grupo 2 - Pesadão Vermelho e Pescoço Pelado; grupo 3 - Carijó e Tricolor; e grupo 4 - Caboclo e Gigante Negro.

Marcadores SNP: conceitos básicos, aplicações no manejo e no melhoramento animal e perspectivas para o futuro SNP markers: basic concepts, applications in animal breeding and management and perspectives for the future

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Alexandre Rodrigues Caetano

2009-07-01

Full Text Available Os primeiros estudos de identificação, caracterização e utilização de marcadores moleculares para a caracterização de recursos genéticos e geração de ferramentas para o melhoramento animal datam do final da década de 80. Nos últimos 20 anos as tecnologias para geração de dados moleculares passaram por vários ciclos de renovação. A última onda de inovações tecnológicas representa uma verdadeira revolução e trouxe metodologias para identificar e genotipar marcadores SNP (do inglês Single Nucleotide Polimorphism de maneira massal. Chips de DNA de alta densidade foram criados para genotipar de dezenas de milhares até centenas de milhares de marcadores SNP em um único ensaio. Além disso, outras tecnologias de média densidade permitem também a genotipagem de dezenas a centenas de marcadores, em números elevados de amostras, com altíssima velocidade e automação. Essas novas tecnologias permitiram a geração de novas aplicações, como as metodologias para avaliação genética e seleção com base no Valor Genômico (Genomic Estimated Breeding Value- GEBV. Os métodos estatísticos para avaliação e seleção genômica estão em pleno desenvolvimento, mas a tecnologia já se tornou uma realidade com o lançamento do primeiro sumário de touros para a raça Holandesa com GEBVs para características de produção e qualidade do leite em janeiro de 2009. Além disso, essas tecnologias também trouxeram novas opções para desenvolvimento de testes diagnósticos para confirmação de paternidade, identificação individual, rastreabilidade, etc. Além dessas inovações, as novas tecnologias de genotipagem de marcadores SNP facilitaram também o desenvolvimento de serviços terceirizados de geração de dados, permitindo que qualquer grupo realize pesquisas avançadas, sempre com as tecnologias mais avançadas, sem a necessidade de investimentos em equipamentos.The first studies to identify, characterize and use

V-MitoSNP: visualization of human mitochondrial SNPs

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Tsui Ke-Hung

2006-08-01

Full Text Available Abstract Background Mitochondrial single nucleotide polymorphisms (mtSNPs constitute important data when trying to shed some light on human diseases and cancers. Unfortunately, providing relevant mtSNP genotyping information in mtDNA databases in a neatly organized and transparent visual manner still remains a challenge. Amongst the many methods reported for SNP genotyping, determining the restriction fragment length polymorphisms (RFLPs is still one of the most convenient and cost-saving methods. In this study, we prepared the visualization of the mtDNA genome in a way, which integrates the RFLP genotyping information with mitochondria related cancers and diseases in a user-friendly, intuitive and interactive manner. The inherent problem associated with mtDNA sequences in BLAST of the NCBI database was also solved. Description V-MitoSNP provides complete mtSNP information for four different kinds of inputs: (1 color-coded visual input by selecting genes of interest on the genome graph, (2 keyword search by locus, disease and mtSNP rs# ID, (3 visualized input of nucleotide range by clicking the selected region of the mtDNA sequence, and (4 sequences mtBLAST. The V-MitoSNP output provides 500 bp (base pairs flanking sequences for each SNP coupled with the RFLP enzyme and the corresponding natural or mismatched primer sets. The output format enables users to see the SNP genotype pattern of the RFLP by virtual electrophoresis of each mtSNP. The rate of successful design of enzymes and primers for RFLPs in all mtSNPs was 99.1%. The RFLP information was validated by actual agarose electrophoresis and showed successful results for all mtSNPs tested. The mtBLAST function in V-MitoSNP provides the gene information within the input sequence rather than providing the complete mitochondrial chromosome as in the NCBI BLAST database. All mtSNPs with rs number entries in NCBI are integrated in the corresponding SNP in V-MitoSNP. Conclusion V-MitoSNP is a web

Characterisation of 1,3-diammonium propylselenate monohydrate by XRD, FT-IR, FT-Raman, DSC and DFT studies

Science.gov (United States)

Thirunarayanan, S.; Arjunan, V.; Marchewka, M. K.; Mohan, S.; Atalay, Yusuf

2016-03-01

The crystals of 1,3-diammonium propylselenate monohydrate (DAPS) were prepared and characterised X-ray diffraction (XRD), FT-IR, FT-Raman spectroscopy, and DFT/B3LYP methods. It comprises protonated propyl ammonium moieties (diammonium propyl cations), selenate anions and water molecule which are held together by a number of hydrogen bonds and form infinite chains. The XRD data confirm the transfer of two protons from selenic acid to 1,3-diaminopropane molecule. The DAPS complex is stabilised by the presence of O-H···O and N-H···O hydrogen bonds and the electrostatic interactions as well. The N···O and O···O bond distances are 2.82-2.91 and 2.77 Å, respectively. The FT-IR and FT-Raman spectra of 1,3-diammonium propyl selenate monohydrate are recorded and the complete vibrational assignments have been discussed. The geometry is optimised by B3LYP method using 6-311G, 6-311+G and 6-311+G* basis sets and the energy, structural parameters, vibrational frequencies, IR and Raman intensities are determined. Differential scanning colorimetry (DSC) data were also presented to analyse the possibility of the phase transition. Complete natural bonding orbital (NBO) analysis is carried out to analyse the intramolecular electronic interactions and their stabilisation energies. The electrostatic potential of the complex lies in the range +1.902e × 10-2 to -1.902e × 10-2. The limits of total electron density of the complex is +8.43e × 10-2 to -8.43e × 10-2.

MDM2 SNP309 and SNP285 Act as Negative Prognostic Markers for Non-small Cell Lung Cancer Adenocarcinoma Patients

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Deben, Christophe; Op de Beeck, Ken; Van den Bossche, Jolien; Jacobs, Julie; Lardon, Filip; Wouters, An; Peeters, Marc; Van Camp, Guy; Rolfo, Christian; Deschoolmeester, Vanessa; Pauwels, Patrick

2017-01-01

Objectives: Two functional polymorphisms in the MDM2 promoter region, SNP309T>G and SNP285G>C, have been shown to impact MDM2 expression and cancer risk. Currently available data on the prognostic value of MDM2 SNP309 in non-small cell lung cancer (NSCLC) is contradictory and unavailable for SNP285. The goal of this study was to clarify the role of these MDM2 SNPs in the outcome of NSCLC patients. Materials and Methods: In this study we genotyped SNP309 and SNP285 in 98 NSCLC adenocarcinoma patients and determined MDM2 mRNA and protein levels. In addition, we assessed the prognostic value of these common SNPs on overall and progression free survival, taking into account the TP53 status of the tumor. Results and Conclusion: We found that the SNP285C allele, but not the SNP309G allele, was significantly associated with increased MDM2 mRNA expression levels (p = 0.025). However, we did not observe an association with MDM2 protein levels for SNP285. The SNP309G allele was significantly associated with the presence of wild type TP53 (p = 0.047) and showed a strong trend towards increased MDM2 protein levels (p = 0.068). In addition, patients harboring the SNP309G allele showed a worse overall survival, but only in the presence of wild type TP53. The SNP285C allele was significantly associated with an early age of diagnosis and metastasis. Additionally, the SNP285C allele acted as an independent predictor for worse progression free survival (HR = 3.97; 95% CI = 1.51 - 10.42; p = 0.005). Our data showed that both SNP309 (in the presence of wild type TP53) and SNP285 act as negative prognostic markers for NSCLC patients, implicating a prominent role for these variants in the outcome of these patients. PMID:28819417

Single-nucleotide polymorphism of INS, INSR, IRS1, IRS2, PPAR-G ...

Indian Academy of Sciences (India)

2017-03-02

Mar 2, 2017 ... Abstract. Polycystic ovary syndrome (PCOS) is the most common and a complex female endocrine disorder, and is one of the leading cause of female infertility. Here, we aimed to investigate the association of single-nucleotide polymorphism of INS, INSR,. IRS1, IRS2, PPAR-G and CAPN10 gene in the ...

Genome-wide SNP detection, validation, and development of an 8K SNP array for apple.

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David Chagné

Full Text Available As high-throughput genetic marker screening systems are essential for a range of genetics studies and plant breeding applications, the International RosBREED SNP Consortium (IRSC has utilized the Illumina Infinium® II system to develop a medium- to high-throughput SNP screening tool for genome-wide evaluation of allelic variation in apple (Malus×domestica breeding germplasm. For genome-wide SNP discovery, 27 apple cultivars were chosen to represent worldwide breeding germplasm and re-sequenced at low coverage with the Illumina Genome Analyzer II. Following alignment of these sequences to the whole genome sequence of 'Golden Delicious', SNPs were identified using SoapSNP. A total of 2,113,120 SNPs were detected, corresponding to one SNP to every 288 bp of the genome. The Illumina GoldenGate® assay was then used to validate a subset of 144 SNPs with a range of characteristics, using a set of 160 apple accessions. This validation assay enabled fine-tuning of the final subset of SNPs for the Illumina Infinium® II system. The set of stringent filtering criteria developed allowed choice of a set of SNPs that not only exhibited an even distribution across the apple genome and a range of minor allele frequencies to ensure utility across germplasm, but also were located in putative exonic regions to maximize genotyping success rate. A total of 7867 apple SNPs was established for the IRSC apple 8K SNP array v1, of which 5554 were polymorphic after evaluation in segregating families and a germplasm collection. This publicly available genomics resource will provide an unprecedented resolution of SNP haplotypes, which will enable marker-locus-trait association discovery, description of the genetic architecture of quantitative traits, investigation of genetic variation (neutral and functional, and genomic selection in apple.

Genome-Wide SNP Detection, Validation, and Development of an 8K SNP Array for Apple

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Chagné, David; Crowhurst, Ross N.; Troggio, Michela; Davey, Mark W.; Gilmore, Barbara; Lawley, Cindy; Vanderzande, Stijn; Hellens, Roger P.; Kumar, Satish; Cestaro, Alessandro; Velasco, Riccardo; Main, Dorrie; Rees, Jasper D.; Iezzoni, Amy; Mockler, Todd; Wilhelm, Larry; Van de Weg, Eric; Gardiner, Susan E.; Bassil, Nahla; Peace, Cameron

2012-01-01

As high-throughput genetic marker screening systems are essential for a range of genetics studies and plant breeding applications, the International RosBREED SNP Consortium (IRSC) has utilized the Illumina Infinium® II system to develop a medium- to high-throughput SNP screening tool for genome-wide evaluation of allelic variation in apple (Malus×domestica) breeding germplasm. For genome-wide SNP discovery, 27 apple cultivars were chosen to represent worldwide breeding germplasm and re-sequenced at low coverage with the Illumina Genome Analyzer II. Following alignment of these sequences to the whole genome sequence of ‘Golden Delicious’, SNPs were identified using SoapSNP. A total of 2,113,120 SNPs were detected, corresponding to one SNP to every 288 bp of the genome. The Illumina GoldenGate® assay was then used to validate a subset of 144 SNPs with a range of characteristics, using a set of 160 apple accessions. This validation assay enabled fine-tuning of the final subset of SNPs for the Illumina Infinium® II system. The set of stringent filtering criteria developed allowed choice of a set of SNPs that not only exhibited an even distribution across the apple genome and a range of minor allele frequencies to ensure utility across germplasm, but also were located in putative exonic regions to maximize genotyping success rate. A total of 7867 apple SNPs was established for the IRSC apple 8K SNP array v1, of which 5554 were polymorphic after evaluation in segregating families and a germplasm collection. This publicly available genomics resource will provide an unprecedented resolution of SNP haplotypes, which will enable marker-locus-trait association discovery, description of the genetic architecture of quantitative traits, investigation of genetic variation (neutral and functional), and genomic selection in apple. PMID:22363718

HOMA1-IR and HOMA2-IR indexes in identifying insulin resistance and metabolic syndrome: Brazilian Metabolic Syndrome Study (BRAMS).

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Geloneze, Bruno; Vasques, Ana Carolina Junqueira; Stabe, Christiane França Camargo; Pareja, José Carlos; Rosado, Lina Enriqueta Frandsen Paez de Lima; Queiroz, Elaine Cristina de; Tambascia, Marcos Antonio

2009-03-01

To investigate cut-off values for HOMA1-IR and HOMA2-IR to identify insulin resistance (IR) and metabolic syndrome (MS), and to assess the association of the indexes with components of the MS. Nondiabetic subjects from the Brazilian Metabolic Syndrome Study were studied (n = 1,203, 18 to 78 years). The cut-off values for IR were determined from the 90th percentile in the healthy group (n = 297) and, for MS, a ROC curve was generated for the total sample. In the healthy group, HOMA-IR indexes were associated with central obesity, triglycerides and total cholesterol (p 2.7 and HOMA2-IR > 1.8; and, for MS were: HOMA1-IR > 2.3 (sensitivity: 76.8%; specificity: 66.7%) and HOMA2-IR > 1.4 (sensitivity: 79.2%; specificity: 61.2%). The cut-off values identified for HOMA1-IR and HOMA2-IR indexes have a clinical and epidemiological application for identifying IR and MS in Westernized admixtured multi-ethnic populations.

Análisis de PCR-RFLP del gen de leptina y su asociación con características de la leche en ganado nativo (Bos indicus de Irán

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Mojtaba Rezaei

2015-01-01

Full Text Available Se utilizó una muestra ganadera experimental para la caracterización de los genes y las frecuencias genotípicas y evaluar la asociación entre los polimorfismos de longitud del fragmento de restricción BsaAI en el gen de leptina y las características lácteas. Se recolectaron muestras de sangre de 390 vacas proporcionadas por el censo ganadero de la provincia de Guilán en Irán. La extracción de ADN genómico se basó en el método modificado de precipitación salina. El fragmento de 522 bp que comprende la región parcial del exón 3 e intrón 2 del locus del gen de leptina se amplificó mediante PCR-RFLP e iniciadores específicos. La digestión del fragmento amplificado con la enzima de restricción BsaAI reveló dos alelos de A y B con frecuencias de 0.447 y 0.553, y tres genotipos de AA, AB, BB con frecuencias de 0.185, 0.526 y 0.289 en la población estudiada, respectivamente. El resultado del contenido de polimorfismo fue 0.372 y para heterocigosis 0.526. Los resultados demostraron que la población estudiada estaba en equilibrio Hardy-Weinberg. El análisis estadístico indicó que el polimorfismo LEP- BsaAI tiene un efecto significativo en la producción de leche, porcentaje de grasa y proteína de la leche ( P <0.01. Animales portadores del genotipo heterocigoto (AB produjeron 1.17 y 0.7 kg/d más leche que los animales homocigotos AA y BB, respectivamente. Los animales con el genotipo AA tuvieron mayor grasa (0.28 % y porcentaje de proteína (0.17 % que el genotipo AB. Tales resultados pueden utilizarse como criterios para facilitar la selección genética en los programas de cría animal.

Vibrational spectroscopic (FT-IR, FT-Raman) and quantum mechanical study of 4-(2-chlorophenyl)-2-ethyl-9-methyl-6H-thieno[3,2-f] [1,2,4]triazolo[4,3-a][1,4] diazepine

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Kuruvilla, Tintu K.; Prasana, Johanan Christian; Muthu, S.; George, Jacob

2018-04-01

The spectroscopic properties of 4-(2-chlorophenyl)-2-ethyl-9-methyl-6H-thieno [3,2-f] [1,2,4] triazolo [4,3-a] [1,4] diazepine were investigated in the present study using FT-IR and FT-Raman techniques. The results obtained were compared with quantum mechanical methods, as it serves as an important tool in interpreting and predicting vibrational spectra. The optimized molecular geometry, the vibrational wavenumbers, the infrared intensities and Raman scattering were calculated using density functional theory B3LYP method with 6-311++g (d,p) basis set. All the experimental results were in line with the theoretical data. The molecular electrostatic potential (MEP) and HOMO LUMO energies of the title compound were accounted. The results indicated that the title compound has a lower softness value (0.27) and high electrophilicity index (4.98) hence describing its biological activity. Further, natural bond orbital was also analyzed as part of the work. Fukui functions were calculated in order to explain the chemical selectivity or the reactivity site in 4-(2-chlorophenyl)-2-ethyl-9-methyl-6H-thieno [3,2-f] [1,2,4] triazolo [4,3-a] [1,4] diazepine. The thermodynamic properties of the title compound were closely examined at different temperatures. It revealed the correlations between heat capacity (C), entropy (S) and enthalpy changes (H) with temperatures. The paper further explains that the title compound can act as good antidepressant through molecular docking studies.

Exhaustive Genome-Wide Search for SNP-SNP Interactions Across 10 Human Diseases

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William Murk

2016-07-01

Full Text Available The identification of statistical SNP-SNP interactions may help explain the genetic etiology of many human diseases, but exhaustive genome-wide searches for these interactions have been difficult, due to a lack of power in most datasets. We aimed to use data from the Resource for Genetic Epidemiology Research on Adult Health and Aging (GERA study to search for SNP-SNP interactions associated with 10 common diseases. FastEpistasis and BOOST were used to evaluate all pairwise interactions among approximately N = 300,000 single nucleotide polymorphisms (SNPs with minor allele frequency (MAF ≥ 0.15, for the dichotomous outcomes of allergic rhinitis, asthma, cardiac disease, depression, dermatophytosis, type 2 diabetes, dyslipidemia, hemorrhoids, hypertensive disease, and osteoarthritis. A total of N = 45,171 subjects were included after quality control steps were applied. These data were divided into discovery and replication subsets; the discovery subset had > 80% power, under selected models, to detect genome-wide significant interactions (P < 10−12. Interactions were also evaluated for enrichment in particular SNP features, including functionality, prior disease relevancy, and marginal effects. No interaction in any disease was significant in both the discovery and replication subsets. Enrichment analysis suggested that, for some outcomes, interactions involving SNPs with marginal effects were more likely to be nominally replicated, compared to interactions without marginal effects. If SNP-SNP interactions play a role in the etiology of the studied conditions, they likely have weak effect sizes, involve lower-frequency variants, and/or involve complex models of interaction that are not captured well by the methods that were utilized.

SNP genotyping technologies

DEFF Research Database (Denmark)

Studer, Bruno; Kölliker, Roland

2013-01-01

In the recent years, single nucleotide polymorphism (SNP) markers have emerged as the marker technology of choice for plant genetics and breeding applications. Besides the efficient technologies available for SNP discovery even in complex genomes, one of the main reasons for this is the availabil...

GEN1 from a thermophilic fungus is functionally closely similar to non-eukaryotic junction-resolving enzymes.

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Freeman, Alasdair D J; Liu, Yijin; Déclais, Anne-Cécile; Gartner, Anton; Lilley, David M J

2014-12-12

Processing of Holliday junctions is essential in recombination. We have identified the gene for the junction-resolving enzyme GEN1 from the thermophilic fungus Chaetomium thermophilum and expressed the N-terminal 487-amino-acid section. The protein is a nuclease that is highly selective for four-way DNA junctions, cleaving 1nt 3' to the point of strand exchange on two strands symmetrically disposed about a diagonal axis. CtGEN1 binds to DNA junctions as a discrete homodimer with nanomolar affinity. Analysis of the kinetics of cruciform cleavage shows that cleavage of the second strand occurs an order of magnitude faster than the first cleavage so as to generate a productive resolution event. All these properties are closely similar to those described for bacterial, phage and mitochondrial junction-resolving enzymes. CtGEN1 is also similar in properties to the human enzyme but lacks the problems with aggregation that currently prevent detailed analysis of the latter protein. CtGEN1 is thus an excellent enzyme with which to engage in biophysical and structural analysis of eukaryotic GEN1. Copyright © 2014. Published by Elsevier Ltd.

Lack of an association of miR-938 SNP in IDDM10 with human type 1 diabetes

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Mi Xiaofan

2011-10-01

Full Text Available Abstract MicroRNAs (miRNAs are a newly discovered type of small non-protein coding RNA that function in the inhibition of effective mRNA translation, and may serve as susceptibility genes for various disease developments. The SNP rs12416605, located in human type 1 diabetes IDDM10 locus, changes the seeding sequence (UGU[G/A]CCC of miRNA miR-938 and potentially alters miR-938 targets, including IL-16 and IL-17A. In an attempt to test whether miR-938 may be a susceptibility gene for IDDM10, we assessed the possible association of the miR-938 SNP with T1D in an American Caucasian cohort of 622 patients and 723 healthy controls by TaqMan assay. Our current data do not support the association between the SNP in miR-938 and type 1 diabetes.

SAQC: SNP Array Quality Control

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Li Ling-Hui

2011-04-01

Full Text Available Abstract Background Genome-wide single-nucleotide polymorphism (SNP arrays containing hundreds of thousands of SNPs from the human genome have proven useful for studying important human genome questions. Data quality of SNP arrays plays a key role in the accuracy and precision of downstream data analyses. However, good indices for assessing data quality of SNP arrays have not yet been developed. Results We developed new quality indices to measure the quality of SNP arrays and/or DNA samples and investigated their statistical properties. The indices quantify a departure of estimated individual-level allele frequencies (AFs from expected frequencies via standardized distances. The proposed quality indices followed lognormal distributions in several large genomic studies that we empirically evaluated. AF reference data and quality index reference data for different SNP array platforms were established based on samples from various reference populations. Furthermore, a confidence interval method based on the underlying empirical distributions of quality indices was developed to identify poor-quality SNP arrays and/or DNA samples. Analyses of authentic biological data and simulated data show that this new method is sensitive and specific for the detection of poor-quality SNP arrays and/or DNA samples. Conclusions This study introduces new quality indices, establishes references for AFs and quality indices, and develops a detection method for poor-quality SNP arrays and/or DNA samples. We have developed a new computer program that utilizes these methods called SNP Array Quality Control (SAQC. SAQC software is written in R and R-GUI and was developed as a user-friendly tool for the visualization and evaluation of data quality of genome-wide SNP arrays. The program is available online (http://www.stat.sinica.edu.tw/hsinchou/genetics/quality/SAQC.htm.

26 CFR 43.0-1 - Introduction.

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2010-04-01

... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Introduction. 43.0-1 Section 43.0-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES EXCISE TAX ON TRANSPORTATION BY WATER § 43.0-1 Introduction. The regulations in this part 43 are designated...

In silico SNP analysis of the breast cancer antigen NY-BR-1.

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Kosaloglu, Zeynep; Bitzer, Julia; Halama, Niels; Huang, Zhiqin; Zapatka, Marc; Schneeweiss, Andreas; Jäger, Dirk; Zörnig, Inka

2016-11-18

Breast cancer is one of the most common malignancies with increasing incidences every year and a leading cause of death among women. Although early stage breast cancer can be effectively treated, there are limited numbers of treatment options available for patients with advanced and metastatic disease. The novel breast cancer associated antigen NY-BR-1 was identified by SEREX analysis and is expressed in the majority (>70%) of breast tumors as well as metastases, in normal breast tissue, in testis and occasionally in prostate tissue. The biological function and regulation of NY-BR-1 is up to date unknown. We performed an in silico analysis on the genetic variations of the NY-BR-1 gene using data available in public SNP databases and the tools SIFT, Polyphen and Provean to find possible functional SNPs. Additionally, we considered the allele frequency of the found damaging SNPs and also analyzed data from an in-house sequencing project of 55 breast cancer samples for recurring SNPs, recorded in dbSNP. Over 2800 SNPs are recorded in the dbSNP and NHLBI ESP databases for the NY-BR-1 gene. Of these, 65 (2.07%) are synonymous SNPs, 191 (6.09%) are non-synoymous SNPs, and 2430 (77.48%) are noncoding intronic SNPs. As a result, 69 non-synoymous SNPs were predicted to be damaging by at least two, and 16 SNPs were predicted as damaging by all three of the used tools. The SNPs rs200639888, rs367841401 and rs377750885 were categorized as highly damaging by all three tools. Eight damaging SNPs are located in the ankyrin repeat domain (ANK), a domain known for its frequent involvement in protein-protein interactions. No distinctive features could be observed in the allele frequency of the analyzed SNPs. Considering these results we expect to gain more insights into the variations of the NY-BR-1 gene and their possible impact on giving rise to splice variants and therefore influence the function of NY-BR-1 in healthy tissue as well as in breast cancer.

DETEKSI GEN-GEN PENYANDI FAKTOR VIRULENSI PADA BAKTERI VIBRIO

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Ince Ayu Khairani Kadriah

2011-04-01

menggunakan isolat bakteri yang diisolasi dari budidaya udang windu di berbagai daerah di Sulawesi Selatan dan Jawa. Pada penelitian ini digunakan primer spesifik untuk mendeteksi gen-gen virulen toxR gene, hemolysin (vvh gene, dan GyrB gene dengan metode PCR. Dari 35 isolat yang diisolasi, 20 isolat terdeteksi memiliki gen virulensi dan 8 di antaranya memiliki dua gen virulen. Spesies bakteri yang memiliki gen virulen adalah: V.harveyi, V. parahaemolyticus, V. mimicus, dan V. campbelli

Evaluación genética preliminar de bovinos Angus en México mediante valores de cría genómicos / Preliminary genetic evaluation of Angus cattle in Mexico using genomic breeding values

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Daniela Elizabeth Briones Martín del Campo

2014-04-01

Full Text Available Con el objeto de evaluar genéticamente bovinos Angus importados a México como embriones, en comparación con una población de referencia internacional y bovinos concebidos localmente, se genotipificaron 143 animales Angus y Angus Rojo con la plataforma BeadChiplllumina BovineSNP50® y se predijeron sus valores de cría genómicos (MVP. En promedio fueron superiores a la media de la población de referencia para características de facilidad de parto directa y materna, habilidad lechera, crecimiento desde el destete hasta el año de edad, peso de la canal, desarrollo muscular, marmoleo y el índice económico de engorda en confinamiento. Los animales originados con germoplasma importado fueron superiores a los concebidos localmente para las características de crecimiento desde el destete hasta el año de edad, desarrollo muscular, marmoleo, terneza de la carne y el índice económico. La población de bovinos Angus evaluada mostró tener potencial genético para seleccionar y utilizar reproductores mejorados.

Resequencing of IRS2 reveals rare variants for obesity but not fasting glucose homeostasis in Hispanic children.

Science.gov (United States)

Butte, Nancy F; Voruganti, V Saroja; Cole, Shelley A; Haack, Karin; Comuzzie, Anthony G; Muzny, Donna M; Wheeler, David A; Chang, Kyle; Hawes, Alicia; Gibbs, Richard A

2011-09-22

Our objective was to resequence insulin receptor substrate 2 (IRS2) to identify variants associated with obesity- and diabetes-related traits in Hispanic children. Exonic and intronic segments, 5' and 3' flanking regions of IRS2 (∼14.5 kb), were bidirectionally sequenced for single nucleotide polymorphism (SNP) discovery in 934 Hispanic children using 3730XL DNA Sequencers. Additionally, 15 SNPs derived from Illumina HumanOmni1-Quad BeadChips were analyzed. Measured genotype analysis tested associations between SNPs and obesity and diabetes-related traits. Bayesian quantitative trait nucleotide analysis was used to statistically infer the most likely functional polymorphisms. A total of 140 SNPs were identified with minor allele frequencies (MAF) ranging from 0.001 to 0.47. Forty-two of the 70 coding SNPs result in nonsynonymous amino acid substitutions relative to the consensus sequence; 28 SNPs were detected in the promoter, 12 in introns, 28 in the 3'-UTR, and 2 in the 5'-UTR. Two insertion/deletions (indels) were detected. Ten independent rare SNPs (MAF = 0.001-0.009) were associated with obesity-related traits (P = 0.01-0.00002). SNP 10510452_139 in the promoter region was shown to have a high posterior probability (P = 0.77-0.86) of influencing BMI, fat mass, and waist circumference in Hispanic children. SNP 10510452_139 contributed between 2 and 4% of the population variance in body weight and composition. None of the SNPs or indels were associated with diabetes-related traits or accounted for a previously identified quantitative trait locus on chromosome 13 for fasting serum glucose. Rare but not common IRS2 variants may play a role in the regulation of body weight but not an essential role in fasting glucose homeostasis in Hispanic children.

Assessing SNP-SNP interactions among DNA repair, modification and metabolism related pathway genes in breast cancer susceptibility.

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Yadav Sapkota

Full Text Available Genome-wide association studies (GWASs have identified low-penetrance common variants (i.e., single nucleotide polymorphisms, SNPs associated with breast cancer susceptibility. Although GWASs are primarily focused on single-locus effects, gene-gene interactions (i.e., epistasis are also assumed to contribute to the genetic risks for complex diseases including breast cancer. While it has been hypothesized that moderately ranked (P value based weak single-locus effects in GWASs could potentially harbor valuable information for evaluating epistasis, we lack systematic efforts to investigate SNPs showing consistent associations with weak statistical significance across independent discovery and replication stages. The objectives of this study were i to select SNPs showing single-locus effects with weak statistical significance for breast cancer in a GWAS and/or candidate-gene studies; ii to replicate these SNPs in an independent set of breast cancer cases and controls; and iii to explore their potential SNP-SNP interactions contributing to breast cancer susceptibility. A total of 17 SNPs related to DNA repair, modification and metabolism pathway genes were selected since these pathways offer a priori knowledge for potential epistatic interactions and an overall role in breast carcinogenesis. The study design included predominantly Caucasian women (2,795 cases and 4,505 controls from Alberta, Canada. We observed two two-way SNP-SNP interactions (APEX1-rs1130409 and RPAP1-rs2297381; MLH1-rs1799977 and MDM2-rs769412 in logistic regression that conferred elevated risks for breast cancer (P(interaction<7.3 × 10(-3. Logic regression identified an interaction involving four SNPs (MBD2-rs4041245, MLH1-rs1799977, MDM2-rs769412, BRCA2-rs1799943 (P(permutation = 2.4 × 10(-3. SNPs involved in SNP-SNP interactions also showed single-locus effects with weak statistical significance, while BRCA2-rs1799943 showed stronger statistical significance (P

Hold your horSSEs: controlling structure-selective endonucleases MUS81 and Yen1/GEN1.

Science.gov (United States)

Blanco, Miguel G; Matos, Joao

2015-01-01

Repair of DNA lesions through homologous recombination promotes the establishment of stable chromosomal interactions. Multiple helicases, topoisomerases and structure-selective endonucleases (SSEs) act upon recombining joint molecules (JMs) to disengage chromosomal connections and safeguard chromosome segregation. Recent studies on two conserved SSEs - MUS81 and Yen1/GEN1- uncovered multiple layers of regulation that operate to carefully tailor JM-processing according to specific cellular needs. Temporal restriction of SSE function imposes a hierarchy in pathway usage that ensures efficient JM-processing while minimizing reciprocal exchanges between the recombining DNAs. Whereas a conserved strategy of fine-tuning SSE functions exists in different model systems, the precise molecular mechanisms to implement it appear to be significantly different. Here, we summarize the current knowledge on the cellular switches that are in place to control MUS81 and Yen1/GEN1 functions.

640 X 480 MOS PtSi IR sensor

Science.gov (United States)

Sauer, Donald J.; Shallcross, Frank V.; Hseuh, Fu-Lung; Meray, Grazyna M.; Levine, Peter A.; Gilmartin, Harvey R.; Villani, Thomas S.; Esposito, Benjamin J.; Tower, John R.

1991-12-01

The design of a 1st and 2nd generation 640(H) X 480(V) element PtSi Schottky-barrier infrared image sensor employing a low-noise MOS X-Y addressable readout multiplexer and on-chip low-noise output amplifier is described. Measured performance characteristics for Gen 1 devices are presented along with calculated performance for the Gen 2 design. A multiplexed horizontal/vertical input address port and on-chip decoding is used to load scan data into CMOS horizontal and vertical scanning registers. This allows random access to any sub-frame in the 640 X 480 element focal plane array. By changing the digital pattern applied to the vertical scan register, the FPA can be operated in either an interlaced or non- interlaced format, and the integration time may be varied over a wide range (60 microsecond(s) to > 30 ms, for RS170 operation) resulting in a form of 'electronic shutter,' or variable exposure control. The pixel size of 24-micrometers X 24-micrometers results in a fill factor of 38% for 1.5-micrometers process design rules. The overall die size for the IR imager is 13.7 mm X 17.2 mm. All digital inputs to the chip are TTL compatible and include ESD protection.

SNP genotyping by DNA photoligation: application to SNP detection of genes from food crops

Energy Technology Data Exchange (ETDEWEB)

Yoshimura, Yoshinaga; Ohtake, Tomoko; Okada, Hajime; Fujimoto, Kenzo [School of Materials Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa 923-1292 (Japan); Ami, Takehiro [Innovation Plaza Ishikawa, Japan Science and Technology Agency, 2-13 Asahidai, Nomi, Ishikawa 923-1211 (Japan); Tsukaguchi, Tadashi, E-mail: kenzo@jaist.ac.j [Faculty of Bioresources and Environmental Sciences, Ishikawa Prefectural University, 1-308 Suematsu, Nonoichi, Ishikawa 921-8836 (Japan)

2009-06-15

We describe a simple and inexpensive single-nucleotide polymorphism (SNP) typing method, using DNA photoligation with 5-carboxyvinyl-2'-deoxyuridine and two fluorophores. This SNP-typing method facilitates qualitative determination of genes from indica and japonica rice, and showed a high degree of single nucleotide specificity up to 10 000. This method can be used in the SNP typing of actual genomic DNA samples from food crops.

SNP genotyping by DNA photoligation: application to SNP detection of genes from food crops

Directory of Open Access Journals (Sweden)

Yoshinaga Yoshimura, Tomoko Ohtake, Hajime Okada, Takehiro Ami, Tadashi Tsukaguchi and Kenzo Fujimoto

2009-01-01

Full Text Available We describe a simple and inexpensive single-nucleotide polymorphism (SNP typing method, using DNA photoligation with 5-carboxyvinyl-2'-deoxyuridine and two fluorophores. This SNP-typing method facilitates qualitative determination of genes from indica and japonica rice, and showed a high degree of single nucleotide specificity up to 10 000. This method can be used in the SNP typing of actual genomic DNA samples from food crops.

APPL1 potentiates insulin sensitivity by facilitating the binding of IRS1/2 to the insulin receptor.

Science.gov (United States)

Ryu, Jiyoon; Galan, Amanda K; Xin, Xiaoban; Dong, Feng; Abdul-Ghani, Muhammad A; Zhou, Lijun; Wang, Changhua; Li, Cuiling; Holmes, Bekke M; Sloane, Lauren B; Austad, Steven N; Guo, Shaodong; Musi, Nicolas; DeFronzo, Ralph A; Deng, Chuxia; White, Morris F; Liu, Feng; Dong, Lily Q

2014-05-22

Binding of insulin receptor substrate proteins 1 and 2 (IRS1/2) to the insulin receptor (IR) is essential for the regulation of insulin sensitivity and energy homeostasis. However, the mechanism of IRS1/2 recruitment to the IR remains elusive. Here, we identify adaptor protein APPL1 as a critical molecule that promotes IRS1/2-IR interaction. APPL1 forms a complex with IRS1/2 under basal conditions, and this complex is then recruited to the IR in response to insulin or adiponectin stimulation. The interaction between APPL1 and IR depends on insulin- or adiponectin-stimulated APPL1 phosphorylation, which is greatly reduced in insulin target tissues in obese mice. appl1 deletion in mice consistently leads to systemic insulin resistance and a significant reduction in insulin-stimulated IRS1/2, but not IR, tyrosine phosphorylation, indicating that APPL1 sensitizes insulin signaling by acting at a site downstream of the IR. Our study uncovers a mechanism regulating insulin signaling and crosstalk between the insulin and adiponectin pathways. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Anticancer effect of genistein on BG-1 ovarian cancer growth induced by 17 β-estradiol or bisphenol A via the suppression of the crosstalk between estrogen receptor alpha and insulin-like growth factor-1 receptor signaling pathways

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Hwang, Kyung-A; Park, Min-Ah; Kang, Nam-Hee; Yi, Bo-Rim; Hyun, Sang-Hwan; Jeung, Eui-Bae; Choi, Kyung-Chul, E-mail: kchoi@cbu.ac.kr

2013-11-01

The interaction between estrogen receptor (ER) and insulin-like growth factor-1 receptor (IGF-1R) signaling pathway plays an important role in proliferation of and resistance to endocrine therapy to estrogen dependent cancers. Estrogen (E2) upregulates the expression of components of IGF-1 system and induces the downstream of mitogenic signaling cascades via phosphorylation of insulin receptor substrate-1 (IRS-1). In the present study, we evaluated the xenoestrogenic effect of bisphenol A (BPA) and antiproliferative activity of genistein (GEN) in accordance with the influence on this crosstalk. BPA was determined to affect this crosstalk by upregulating mRNA expressions of ERα and IGF-1R and inducing phosphorylation of IRS-1 and Akt in protein level in BG-1 ovarian cancer cells as E2 did. In the mouse model xenografted with BG-1 cells, BPA significantly increased a tumor burden of mice and expressions of ERα, pIRS-1, and cyclin D1 in tumor mass compared to vehicle, indicating that BPA induces ovarian cancer growth by promoting the crosstalk between ER and IGF-1R signals. On the other hand, GEN effectively reversed estrogenicity of BPA by reversing mRNA and protein expressions of ERα, IGF-1R, pIRS-1, and pAkt induced by BPA in cellular model and also significantly decreased tumor growth and in vivo expressions of ERα, pIRS-1, and pAkt in xenografted mouse model. Also, GEN was confirmed to have an antiproliferative effect by inducing apoptotic signaling cascades. Taken together, these results suggest that GEN effectively reversed the increased proliferation of BG-1 ovarian cancer by suppressing the crosstalk between ERα and IGF-1R signaling pathways upregulated by BPA or E2.

Anticancer effect of genistein on BG-1 ovarian cancer growth induced by 17 β-estradiol or bisphenol A via the suppression of the crosstalk between estrogen receptor alpha and insulin-like growth factor-1 receptor signaling pathways

International Nuclear Information System (INIS)

Hwang, Kyung-A; Park, Min-Ah; Kang, Nam-Hee; Yi, Bo-Rim; Hyun, Sang-Hwan; Jeung, Eui-Bae; Choi, Kyung-Chul

2013-01-01

The interaction between estrogen receptor (ER) and insulin-like growth factor-1 receptor (IGF-1R) signaling pathway plays an important role in proliferation of and resistance to endocrine therapy to estrogen dependent cancers. Estrogen (E2) upregulates the expression of components of IGF-1 system and induces the downstream of mitogenic signaling cascades via phosphorylation of insulin receptor substrate-1 (IRS-1). In the present study, we evaluated the xenoestrogenic effect of bisphenol A (BPA) and antiproliferative activity of genistein (GEN) in accordance with the influence on this crosstalk. BPA was determined to affect this crosstalk by upregulating mRNA expressions of ERα and IGF-1R and inducing phosphorylation of IRS-1 and Akt in protein level in BG-1 ovarian cancer cells as E2 did. In the mouse model xenografted with BG-1 cells, BPA significantly increased a tumor burden of mice and expressions of ERα, pIRS-1, and cyclin D1 in tumor mass compared to vehicle, indicating that BPA induces ovarian cancer growth by promoting the crosstalk between ER and IGF-1R signals. On the other hand, GEN effectively reversed estrogenicity of BPA by reversing mRNA and protein expressions of ERα, IGF-1R, pIRS-1, and pAkt induced by BPA in cellular model and also significantly decreased tumor growth and in vivo expressions of ERα, pIRS-1, and pAkt in xenografted mouse model. Also, GEN was confirmed to have an antiproliferative effect by inducing apoptotic signaling cascades. Taken together, these results suggest that GEN effectively reversed the increased proliferation of BG-1 ovarian cancer by suppressing the crosstalk between ERα and IGF-1R signaling pathways upregulated by BPA or E2

Evaluation of Connexin 43 Redistribution and Endocytosis in Astrocytes Subjected to Ischemia/Reperfusion or Oxygen-Glucose Deprivation and Reoxygenation

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Hongyan Xie

2017-01-01

Full Text Available Connexin 43 (Cx43 is the major component protein in astrocytic gap junction communication. Recent studies have shown the cellular processes of gap junction internalization and degradation, but many details remain unknown. This study investigated the distribution of Cx43 and its mechanism after ischemic insult. Astrocyte culture system and a model of ischemia/reperfusion (IR or oxygen-glucose deprivation and reoxygenation (OGDR were established. Cx43 distribution was observed by laser scanning confocal microscopy under different cultivation conditions. Western blot and RT-PCR assays were applied to quantify Cx43 and MAPRE1 (microtubule-associated protein RP/EB family member 1 expression at different time points. The total number of Cx43 was unchanged in the normal and IR/OGDR groups, but Cx43 particles in the cytoplasm of the IR/OGDR group were significantly greater than that of the normal group. Particles in the cytoplasm were significantly fewer after endocytosis was blocked by dynasore. There was no difference among the groups at each time point regarding protein or gene expression of MAPRE1. We concluded that internalization of Cx43 into the cytoplasm occurred during ischemia, which was partially mediated through endocytosis, not by the change of Cx43 quantity. Moreover, internalization was not related to microtubule transport.

16 CFR 1.43 - Recommendations.

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2010-01-01

... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Recommendations. 1.43 Section 1.43 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE GENERAL... investigation. If, after investigation, it concludes that the law has been violated, it may make to such...

46 CFR 167.43-1 - Application.

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2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Application. 167.43-1 Section 167.43-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS PUBLIC NAUTICAL SCHOOL SHIPS Work Vests § 167.43-1 Application. (a) Provisions of this subpart shall apply to all vessels inspected and...

Application of FT-IR spectroscopy on breast cancer serum analysis

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Elmi, Fatemeh; Movaghar, Afshin Fayyaz; Elmi, Maryam Mitra; Alinezhad, Heshmatollah; Nikbakhsh, Novin

2017-12-01

Breast cancer is regarded as the most malignant tumor among women throughout the world. Therefore, early detection and proper diagnostic methods have been known to help save women's lives. Fourier Transform Infrared (FT-IR) spectroscopy, coupled with PCA-LDA analysis, is a new technique to investigate the characteristics of serum in breast cancer. In this study, 43 breast cancer and 43 healthy serum samples were collected, and the FT-IR spectra were recorded for each one. Then, PCA analysis and linear discriminant analysis (LDA) were used to analyze the spectral data. The results showed that there were differences between the spectra of the two groups. Discriminating wavenumbers were associated with several spectral differences over the 950-1200 cm- 1(sugar), 1190-1350 cm- 1 (collagen), 1475-1710 cm- 1 (protein), 1710-1760 cm- 1 (ester), 2800-3000 cm- 1 (stretching motions of -CH2 & -CH3), and 3090-3700 cm- 1 (NH stretching) regions. PCA-LDA performance on serum IR could recognize changes between the control and the breast cancer cases. The diagnostic accuracy, sensitivity, and specificity of PCA-LDA analysis for 3000-3600 cm- 1 (NH stretching) were found to be 83%, 84%, 74% for the control and 80%, 76%, 72% for the breast cancer cases, respectively. The results showed that the major spectral differences between the two groups were related to the differences in protein conformation in serum samples. It can be concluded that FT-IR spectroscopy, together with multivariate data analysis, is able to discriminate between breast cancer and healthy serum samples.

On the separation of enantiomers of 1,1,1,2-tetrafluoroiodoethane by IR multiphoton excitation

International Nuclear Information System (INIS)

Pochert, J.; Quack, M.; Seyfang, G.

2002-01-01

The first attempt to separate enantiomers of chiral molecules using IR-multiphoton excitation with circularly polarized light is reported. 1,1,1,2-Tetrafuoroiodoethane CF 3 CHFI has been chosen as its IR-spectroscopy and its IR-photochemistry is well characterized by our previous work. A theoretical model based on a master equation is presented to predict the enrichment factor. The experimental results show that the experimental sensitivity must be improved to reach the limit of the theoretical prediction. (author)

Composición de Ácidos Grasos (MUFA y CLA) en Tejido Muscular de Bovino Relacionado con la Presencia del Polimorfismo g.878TC en el Gen SCD

OpenAIRE

Inostroza, K; Larama, G; Sepúlveda, N

2012-01-01

El tejido muscular de muchos animales domésticos es fuente de proteínas, grasa y minerales para los seres humanos y está compuesto por una serie de estructuras que le otorgan propiedades nutricionales y bioquímicas. En los ultimos años se ha identificado un polimorfismo de único nucleótido (SNP) en el gen SCD (g.878TC), que influye sobre la composición de ácidos grasos en los bovinos. El objetivo de este estudio fue determinar la presencia del SNP g.878TC en músculo Longissimus dorsi de bovin...

SNPServer: a real-time SNP discovery tool.

Science.gov (United States)

Savage, David; Batley, Jacqueline; Erwin, Tim; Logan, Erica; Love, Christopher G; Lim, Geraldine A C; Mongin, Emmanuel; Barker, Gary; Spangenberg, German C; Edwards, David

2005-07-01

SNPServer is a real-time flexible tool for the discovery of SNPs (single nucleotide polymorphisms) within DNA sequence data. The program uses BLAST, to identify related sequences, and CAP3, to cluster and align these sequences. The alignments are parsed to the SNP discovery software autoSNP, a program that detects SNPs and insertion/deletion polymorphisms (indels). Alternatively, lists of related sequences or pre-assembled sequences may be entered for SNP discovery. SNPServer and autoSNP use redundancy to differentiate between candidate SNPs and sequence errors. For each candidate SNP, two measures of confidence are calculated, the redundancy of the polymorphism at a SNP locus and the co-segregation of the candidate SNP with other SNPs in the alignment. SNPServer is available at http://hornbill.cspp.latrobe.edu.au/snpdiscovery.html.

IGF-IR internalizes with Caveolin-1 and PTRF/Cavin in HaCat cells.

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Barbara Salani

Full Text Available BACKGROUND: Insulin-like growth factor-I receptor (IGF-IR is a tyrosine kinase receptor (RTK associated with caveolae, invaginations of the plasma membrane that regulate vesicular transport, endocytosis and intracellular signaling. IGF-IR internalization represents a key mechanism of down-modulation of receptors number on plasma membrane. IGF-IR interacts directly with Caveolin-1 (Cav-1, the most relevant protein of caveolae. Recently it has been demonstrated that the Polymerase I and Transcript Release Factor I (PTRF/Cavin is required for caveolae biogenesis and function. The role of Cav-1 and PTRF/Cavin in IGF-IR internalization is still to be clarified. METHODOLOGY/PRINCIPAL FINDINGS: We have investigated the interaction of IGF-IR with Cav-1 and PTRF/Cavin in the presence of IGF1in human Hacat cells. We show that IGF-IR internalization triggers Cav-1 and PTRF/Cavin translocation from plasma membrane to cytosol and increases IGF-IR interaction with these proteins. In fact, Cav-1 and PTRF/Cavin co-immunoprecipitate with IGF-IR during receptor internalization. We found a different time course of co-immunoprecipitation between IGF-IR and Cav-1 compared to IGF-IR and PTRF/Cavin. Cav-1 and PTRF/Cavin silencing by siRNA differently affect surface IGF-IR levels following IGF1 treatment: Cav-1 and PTRF/Cavin silencing significantly affect IGF-IR rate of internalization, while PTRF/Cavin silencing also decreases IGF-IR plasma membrane recovery. Since Cav-1 phosphorylation could have a role in IGF-IR internalization, the mutant Cav-1Y14F lacking Tyr14 was transfected. Cav-1Y14F transfected cells showed a reduced internalization of IGF-IR compared with cells expressing wild type Cav-1. Receptor internalization was not impaired by Clathrin silencing. These findings support a critical role of caveolae in IGF-IR intracellular traveling. CONCLUSIONS/SIGNIFICANCE: These data indicate that Caveolae play a role in IGF-IR internalization. Based on these findings

Birth-weight, insulin levels, and HOMA-IR in newborns at term.

Science.gov (United States)

Simental-Mendía, Luis E; Castañeda-Chacón, Argelia; Rodríguez-Morán, Martha; Guerrero-Romero, Fernando

2012-07-07

Recent studies have demonstrated that low and high birth-weight at birth are risk factors of developing diabetes. The aim of this study was to determine if the abnormal birth-weight is related with hyperinsulinemia and elevated index of the Homeostasis Model assessment for Insulin Resistance (HOMA-IR) at birth, in at term newborns. Newborns with gestational age between 38 and 41 weeks, products of normal pregnancies of healthy mothers aged 18 to 39 years, were eligible to participate. Small-for-gestational age (SGA) and large-for-gestational age (LGA) newborns were compared with appropriate-for-gestational (AGA) age newborns. Incomplete or unclear data about mother's health status, diabetes, gestational diabetes, history of gestational diabetes, hypertension, pre-eclampsia, eclampsia, and other conditions that affect glucose metabolism were exclusion criteria. Hyperinsulinemia was defined by serum insulin levels ≥13.0 μU/mL and IR by HOMA-IR ≥2.60. Multiple logistic regression analysis was used to determine the odds ratio (OR) that computes the association between birth-weight (independent variable) with hyperinsulinemia and HOMA-IR index (dependent variables). A total of 107 newborns were enrolled; 13, 22, and 72 with SGA, LGA, and AGA, respectively. Hyperinsulinemia was identified in 2 (15.4%), 6 (27.3%), and 5 (6.9%) with SGA, LGA, and AGA (p=0.03), whereas IR in 3 (23.1%), 8 (36.4%), and 10 (13.9%) newborns with SGA, LGA and AGA (p=0.06). The LGA showed a strong association with hyperinsulinemia (OR 5.02; CI 95%, 1.15-22.3; p=0.01) and HOMA-IR (OR 3.54; CI 95%, 1.03-12.16; p=0.02); although without statistical significance, the SGA showed a tendency of association with hyperinsulinemia (OR 2.43; CI 95%, 0.43-17.3 p=0.29) and HOMA-IR (OR 1.86; CI 95%, 0.33-9.37; p=0.41). Our results suggest that LGA is associated with hyperinsulinemia and elevated HOMA-IR at birth whereas the SGA show a tendency of association.

Taxonomic dissection of the genus Micrococcus: Kocuria gen. nov., Nesterenkonia gen. nov., Kytococcus gen. nov., Dermacoccus gen. nov., and Micrococcus Cohn 1872 gen. emend.

Science.gov (United States)

Stackebrandt, E; Koch, C; Gvozdiak, O; Schumann, P

1995-10-01

The results of a phylogenetic and chemotaxonomic analysis of the genus Micrococcus indicated that it is significantly heterogeneous. Except for Micrococcus lylae, no species groups phylogenetically with the type species of the genus, Micrococcus luteus. The other members of the genus form three separate phylogenetic lines which on the basis of chemotaxonomic properties can be assigned to four genera. These genera are the genus Kocuria gen. nov. for Micrococcus roseus, Micrococcus varians, and Micrococcus kristinae, described as Kocuria rosea comb. nov., Kocuria varians comb. nov., and Kocuria kristinae comb. nov., respectively; the genus Nesterenkonia gen. nov. for Micrococcus halobius, described as Nesterenkonia halobia comb. nov.; the genus Nesterenkonia gen. nov. for Micrococcus halobius, described as Nesterenkonia halobia comb. nov.; the genus Dermacoccus gen. nov. for Micrococcus nishinomiyaensis, described as Dermacoccus nishinomiyaensis comb. nov.; and the genus Kytocossus gen. nov. for Micrococcus sedentarius, described as Kytococcus sedentarius comb. nov. M. luteus and M. lylae, which are closely related phylogenetically but differ in some chemotaxonomic properties, are the only species that remain in the genus Micrococcus Cohn 1872. An emended description of the genus Micrococcus is given [corrected].

4PS/insulin receptor substrate (IRS)-2 is the alternative substrate of the insulin receptor in IRS-1-deficient mice.

Science.gov (United States)

Patti, M E; Sun, X J; Bruening, J C; Araki, E; Lipes, M A; White, M F; Kahn, C R

1995-10-20

Insulin receptor substrate-1 (IRS-1) is the major cytoplasmic substrate of the insulin and insulin-like growth factor (IGF)-1 receptors. Transgenic mice lacking IRS-1 are resistant to insulin and IGF-1, but exhibit significant residual insulin action which corresponds to the presence of an alternative high molecular weight substrate in liver and muscle. Recently, Sun et al. (Sun, X.-J., Wang, L.-M., Zhang, Y., Yenush, L. P., Myers, M. G., Jr., Glasheen, E., Lane, W.S., Pierce, J. H., and White, M. F. (1995) Nature 377, 173-177) purified and cloned 4PS, the major substrate of the IL-4 receptor-associated tyrosine kinase in myeloid cells, which has significant structural similarity to IRS-1. To determine if 4PS is the alternative substrate of the insulin receptor in IRS-1-deficient mice, we performed immunoprecipitation, immunoblotting, and phosphatidylinositol (PI) 3-kinase assays using specific antibodies to 4PS. Following insulin stimulation, 4PS is rapidly phosphorylated in liver and muscle, binds to the p85 subunit of PI 3-kinase, and activates the enzyme. Insulin stimulation also results in the association of 4PS with Grb 2 in both liver and muscle. In IRS-1-deficient mice, both the phosphorylation of 4PS and associated PI 3-kinase activity are enhanced, without an increase in protein expression. Immunodepletion of 4PS from liver and muscle homogenates removes most of the phosphotyrosine-associated PI 3-kinase activity in IRS-1-deficient mice. Thus, 4PS is the primary alternative substrate, i.e. IRS-2, which plays a major role in physiologic insulin signal transduction via both PI 3-kinase activation and Grb 2/Sos association. In IRS-1-deficient mice, 4PS/IRS-2 provides signal transduction to these two major pathways of insulin signaling.

Variabilidad genética de la respuesta inflamatoria: I. Polimorfismo -511 C/T en el gen IL1β en diferentes subpoblaciones peruanas

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Óscar Acosta

2012-07-01

Full Text Available El polimorfismo -511 citosina/timina (-511 C/T en la región promotora del gen interleuquina 1 beta (IL1β estα implicado en la producciσn diferencial de la citoquina y por tanto puede estar asociado a la respuesta inmuno-inflamatoria en obesidad, dislipidemias, cardiopatías, cáncer, infecciones, y el tratamiento con nutrientes y fármacos. Objetivos: Establecer la distribución de frecuencias de los genotipos y alelos del polimorfismo -511 C/T del gen IL1β en diferentes subpoblaciones peruanas. Diseño: Estudio descriptivo, observacional, transversal. Instituciones: Centro de Investigación de Bioquímica y Nutrición e Instituto de Medicina Tropical D.A. Carrión, Facultad de Medicina, UNMSM y Centro de Genética y Biología Molecular, Facultad de Medicina, USMP, Lima, Perú. Participantes: Pobladores peruanos. Intervenciones: Extracción de ADN genómico a partir de muestras sanguíneas o epitelio bucal según metodología estándar, de 168 individuos de 9 grupos subpoblacionales: 23 mestizos de Lima, 33 amazónicos (20 de Pucallpa y 13 de Amazonas y 112 andinos (12 de Ancash, 10 de Cajamarca, 18 de Huarochirí-Lima, 25 de Puno-Taquile, 25 de Puno-Uros y 22 de Puno-Anapia. Análisis del polimorfismo -511 C/T mediante la técnica de PCR/RFLP, con primers específicos y digestión con la enzima de restricción AvaI, detectándose los fragmentos por electroforesis en geles de agarosa al 2% y tinción con bromuro de etidio. Principales medidas de resultados: Frecuencias genotípicas y alélicas del gen IL1β. Resultados: Se encontró las siguientes frecuencias genotípicas CC=0,024; CT=0,369 y TT=0,607, consistentes con el equilibrio de Hardy-Weinberg; y las frecuencias alélicas fueron alelo C=0,208 y aleloT= 0,792. La frecuencia del alelo T, considerado el mutante, fue muy alta en los Uros de Puno (0.940 y más baja en los mestizos de Lima (0.609. La comparación de las frecuencias genotípicas (TT versus CT+CC y alélicas (T versus C

Caracterização físico-química de frutos de genótipos de aceroleira (Malpighia emarginata D.C.

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Maria Inês Sucupira Maciel

2010-12-01

Full Text Available No Brasil, a aceroleira, decorrente principalmente da propagação por sementes, tem dado origem a plantios comerciais cujos frutos apresentam parâmetros de qualidade diferenciados. Características físico-químicas de frutos de 18 genótipos de aceroleira (Malpighia emarginata DC. do Banco Ativo de Germoplasma da Universidade Federal Rural de Pernambuco - UFRPE foram avaliados. O rendimento em polpa variou de 41,06% (PL 40 a 72,54% (PL 43 e, com exceção do genótipo PL 37, os demais apresentaram frutos com teores de ácido ascórbico superiores a 1000 mg.100 g-1. O genótipo PL 39 destacou-se por apresentar o maior teor de ácido ascórbico (1667 mg.100 g-1, SST e flavonóis (15,04 mg.100 g-1, além de elevado teor de antocianinas, sendo, portanto, o mais promissor. Os frutos do genótipo PL 34 revelaram o maior valor de SST/ATT, indicando ser o mais doce

High-pressure synthesis and structural, physical properties of CaIr1-xPtxO3 and CaIr1-xRhxO3

Science.gov (United States)

Hirai, S.; Bromiley, G. D.; Klemme, S.; Irifune, T.; Ohfuji, H.; Attfield, P.; Nishiyama, N.

2010-12-01

in terms of materials science applications. To our knowledge, this will be the first report on structural, magnetic and charge-transport properties of B-site substituted solid solutions of post-perovskite oxides with 4d/5d transition metals. High-quality polycrystalline samples of CaIr1-xPtxO3 and CaIr1-xRhxO3 have been obtained at high pressures, and structural, magnetic and charge-transport properties of the compounds will be reported. ODF analysis reveals that solutions of CaIrO3, CaPtO3 and CaRhO3 exhibit similar grain growth features to the mother compound, although growth in [0 1 0] plays a more dominant role than the growth in [0 0 1] for the solid solutions. CaIrO3 is a characteristic hard magnet suitable for applications such as magnetic recording, with TN = 108K. A new phase of CaIr1-xPtxO3 synthesized at a high P/T condition has Raman modes which resemble those of CaIrO3 perovskite, suggesting this phase has a perovskite structure.The instability of the perovskite phase of CaIr1-xPtxO3 reveals why the post-perovskite to peovskite phase transition has not been observed for CaPtO3 unlike the case for CaIrO3, CaRhO3 and CaRuO3.

A functional SNP associated with atopic dermatitis controls cell type-specific methylation of the VSTM1 gene locus

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Dilip Kumar

2017-02-01

Full Text Available Abstract Background Expression quantitative trait loci (eQTL databases represent a valuable resource to link disease-associated SNPs to specific candidate genes whose gene expression is significantly modulated by the SNP under investigation. We previously identified signal inhibitory receptor on leukocytes-1 (SIRL-1 as a powerful regulator of human innate immune cell function. While it is constitutively high expressed on neutrophils, on monocytes the SIRL-1 surface expression varies strongly between individuals. The underlying mechanism of regulation, its genetic control as well as potential clinical implications had not been explored yet. Methods Whole blood eQTL data of a Chinese cohort was used to identify SNPs regulating the expression of VSTM1, the gene encoding SIRL-1. The genotype effect was validated by flow cytometry (cell surface expression, correlated with electrophoretic mobility shift assay (EMSA, chromatin immunoprecipitation (ChIP and bisulfite sequencing (C-methylation and its functional impact studied the inhibition of reactive oxygen species (ROS. Results We found a significant association of a single CpG-SNP, rs612529T/C, located in the promoter of VSTM1. Through flow cytometry analysis we confirmed that primarily in the monocytes the protein level of SIRL-1 is strongly associated with genotype of this SNP. In monocytes, the T allele of this SNP facilitates binding of the transcription factors YY1 and PU.1, of which the latter has been recently shown to act as docking site for modifiers of DNA methylation. In line with this notion rs612529T associates with a complete demethylation of the VSTM1 promoter correlating with the allele-specific upregulation of SIRL-1 expression. In monocytes, this upregulation strongly impacts the IgA-induced production of ROS by these cells. Through targeted association analysis we found a significant Meta P value of 1.14 × 10–6 for rs612529 for association to atopic dermatitis (AD

A set of 14 DIP-SNP markers to detect unbalanced DNA mixtures.

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Liu, Zhizhen; Liu, Jinding; Wang, Jiaqi; Chen, Deqing; Liu, Zidong; Shi, Jie; Li, Zeqin; Li, Wenyan; Zhang, Gengqian; Du, Bing

2018-03-04

Unbalanced DNA mixture is still a difficult problem for forensic practice. DIP-STRs are useful markers for detection of minor DNA but they are not widespread in the human genome and having long amplicons. In this study, we proposed a novel type of genetic marker, termed DIP-SNP. DIP-SNP refers to the combination of INDEL and SNP in less than 300bp length of human genome. The multiplex PCR and SNaPshot assay were established for 14 DIP-SNP markers in a Chinese Han population from Shanxi, China. This novel compound marker allows detection of the minor DNA contributor with sensitivity from 1:50 to 1:1000 in a DNA mixture of any gender with 1 ng-10 ng DNA template. Most of the DIP-SNP markers had a relatively high probability of informative alleles with an average I value of 0.33. In all, we proposed DIP-SNP as a novel kind of genetic marker for detection of minor contributor from unbalanced DNA mixture and established the detection method by associating the multiplex PCR and SNaPshot assay. DIP-SNP polymorphisms are promising markers for forensic or clinical mixture examination because they are shorter, widespread and higher sensitive. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of Dioscorea esculenta and Eubacterium rectale on insulin receptor substrate 1 (Irs1 Expression in skeletal muscle and homeostatic model assessment-insulin resistance (HOMA-IR in diabetic rats

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. Sunarti

2017-01-01

Full Text Available Low expression of insulin receptor substrate 1 (Irs1 is associated with insulin resistance and type 2 diabetes mellitus (type 2 DM. This study was performed to evaluate the effects of Dioscorea esculenta and Eubacterium rectale on the Irs1 expression in the skeletal muscle and the homeostatic model assessment-insulin resistance (HOMA-IR of diabetic rats. Twenty-five male Wistar rats were divided into five groups i.e. non diabetic rats Group 1; diabetic rats as Group 2; diabetic rats + D. esculenta as Group 3; diabetic rats + E.rectale as Group 4 and diabetic rats + both E. rectale and D. esculenta as Group 5. Rats were made diabetic with induction of intraperitoneally injection of nicotinamide and streptozotocin. After four weeks of the interventions, the blood and skeletal muscles were taken. The Irs1 expression was analyzed with immunohistochemical staining, plasma glucose levels was analyzed using a spectrophotometer, and insulin was analyzed using ELISA methods. All intervention groups reduced plasma glucose levels and HOMA-IRs (p<0.001 and increased Irs1 expression. The greatest reduction of  plasma glucose levels and increase of Irs1 expression in the skeletal muscle were found in Group 4, however, the lowest of HOMA-IR was seen in Group 5. These results suggested that D.esculenta, E.rectale, and the combination reduced plasma glucose levels and HOMA-IR by increasing Irs1 expression in skeletal muscle.

Par and IR reflectance, transmittance, and absorptance of four crop canopies

International Nuclear Information System (INIS)

Wanjura, D.F.; Hatfield, J.L.

1986-01-01

Reflectance, transmittance and absorptance of electromagnetic radiation by cotton, soybeans, grain sorghum, and sunflower was measured at three growth stages in two wavebands (PAR: 0.4 to 0.7 pun and IR: 0.7 to 1.1 yim). As leaf area increased in each crop there were increases in IR reflectance and PAR absorptance and decreases in PAR reflectance and both PAR and IR transmittance. IR radiation was concentrated at the soil surface between rows by reflectance from the sides of canopies when crop cover was less than 80%. Across all crops one parameter, leaf overlap index, explained 81 and 71% of the PAR reflectance and another, crop cover, explained 86 and 94% of IR reflectance from rows and interrows, respectively. Attenuation of PAR radiation through the canopies of cotton and sunflower was similar (K = 0.62 and 0.67) but different from that of soybeans and grain sorghum (K = 0.46 and 0.43) which were the same

Plk1 phosphorylation of IRS2 prevents premature mitotic exit via AKT inactivation

Science.gov (United States)

Chen, Long; Li, Zhiguo; Ahmad, Nihal; Liu, Xiaoqi

2016-01-01

Insulin receptor substrate (IRS) proteins play important roles by acting as a platform in transducing signals from transmembrane receptors upon growth factor stimulation. Although tyrosine phosphorylation on IRS proteins plays critical roles in signal transduction, phosphorylation of IRS proteins on serine/threonine residues are believed to play various regulatory roles on IRS protein function. However, studies on serine/threonine phosphorylation of IRS proteins are very limited, especially for insulin receptor substrate 2 (IRS2), one member of the IRS protein family. In this study, we identify Polo-like kinase 1 (Plk1) as the responsible kinase for phosphorylation of IRS2 on two serine residues, Ser 556 and Ser 1098. Phosphorylation of IRS2 on these two serine residues by Plk1 prevents the activation of the PI3K pathway upon growth factor stimulation by inhibiting the binding between IRS2 and the PI3K pathway components and increasing IRS2 protein degradation. Of significance, we show that IRS2 phosphorylation is cell cycle regulated and that Plk1 phosphorylation of IRS2 prevents premature mitotic exit via AKT inactivation. PMID:25830382

dbSNP

Data.gov (United States)

U.S. Department of Health & Human Services — dbSNP is a database of single nucleotide polymorphisms (SNPs) and multiple small-scale variations that include insertions/deletions, microsatellites, and...

PredictSNP: robust and accurate consensus classifier for prediction of disease-related mutations.

Directory of Open Access Journals (Sweden)

Jaroslav Bendl

2014-01-01

Full Text Available Single nucleotide variants represent a prevalent form of genetic variation. Mutations in the coding regions are frequently associated with the development of various genetic diseases. Computational tools for the prediction of the effects of mutations on protein function are very important for analysis of single nucleotide variants and their prioritization for experimental characterization. Many computational tools are already widely employed for this purpose. Unfortunately, their comparison and further improvement is hindered by large overlaps between the training datasets and benchmark datasets, which lead to biased and overly optimistic reported performances. In this study, we have constructed three independent datasets by removing all duplicities, inconsistencies and mutations previously used in the training of evaluated tools. The benchmark dataset containing over 43,000 mutations was employed for the unbiased evaluation of eight established prediction tools: MAPP, nsSNPAnalyzer, PANTHER, PhD-SNP, PolyPhen-1, PolyPhen-2, SIFT and SNAP. The six best performing tools were combined into a consensus classifier PredictSNP, resulting into significantly improved prediction performance, and at the same time returned results for all mutations, confirming that consensus prediction represents an accurate and robust alternative to the predictions delivered by individual tools. A user-friendly web interface enables easy access to all eight prediction tools, the consensus classifier PredictSNP and annotations from the Protein Mutant Database and the UniProt database. The web server and the datasets are freely available to the academic community at http://loschmidt.chemi.muni.cz/predictsnp.

HOMA1-IR and HOMA2-IR indexes in identifying insulin resistance and metabolic syndrome - Brazilian Metabolic Syndrome Study (BRAMS)

OpenAIRE

Geloneze, B; Vasques, ACJ; Stabe, CFC; Pareja, JC; Rosado, LEFPD; de Queiroz, EC; Tambascia, MA

2009-01-01

Objective: To investigate cut-off values for HOMA1-IR and HOMA2-IR to identify insulin resistance (IR) and metabolic syndrome (MS), and to assess the association of the indexes with components of the MS. Methods: Nondiabetic subjects from the Brazilian Metabolic Syndrome Study were studied (n = 1,203, 18 to 78 years). The cut-off values for IR were determined from the 9011 percentile in the healthy group (n = 297) and, for MS, a ROC curve was generated for the total sample. Results: In the he...

Birth-weight, insulin levels, and HOMA-IR in newborns at term

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Simental-Mendía Luis E

2012-07-01

Full Text Available Abstract Background Recent studies have demonstrated that low and high birth-weight at birth are risk factors of developing diabetes. The aim of this study was to determine if the abnormal birth-weight is related with hyperinsulinemia and elevated index of the Homeostasis Model assessment for Insulin Resistance (HOMA-IR at birth, in at term newborns. Methods Newborns with gestational age between 38 and 41 weeks, products of normal pregnancies of healthy mothers aged 18 to 39 years, were eligible to participate. Small-for-gestational age (SGA and large-for-gestational age (LGA newborns were compared with appropriate-for-gestational (AGA age newborns. Incomplete or unclear data about mother’s health status, diabetes, gestational diabetes, history of gestational diabetes, hypertension, pre-eclampsia, eclampsia, and other conditions that affect glucose metabolism were exclusion criteria. Hyperinsulinemia was defined by serum insulin levels ≥13.0 μU/mL and IR by HOMA-IR ≥2.60. Multiple logistic regression analysis was used to determine the odds ratio (OR that computes the association between birth-weight (independent variable with hyperinsulinemia and HOMA-IR index (dependent variables. Results A total of 107 newborns were enrolled; 13, 22, and 72 with SGA, LGA, and AGA, respectively. Hyperinsulinemia was identified in 2 (15.4%, 6 (27.3%, and 5 (6.9% with SGA, LGA, and AGA (p=0.03, whereas IR in 3 (23.1%, 8 (36.4%, and 10 (13.9% newborns with SGA, LGA and AGA (p=0.06. The LGA showed a strong association with hyperinsulinemia (OR 5.02; CI 95%, 1.15-22.3; p=0.01 and HOMA-IR (OR 3.54; CI 95%, 1.03-12.16; p=0.02; although without statistical significance, the SGA showed a tendency of association with hyperinsulinemia (OR 2.43; CI 95%, 0.43-17.3 p=0.29 and HOMA-IR (OR 1.86; CI 95%, 0.33-9.37; p=0.41. Conclusions Our results suggest that LGA is associated with hyperinsulinemia and elevated HOMA-IR at birth whereas the SGA show a tendency of

GenBank

OpenAIRE

Benson, Dennis A.; Karsch-Mizrachi, Ilene; Lipman, David J.; Ostell, James; Rapp, Barbara A.; Wheeler, David L.

2002-01-01

The GenBank sequence database incorporates publicly available DNA sequences of more than 105 000 different organisms, primarily through direct submission of sequence data from individual laboratories and large-scale sequencing projects. Most submissions are made using the BankIt (web) or Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Data exchange with the EMBL Data Library and the DNA Data Bank of Japan helps ensure comprehensive worldwide coverage. GenBank...

SNP-based typing: a useful tool to study Bordetella pertussis populations.

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Marjolein van Gent

Full Text Available To monitor changes in Bordetella pertussis populations, mainly two typing methods are used; Pulsed-Field Gel Electrophoresis (PFGE and Multiple-Locus Variable-Number Tandem Repeat Analysis (MLVA. In this study, a single nucleotide polymorphism (SNP typing method, based on 87 SNPs, was developed and compared with PFGE and MLVA. The discriminatory indices of SNP typing, PFGE and MLVA were found to be 0.85, 0.95 and 0.83, respectively. Phylogenetic analysis, using SNP typing as Gold Standard, revealed false homoplasies in the PFGE and MLVA trees. Further, in contrast to the SNP-based tree, the PFGE- and MLVA-based trees did not reveal a positive correlation between root-to-tip distance and the isolation year of strains. Thus PFGE and MLVA do not allow an estimation of the relative age of the selected strains. In conclusion, SNP typing was found to be phylogenetically more informative than PFGE and more discriminative than MLVA. Further, in contrast to PFGE, it is readily standardized allowing interlaboratory comparisons. We applied SNP typing to study strains with a novel allele for the pertussis toxin promoter, ptxP3, which have a worldwide distribution and which have replaced the resident ptxP1 strains in the last 20 years. Previously, we showed that ptxP3 strains showed increased pertussis toxin expression and that their emergence was associated with increased notification in The Netherlands. SNP typing showed that the ptxP3 strains isolated in the Americas, Asia, Australia and Europe formed a monophyletic branch which recently diverged from ptxP1 strains. Two predominant ptxP3 SNP types were identified which spread worldwide. The widespread use of SNP typing will enhance our understanding of the evolution and global epidemiology of B. pertussis.

SNP-Based Typing: A Useful Tool to Study Bordetella pertussis Populations

Science.gov (United States)

van der Heide, Han G. J.; Heuvelman, Kees J.; Kallonen, Teemu; He, Qiushui; Mertsola, Jussi; Advani, Abdolreza; Hallander, Hans O.; Janssens, Koen; Hermans, Peter W.; Mooi, Frits R.

2011-01-01

To monitor changes in Bordetella pertussis populations, mainly two typing methods are used; Pulsed-Field Gel Electrophoresis (PFGE) and Multiple-Locus Variable-Number Tandem Repeat Analysis (MLVA). In this study, a single nucleotide polymorphism (SNP) typing method, based on 87 SNPs, was developed and compared with PFGE and MLVA. The discriminatory indices of SNP typing, PFGE and MLVA were found to be 0.85, 0.95 and 0.83, respectively. Phylogenetic analysis, using SNP typing as Gold Standard, revealed false homoplasies in the PFGE and MLVA trees. Further, in contrast to the SNP-based tree, the PFGE- and MLVA-based trees did not reveal a positive correlation between root-to-tip distance and the isolation year of strains. Thus PFGE and MLVA do not allow an estimation of the relative age of the selected strains. In conclusion, SNP typing was found to be phylogenetically more informative than PFGE and more discriminative than MLVA. Further, in contrast to PFGE, it is readily standardized allowing interlaboratory comparisons. We applied SNP typing to study strains with a novel allele for the pertussis toxin promoter, ptxP3, which have a worldwide distribution and which have replaced the resident ptxP1 strains in the last 20 years. Previously, we showed that ptxP3 strains showed increased pertussis toxin expression and that their emergence was associated with increased notification in the Netherlands. SNP typing showed that the ptxP3 strains isolated in the Americas, Asia, Australia and Europe formed a monophyletic branch which recently diverged from ptxP1 strains. Two predominant ptxP3 SNP types were identified which spread worldwide. The widespread use of SNP typing will enhance our understanding of the evolution and global epidemiology of B. pertussis. PMID:21647370

Capacidad transactivadora del gen pttg1 y su implicación en tumorigénesis

OpenAIRE

Romero Franco, Ana

2016-01-01

Falta palabras clave Objetivos: Los objetivos planteados en esta tesis doctoral son los que se enumeran a continuación: 1) Estudiar la capacidad moduladora que ejerce el gen pttg1 sobre la expresión de genes relacionados con el microambiente del tumor, en células inmortalizadas de ratón NIH3T3. 2) Estudiar la capacidad transactivadora del gen pttg1 en células tumorales humanas y establecer nexos con su posible implicación biológica en el desarrollo del tumor. 3) Estudiar el efecto en el de...

GenBank

Data.gov (United States)

U.S. Department of Health & Human Services — GenBank is the NIH genetic sequence database, an annotated collection of all publicly available DNA sequences. GenBank is designed to provide and encourage access...

Genome-Wide SNP Detection, Validation, and Development of an 8K SNP Array for Apple

NARCIS (Netherlands)

Chagné, D.; Crowhurst, R.N.; Troggio, M.; Davey, M.W.; Gilmore, B.; Lawley, C.; Vanderzande, S.; Hellens, R.P.; Kumar, S.; Cestaro, A.; Velasco, R.; Main, D.; Rees, J.D.; Iezzoni, A.F.; Mockler, T.; Wilhelm, L.; Weg, van de W.E.; Gardiner, S.E.; Bassil, N.; Peace, C.

2012-01-01

As high-throughput genetic marker screening systems are essential for a range of genetics studies and plant breeding applications, the International RosBREED SNP Consortium (IRSC) has utilized the Illumina Infinium® II system to develop a medium- to high-throughput SNP screening tool for genome-wide

[Association Between SNP rs6007897 of CELSR1 and Acute Ischemic Stroke in Western China Han Population: a Case-control Study].

Science.gov (United States)

Qin, Feng-qin; Yu, Li-hua; Hu, Wen-ting; Guo, Jian; Chen, Ning; Guo, Jiang; Fang, Jing-huan; He, Li

2015-07-01

To investigate the relationship between single nucleotide polymorphism (SNP) rs6007897 of CELSR1 and acute ischemic stroke in Western China Han population. All subjects (759 acute ischemic stroke patients and 786 controls) were genotyped using ligation detection reaction (LDR). We analyzed the differences between SNP rs6007897 genotypes and allele frequencies between two groups. Two genotypes (AA, AG) of rs6007897 were found in both stroke and control group. There was no statistically significance between two groups about genotype and allele frequency. After adjusting for risk factors, we found there was no significant association between rs6007897 and ischemic stroke CP = 0.797, odds ratio (OR) = 0.886, 95% confidence interval (CI) = 0.352-2.227). SNP rs6007897 of CELSR1 was not significantly associated with ischemic stroke in Western China Han population.

rSNPBase 3.0: an updated database of SNP-related regulatory elements, element-gene pairs and SNP-based gene regulatory networks.

Science.gov (United States)

Guo, Liyuan; Wang, Jing

2018-01-04

Here, we present the updated rSNPBase 3.0 database (http://rsnp3.psych.ac.cn), which provides human SNP-related regulatory elements, element-gene pairs and SNP-based regulatory networks. This database is the updated version of the SNP regulatory annotation database rSNPBase and rVarBase. In comparison to the last two versions, there are both structural and data adjustments in rSNPBase 3.0: (i) The most significant new feature is the expansion of analysis scope from SNP-related regulatory elements to include regulatory element-target gene pairs (E-G pairs), therefore it can provide SNP-based gene regulatory networks. (ii) Web function was modified according to data content and a new network search module is provided in the rSNPBase 3.0 in addition to the previous regulatory SNP (rSNP) search module. The two search modules support data query for detailed information (related-elements, element-gene pairs, and other extended annotations) on specific SNPs and SNP-related graphic networks constructed by interacting transcription factors (TFs), miRNAs and genes. (3) The type of regulatory elements was modified and enriched. To our best knowledge, the updated rSNPBase 3.0 is the first data tool supports SNP functional analysis from a regulatory network prospective, it will provide both a comprehensive understanding and concrete guidance for SNP-related regulatory studies. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

An improved PSO algorithm for generating protective SNP barcodes in breast cancer.

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Li-Yeh Chuang

Full Text Available BACKGROUND: Possible single nucleotide polymorphism (SNP interactions in breast cancer are usually not investigated in genome-wide association studies. Previously, we proposed a particle swarm optimization (PSO method to compute these kinds of SNP interactions. However, this PSO does not guarantee to find the best result in every implement, especially when high-dimensional data is investigated for SNP-SNP interactions. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we propose IPSO algorithm to improve the reliability of PSO for the identification of the best protective SNP barcodes (SNP combinations and genotypes with maximum difference between cases and controls associated with breast cancer. SNP barcodes containing different numbers of SNPs were computed. The top five SNP barcode results are retained for computing the next SNP barcode with a one-SNP-increase for each processing step. Based on the simulated data for 23 SNPs of six steroid hormone metabolisms and signalling-related genes, the performance of our proposed IPSO algorithm is evaluated. Among 23 SNPs, 13 SNPs displayed significant odds ratio (OR values (1.268 to 0.848; p<0.05 for breast cancer. Based on IPSO algorithm, the jointed effect in terms of SNP barcodes with two to seven SNPs show significantly decreasing OR values (0.84 to 0.57; p<0.05 to 0.001. Using PSO algorithm, two to four SNPs show significantly decreasing OR values (0.84 to 0.77; p<0.05 to 0.001. Based on the results of 20 simulations, medians of the maximum differences for each SNP barcode generated by IPSO are higher than by PSO. The interquartile ranges of the boxplot, as well as the upper and lower hinges for each n-SNP barcode (n = 3∼10 are more narrow in IPSO than in PSO, suggesting that IPSO is highly reliable for SNP barcode identification. CONCLUSIONS/SIGNIFICANCE: Overall, the proposed IPSO algorithm is robust to provide exact identification of the best protective SNP barcodes for breast cancer.

Mechanism of Mitochondrial Connexin43′s Protection of the Neurovascular Unit under Acute Cerebral Ischemia-Reperfusion Injury

Directory of Open Access Journals (Sweden)

Shuai Hou

2016-05-01

Full Text Available We observed mitochondrial connexin43 (mtCx43 expression under cerebral ischemia-reperfusion (I/R injury, analyzed its regulation, and explored its protective mechanisms. Wistar rats were divided into groups based on injections received before middle cerebral artery occlusion (MCAO. Cerebral infarction volume was detected by 2,3,5-triphenyltetrazolim chloride staining, and cell apoptosis was observed by transferase dUTP nick end labeling. We used transmission electron microscopy to observe mitochondrial morphology and determined superoxide dismutase (SOD activity and malondialdehyde (MDA content. MtCx43, p-mtCx43, protein kinase C (PKC, and p-PKC expression were detected by Western blot. Compared with those in the IR group, cerebral infarction volumes in the carbenoxolone (CBX and diazoxide (DZX groups were obviously smaller, and the apoptosis indices were down-regulated. Mitochondrial morphology was damaged after I/R, especially in the IR and 5-hydroxydecanoic acid (5-HD groups. Similarly, decreased SOD activity and increased MDA were observed after MCAO; CBX, DZX, and phorbol-12-myristate-13-acetate (PMA reduced mitochondrial functional injury. Expression of mtCx43 and p-mtCx43 and the p-Cx43/Cx43 ratio were significantly lower in the IR group than in the sham group. These abnormalities were ameliorated by CBX, DZX, and PMA. MtCx43 may protect the neurovascular unit from acute cerebral IR injury via PKC activation induced by mitoKATP channel agonists.

Validity and reproducibility of HOMA-IR, 1/HOMA-IR, QUICKI and McAuley's indices in patients with hypertension and type II diabetes.

Science.gov (United States)

Sarafidis, P A; Lasaridis, A N; Nilsson, P M; Pikilidou, M I; Stafilas, P C; Kanaki, A; Kazakos, K; Yovos, J; Bakris, G L

2007-09-01

The aim of this study was to evaluate the validity and reliability of homeostasis model assessment-insulin resistance (HOMA-IR) index, its reciprocal (1/HOMA-IR), quantitative insulin sensitivity check index (QUICKI) and McAuley's index in hypertensive diabetic patients. In 78 patients with hypertension and type II diabetes glucose, insulin and triglyceride levels were determined after a 12-h fast to calculate these indices, and insulin sensitivity (IS) was measured with the hyperinsulinemic euglycemic clamp technique. Two weeks later, subjects had again their glucose, insulin and triglycerides measured. Simple and multiple linear regression analysis were applied to assess the validity of these indices compared to clamp IS and coefficients of variation between the two visits were estimated to assess their reproducibility. HOMA-IR index was strongly and inversely correlated with the basic IS clamp index, the M-value (r=-0.572, PHOMA-IR and QUICKI indices were positively correlated with the M-value (r=0.342, PHOMA-IR was the best fit of clamp-derived IS. Coefficients of variation between the two visits were 23.5% for HOMA-IR, 19.2% for 1/HOMA-IR, 7.8% for QUICKI and 15.1% for McAuley's index. In conclusion, HOMA-IR, 1/HOMA-IR and QUICKI are valid estimates of clamp-derived IS in patients with hypertension and type II diabetes, whereas the validity of McAuley's index needs further evaluation. QUICKI displayed better reproducibility than the other indices.

Population genetic analysis of ascertained SNP data

Directory of Open Access Journals (Sweden)

Nielsen Rasmus

2004-03-01

Full Text Available Abstract The large single nucleotide polymorphism (SNP typing projects have provided an invaluable data resource for human population geneticists. Almost all of the available SNP loci, however, have been identified through a SNP discovery protocol that will influence the allelic distributions in the sampled loci. Standard methods for population genetic analysis based on the available SNP data will, therefore, be biased. This paper discusses the effect of this ascertainment bias on allelic distributions and on methods for quantifying linkage disequilibrium and estimating demographic parameters. Several recently developed methods for correcting for the ascertainment bias will also be discussed.

When whole-genome alignments just won't work: kSNP v2 software for alignment-free SNP discovery and phylogenetics of hundreds of microbial genomes.

Science.gov (United States)

Gardner, Shea N; Hall, Barry G

2013-01-01

Effective use of rapid and inexpensive whole genome sequencing for microbes requires fast, memory efficient bioinformatics tools for sequence comparison. The kSNP v2 software finds single nucleotide polymorphisms (SNPs) in whole genome data. kSNP v2 has numerous improvements over kSNP v1 including SNP gene annotation; better scaling for draft genomes available as assembled contigs or raw, unassembled reads; a tool to identify the optimal value of k; distribution of packages of executables for Linux and Mac OS X for ease of installation and user-friendly use; and a detailed User Guide. SNP discovery is based on k-mer analysis, and requires no multiple sequence alignment or the selection of a single reference genome. Most target sets with hundreds of genomes complete in minutes to hours. SNP phylogenies are built by maximum likelihood, parsimony, and distance, based on all SNPs, only core SNPs, or SNPs present in some intermediate user-specified fraction of targets. The SNP-based trees that result are consistent with known taxonomy. kSNP v2 can handle many gigabases of sequence in a single run, and if one or more annotated genomes are included in the target set, SNPs are annotated with protein coding and other information (UTRs, etc.) from Genbank file(s). We demonstrate application of kSNP v2 on sets of viral and bacterial genomes, and discuss in detail analysis of a set of 68 finished E. coli and Shigella genomes and a set of the same genomes to which have been added 47 assemblies and four "raw read" genomes of H104:H4 strains from the recent European E. coli outbreak that resulted in both bloody diarrhea and hemolytic uremic syndrome (HUS), and caused at least 50 deaths.

MDM2 promoter SNP344T>A (rs1196333 status does not affect cancer risk.

Directory of Open Access Journals (Sweden)

Stian Knappskog

Full Text Available The MDM2 proto-oncogene plays a key role in central cellular processes like growth control and apoptosis, and the gene locus is frequently amplified in sarcomas. Two polymorphisms located in the MDM2 promoter P2 have been shown to affect cancer risk. One of these polymorphisms (SNP309T>G; rs2279744 facilitates Sp1 transcription factor binding to the promoter and is associated with increased cancer risk. In contrast, SNP285G>C (rs117039649, located 24 bp upstream of rs2279744, and in complete linkage disequilibrium with the SNP309G allele, reduces Sp1 recruitment and lowers cancer risk. Thus, fine tuning of MDM2 expression has proven to be of significant importance with respect to tumorigenesis. We assessed the potential functional effects of a third MDM2 promoter P2 polymorphism (SNP344T>A; rs1196333 located on the SNP309T allele. While in silico analyses indicated SNP344A to modulate TFAP2A, SPIB and AP1 transcription factor binding, we found no effect of SNP344 status on MDM2 expression levels. Assessing the frequency of SNP344A in healthy Caucasians (n = 2,954 and patients suffering from ovarian (n = 1,927, breast (n = 1,271, endometrial (n = 895 or prostatic cancer (n = 641, we detected no significant difference in the distribution of this polymorphism between any of these cancer forms and healthy controls (6.1% in healthy controls, and 4.9%, 5.0%, 5.4% and 7.2% in the cancer groups, respectively. In conclusion, our findings provide no evidence indicating that SNP344A may affect MDM2 transcription or cancer risk.

SNP-SNP interaction analysis of NF-κB signaling pathway on breast cancer survival

DEFF Research Database (Denmark)

Jamshidi, Maral; Fagerholm, Rainer; Khan, Sofia

2015-01-01

of SNP pairs without and with an interaction term. We found two interacting pairs associating with prognosis: patients simultaneously homozygous for the rare alleles of rs5996080 and rs7973914 had worse survival (HRinteraction 6.98, 95% CI=3.3-14.4, P=1.42E-07), and patients carrying at least one rare...

Design and characterization of a 52K SNP chip for goats.

Directory of Open Access Journals (Sweden)

Gwenola Tosser-Klopp

Full Text Available The success of Genome Wide Association Studies in the discovery of sequence variation linked to complex traits in humans has increased interest in high throughput SNP genotyping assays in livestock species. Primary goals are QTL detection and genomic selection. The purpose here was design of a 50-60,000 SNP chip for goats. The success of a moderate density SNP assay depends on reliable bioinformatic SNP detection procedures, the technological success rate of the SNP design, even spacing of SNPs on the genome and selection of Minor Allele Frequencies (MAF suitable to use in diverse breeds. Through the federation of three SNP discovery projects consolidated as the International Goat Genome Consortium, we have identified approximately twelve million high quality SNP variants in the goat genome stored in a database together with their biological and technical characteristics. These SNPs were identified within and between six breeds (meat, milk and mixed: Alpine, Boer, Creole, Katjang, Saanen and Savanna, comprising a total of 97 animals. Whole genome and Reduced Representation Library sequences were aligned on >10 kb scaffolds of the de novo goat genome assembly. The 60,000 selected SNPs, evenly spaced on the goat genome, were submitted for oligo manufacturing (Illumina, Inc and published in dbSNP along with flanking sequences and map position on goat assemblies (i.e. scaffolds and pseudo-chromosomes, sheep genome V2 and cattle UMD3.1 assembly. Ten breeds were then used to validate the SNP content and 52,295 loci could be successfully genotyped and used to generate a final cluster file. The combined strategy of using mainly whole genome Next Generation Sequencing and mapping on a contig genome assembly, complemented with Illumina design tools proved to be efficient in producing this GoatSNP50 chip. Advances in use of molecular markers are expected to accelerate goat genomic studies in coming years.

Report on ISFG SNP Panel Discussion

DEFF Research Database (Denmark)

Butler, John M.; Budowle, B.; Gill, P.

2008-01-01

Six scientists presented their views and experience with single nucleotide polymorphism (SNP) markers, multiplexes, and methods regarding their potential application in forensic identity and relationship testing. Benefits and limitations of SNPs were reviewed, as were different SNP marker...

76 FR 55740 - Proposed Collection; Comment Request for Notice 99-43

Science.gov (United States)

2011-09-08

... Notice 99-43 AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments... Notice 99-43, Nonrecognition Exchanges under Section 897. DATES: Written comments should be received on... Number: Notice 99-43. Abstract: Notice 99-43 announces modification of the current rules under Temporary...

Oryza sativa Chloroplast Signal Recognition Particle 43 (OscpSRP43 Is Required for Chloroplast Development and Photosynthesis.

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Xiang-guang Lv

Full Text Available A rice chlorophyll-deficient mutant w67 was isolated from an ethyl methane sulfonate (EMS-induced IR64 (Oryza sativa L. ssp. indica mutant bank. The mutant exhibited a distinct yellow-green leaf phenotype in the whole plant growth duration with significantly reduced levels of chlorophyll and carotenoid, impaired chloroplast development and lowered capacity of photosynthesis compared with the wild-type IR64. Expression of a number of genes associated with chlorophyll metabolism, chloroplast biogenesis and photosynthesis was significantly altered in the mutant. Genetic analysis indicated that the yellow-green phenotype was controlled by a single recessive nuclear gene located on the short arm of chromosome 3. Using map-based strategy, the mutation was isolated and predicted to encode a chloroplast signal recognition particle 43 KD protein (cpSRP43 with 388 amino acid residuals. A single base substitution from A to T at position 160 resulted in a premature stop codon. OscpSRP43 was constitutively expressed in various organs with the highest level in the leaf. Functional complementation could rescue the mutant phenotype and subcellular localization showed that the cpSRP43:GFP fusion protein was targeted to the chloroplast. The data suggested that Oryza sativa cpSRP43 (OscpSRP43 was required for the normal development of chloroplasts and photosynthesis in rice.

Marcadores SNP: conceitos básicos, aplicações no manejo e no melhoramento animal e perspectivas para o futuro

OpenAIRE

Caetano,Alexandre Rodrigues

2009-01-01

Os primeiros estudos de identificação, caracterização e utilização de marcadores moleculares para a caracterização de recursos genéticos e geração de ferramentas para o melhoramento animal datam do final da década de 80. Nos últimos 20 anos as tecnologias para geração de dados moleculares passaram por vários ciclos de renovação. A última onda de inovações tecnológicas representa uma verdadeira revolução e trouxe metodologias para identificar e genotipar marcadores SNP (do inglês Single Nucleo...

The image of God (Gen. 1:26-27) in the Pentateuch : a biblical-theological approach / Daniel Simango

OpenAIRE

Simango, Daniel

2006-01-01

This dissertation focuses on how the theme of the image of God (Gen 1 :26-27) is seen and developed in the Pentateuch. The image of God in man (Gen 1 :26-27) has been interpreted in various ways. Predominant opinions have changed over time from the Early Jewish interpretation to the present period. Today there is a wider range of opinion regarding the image of God than ever. This dissertation follows a biblical-theological approach from a Reformed tradition of Genesis 1 :26-...

Partitioned learning of deep Boltzmann machines for SNP data.

Science.gov (United States)

Hess, Moritz; Lenz, Stefan; Blätte, Tamara J; Bullinger, Lars; Binder, Harald

2017-10-15

Learning the joint distributions of measurements, and in particular identification of an appropriate low-dimensional manifold, has been found to be a powerful ingredient of deep leaning approaches. Yet, such approaches have hardly been applied to single nucleotide polymorphism (SNP) data, probably due to the high number of features typically exceeding the number of studied individuals. After a brief overview of how deep Boltzmann machines (DBMs), a deep learning approach, can be adapted to SNP data in principle, we specifically present a way to alleviate the dimensionality problem by partitioned learning. We propose a sparse regression approach to coarsely screen the joint distribution of SNPs, followed by training several DBMs on SNP partitions that were identified by the screening. Aggregate features representing SNP patterns and the corresponding SNPs are extracted from the DBMs by a combination of statistical tests and sparse regression. In simulated case-control data, we show how this can uncover complex SNP patterns and augment results from univariate approaches, while maintaining type 1 error control. Time-to-event endpoints are considered in an application with acute myeloid leukemia patients, where SNP patterns are modeled after a pre-screening based on gene expression data. The proposed approach identified three SNPs that seem to jointly influence survival in a validation dataset. This indicates the added value of jointly investigating SNPs compared to standard univariate analyses and makes partitioned learning of DBMs an interesting complementary approach when analyzing SNP data. A Julia package is provided at 'http://github.com/binderh/BoltzmannMachines.jl'. binderh@imbi.uni-freiburg.de. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Effect of GenF20 Plus on serum IGF-1 levels in healthy adults: a randomized controlled study

Directory of Open Access Journals (Sweden)

Sonawane N

2015-03-01

Full Text Available Navneet Sonawane,1 Vinayak Kale,2 Suhas Erande,3 Jayesh Chaudhary1 1Vedic Lifesciences Pvt Ltd, Mumbai, India; 2Lokmanya Hospital, Pune, India; 3Akshay Hospital, Pune, India Background: Aging is related to a reduction of growth hormones, resulting in physiological derailment and affects overall wellbeing. GenF20 Plus is a dietary supplement postulated to naturally stimulate the secretion of human growth hormone (HGH through the anterior pituitary. This study sought to evaluate the effect of GenF20 Plus in enhancing the levels of insulin-like growth factor-1 (IGF-1, which is a marker of HGH levels. Methods: Seventy subjects aged 35–65 years visiting outpatient departments at five study centers across India, presenting with at least two of the following age-related complaints: decreased memory, decreased libido, low energy levels, or poor quality of sleep were randomly assigned to either GenF20 Plus (n=35 or placebo (n=35 for a period of 12 weeks (84 days. Randomization was carried out using computerized software. The primary outcome measure was serum IGF-1 levels. Changes in waist circumference, body mass index, body fat percentage, lean muscle mass, and scores for memory, libido, energy levels, and quality of sleep were also assessed. Trial registration: CTRI/2011/06/001784. Results: Sixty-one subjects completed the study as per protocol and were analyzed. The mean increase (mean ± standard deviation in IGF-1 levels at day 84 in the GenF20 Plus group was 13.46±36.12 ng/mL and in the placebo group was 6.35±36.56 ng/mL, which was not statistically significantly different (P>0.05 when compared across the groups. In the ≥40 years subgroup, the mean increase in IGF-1 in the GenF20 Plus group (14.59±40.08 ng/mL was not statistically significantly different when compared to the placebo group (3.17±16.09 ng/mL using analysis of variance (ANOVA; P>0.05. However, when this change was analyzed using analysis of covariance (ANCOVA considering

The yo-yo IR2 test: physiological response, reliability, and application to elite soccer

DEFF Research Database (Denmark)

Krustrup, Peter; Mohr, Magni; Nybo, Lars

2006-01-01

biopsies and blood samples were obtained, and heart rate was measured before, during, and after the Yo-Yo IR2 test. Additionally, 119 Scandinavian elite soccer players carried out the Yo-Yo IR2 test on two to four occasions. Results: Yo-Yo IR2 performance was 591 +/- 43 (320-920) m or 4.3 (2.6-7.9) min...... was better (P elite soccer players than for moderate elite players (1059 +/- 35 vs 771 +/- 26 m) and better (P elite soccer players...... turnover. Specifically, the Yo-Yo IR2 test was shown to be a sensitive tool to differentiate between intermittent exercise performance of soccer players in different seasonal periods and at different competitive levels and playing positions....

saSNP Approach for Scalable SNP Analyses of Multiple Bacterial or Viral Genomes

Energy Technology Data Exchange (ETDEWEB)

Gardner, Shea [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Slezak, Tom [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2010-07-27

With the flood of whole genome finished and draft microbial sequences, we need faster, more scalable bioinformatics tools for sequence comparison. An algorithm is described to find single nucleotide polymorphisms (SNPs) in whole genome data. It scales to hundreds of bacterial or viral genomes, and can be used for finished and/or draft genomes available as unassembled contigs. The method is fast to compute, finding SNPs and building a SNP phylogeny in seconds to hours. We use it to identify thousands of putative SNPs from all publicly available Filoviridae, Poxviridae, foot-and-mouth disease virus, Bacillus, and Escherichia coli genomes and plasmids. The SNP-based trees that result are consistent with known taxonomy and trees determined in other studies. The approach we describe can handle as input hundreds of gigabases of sequence in a single run. The algorithm is based on k-mer analysis using a suffix array, so we call it saSNP.

KLONING GEN PUTATIVE CLEAVAGE PROTEIN 1 (PCP-1 PADA UDANG VANAME (Litopenaeus vannamei YANG TERSERANG INFECTIOUS MYONECROSIS VIRUS

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Hessy Novita

2016-12-01

Full Text Available Penanggulangan penyakit ikan dapat dilakukan dengan cara meningkatkan kekebalan tubuh ikan melalui program vaksinasi. Namun vaksinasi tidak tepat untuk udang, karena udang tidak mempunyai immunological memory seperti ikan. Oleh karena itu, perlindungan udang terhadap serangan penyakit viral dengan menggunakan RNA interference (RNAi. Teknologi RNAi digunakan untuk menghalangi (interfere proses replikasi infectious myonecrosis virus (IMNV pada udang vaname dengan cara menon-aktifkan gen putative cleavage protein 1 (PCP-1, yang berfungsi dalam pembentukan capsid dan proses transkripsi RNA IMNV. Penelitian ini bertujuan untuk melakukan kloning gen putative cleavage protein 1 dalam rangka perakitan teknologi RNAi untuk pengendalian penyakit IMNV pada udang vaname. Tahapan penelitian meliputi koleksi sampel, isolasi RNA, sintesis cDNA, amplifikasi PCR, purifikasi DNA, transformasi, isolasi plasmid, serta sekuensing dan analisis data. Hasil isolasi plasmid cDNA PCP-1 memperlihatkan semua koloni bakteri terseleksi ternyata membawa plasmid hasil insersi DNA gen PCP–1, hasil sekuen dengan nilai homologinya mencapai 100% dan 99% yang dibandingkan dengan sekuen di Genebank. Hasil penelitian menunjukkan bahwa kloning gen putative cleavage protein 1 (PCP-1 dari udang vaname yang terserang Infectious Myonecrosis Virus berhasil dikloning yang nantinya digunakan untuk perakitan RNAi. The prevention of fish diseases can be done by increasing of the fish immune through vaccination programs. However, the vaccination can not be done for the shrimp,due to the absence of  immunological memory. Therefore, the protection of shrimp against viral diseases was done by using of RNA interference (RNAi. RNAi technology is used to interfere infectious myonecrosis virus (IMNV replication process on white shrimp by disabling of putative cleavage protein 1 (PCP-1gene, which functions in capsid formation and RNA transcription process. The study was conducted to perform putative

IRS-1 acts as an endocytic regulator of IGF-I receptor to facilitate sustained IGF signaling.

Science.gov (United States)

Yoneyama, Yosuke; Lanzerstorfer, Peter; Niwa, Hideaki; Umehara, Takashi; Shibano, Takashi; Yokoyama, Shigeyuki; Chida, Kazuhiro; Weghuber, Julian; Hakuno, Fumihiko; Takahashi, Shin-Ichiro

2018-04-11

Insulin-like growth factor-I receptor (IGF-IR) preferentially regulates the long-term IGF activities including growth and metabolism. Kinetics of ligand-dependent IGF-IR endocytosis determines how IGF induces such downstream signaling outputs. Here, we find that the insulin receptor substrate (IRS)-1 modulates how long ligand-activated IGF-IR remains at the cell surface before undergoing endocytosis in mammalian cells. IRS-1 interacts with the clathrin adaptor complex AP2. IRS-1, but not an AP2-binding-deficient mutant, delays AP2-mediated IGF-IR endocytosis after the ligand stimulation. Mechanistically, IRS-1 inhibits the recruitment of IGF-IR into clathrin-coated structures; for this reason, IGF-IR avoids rapid endocytosis and prolongs its activity on the cell surface. Accelerating IGF-IR endocytosis via IRS-1 depletion induces the shift from sustained to transient Akt activation and augments FoxO-mediated transcription. Our study establishes a new role for IRS-1 as an endocytic regulator of IGF-IR that ensures sustained IGF bioactivity, independent of its classic role as an adaptor in IGF-IR signaling. © 2018, Yoneyama et al.

Association between cytochrome CYP17A1, CYP3A4, and CYP3A43 polymorphisms and prostate cancer risk and aggressiveness in a Korean study population

OpenAIRE

Han, Jun Hyun; Lee, Yong Seong; Kim, Hae Jong; Lee, Shin Young; Myung, Soon Chul

2014-01-01

In this study, we evaluated genetic variants of the androgen metabolism genes CYP17A1, CYP3A4, and CYP3A43 to determine whether they play a role in the development of prostate cancer (PCa) in Korean men. The study population included 240 pathologically diagnosed cases of PCa and 223 age-matched controls. Among the 789 single-nucleotide polymorphism (SNP) database variants detected, 129 were reported in two Asian groups (Han Chinese and Japanese) in the HapMap database. Only 21 polymorphisms o...

GenLab, Laboratorio Virtual de Genética

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Fidel Ramírez

2000-07-01

Full Text Available GenLab es el nombre que tiene el software diseñado por nosotros, en el cual se modela el proceso meiótico y la fecundación en organismos diploides. El objetivo de esta aplicación es ilustrar el resultado de un cruce determinado, tratando de ser lo más ajustados a la realidad. La modelación de la reproducción sexual se realiza internamente y el GenLab se limita a presentar los resultados según el número de descendencia seleccionado para un cruce específico, esto significa que se puede escoger una gran cantidad de características para los parentales y se puede estudiar la frecuencia de estos en la descendencia. El modelo cuenta con base de datos donde están almacenados algunos de los locus de Drosophila melanogaster junto con su ubicación en centimorgans 1. EI propósito de este modelo es servir como herramienta pedagógica  y didáctica tanto en universidades como en colegios, facilitando el aprendizaje de algunos principios básicos de la genética, por lo cual puede ser usado si se cuenta con una conexión a Internet y un navegador visitando http://biologia.unal.edu.co/fidel.

Grouping and clustering of maize Lancaster germplasm inbreds according to the results of SNP-analysis

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K. V. Derkach

2017-08-01

group within the general set of analyzed inbred lines. Two-dimensional component analysis showed that the first principal component (PCA1 accounted for 36.0% of total variation and divided the investigated set of 91 inbred lines into two fractions, while all the inbred lines which are considered Lancaster based on pedigree information were included in one of the fractions. The second principal component (PCA2, which accounted for 12.1% of total variation, separated most of the Lancaster germplasm inbred lines from the others in this fraction, although the overlapping of the locations of Lancaster and non-Lancaster inbred lines was observed. Qualitative cluster analysis of 31 Lancaster germplasm inbred lines allowed to identify two clusters: the first one includes 23 inbred lines of Ukrainian selection and the well known Mo17 inbred line (77.4% of total number of analysed lines inbred line, and the second cluster included 6 inbred lines of Ukrainian selection and the well known Oh43 inbred line (22.6% of total number of analysed lines inbred line. The isolation of two clusters within Lancaster germplasm indicates the genetic diversity in this plasm. The evaluation of genome similarities through allelic states of SNP-markers can successfully be used for classification and systematization of the gene pool of maize genetic resources.

Algoritmos genéticos locales

OpenAIRE

García-Martínez, Carlos; Lozano, Manuel

2007-01-01

Los Algoritmos Genéticos Locales son procedimientos que iterativamente re nan soluciones dadas. Su diferencia con procedimientos de mejora iterativa clásicos reside en el uso de operadores genéticos para realizar el re namiento. En este estudio presentamos un nuevo Algoritmo Genético Local Binario basado en un Algoritmo Genético Estacionario. Hemos comparado el Algoritmo Genético Local Binario con otros procedimientos de mejora iterativa de la literatura. Los res...

Epidemiología genómica y paraparesia espástica tropical asociada a la infección por el virus linfotrópico humano de células T tipo 1 Genome epidemiology and tropical spastic paraparesis associated with human T-cell lymphotropic virus type 1

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Mercedes Salcedo-Cifuentes

2011-11-01

Full Text Available OBJETIVO: Caracterizar el ambiente genómico de las secuencias adyacentes al virus linfotrópico humano de células T tipo 1 (HTLV-1 en pacientes con paraparesia espástica tropical y mielopatía asociada a la infección con HTLV-1 (PET/MAH de diferentes regiones de Colombia y del Japón. MÉTODOS: Se enfrentaron 71 clones recombinantes con secuencias del genoma humano adyacentes al 5'-LTR de pacientes con PET/MAH, a las bases de datos del Genome Browser y del Gen-Bank. Se identificaron y analizaron estadísticamente 16 variables genómicas estructurales y composicionales mediante el programa informático R, versión 2.8.1, en una ventana de 0,5 Mb. RESULTADOS: El 43,0% de los provirus se localizaron en los cromosomas del grupo C; 74% de las secuencias se ubicaron en regiones teloméricas y subteloméricas (P OBJECTIVE: Characterize the genomic environment of the sequences adjacent to human T-cell lymphotropic virus type 1 (HTLV-1 in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP in different regions of Colombia and Japan. METHODS: A total of 71 recombinant clones with human genome sequences adjacent to 5' LTR in patients with HAM/TSP were compared to the Genome Browser and GenBank databases. Sixteen structural and compositional genome variables were identified, and statistical analysis was conducted in the R computer program, version 2.8.1, in a 0.5 Mb window. RESULTS: A total of 43.0% of the proviruses were located in the group C chromosomes; 74% of the sequences were located in the telomeric and subtelomeric regions (P < 0.05. A cluster analysis was used to establish the hierarchical relations between the genome characteristics included in the study. The analysis of principal components identified the components that defined the preferred genome environments for proviral integration in cases of HAM/TSP. CONCLUSIONS: HTLV-1 was integrated more often in chromatin regions rich in CpG islands with a high density

Imputation of microsatellite alleles from dense SNP genotypes for parental verification

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Matthew eMcclure

2012-08-01

Full Text Available Microsatellite (MS markers have recently been used for parental verification and are still the international standard despite higher cost, error rate, and turnaround time compared with Single Nucleotide Polymorphisms (SNP-based assays. Despite domestic and international interest from producers and research communities, no viable means currently exist to verify parentage for an individual unless all familial connections were analyzed using the same DNA marker type (MS or SNP. A simple and cost-effective method was devised to impute MS alleles from SNP haplotypes within breeds. For some MS, imputation results may allow inference across breeds. A total of 347 dairy cattle representing 4 dairy breeds (Brown Swiss, Guernsey, Holstein, and Jersey were used to generate reference haplotypes. This approach has been verified (>98% accurate for imputing the International Society of Animal Genetics (ISAG recommended panel of 12 MS for cattle parentage verification across a validation set of 1,307 dairy animals.. Implementation of this method will allow producers and breed associations to transition to SNP-based parentage verification utilizing MS genotypes from historical data on parents where SNP genotypes are missing. This approach may be applicable to additional cattle breeds and other species that wish to migrate from MS- to SNP- based parental verification.

Multi-pollutants sensors based on near-IR telecom lasers and mid-IR difference frequency generation: development and applications

International Nuclear Information System (INIS)

Cousin, J.

2006-12-01

At present the detection of VOC and other anthropic trace pollutants is an important challenge in the measurement of air quality. Infrared spectroscopy, allowing spectral regions rich in molecular absorption to be probed, is a suitable technique for in-situ monitoring of the air pollution. Thus the aim of this work was to develop instruments capable of detecting multiple pollutants for in-situ monitoring by IR spectroscopy. A first project benefited from the availability of the telecommunications lasers emitting in near-IR. This instrument was based on an external cavity diode laser (1500 - 1640 nm) in conjunction with a multipass cell (100 m). The detection sensitivity was optimised by employing a balanced detection and a sweep integration procedure. The instrument developed is deployable for in-situ measurements with a sensitivity of -8 cm -1 Hz -1/2 and allowed the quantification of chemical species such as CO 2 , CO, C 2 H 2 , CH 4 and the determination of the isotopic ratio 13 CO 2 / 12 CO 2 in combustion environment The second project consisted in mixing two near-IR fiber lasers in a non-linear crystal (PPLN) in order to produce a laser radiation by difference frequency generation in the middle-IR (3.15 - 3.43 μm), where the absorption bands of the molecules are the most intense. The first studies with this source were carried out on detection of ethylene (C 2 H 4 ) and benzene (C 6 H 6 ). Developments, characterizations and applications of these instruments in the near and middle IR are detailed and the advantages of the 2 spectral ranges is highlighted. (author)

Vibrational spectroscopy (FT-IR and Laser-Raman) investigation, and computational (M06-2X and B3LYP) analysis on the structure of 4-(3-fluorophenyl)-1-(propan-2-ylidene)-thiosemicarbazone.

Science.gov (United States)

Sert, Yusuf; Miroslaw, Barbara; Çırak, Çağrı; Doğan, Hatice; Szulczyk, Daniel; Struga, Marta

2014-07-15

In this study, the experimental and theoretical vibrational spectral analysis of 4-(3-fluorophenyl)-1-(propan-2-ylidene)-thiosemicarbazone have been carried out. The experimental FT-IR (4000-400 cm(-1)) and Laser-Raman spectra (4000-100 cm(-1)) have been recorded for the solid state samples. The theoretical vibrational frequencies and the optimized geometric parameters (bond lengths and angles) have been calculated for gas phase using density functional theory (DFT/B3LYP: Becke, 3-parameter, Lee-Yang-Parr) and M06-2X (the highly parametrized, empirical exchange correlation function) quantum chemical methods with 6-311++G(d,p) basis set. The diversity in molecular geometry of fluorophenyl substituted thiosemicarbazones has been discussed based on the X-ray crystal structure reports and theoretical calculation results from the literature. The assignments of the vibrational frequencies have been done on the basis of potential energy distribution (PED) analysis by using VEDA4 software. A good correlation was found between the computed and experimental geometric and vibrational data. In addition, the highest occupied (HOMO) and lowest unoccupied (LUMO) molecular orbital energy levels and other related molecular energy values of the compound have been determined using the same level of theoretical calculations. Copyright © 2014 Elsevier B.V. All rights reserved.

MDM2 SNP309 promoter polymorphism and p53 mutations in urinary bladder carcinoma stage T1

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Olsson Hans

2013-01-01

Full Text Available Abstract Background Urinary bladder carcinoma stage T1 is an unpredictable disease that in some cases has a good prognosis with only local or no recurrence, but in others can appear as a more aggressive tumor with progression to more advanced stages. The aim here was to investigate stage T1 tumors regarding MDM2 promoter SNP309 polymorphism, mutations in the p53 gene, and expression of p53 and p16 measured by immunohistochemistry, and subsequently relate these changes to tumor recurrence and progression. We examined a cohort of patients with primary stage T1 urothelial carcinoma of the bladder and their tumors. Methods After re-evaluation of the original slides and exclusions, the study population comprised 141 patients, all with primary stage T1 urothelial carcinoma of the bladder. The hospital records were screened for clinical parameters and information concerning presence of histologically proven recurrence and progression. The paraffin-embedded tumor material was evaluated by immunohistochemistry. Any mutations found in the p53 gene were studied by single-strand conformation analysis and Sanger sequencing. The MDM2 SNP309 polymorphism was investigated by pyrosequencing. Multivariate analyses concerning association with prognosis were performed, and Kaplan-Meier analysis was conducted for a combination of changes and time to progression. Results Of the 141 patients, 82 had at least one MDM2 SNP309 G allele, and 53 had a mutation in the p53 gene, but neither of those anomalies was associated with a worse prognosis. A mutation in the p53 gene was associated with immunohistochemically visualized p53 protein expression at a cut-off value of 50%. In the group with p53 mutation Kaplan-Meier analysis showed higher rate of progression and shorter time to progression in patients with immunohistochemically abnormal p16 expression compared to them with normal p16 expression (p = 0.038. Conclusions MDM2 SNP309 promoter polymorphism and mutations in

Identification of T1D susceptibility genes within the MHC region by combining protein interaction networks and SNP genotyping data

DEFF Research Database (Denmark)

Brorsson, C.; Hansen, Niclas Tue; Hansen, Kasper Lage

2009-01-01

genes. We have developed a novel method that combines single nucleotide polymorphism (SNP) genotyping data with protein-protein interaction (ppi) networks to identify disease-associated network modules enriched for proteins encoded from the MHC region. Approximately 2500 SNPs located in the 4 Mb MHC......To develop novel methods for identifying new genes that contribute to the risk of developing type 1 diabetes within the Major Histocompatibility Complex (MHC) region on chromosome 6, independently of the known linkage disequilibrium (LD) between human leucocyte antigen (HLA)-DRB1, -DQA1, -DQB1...... region were analysed in 1000 affected offspring trios generated by the Type 1 Diabetes Genetics Consortium (T1DGC). The most associated SNP in each gene was chosen and genes were mapped to ppi networks for identification of interaction partners. The association testing and resulting interacting protein...

A influência do genótipo da ECA sobre a aptidão cardiovascular de jovens do sexo masculino moderadamente ativos

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Jeeser Alves Almeida

2012-04-01

Full Text Available FUNDAMENTO: O gene da enzima conversora de angiotensina (gene ECA tem sido amplamente estudado em relação a fenótipos de aptidão cardiorrespiratória, contudo a associação do genótipo da ECA com corridas de meia-distância tem sido pouco investigada. OBJETIVO: O presente estudo investigou a possível influência da enzima conversora de angiotensina (ECA (I/D sobre a aptidão cardiovascular e o desempenho em corridas de meia-distância por parte de brasileiros jovens do sexo masculino. A validade da previsão de VO2max em relação ao genótipo da ECA também foi analisada. MÉTODOS: Um grupo homogêneo de homens jovens moderadamente ativos foi avaliado em um teste de corrida (V1600 m; m.min-1 e em um teste adicional em esteira ergométrica para a determinação de VO2max. Posteriormente, o [(0,177*V1600m + 8.101] VO2max real e previsto foi comparado com os genótipos da ECA. RESULTADOS: O VO2max e V1600m registrados para os genótipos DD, ID e II foram 45,6 (1,8; 51,9 (0,8 e 54,4 (1,0 mL.kg-1.min-1 e 211,2 (8,3; 249,1 (4,3 e 258,6 (5,4 m.min-1, respectivamente e foram significativamente mais baixos para os genótipos DD (p < 0,05. O VO2max real e previsto não diferiram entre si, apesar do genótipo da ECA, mas o nível de concordância entre os métodos de VO2max real e estimado foi menor para o genótipo DD. CONCLUSÃO: Concluiu-se que existe uma possível associação entre o genótipo da ECA, a aptidão cardiovascular e o desempenho em corridas de média distância de jovens do sexo masculino moderadamente ativos e que a precisão da previsão do VO2max também pode ser dependente do genótipo da ECA dos participantes.

IGF-IR promotes prostate cancer growth by stabilizing α5β1 integrin protein levels.

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Aejaz Sayeed

Full Text Available Dynamic crosstalk between growth factor receptors, cell adhesion molecules and extracellular matrix is essential for cancer cell migration and invasion. Integrins are transmembrane receptors that bind extracellular matrix proteins and enable cell adhesion and cytoskeletal organization. They also mediate signal transduction to regulate cell proliferation and survival. The type 1 insulin-like growth factor receptor (IGF-IR mediates tumor cell growth, adhesion and inhibition of apoptosis in several types of cancer. We have previously demonstrated that β1 integrins regulate anchorage-independent growth of prostate cancer (PrCa cells by regulating IGF-IR expression and androgen receptor-mediated transcriptional functions. Furthermore, we have recently reported that IGF-IR regulates the expression of β1 integrins in PrCa cells. We have dissected the mechanism through which IGF-IR regulates β1 integrin expression in PrCa. Here we report that IGF-IR is crucial for PrCa cell growth and that β1 integrins contribute to the regulation of proliferation by IGF-IR. We demonstrate that β1 integrin regulation by IGF-IR does not occur at the mRNA level. Exogenous expression of a CD4 - β1 integrin cytoplasmic domain chimera does not interfere with such regulation and fails to stabilize β1 integrin expression in the absence of IGF-IR. This appears to be due to the lack of interaction between the β1 cytoplasmic domain and IGF-IR. We demonstrate that IGF-IR stabilizes the β1 subunit by protecting it from proteasomal degradation. The α5 subunit, one of the binding partners of β1, is also downregulated along with β1 upon IGF-IR knockdown while no change is observed in the expression of the α2, α3, α4, α6 and α7 subunits. Our results reveal a crucial mechanistic role for the α5β1 integrin, downstream of IGF-IR, in regulating cancer growth.

Honey bee-inspired algorithms for SNP haplotype reconstruction problem

Science.gov (United States)

PourkamaliAnaraki, Maryam; Sadeghi, Mehdi

2016-03-01

Reconstructing haplotypes from SNP fragments is an important problem in computational biology. There have been a lot of interests in this field because haplotypes have been shown to contain promising data for disease association research. It is proved that haplotype reconstruction in Minimum Error Correction model is an NP-hard problem. Therefore, several methods such as clustering techniques, evolutionary algorithms, neural networks and swarm intelligence approaches have been proposed in order to solve this problem in appropriate time. In this paper, we have focused on various evolutionary clustering techniques and try to find an efficient technique for solving haplotype reconstruction problem. It can be referred from our experiments that the clustering methods relying on the behaviour of honey bee colony in nature, specifically bees algorithm and artificial bee colony methods, are expected to result in more efficient solutions. An application program of the methods is available at the following link. http://www.bioinf.cs.ipm.ir/software/haprs/

43 CFR 24.1 - Introduction.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Introduction. 24.1 Section 24.1 Public Lands: Interior Office of the Secretary of the Interior DEPARTMENT OF THE INTERIOR FISH AND WILDLIFE POLICY: STATE-FEDERAL RELATIONSHIPS § 24.1 Introduction. (a) In 1970, the Secretary of the Interior...

43 CFR 32.1 - Introduction.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Introduction. 32.1 Section 32.1 Public Lands: Interior Office of the Secretary of the Interior GRANTS TO STATES FOR ESTABLISHING YOUNG ADULT CONSERVATION CORPS (YACC) PROGRAM § 32.1 Introduction. (a) The Young Adult Conservation Corps (YACC) is...

Identification of Laying-Related SNP Markers in Geese Using RAD Sequencing.

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ShiGang Yu

candidate laying-related SNP, including membrane associated guanylate kinase (MAGI-1, KIAA1462, Rho GTPase activating protein 21 (ARHGAP21, acyl-CoA synthetase family member 2 (ACSF2, astrotactin 2 (ASTN2. Collectively, our data suggests that 8 SNP and 5 genes might be promising candidate markers or targets for marker-assisted selection of egg numbers in geese.

The Introduction of an Undergraduate Interventional Radiology (IR) Curriculum: Impact on Medical Student Knowledge and Interest in IR

International Nuclear Information System (INIS)

Shaikh, M.; Shaygi, B.; Asadi, H.; Thanaratnam, P.; Pennycooke, K.; Mirza, M.; Lee, M.

2016-01-01

IntroductionInterventional radiology (IR) plays a vital role in modern medicine, with increasing demand for services, but with a shortage of experienced interventionalists. The aim of this study was to determine the impact of a recently introduced IR curriculum on perception, knowledge, and interest of medical students regarding various aspects of IR.MethodsIn 2014, an anonymous web-based questionnaire was sent to 309 4th year medical students in a single institution within an EU country, both before and after delivery of a 10-h IR teaching curriculum.ResultsSeventy-six percent (236/309) of the respondents participated in the pre-IR module survey, while 50 % (157/309) responded to the post-IR module survey. While 62 % (147/236) of the respondents reported poor or no knowledge of IR compared to other medical disciplines in the pre-IR module survey, this decreased to 17 % (27/157) in the post-IR module survey. The correct responses regarding knowledge of selected IR procedures improved from 70 to 94 % for venous access, 78 to 99 % for uterine fibroid embolization, 75 to 97 % for GI bleeding embolization, 60 to 92 % for trauma embolization, 71 to 92 % for tumor ablation, and 81 to 94 % for angioplasty and stenting in peripheral arterial disease. With regard to knowledge of IR clinical roles, responses improved from 42 to 59 % for outpatient clinic review of patients and having inpatient beds, 63–76 % for direct patient consultation, and 43–60 % for having regular ward rounds. The number of students who would consider a career in IR increased from 60 to 73 %.ConclusionDelivering an undergraduate IR curriculum increased the knowledge and understanding of various aspects of IR and also the general enthusiasm for pursuing this specialty as a future career choice.

The Introduction of an Undergraduate Interventional Radiology (IR) Curriculum: Impact on Medical Student Knowledge and Interest in IR

Energy Technology Data Exchange (ETDEWEB)

Shaikh, M. [Bradford Royal Infirmary, Department of Radiology, Bradford Teaching Hospital Foundation Trust (United Kingdom); Shaygi, B. [Royal Devon and Exeter Hospital, Interventional Radiology Department (United Kingdom); Asadi, H., E-mail: asadi.hamed@gmail.com; Thanaratnam, P.; Pennycooke, K.; Mirza, M.; Lee, M., E-mail: mlee@rcsi.ie [Beaumont Hospital, Interventional Radiology Service, Department of Radiology (Ireland)

2016-04-15

IntroductionInterventional radiology (IR) plays a vital role in modern medicine, with increasing demand for services, but with a shortage of experienced interventionalists. The aim of this study was to determine the impact of a recently introduced IR curriculum on perception, knowledge, and interest of medical students regarding various aspects of IR.MethodsIn 2014, an anonymous web-based questionnaire was sent to 309 4th year medical students in a single institution within an EU country, both before and after delivery of a 10-h IR teaching curriculum.ResultsSeventy-six percent (236/309) of the respondents participated in the pre-IR module survey, while 50 % (157/309) responded to the post-IR module survey. While 62 % (147/236) of the respondents reported poor or no knowledge of IR compared to other medical disciplines in the pre-IR module survey, this decreased to 17 % (27/157) in the post-IR module survey. The correct responses regarding knowledge of selected IR procedures improved from 70 to 94 % for venous access, 78 to 99 % for uterine fibroid embolization, 75 to 97 % for GI bleeding embolization, 60 to 92 % for trauma embolization, 71 to 92 % for tumor ablation, and 81 to 94 % for angioplasty and stenting in peripheral arterial disease. With regard to knowledge of IR clinical roles, responses improved from 42 to 59 % for outpatient clinic review of patients and having inpatient beds, 63–76 % for direct patient consultation, and 43–60 % for having regular ward rounds. The number of students who would consider a career in IR increased from 60 to 73 %.ConclusionDelivering an undergraduate IR curriculum increased the knowledge and understanding of various aspects of IR and also the general enthusiasm for pursuing this specialty as a future career choice.

SNP mining porcine ESTs with MAVIANT, a novel tool for SNP evaluation and annotation

DEFF Research Database (Denmark)

Panitz, Frank; Stengaard, Henrik; Hornshoj, Henrik

2007-01-01

MOTIVATION: Single nucleotide polymorphisms (SNPs) analysis is an important means to study genetic variation. A fast and cost-efficient approach to identify large numbers of novel candidates is the SNP mining of large scale sequencing projects. The increasing availability of sequence trace data...... manual annotation, which is immediately accessible and can be easily shared with external collaborators. RESULTS: Large-scale SNP mining of polymorphisms bases on porcine EST sequences yielded more than 7900 candidate SNPs in coding regions (cSNPs), which were annotated relative to the human genome. Non...

43 CFR 26.1 - Introduction.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Introduction. 26.1 Section 26.1 Public Lands: Interior Office of the Secretary of the Interior GRANTS TO STATES FOR ESTABLISHING YOUTH CONSERVATION CORPS PROGRAMS § 26.1 Introduction. (a) The Youth Conservation Corps (YCC) is a program of summer...

GenBank

OpenAIRE

Benson, Dennis A.; Cavanaugh, Mark; Clark, Karen; Karsch-Mizrachi, Ilene; Lipman, David J.; Ostell, James; Sayers, Eric W.

2012-01-01

GenBank? (http://www.ncbi.nlm.nih.gov) is a comprehensive database that contains publicly available nucleotide sequences for almost 260 000 formally described species. These sequences are obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole-genome shotgun (WGS) and environmental sampling projects. Most submissions are made using the web-based BankIt or standalone Sequin programs, and GenBank staff assig...

Reação de genótipos de meloeiro a Myrothecium Reaction of melon genotypes to Myrothecium roridum

Directory of Open Access Journals (Sweden)

Marissônia A Noronha

2006-12-01

Full Text Available A expansão da cultura do meloeiro (Cucumis melo L. no Nordeste brasileiro tem favorecido a ocorrência de doenças como o cancro-de-mirotécio, causado pelo fungo Myrothecium roridum. Visando selecionar genótipos com potencial de utilização nos programas de melhoramento e/ou no manejo integrado da doença, foram avaliados 150 genótipos de meloeiro. Plantas com 22 dias de idade, desenvolvidas em casa de vegetação, foram feridas no colo e inoculadas com uma suspensão do patógeno (3x10(6 conídios/ml. As avaliações foram realizadas diariamente, até seis dias após a retirada da câmara úmida, com o auxílio de uma escala descritiva de notas de 0 a 4. Com os dados da última avaliação, os genótipos foram distribuídos em cinco classes de reação à doença. Nenhum genótipo foi imune ou altamente resistente ao patógeno, enquanto 26,7% foram medianamente resistentes (MR e 73,3% foram suscetíveis (S ou altamente suscetíveis (AS. Esses resultados evidenciam a dificuldade na obtenção de fontes com elevados níveis de resistência a M. roridum. Os grupos Cantaloupe, Charentais, Gália e 'Indefinido' apresentaram a maior freqüência de genótipos com a reação MR e a menor freqüência de genótipos AS. A maioria dos genótipos dos grupos Valenciano Verde (66,7%, Cantaloupe (57,4%, Gália (60,0% e 'Indefinido' (53,8% foram S. Os genótipos 'PI 420149', 'Caroline', 'A3', 'Chilton' e 'PS-1 Pele de Sapo' apresentaram os menores valores de severidade final da doença e mostraram-se promissoras fontes de resistência ao patógeno e devem ser preferidos sob condições favoráveis à doença.The expansion of the melon (Cucumis melo L. fields in the Brazilian Northeast favored the occurrence of diseases such as the Myrothecium stem canker caused by the fungus Myrothecium roridum. In order to select genotypes with potential use in genetic breeding programs and in integrated disease management, 150 melon genotypes were evaluated. Twenty

43 CFR 424.1 - Regulations.

Science.gov (United States)

2010-10-01

... provisions of Article 34 and 25 of repayment contract I1r-1534, dated September 20, 1948, between the United... supplemented, Articles 34, and 25 of the Repayment Contract I1r-1534 dated Sept. 20, 1948, between the United... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Regulations. 424.1 Section 424.1 Public...

A SNP resource for studying North American moose [version 1; referees: 2 approved, 1 approved with reservations

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Theodore S. Kalbfleisch

2018-01-01

Full Text Available Background: Moose (Alces alces colonized the North American continent from Asia less than 15,000 years ago, and spread across the boreal forest regions of Canada and the northern United States (US.  Contemporary populations have low genetic diversity, due either to low number of individuals in the original migration (founder effect, and/or subsequent population bottlenecks in North America.  Genetic tests based on informative single nucleotide polymorphism (SNP markers are helpful in forensic and wildlife conservation activities, but have been difficult to develop for moose, due to the lack of a reference genome assembly and whole genome sequence (WGS data. Methods:  WGS data were generated for four individual moose from the US states of Alaska, Idaho, Wyoming, and Vermont with minimum and average genome coverage depths of 14- and 19-fold, respectively.  Cattle and sheep reference genomes were used for aligning sequence reads and identifying moose SNPs. Results:  Approximately 11% and 9% of moose WGS reads aligned to cattle and sheep genomes, respectively.  The reads clustered at genomic segments, where sequence identity between these species was greater than 95%.  In these segments, average mapped read depth was approximately 19-fold.  Sets of 46,005 and 36,934 high-confidence SNPs were identified from cattle and sheep comparisons, respectively, with 773 and 552 of those having minor allele frequency of 0.5 and conserved flanking sequences in all three species.  Among the four moose, heterozygosity and allele sharing of SNP genotypes were consistent with decreasing levels of moose genetic diversity from west to east.  A minimum set of 317 SNPs, informative across all four moose, was selected as a resource for future SNP assay design. Conclusions:  All SNPs and associated information are available, without restriction, to support development of SNP-based tests for animal identification, parentage determination, and estimating

Trans-Fatty Acids Aggravate Obesity, Insulin Resistance and Hepatic Steatosis in C57BL/6 Mice, Possibly by Suppressing the IRS1 Dependent Pathway.

Science.gov (United States)

Zhao, Xiaona; Shen, Cheng; Zhu, Hong; Wang, Cong; Liu, Xiangwei; Sun, Xiaolei; Han, Shasha; Wang, Peng; Dong, Zhen; Ma, Xin; Hu, Kai; Sun, Aijun; Ge, Junbo

2016-05-30

Trans-fatty acid consumption has been reported as a risk factor for metabolic disorders and targeted organ damages. Nonetheless, little is known about the roles and mechanisms of trans-fatty acids in obesity, insulin resistance (IR) and hepatic steatosis. Adult C57BL/6 male mice were fed with four different diets for 20 weeks: normal diet (ND), high fat diet (HFD), low trans-fatty acids diet (LTD) and high trans-fatty acid diet (HTD). The diet-induced metabolic disorders were assessed by evaluating body weight, glucose tolerance test, hepatic steatosis and plasma lipid profiles post 20-week diet. Histological (H&E, Oil-Red-O) staining and western blot analysis were employed to assess liver steatosis and potential signaling pathways. After 20-weeks of diet, the body weights of the four groups were 29.61 ± 1.89 g (ND), 39.04 ± 4.27 g (HFD), 34.09 ± 2.62 g (LTD) and 43.78 ± 4.27 g (HTD) (p steatosis compared with HFD group possibly through regulating adipose triglyceride lipase. The group consuming the HTD also exhibited significantly reduced levels of IRS1, phosphor-PKC and phosphor-AKT. These results support our hypothesis that consumption of a diet high in trans-fatty acids induces higher rates of obesity, IR and hepatic steatosis in male C57BL/6 mice, possibly by suppressing the IRS1dependent pathway.

Diversidad genética de las variedades de arroz FLAR liberadas entre 2003-2014.

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Luis Eduardo Berrio-Orozco

2016-06-01

Full Text Available El objetivo de este trabajo fue determinar la base genética, el coeficiente de parentesco y la diversidad genética de las variedades de arroz liberadas entre el 2003 - 2014 en trece países miembros del Fondo Latinoamericano para Arroz de Riego (FLAR. Para ello, se analizaron las genealogías de 51 variedades, en el Centro Internacional de Agricultura Tropical (CIAT, Palmira, Colombia, durante los años 2014 y 2015. La variabilidad genética de las variedades estuvo representada por 120 ancestrales (2,4 ancestral/variedad; 33 de estos contribuyeron con el 83,9% de sus genes, de los cuales tres (ancestrales que originaron IR8 aportaron el 35,6% de sus genes. También se mostró que el coeficiente de parentesco (rxy entre las diferentes variedades comerciales varió de 0,03 (muy poco relacionadas, hasta 0,99 (altamente relacionadas. El promedio de todas las 51 variedades fue de (rxy 0,19. A nivel de variedades por país, se encontró que el promedio fue variable, el mínimo lo obtuvo Ecuador con 0,13, y el máximo fue de 0,31 para las variedades de Venezuela. El análisis de agrupamiento separó a los genotipos en catorce grupos distintos, donde existen materiales bastante relacionados y otros muy poco relacionados. Estos resultados muestran que se ha obtenido una ampliación de la base genética. 

New generation pharmacogenomic tools: a SNP linkage disequilibrium Map, validated SNP assay resource, and high-throughput instrumentation system for large-scale genetic studies.

Science.gov (United States)

De La Vega, Francisco M; Dailey, David; Ziegle, Janet; Williams, Julie; Madden, Dawn; Gilbert, Dennis A

2002-06-01

Since public and private efforts announced the first draft of the human genome last year, researchers have reported great numbers of single nucleotide polymorphisms (SNPs). We believe that the availability of well-mapped, quality SNP markers constitutes the gateway to a revolution in genetics and personalized medicine that will lead to better diagnosis and treatment of common complex disorders. A new generation of tools and public SNP resources for pharmacogenomic and genetic studies--specifically for candidate-gene, candidate-region, and whole-genome association studies--will form part of the new scientific landscape. This will only be possible through the greater accessibility of SNP resources and superior high-throughput instrumentation-assay systems that enable affordable, highly productive large-scale genetic studies. We are contributing to this effort by developing a high-quality linkage disequilibrium SNP marker map and an accompanying set of ready-to-use, validated SNP assays across every gene in the human genome. This effort incorporates both the public sequence and SNP data sources, and Celera Genomics' human genome assembly and enormous resource ofphysically mapped SNPs (approximately 4,000,000 unique records). This article discusses our approach and methodology for designing the map, choosing quality SNPs, designing and validating these assays, and obtaining population frequency ofthe polymorphisms. We also discuss an advanced, high-performance SNP assay chemisty--a new generation of the TaqMan probe-based, 5' nuclease assay-and high-throughput instrumentation-software system for large-scale genotyping. We provide the new SNP map and validation information, validated SNP assays and reagents, and instrumentation systems as a novel resource for genetic discoveries.

GenBank

OpenAIRE

Benson, Dennis A.; Karsch-Mizrachi, Ilene; Lipman, David J.; Ostell, James; Sayers, Eric W.

2008-01-01

GenBank? is a comprehensive database that contains publicly available nucleotide sequences for more than 300 000 organisms named at the genus level or lower, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Most submissions are made using the web-based BankIt or standalone Sequin programs, and accession numbers are assigned by GenBank? staff upon receipt. Daily data exchange with the European Molecular Biology Labo...

Interest in genomic SNP testing for prostate cancer risk: a pilot survey.

Science.gov (United States)

Hall, Michael J; Ruth, Karen J; Chen, David Yt; Gross, Laura M; Giri, Veda N

2015-01-01

Advancements in genomic testing have led to the identification of single nucleotide polymorphisms (SNPs) associated with prostate cancer. The clinical utility of SNP tests to evaluate prostate cancer risk is unclear. Studies have not examined predictors of interest in novel genomic SNP tests for prostate cancer risk in a diverse population. Consecutive participants in the Fox Chase Prostate Cancer Risk Assessment Program (PRAP) (n = 40) and unselected men from surgical urology clinics (n = 40) completed a one-time survey. Items examined interest in genomic SNP testing for prostate cancer risk, knowledge, impact of unsolicited findings, and psychosocial factors including health literacy. Knowledge of genomic SNP tests was low in both groups, but interest was higher among PRAP men (p testing in both groups. Multivariable modeling identified several predictors of higher interest in a genomic SNP test including higher perceived risk (p = 0.025), indicating zero reasons for not wanting testing (vs ≥1 reason) (p = 0.013), and higher health literacy (p = 0.016). Knowledge of genomic SNP testing was low in this sample, but higher among high-risk men. High-risk status may increase interest in novel genomic tests, while low literacy may lessen interest.

Feeding of the 1 1/2- isomers in stable Ir and Au isotopes

Energy Technology Data Exchange (ETDEWEB)

Fotiadis, Nikolaos [Los Alamos National Laboratory; Nelson, Ronald O [Los Alamos National Laboratory; Devlin, Matthew [Los Alamos National Laboratory; Holloway, Shannon T [Los Alamos National Laboratory; Kawano, Toshihiko [Los Alamos National Laboratory; Talou, Patrick [Los Alamos National Laboratory; Chadwick, Mark B [Los Alamos National Laboratory; Becker, John A [LLNL; Garrett, Paul E [U GUELPH, CANADA

2008-01-01

Excited states were studied and absolute partial {gamma}-ray cross sections were measured using the ({eta}, {eta}'{gamma}) reaction in {sup 191}Ir, {sup 193}Ir and {sup 197}Au. A Compton-suppressed germanium-detector array (GEANIE) for {gamma}-ray spectroscopy and the broad-spectrum pulsed neutron source of the Los Alamos Neutron Science Center's WNR facility were used for the measurement. The energy of the incident neutrons was determined using the time-of-flight technique. Absolute partial {gamma}-ray cross sections were measured up to incident neutron energy of 20 MeV for several transitions feeding directly the 1 1/2- isomers and ground states in {sup 191}Ir, {sup 193}Ir and {sup 197}Au. The feeding of the 1 1/2- isomers, which originate from the odd proton occupying the h{sub 1 1/2} orbital, was found for the three targets to be very similar and increasing relative to the feeding of the corresponding ground state with increasing neutron energy up to E{sub n} {approx} 10 MeV. Above this neutron energy the opening of the (n, 2{sub n}) reaction channel strongly affects the population of the isomers and leads to a decrease of their relative population compared to the population of the ground states. The experimental results are compared with theoretical predictions from the GNASH reaction model calculation implementing a version of the spin distribution for the pre-equilibrium reaction piece with either a compound nucleus spin distribution (CN-GNASH) or a Feshbach-Kerman-Koonin (FKK-GNASH) quantum mechanical spin distribution. The effects of the spin cutoff parameter values on the population of states are examined. Evidence is presented that FKK-GNASH provides a description of the experimental data that mitigates the need for adjustment of the level density parameter to fit the data.

The Fyn tyrosine kinase binds Irs-1 and forms a distinct signaling complex during insulin stimulation.

Science.gov (United States)

Sun, X J; Pons, S; Asano, T; Myers, M G; Glasheen, E; White, M F

1996-05-03

Irs-proteins link the receptors for insulin/IGF-1, growth hormones, and several interleukins and interferons to signaling proteins that contain Src homology-2 (SH2). To identify new Irs-1-binding proteins, we screened a mouse embryo expression library with recombinant [32P]Irs-1, which revealed a specific association between p59fyn and Irs-1. The SH2 domain in p59fyn bound to phosphorylated Tyr895 and Tyr1172, which are located in YXX(L/I) motifs. Mutation of p59fyn at the COOH-terminal tyrosine phosphorylation site (Tyr531) enhanced its binding to Irs-1 during insulin stimulation. Binding experiments with various SH2 protein revealed that Grb-2 was largely excluded from Irs-1 complexes containing p59fyn, whereas Grb-2 and p85 occurred in the same Irs-1 complex. By comparison with the insulin receptor, p59fyn kinase phosphorylated a unique cohort of tyrosine residues in Irs-1. These results outline a role for p59fyn or other related Src-kinases during insulin and cytokine signaling.

FunctSNP: an R package to link SNPs to functional knowledge and dbAutoMaker: a suite of Perl scripts to build SNP databases

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Watson-Haigh Nathan S

2010-06-01

Full Text Available Abstract Background Whole genome association studies using highly dense single nucleotide polymorphisms (SNPs are a set of methods to identify DNA markers associated with variation in a particular complex trait of interest. One of the main outcomes from these studies is a subset of statistically significant SNPs. Finding the potential biological functions of such SNPs can be an important step towards further use in human and agricultural populations (e.g., for identifying genes related to susceptibility to complex diseases or genes playing key roles in development or performance. The current challenge is that the information holding the clues to SNP functions is distributed across many different databases. Efficient bioinformatics tools are therefore needed to seamlessly integrate up-to-date functional information on SNPs. Many web services have arisen to meet the challenge but most work only within the framework of human medical research. Although we acknowledge the importance of human research, we identify there is a need for SNP annotation tools for other organisms. Description We introduce an R package called FunctSNP, which is the user interface to custom built species-specific databases. The local relational databases contain SNP data together with functional annotations extracted from online resources. FunctSNP provides a unified bioinformatics resource to link SNPs with functional knowledge (e.g., genes, pathways, ontologies. We also introduce dbAutoMaker, a suite of Perl scripts, which can be scheduled to run periodically to automatically create/update the customised SNP databases. We illustrate the use of FunctSNP with a livestock example, but the approach and software tools presented here can be applied also to human and other organisms. Conclusions Finding the potential functional significance of SNPs is important when further using the outcomes from whole genome association studies. FunctSNP is unique in that it is the only R

GenBank

OpenAIRE

Benson, Dennis A.; Karsch-Mizrachi, Ilene; Lipman, David J.; Ostell, James; Wheeler, David L.

2006-01-01

GenBank (R) is a comprehensive database that contains publicly available nucleotide sequences for more than 240 000 named organisms, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Most submissions are made using the web-based BankIt or standalone Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the EMBL Data Library in Europe and the DNA Data Bank of Japan...

Homa1-ir And Homa2-ir Indexes In Identifying Insulin Resistance And Metabolic Syndrome - Brazilian Metabolic Syndrome Study (brams) [Índices Homa1-ir E Homa2-ir Para Identificação De Resistência à Insulina E Síndrome Metabólica - Estudo Brasileiro De Síndrome Metabólica (brams)

OpenAIRE

Geloneze B.; Vasques A.C.J.; Stabe C.F.C.; Pareja J.C.; de Lima Rosado L.E.F.P.; de Queiroz E.C.; Tambascia M.A.

2009-01-01

Objective: To investigate cut-off values for HOMA1-IR and HOMA2-IR to identify insulin resistance (IR) and metabolic syndrome (MS), and to assess the association of the indexes with components of the MS. Methods: Nondiabetic subjects from the Brazilian Metabolic Syndrome Study were studied (n = 1,203, 18 to 78 years). The cut-off values for IR were determined from the 90th percentile in the healthy group (n = 297) and, for MS, a ROC curve was generated for the total sample. Results: In the he...

A novel polymer of Al2(SO43-poly(acrylamide-co-2-acrylamido-2-methyl-1-propanesulfonate ionic hybrid prepared by dispersion polymerization

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2010-03-01

Full Text Available A novel polymer Al2(SO43-poly(acrylamide-co-2-acrylamido-2-methyl-1-propanesulfonate (Al2(SO43-P(AM/AMPS had been synthesized by dispersion polymerization in an aqueous solution of ammonium sulfate and aluminum sulfate, using poly(2-acrylamido-2-methyl-1-propanesulfonate P(AMPS as stabilizer, acrylamide (AM and 2-acrylamido-2-methyl-1-propanesulfonate (AMPS as monomers, poly(2-acrylamido-2-methyl-1-propanesulfonate (PAMPS as stabilizer and [2-(2-imidazdino-2-ylpropane]dihydrochloride (VA-044 as initiator. The average particle size of polymer dispersion ranged from 0.2 to 0.3 µm, the molecular weight was from 4.3•106 to 5.7•106 g•mol-1. The polymer was characterized by infrared (IR spectroscopy, thermogravimetry (TGA and transmission electron microscopy (TEM. The swelling property of the dispersion polymer was studied by particle size distribution. When the polymer dispersion was diluted with deionized water, particle sizes decreased several times. When the polymer dispersion was diluted with salt water, the particle size increased with increasing concentration of salt. The effects of Al2(SO43 and stabilizer on the particle size and the relative molecular weight of the polymer were investigated, respectively. The optimum conditions for the stable Al2(SO43-P(AM/AMPS dispersion were that the concentration of Al2(SO43 was 1.12 wt%, the concentration of PAMPS stabilizer was 3 wt% and the concentration of initiator was 0.2 mol•l-1 and the monomers concentration was 14 wt%.

Identification of SNP barcode biomarkers for genes associated with facial emotion perception using particle swarm optimization algorithm.

Science.gov (United States)

Chuang, Li-Yeh; Lane, Hsien-Yuan; Lin, Yu-Da; Lin, Ming-Teng; Yang, Cheng-Hong; Chang, Hsueh-Wei

2014-01-01

Facial emotion perception (FEP) can affect social function. We previously reported that parts of five tested single-nucleotide polymorphisms (SNPs) in the MET and AKT1 genes may individually affect FEP performance. However, the effects of SNP-SNP interactions on FEP performance remain unclear. This study compared patients with high and low FEP performances (n = 89 and 93, respectively). A particle swarm optimization (PSO) algorithm was used to identify the best SNP barcodes (i.e., the SNP combinations and genotypes that revealed the largest differences between the high and low FEP groups). The analyses of individual SNPs showed no significant differences between the high and low FEP groups. However, comparisons of multiple SNP-SNP interactions involving different combinations of two to five SNPs showed that the best PSO-generated SNP barcodes were significantly associated with high FEP score. The analyses of the joint effects of the best SNP barcodes for two to five interacting SNPs also showed that the best SNP barcodes had significantly higher odds ratios (2.119 to 3.138; P < 0.05) compared to other SNP barcodes. In conclusion, the proposed PSO algorithm effectively identifies the best SNP barcodes that have the strongest associations with FEP performance. This study also proposes a computational methodology for analyzing complex SNP-SNP interactions in social cognition domains such as recognition of facial emotion.

An economical mtDNA SNP assay detecting different mitochondrial haplogroups in identical HVR 1 samples of Caucasian ancestry.

Science.gov (United States)

Köhnemann, Stephan; Hohoff, Carsten; Pfeiffer, Heidi

2009-09-01

We had sequenced 329 Caucasian samples in Hypervariable Region 1 (HVR 1) and found that they belong to eleven different mitochondrial DNA (mtDNA) haplotypes. The sample set was further analysed by an mtDNA assay examining 32 single nucleotide polymorphisms (SNPs) for haplogroup discrimination. In a validation study on 160 samples of different origin it was shown that these SNPs were able to discriminate between the evolved superhaplogroups worldwide (L, M and N) and between the nine most common Caucasian haplogroups (H, I, J, K, T, U, V, W and X). The 32 mtDNA SNPs comprised 42 different SNP haplotypes instead of only eleven haplotypes after HVR 1 sequencing. The assay provided stable results in a range of 5ng genomic DNA down to virtually no genomic DNA per reaction. It was possible to detect samples of African, Asian and Eurasian ancestry, respectively. The 32 mtDNA SNP assay is a helpful adjunct to further distinguish between identical HVR 1 sequences of Caucasian origin. Our results suggest that haplogroup prediction using HVR 1 sequencing provides instable results. The use of coding region SNPs for haplogroup assignment is more suited than using HVR 1 haplotypes.

Demonstrated brain insulin resistance in Alzheimer’s disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline

Science.gov (United States)

Talbot, Konrad; Wang, Hoau-Yan; Kazi, Hala; Han, Li-Ying; Bakshi, Kalindi P.; Stucky, Andres; Fuino, Robert L.; Kawaguchi, Krista R.; Samoyedny, Andrew J.; Wilson, Robert S.; Arvanitakis, Zoe; Schneider, Julie A.; Wolf, Bryan A.; Bennett, David A.; Trojanowski, John Q.; Arnold, Steven E.

2012-01-01

While a potential causal factor in Alzheimer’s disease (AD), brain insulin resistance has not been demonstrated directly in that disorder. We provide such a demonstration here by showing that the hippocampal formation (HF) and, to a lesser degree, the cerebellar cortex in AD cases without diabetes exhibit markedly reduced responses to insulin signaling in the IR→IRS-1→PI3K signaling pathway with greatly reduced responses to IGF-1 in the IGF-1R→IRS-2→PI3K signaling pathway. Reduced insulin responses were maximal at the level of IRS-1 and were consistently associated with basal elevations in IRS-1 phosphorylated at serine 616 (IRS-1 pS616) and IRS-1 pS636/639. In the HF, these candidate biomarkers of brain insulin resistance increased commonly and progressively from normal cases to mild cognitively impaired cases to AD cases regardless of diabetes or APOE ε4 status. Levels of IRS-1 pS616 and IRS-1 pS636/639 and their activated kinases correlated positively with those of oligomeric Aβ plaques and were negatively associated with episodic and working memory, even after adjusting for Aβ plaques, neurofibrillary tangles, and APOE ε4. Brain insulin resistance thus appears to be an early and common feature of AD, a phenomenon accompanied by IGF-1 resistance and closely associated with IRS-1 dysfunction potentially triggered by Aβ oligomers and yet promoting cognitive decline independent of classic AD pathology. PMID:22476197

Development and Applications of a High Throughput Genotyping Tool for Polyploid Crops: Single Nucleotide Polymorphism (SNP Array

Directory of Open Access Journals (Sweden)

Qian You

2018-02-01

Full Text Available Polypoid species play significant roles in agriculture and food production. Many crop species are polyploid, such as potato, wheat, strawberry, and sugarcane. Genotyping has been a daunting task for genetic studies of polyploid crops, which lags far behind the diploid crop species. Single nucleotide polymorphism (SNP array is considered to be one of, high-throughput, relatively cost-efficient and automated genotyping approaches. However, there are significant challenges for SNP identification in complex, polyploid genomes, which has seriously slowed SNP discovery and array development in polyploid species. Ploidy is a significant factor impacting SNP qualities and validation rates of SNP markers in SNP arrays, which has been proven to be a very important tool for genetic studies and molecular breeding. In this review, we (1 discussed the pros and cons of SNP array in general for high throughput genotyping, (2 presented the challenges of and solutions to SNP calling in polyploid species, (3 summarized the SNP selection criteria and considerations of SNP array design for polyploid species, (4 illustrated SNP array applications in several different polyploid crop species, then (5 discussed challenges, available software, and their accuracy comparisons for genotype calling based on SNP array data in polyploids, and finally (6 provided a series of SNP array design and genotype calling recommendations. This review presents a complete overview of SNP array development and applications in polypoid crops, which will benefit the research in molecular breeding and genetics of crops with complex genomes.

MicroRNA-145 suppresses hepatocellular carcinoma by targeting IRS1 and its downstream Akt signaling

Energy Technology Data Exchange (ETDEWEB)

Wang, Yelin [Department of Anesthesiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Hu, Chen; Cheng, Jun [Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Chen, Binquan [Department of Anesthesiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Ke, Qinghong; Lv, Zhen; Wu, Jian [Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Zhou, Yanfeng, E-mail: zyfhdj@yahoo.com [Department of Anesthesiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou (China)

2014-04-18

Highlights: • MiR-145 expression is down-regulated in HCC tissues and inversely related with IRS1 levels. • MiR-145 directly targets IRS1 in HCC cells. • Restored expression of miR-145 suppressed HCC cell proliferation and growth. • MiR-145 induced IRS1 under-expression potentially reduced downstream AKT signaling. - Abstract: Accumulating evidences have proved that dysregulation of microRNAs (miRNAs) is involved in cancer initiation and progression. In this study, we showed that miRNA-145 level was significantly decreased in hepatocellular cancer (HCC) tissues and cell lines, and its low expression was inversely associated with the abundance of insulin receptor substrate 1 (IRS1), a key mediator in oncogenic insulin-like growth factor (IGF) signaling. We verified IRS1 as a direct target of miR-145 using Western blotting and luciferase reporter assay. Further, the restoration of miR-145 in HCC cell lines suppressed cancer cell growth, owing to down-regulated IRS1 expression and its downstream Akt/FOXO1 signaling. Our results demonstrated that miR-145 could inhibit HCC through targeting IRS1 and its downstream signaling, implicating the loss of miR-145 regulation may be a potential molecular mechanism causing aberrant oncogenic signaling in HCC.

Use of allele-specific FAIRE to determine functional regulatory polymorphism using large-scale genotyping arrays.

Directory of Open Access Journals (Sweden)

Andrew J P Smith

Full Text Available Following the widespread use of genome-wide association studies (GWAS, focus is turning towards identification of causal variants rather than simply genetic markers of diseases and traits. As a step towards a high-throughput method to identify genome-wide, non-coding, functional regulatory variants, we describe the technique of allele-specific FAIRE, utilising large-scale genotyping technology (FAIRE-gen to determine allelic effects on chromatin accessibility and regulatory potential. FAIRE-gen was explored using lymphoblastoid cells and the 50,000 SNP Illumina CVD BeadChip. The technique identified an allele-specific regulatory polymorphism within NR1H3 (coding for LXR-α, rs7120118, coinciding with a previously GWAS-identified SNP for HDL-C levels. This finding was confirmed using FAIRE-gen with the 200,000 SNP Illumina Metabochip and verified with the established method of TaqMan allelic discrimination. Examination of this SNP in two prospective Caucasian cohorts comprising 15,000 individuals confirmed the association with HDL-C levels (combined beta = 0.016; p = 0.0006, and analysis of gene expression identified an allelic association with LXR-α expression in heart tissue. Using increasingly comprehensive genotyping chips and distinct tissues for examination, FAIRE-gen has the potential to aid the identification of many causal SNPs associated with disease from GWAS.

The insulin receptor substrate (IRS)-1 pleckstrin homology domain functions in downstream signaling.

Science.gov (United States)

Vainshtein, I; Kovacina, K S; Roth, R A

2001-03-16

The pleckstrin homology (PH) domain of the insulin receptor substrate-1 (IRS-1) plays a role in directing this molecule to the insulin receptor, thereby regulating its tyrosine phosphorylation. In this work, the role of the PH domain in subsequent signaling was studied by constructing constitutively active forms of IRS-1 in which the inter-SH2 domain of the p85 subunit of phosphatidylinositol 3-kinase was fused to portions of the IRS-1 molecule. Chimeric molecules containing the PH domain were found to activate the downstream response of stimulating the Ser/Thr kinase Akt. A chimera containing point mutations in the PH domain that abolished the ability of this domain to bind phosphatidylinositol 4,5-bisphosphate prevented these molecules from activating Akt. These mutations also decreased by about 70% the amount of the constructs present in a particulate fraction of the cells. These results indicate that the PH domain of IRS-1, in addition to directing this protein to the receptor for tyrosine phosphorylation, functions in the ability of this molecule to stimulate subsequent responses. Thus, compromising the function of the PH domain, e.g. in insulin-resistant states, could decrease both the ability of IRS-1 to be tyrosine phosphorylated by the insulin receptor and to link to subsequent downstream targets.

A genetic linkage map with 178 SSR and 1 901 SNP markers constructed using a RIL population in wheat （Triticum aestivum L.）

Institute of Scientific and Technical Information of China (English)

ZHAI Hui-jie; FENG Zhi-yu; LIU Xin-ye; CHENG Xue-jiao; PENG Hui-ru; YAO Ying-yin; SUN Qi-xin; NI Zhong-fu

2015-01-01

The construction of high density genetic linkage map provides a powerful tool to detect and map quantitative trait loci （QTLs） controlling agronomically important traits. In this study, simple sequence repeat （SSR） markers and Illumina 9K iSelect single nucleotide polymorphism （SNP） genechip were employed to construct one genetic linkage map of common wheat （Triticum aestivum L.） using 191 recombinant inbred lines （RILs） derived from cross Yu 8679xJing 411. This map included 1 901 SNP loci and 178 SSR loci, covering 1 659.9 cM and 1 000 marker bins, with an average interval distance of 1.66 cM. A, B and D genomes covered 719.1,703.5 and 237.3 cM, with an average interval distance of 1.66, 1.45 and 2.9 cM, respectively. Notably, the genetic linkage map covered 20 chromosomes, with the exception of chromosome 5D. Bioinformatics analysis revealed that 1 754 （92.27%） of 1 901 mapped SNP loci could be aligned to 1 215 distinct wheat unigenes, among which 1 184 （97.4%） were located on one single chromosome, and the rest 31 （2.6%） were located on 2 to 3 chromosomes. By performing in silico comparison, 214 chromosome deletion bin-mapped expressed sequence tags （ESTs）, 1 043 Brachypodium genes and 1 033 rice genes were further added onto the genetic linkage map. This map not only integrated genetic and physical maps, SSR and SNP loci, respectively, but also provided the information of Brachypodium and rice genes corresponding to 1 754 SNP loci. Therefore, it will be a useful tool for comparative genomics analysis, fine mapping of QTL/gene controlling agronomically important traits and marker-assisted selection breeding in wheat.

Characterization of Romboutsia ilealis gen. nov., sp. nov., isolated from the gastro-intestinal tract of a rat, and proposal for the reclassification of five closely related members of the genus Clostridium into the genera Romboutsia gen. nov., Intestinibacter gen. nov., Terrisporobacter gen. nov. and Asaccharospora gen. nov.

Science.gov (United States)

Gerritsen, Jacoline; Fuentes, Susana; Grievink, Wieke; van Niftrik, Laura; Tindall, Brian J; Timmerman, Harro M; Rijkers, Ger T; Smidt, Hauke

2014-05-01

A Gram-positive staining, rod-shaped, non-motile, spore-forming obligately anaerobic bacterium, designated CRIBT, was isolated from the gastro-intestinal tract of a rat and characterized. The major cellular fatty acids of strain CRIBT were saturated and unsaturated straight-chain C12-C19 fatty acids, with C16:0 being the predominant fatty acid. The polar lipid profile comprised six glycolipids, four phospholipids and one lipid that did not stain with any of the specific spray reagents used. The only quinone was MK-6. The predominating cell-wall sugars were glucose and galactose. The peptidoglycan type of strain CRIBT was A1σ lanthionine-direct. The genomic DNA G+C content of strain CRIBT was 28.1 mol%. On the basis of 16S rRNA gene sequence similarity, strain CRIBT was most closely related to a number of species of the genus Clostridium, including Clostridium lituseburense (97.2%), Clostridium glycolicum (96.2%), Clostridium mayombei (96.2%), Clostridium bartlettii (96.0%) and Clostridium irregulare (95.5%). All these species show very low 16S rRNA gene sequence similarity (genus Clostridium. DNA-DNA hybridization with closely related reference strains indicated reassociation values below 32%. On the basis of phenotypic and genetic studies, a novel genus, Romboutsia gen. nov., is proposed. The novel isolate CRIBT (=DSM 25109T=NIZO 4048T) is proposed as the type strain of the type species, Romboutsia ilealis gen. nov., sp. nov., of the proposed novel genus. It is proposed that C. lituseburense is transferred to this genus as Romboutsia lituseburensis comb. nov. Furthermore, the reclassification into novel genera is proposed for C. bartlettii, as Intestinibacter bartlettii gen. nov., comb. nov. (type species of the genus), C. glycolicum, as Terrisporobacter glycolicus gen. nov., comb. nov. (type species of the genus), C. mayombei, as Terrisporobacter mayombei gen. nov., comb. nov., and C. irregulare, as Asaccharospora irregularis gen. nov., comb. nov. (type species

Mars atmosphere studies with the SPICAM IR emission phase function observations

Science.gov (United States)

Trokhimovskiy, Alexander; Fedorova, Anna; Montmessin, Franck; Korablev, Oleg; Bertaux, Jean-Loup

Emission Phase Function (EPF) observations is a powerful tool for characterization of atmosphere and surface. EPF sequence provides the extensive coverage of scattering angles above the targeted surface location which allow to separate the surface and aerosol scattering, study a vertical distribution of minor species and aerosol properties. SPICAM IR instrument on Mars Express mission provides continuous atmospheric observations in near IR (1-1.7 mu) in nadir and limb starting from 2004. For the first years of SPICAM operation only a very limited number of EPFs was performed. But from the mid 2013 (Ls=225, MY31) SPICAM EPF observations become rather regular. Based on the multiple-scattering radiative transfer model SHDOM, we analyze equivalent depths of carbon dioxide (1,43 mu) and water vapour (1,38 mu) absorption bands and their dependence on airmass during observation sequence to get aerosol optical depths and properties. The derived seasonal dust opacities from near IR can be used to retrieve the size distribution from comparison with simultaneous results of other instruments in different spectral ranges. Moreover, the EPF observations of water vapour band allow to access poorly known H2O vertical distribution for different season and locations.

Phenylethynylpyrene excimer forming hybridization probes for fluorescence SNP detection

DEFF Research Database (Denmark)

Prokhorenko, Igor A.; Astakhova, Irina V.; Momynaliev, Kuvat T.

2009-01-01

Excimer formation is a unique feature of some fluorescent dyes (e.g., pyrene) which can be used for probing the proximity of biomolecules. Pyrene excimer fluorescence has previously been used for homogeneous detection of single nucleotide polymorphism (SNP) on DNA. 1-Phenylethynylpyrene (1-1-PEPy...

Polycyclic aromatic hydrocarbon degradation by biosurfactant-producing Pseudomonas sp. IR1

Energy Technology Data Exchange (ETDEWEB)

Kumar, M. [Unidad de Biotecnologia del Petroleo, Centro de Biotecnologia, Fundacion Inst. de Estudios Avanzados (IDEA), Caracas (Venezuela); Synthesis and Biotics Div., Indian Oil Corp., Research and Development Center, Haryana (India); Leon, V.; Materano, A.D.S.; Ilzins, O.A.; Galindo-Castro, I.; Fuenmayor, S.L. [Unidad de Biotecnologia del Petroleo, Centro de Biotecnologia, Fundacion Inst. de Estudios Avanzados (IDEA), Caracas (Venezuela)

2006-03-15

We characterized a newly isolated bacterium, designated as IR1, with respect to its ability to degrade polycyclic aromatic hydrocarbons (PAHs) and to produce biosurfactants. Isolated IR1 was identified as Pseudomonas putida by analysis of 16S rRNA sequences (99.6% homology). It was capable of utilizing two-, three- and four-ring PAHs but not hexadecane and octadecane as a sole carbon and energy source. PCR and DNA hybridization studies showed that enzymes involved in PAH metabolism were related to the naphthalene dioxygenase pathway. Observation of both tensio-active and emulsifying activities indicated that biosurfactants were produced by IR1 during growth on both water miscible and immiscible substrates. The biosurfactants lowered the surface tension of medium from 54.9 dN cm{sup -1} to 35.4 dN cm{sup -1} and formed a stable and compact emulsion with an emulsifying activity of 74% with diesel oil, when grown on dextrose. These findings indicate that this isolate may be useful for bioremediation of sites contaminated with aromatic hydrocarbons. (orig.)

Divergência, variabilidade genética e desempenho agronômico em genótipos de couve.

OpenAIRE

Azevedo, Alcinei Mistico

2012-01-01

Embora haja grande variabilidade genética para a couve, são poucos trabalhos no Brasil que visão obter informações para programas de melhoramento genético nesta cultura. Assim, objetivou-se neste trabalho caracterizar 30 genótipos de couve a partir de caracteres morfo-agronômicos para estimar a divergência genética, a importância dos caracteres para a divergência, o desempenho agronômico, os parâmetros genéticos e a correlação entre as características avaliadas. O experimento foi conduzido na...

28 CFR 43.1 - Administrative determination and assertion of claims.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Administrative determination and assertion of claims. 43.1 Section 43.1 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) RECOVERY OF COST OF HOSPITAL AND MEDICAL CARE AND TREATMENT FURNISHED BY THE UNITED STATES § 43.1 Administrative...

Market share scenarios for Gen-DIII and gen-IV reactors in Europe

International Nuclear Information System (INIS)

Roelofs, F.; Heek, A. V.; Durpel, L. V. D.

2008-01-01

Nuclear energy is back on the agenda worldwide in order to meet growing energy demand and especially the growth in electricity demand. Many objectives direct to an increased use of nuclear energy, i.e. minimising energy costs, reducing climate change effects and others. In the light of the potential renewed growth of nuclear energy, the public demands a clear view on what nuclear energy may contribute towards meeting these objectives and especially how nuclear energy may address some socio-political obstructions with respect to economics, radioactive waste, safety and proliferation of fissile materials. To address these questions, the future nuclear reactor park mix in Europe has been analysed applying an integrated dynamic process modelling technique. Various market share scenarios for nuclear energy are derived including sub-variants with regard to the intra-nuclear options. In the analyses, it is assumed that different types of new reactors may be built, taking into account the introduction date of considered Gen-Ill (i.e. EPR) and Gen-IV (i.e. SCWR, HTR, FR) reactors, and the economic evaluation of the complete fuel cycle. The assessment was undertaken using the DANESS code (Dynamic Analysis of Nuclear Energy System Strategies). The analyses show that given the considered realistic nuclear energy demand and given a limited number of available Gen-III and Gen-IV reactor types, the future European nuclear park will exist of combinations of Gen-III and Gen-IV reactors. This mix will always consist of a set of reactor types each having its specific strengths. The analyses also highlight the triggers influencing the choice between different nuclear energy deployment scenarios. (authors)

Diversidade genética intra e interespecífica de pitaya com base nas características físico-químicas de frutos

Directory of Open Access Journals (Sweden)

Cristiane Andréa de Lima

2013-12-01

Full Text Available Neste trabalho, objetivou-se avaliar a diversidade genética intra e interespecífica de 21 acessos de duas espécies de pitaya, Hylocereus undatus (Haw Britton & Rose e Selenicereus setaceus Salm-Dyck. A. Bereger ex Werderm., com base nas características físico-químicas dos frutos. Foram avaliadas as características: comprimento, diâmetro, sólidos solúveis, massa total da casca e da polpa dos frutos. Com base na média das características físico-químicas de cada acesso, foram calculados índices de distância genética entre cada par de acessos com base na distância euclidiana média padronizada. A partir da matriz de distâncias genéticas, realizaram-se análises de agrupamento por meio de dendograma e dispersão gráfica baseada em escalas multidimensionais. As variáveis analisadas apresentaram diferentes contribuições relativas para a diversidade genética. O diâmetro do fruto foi a variável que teve maior contribuição no índice de diversidade genética (27,45 %, seguido pela massa total do fruto (25,43 % e pela massa da polpa do fruto (24,67 %. As distâncias genéticas entre os 21 acessos de pitaya variaram entre 2,2 e 540,1. A análise de agrupamento permitiu subdividir os 21 acessos em dois grupos de similaridade genética, Hylocereus e Selenicereus, a uma distância genética relativa de 100. As características físico-químicas dos frutos evidenciaram alta diversidade genética entre os acessos das espécies H. undatus e S. setaceus.

Subarcsecond observations of NGC 7538 IRS 1: Continuum distribution and dynamics of molecular gas

Energy Technology Data Exchange (ETDEWEB)

Zhu, Lei; Shi, Hui [National Astronomical Observatories, Chinese Academy of Sciences, A20 Datun Road, Chaoyang District, Beijing 100012 (China); Zhao, Jun-Hui [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Wright, M. C. H. [Department of Astronomy, University of California, Berkeley, Berkeley, CA 94720 (United States); Sandell, Göran [SOFIA-USRA, NASA Ames Research Center, MS 232-12, Building N232, Rm. 146, P.O. Box 1, Moffett Field, CA 94035-0001 (United States); Wu, Yue-Fang [Department of Astronomy, Peking University, Beijing 100871 (China); Brogan, Crystal; Corder, Stuartt, E-mail: lzhu@nao.cas.cn [NRAO, 520 Edgemont Road, Charlottesville, VA 22903 (United States)

2013-12-10

We report new results based on the analysis of the Submillimeter Array (SMA) and Combined Array for Research in Millimeter-wave Astronomy (CARMA) observations of NGC 7538 IRS 1 at 1.3 and 3.4 mm with subarcsecond resolutions. With angular resolutions ∼0.''7, the SMA and CARMA observations show that the continuum emission at 1.3 and 3.4 mm from the hyper-compact H II region IRS 1 is dominated by a compact source with a tail-like extended structure to the southwest of IRS 1. With a CARMA B-array image at 1.3 mm convolved to 0.''1, we resolve the hyper-compact H II region into two components: an unresolved hyper-compact core, and a north-south extension with linear sizes of <270 AU and ∼2000 AU, respectively. The fine structure observed with CARMA is in good agreement with the previous Very Large Array results at centimeter wavelengths, suggesting that the hyper-compact H II region at the center of IRS 1 is associated with an ionized bipolar outflow. We image the molecular lines OCS(19-18) and CH{sub 3}CN(12-11) as well as {sup 13}CO(2-1) surrounding IRS 1, showing a velocity gradient along the southwest-northeast direction. The spectral line profiles in {sup 13}CO(2-1), CO(2-1), and HCN(1-0) observed toward IRS 1 show broad redshifted absorption, providing evidence for gas infall with rates in the range of 3-10 × 10{sup –3} M {sub ☉} yr{sup –1} inferred from our observations.

43 CFR 427.1 - Water conservation.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Water conservation. 427.1 Section 427.1... INTERIOR WATER CONSERVATION RULES AND REGULATIONS § 427.1 Water conservation. (a) In general. The Secretary shall encourage the full consideration and incorporation of prudent and responsible water conservation...

Effectiveness of Co intercalation between Graphene and Ir(1 1 1)

Science.gov (United States)

Carlomagno, I.; Drnec, J.; Scaparro, A. M.; Cicia, S.; Mobilio, S.; Felici, R.; Meneghini, C.

2018-04-01

Graphene can be used to avoid the oxidation of metallic films. This work explores the effectiveness of such stabilizing effect on Cobalt (Co) films intercalated between Graphene and Ir(1 1 1). After intercalation at 300 °C, two Co films are exposed to ambient pressure and investigated using Co-K edge X-ray Absorption Near Edge Spectroscopy. The formation of a disordered oxide phase is observed, and associated to the presence of some non-intercalated Co. Further annealing at 500 °C causes the oxide reduction to metallic Co which further intercalates below the Graphene. Once the intercalation is completed, Graphene prevents the Co from oxidation under ambient pressure conditions.

SNP markers retrieval for a non-model species: a practical approach

Directory of Open Access Journals (Sweden)

Shahin Arwa

2012-01-01

Full Text Available Abstract Background SNP (Single Nucleotide Polymorphism markers are rapidly becoming the markers of choice for applications in breeding because of next generation sequencing technology developments. For SNP development by NGS technologies, correct assembly of the huge amounts of sequence data generated is essential. Little is known about assembler's performance, especially when dealing with highly heterogeneous species that show a high genome complexity and what the possible consequences are of differences in assemblies on SNP retrieval. This study tested two assemblers (CAP3 and CLC on 454 data from four lily genotypes and compared results with respect to SNP retrieval. Results CAP3 assembly resulted in higher numbers of contigs, lower numbers of reads per contig, and shorter average read lengths compared to CLC. Blast comparisons showed that CAP3 contigs were highly redundant. Contrastingly, CLC in rare cases combined paralogs in one contig. Redundant and chimeric contigs may lead to erroneous SNPs. Filtering for redundancy can be done by blasting selected SNP markers to the contigs and discarding all the SNP markers that show more than one blast hit. Results on chimeric contigs showed that only four out of 2,421 SNP markers were selected from chimeric contigs. Conclusion In practice, CLC performs better in assembling highly heterogeneous genome sequences compared to CAP3, and consequently SNP retrieval is more efficient. Additionally a simple flow scheme is suggested for SNP marker retrieval that can be valid for all non-model species.

Discusión: Explicaciones genéticas y psicológicas de la esquizofrenia.Genética de la esperanza

Directory of Open Access Journals (Sweden)

Silvio Bolaños-Salvatierra

2003-01-01

Full Text Available En este documento se rebaten críticas hechas por Raventós y Jensen al artículo “Genética y comportamiento”. Cuatro temas fueron seleccionados: 1 se determina que los antipsicóticos aparecieron veinte años después de la concepción hereditaria de la esquizofrenia; 2 se considera que la discusión es altamente pertinente, para nada bizantina o irrelevante, debido que persisten prácticas epistémicas riesgosas en los investigadores genético-conductuales; 3 aunque ninguna conducta humana está exenta de influencia constitucional, el enfoque biologicista se ha propasado al pretender explicar genéticamente casi todo, desconfirmando solapadamente la importancia de la historia personal; y, 4 se plantea que la investigación biológica sobrevalora el peso de las anomalías genéticas frente a la historia social, por lo que solo aparenta cautela. Se propone investigar genéticamente la esperanza con el objetivo de saturar a la humanidad con ese tipo de explicaciones, para alcanzar más rápido una convivencia basada en la tolerancia y el respeto.

Facile electrochemical transfer of large-area single crystal epitaxial graphene from Ir(1 1 1)

DEFF Research Database (Denmark)

Koefoed, Line; Kongsfelt, Mikkel; Ulstrup, Søren

2015-01-01

they are grown on (diameter ≈7 mm). In addition, the substrate can be reused for further growth cycles. A detailed Raman map analysis of the transferred graphene reveals straight lines, in which the Raman peaks characteristic for graphene are shifted. These lines originate from scratches in the Ir(1 1 1) crystal...

Optimal Design of Low-Density SNP Arrays for Genomic Prediction: Algorithm and Applications.

Directory of Open Access Journals (Sweden)

Xiao-Lin Wu

Full Text Available Low-density (LD single nucleotide polymorphism (SNP arrays provide a cost-effective solution for genomic prediction and selection, but algorithms and computational tools are needed for the optimal design of LD SNP chips. A multiple-objective, local optimization (MOLO algorithm was developed for design of optimal LD SNP chips that can be imputed accurately to medium-density (MD or high-density (HD SNP genotypes for genomic prediction. The objective function facilitates maximization of non-gap map length and system information for the SNP chip, and the latter is computed either as locus-averaged (LASE or haplotype-averaged Shannon entropy (HASE and adjusted for uniformity of the SNP distribution. HASE performed better than LASE with ≤1,000 SNPs, but required considerably more computing time. Nevertheless, the differences diminished when >5,000 SNPs were selected. Optimization was accomplished conditionally on the presence of SNPs that were obligated to each chromosome. The frame location of SNPs on a chip can be either uniform (evenly spaced or non-uniform. For the latter design, a tunable empirical Beta distribution was used to guide location distribution of frame SNPs such that both ends of each chromosome were enriched with SNPs. The SNP distribution on each chromosome was finalized through the objective function that was locally and empirically maximized. This MOLO algorithm was capable of selecting a set of approximately evenly-spaced and highly-informative SNPs, which in turn led to increased imputation accuracy compared with selection solely of evenly-spaced SNPs. Imputation accuracy increased with LD chip size, and imputation error rate was extremely low for chips with ≥3,000 SNPs. Assuming that genotyping or imputation error occurs at random, imputation error rate can be viewed as the upper limit for genomic prediction error. Our results show that about 25% of imputation error rate was propagated to genomic prediction in an Angus

Temperature-dependent absorption cross-section measurements of 1-butene (1-C4H8) in VUV and IR

KAUST Repository

Es-sebbar, Et-touhami

2013-01-01

Vacuum ultraviolet (VUV) and infrared (IR) absorption cross-section measurements of 1-butene (1-C4H8; CH2=CHCH2CH3; Butylene) are reported over the temperature range of 296-529K. The VUV measurements are performed between 115 and 205nm using synchrotron radiation as a tunable VUV light source. Fourier Transform Infrared (FTIR) spectroscopy is employed to measure absorption cross-section and band strengths in the IR region between 1.54 and 25μm (~6500-400cm-1). The measured room-temperature VUV and IR absorption cross-sections are compared with available literature data and are found to be in good agreement. The oscillator strength for the electronic transition (A1A\\'→X1A\\') around 150-205nm is determined to be 0.32±0.01.The gas temperature has a strong effect on both VUV and IR spectra. Measurements made in the VUV region show that the peak value of the band cross-section decreases and the background continuum increases with increasing gas temperature. This behavior is due to a change in the rotational and vibrational population distribution of 1-butene molecule. Similar changes in rotational population are observed in the IR spectra. Moreover, variation of the IR spectra with temperature is used to measure the enthalpy difference between syn and skew conformations of 1-butene and is found to be 0.24±0.03. kcal/mol, which is in excellent agreement with values reported in the literature. The measurements reported in this work will provide the much-needed spectroscopic information for the development of high-temperature quantitative diagnostics in combustion applications and validation of atmospheric chemistry models of extra-solar planets. © 2012 Elsevier Ltd.

A robust SNP barcode for typing Mycobacterium tuberculosis complex strains

KAUST Repository

Coll, Francesc

2014-09-01

Strain-specific genomic diversity in the Mycobacterium tuberculosis complex (MTBC) is an important factor in pathogenesis that may affect virulence, transmissibility, host response and emergence of drug resistance. Several systems have been proposed to classify MTBC strains into distinct lineages and families. Here, we investigate single-nucleotide polymorphisms (SNPs) as robust (stable) markers of genetic variation for phylogenetic analysis. We identify ∼92k SNP across a global collection of 1,601 genomes. The SNP-based phylogeny is consistent with the gold-standard regions of difference (RD) classification system. Of the ∼7k strain-specific SNPs identified, 62 markers are proposed to discriminate known circulating strains. This SNP-based barcode is the first to cover all main lineages, and classifies a greater number of sublineages than current alternatives. It may be used to classify clinical isolates to evaluate tools to control the disease, including therapeutics and vaccines whose effectiveness may vary by strain type. © 2014 Macmillan Publishers Limited.

Genetic and functional analysis of the gene encoding GAP-43 in schizophrenia.

Science.gov (United States)

Shen, Yu-Chih; Tsai, Ho-Min; Cheng, Min-Chih; Hsu, Shih-Hsin; Chen, Shih-Fen; Chen, Chia-Hsiang

2012-02-01

In earlier reports, growth-associated protein 43 (GAP-43) has been shown to be critical for initial establishment or reorganization of synaptic connections, a process thought to be disrupted in schizophrenia. Additionally, abnormal GAP-43 expression in different brain regions has been linked to this disorder in postmortem brain studies. In this study, we investigated the involvement of the gene encoding GAP-43 in the susceptibility to schizophrenia. We searched for genetic variants in the promoter region and 3 exons (including both UTR ends) of the GAP-43 gene using direct sequencing in a sample of patients with schizophrenia (n=586) and non-psychotic controls (n=576), both being Han Chinese from Taiwan, and conducted an association and functional study. We identified 11 common polymorphisms in the GAP-43 gene. SNP and haplotype-based analyses displayed no associations with schizophrenia. Additionally, we identified 4 rare variants in 5 out of 586 patients, including 1 variant located at the promoter region (c.-258-4722G>T) and 1 synonymous (V110V) and 2 missense (G150R and P188L) variants located at exon 2. No rare variants were found in the control subjects. The results of the reporter gene assay demonstrated that the regulatory activity of construct containing c.-258-4722T was significantly lower as compared to the wild type construct (c.-258-4722G; panalysis also demonstrated the functional relevance of other rare variants. Our study lends support to the hypothesis of multiple rare mutations in schizophrenia, and it provides genetic clues that indicate the involvement of GAP-43 in this disorder. Copyright © 2011 Elsevier B.V. All rights reserved.

MDM2 gene SNP309 T/G and p53 gene SNP72 G/C do not influence diffuse large B-cell non-Hodgkin lymphoma onset or survival in central European Caucasians

Directory of Open Access Journals (Sweden)

Landt Olfert

2008-04-01

Full Text Available Abstract Background SNP309 T/G (rs2279744 causes higher levels of MDM2, the most important negative regulator of the p53 tumor suppressor. SNP72 G/C (rs1042522 gives rise to a p53 protein with a greatly reduced capacity to induce apoptosis. Both polymorphisms have been implicated in cancer. The SNP309 G-allele has recently been reported to accelerate diffuse large B-cell lymphoma (DLBCL formation in pre-menopausal women and suggested to constitute a genetic basis for estrogen affecting human tumorigenesis. Here we asked whether SNP309 and SNP72 are associated with DLBCL in women and are correlated with age of onset, diagnosis, or patient's survival. Methods SNP309 and SNP72 were PCR-genotyped in a case-control study that included 512 controls and 311 patients diagnosed with aggressive NHL. Of these, 205 were diagnosed with DLBCL. Results The age of onset was similar in men and women. The control and patients group showed similar SNP309 and SNP72 genotype frequencies. Importantly and in contrast to the previous findings, similar genotype frequencies were observed in female patients diagnosed by 51 years of age and those diagnosed later. Specifically, 3/20 female DLBCL patients diagnosed by 51 years of age were homozygous for SNP309 G and 2/20 DLBCL females in that age group were homozygous for SNP72 C. Neither SNP309 nor SNP72 had a significant influence on event-free and overall survival in multivariate analyses. Conclusion In contrast to the previous study on Ashkenazi Jewish Caucasians, DLBCL in pre-menopausal women of central European Caucasian ethnicity was not associated with SNP309 G. Neither SNP309 nor SNP72 seem to be correlated with age of onset, diagnosis, or survival of patients.

IRS-1: essential for insulin- and IL-4-stimulated mitogenesis in hematopoietic cells.

Science.gov (United States)

Wang, L M; Myers, M G; Sun, X J; Aaronson, S A; White, M; Pierce, J H

1993-09-17

Although several interleukin-3 (IL-3)-dependent cell lines proliferate in response to IL-4 or insulin, the 32D line does not. Insulin and IL-4 sensitivity was restored to 32D cells by expression of IRS-1, the principal substrate of the insulin receptor. Although 32D cells possessed receptors for both factors, they lacked the IRS-1--related protein, 4PS, which becomes phosphorylated by tyrosine in insulin- or IL-4--responsive lines after stimulation. These results indicate that factors that bind unrelated receptors can use similar mitogenic signaling pathways in hematopoietic cells and that 4PS and IRS-1 are functionally similar proteins that are essential for insulin- and IL-4--induced proliferation.

Marcadores ancestrales culturales y genéticos: investigación de apellidos mapuche

Directory of Open Access Journals (Sweden)

Corach, Daniel

2007-01-01

Full Text Available Las comunidades aborígenes que habitan las regiones andinas se caracterizan por haber conservado elementos lingüísticos originarios en sus apellidos. Estos han sufrido procesos de “occidentalización”, manteniendo, no obstante, rasgos etnia-específicos. Tal situación permite disponer de un criterio simple para identificar con cierto grado de certeza la ancestralidad de un individuo. Con el objeto de evaluar el grado de correlación entre este marcador cultural y marcadores genéticos hemos llevado a cabo una investigación con individuos varones no relacionados provenientes de las provincias de Río Negro y Chubut (N=136. Los donantes se seleccionaron de acuerdo a la presencia de elementos lingüísticos Mapuche en sus apellidos e individuos con apellidos europeos. Se emplearon tres criterios de clasificación: apellidos, presencia del haplogrupo Q-M3 y presencia de Haplogrupos mitocondriales amerindios (ABCD. Los grupos clasificados de acuerdo con estos criterios fueron analizados mediante 15 STRs autosómicos y 9 Y-STRs. En ambas provincias más del 95% de los individuos portadores de apellidos Mapuche exhibían hgs matri y/o patrilineales amerindios. Por otro lado, en Río Negro y Chubut sólo 18 y 17%, respectivamente, no exhibieron ni apellidos ni marcadores genéticos asociables con ancestros amerindios; en éstos los hgmt más representados fueron H (6.5%, U5 (4.3% y K (2.8%, seguidos por T (1.4%, V (0.7%, X (0.7% y M (0.7%. También fue detectado el hg Africano en baja frecuencia (1.4%. Nuestros resultados confirman una correlación estrecha entre apellidos Mapuche y polimorfismos genéticos étnia-específicos.

EvoSNP-DB: A database of genetic diversity in East Asian populations.

Science.gov (United States)

Kim, Young Uk; Kim, Young Jin; Lee, Jong-Young; Park, Kiejung

2013-08-01

Genome-wide association studies (GWAS) have become popular as an approach for the identification of large numbers of phenotype-associated variants. However, differences in genetic architecture and environmental factors mean that the effect of variants can vary across populations. Understanding population genetic diversity is valuable for the investigation of possible population specific and independent effects of variants. EvoSNP-DB aims to provide information regarding genetic diversity among East Asian populations, including Chinese, Japanese, and Korean. Non-redundant SNPs (1.6 million) were genotyped in 54 Korean trios (162 samples) and were compared with 4 million SNPs from HapMap phase II populations. EvoSNP-DB provides two user interfaces for data query and visualization, and integrates scores of genetic diversity (Fst and VarLD) at the level of SNPs, genes, and chromosome regions. EvoSNP-DB is a web-based application that allows users to navigate and visualize measurements of population genetic differences in an interactive manner, and is available online at [http://biomi.cdc.go.kr/EvoSNP/].

Efeito de diferentes substratos na germinação de genótipos de girassol

Directory of Open Access Journals (Sweden)

Viviane Farias Silva

2014-10-01

Full Text Available Reutilizar resíduos provenientes de agroindústrias como substrato é uma alternativa que beneficia o meio ambiente e ao produtor. Nesse contexto, pesquisa foi realizada na Universidade Federal de Campina Grande/PB, objetivando-se avaliar o efeito de diferentes substratos provenientes de resíduos agroindustriais na germinação de genótipos de girassol. Foram avaliados a porcentagem de germinação (PG, o índice de velocidade de germinação (IVG, a velocidade média (Vm e o tempo médio (Tm de germinação de cada variedade de girassol estudada nos diferentes substratos utilizados. O delineamento foi o de bloco ao acaso e as análises foram realizadas, pelo programa computacional Sistema para Análise de Variância - SISVAR.Em relação ao substrato a porcentagem de germinação variou de 48,17 % a 65,47 %. O Helio 253 com menor valor de IVG (1,41, enquanto que o Olisum 3 com maior valor (4,80 seguido pelos genótipos AG 262 (4,43 e Embrapa 122- v2000 (3,26.  O tempo médio (Tm de germinação variou de 8,0 a 8,92. Os substratos considerados mais adequados para a germinação de todos os genótipos foram a areia, fibra de coco e a composição fibra de coco + areia.

Sequential sentinel SNP Regional Association Plots (SSS-RAP): an approach for testing independence of SNP association signals using meta-analysis data.

Science.gov (United States)

Zheng, Jie; Gaunt, Tom R; Day, Ian N M

2013-01-01

Genome-Wide Association Studies (GWAS) frequently incorporate meta-analysis within their framework. However, conditional analysis of individual-level data, which is an established approach for fine mapping of causal sites, is often precluded where only group-level summary data are available for analysis. Here, we present a numerical and graphical approach, "sequential sentinel SNP regional association plot" (SSS-RAP), which estimates regression coefficients (beta) with their standard errors using the meta-analysis summary results directly. Under an additive model, typical for genes with small effect, the effect for a sentinel SNP can be transformed to the predicted effect for a possibly dependent SNP through a 2×2 2-SNP haplotypes table. The approach assumes Hardy-Weinberg equilibrium for test SNPs. SSS-RAP is available as a Web-tool (http://apps.biocompute.org.uk/sssrap/sssrap.cgi). To develop and illustrate SSS-RAP we analyzed lipid and ECG traits data from the British Women's Heart and Health Study (BWHHS), evaluated a meta-analysis for ECG trait and presented several simulations. We compared results with existing approaches such as model selection methods and conditional analysis. Generally findings were consistent. SSS-RAP represents a tool for testing independence of SNP association signals using meta-analysis data, and is also a convenient approach based on biological principles for fine mapping in group level summary data. © 2012 Blackwell Publishing Ltd/University College London.

Genome wide in silico SNP-tumor association analysis

International Nuclear Information System (INIS)

Qiu, Ping; Wang, Luquan; Kostich, Mitch; Ding, Wei; Simon, Jason S; Greene, Jonathan R

2004-01-01

Carcinogenesis occurs, at least in part, due to the accumulation of mutations in critical genes that control the mechanisms of cell proliferation, differentiation and death. Publicly accessible databases contain millions of expressed sequence tag (EST) and single nucleotide polymorphism (SNP) records, which have the potential to assist in the identification of SNPs overrepresented in tumor tissue. An in silico SNP-tumor association study was performed utilizing tissue library and SNP information available in NCBI's dbEST (release 092002) and dbSNP (build 106). A total of 4865 SNPs were identified which were present at higher allele frequencies in tumor compared to normal tissues. A subset of 327 (6.7%) SNPs induce amino acid changes to the protein coding sequences. This approach identified several SNPs which have been previously associated with carcinogenesis, as well as a number of SNPs that now warrant further investigation This novel in silico approach can assist in prioritization of genes and SNPs in the effort to elucidate the genetic mechanisms underlying the development of cancer

Genomewide high-density SNP linkage analysis of non-BRCA1/2 breast cancer families identifies various candidate regions and has greater power than microsatellite studies

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Gonzalez-Neira Anna

2007-08-01

Full Text Available Abstract Background The recent development of new high-throughput technologies for SNP genotyping has opened the possibility of taking a genome-wide linkage approach to the search for new candidate genes involved in heredity diseases. The two major breast cancer susceptibility genes BRCA1 and BRCA2 are involved in 30% of hereditary breast cancer cases, but the discovery of additional breast cancer predisposition genes for the non-BRCA1/2 breast cancer families has so far been unsuccessful. Results In order to evaluate the power improvement provided by using SNP markers in a real situation, we have performed a whole genome screen of 19 non-BRCA1/2 breast cancer families using 4720 genomewide SNPs with Illumina technology (Illumina's Linkage III Panel, with an average distance of 615 Kb/SNP. We identified six regions on chromosomes 2, 3, 4, 7, 11 and 14 as candidates to contain genes involved in breast cancer susceptibility, and additional fine mapping genotyping using microsatellite markers around linkage peaks confirmed five of them, excluding the region on chromosome 3. These results were consistent in analyses that excluded SNPs in high linkage disequilibrium. The results were compared with those obtained previously using a 10 cM microsatellite scan (STR-GWS and we found lower or not significant linkage signals with STR-GWS data compared to SNP data in all cases. Conclusion Our results show the power increase that SNPs can supply in linkage studies.

Observations sur la définition du droit des gens1

OpenAIRE

Dominicé, Christian

2014-01-01

I 1. Jurisconsulte, diplomate, Rudolf Bindschedler a également exercé ses talents dans l’enseignement. Professeur de droit international public, il a rencontré, comme tous ses collègues, le problème de la définition de cette discipline, qu’il convient d’exposer à l’étudiant au seuil d’un cours. En hommage à l’internationaliste qui, associé de près à la pratique du droit des gens, a également manifesté son intérêt pour les questions théoriques, nous nous proposons d’aborder ce problème. Peut-ê...

Generación de un modelo knock-out del gen SCN1A en Drosophila melanogaster para el estudio del síndrome de Dravet.

OpenAIRE

PLANELLS CÁRCEL, ANDRÉS

2017-01-01

[ES] El Síndrome de Dravet (SD) es una enfermedad rara infantil que se manifiesta en crisis epilépticas a temprana edad y provoca un deterioro cognitivo y conductual. Esta enfermedad es causada por mutaciones dominantes en el gen SCN1A. Este trabajo se centra en la generación de un modelo knock-out (KO) del gen paralytic en Drosophila melanogaster, homólogo al gen SCN1A en humanos, para su aplicación en el estudio del SD. A la vez se ha estudiado la conducta de cepas sensibles ...

MDM2 SNP309, gene-gene interaction, and tumor susceptibility: an updated meta-analysis

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Wu Wei

2011-05-01

Full Text Available Abstract Background The tumor suppressor gene p53 is involved in multiple cellular pathways including apoptosis, transcriptional control, and cell cycle regulation. In the last decade it has been demonstrated that the single nucleotide polymorphism (SNP at codon 72 of the p53 gene is associated with the risk for development of various neoplasms. MDM2 SNP309 is a single nucleotide T to G polymorphism located in the MDM2 gene promoter. From the time that this well-characterized functional polymorphism was identified, a variety of case-control studies have been published that investigate the possible association between MDM2 SNP309 and cancer risk. However, the results of the published studies, as well as the subsequent meta-analyses, remain contradictory. Methods To investigate whether currently published epidemiological studies can clarify the potential interaction between MDM2 SNP309 and the functional genetic variant in p53 codon72 (Arg72Pro and p53 mutation status, we performed a meta-analysis of the risk estimate on 27,813 cases with various tumor types and 30,295 controls. Results The data we reviewed indicated that variant homozygote 309GG and heterozygote 309TG were associated with a significant increased risk of all tumor types (homozygote comparison: odds ratio (OR = 1.25, 95% confidence interval (CI = 1.13-1.37; heterozygote comparison: OR = 1.10, 95% CI = 1.03-1.17. We also found that the combination of GG and Pro/Pro, TG and Pro/Pro, GG and Arg/Arg significantly increased the risk of cancer (OR = 3.38, 95% CI = 1.77-6.47; OR = 1.88, 95% CI = 1.26-2.81; OR = 1.96, 95% CI = 1.01-3.78, respectively. In a stratified analysis by tumor location, we also found a significant increased risk in brain, liver, stomach and uterus cancer (OR = 1.47, 95% CI = 1.06-2.03; OR = 2.24, 95%CI = 1.57-3.18; OR = 1.54, 95%CI = 1.04-2.29; OR = 1.34, 95%CI = 1.07-1.29, respectively. However, no association was seen between MDM2 SNP309 and tumor susceptibility

Association between cytochrome CYP17A1, CYP3A4, and CYP3A43 polymorphisms and prostate cancer risk and aggressiveness in a Korean study population

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Jun Hyun Han

2015-04-01

Full Text Available In this study, we evaluated genetic variants of the androgen metabolism genes CYP17A1, CYP3A4, and CYP3A43 to determine whether they play a role in the development of prostate cancer (PCa in Korean men. The study population included 240 pathologically diagnosed cases of PCa and 223 age-matched controls. Among the 789 single-nucleotide polymorphism (SNP database variants detected, 129 were reported in two Asian groups (Han Chinese and Japanese in the HapMap database. Only 21 polymorphisms of CYP17A1, CYP3A4, and CYP3A43 were selected based on linkage disequilibrium in Asians (r2 = 1, locations (SNPs in exons were preferred, and amino acid changes and were assessed. In addition, we performed haplotype analysis for the 21 SNPs in CYP17A1, CYP3A4, and CYP3A43 genes. To determine the association between genotype and haplotype distributions of patients and controls, logistic analyses were carried out, controlling for age. Twelve sequence variants and five major haplotypes were identified in CYP17A1. Five sequence variants and two major haplotypes were identified in CYP3A4. Four sequence variants and four major haplotypes were observed in CYP3A43. CYP17A1 haplotype-2 (Ht-2 (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.04-2.18 was associated with PCa susceptibility. CYP3A4 Ht-2 (OR: 1.87; 95% CI: 1.02-3.43 was associated with PCa metastatic potential according to tumor stage. rs17115149 (OR: 1.96; 95% CI: 1.04-3.68 and CYP17A1 Ht-4 (OR: 2.01; 95% CI: 1.07-4.11 showed a significant association with histologic aggressiveness according to Gleason score. Genetic variants of CYP17A1 and CYP3A4 may play a role in the development of PCa in Korean men.

Association between cytochrome CYP17A1, CYP3A4, and CYP3A43 polymorphisms and prostate cancer risk and aggressiveness in a Korean study population.

Science.gov (United States)

Han, Jun Hyun; Lee, Yong Seong; Kim, Hae Jong; Lee, Shin Young; Myung, Soon Chul

2015-01-01

In this study, we evaluated genetic variants of the androgen metabolism genes CYP17A1, CYP3A4, and CYP3A43 to determine whether they play a role in the development of prostate cancer (PCa) in Korean men. The study population included 240 pathologically diagnosed cases of PCa and 223 age-matched controls. Among the 789 single-nucleotide polymorphism (SNP) database variants detected, 129 were reported in two Asian groups (Han Chinese and Japanese) in the HapMap database. Only 21 polymorphisms of CYP17A1, CYP3A4, and CYP3A43 were selected based on linkage disequilibrium in Asians (r2 = 1), locations (SNPs in exons were preferred), and amino acid changes and were assessed. In addition, we performed haplotype analysis for the 21 SNPs in CYP17A1, CYP3A4, and CYP3A43 genes. To determine the association between genotype and haplotype distributions of patients and controls, logistic analyses were carried out, controlling for age. Twelve sequence variants and five major haplotypes were identified in CYP17A1. Five sequence variants and two major haplotypes were identified in CYP3A4. Four sequence variants and four major haplotypes were observed in CYP3A43. CYP17A1 haplotype-2 (Ht-2) (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.04-2.18) was associated with PCa susceptibility. CYP3A4 Ht-2 (OR: 1.87; 95% CI: 1.02-3.43) was associated with PCa metastatic potential according to tumor stage. rs17115149 (OR: 1.96; 95% CI: 1.04-3.68) and CYP17A1 Ht-4 (OR: 2.01; 95% CI: 1.07-4.11) showed a significant association with histologic aggressiveness according to Gleason score. Genetic variants of CYP17A1 and CYP3A4 may play a role in the development of PCa in Korean men.

p.Q192R SNP of PON1 seems not to be Associated with Carotid Atherosclerosis Risk Factors in an Asymptomatic and Normolipidemic Brazilian Population Sample

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Daniel Zanetti Scherrer

2015-07-01

Full Text Available Background:Evidences suggest that paraoxonase 1 (PON1 confers important antioxidant and anti-inflammatory properties when associated with high-density lipoprotein (HDL.Objective:To investigate the relationships between p.Q192R SNP of PON1, biochemical parameters and carotid atherosclerosis in an asymptomatic, normolipidemic Brazilian population sample.Methods:We studied 584 volunteers (females n = 326, males n = 258; 19-75 years of age. Total genomic DNA was extracted and SNP was detected in the TaqMan® SNP OpenArray® genotyping platform (Applied Biosystems, Foster City, CA. Plasma lipoproteins and apolipoproteins were determined and PON1 activity was measured using paraoxon as a substrate. High-resolution β-mode ultrasonography was used to measure cIMT and the presence of carotid atherosclerotic plaques in a subgroup of individuals (n = 317.Results:The presence of p.192Q was associated with a significant increase in PON1 activity (RR = 12.30 (11.38; RQ = 46.96 (22.35; QQ = 85.35 (24.83 μmol/min; p Conclusion:In low-risk individuals, the presence of the p.192Q variant of PON1 is associated with a beneficial plasma lipid profile but not with carotid atherosclerosis.

Ngc7538 Irs1 - A Highly Collimated Ionized Wind Source Powered By Accretion

Science.gov (United States)

Sandell, Goran H. L.; Wright, M.; Goss, W.; Corder, S.

2009-01-01

Recent images show that NGC7538 IRS1 is not a conventional Ultracompact or Hypercompact HII region, but is completely wind-excited (other broad recombination line hypercompact HII regions may be similar to IRS1). NGC 7538 IRS1 is a well studied young high-mass star (L 2 10^5 L_Sun).VLA images at 6 and 2 cm (Cambell 1984; ApJ, 282, L27) showed a compact bipolar core (lobe separation 0.2") with more extended faint lobes. Recombination line observations (Gaume et al. 1995, ApJ, 438, 776) show extremely wide line profiles indicating substantial mass motion of the ionized gas. We re-analyzed high angular resolution VLA archive data from 6 cm to 7 mm, and measured the flux from the compact core and the extended (1.5 - 2") bipolar lobes. We find that the compact core has a spectral index, alpha 0.6, which could be explained by an optically thick hypercompact core with a density gradient. However, the size of the core shrinks with increasing frequency; from 0.24" at 6 cm to 0.1" at 7 mm, consistent with that expected for a collimated jet (Reynolds 1986, ApJ, 304, 713). If we do a crude size correction so that we compare emission from the optically thick inner part of the jet for a set of 2 cm and 7 mm observations we get alpha 1.6, i.e. close to the optically thick value. BIMA and CARMA continuum observations at 3 mm show some dust excess, while. HCO+ J=1-0 observations combined with FCRAO single dish data show a clear inverse P Cygni profile towards IRS1. These observations confirm that IRS1 is heavily accreting with an accretion rate 2 10^-4 M_Sun/year, sufficient to quench the formation of an HII region.

IRS-1 serine phosphorylation and insulin resistance in skeletal muscle from pancreas tranplant recipient

DEFF Research Database (Denmark)

Bouzakri, K; Karlsson, HRK; Vestergaard, Henrik

2006-01-01

Insulin-dependent diabetic recipients of successful pancreas allografts achieve self-regulatory insulin secretion and discontinue exogenous insulin therapy; however, chronic hyperinsulinemia and impaired insulin sensitivity generally develop. To determine whether insulin resistance is accompanied....... In conclusion, peripheral insulin resistance in pancreas-kidney transplant recipients may arise from a negative feedback regulation of the canonical insulin-signaling cascade from excessive serine phosphorylation of IRS-1, possibly as a consequence of immunosuppressive therapy and hyperinsulinemia....... insulin receptor substrate (IRS)-1 Ser (312) and Ser (616) phosphorylation, IRS-1-associated phosphatidylinositol 3-kinase activity, and extracellular signal-regulated kinase (ERK)-1/2 phosphorylation were elevated in pancreas-kidney transplant recipients, coincident with fasting hyperinsulinemia. Basal...

Involvement of Sodium Nitroprusside (SNP in the Mechanism That Delays Stem Bending of Different Gerbera Cultivars

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Aung H. Naing

2017-11-01

Full Text Available Longevity of cut flowers of many gerbera cultivars (Gerbera jamesonii is typically short because of stem bending; hence, stem bending that occurs during the early vase life period is a major problem in gerbera. Here, we investigated the effects of sodium nitroprusside (SNP on the delay of stem bending in the gerbera cultivars, Alliance, Rosalin, and Bintang, by examining relative fresh weight, bacterial density in the vase solution, transcriptional analysis of a lignin biosynthesis gene, antioxidant activity, and xylem blockage. All three gerbera cultivars responded to SNP by delaying stem bending, compared to the controls; however, the responses were dose- and cultivar-dependent. Among the treatments, SNP at 20 mg L-1 was the best to delay stem bending in Alliance, while dosages of 10 and 5 mg L-1 were the best for Rosalin and Bintang, respectively. However, stem bending in Alliance and Rosalin was faster than in Bintang, indicating a discrepancy influenced by genotype. According to our analysis of the role of SNP in the delay of stem bending, the results revealed that SNP treatment inhibited bacterial growth and xylem blockage, enhanced expression levels of a lignin biosynthesis gene, and maintained antioxidant activities. Therefore, it is suggested that the cause of stem bending is associated with the above-mentioned parameters and SNP is involved in the mechanism that delays stem bending in the different gerbera cultivars.

Differential cellular responses to prolonged LDR-IR in MLH1-proficient and MLH1-deficient colorectal cancer HCT116 cells.

Science.gov (United States)

Yan, Tao; Seo, Yuji; Kinsella, Timothy J

2009-11-15

MLH1 is a key DNA mismatch repair (MMR) protein involved in maintaining genomic stability by participating in the repair of endogenous and exogenous mispairs in the daughter strands during S phase. Exogenous mispairs can result following treatment with several classes of chemotherapeutic drugs, as well as with ionizing radiation. In this study, we investigated the role of the MLH1 protein in determining the cellular and molecular responses to prolonged low-dose rate ionizing radiation (LDR-IR), which is similar to the clinical use of cancer brachytherapy. An isogenic pair of MMR(+) (MLH1(+)) and MMR(-) (MLH1(-)) human colorectal cancer HCT116 cells was exposed to prolonged LDR-IR (1.3-17 cGy/h x 24-96 h). The clonogenic survival and gene mutation rates were examined. Cell cycle distribution was analyzed with flow cytometry. Changes in selected DNA damage repair proteins, DNA damage response proteins, and cell death marker proteins were examined with Western blotting. MLH1(+) HCT116 cells showed greater radiosensitivity with enhanced expression of apoptotic and autophagic markers, a reduced HPRT gene mutation rate, and more pronounced cell cycle alterations (increased late-S population and a G(2)/M arrest) following LDR-IR compared with MLH1(-) HCT116 cells. Importantly, a progressive increase in MLH1 protein levels was found in MLH1(+) cells during prolonged LDR-IR, which was temporally correlated with a progressive decrease in Rad51 protein (involved in homologous recombination) levels. MLH1 status significantly affects cellular responses to prolonged LDR-IR. MLH1 may enhance cell radiosensitivity to prolonged LDR-IR through inhibition of homologous recombination (through inhibition of Rad51).

Electrochemical Li Topotactic Reaction in Layered SnP3 for Superior Li-Ion Batteries

Science.gov (United States)

Park, Jae-Wan; Park, Cheol-Min

2016-10-01

The development of new anode materials having high electrochemical performances and interesting reaction mechanisms is highly required to satisfy the need for long-lasting mobile electronic devices and electric vehicles. Here, we report a layer crystalline structured SnP3 and its unique electrochemical behaviors with Li. The SnP3 was simply synthesized through modification of Sn crystallography by combination with P and its potential as an anode material for LIBs was investigated. During Li insertion reaction, the SnP3 anode showed an interesting two-step electrochemical reaction mechanism comprised of a topotactic transition (0.7-2.0 V) and a conversion (0.0-2.0 V) reaction. When the SnP3-based composite electrode was tested within the topotactic reaction region (0.7-2.0 V) between SnP3 and LixSnP3 (x ≤ 4), it showed excellent electrochemical properties, such as a high volumetric capacity (1st discharge/charge capacity was 840/663 mA h cm-3) with a high initial coulombic efficiency, stable cycle behavior (636 mA h cm-3 over 100 cycles), and fast rate capability (550 mA h cm-3 at 3C). This layered SnP3 anode will be applicable to a new anode material for rechargeable LIBs.

Evaluation of the Ion Torrent™ HID SNP 169-plex

DEFF Research Database (Denmark)

Børsting, Claus; Fordyce, Sarah L; Olofsson, Jill Katharina

2014-01-01

The Ion Torrent™ HID SNP assay amplified 136 autosomal SNPs and 33 Y-chromosome markers in one PCR and the markers were subsequently typed using the Ion PGM™ second generation sequencing platform. A total of 51 of the autosomal SNPs were selected from the SNPforID panel that is routinely used...... in our ISO 17025 accredited laboratory. Concordance between the Ion Torrent™ HID SNP assay and the SNPforID assay was tested by typing 44 Iraqis twice with the Ion Torrent™ HID SNP assay. The same samples were previously typed with the SNPforID assay and the Y-chromosome haplogroups of the individuals...

Compression and fast retrieval of SNP data.

Science.gov (United States)

Sambo, Francesco; Di Camillo, Barbara; Toffolo, Gianna; Cobelli, Claudio

2014-11-01

The increasing interest in rare genetic variants and epistatic genetic effects on complex phenotypic traits is currently pushing genome-wide association study design towards datasets of increasing size, both in the number of studied subjects and in the number of genotyped single nucleotide polymorphisms (SNPs). This, in turn, is leading to a compelling need for new methods for compression and fast retrieval of SNP data. We present a novel algorithm and file format for compressing and retrieving SNP data, specifically designed for large-scale association studies. Our algorithm is based on two main ideas: (i) compress linkage disequilibrium blocks in terms of differences with a reference SNP and (ii) compress reference SNPs exploiting information on their call rate and minor allele frequency. Tested on two SNP datasets and compared with several state-of-the-art software tools, our compression algorithm is shown to be competitive in terms of compression rate and to outperform all tools in terms of time to load compressed data. Our compression and decompression algorithms are implemented in a C++ library, are released under the GNU General Public License and are freely downloadable from http://www.dei.unipd.it/~sambofra/snpack.html. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Suppression of superconductivity in Nb by IrMn in IrMn/Nb bilayers

KAUST Repository

Wu, B. L.

2013-10-10

Effect of antiferromagnet on superconductivity has been investigated in IrMn/Nb bilayers. Significant suppression of both transition temperature (Tc) and lower critical field (Hc1) of Nb is found in IrMn/Nb bilayers as compared to a single layer Nb of same thickness; the suppression effect is even stronger than that of a ferromagnet in NiFe/Nb bilayers. The addition of an insulating MgO layer at the IrMn-Nb interface nearly restores Tc to that of the single layer Nb, but Hc1 still remains suppressed. These results suggest that, in addition to proximity effect and magnetic impurity scattering, magnetostatic interaction also plays a role in suppressing superconductivity of Nb in IrMn/Nb bilayers. In addition to reduced Tc and Hc1, the IrMn layer also induces broadening in the transition temperature of Nb, which can be accounted for by a finite distribution of stray field from IrMn.

A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff

Science.gov (United States)

Cingolani, Pablo; Platts, Adrian; Wang, Le Lily; Coon, Melissa; Nguyen, Tung; Wang, Luan; Land, Susan J.; Lu, Xiangyi; Ruden, Douglas M.

2012-01-01

We describe a new computer program, SnpEff, for rapidly categorizing the effects of variants in genome sequences. Once a genome is sequenced, SnpEff annotates variants based on their genomic locations and predicts coding effects. Annotated genomic locations include intronic, untranslated region, upstream, downstream, splice site, or intergenic regions. Coding effects such as synonymous or non-synonymous amino acid replacement, start codon gains or losses, stop codon gains or losses, or frame shifts can be predicted. Here the use of SnpEff is illustrated by annotating ~356,660 candidate SNPs in ~117 Mb unique sequences, representing a substitution rate of ~1/305 nucleotides, between the Drosophila melanogaster w1118; iso-2; iso-3 strain and the reference y1; cn1 bw1 sp1 strain. We show that ~15,842 SNPs are synonymous and ~4,467 SNPs are non-synonymous (N/S ~0.28). The remaining SNPs are in other categories, such as stop codon gains (38 SNPs), stop codon losses (8 SNPs), and start codon gains (297 SNPs) in the 5′UTR. We found, as expected, that the SNP frequency is proportional to the recombination frequency (i.e., highest in the middle of chromosome arms). We also found that start-gain or stop-lost SNPs in Drosophila melanogaster often result in additions of N-terminal or C-terminal amino acids that are conserved in other Drosophila species. It appears that the 5′ and 3′ UTRs are reservoirs for genetic variations that changes the termini of proteins during evolution of the Drosophila genus. As genome sequencing is becoming inexpensive and routine, SnpEff enables rapid analyses of whole-genome sequencing data to be performed by an individual laboratory. PMID:22728672

(SNP) markers for the Chinese black sleeper, Bostrychus sinensis

African Journals Online (AJOL)

We characterized 11 single nucleotide ploymorphism (SNP) markers for the Chinese black sleeper, Bostrychus sinensis. These markers were isolated from a genomic library and tested in ten geographically distant individuals of B. sinensis. Polymorphisms of these SNP loci were assessed using a wild population including ...

Seleção de genótipos parentais de acerola com base na divergência genética multivariada

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CARPENTIERI-PÍPOLO VALÉRIA

2000-01-01

Full Text Available Este trabalho teve por objetivo identificar e selecionar genótipos parentais de acerola (Malpighia emarginata L. adequadas a programas de melhoramento genético. Nove caracteres quantitativos de maior importância agronômica foram usados para determinação da distância genética e formação de grupos similares de acessos. O agrupamento pelo método de Tocher, a partir das distâncias generalizadas de Mahalanobis, possibilitou a divisão de 14 genótipos em três grupos. Com base na divergência genética e no caráter agronômico-chave (teor de vitamina C, destacaram-se como mais promissores os cruzamentos dos genótipos: AM Mole pertencente ao grupo III, com os genótipos PR AM, N° 18, PR 17, PR 16, Eclipse, AM 22 e Dominga, todos pertencentes ao grupo I.

Trans-Fatty Acids Aggravate Obesity, Insulin Resistance and Hepatic Steatosis in C57BL/6 Mice, Possibly by Suppressing the IRS1 Dependent Pathway

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Xiaona Zhao

2016-05-01

Full Text Available Trans-fatty acid consumption has been reported as a risk factor for metabolic disorders and targeted organ damages. Nonetheless, little is known about the roles and mechanisms of trans-fatty acids in obesity, insulin resistance (IR and hepatic steatosis. Adult C57BL/6 male mice were fed with four different diets for 20 weeks: normal diet (ND, high fat diet (HFD, low trans-fatty acids diet (LTD and high trans-fatty acid diet (HTD. The diet-induced metabolic disorders were assessed by evaluating body weight, glucose tolerance test, hepatic steatosis and plasma lipid profiles post 20-week diet. Histological (H&E, Oil-Red-O staining and western blot analysis were employed to assess liver steatosis and potential signaling pathways. After 20-weeks of diet, the body weights of the four groups were 29.61 ± 1.89 g (ND, 39.04 ± 4.27 g (HFD, 34.09 ± 2.62 g (LTD and 43.78 ± 4.27 g (HTD (p < 0.05, respectively. HFD intake significantly impaired glucose tolerance, which was impaired further in the mice consuming the HTD diet. The effect was further exacerbated by HTD diet. Moreover, the HTD group exhibited significantly more severe liver steatosis compared with HFD group possibly through regulating adipose triglyceride lipase. The group consuming the HTD also exhibited significantly reduced levels of IRS1, phosphor-PKC and phosphor-AKT. These results support our hypothesis that consumption of a diet high in trans-fatty acids induces higher rates of obesity, IR and hepatic steatosis in male C57BL/6 mice, possibly by suppressing the IRS1dependent pathway.

Tri-allelic SNP markers enable analysis of mixed and degraded DNA samples.

Science.gov (United States)

Westen, Antoinette A; Matai, Anuska S; Laros, Jeroen F J; Meiland, Hugo C; Jasper, Mandy; de Leeuw, Wiljo J F; de Knijff, Peter; Sijen, Titia

2009-09-01

For the analysis of degraded DNA in disaster victim identification (DVI) and criminal investigations, single nucleotide polymorphisms (SNPs) have been recognized as promising markers mainly because they can be analyzed in short sized amplicons. Most SNPs are bi-allelic and are thereby ineffective to detect mixtures, which may lead to incorrect genotyping. We developed an algorithm to find non-binary (i.e. tri-allelic or tetra-allelic) SNPs in the NCBI dbSNP database. We selected 31 potential tri-allelic SNPs with a minor allele frequency of at least 10%. The tri-allelic nature was confirmed for 15 SNPs residing on 14 different chromosomes. Multiplex SNaPshot assays were developed, and the allele frequencies of 16 SNPs were determined among 153 Dutch and 111 Netherlands Antilles reference samples. Using these multiplex SNP assays, the presence of a mixture of two DNA samples in a ratio up to 1:8 could be recognized reliably. Furthermore, we compared the genotyping efficiency of the tri-allelic SNP markers and short tandem repeat (STR) markers by analyzing artificially degraded DNA and DNA from 30 approximately 500-year-old bone and molar samples. In both types of degraded DNA samples, the larger sized STR amplicons failed to amplify whereas the tri-allelic SNP markers still provided valuable information. In conclusion, tri-allelic SNP markers are suited for the analysis of degraded DNA and enable the detection of a second DNA source in a sample.

IGF1 regulates RUNX1 expression via IRS1/2: Implications for antler chondrocyte differentiation

OpenAIRE

Yang, Zhan-Qing; Zhang, Hong-Liang; Duan, Cui-Cui; Geng, Shuang; Wang, Kai; Yu, Hai-Fan; Yue, Zhan-Peng; Guo, Bin

2017-01-01

Although IGF1 is important for the proliferation and differentiation of chondrocytes, its underlying molecular mechanism is still unknown. Here we addressed the physiologic function of IGF1 in antler cartilage and explored the interplay of IGF1, IRS1/2 and RUNX1 in chondrocyte differentiation. The results showed that IGF1 was highly expressed in antler chondrocytes. Exogenous rIGF1 could increase the proliferation of chondrocytes and cell proportion in the S phase, whereas IGF1R inhibitor PQ4...

Preserving Accuracy in GenBank

DEFF Research Database (Denmark)

Bidartondo, M.I.; Bruns, T. D.; Blackwell, M.

2008-01-01

GenBank, the public repository for nucleotide and protein sequences, is a critical resource for molecular biology, evolutionary biology, and ecology. While some attention has been drawn to sequence errors (1), common annotation errors also reduce the value of this database. In fact, for organisms...

Distributed Generation Market Demand Model (dGen): Documentation

Energy Technology Data Exchange (ETDEWEB)

Sigrin, Benjamin [National Renewable Energy Lab. (NREL), Golden, CO (United States); Gleason, Michael [National Renewable Energy Lab. (NREL), Golden, CO (United States); Preus, Robert [National Renewable Energy Lab. (NREL), Golden, CO (United States); Baring-Gould, Ian [National Renewable Energy Lab. (NREL), Golden, CO (United States); Margolis, Robert [National Renewable Energy Lab. (NREL), Golden, CO (United States)

2016-02-01

The Distributed Generation Market Demand model (dGen) is a geospatially rich, bottom-up, market-penetration model that simulates the potential adoption of distributed energy resources (DERs) for residential, commercial, and industrial entities in the continental United States through 2050. The National Renewable Energy Laboratory (NREL) developed dGen to analyze the key factors that will affect future market demand for distributed solar, wind, storage, and other DER technologies in the United States. The new model builds off, extends, and replaces NREL's SolarDS model (Denholm et al. 2009a), which simulates the market penetration of distributed PV only. Unlike the SolarDS model, dGen can model various DER technologies under one platform--it currently can simulate the adoption of distributed solar (the dSolar module) and distributed wind (the dWind module) and link with the ReEDS capacity expansion model (Appendix C). The underlying algorithms and datasets in dGen, which improve the representation of customer decision making as well as the spatial resolution of analyses (Figure ES-1), also are improvements over SolarDS.

Structural and magnetic properties of Sr{sub 2}Y{sub 1+x}Ir{sub 1-x}O{sub 6} materials

Energy Technology Data Exchange (ETDEWEB)

Aslan Cansever, Gizem; Geyer, Maximilian; Blum, Christian G.F.; Gass, Sebastian; Corredor, Laura T.; Maljuk, Andrey; Wolter, A.U.B. [Leibniz Institute for Solid State and Materials Research Dresden, IFW Dresden (Germany); Manna, Kaustuv [Max-Planck-Institute for Chemical Physics of Solids, Dresden (Germany); Hammerath, Franziska; Wurmehl, Sabine; Buechner, Bernd [Leibniz Institute for Solid State and Materials Research Dresden, IFW Dresden (Germany); Institute for Solid State Physics, TU Dresden (Germany)

2016-07-01

Ir-based materials have attracted a lot of attention because of the competition between the spin-orbit coupling, Coulomb interaction and crystal field. Sr{sub 2}YIrO{sub 6} double perovskites with Ir{sup +5} (5d{sup 4}) ions are generally considered to have a nonmagnetic ground state (J=0). However, Sr{sub 2}YIrO{sub 6} double perovskites have been reported to exhibit long-range magnetic order at low temperature and the distorted IrO{sub 6} octahedra were discussed to cause the magnetism in this compound [2]. In this study Sr{sub 2}Y{sub 1+x}Ir{sub 1-x}O{sub 6} materials were investigated in relation to structural and magnetic properties with varying Y and Ir concentrations. The samples were prepared by solid-state chemical reaction method. Magnetic susceptibility measurements were performed down to 0.4 K.

Detecting imbalanced expression of SNP alleles by minisequencing on microarrays

Directory of Open Access Journals (Sweden)

Dahlgren Andreas

2004-10-01

Full Text Available Abstract Background Each of the human genes or transcriptional units is likely to contain single nucleotide polymorphisms that may give rise to sequence variation between individuals and tissues on the level of RNA. Based on recent studies, differential expression of the two alleles of heterozygous coding single nucleotide polymorphisms (SNPs may be frequent for human genes. Methods with high accuracy to be used in a high throughput setting are needed for systematic surveys of expressed sequence variation. In this study we evaluated two formats of multiplexed, microarray based minisequencing for quantitative detection of imbalanced expression of SNP alleles. We used a panel of ten SNPs located in five genes known to be expressed in two endothelial cell lines as our model system. Results The accuracy and sensitivity of quantitative detection of allelic imbalance was assessed for each SNP by constructing regression lines using a dilution series of mixed samples from individuals of different genotype. Accurate quantification of SNP alleles by both assay formats was evidenced for by R2 values > 0.95 for the majority of the regression lines. According to a two sample t-test, we were able to distinguish 1–9% of a minority SNP allele from a homozygous genotype, with larger variation between SNPs than between assay formats. Six of the SNPs, heterozygous in either of the two cell lines, were genotyped in RNA extracted from the endothelial cells. The coefficient of variation between the fluorescent signals from five parallel reactions was similar for cDNA and genomic DNA. The fluorescence signal intensity ratios measured in the cDNA samples were compared to those in genomic DNA to determine the relative expression levels of the two alleles of each SNP. Four of the six SNPs tested displayed a higher than 1.4-fold difference in allelic ratios between cDNA and genomic DNA. The results were verified by allele-specific oligonucleotide hybridisation and

SNPdetector: a software tool for sensitive and accurate SNP detection.

Directory of Open Access Journals (Sweden)

Jinghui Zhang

2005-10-01

Full Text Available Identification of single nucleotide polymorphisms (SNPs and mutations is important for the discovery of genetic predisposition to complex diseases. PCR resequencing is the method of choice for de novo SNP discovery. However, manual curation of putative SNPs has been a major bottleneck in the application of this method to high-throughput screening. Therefore it is critical to develop a more sensitive and accurate computational method for automated SNP detection. We developed a software tool, SNPdetector, for automated identification of SNPs and mutations in fluorescence-based resequencing reads. SNPdetector was designed to model the process of human visual inspection and has a very low false positive and false negative rate. We demonstrate the superior performance of SNPdetector in SNP and mutation analysis by comparing its results with those derived by human inspection, PolyPhred (a popular SNP detection tool, and independent genotype assays in three large-scale investigations. The first study identified and validated inter- and intra-subspecies variations in 4,650 traces of 25 inbred mouse strains that belong to either the Mus musculus species or the M. spretus species. Unexpected heterozygosity in CAST/Ei strain was observed in two out of 1,167 mouse SNPs. The second study identified 11,241 candidate SNPs in five ENCODE regions of the human genome covering 2.5 Mb of genomic sequence. Approximately 50% of the candidate SNPs were selected for experimental genotyping; the validation rate exceeded 95%. The third study detected ENU-induced mutations (at 0.04% allele frequency in 64,896 traces of 1,236 zebra fish. Our analysis of three large and diverse test datasets demonstrated that SNPdetector is an effective tool for genome-scale research and for large-sample clinical studies. SNPdetector runs on Unix/Linux platform and is available publicly (http://lpg.nci.nih.gov.

43 CFR 43.655 - Individual.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Individual. 43.655 Section 43.655 Public Lands: Interior Office of the Secretary of the Interior GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 43.655 Individual. Individual means a natural person. ...

Preparation and Characterization of cis- and trans-[Ir(tn)2Cl2]CF3SO3 and of [Ir(tn)3]Cl3 (tn=propane-1,3-diamine)

DEFF Research Database (Denmark)

Brorson, Michael; Galsbøl, Frode; Simonsen, Kim

1998-01-01

for the preparation of [Rh(tn)3]Cl3 in quantitative yield from Rh(thtp)3Cl3 is also given. The complexes were characterized by 1H and 13C NMR and by UV/VIS spectroscopy. The conformation of the six-membered chelate rings of [Ir(tn)3]3+ in the solid state was determined by single-crystal X-ray diffraction of [Ir(tn)3......Procedures are given for the preparation and isolation of cis- and trans-[Ir(tn)2Cl2]CF3SO3 and of [Ir(tn)3]Cl3, (tn=propane-1,3-diamine). The compounds were prepared by the use of Ir(thtp)3Cl3 (thtp=tetrahydrothiophene) as starting material, using either DMSO or neat tn as solvent. A procedure......] [Co(CN)6] x 5H2O. The three chelate rings all adopt the energetically favoured chair conformation; however, the overall idealized symmetry is C1. A comparative ligand field analysis, based on Gaussian resolution of the solution UV/VIS spectra for a number of homoleptic [M(N6)]3+ (M=CoIII, RhIII, Ir...

Una variante del gen CAPN10 y los factores ambientales muestran asociación con el exceso de peso en jóvenes colombianos

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Ana C. Orozco

2014-12-01

Full Text Available Introducción. La obesidad resulta de la interacción entre factores de riesgo genéticos y ambientales. Objetivo. Evaluar el efecto de tres variantes genéticas y factores ambientales en el exceso de peso en jóvenes de 10 a 18 años de Medellín, Colombia. Materiales y métodos. Se hizo un estudio transversal en 424 jóvenes divididos en tres grupos: 100 obesos, 112 jóvenes con sobrepeso, y, pareados con ellos, 212 jóvenes con peso adecuado, que conformaron el grupo de control. Se evaluó la asociación entre tres polimorfismos genéticos (UCP3-rs1800849, FTO-rs17817449 y CAPN10-rs3842570 y el exceso de peso, así como su interacción con antecedentes familiares de enfermedad, el tiempo dedicado a ver televisión y a jugar videojuegos y el consumo de alimentos. Resultados. Los antecedentes familiares de obesidad, la dedicación de más de dos horas al día a ver televisión y jugar videojuegos, la falta de lactancia materna, el bajo consumo de cereales, legumbres, frutas y verduras y el gran consumo de comidas rápidas fueron más frecuentes entre los obesos que en los controles. Se observó una asociación significativa entre el genotipo I/I (SNP19 del CAPN10 y el exceso de peso, incluso en los jóvenes que llevaban una vida activa. Además, se encontró una asociación significativa entre los genotipos C/C del UCP3 y G/G y T/T del FTO y el exceso de peso, pero solo en los jóvenes sedentarios. Conclusiones. En esta población, la alimentación inadecuada y el sedentarismo aumentaron el riesgo de exceso de peso. El genotipo I/I de SNP19 del CAPN10 se asoció significativamente con el exceso de peso. Algunas variantes del FTO y el UCP3 mostraron tener efecto solo en jóvenes sedentarios.

An investigation into the accuracy of Acuros(TM) BV in heterogeneous phantoms for a (192)Ir HDR source using LiF TLDs.

Science.gov (United States)

Manning, Siobhan; Nyathi, Thulani

2014-09-01

The aim of this study was to evaluate the accuracy of the new Acuros(TM) BV algorithm using well characterized LiF:Mg,Ti TLD 100 in heterogeneous phantoms. TLDs were calibrated using an (192)Ir source and the AAPM TG-43 calculated dose. The Tölli and Johansson Large Cavity principle and Modified Bragg Gray principle methods confirm the dose calculated by TG-43 at a distance of 5 cm from the source to within 4 %. These calibrated TLDs were used to measure the dose in heterogeneous phantoms containing air, stainless steel, bone and titanium. The TLD results were compared with the AAPM TG-43 calculated dose and the Acuros calculated dose. Previous studies by other authors have shown a change in TLD response with depth when irradiated with an (192)Ir source. This TLD depth dependence was assessed by performing measurements at different depths in a water phantom with an (192)Ir source. The variation in the TLD response with depth in a water phantom was not found to be statistically significant for the distances investigated. The TLDs agreed with Acuros(TM) BV within 1.4 % in the air phantom, 3.2 % in the stainless steel phantom, 3 % in the bone phantom and 5.1 % in the titanium phantom. The TLDs showed a larger discrepancy when compared to TG-43 with a maximum deviation of 9.3 % in the air phantom, -11.1 % in the stainless steel phantom, -14.6 % in the bone phantom and -24.6 % in the titanium phantom. The results have shown that Acuros accounts for the heterogeneities investigated with a maximum deviation of -5.1 %. The uncertainty associated with the TLDs calibrated in the PMMA phantom is ±8.2 % (2SD).

Protection of p+-n-Si Photoanodes by Sputter-Deposited Ir/IrOxThin Films

DEFF Research Database (Denmark)

Mei, Bastian Timo; Seger, Brian; Pedersen, Thomas

2014-01-01

Sputter deposition of Ir/IrOx on p+-n-Si without interfacial corrosion protection layers yielded photoanodes capable of efficient water oxidation (OER) in acidic media (1 M H2SO4). Stability of at least 18 h was shown by chronoamperomety at 1.23 V versus RHE (reversible hydrogen electrode) under 38...... density of 1 mA/cm2 at 1.05 V vs. RHE. Further improvement by heat treatment resulted in a cathodic shift of 40 mV and enabled a current density of 10 mA/cm2 (requirements for a 10% efficient tandem device) at 1.12 V vs. RHS under irradiation. Thus, the simple IrOx/Ir/p+-n-Si structures not only provide...

Direct inference of SNP heterozygosity rates and resolution of LOH detection.

Directory of Open Access Journals (Sweden)

Xiaohong Li

2007-11-01

Full Text Available Single nucleotide polymorphisms (SNPs have been increasingly utilized to investigate somatic genetic abnormalities in premalignancy and cancer. LOH is a common alteration observed during cancer development, and SNP assays have been used to identify LOH at specific chromosomal regions. The design of such studies requires consideration of the resolution for detecting LOH throughout the genome and identification of the number and location of SNPs required to detect genetic alterations in specific genomic regions. Our study evaluated SNP distribution patterns and used probability models, Monte Carlo simulation, and real human subject genotype data to investigate the relationships between the number of SNPs, SNP HET rates, and the sensitivity (resolution for detecting LOH. We report that variances of SNP heterozygosity rate in dbSNP are high for a large proportion of SNPs. Two statistical methods proposed for directly inferring SNP heterozygosity rates require much smaller sample sizes (intermediate sizes and are feasible for practical use in SNP selection or verification. Using HapMap data, we showed that a region of LOH greater than 200 kb can be reliably detected, with losses smaller than 50 kb having a substantially lower detection probability when using all SNPs currently in the HapMap database. Higher densities of SNPs may exist in certain local chromosomal regions that provide some opportunities for reliably detecting LOH of segment sizes smaller than 50 kb. These results suggest that the interpretation of the results from genome-wide scans for LOH using commercial arrays need to consider the relationships among inter-SNP distance, detection probability, and sample size for a specific study. New experimental designs for LOH studies would also benefit from considering the power of detection and sample sizes required to accomplish the proposed aims.

43 CFR 43.640 - Employee.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Employee. 43.640 Section 43.640 Public... WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 43.640 Employee. (a) Employee means the employee of a... employees; (2) All indirect charge employees, unless their impact or involvement in the performance of work...

Leveraging ethnic group incidence variation to investigate genetic susceptibility to glioma: A novel candidate SNP approach

Directory of Open Access Journals (Sweden)

Daniel Ian Jacobs

2012-10-01

Full Text Available Objectives: Using a novel candidate SNP approach, we aimed to identify a possible genetic basis for the higher glioma incidence in Whites relative to East Asians and African-Americans. Methods: We hypothesized that genetic regions containing SNPs with extreme differences in allele frequencies across ethnicities are most likely to harbor susceptibility variants. We used International HapMap Project data to identify 3,961 candidate SNPs with the largest allele frequency differences in Whites compared to East Asians and Africans and tested these SNPs for association with glioma risk in a set of White cases and controls. Top SNPs identified in the discovery dataset were tested for association with glioma in five independent replication datasets. Results: No SNP achieved statistical significance in either the discovery or replication datasets after accounting for multiple testing. However, the most strongly associated SNP, rs879471, was found to be in linkage disequilibrium with a previously identified risk SNP, rs6010620, in RTEL1. We estimate rs6010620 to account for a glioma incidence rate ratio of 1.34 for Whites relative to East Asians. Conclusions: We explored genetic susceptibility to glioma using a novel candidate SNP method which may be applicable to other diseases with appropriate epidemiologic patterns.

GenHtr: a tool for comparative assessment of genetic heterogeneity in microbial genomes generated by massive short-read sequencing

Directory of Open Access Journals (Sweden)

Yu GongXin

2010-10-01

-consuming when compared to Maq, a popular tool for SNP analysis, GenHtr is able to predict potential multiple variants that pre-exist in the bacterial population as well as SNPs that occur in the highly duplicated gene families. It is expected that, with the proper experimental design, this analysis can improve our understanding of the molecular mechanism underlying the dynamics and the evolution of drug-resistant bacterial pathogens.

26 CFR 1.43-4 - Qualified enhanced oil recovery costs.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 1 2010-04-01 2010-04-01 true Qualified enhanced oil recovery costs. 1.43-4... TAXES Credits Against Tax § 1.43-4 Qualified enhanced oil recovery costs. (a) Qualifying costs—(1) In... “qualified enhanced oil recovery costs” if the amounts are paid or incurred with respect to an asset which is...

An updated meta-analysis on the association of MDM2 SNP309 polymorphism with colorectal cancer risk.

Directory of Open Access Journals (Sweden)

Xue Qin

Full Text Available The mouse double minute 2 (MDM2 gene encodes a phosphoprotein that interacts with P53 and negatively regulates its activity. The SNP309 polymorphism (T-G in the promoter of MDM2 gene has been reported to be associated with enhanced MDM2 expression and tumor development. Studies investigating the association between MDM2 SNP309 polymorphism and colorectal cancer (CRC risk reported conflicting results. We performed a meta-analysis of all available studies to explore the association of this polymorphism with CRC risk.All studies published up to July 2013 on the association between MDM2 SNP309 polymorphism and CRC risk were identified by searching electronic databases PubMed, EMBASE, and Chinese Biomedical Literature database (CBM databases. The association between the MDM2 SNP309 polymorphism and CRC risk was assessed by odds ratios (ORs together with their 95% confidence intervals (CIs.A total of 14 case-control studies including 4460 CRC cases and 4828 controls were identified. We did not find a significant association between the MDM2 SNP309 polymorphism and CRC risk in all genetic models in overall population. However, in subgroup analysis by ethnicity, significant associations were found in Asians (TG vs. TT: OR = 1.197, 95% CI = 1.055-1.358, P=0.005; GG+TG vs. TT: OR = 1.246, 95% CI = 1.106-1.404, P=0.000 and Africans. When stratified by HWE in controls, significantly increased risk was also found among the studies consistent with HWE (TG vs. TT: OR = 1.166, 95% CI = 1.037-1.311, P= 0.010. In subgroup analysis according to p53 mutation status, and gender, no any significant association was detected.The present meta-analysis suggests that the MDM2 is a candidate gene for CRC susceptibility. The MDM2 SNP309 polymorphism may be a risk factor for CRC in Asians.

Spin orientations of the spin-half Ir(4+) ions in Sr3NiIrO6, Sr2IrO4, and Na2IrO3: Density functional, perturbation theory, and Madelung potential analyses.

Science.gov (United States)

Gordon, Elijah E; Xiang, Hongjun; Köhler, Jürgen; Whangbo, Myung-Hwan

2016-03-21

The spins of the low-spin Ir(4+) (S = 1/2, d(5)) ions at the octahedral sites of the oxides Sr3NiIrO6, Sr2IrO4, and Na2IrO3 exhibit preferred orientations with respect to their IrO6 octahedra. We evaluated the magnetic anisotropies of these S = 1/2 ions on the basis of density functional theory (DFT) calculations including spin-orbit coupling (SOC), and probed their origin by performing perturbation theory analyses with SOC as perturbation within the LS coupling scheme. The observed spin orientations of Sr3NiIrO6 and Sr2IrO4 are correctly predicted by DFT calculations, and are accounted for by the perturbation theory analysis. As for the spin orientation of Na2IrO3, both experimental studies and DFT calculations have not been unequivocal. Our analysis reveals that the Ir(4+) spin orientation of Na2IrO3 should have nonzero components along the c- and a-axis directions. The spin orientations determined by DFT calculations are sensitive to the accuracy of the crystal structures employed, which is explained by perturbation theory analyses when interactions between adjacent Ir(4+) ions are taken into consideration. There are indications implying that the 5d electrons of Na2IrO3 are less strongly localized compared with those of Sr3NiIrO6 and Sr2IrO4. This implication was confirmed by showing that the Madelung potentials of the Ir(4+) ions are less negative in Na2IrO3 than in Sr3NiIrO6 and Sr2IrO4. Most transition-metal S = 1/2 ions do have magnetic anisotropies because the SOC induces interactions among their crystal-field split d-states, and the associated mixing of the states modifies only the orbital parts of the states. This finding cannot be mimicked by a spin Hamiltonian because this model Hamiltonian lacks the orbital degree of freedom, thereby leading to the spin-half syndrome. The spin-orbital entanglement for the 5d spin-half ions Ir(4+) is not as strong as has been assumed.

LS-SNP/PDB: annotated non-synonymous SNPs mapped to Protein Data Bank structures.

Science.gov (United States)

Ryan, Michael; Diekhans, Mark; Lien, Stephanie; Liu, Yun; Karchin, Rachel

2009-06-01

LS-SNP/PDB is a new WWW resource for genome-wide annotation of human non-synonymous (amino acid changing) SNPs. It serves high-quality protein graphics rendered with UCSF Chimera molecular visualization software. The system is kept up-to-date by an automated, high-throughput build pipeline that systematically maps human nsSNPs onto Protein Data Bank structures and annotates several biologically relevant features. LS-SNP/PDB is available at (http://ls-snp.icm.jhu.edu/ls-snp-pdb) and via links from protein data bank (PDB) biology and chemistry tabs, UCSC Genome Browser Gene Details and SNP Details pages and PharmGKB Gene Variants Downloads/Cross-References pages.

V{sub 1+x}Nb{sub 1-x}IrB{sub 2} (x ∼ 0.1), the first quaternary metal-rich -boride adopting the Mo{sub 2}IrB{sub 2}-type structure: Synthesis, crystal and electronic structure and bonding analysis

Energy Technology Data Exchange (ETDEWEB)

Goerens, Christian; Fokwa, Boniface P.T. [Institute of Inorganic Chemistry, RWTH Aachen University (Germany)

2013-02-15

Polycrystalline samples and single crystals of the new metal-rich boride V{sub 1+x}Nb{sub 1-x}IrB{sub 2} (x ∼ 0.1), were synthesized by arc-melting the elements in a water-cooled copper crucible under an argon atmosphere and characterized by X-ray diffraction and EDX measurements. The crystal structure was refined on the basis of single crystal data. The new phase adopts the Mo{sub 2}IrB{sub 2}-type structure (space group Pnnm, no. 58) with the lattice parameters a = 7.301(7) Aa, b = 9.388(9) Aa and c = 3.206(5) Aa. It is the first quaternary representative of Mo{sub 2}IrB{sub 2}-type structure. The structure contains zigzag B{sub 4}-fragments with boron-boron distances of 1.83-1.85 Aa. The electronic density of states and crystal orbital Hamilton population (for bonding analysis) were calculated, using the linear muffin-tin orbital atomic sphere approximation (LMTO-ASA) method. According to these calculations, this metal-rich compound should be metallic, as expected. Furthermore, very strong boron-boron interactions are observed in the zigzag B{sub 4}-fragment and two significantly different Ir-B interactions are observed in the new phase and the prototype Mo{sub 2}IrB{sub 2}. (Copyright copyright 2013 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

43 CFR 43.665 - State.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false State. 43.665 Section 43.665 Public Lands... (FINANCIAL ASSISTANCE) Definitions § 43.665 State. State means any of the States of the United States, the District of Columbia, the Commonwealth of Puerto Rico, or any territory or possession of the United States. ...

Revision of Corallinaceae (Corallinales, Rhodophyta): recognizing Dawsoniolithon gen. nov., Parvicellularium gen. nov. and Chamberlainoideae subfam. nov. containing Chamberlainium gen. nov. and Pneophyllum.

Science.gov (United States)

Caragnano, Annalisa; Foetisch, Alexandra; Maneveldt, Gavin W; Millet, Laurent; Liu, Li-Chia; Lin, Showe-Mei; Rodondi, Graziella; Payri, Claude E

2018-03-25

A multi-gene (SSU, LSU, psbA and COI) molecular phylogeny of the family Corallinaceae (excluding the subfamilies Lithophylloideae and Corallinoideae) showed a paraphyletic grouping of six monophyletic clades. Pneophyllum and Spongites were reassessed and recircumscribed using DNA sequence data integrated with morpho-anatomical comparisons of type material and recently collected specimens. We propose Chamberlainoideae subfam. nov., including the type genus Chamberlainium gen. nov., with C. tumidum comb. nov. as the generitype, and Pneophyllum. Chamberlainium is established to include several taxa previously ascribed to Spongites, the generitype of which currently resides in Neogoniolithoideae. Additionally we propose two new genera, Dawsoniolithon gen. nov. (Metagoniolithoideae), with D. conicum comb. nov. as the generitype and Parvicellularium gen. nov. (subfamily incertae sedis), with P. leonardi sp. nov. as the generitype. Chamberlainoideae has no diagnostic morpho-anatomical features that enable one to assign specimens to it without DNA sequence data, and it is the first subfamily to possess both Type 1 (Chamberlainium) and Type 2 (Pneophyllum) tetra/bisporangial conceptacle roof development. Two characters distinguish Chamberlainium from Spongites: tetra/biasporangial conceptacle chamber diameter (300 μm in Spongites) and tetra/bisporangial conceptacle roof thickness (8 cells in Spongites). Two characters also distinguish Pneophyllum from Dawsoniolithon: tetra/bisporangial conceptacle roof thickness (8 cells in Dawsoniolithon) and thallus construction (dimerous in Pneophyllum vs. monomerous in Dawsoniolithon). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Bovine exome sequence analysis and targeted SNP genotyping of recessive fertility defects BH1, HH2, and HH3 reveal a putative causative mutation in SMC2 for HH3.

Science.gov (United States)

McClure, Matthew C; Bickhart, Derek; Null, Dan; Vanraden, Paul; Xu, Lingyang; Wiggans, George; Liu, George; Schroeder, Steve; Glasscock, Jarret; Armstrong, Jon; Cole, John B; Van Tassell, Curtis P; Sonstegard, Tad S

2014-01-01

The recent discovery of bovine haplotypes with negative effects on fertility in the Brown Swiss, Holstein, and Jersey breeds has allowed producers to identify carrier animals using commercial single nucleotide polymorphism (SNP) genotyping assays. This study was devised to identify the causative mutations underlying defective bovine embryo development contained within three of these haplotypes (Brown Swiss haplotype 1 and Holstein haplotypes 2 and 3) by combining exome capture with next generation sequencing. Of the 68,476,640 sequence variations (SV) identified, only 1,311 genome-wide SNP were concordant with the haplotype status of 21 sequenced carriers. Validation genotyping of 36 candidate SNP identified only 1 variant that was concordant to Holstein haplotype 3 (HH3), while no variants located within the refined intervals for HH2 or BH1 were concordant. The variant strictly associated with HH3 is a non-synonymous SNP (T/C) within exon 24 of the Structural Maintenance of Chromosomes 2 (SMC2) on Chromosome 8 at position 95,410,507 (UMD3.1). This polymorphism changes amino acid 1135 from phenylalanine to serine and causes a non-neutral, non-tolerated, and evolutionarily unlikely substitution within the NTPase domain of the encoded protein. Because only exome capture sequencing was used, we could not rule out the possibility that the true causative mutation for HH3 might lie in a non-exonic genomic location. Given the essential role of SMC2 in DNA repair, chromosome condensation and segregation during cell division, our findings strongly support the non-synonymous SNP (T/C) in SMC2 as the likely causative mutation. The absence of concordant variations for HH2 or BH1 suggests either the underlying causative mutations lie within a non-exomic region or in exome regions not covered by the capture array.

Bovine exome sequence analysis and targeted SNP genotyping of recessive fertility defects BH1, HH2, and HH3 reveal a putative causative mutation in SMC2 for HH3.

Directory of Open Access Journals (Sweden)

Matthew C McClure

Full Text Available The recent discovery of bovine haplotypes with negative effects on fertility in the Brown Swiss, Holstein, and Jersey breeds has allowed producers to identify carrier animals using commercial single nucleotide polymorphism (SNP genotyping assays. This study was devised to identify the causative mutations underlying defective bovine embryo development contained within three of these haplotypes (Brown Swiss haplotype 1 and Holstein haplotypes 2 and 3 by combining exome capture with next generation sequencing. Of the 68,476,640 sequence variations (SV identified, only 1,311 genome-wide SNP were concordant with the haplotype status of 21 sequenced carriers. Validation genotyping of 36 candidate SNP identified only 1 variant that was concordant to Holstein haplotype 3 (HH3, while no variants located within the refined intervals for HH2 or BH1 were concordant. The variant strictly associated with HH3 is a non-synonymous SNP (T/C within exon 24 of the Structural Maintenance of Chromosomes 2 (SMC2 on Chromosome 8 at position 95,410,507 (UMD3.1. This polymorphism changes amino acid 1135 from phenylalanine to serine and causes a non-neutral, non-tolerated, and evolutionarily unlikely substitution within the NTPase domain of the encoded protein. Because only exome capture sequencing was used, we could not rule out the possibility that the true causative mutation for HH3 might lie in a non-exonic genomic location. Given the essential role of SMC2 in DNA repair, chromosome condensation and segregation during cell division, our findings strongly support the non-synonymous SNP (T/C in SMC2 as the likely causative mutation. The absence of concordant variations for HH2 or BH1 suggests either the underlying causative mutations lie within a non-exomic region or in exome regions not covered by the capture array.

IR and visible luminescence studies in the infrared multiphoton dissociation of 1,2-dibromo-1,1-difluoroethane

Science.gov (United States)

Pushpa, K. K.; Kumar, Awadhesh; Vatsa, R. K.; Naik, P. D.; Annaji Rao, K.; Mittal, J. P.; Parthasarathy, V.; Sarkar, S. K.

1995-07-01

The infrared multiphoton dissociation of 1,2-dibromo-1,1-difluoroethane gives rise to IR and visible luminescence. Vibrationally excited parent molecules dissociate via two primary channels yielding bromine and vibrationally excited HBr. The strong visible emission observed between 350 to 750 nm has been assigned to electronically excited carbene CF 2Br CH.

FutureGen Project Report

Energy Technology Data Exchange (ETDEWEB)

Cabe, Jim; Elliott, Mike

2010-09-30

This report summarizes the comprehensive siting, permitting, engineering, design, and costing activities completed by the FutureGen Industrial Alliance, the Department of Energy, and associated supporting subcontractors to develop a first of a kind near zero emissions integrated gasification combined cycle power plant and carbon capture and storage project (IGCC-CCS). With the goal to design, build, and reliably operate the first IGCC-CCS facility, FutureGen would have been the lowest emitting pulverized coal power plant in the world, while providing a timely and relevant basis for coal combustion power plants deploying carbon capture in the future. The content of this report summarizes key findings and results of applicable project evaluations; modeling, design, and engineering assessments; cost estimate reports; and schedule and risk mitigation from initiation of the FutureGen project through final flow sheet analyses including capital and operating reports completed under DOE award DE-FE0000587. This project report necessarily builds upon previously completed siting, design, and development work executed under DOE award DE-FC26- 06NT4207 which included the siting process; environmental permitting, compliance, and mitigation under the National Environmental Policy Act; and development of conceptual and design basis documentation for the FutureGen plant. For completeness, the report includes as attachments the siting and design basis documents, as well as the source documentation for the following: • Site evaluation and selection process and environmental characterization • Underground Injection Control (UIC) Permit Application including well design and subsurface modeling • FutureGen IGCC-CCS Design Basis Document • Process evaluations and technology selection via Illinois Clean Coal Review Board Technical Report • Process flow diagrams and heat/material balance for slurry-fed gasifier configuration • Process flow diagrams and heat/material balance

The GenABEL Project for statistical genomics [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Lennart C. Karssen

2016-05-01

Full Text Available Development of free/libre open source software is usually done by a community of people with an interest in the tool. For scientific software, however, this is less often the case. Most scientific software is written by only a few authors, often a student working on a thesis. Once the paper describing the tool has been published, the tool is no longer developed further and is left to its own device. Here we describe the broad, multidisciplinary community we formed around a set of tools for statistical genomics. The GenABEL project for statistical omics actively promotes open interdisciplinary development of statistical methodology and its implementation in efficient and user-friendly software under an open source licence. The software tools developed withing the project collectively make up the GenABEL suite, which currently consists of eleven tools. The open framework of the project actively encourages involvement of the community in all stages, from formulation of methodological ideas to application of software to specific data sets. A web forum is used to channel user questions and discussions, further promoting the use of the GenABEL suite. Developer discussions take place on a dedicated mailing list, and development is further supported by robust development practices including use of public version control, code review and continuous integration. Use of this open science model attracts contributions from users and developers outside the “core team”, facilitating agile statistical omics methodology development and fast dissemination.

SNP8NRG433E1006 NEUREGULIN-1 GENETIC VARIATION IN BATAKS ETHNIC WITH SCHIZOPHRENIA PARANOID AND HEALTHY CONTROL

Directory of Open Access Journals (Sweden)

Elmeida Effendy

2014-05-01

Full Text Available The neuregulin 1 (NRG1 gene which influences the development of white matter connectivity has been associated with schizophrenia. It influences neuronal migration, synaptogenesis, gliogenesis, neuron-glia communication, myelination, and neurotransmission in the brain and others. NRG1 is located in 8p13, and it is frequently replicated in schizphrenia. SNP8NRG433E1006 gene NRG1 is one of core at risk haplotype of schizphrenia. This study looked forward differences SNP8NRG433E1006 neuregulin 1 between Bataks ethnic with schizophrenia paranoid and Bataks ethnic healthy control. Methods: Batak ethnic with schizophrenia paranoid were recruited and interviewed with semi-structured MINI ICD-X to establish the diagnosis. All the eligible subjects were requested their permission for blood sampling. Healthy Batak ethnic were also recruited by mathcing the age and gender. The blood samples went through DNA isolation, Nested PCR, and DNA sequencing. Results: Ninety three subjects were recruited, but only 74 blood samples were succesfully sequenced. We found three types of polymorphisms, i.e. G/A allele at base pair (bp 76, G/T allele at bp 112, and deletion at bp 110 in Batak ethnic with schizophrenia. There were two kind sequences at bp 113-116 in Batak ethnics, and Batak ethnics with ATCG were at higher risk for having schizophrenia. This study support that NRG1 is a schizophrenia-susceptibility gene.

Mesoporous silica nanoparticle supported PdIr bimetal catalyst for selective hydrogenation, and the significant promotional effect of Ir

Energy Technology Data Exchange (ETDEWEB)

Yang, Hui; Huang, Chao; Yang, Fan [The Key Laboratory of Fuel Cell Technology of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510641 (China); Yang, Xu [Key Laboratory of Renewable Energy, Guangzhou Institute of Energy Conversion, Chinese Academy of Sciences, Guangzhou (China); Du, Li [The Key Laboratory of Fuel Cell Technology of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510641 (China); Key Laboratory of Renewable Energy, Guangzhou Institute of Energy Conversion, Chinese Academy of Sciences, Guangzhou (China); Liao, Shijun, E-mail: chsjliao@scut.edu.cn [The Key Laboratory of Fuel Cell Technology of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510641 (China); Key Laboratory of Renewable Energy, Guangzhou Institute of Energy Conversion, Chinese Academy of Sciences, Guangzhou (China)

2015-12-01

Graphical abstract: A mesoporous silica nanoparticle (MSN) supported bimetal catalyst, PdIr/MSN, was prepared by a facile impregnation and hydrogen reduction method. The strong promotional effect of Ir was observed and thoroughly investigated. At the optimal molar ratio of Ir to Pd (N{sub Ir}/N{sub Pd} = 0.1), the activity of PdIr{sub 0.1}/MSN was up to eight times and 28 times higher than that of monometallic Pd/MSN and Ir/MSN, respectively. The catalysts were characterized comprehensively by X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy, and hydrogen temperature programmed reduction, which revealed that the promotional effect of Ir may be due to the enhanced dispersion of active components on the MSN, and to the intensified Pd–Ir electronic interaction caused by the addition of Ir. - Highlights: • Mesoporous nanoparticles were synthesized and used as support for metal catalyst. • PdIr bimetallic catalyst exhibited significantly improved hydrogenation activity. • The strong promotion of Ir was recognized firstly and investigated intensively. • PdIr exhibits 18 times higher activity than Pd to the hydrogenation of nitrobenzene. - Abstract: A mesoporous silica nanoparticle (MSN) supported bimetal catalyst, PdIr/MSN, was prepared by a facile impregnation and hydrogen reduction method. The strong promotional effect of Ir was observed and thoroughly investigated. At the optimal molar ratio of Ir to Pd (N{sub Ir}/N{sub Pd} = 0.1), the activity of PdIr{sub 0.1}/MSN was up to eight times and 28 times higher than that of monometallic Pd/MSN and Ir/MSN, respectively. The catalysts were characterized comprehensively by X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy, and hydrogen temperature programmed reduction, which revealed that the promotional effect of Ir may be due to the enhanced dispersion of active components on the MSN, and to the intensified Pd–Ir electronic interaction

Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia

DEFF Research Database (Denmark)

Rung, Johan; Cauchi, Stéphane; Albrechtsen, Anders

2009-01-01

sample of 4,977 French individuals. We then selected the 28 best hits for replication in 7,698 Danish subjects and identified 4 SNPs showing strong association with T2D, one of which (rs2943641, P = 9.3 x 10(-12), OR = 1.19) was located adjacent to the insulin receptor substrate 1 gene (IRS1). Unlike...... previously reported T2D risk loci, which predominantly associate with impaired beta cell function, the C allele of rs2943641 was associated with insulin resistance and hyperinsulinemia in 14,358 French, Danish and Finnish participants from population-based cohorts; this allele was also associated...... with reduced basal levels of IRS1 protein and decreased insulin induction of IRS1-associated phosphatidylinositol-3-OH kinase activity in human skeletal muscle biopsies....

From AWE-GEN to AWE-GEN-2d: a high spatial and temporal resolution weather generator

Science.gov (United States)

Peleg, Nadav; Fatichi, Simone; Paschalis, Athanasios; Molnar, Peter; Burlando, Paolo

2016-04-01

A new weather generator, AWE-GEN-2d (Advanced WEather GENerator for 2-Dimension grid) is developed following the philosophy of combining physical and stochastic approaches to simulate meteorological variables at high spatial and temporal resolution (e.g. 2 km x 2 km and 5 min for precipitation and cloud cover and 100 m x 100 m and 1 h for other variables variable (temperature, solar radiation, vapor pressure, atmospheric pressure and near-surface wind). The model is suitable to investigate the impacts of climate variability, temporal and spatial resolutions of forcing on hydrological, ecological, agricultural and geomorphological impacts studies. Using appropriate parameterization the model can be used in the context of climate change. Here we present the model technical structure of AWE-GEN-2d, which is a substantial evolution of four preceding models (i) the hourly-point scale Advanced WEather GENerator (AWE-GEN) presented by Fatichi et al. (2011, Adv. Water Resour.) (ii) the Space-Time Realizations of Areal Precipitation (STREAP) model introduced by Paschalis et al. (2013, Water Resour. Res.), (iii) the High-Resolution Synoptically conditioned Weather Generator developed by Peleg and Morin (2014, Water Resour. Res.), and (iv) the Wind-field Interpolation by Non Divergent Schemes presented by Burlando et al. (2007, Boundary-Layer Meteorol.). The AWE-GEN-2d is relatively parsimonious in terms of computational demand and allows generating many stochastic realizations of current and projected climates in an efficient way. An example of model application and testing is presented with reference to a case study in the Wallis region, a complex orography terrain in the Swiss Alps.

Effect of Myostatin SNP on muscle fiber properties in male Thoroughbred horses during training period.

Science.gov (United States)

Miyata, Hirofumi; Itoh, Rika; Sato, Fumio; Takebe, Naoya; Hada, Tetsuro; Tozaki, Teruaki

2017-10-20

Variants of the Myostatin gene have been shown to have an influence on muscle hypertrophy phenotypes in a wide range of mammalian species. Recently, a Thoroughbred horse with a C-Allele at the g.66493737C/T single-nucleotide polymorphism (SNP) has been reported to be suited to short-distance racing. In this study, we examined the effect of the Myostatin SNP on muscle fiber properties in young Thoroughbred horses during a training period. To investigate the effect of the Myostatin SNP on muscle fiber before training, several mRNA expressions were relatively quantified in biopsy samples from the middle gluteal muscle of 27 untrained male Thoroughbred horses (1.5 years old) using real-time RT-PCR analysis. The remaining muscle samples were used for immunohistochemical analysis to determine the population and area of each fiber type. All measurements were revaluated in biopsy samples of the same horses after a 5-month period of conventional training. Although the expressions of Myostatin mRNA decreased in all SNP genotypes, a significant decrease was found in only the C/C genotype after training. While, expression of VEGFa, PGC1α, and SDHa mRNAs, which relate to the biogenesis of mitochondria and capillaries, was significantly higher (54-82%) in the T/T than the C/C genotypes after training. It is suggested that hypertrophy of muscle fiber is directly associated with a decrease in Myostatin mRNA expression in the C/C genotype, and that increased expressions of VEGFa, PGC1α, and SDHa in the T/T genotype might be indirectly caused by the Myostatin SNP.

Gen IV Materials Handbook Implementation Plan

International Nuclear Information System (INIS)

Rittenhouse, P.; Ren, W.

2005-01-01

A Gen IV Materials Handbook is being developed to provide an authoritative single source of highly qualified structural materials information and materials properties data for use in design and analyses of all Generation IV Reactor Systems. The Handbook will be responsive to the needs expressed by all of the principal government, national laboratory, and private company stakeholders of Gen IV Reactor Systems. The Gen IV Materials Handbook Implementation Plan provided here addresses the purpose, rationale, attributes, and benefits of the Handbook and will detail its content, format, quality assurance, applicability, and access. Structural materials, both metallic and ceramic, for all Gen IV reactor types currently supported by the Department of Energy (DOE) will be included in the Gen IV Materials Handbook. However, initial emphasis will be on materials for the Very High Temperature Reactor (VHTR). Descriptive information (e.g., chemical composition and applicable technical specifications and codes) will be provided for each material along with an extensive presentation of mechanical and physical property data including consideration of temperature, irradiation, environment, etc. effects on properties. Access to the Gen IV Materials Handbook will be internet-based with appropriate levels of control. Information and data in the Handbook will be configured to allow search by material classes, specific materials, specific information or property class, specific property, data parameters, and individual data points identified with materials parameters, test conditions, and data source. Details on all of these as well as proposed applicability and consideration of data quality classes are provided in the Implementation Plan. Website development for the Handbook is divided into six phases including (1) detailed product analysis and specification, (2) simulation and design, (3) implementation and testing, (4) product release, (5) project/product evaluation, and (6) product

p.Q192R SNP of PON1 seems not to be Associated with Carotid Atherosclerosis Risk Factors in an Asymptomatic and Normolipidemic Brazilian Population Sample

Science.gov (United States)

Scherrer, Daniel Zanetti; Zago, Vanessa Helena de Souza; Vieira, Isabela Calanca; Parra, Eliane Soler; Panzoldo, Natália Baratella; Alexandre, Fernanda; Secolin, Rodrigo; Baracat, Jamal; Quintão, Eder Carlos Rocha; de Faria, Eliana Cotta

2015-01-01

Background Evidences suggest that paraoxonase 1 (PON1) confers important antioxidant and anti-inflammatory properties when associated with high-density lipoprotein (HDL). Objective To investigate the relationships between p.Q192R SNP of PON1, biochemical parameters and carotid atherosclerosis in an asymptomatic, normolipidemic Brazilian population sample. Methods We studied 584 volunteers (females n = 326, males n = 258; 19-75 years of age). Total genomic DNA was extracted and SNP was detected in the TaqMan® SNP OpenArray® genotyping platform (Applied Biosystems, Foster City, CA). Plasma lipoproteins and apolipoproteins were determined and PON1 activity was measured using paraoxon as a substrate. High-resolution β-mode ultrasonography was used to measure cIMT and the presence of carotid atherosclerotic plaques in a subgroup of individuals (n = 317). Results The presence of p.192Q was associated with a significant increase in PON1 activity (RR = 12.30 (11.38); RQ = 46.96 (22.35); QQ = 85.35 (24.83) μmol/min; p < 0.0001), HDL-C (RR= 45 (37); RQ = 62 (39); QQ = 69 (29) mg/dL; p < 0.001) and apo A-I (RR = 140.76 ± 36.39; RQ = 147.62 ± 36.92; QQ = 147.49 ± 36.65 mg/dL; p = 0.019). Stepwise regression analysis revealed that heterozygous and p.192Q carriers influenced by 58% PON1 activity towards paraoxon. The univariate linear regression analysis demonstrated that p.Q192R SNP was not associated with mean cIMT; as a result, in the multiple regression analysis, no variables were selected with 5% significance. In logistic regression analysis, the studied parameters were not associated with the presence of carotid plaques. Conclusion In low-risk individuals, the presence of the p.192Q variant of PON1 is associated with a beneficial plasma lipid profile but not with carotid atherosclerosis. PMID:26039660

Density functional study of the L10-αIrV transition in IrV and RhV

International Nuclear Information System (INIS)

Mehl, Michael J.; Hart, Gus L.W.; Curtarolo, Stefano

2011-01-01

Research highlights: → The computational determination of the ground state of a material can be a difficult task, particularly if the ground state is uncommon and so not found in usual databases. In this paper we consider the alpha-IrV structure, a low temperature structure found only in two compounds, IrV and RhV. In both cases this structure can be considered as a distorted tetragonal structure, and the tetragonal 'L1 0 ' structure is the high temperature structure for both compounds. We show, however, that the logical path for the transition from the L1 0 to the alpha-IrV structure is energetically forbidden, and find a series of unstable and metastable structures which have a lower energy than the L1 0 phase, but are higher in energy than the alpha-IrV phase. We also consider the possibility of the alpha-IrV structure appearing in neighboring compounds. We find that both IrTi and RhTi are candidates. - Abstract: Both IrV and RhV crystallize in the αIrV structure, with a transition to the higher symmetry L1 0 structure at high temperature, or with the addition of excess Ir or Rh. Here we present evidence that this transition is driven by the lowering of the electronic density of states at the Fermi level of the αIrV structure. The transition has long been thought to be second order, with a simple doubling of the L1 0 unit cell due to an unstable phonon at the R point (0 1/2 1/2). We use first-principles calculations to show that all phonons at the R point are, in fact, stable, but do find a region of reciprocal space where the L1 0 structure has unstable (imaginary frequency) phonons. We use the frozen phonon method to examine two of these modes, relaxing the structures associated with the unstable phonon modes to obtain new structures which are lower in energy than L1 0 but still above αIrV. We examine the phonon spectra of these structures as well, looking for instabilities, and find further instabilities, and more relaxed structures, all of which have

snpTree - a web-server to identify and construct SNP trees from whole genome sequence data

DEFF Research Database (Denmark)

Leekitcharoenphon, Pimlapas; Kaas, Rolf Sommer; Thomsen, Martin Christen Frølund

2012-01-01

identify SNPs and construct phylogenetic trees from WGS as well as from assembled genomes or contigs. WGS data in fastq format are aligned to reference genomes by BWA while contigs in fasta format are processed by Nucmer. SNPs are concatenated based on position on reference genome and a tree is constructed...... to differentiate and classify isolates. One of the successfully and broadly used methods is analysis of single nucletide polymorphisms (SNPs). Currently, there are different tools and methods to identify SNPs including various options and cut-off values. Furthermore, all current methods require bioinformatic...... skills. Thus, we lack a standard and simple automatic tool to determine SNPs and construct phylogenetic tree from WGS data. Results Here we introduce snpTree, a server for online-automatic SNPs analysis. This tool is composed of different SNPs analysis suites, perl and python scripts. snpTree can...

Genome-Wide Association Study for Identification and Validation of Novel SNP Markers for Sr6 Stem Rust Resistance Gene in Bread Wheat.

Science.gov (United States)

Mourad, Amira M I; Sallam, Ahmed; Belamkar, Vikas; Wegulo, Stephen; Bowden, Robert; Jin, Yue; Mahdy, Ezzat; Bakheit, Bahy; El-Wafaa, Atif A; Poland, Jesse; Baenziger, Peter S

2018-01-01

Stem rust (caused by Puccinia graminis f. sp. tritici Erikss. & E. Henn.), is a major disease in wheat ( Triticum aestivium L.). However, in recent years it occurs rarely in Nebraska due to weather and the effective selection and gene pyramiding of resistance genes. To understand the genetic basis of stem rust resistance in Nebraska winter wheat, we applied genome-wide association study (GWAS) on a set of 270 winter wheat genotypes (A-set). Genotyping was carried out using genotyping-by-sequencing and ∼35,000 high-quality SNPs were identified. The tested genotypes were evaluated for their resistance to the common stem rust race in Nebraska (QFCSC) in two replications. Marker-trait association identified 32 SNP markers, which were significantly (Bonferroni corrected P < 0.05) associated with the resistance on chromosome 2D. The chromosomal location of the significant SNPs (chromosome 2D) matched the location of Sr6 gene which was expected in these genotypes based on pedigree information. A highly significant linkage disequilibrium (LD, r 2 ) was found between the significant SNPs and the specific SSR marker for the Sr6 gene ( Xcfd43 ). This suggests the significant SNP markers are tagging Sr6 gene. Out of the 32 significant SNPs, eight SNPs were in six genes that are annotated as being linked to disease resistance in the IWGSC RefSeq v1.0. The 32 significant SNP markers were located in nine haplotype blocks. All the 32 significant SNPs were validated in a set of 60 different genotypes (V-set) using single marker analysis. SNP markers identified in this study can be used in marker-assisted selection, genomic selection, and to develop KASP (Kompetitive Allele Specific PCR) marker for the Sr6 gene. Novel SNPs for Sr6 gene, an important stem rust resistant gene, were identified and validated in this study. These SNPs can be used to improve stem rust resistance in wheat.

OTG-snpcaller: an optimized pipeline based on TMAP and GATK for SNP calling from ion torrent data.

Directory of Open Access Journals (Sweden)

Pengyuan Zhu

Full Text Available Because the new Proton platform from Life Technologies produced markedly different data from those of the Illumina platform, the conventional Illumina data analysis pipeline could not be used directly. We developed an optimized SNP calling method using TMAP and GATK (OTG-snpcaller. This method combined our own optimized processes, Remove Duplicates According to AS Tag (RDAST and Alignment Optimize Structure (AOS, together with TMAP and GATK, to call SNPs from Proton data. We sequenced four sets of exomes captured by Agilent SureSelect and NimbleGen SeqCap EZ Kit, using Life Technology's Ion Proton sequencer. Then we applied OTG-snpcaller and compared our results with the results from Torrent Variants Caller. The results indicated that OTG-snpcaller can reduce both false positive and false negative rates. Moreover, we compared our results with Illumina results generated by GATK best practices, and we found that the results of these two platforms were comparable. The good performance in variant calling using GATK best practices can be primarily attributed to the high quality of the Illumina sequences.

OTG-snpcaller: an optimized pipeline based on TMAP and GATK for SNP calling from ion torrent data.

Science.gov (United States)

Zhu, Pengyuan; He, Lingyu; Li, Yaqiao; Huang, Wenpan; Xi, Feng; Lin, Lin; Zhi, Qihuan; Zhang, Wenwei; Tang, Y Tom; Geng, Chunyu; Lu, Zhiyuan; Xu, Xun

2014-01-01

Because the new Proton platform from Life Technologies produced markedly different data from those of the Illumina platform, the conventional Illumina data analysis pipeline could not be used directly. We developed an optimized SNP calling method using TMAP and GATK (OTG-snpcaller). This method combined our own optimized processes, Remove Duplicates According to AS Tag (RDAST) and Alignment Optimize Structure (AOS), together with TMAP and GATK, to call SNPs from Proton data. We sequenced four sets of exomes captured by Agilent SureSelect and NimbleGen SeqCap EZ Kit, using Life Technology's Ion Proton sequencer. Then we applied OTG-snpcaller and compared our results with the results from Torrent Variants Caller. The results indicated that OTG-snpcaller can reduce both false positive and false negative rates. Moreover, we compared our results with Illumina results generated by GATK best practices, and we found that the results of these two platforms were comparable. The good performance in variant calling using GATK best practices can be primarily attributed to the high quality of the Illumina sequences.

Insulin receptor substrates 1 and 2 but not Shc can activate the insulin receptor independent of insulin and induce proliferation in CHO-IR cells

International Nuclear Information System (INIS)

Niessen, Markus; Jaschinski, Frank; Item, Flurin; McNamara, Morgan P.; Spinas, Giatgen A.; Trueb, Thomas

2007-01-01

Ligand-activated insulin receptor (IR) attracts and phosphorylates various substrates such as insulin receptor substrates 1-4 (IRS) and Shc. To investigate how binding affinity for substrate affects signalling we generated chimeric receptors with the β-chain of the insulin receptor containing NPXY motives with different affinities for receptor substrates. We found that the extent of receptor tyrosine phosphorylation positively correlates with binding affinity towards IRS1/2 but not towards Shc. Moreover, overexpression of IRS1 or IRS2 but not of Shc increased IR tyrosine phosphorylation in a dose-dependent manner, also independent of insulin. Molecular truncations of IRS1 revealed that neither the isolated PH and PTB domains nor the C-terminus with the tyrosine phosphorylation sites alone are sufficient for substrate-dependent receptor activation. Overexpression of IRS1 and IRS2 impaired insulin-induced internalization of the IR in a dose-dependent manner suggesting that IRS proteins prevent endosome-associated receptor dephosphorylation/inactivation. IRS1 and IRS2 could therefore target the activated IR to different cellular compartments. Overexpression of IRS1 and IRS2 inhibited insulin-stimulated activation of the MAP kinases Erk1/2 while it increased/induced activation of Akt/PKB. Finally, overexpression of IRS1 and IRS2 but not of Shc induced DNA synthesis in starved CHO-IR cells independent of exogenous growth factors. Our results demonstrate that variations in cellular IRS1 and IRS2 concentration affect insulin signalling both upstream and downstream and that IRS proteins could play instructive rather than just permissive roles in signal transmission

A custom correlation coefficient (CCC) approach for fast identification of multi-SNP association patterns in genome-wide SNPs data.

Science.gov (United States)

Climer, Sharlee; Yang, Wei; de las Fuentes, Lisa; Dávila-Román, Victor G; Gu, C Charles

2014-11-01

Complex diseases are often associated with sets of multiple interacting genetic factors and possibly with unique sets of the genetic factors in different groups of individuals (genetic heterogeneity). We introduce a novel concept of custom correlation coefficient (CCC) between single nucleotide polymorphisms (SNPs) that address genetic heterogeneity by measuring subset correlations autonomously. It is used to develop a 3-step process to identify candidate multi-SNP patterns: (1) pairwise (SNP-SNP) correlations are computed using CCC; (2) clusters of so-correlated SNPs identified; and (3) frequencies of these clusters in disease cases and controls compared to identify disease-associated multi-SNP patterns. This method identified 42 candidate multi-SNP associations with hypertensive heart disease (HHD), among which one cluster of 22 SNPs (six genes) included 13 in SLC8A1 (aka NCX1, an essential component of cardiac excitation-contraction coupling) and another of 32 SNPs had 29 from a different segment of SLC8A1. While allele frequencies show little difference between cases and controls, the cluster of 22 associated alleles were found in 20% of controls but no cases and the other in 3% of controls but 20% of cases. These suggest that both protective and risk effects on HHD could be exerted by combinations of variants in different regions of SLC8A1, modified by variants from other genes. The results demonstrate that this new correlation metric identifies disease-associated multi-SNP patterns overlooked by commonly used correlation measures. Furthermore, computation time using CCC is a small fraction of that required by other methods, thereby enabling the analyses of large GWAS datasets. © 2014 WILEY PERIODICALS, INC.

Recommendations and Requirements for GenCade Simluations

Science.gov (United States)

2014-08-01

will report whether or not GenCade is enabled. If GenCade is disabled , the user will need a new license that includes GenCade...any depth but usually are not deeper than the seaward edge of the surf - zone. In the same way that some shorelines are less desirable for use in...Conference, 1919–1937. ASCE. Wang, P., N. C. Kraus, and R. A. Davis. 1998. Total rate of longshore sediment transport in the surf zone: Field

Comparación y utilidad de las regiones mitocondriales de los genes 16S y COX1 para los análisis genéticos en garrapatas (Acari: Ixodidae

Directory of Open Access Journals (Sweden)

Luis Enrique Paternina

2016-06-01

Conclusión. Los resultados indicaron que el gen 16S parece tener mejores características para los análisis filogenéticos interespecíficos dada su alta divergencia genética y baja saturación de transiciones, mientras que el gen COX1 parece ser más útil para estudios de variabilidad genética intraespecífica. Sin embargo, dado que el estudio se hizo a escala local, se requieren más investigaciones en diferentes escalas biogeográficas para establecer su utilidad en circunstancias más amplias y complejas.

Application of high resolution SNP arrays in patients with congenital ...

Indian Academy of Sciences (India)

TING-YING LEI

lent oligonucleotide-based array-CGH to determine the exact breakpoints in 14 patients with partial deletions of chromo- some 13q21.1-qter. They were able to refine the smallest deletion region linked to cleft lip/palate (13q31.3–13q33.1). Except for the arrays that measure DNA copy number differ- ences only, SNP arrays, ...

Análisis de la diversidad genética de una población de caballos Criollo Argentino mediante polimorfismos de nucleótido simple de los genes IL12B y TNF-α

Directory of Open Access Journals (Sweden)

Claudia Corbi Botto

2016-12-01

Full Text Available La caracterización de una población es el primer paso en el camino hacia su conservación y utilización. La raza Criollo Argentino es una de las referentes de la especie equina en Argentina y, por lo tanto, un patrimonio ganadero local que representa un recurso único en cuanto a la identidad y al sistema productivo del país. El objetivo de este trabajo fue analizar una población de caballos Criollo Argentino del norte de Argentina por medio de la caracterización de la variabilidad genética de cuatro marcadores moleculares del tipo single nucleotide polymorphism (SNP localizados en los genes que codifican para las citoquinas IL-12B y TNF-α. Se recolectaron muestras de 50 caballos Criollo Argentino y se extrajo ADN genómico que se utilizó para tipificar mediante PCR-Pirosecuenciación®, tres SNPs en el promotor del gen TNF-α y uno localizado en el exón 5 del gen IL-12B. Se estimaron frecuencias génicas y genotípicas, equilibrio de Hardy-Weinberg y diversidad genética. En IL-12B se detectaron dos alelos, mientras que en TNF-α se observaron 4 haplotipos, entre ellos uno no descripto hasta el momento en equinos. Los resultados muestran que la heterocigosis esperada fue superior en TNF-α (He=0,764 y la población se encuentra en equilibrio para el locus IL-12B (p-valor ≥0,05. Se destaca la importancia del caballo Criollo Argentino como acervo génico para el estudio de características genéticas y enfermedades de la especie equina.

Unleashing Gen Y: Marketing Mars to Millennials

Science.gov (United States)

Leahy, Bart D.; Hidalgo, Loretta; Kloberdanz, Cassie

2007-01-01

Space advocates need to engage Generation Y (born 1977-1999).This outreach is necessary to recruit the next generation of scientists and engineers to explore Mars. Space advocates in the non-profit, private, and government sectors need to use a combination of technical communication, marketing, and politics, to develop messages that resonate with Gen Y. Until now, space messages have been generated by and for college-educated white males; Gen Y is much more diverse, including as much as one third minorities. Young women, too, need to be reached. My research has shown that messages emphasizing technology, fun, humor, and opportunity are the best means of reaching the Gen Y audience of 60 million (US population is 300 million). The important things space advocates must avoid are talking down to this generation, making false promises, or expecting them to "wait their turn" before they can participate. This is the MTV generation! We need to find ways of engaging Gen Y now to build a future where human beings can live and work on the planet Mars. In addition to the messages themselves, advocates need to keep up with Gen Y' s social networking and use of iPods, cell phones, and the Internet. NASA and space advocacy groups can use these tools for "viral marketing," where young people share targeted space-related information via cell phones or the Internet because they like it. Overall, Gen Y is a socially dynamic and media-savvy group; advocates' space messages need to be sincere, creative, and placed in locations where Gen Y lives. Mars messages must be memorable!

Transition metal-centered trigonal prisms as building units in RE{sub 14}T{sub 3}In{sub 3} (RE = Y, Ho, Er, Tm, Lu; T = Pd, Ir, Pt) and Y{sub 4}IrIn

Energy Technology Data Exchange (ETDEWEB)

Zaremba, R.; Rodewald, U.C.; Poettgen, R. [Inst. fuer Anorganische und Analytische Chemie, Univ. Muenster (Germany)

2007-12-15

The indides RE{sub 14}T{sub 3}In{sub 3} (RE = Y, Ho, Er, Tm, Lu; T = Pd, Ir, Pt) and Y{sub 4}IrIn were synthesized from the elements by are-melting and subsequent annealing for crystal growth. Their structures were characterized on the basis of X-ray powder and single crystal data: Lu{sub 14}Co{sub 3}In{sub 3}-type, space group P4{sub 2}/nmc, a = 970.2(1), c = 2340.7(5) pm for Y{sub 13.95}Pd{sub 3}In{sub 3.05}, a = 959.7(1), c = 2309.0(5) pm for Ho{sub 14}Pd{sub 2.95}In{sub 3}, a = 955.5(1), c = 2305.1(5) pm for Er{sub 14}Pd{sub 3}In{sub 3}, a = 950.9(1), c = 2291.6(5) pm for Tm{sub 13.90}Pd{sub 3}In{sub 3.10}, a = 944.4(1), c = 2275.5(5) pm for Lu{sub 13.93}Pd{sub 3}In{sub 3.07}, a = 962.9(1), c = 2343.0(5) pm for Y{sub 13.86}Ir{sub 2.97}In{sub 3.02}, a = 967.6(1), c = 2347.8(5) pm for Y{sub 13.92}Pt{sub 3.05}In{sub 2.91}, and Gd{sub 4}RhIn-type, space group F anti 43m, a = 1368.6(2) pm for Y{sub 4}IrIn. The main structural motifs are transition metal-centered trigonal prisms of the rare Earth elements which are condensed to two-dimensional networks in the RE{sub 14}T{sub 3}In{sub 3} indides and to a three-dimensional one in Y{sub 4}IrIn. The indium atoms in both structure types show segregation in the metal-rich matrix, i.e. In{sub 2} dumbbells in the RE{sub 14}T{sub 3}In{sub 3} indides (309 pm In2-In2 in Y{sub 13.86}Ir{sub 2.97}In{sub 3.02}) and In{sub 4} tetrahedra (322 pm In-In) in Y{sub 4}IrIn. The crystal chemical peculiarities of both structure types are discussed. (orig.)

Genetic Polymorphism of MDM2 SNP309 in Patients with Helicobacter Pylori-Associated Gastritis.

Science.gov (United States)

Tongtawee, Taweesak; Dechsukhum, Chavaboon; Leeanansaksiri, Wilairat; Kaewpitoon, Soraya; Kaewpitoon, Natthawut; Loyd, Ryan A; Matrakool, Likit; Panpimanmas, Sukij

2015-01-01

Helicobacter pylori plays an important role in gastric cancer, which has a relatively low inciduence in Thailand. MDM2 is a major negative regulator of p53, the key tumor suppressor involved in tumorigenesis of the majority of human cancers. Whether its expression might explain the relative lack of gastric cancer in Thailand was assessed here. This single-center study was conducted in the northeast region of Thailand. Gastric mucosa from 100 patients with Helicobacter pylori associated gastritis was analyzed for MDM2 SNP309 using real-time PCR hybridization (light-cycler) probes. In the total 100 Helicobacter pylori associated gastritis cases the incidence of SNP 309 T/T homozygous was 78 % with SNP309 G/T heterozygous found in 19% and SNP309 G/G homozygous in 3%. The result show SNP 309 T/T and SNP 309 G/T to be rather common in the Thai population. Our study indicates that the MDM2 SNP309 G/G homozygous genotype might be a risk factor for gastric cancer in Thailand and the fact that it is infrequent could explain to some extent the low incidence of gastric cancer in the Thai population.

Forensic SNP genotyping with SNaPshot

DEFF Research Database (Denmark)

Fondevila, M; Børsting, C; Phillips, C

2017-01-01

to routine STR profiling, use of SNaPshot is an important part of the development of SNP sets for a wide range of forensic applications with these markers, from genotyping highly degraded DNA with very short amplicons to the introduction of SNPs to ascertain the ancestry and physical characteristics......This review explores the key factors that influence the optimization, routine use, and profile interpretation of the SNaPshot single-base extension (SBE) system applied to forensic single-nucleotide polymorphism (SNP) genotyping. Despite being a mainly complimentary DNA genotyping technique...... of an unidentified contact trace donor. However, this technology, as resourceful as it is, displays several features that depart from the usual STR genotyping far enough to demand a certain degree of expertise from the forensic analyst before tackling the complex casework on which SNaPshot application provides...

SUPLEMENTASI Lactobacillus acidophilus SNP-2 PADA TAPE DAN PENGARUHNYA PADA RELAWAN [Supplementation of Lactocbacillus acidophilus SNP-2 Into Tape and its Effect to the Volunteer

Directory of Open Access Journals (Sweden)

Endang S Rahayu1

2004-08-01

Full Text Available Functional food is defined as any potentially healthful food or food ingredient that may provide a health benefit beyond the traditional nutrients it contains. Many researches have been conducted on the health benefit of probiotic (life bacterial cells, one of the ingredient of functional foods. One of the potential bacteria used for probiotic agent and also involved in traditional fermented foods are lactic acid bacteria (LAB. Previous research showed that Lactobacillus acidophilus SNP-2 isolated from faecal material of healthy infant is resistant to acid and bile salt, and has an antagonistic effect against several enteric bacterial pathogens. The objective of this research was to study the effect of L. acidophilus SNP-2 as probiotic agent to the health benefits. These bacteria were supplemented into tape ketan (fermented sticky rice, the indigenous Indonesian fermented food. Tape ketan was chosen as the carrier of probiotic biomass based on the high population of LAB in this product, i.e., 1.3 x 108 CFU/g. Addition of L. acidophilus SNP-2 biomass prior to fermentation of tape ketan resulted in a higher total of LAB cells, i.e. 2.1 x 109 CFU/g compared to the amount of 1.5 x 108 CFU/g when the addition was done after fermentation. Consumption of tape ketan containing probiotic agent by the volunteers increased the population of lactobacilli (from 1.7x107 CFU/g to 9.9x107 CFU/g and decreased the population of enterobacteriacea (from 5.4x109 CFU/g to 4.4x108 in their faecal material. This phenomenon revealed that probiotic agent was able to colonize and inhibit the growth of enterobacteriaceae in the gastrointestinal tract. The result implied that tape ketan can be used as a carrier for probiotic agent and it can be categorized as functional food

Association between IRS1 Gene Polymorphism and Autism Spectrum Disorder: A Pilot Case-Control Study in Korean Males

Directory of Open Access Journals (Sweden)

Hae Jeong Park

2016-07-01

Full Text Available The insulin-like growth factor (IGF pathway is thought to play an important role in brain development. Altered levels of IGFs and their signaling regulators have been shown in autism spectrum disorder (ASD patients. In this study, we investigated whether coding region single-nucleotide polymorphisms (cSNPs of the insulin receptor substrates (IRS1 and IRS2, key mediators of the IGF pathway, were associated with ASD in Korean males. Two cSNPs (rs1801123 of IRS1, and rs4773092 of IRS2 were genotyped using direct sequencing in 180 male ASD patients and 147 male control subjects. A significant association between rs1801123 of IRS1 and ASD was shown in additive (p = 0.022, odds ratio (OR = 0.66, 95% confidence interval (CI = 0.46–0.95 and dominant models (p = 0.013, OR = 0.57, 95% CI = 0.37–0.89. Allele frequency analysis also showed an association between rs1801123 and ASD (p = 0.022, OR = 0.66, 95% CI = 0.46–0.94. These results suggest that IRS1 may contribute to the susceptibility of ASD in Korean males.

Gradiente de riesgo genético HLA-DQ para diabetes tipo 1 y enfermedad celíaca en el noroeste de México

OpenAIRE

Mejía-León, M.E.; Ruiz-Dyck, K.M.; Calderón de la Barca, A.M.

2015-01-01

Antecedentes: La diabetes tipo 1 (DT1) y la enfermedad celíaca (EC) son 2 enfermedades autoinmunes frecuentes en la infancia y comparten su predisposición genética (HLA-DQ2 y DQ8). La prevalencia de ambas se ha incrementado en el mundo. En el estado de Sonora (15 habitantes/km2), se desconoce información sobre su riesgo genético o la distribución de los alelos asociados en la población general. Objetivo: Comparar la frecuencia alélica HLA-DQ de una muestra representativa de recién nacidos ...

Connexin 43-targeted T1 contrast agent for MRI diagnosis of glioma.

Science.gov (United States)

Abakumova, Tatiana; Abakumov, Maxim; Shein, Sergey; Chelushkin, Pavel; Bychkov, Dmitry; Mukhin, Vladimir; Yusubalieva, Gaukhar; Grinenko, Nadezhda; Kabanov, Alexander; Nukolova, Natalia; Chekhonin, Vladimir

2016-01-01

Glioblastoma multiforme is the most aggressive form of brain tumor. Early and accurate diagnosis of glioma and its borders is an important step for its successful treatment. One of the promising targets for selective visualization of glioma and its margins is connexin 43 (Cx43), which is highly expressed in reactive astrocytes and migrating glioma cells. The purpose of this study was to synthesize a Gd-based contrast agent conjugated with specific antibodies to Cx43 for efficient visualization of glioma C6 in vivo. We have prepared stable nontoxic conjugates of monoclonal antibody to Cx43 and polylysine-DTPA ligands complexed with Gd(III), which are characterized by higher T1 relaxivity (6.5 mM(-1) s(-1) at 7 T) than the commercial agent Magnevist® (3.4 mM(-1) s(-1)). Cellular uptake of Cx43-specific T1 contrast agent in glioma C6 cells was more than four times higher than the nonspecific IgG-contrast agent, as detected by flow cytometry and confocal analysis. MRI experiments showed that the obtained agents could markedly enhance visualization of glioma C6 in vivo after their intravenous administration. Significant accumulation of Cx43-targeted contrast agents in glioma and the peritumoral zone led not only to enhanced contrast but also to improved detection of the tumor periphery. Fluorescence imaging confirmed notable accumulation of Cx43-specific conjugates in the peritumoral zone compared with nonspecific IgG conjugates at 24 h after intravenous injection. All these features of Cx43-targeted contrast agents might be useful for more precise diagnosis of glioma and its borders by MRI. Copyright © 2015 John Wiley & Sons, Ltd.

Development and application of a 20K SNP array in potato

NARCIS (Netherlands)

Vos, Peter

2016-01-01

In this thesis the results are described of investigations of various application of genome wide SNP (single nucleotide polymorphism) markers. The set of SNP markers was identified by GBS (genotyping by sequencing) strategy. The resulting dataset of 129,156 SNPs across 83 tetraploid varieties was

Robust Demographic Inference from Genomic and SNP Data

Science.gov (United States)

Excoffier, Laurent; Dupanloup, Isabelle; Huerta-Sánchez, Emilia; Sousa, Vitor C.; Foll, Matthieu

2013-01-01

We introduce a flexible and robust simulation-based framework to infer demographic parameters from the site frequency spectrum (SFS) computed on large genomic datasets. We show that our composite-likelihood approach allows one to study evolutionary models of arbitrary complexity, which cannot be tackled by other current likelihood-based methods. For simple scenarios, our approach compares favorably in terms of accuracy and speed with , the current reference in the field, while showing better convergence properties for complex models. We first apply our methodology to non-coding genomic SNP data from four human populations. To infer their demographic history, we compare neutral evolutionary models of increasing complexity, including unsampled populations. We further show the versatility of our framework by extending it to the inference of demographic parameters from SNP chips with known ascertainment, such as that recently released by Affymetrix to study human origins. Whereas previous ways of handling ascertained SNPs were either restricted to a single population or only allowed the inference of divergence time between a pair of populations, our framework can correctly infer parameters of more complex models including the divergence of several populations, bottlenecks and migration. We apply this approach to the reconstruction of African demography using two distinct ascertained human SNP panels studied under two evolutionary models. The two SNP panels lead to globally very similar estimates and confidence intervals, and suggest an ancient divergence (>110 Ky) between Yoruba and San populations. Our methodology appears well suited to the study of complex scenarios from large genomic data sets. PMID:24204310

No association of the G972S polymorphism of the insulin receptor substrate-1 gene with polycystic ovary syndrome in lean PCOS women with biochemical hyperandrogenemia.

Science.gov (United States)

Marioli, Dimitra J; Koika, Vasiliki; Adonakis, George L; Saltamavros, Alexandros D; Karela, Anastasia; Armeni, Anastasia K; Tsapanos, Vasilios S; Decavalas, George O; Georgopoulos, Neoklis A

2010-06-01

The aim of the present study was to determine the prevalence and association of the G972S polymorphism of the insulin receptor substrate-1 gene (IRS-1 G972S SNP) with polycystic ovary syndrome (PCOS) and insulin resistance-related traits in a distinct phenotypic group of lean PCOS women with biochemical hyperandrogenemia, excluding obesity, which is considered to be an aggravating parameter of insulin resistance. The study included 162 women with PCOS and 122 regularly menstruating, ovulatory women as controls. Physical measurements included weight, height, fat-free mass, fat mass, systolic and diastolic blood pressure and resting heart rate. Biochemical parameters included the serum testosterone, free testosterone, androstenedione, total cholesterol, triglycerides, HDL and LDL cholesterol and glucose levels. Insulin resistance was assessed by determining fasting insulin levels, fasting glucose levels, the fasting glucose/insulin ratio, as well as the HOMA and QUICKI indexes. All DNA samples were genotyped by a PCR-restriction fragment length polymorphism (RLFP) assay. No association of the genotype frequencies of the G972S polymorphism in insulin receptor substrate-1 gene (IRS-1 G972S SNP) with PCOS phenotype and insulin resistance was detected. The G972S polymorphism of the IRS-1 gene should not be viewed as major contributor to the development of PCOS or as a causative variant for insulin resistance.

Modelo poblacional con algoritmos genéticos

OpenAIRE

Veliz Quintero, Eduardo; Rodriguez Ojeda, Luis

2009-01-01

Para el desarrollo de este trabajo, “MODELO POBLACIONAL CON ALGORITMOS GENÉTICOS”, he investigado la rama de la inteligencia artificial, como son los algoritmos genéticos. Primero presento en forma general los aspectos que envuelven los algoritmos genéticos, parto de la necesidad de optimizar, así como su historia y posibles aplicaciones y luego he cubierto detalladamente todo lo que pude investigar sobre la teoría de los algoritmos genéticos, sus fundamentos matemáticos, tipos de algoritmos ...

Optical Response of Cu1-xZnxIr2S4 Due to Metal--Insulator Transition

International Nuclear Information System (INIS)

Chen, L.; Matsunami, M.; Nanba, T.; Cao, G.; Suzuki, H.; Isobe, M.; Matsumoto, T.

2003-01-01

The mother material CuIr 2 S 4 of the thiospinel system Cu 1-x Zn x Ir 2 S 4 undergoes a temperature-induced metal--insulator (Mi) transition. We report the temperature dependence of the optical reflection spectra of Cu 1-x Zn x Ir 2 S 4 (x ≤ 0.5) at the temperatures of 8-300 K in the energy regions of 0.005--30 eV in order to study the change in the electronic structure due to the Zn substitution for Cu. Zn substitution induced mainly the splitting of the hybridization band between the Ir-5d(t 2g ) and S-3 p states crossing the E F . Obtained optical conductivity (σ ) spectrum is discussed in relation to the change in the electronic structure close to the E F . (author)

Effects of exendin-4 and selenium on the expression of GLP-1R, IRS-1, and preproinsulin in the pancreas of diabetic rats.

Science.gov (United States)

Barakat, Ghinwa; Moustafa, Mohamed E; Khalifeh, Ibrahim; Hodroj, Mohammad H; Bikhazi, Anwar; Rizk, Sandra

2016-08-01

The mechanisms by which exendin-4 and selenium exert their antidiabetic actions are still unclear. Here, we investigated the effects of exendin-4 or selenium administration on the expression of glucagon-like peptide-1 receptor (GLP-1R), insulin receptor substrate-1 (IRS-1), and preproinsulin in the pancreas of diabetic rats. Diabetes was induced by streptozotocin administration. Diabetic rats were injected intraperitoneally with 0.03 μg exendin-4/kg body weight/daily or treated with 5 ppm selenium in drinking water for a period of 4 weeks. GLP-1R and IRS-1 levels were decreased while the level of preproinsulin messenger RNA (mRNA) was increased in the pancreas of diabetic untreated rats, as compared to that in control rats. Treatment of diabetic rats with exendin-4 increased protein and mRNA levels of GLP-1R, and IRS-1, and the mRNA level of preproinsulin in the pancreas, as compared to their levels in diabetic untreated rats. Selenium treatment of diabetic rats increased the pancreatic mRNA levels of GLP-1R, IRS-1, and preproinsulin. Exendin-4 or selenium treatment of diabetic rats also increased the numbers of pancreatic islets and GLP-1R molecules in the pancreas. Therefore, exendin-4 and selenium may exert their antidiabetic effects by increasing GLP-1R, IRS-1, and preproinsulin expression in the pancreas and by increasing the number of pancreatic islets.

RS-SNP: a random-set method for genome-wide association studies

Directory of Open Access Journals (Sweden)

Mukherjee Sayan

2011-03-01

Full Text Available Abstract Background The typical objective of Genome-wide association (GWA studies is to identify single-nucleotide polymorphisms (SNPs and corresponding genes with the strongest evidence of association (the 'most-significant SNPs/genes' approach. Borrowing ideas from micro-array data analysis, we propose a new method, named RS-SNP, for detecting sets of genes enriched in SNPs moderately associated to the phenotype. RS-SNP assesses whether the number of significant SNPs, with p-value P ≤ α, belonging to a given SNP set is statistically significant. The rationale of proposed method is that two kinds of null hypotheses are taken into account simultaneously. In the first null model the genotype and the phenotype are assumed to be independent random variables and the null distribution is the probability of the number of significant SNPs in greater than observed by chance. The second null model assumes the number of significant SNPs in depends on the size of and not on the identity of the SNPs in . Statistical significance is assessed using non-parametric permutation tests. Results We applied RS-SNP to the Crohn's disease (CD data set collected by the Wellcome Trust Case Control Consortium (WTCCC and compared the results with GENGEN, an approach recently proposed in literature. The enrichment analysis using RS-SNP and the set of pathways contained in the MSigDB C2 CP pathway collection highlighted 86 pathways rich in SNPs weakly associated to CD. Of these, 47 were also indicated to be significant by GENGEN. Similar results were obtained using the MSigDB C5 pathway collection. Many of the pathways found to be enriched by RS-SNP have a well-known connection to CD and often with inflammatory diseases. Conclusions The proposed method is a valuable alternative to other techniques for enrichment analysis of SNP sets. It is well founded from a theoretical and statistical perspective. Moreover, the experimental comparison with GENGEN highlights that it is

SNP discovery in candidate adaptive genes using exon capture in a free-ranging alpine ungulate

Science.gov (United States)

Roffler, Gretchen H.; Amish, Stephen J.; Smith, Seth; Cosart, Ted F.; Kardos, Marty; Schwartz, Michael K.; Luikart, Gordon

2016-01-01

Identification of genes underlying genomic signatures of natural selection is key to understanding adaptation to local conditions. We used targeted resequencing to identify SNP markers in 5321 candidate adaptive genes associated with known immunological, metabolic and growth functions in ovids and other ungulates. We selectively targeted 8161 exons in protein-coding and nearby 5′ and 3′ untranslated regions of chosen candidate genes. Targeted sequences were taken from bighorn sheep (Ovis canadensis) exon capture data and directly from the domestic sheep genome (Ovis aries v. 3; oviAri3). The bighorn sheep sequences used in the Dall's sheep (Ovis dalli dalli) exon capture aligned to 2350 genes on the oviAri3 genome with an average of 2 exons each. We developed a microfluidic qPCR-based SNP chip to genotype 476 Dall's sheep from locations across their range and test for patterns of selection. Using multiple corroborating approaches (lositan and bayescan), we detected 28 SNP loci potentially under selection. We additionally identified candidate loci significantly associated with latitude, longitude, precipitation and temperature, suggesting local environmental adaptation. The three methods demonstrated consistent support for natural selection on nine genes with immune and disease-regulating functions (e.g. Ovar-DRA, APC, BATF2, MAGEB18), cell regulation signalling pathways (e.g. KRIT1, PI3K, ORRC3), and respiratory health (CYSLTR1). Characterizing adaptive allele distributions from novel genetic techniques will facilitate investigation of the influence of environmental variation on local adaptation of a northern alpine ungulate throughout its range. This research demonstrated the utility of exon capture for gene-targeted SNP discovery and subsequent SNP chip genotyping using low-quality samples in a nonmodel species.

KARAKTERISTIK SEKUEN cDNA PENGKODE GEN ANTI VIRUS DARI UDANG WINDU, Penaeus monodon

Directory of Open Access Journals (Sweden)

Andi Parenrengi

2016-11-01

Full Text Available Transgenesis pada ikan merupakan sebuah teknik modern yang berpotensi besar dalam menghasilkan organisme yang memiliki karakter lebih baik melalui rekombinan DNA gen target termasuk gen anti virus dalam peningkatan resistensi pada udang. Gen anti virus PmAV (Penaeus monodon Anti Viral gene merupakan salah satu gen pengkode anti virus yang berasal dari spesies krustase. Penelitian ini dilakukan untuk mengetahui karakteristik gen anti virus yang diisolasi dari udang windu, Penaeus monodon. Isolasi gen anti virus menggunakan metode Polymerase Chain Reaction (PCR dan selanjutnya dipurifikasi untuk sekuensing. Data yang dihasilkan dianalisis dengan program Genetyx Versi 7 dan basic local alignment search tool (BLAST. Hasil penelitian menunjukkan bahwa gen anti virus PmAV yang berhasil diisolasi dari cDNA udang windu dengan panjang sekuen 520 bp yang mengkodekan 170 asam amino. BLAST-N menunjukkan tingkat similaritas yang sangat tinggi (100% dengan gen anti virus yang ada di GeneBank. Komposisi asam amino penyusun gen anti virus yang paling besar adalah serin (10,00%, sedangkan yang terkecil adalah asam amino prolin dan lisin masing-masing 1,76%. Analisis sekuen gen dan deduksi asam amino (BLAST-P memperlihatkan adanya C-type lectin-like domain (CTLD yang memiliki kemiripan dengan gen C-type lectin yang diisolasi dari beberapa spesies krustase. Transgenic fish technology is a potential modern technique in producing better character organism through DNA recombinant of target genes including anti viral gene for improvement of shrimp immunity. PmAV (Penaeus monodon Anti Viral gene is one of anti viral genes isolated from crustacean species. The research was conducted to analyze the characteristics anti viral gene isolated from tiger prawn, Penaeus monodon. Anti viral gene was isolated using Polymerase Chain Reaction (PCR technique and then purified for sequencing. Data obtained were analyzed using Genetyx Version 7 software and basic local alignment

Development and Evaluation of a Barley 50k iSelect SNP Array

Directory of Open Access Journals (Sweden)

Micha M. Bayer

2017-10-01

Full Text Available High-throughput genotyping arrays continue to be an attractive, cost-effective alternative to sequencing based approaches. We have developed a new 50k Illumina Infinium iSelect genotyping array for barley, a cereal crop species of major international importance. The majority of SNPs on the array have been extracted from variants called in exome capture data of a wide range of European barley germplasm. We used the recently published barley pseudomolecule assembly to map the exome capture data, which allowed us to generate markers with accurate physical positions and detailed gene annotation. Markers from an existing and widely used barley 9k Infinium iSelect array were carried over onto the 50k chip for backward compatibility. The array design featured 49,267 SNP markers that converted into 44,040 working assays, of which 43,461 were scorable in GenomeStudio. Of the working assays, 6,251 are from the 9k iSelect platform. We validated the SNPs by comparing the genotype calls from the new array to legacy datasets. Rates of agreement averaged 98.1 and 93.9% respectively for the legacy 9k iSelect SNP set (Comadran et al., 2012 and the exome capture SNPs. To test the utility of the 50k chip for genetic mapping, we genotyped a segregating population derived from a Golden Promise × Morex cross (Liu et al., 2014 and mapped over 14,000 SNPs to genetic positions which showed a near exact correspondence to their known physical positions. Manual adjustment of the cluster files used by the interpreting software for genotype scoring improved results substantially, but migration of cluster files between sites led to a deterioration of results, suggesting that local adjustment of cluster files is required on a site-per-site basis. Information relating to the markers on the chip is available online at https://ics.hutton.ac.uk/50k.

Synthesis and characterization of Sr2Ir1−xMxO4 (M=Ti, Fe, Co) solid solutions

International Nuclear Information System (INIS)

Gatimu, Alvin J.; Berthelot, Romain; Muir, Sean; Sleight, Arthur W.; Subramanian, M.A.

2012-01-01

The effects of Ti, Fe and Co substitutions for Ir on the structure and on the physical properties of Sr 2 IrO 4 are investigated. A complete solid solution Sr 2 Ir 1−x Ti x O 4 is obtained while both Fe and Co doping are relatively limited. In each case however, the c-axis cell parameter and the initial IrO 6 octahedra tilting decreases with substitution. Doping with Ti, Fe and Co results in a decrease of the magnetic susceptibility and in an increase in the paramagnetic effective moment for Co and Fe doped samples and a suppression of the weak ferromagnetic ordering observed for Sr 2 IrO 4 . - Graphical abstract: Solid solutions of Sr 2 Ir 1−x M x O 4 (M=Ti, Fe, Co) have been synthesized and characterized by powder X-ray diffraction, magnetism and electrical measurements. Changes in the a parameter and decreases in both the c-axis cell parameters and the initial IrO 6 octahedra tilting are found to be correlated. Highlights: ► Solid Solutions of Sr 2 Ir 1−x M x O 4 (M=Ti, Fe, Co) are synthesized. ► The Sr 2 Ir 1−x Ti x O 4 solid solution is complete while those of Fe and Co are relatively limited. ► The change in a cell parameter with substitution is much less than that of the c parameter. ► Decreased tilting and the smaller size of the M cation contrastingly affect the a parameter. ► Doping results in a suppression of the weak ferromagnetic ordering in Sr 2 IrO 4 .

Factors Influencing Retention of Gen Y and Non-Gen Y Teachers Working at International Schools in Asia

Science.gov (United States)

Fong, Hoi Wah Benny

2018-01-01

Quantitative studies on international-school teacher retention are few, especially studies that differentiate between Gen Y and non-Gen Y teachers. This article reports on the findings of a study that examined the relationship of job satisfaction factors to the likelihood of contract renewal by international-school teachers. Results from the study…

Heterogeneous computing architecture for fast detection of SNP-SNP interactions.

Science.gov (United States)

Sluga, Davor; Curk, Tomaz; Zupan, Blaz; Lotric, Uros

2014-06-25

The extent of data in a typical genome-wide association study (GWAS) poses considerable computational challenges to software tools for gene-gene interaction discovery. Exhaustive evaluation of all interactions among hundreds of thousands to millions of single nucleotide polymorphisms (SNPs) may require weeks or even months of computation. Massively parallel hardware within a modern Graphic Processing Unit (GPU) and Many Integrated Core (MIC) coprocessors can shorten the run time considerably. While the utility of GPU-based implementations in bioinformatics has been well studied, MIC architecture has been introduced only recently and may provide a number of comparative advantages that have yet to be explored and tested. We have developed a heterogeneous, GPU and Intel MIC-accelerated software module for SNP-SNP interaction discovery to replace the previously single-threaded computational core in the interactive web-based data exploration program SNPsyn. We report on differences between these two modern massively parallel architectures and their software environments. Their utility resulted in an order of magnitude shorter execution times when compared to the single-threaded CPU implementation. GPU implementation on a single Nvidia Tesla K20 runs twice as fast as that for the MIC architecture-based Xeon Phi P5110 coprocessor, but also requires considerably more programming effort. General purpose GPUs are a mature platform with large amounts of computing power capable of tackling inherently parallel problems, but can prove demanding for the programmer. On the other hand the new MIC architecture, albeit lacking in performance reduces the programming effort and makes it up with a more general architecture suitable for a wider range of problems.

43 CFR 43.635 - Drug-free workplace.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Drug-free workplace. 43.635 Section 43.635 Public Lands: Interior Office of the Secretary of the Interior GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 43.635 Drug-free workplace. Drug-free workplace means a site...

TMEPAI regulates EMT in lung cancer cells by modulating the ROS and IRS-1 signaling pathways.

Science.gov (United States)

Hu, Ying; He, Kai; Wang, Dongmei; Yuan, Xinwang; Liu, Yi; Ji, Hongbin; Song, Jianguo

2013-08-01

The epithelial-mesenchymal transition (EMT) has been implicated in various pathophysiological processes, including cancer cell migration and distal metastasis. Reactive oxygen species (ROS) and insulin receptor substrate-1 (IRS-1) are important in cancer progression and regulation of EMT. To explore the biological significance and regulatory mechanism of EMT, we determined the expression, the biological function and the signaling pathway of prostate transmembrane protein, androgen induced-1 (TMEPAI), during the induction of EMT and cell migration. Transforming growth factor (TGF)-β1 significantly upregulated the expression of TMEPAI during EMT in human lung adenocarcinoma. Depletion of TMEPAI abolished TGF-β1-induced downregulation of ferritin heavy chain and the subsequent generation of ROS, thus suppressing TGF-β1-induced EMT and cell migration. In addition, increased ROS production and overexpression of TMEPAI downregulated the level of IRS-1. Both the addition of H2O2 and IRS-1 small interfering RNA rescued the ability of TGF-β1 to induce EMT in TMEPAI-depleted cells. Remarkably, the levels of TMEPAI in lung tumor tissues are very high, whereas its expression in normal lung epithelium is very low. Moreover, TMEPAI expression was positively correlated with the cell mesenchymal phenotype and migration potential. Our work reveals that TMEPAI contributes to TGF-β1-induced EMT through ROS production and IRS-1 downregulation in lung cancer cells.

Mena associates with Rac1 and modulates connexin 43 remodeling in cardiomyocytes.

Science.gov (United States)

Ram, Rashmi; Wescott, Andrew P; Varandas, Katherine; Dirksen, Robert T; Blaxall, Burns C

2014-01-01

Mena, a member of the Ena/VASP family of actin regulatory proteins, modulates microfilaments and interacts with cytoskeletal proteins associated with heart failure. Mena is localized at the intercalated disc (ICD) of adult cardiac myocytes, colocalizing with numerous cytoskeletal proteins. Mena's role in the maintainence of mechanical myocardial stability at the cardiomyocyte ICD remains unknown. We hypothesized that Mena may modulate signals from the sarcolemma to the actin cytoskeleton at the ICD to regulate the expression and localization of connexin 43 (Cx43). The small GTPase Rac1 plays a pivotal role in the regulation of actin cytoskeletal reorganization and mediating morphological and transcriptional changes in cardiomyocytes. We found that Mena is associated with active Rac1 in cardiomyocytes and that RNAi knockdown of Mena increased Rac1 activity significantly. Furthermore, Mena knockdown increased Cx43 expression and altered Cx43 localization and trafficking at the ICD, concomitant with faster intercellular communication, as assessed by dye transfer between cardiomyocyte pairs. In mice overexpressing constitutively active Rac1, left ventricular Mena expression was increased significantly, concomitant with lateral redistribution of Cx43. These results suggest that Mena is a critical regulator of the ICD and is required for normal localization of Cx43 in part via regulation of Rac1.

Factores genéticos en casos graves de gripe (H1N1 2009

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Francesc Calafell i Majó

2011-01-01

Full Text Available La pandemia de gripe (H1N1 2009 generó una serie de cuestiones, entre las cuales estuvo que entre un 25 y un 30% de los casos graves de gripe no presentaron ningún factor de riesgo obvio. Hipotetizamos que un elemento que puede contribuir a la respuesta son factores de riesgo gené ticos del huésped involucrados en la mala progresió n de la enfermedad. Varios indicios nos llevaron a esta hipótesis: estudios de agregación familiar en islandeses y mormones de Utah muestran una cierta heredabilidad de la mortalidad por gripe; se conocen casi 300 genes humanos necesarios para la replicació n del virus de la gripe; y los pacientes más graves de gripe (H1N12009 mostraron una desregulació n del sistema inmune adaptativo. Estamos abordando este problema mediante un diseñ o caso-control (casos hospitalizados de gripe (H1N12009 confirmados contra casos ambulatorios, tambié n confirmados para (H1N12009, en el que se genotiparán más de un milló n de polimorfismos de cambios de nucleó tido (SNPs y de variació n de número de copia (CNVs en casos y controles.

Interference of Homologous Sequences on the SNP Study of CYP2A13 Gene

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Qinghua ZHOU

2010-02-01

Full Text Available Background and objective It has been proven that cytochrome P450 enzyme 2A13 (CYP2A13 played an important role in the association between single nucleotide polymorphisms (SNP and human diseases. Cytochrome P450 enzymes are a group of isoenzymes, whose sequence homology may interfere with the study for SNP. The aim of this study is to explore the interference on the SNP study of CYP2A13 caused by homologous sequences. Methods Taqman probe was applied to detect distribution of rs8192789 sites in 573 subjects, and BLAST method was used to analyze the amplified sequences. Partial sequences of CYP2A13 were emplified by PCR from 60 cases. The emplified sequences were TA cloned and sequenced. Results For rs8192789 loci in 573 cases, only 3 cases were TT, while the rest were CT heterozygotes, which was caused by homologous sequences. There are a large number of overlapping peaks in identical sequences of 60 cases, and the SNP of 101 amino acid site reported in the SNP database is not found. The cloned sequences are 247 bp, 235 bp fragments. Conclusion The homologous sequences may interfere the study for SNP of CYP2A13, and some SNP may not exist.

Metode Transfer Asam Nukleat sebagai Dasar Terapi Gen

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Novi Silvia Hardiany

2017-01-01

Full Text Available Kemajuan ilmu biologi molekuler memberikan manfaat dalam bidang kedokteran untuk mengembangkanterapi gen. Tujuan terapi gen adalah untuk memperbaiki kerusakan gen atau mengganti gen yang rusakdengan gen yang normal. Pemindahan gen dilakukan dengan teknik transfeksi. Transfeksi merupakanproses pemindahan asam nukleat baik menggunakan vektor virus (transduksi atau menggunakan metodenonviral yaitu zat kimia, lipid dan metode fisik. Vektor virus yang digunakan pada transduksi adalahretrovirus, adenovirus, adeno-associated virus (AAV dan herpes simplex virus (HSV. Keberhasilantransfeksi ditentukan oleh berbagai faktor yang dapat dapat dinilai dengan menggunakan reporter sepertigreen fluorescence protein (GFP. Kata Kunci: terapi gen, transfeksi non viral, transduksi, vektor virus   Methods of Nucleic Acid Transfer as Basic Gene Therapy Abstract The advancement of molecular biology provides benefit in the field of medicine to develop genetherapy. The aim of gene therapy is to repair the genetic damage or to replace damaged gene with thenormal gene. Delivery of gene is carried out by transfection technique, a technique to transfer nucleic acidinto eukaryote cells either using viral vectors (known as transduction, and also using non viral methodsuch as chemical substance, lipid and physical method. Some of the viral vectors used in the transductionare retrovirus, adenovirus, Adeno-associated virus (AAV and Herpes Simplex Virus (HSV. The success oftransfection is determined by various factors which can be assessed using several reporters such as GreenFluorescence Protein (GFP. Key words: gene therapy, non viral transfection, transduction, viral vector. Normal 0 false false false IN X-NONE X-NONE

TRANSFER GEN ANTIVIRUS PADA EMBRIO UDANG WINDU, Penaeus monodon DALAM BERBAGAI KONSENTRASI DEOXYRIBO NUCLEIC ACID

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Andi Parenrengi

2011-12-01

Full Text Available Teknologi transgenesis khususnya rekayasa genetik untuk menghasilkan udang windu resisten penyakit merupakan salah satu strategi yang dapat dilakukan dalam upaya pemecahan masalah penyakit yang menimpa budidaya udang windu. Teknologi transgenesis khususnya transfer gen antivirus pada udang windu telah berhasil dilakukan melalui teknik transfeksi. Meskipun demikian optimalisasi komponen teknologi tersebut masih perlu dilakukan. Konsentrasi DNA gen merupakan salah satu komponen teknologi transgenesis yang harus dioptimalkan untuk mendapatkan efisiensi dalam transfer gen. Penelitian bertujuan untuk mengetahui konsentrasi DNA gen antivirus yang optimal sebagai bahan transfer gen ke embrio menggunakan metode transfeksi. Embrio udang windu yang diperoleh dari hasil pemijahan induk asal Aceh, dikoleksi 5-10 menit setelah memijah dengan kepadatan 625 telur/2 mL. Transfeksi dilakukan dengan menggunakan media larutan transfeksi jetPEI dengan konsentrasi DNA gen antivirus sebagai perlakuan, yakni: 5, 10, dan 15 µg serta kontrol positif (tanpa plasmid DNA dan negatif (tanpa plasmid DNA dan larutan transfeksi, masing-masing 3 ulangan. Embrio hasil transfeksi ditetaskan pada stoples berisi air laut sebanyak 2 L yang diletakkan pada waterbath. Hasil penelitian menunjukkan bahwa gen antivirus telah berhasil diintroduksi ke embrio udang windu. Hasil analisis ragam menunjukkan bahwa perbedaan konsentrasi DNA (5-15 µg tidak berpengaruh nyata (P>0,05 terhadap daya tetas embrio udang windu. Analisis ekspresi gen pada larva udang windu juga menunjukkan adanya aktivitas ekspresi gen antivirus pada semua perlakuan konsentrasi DNA, di mana ekspresi gen antivirus pada larva transgenik lebih tinggi dibandingkan dengan kontrol (tanpa transfeksi. Sintasan pasca-larva PL-1 yang didapatkan pada penelitian ini adalah 12,0%; 10,0%; 10,6%; 12,3%; dan 14,2% masing-masing untuk perlakuan konsentrasi plasmid DNA 5 µg, 10 µg, 15 µg, kontrol positif dan negatif, di mana

Desempenho de genótipos de girassol sob irrigação nas condições do semiárido Performance of sunflower genotypes under irrigation in semiarid conditions

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Aureliano José Vieira Pires

2011-09-01

Full Text Available Objetivou-se com este trabalho avaliar o potencial de produção, os parâmetros agronômicos e a composição bromatológica de nove genótipos de girassol, sob irrigação, no semiárido. A semeadura ocorreu em 13/05/2008 e a colheita em 30/08/2008. Utilizou-se o delineamento em blocos ao acaso com três repetições em esquema fatorial (2x9, sendo dois espaçamentos (70 e 90cm e nove genótipos. O genótipo Catissol 4 apresentou maior curvatura de caule (4,3 independente do espaçamento utilizado. No espaçamento de 70cm observaram-se maiores produções de massa seca (16,6t/ha, massa verde de caule e folhas (16,6t/ha, massa seca de caule e folhas (6,1t/ha e aquênios (3,3t/ha. O genótipo Hélio 251 produziu maior quantidade de aquênios por planta (1.235. No espaçamento de 70cm o genótipo Catissol 4 apresentou teor de matéria seca (41,4%, superior aos demais genótipos. No entanto, não foram observadas diferenças para a produção de matéria seca pelos genótipos Aguará 3, Aguará 4, Charrua, Hélio 250, Hélio 251 e Hélio 360 no espaçamento de 90cm. Os genótipos apresentaram melhor teor de hemicelulose (12,2% sob espaçamento de 70cm, bem como aumento dos teores de matéria seca (64,8% e fibra insolúvel em detergente neutro (54,8%. Concluiu-se que o girassol apresentou características favoráveis no semiárido, que a maior produtividade dos genótipos ocorreu no espaçamento de 70cm entre fileiras, que o genótipo Hélio 251 correspondeu à melhor opção para produção de grãos e que os teores de proteína e extrato etéreo foram significativos.The purpose of this study was to evaluate yield potential, agronomic parameters and chemical composition of nine sunflower genotypes under irrigation in the semiarid. The sowing took place in May 13, 2008 and the harvest in August 13, 2008. We used a randomized block design with three replications in a factorial (2x9 and two spacings (70 and 90cm and nine genotypes. The genotype

Psoriasis prediction from genome-wide SNP profiles

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Fang Xiangzhong

2011-01-01

Full Text Available Abstract Background With the availability of large-scale genome-wide association study (GWAS data, choosing an optimal set of SNPs for disease susceptibility prediction is a challenging task. This study aimed to use single nucleotide polymorphisms (SNPs to predict psoriasis from searching GWAS data. Methods Totally we had 2,798 samples and 451,724 SNPs. Process for searching a set of SNPs to predict susceptibility for psoriasis consisted of two steps. The first one was to search top 1,000 SNPs with high accuracy for prediction of psoriasis from GWAS dataset. The second one was to search for an optimal SNP subset for predicting psoriasis. The sequential information bottleneck (sIB method was compared with classical linear discriminant analysis(LDA for classification performance. Results The best test harmonic mean of sensitivity and specificity for predicting psoriasis by sIB was 0.674(95% CI: 0.650-0.698, while only 0.520(95% CI: 0.472-0.524 was reported for predicting disease by LDA. Our results indicate that the new classifier sIB performs better than LDA in the study. Conclusions The fact that a small set of SNPs can predict disease status with average accuracy of 68% makes it possible to use SNP data for psoriasis prediction.

Pitfalls in genetic testing: a case of a SNP in primer-annealing region leading to allele dropout in BRCA1.

Science.gov (United States)

Silva, Felipe Carneiro; Torrezan, Giovana Tardin; Brianese, Rafael Canfield; Stabellini, Raquel; Carraro, Dirce Maria

2017-07-01

Hereditary breast and ovarian cancer is characterized by mutations in BRCA1 or BRCA2 genes and PCR-based screening techniques, such as capillary sequencing and next-generation sequencing (NGS), are considered gold standard methods for detection of pathogenic mutations in these genes. Single-nucleotide polymorphisms (SNPs) constitute a vast source of variation in the human genome and represent a risk for misdiagnosis in genetic testing, since the presence of a SNP in primer-annealing sites may cause false negative results due to allele dropout. However, few reports are available and the frequency of this phenomenon in diagnostic assays remains unknown. In this article, we investigated the causes of a false negative capillary sequencing result in BRCA1 involving a mother-daughter dyad. Using several molecular strategies, including different DNA polymerases, primer redesign, allele-specific PCR and NGS, we established that the initial misdiagnosis was caused by a SNP located in the primer-annealing region, leading to allele dropout of the mutated allele. Assuming that this problem can also occur in any PCR-based method that are widely used in diagnostic settings, the clinical report presented here draws attention for one of the limitations of genetic testing in general, for which medical and laboratory communities need to be aware.

Discrimination of Chinese Sauce liquor using FT-IR and two-dimensional correlation IR spectroscopy

Science.gov (United States)

Sun, Su-Qin; Li, Chang-Wen; Wei, Ji-Ping; Zhou, Qun; Noda, Isao

2006-11-01

We applied the three-step IR macro-fingerprint identification method to obtain the IR characteristic fingerprints of so-called Chinese Sauce liquor (Moutai liquor and Kinsly liquor) and a counterfeit Moutai. These fingerprints can be used for the identification and discrimination of similar liquor products. The comparison of their conventional IR spectra, as the first step of identification, shows that the primary difference in Sauce liquor is the intensity of characteristic peaks at 1592 and 1225 cm -1. The comparison of the second derivative IR spectra, as the second step of identification, shows that the characteristic absorption in 1400-1800 cm -1 is substantially different. The comparison of 2D-IR correlation spectra, as the third and final step of identification, can discriminate the liquors from another direction. Furthermore, the method was successfully applied to the discrimination of a counterfeit Moutai from the genuine Sauce liquor. The success of the three-step IR macro-fingerprint identification to provide a rapid and effective method for the identification of Chinese liquor suggests the potential extension of this technique to the identification and discrimination of other wine and spirits, as well.

Interim report on updated microarray probes for the LLNL Burkholderia pseudomallei SNP array

Energy Technology Data Exchange (ETDEWEB)

Gardner, S; Jaing, C

2012-03-27

The overall goal of this project is to forensically characterize 100 unknown Burkholderia isolates in the US-Australia collaboration. We will identify genome-wide single nucleotide polymorphisms (SNPs) from B. pseudomallei and near neighbor species including B. mallei, B. thailandensis and B. oklahomensis. We will design microarray probes to detect these SNP markers and analyze 100 Burkholderia genomic DNAs extracted from environmental, clinical and near neighbor isolates from Australian collaborators on the Burkholderia SNP microarray. We will analyze the microarray genotyping results to characterize the genetic diversity of these new isolates and triage the samples for whole genome sequencing. In this interim report, we described the SNP analysis and the microarray probe design for the Burkholderia SNP microarray.

Alkoholio ir tabako pasiūlos ir paklausos teisinio reguliavimo raida Lietuvos Respublikoje: problemos ir sprendimai

OpenAIRE

Mockevičius, Arminas

2014-01-01

Viešosios teisės magistro studijų programos studento Armino Mockevičiaus buvo parašytas magistro baigiamasis darbas „Alkoholio ir tabako pasiūlos ir paklausos teisinio reguliavimo raida Lietuvos Respublikoje: problemos ir sprendimai“. Šis darbas parašytas Vilniuje, 2014 metais, Mykolo Romerio universiteto Teisės fakulteto Konstitucinės ir administracinės teisės institute, vadovaujant dr. Gintautui Vilkeliui, apimtis 98 p. Darbo tikslas yra atskleisti alkoholio ir tabako pasiūlos ir paklau...

Comparison of the hypothetical (57)Co brachytherapy source with the (192)Ir source.

Science.gov (United States)

Toossi, Mohammad Taghi Bahreyni; Ghorbani, Mahdi; Rostami, Atefeh; Khosroabadi, Mohsen; Khademi, Sara; Knaup, Courtney

2016-01-01

The (57)Co radioisotope has recently been proposed as a hypothetical brachytherapy source due to its high specific activity, appropriate half-life (272 days) and medium energy photons (114.17 keV on average). In this study, Task Group No. 43 dosimetric parameters were calculated and reported for a hypothetical (57)Co source. A hypothetical (57)Co source was simulated in MCNPX, consisting of an active cylinder with 3.5 mm length and 0.6 mm radius encapsulated in a stainless steel capsule. Three photon energies were utilized (136 keV [10.68%], 122 keV [85.60%], 14 keV [9.16%]) for the (57)Co source. Air kerma strength, dose rate constant, radial dose function, anisotropy function, and isodose curves for the source were calculated and compared to the corresponding data for a (192)Ir source. The results are presented as tables and figures. Air kerma strength per 1 mCi activity for the (57)Co source was 0.46 cGyh(-1) cm 2 mCi(-1). The dose rate constant for the (57)Co source was determined to be 1.215 cGyh(-1)U(-1). The radial dose function for the (57)Co source has an increasing trend due to multiple scattering of low energy photons. The anisotropy function for the (57)Co source at various distances from the source is more isotropic than the (192)Ir source. The (57)Co source has advantages over (192)Ir due to its lower energy photons, longer half-life, higher dose rate constant and more isotropic anisotropic function. However, the (192)Ir source has a higher initial air kerma strength and more uniform radial dose function. These properties make (57)Co a suitable source for use in brachytherapy applications.

Gridded precipitation dataset for the Rhine basin made with the genRE interpolation method

NARCIS (Netherlands)

Osnabrugge, van B.; Uijlenhoet, R.

2017-01-01

A high resolution (1.2x1.2km) gridded precipitation dataset with hourly time step that covers the whole Rhine basin for the period 1997-2015. Made from gauge data with the genRE interpolation scheme. See "genRE: A method to extend gridded precipitation climatology datasets in near real-time for

Mouse SNP Miner: an annotated database of mouse functional single nucleotide polymorphisms

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Ramensky Vasily E

2007-01-01

Full Text Available Abstract Background The mapping of quantitative trait loci in rat and mouse has been extremely successful in identifying chromosomal regions associated with human disease-related phenotypes. However, identifying the specific phenotype-causing DNA sequence variations within a quantitative trait locus has been much more difficult. The recent availability of genomic sequence from several mouse inbred strains (including C57BL/6J, 129X1/SvJ, 129S1/SvImJ, A/J, and DBA/2J has made it possible to catalog DNA sequence differences within a quantitative trait locus derived from crosses between these strains. However, even for well-defined quantitative trait loci ( Description To help identify functional DNA sequence variations within quantitative trait loci we have used the Ensembl annotated genome sequence to compile a database of mouse single nucleotide polymorphisms (SNPs that are predicted to cause missense, nonsense, frameshift, or splice site mutations (available at http://bioinfo.embl.it/SnpApplet/. For missense mutations we have used the PolyPhen and PANTHER algorithms to predict whether amino acid changes are likely to disrupt protein function. Conclusion We have developed a database of mouse SNPs predicted to cause missense, nonsense, frameshift, and splice-site mutations. Our analysis revealed that 20% and 14% of missense SNPs are likely to be deleterious according to PolyPhen and PANTHER, respectively, and 6% are considered deleterious by both algorithms. The database also provides gene expression and functional annotations from the Symatlas, Gene Ontology, and OMIM databases to further assess candidate phenotype-causing mutations. To demonstrate its utility, we show that Mouse SNP Miner successfully finds a previously identified candidate SNP in the taste receptor, Tas1r3, that underlies sucrose preference in the C57BL/6J strain. We also use Mouse SNP Miner to derive a list of candidate phenotype-causing mutations within a previously

NextGen UAS Research, Development and Demonstration Roadmap. Version 1.0

Science.gov (United States)

2012-03-15

18. NUMBER OF PAGES 80 19a. NAME OF RESPONSIBLE PERSON a. REPORT unclassified b. ABSTRACT unclassified c. THIS PAGE unclassified Standard ...individual COA, UAS may operate under both Visual Flight Rules (VFR) and Instrument Flight Rules ( IFR ), in both special use airspace and non- segregated...National Aeronautics Research and Development Plan,” February 2010 , which cites the importance of integrating UAS into the NextGen NAS and establishes

Suppression of superconductivity in Nb by IrMn in IrMn/Nb bilayers

KAUST Repository

Wu, B. L.; Yang, Y. M.; Guo, Z. B.; Wu, Y. H.; Qiu, J. J.

2013-01-01

Effect of antiferromagnet on superconductivity has been investigated in IrMn/Nb bilayers. Significant suppression of both transition temperature (Tc) and lower critical field (Hc1) of Nb is found in IrMn/Nb bilayers as compared to a single layer Nb

First-principles study on cubic pyrochlore iridates Y2Ir2O7 and Pr2Ir2O7

International Nuclear Information System (INIS)

Ishii, Fumiyuki; Mizuta, Yo Pierre; Kato, Takehiro; Ozaki, Taisuke; Weng Hongming; Onoda, Shigeki

2015-01-01

Fully relativistic first-principles electronic structure calculations based on a noncollinear local spin density approximation (LSDA) are performed for pyrochlore iridates Y 2 Ir 2 O 7 and Pr 2 Ir 2 O 7 . The all-in, all-out antiferromagnetic (AF) order is stablized by the on-site Coulomb repulsion U > U c in the LSDA+U scheme, with U c ∼ 1.1 eV and 1.3 eV for Y 2 Ir 2 O 7 and Pr 2 Ir 2 O 7 , respectively. AF semimetals with and without Weyl points and then a topologically trivial AF insulator successively appear with further increasing U. For U = 1.3 eV, Y 2 Ir 2 O 7 is a topologically trivial narrow-gap AF insulator having an ordered local magnetic moment ∼0.5μ B /Ir, while Pr 2 Ir 2 O 7 is barely a paramagnetic semimetal with electron and hole concentrations of 0.016/Ir, in overall agreements with experiments. With decreasing oxygen position parameter x describing the trigonal compression of IrO 6 octahedra, Pr 2 Ir 2 O 7 is driven through a non-Fermi-liquid semimetal having only an isolated Fermi point of Γ 8 + , showing a quadratic band touching, to a Z 2 topological insulator. (author)

Vitis phylogenomics: hybridization intensities from a SNP array outperform genotype calls.

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Allison J Miller

Full Text Available Understanding relationships among species is a fundamental goal of evolutionary biology. Single nucleotide polymorphisms (SNPs identified through next generation sequencing and related technologies enable phylogeny reconstruction by providing unprecedented numbers of characters for analysis. One approach to SNP-based phylogeny reconstruction is to identify SNPs in a subset of individuals, and then to compile SNPs on an array that can be used to genotype additional samples at hundreds or thousands of sites simultaneously. Although powerful and efficient, this method is subject to ascertainment bias because applying variation discovered in a representative subset to a larger sample favors identification of SNPs with high minor allele frequencies and introduces bias against rare alleles. Here, we demonstrate that the use of hybridization intensity data, rather than genotype calls, reduces the effects of ascertainment bias. Whereas traditional SNP calls assess known variants based on diversity housed in the discovery panel, hybridization intensity data survey variation in the broader sample pool, regardless of whether those variants are present in the initial SNP discovery process. We apply SNP genotype and hybridization intensity data derived from the Vitis9kSNP array developed for grape to show the effects of ascertainment bias and to reconstruct evolutionary relationships among Vitis species. We demonstrate that phylogenies constructed using hybridization intensities suffer less from the distorting effects of ascertainment bias, and are thus more accurate than phylogenies based on genotype calls. Moreover, we reconstruct the phylogeny of the genus Vitis using hybridization data, show that North American subgenus Vitis species are monophyletic, and resolve several previously poorly known relationships among North American species. This study builds on earlier work that applied the Vitis9kSNP array to evolutionary questions within Vitis vinifera

The rs3957357C>T SNP in GSTA1 Is Associated with a Higher Risk of Occurrence of Hepatocellular Carcinoma in European Individuals.

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Hanane Akhdar

Full Text Available Glutathione S-transferases (GSTs detoxify toxic molecules by conjugation with reduced glutathione and regulate cell signaling. Single nucleotide polymorphisms (SNPs of GST genes have been suggested to affect GST functions and thus to increase the risk of human hepatocellular carcinoma (HCC. As GSTA1 is expressed in hepatocytes and the rs3957357C>T (TT SNP is known to downregulate GSTA1 mRNA expression, the aims of this study were: (i to explore the relationship between the TT SNP in GSTA1 and the occurrence of HCC; (ii to measure GSTA1 mRNA expression in HCCs. For that purpose, we genotyped non-tumor-tissue-derived DNA from 48 HCC patients and white-blood-cell-derived DNA from 37 healthy individuals by restriction fragment length polymorphism (RFLP. In addition, expression of GSTA1 mRNA was assessed by real-time PCR in 18 matching pairs of HCCs and non-tumor livers. Survival analysis was performed on an annotated microarray dataset containing 247 HCC patients (GSE14520. The GSTA1 TT genotype was more frequent in HCC than in non-HCC patients (27% versus 5%, respectively, suggesting that individuals carrying this genotype could be associated with 2-fold higher risk of developing HCCs (odds ratio = 2.1; p = 0.02. Also, we found that GSTA1 mRNA expression was lower in HCCs than in non-tumor livers. HCCs expressing the highest GSTA1 mRNA levels were the smallest in size (R = -0.67; p = 0.007, expressed the highest levels of liver-enriched genes such as ALB (albumin, R = -0.67; p = 0.007 and COL18A1 (procollagen type XVIII, R = -0.50; p = 0.03 and showed the most favorable disease-free (OR = 0.54; p<0.001 and overall (OR = 0.56; p = 0.006 outcomes. Moreover, GSTA1 was found within a 263-gene network involved in well-differentiated hepatocyte functions. In conclusion, HCCs are characterized by two GSTA1 features: the TT SNP and reduced GSTA1 gene expression in a context of hepatocyte de-differentiation.

Identification of the fragment of the 1-methylpyrene cation by mid-IR spectroscopy

Science.gov (United States)

Jusko, Pavol; Simon, Aude; Wenzel, Gabi; Brünken, Sandra; Schlemmer, Stephan; Joblin, Christine

2018-04-01

The fragment of the 1-methylpyrene cation, 17C 11H+, is expected to exist in two isomeric forms, 1-pyrenemethylium PyrCH2+ and the tropylium containing species PyrC7+. We measured the infrared (IR) action spectrum of cold 17C 11H+ tagged with Ne using a cryogenic ion trap instrument coupled to the FELIX laser. Comparison of the experimental data with density functional theory calculations allows us to identify the PyrCH2+ isomer in our experiments. The IR Multi-Photon Dissociation spectrum was also recorded following the C2H2 loss channel. Its analysis suggests combined effects of anharmonicity and isomerisation while heating the trapped ions, as shown by molecular dynamics simulations.

Two combinatorial optimization problems for SNP discovery using base-specific cleavage and mass spectrometry.

Science.gov (United States)

Chen, Xin; Wu, Qiong; Sun, Ruimin; Zhang, Louxin

2012-01-01

The discovery of single-nucleotide polymorphisms (SNPs) has important implications in a variety of genetic studies on human diseases and biological functions. One valuable approach proposed for SNP discovery is based on base-specific cleavage and mass spectrometry. However, it is still very challenging to achieve the full potential of this SNP discovery approach. In this study, we formulate two new combinatorial optimization problems. While both problems are aimed at reconstructing the sample sequence that would attain the minimum number of SNPs, they search over different candidate sequence spaces. The first problem, denoted as SNP - MSP, limits its search to sequences whose in silico predicted mass spectra have all their signals contained in the measured mass spectra. In contrast, the second problem, denoted as SNP - MSQ, limits its search to sequences whose in silico predicted mass spectra instead contain all the signals of the measured mass spectra. We present an exact dynamic programming algorithm for solving the SNP - MSP problem and also show that the SNP - MSQ problem is NP-hard by a reduction from a restricted variation of the 3-partition problem. We believe that an efficient solution to either problem above could offer a seamless integration of information in four complementary base-specific cleavage reactions, thereby improving the capability of the underlying biotechnology for sensitive and accurate SNP discovery.

Comparison of SSR and SNP markers in estimation of genetic diversity and population structure of Indian rice varieties.

Science.gov (United States)

Singh, Nivedita; Choudhury, Debjani Roy; Singh, Amit Kumar; Kumar, Sundeep; Srinivasan, Kalyani; Tyagi, R K; Singh, N K; Singh, Rakesh

2013-01-01

Simple sequence repeat (SSR) and Single Nucleotide Polymorphic (SNP), the two most robust markers for identifying rice varieties were compared for assessment of genetic diversity and population structure. Total 375 varieties of rice from various regions of India archived at the Indian National GeneBank, NBPGR, New Delhi, were analyzed using thirty six genetic markers, each of hypervariable SSR (HvSSR) and SNP which were distributed across 12 rice chromosomes. A total of 80 alleles were amplified with the SSR markers with an average of 2.22 alleles per locus whereas, 72 alleles were amplified with SNP markers. Polymorphic information content (PIC) values for HvSSR ranged from 0.04 to 0.5 with an average of 0.25. In the case of SNP markers, PIC values ranged from 0.03 to 0.37 with an average of 0.23. Genetic relatedness among the varieties was studied; utilizing an unrooted tree all the genotypes were grouped into three major clusters with both SSR and SNP markers. Analysis of molecular variance (AMOVA) indicated that maximum diversity was partitioned between and within individual level but not between populations. Principal coordinate analysis (PCoA) with SSR markers showed that genotypes were uniformly distributed across the two axes with 13.33% of cumulative variation whereas, in case of SNP markers varieties were grouped into three broad groups across two axes with 45.20% of cumulative variation. Population structure were tested using K values from 1 to 20, but there was no clear population structure, therefore Ln(PD) derived Δk was plotted against the K to determine the number of populations. In case of SSR maximum Δk was at K=5 whereas, in case of SNP maximum Δk was found at K=15, suggesting that resolution of population was higher with SNP markers, but SSR were more efficient for diversity analysis.

Novel Polymorphisms of Adrenergic, Alpha-1B-, Receptor and Peroxisome Proliferator-activated Receptor Gamma, Coactivator 1 Beta Genes and Their Association with Egg Production Traits in Local Chinese Dagu Hens

Directory of Open Access Journals (Sweden)

F. Mu

2016-09-01

Full Text Available Adrenergic, alpha-1B-, receptor (ADRA1B and peroxisome proliferator-activated receptor gamma, coactivator 1 beta (PPARGC1B genes are involved in regulation of hen ovarian development. In this study, these two genes were investigated as possible molecular markers associated with hen-housed egg production, egg weight (EW and body weight in Chinese Dagu hens. Samples were analyzed using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP technique, followed by sequencing analysis. Two novel single nucleotide polymorphisms (SNPs were identified within the candidate genes. Among them, an A/G transition at base position 1915 in exon 2 of ADRA1B gene and a T/C mutation at base position 6146 in the 3′-untranslated region (UTR of PPARGC1B gene were found to be polymorphic and named SNP A1915G and T6146C, respectively. The SNP A1915G (ADRA1B leads to a non-synonymous substitution (aspartic acid 489-to-glycine. The 360 birds from the Dagu population were divided into genotypes AA and AG, allele A was found to be present at a higher frequency. Furthermore, the AG genotype correlated with significantly higher hen-housed egg production (HHEP at 30, 43, 57, and 66 wks of age and with a higher EW at 30 and 43 wks (p<0.05. For the SNP T6146C (PPARGC1B, the hens were typed into TT and TC genotypes, with the T allele shown to be dominant. The TC genotype was also markedly correlated with higher HHEP at 57 and 66 wks of age and EW at 30 and 43 wks (p<0.05. Moreover, four haplotypes were reconstructed based on these two SNPs, with the AGTC haplotype found to be associated with the highest HHEP at 30 to 66 wks of age and with higher EW at 30 and 43 wks (p<0.05. Collectively, the two SNPs identified in this study might be used as potential genetic molecular markers favorable in the improvement of egg productivity in chicken breeding.

Mycobacterium leprae in Colombia described by SNP7614 in gyrA, two minisatellites and geography

Science.gov (United States)

Cardona-Castro, Nora; Beltrán-Alzate, Juan Camilo; Romero-Montoya, Irma Marcela; Li, Wei; Brennan, Patrick J; Vissa, Varalakshmi

2013-01-01

New cases of leprosy are still being detected in Colombia after the country declared achievement of the WHO defined ‘elimination’ status. To study the ecology of leprosy in endemic regions, a combination of geographic and molecular tools were applied for a group of 201 multibacillary patients including six multi-case families from eleven departments. The location (latitude and longitude) of patient residences were mapped. Slit skin smears and/or skin biopsies were collected and DNA was extracted. Standard agarose gel electrophoresis following a multiplex PCR-was developed for rapid and inexpensive strain typing of M. leprae based on copy numbers of two VNTR minisatellite loci 27-5 and 12-5. A SNP (C/T) in gyrA (SNP7614) was mapped by introducing a novel PCR-RFLP into an ongoing drug resistance surveillance effort. Multiple genotypes were detected combining the three molecular markers. The two frequent genotypes in Colombia were SNP7614(C)/27-5(5)/12-5(4) [C54] predominantly distributed in the Atlantic departments and SNP7614 (T)/27-5(4)/12-5(5) [T45] associated with the Andean departments. A novel genotype SNP7614 (C)/27-5(6)/12-5(4) [C64] was detected in cities along the Magdalena river which separates the Andean from Atlantic departments; a subset was further characterized showing association with a rare allele of minisatellite 23-3 and the SNP type 1 of M. leprae. The genotypes within intra-family cases were conserved. Overall, this is the first large scale study that utilized simple and rapid assay formats for identification of major strain types and their distribution in Colombia. It provides the framework for further strain type discrimination and geographic information systems as tools for tracing transmission of leprosy. PMID:23291420

Mycobacterium leprae in Colombia described by SNP7614 in gyrA, two minisatellites and geography.

Science.gov (United States)

Cardona-Castro, Nora; Beltrán-Alzate, Juan Camilo; Romero-Montoya, Irma Marcela; Li, Wei; Brennan, Patrick J; Vissa, Varalakshmi

2013-03-01

New cases of leprosy are still being detected in Colombia after the country declared achievement of the WHO defined 'elimination' status. To study the ecology of leprosy in endemic regions, a combination of geographic and molecular tools were applied for a group of 201 multibacillary patients including six multi-case families from eleven departments. The location (latitude and longitude) of patient residences were mapped. Slit skin smears and/or skin biopsies were collected and DNA was extracted. Standard agarose gel electrophoresis following a multiplex PCR-was developed for rapid and inexpensive strain typing of Mycobacterium leprae based on copy numbers of two VNTR minisatellite loci 27-5 and 12-5. A SNP (C/T) in gyrA (SNP7614) was mapped by introducing a novel PCR-RFLP into an ongoing drug resistance surveillance effort. Multiple genotypes were detected combining the three molecular markers. The two frequent genotypes in Colombia were SNP7614(C)/27-5(5)/12-5(4) [C54] predominantly distributed in the Atlantic departments and SNP7614 (T)/27-5(4)/12-5(5) [T45] associated with the Andean departments. A novel genotype SNP7614 (C)/27-5(6)/12-5(4) [C64] was detected in cities along the Magdalena river which separates the Andean from Atlantic departments; a subset was further characterized showing association with a rare allele of minisatellite 23-3 and the SNP type 1 of M. leprae. The genotypes within intra-family cases were conserved. Overall, this is the first large scale study that utilized simple and rapid assay formats for identification of major strain types and their distribution in Colombia. It provides the framework for further strain type discrimination and geographic information systems as tools for tracing transmission of leprosy. Copyright © 2012 Elsevier B.V. All rights reserved.

New infrared observations of IRS 1, IRS 3, and the adjacent nebula in the OMC-2 cluster

International Nuclear Information System (INIS)

Pendelton, Y.; Werner, M.; Dinerstein, H.

1984-01-01

Recent reports show that near infrared reflection nebulae are often observed around embedded protostellar objects. New observations are here reported of the infrared cluster of low luminosity protostars in Orion Molecular Cloud 2 (OMC2). It has been determined that the asymmetric distribution of the extended emission seen about IRS1 is in fact another infrared reflection nebula. Observations of near infrared polarimetry, photometry, and spectrophotometry were carried out at the NASA Infrared Telescope Facility October 1982 and January 1983. (author)

26 CFR 1.43-1 - The enhanced oil recovery credit-general rules.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 1 2010-04-01 2010-04-01 true The enhanced oil recovery credit-general rules. 1... INCOME TAXES Credits Against Tax § 1.43-1 The enhanced oil recovery credit—general rules. (a) Claiming the credit—(1) In general. The enhanced oil recovery credit (the “credit”) is a component of the...

Snap: an integrated SNP annotation platform

DEFF Research Database (Denmark)

Li, Shengting; Ma, Lijia; Li, Heng

2007-01-01

Snap (Single Nucleotide Polymorphism Annotation Platform) is a server designed to comprehensively analyze single genes and relationships between genes basing on SNPs in the human genome. The aim of the platform is to facilitate the study of SNP finding and analysis within the framework of medical...

Isolated Gramicidin Peptides Probed by IR Spectroscopy

NARCIS (Netherlands)

Rijs, A. M.; Kabelac, M.; Abo-Riziq, A.; Hobza, P.; de Vries, M. S.

2011-01-01

We report double-resonant IR/UV ion-dip spectroscopy of neutral gramicidin peptides in the gas phase. The IR spectra of gramicidin A and C, recorded in both the 1000 cm(-1) to 1800 cm(-1) and the 2700 to 3750 cm(-1) region, allow structural analysis. By studying this broad IR range, various local

GenBank blastn search result: AK064582 [KOME

Lifescience Database Archive (English)

Full Text Available AK064582 002-112-F03 AY007820.1 Daucus carota ATPase8 (ATP8) gene, ATP8-Sp1b allele, complete cds; chimeric... ATPase9 (ATP9) gene, ATP9-Sp3 allele, complete cds; and chimeric ATPase6 (ATP6) gen

A Nonsynonymous Polymorphism in IRS1 Modifies Risk of Developing Breast and Ovarian Cancers in BRCA1 and Ovarian Cancer in BRCA2 Mutation Carriers

NARCIS (Netherlands)

Ding, Yuan C.; McGuffog, Lesley; Healey, Sue; Friedman, Eitan; Laitman, Yael; Paluch-Shimon, Shani-; Kaufman, Bella; Liljegren, Annelie; Lindblom, Annika; Olsson, Håkan; Kristoffersson, Ulf; Stenmark-Askmalm, Marie; Melin, Beatrice; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Gronwald, Jacek; Huzarski, Tomasz; Cybulski, Cezary; Byrski, Tomasz; Osorio, Ana; Cajal, Teresa Ramóny; Stavropoulou, Alexandra V.; Benítez, Javier; Hamann, Ute; Rookus, Matti; Aalfs, Cora M.; de Lange, Judith L.; Meijers-Heijboer, Hanne E. J.; Oosterwijk, Jan C.; van Asperen, Christi J.; Gómez García, Encarna B.; Hoogerbrugge, Nicoline; Jager, Agnes; van der Luijt, Rob B.; Easton, Douglas F.; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; Evans, D. Gareth; Lalloo, Fiona; Izatt, Louise; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Cole, Trevor; Cook, Jackie; Brewer, Carole; Tischkowitz, Marc; Godwin, Andrew K.; Pathak, Harsh; Stoppa-Lyonnet, Dominique; Sinilnikova, Olga M.; Mazoyer, Sylvie; Barjhoux, Laure; Léoné, Mélanie; Gauthier-Villars, Marion; Caux-Moncoutier, Virginie; de Pauw, Antoine; Hardouin, Agnès; Berthet, Pascaline; Dreyfus, Hélène; Ferrer, Sandra Fert; Collonge-Rame, Marie-Agnès; Sokolowska, Johanna; Buys, Saundra; Daly, Mary; Miron, Alex; Terry, Mary Beth; Chung, Wendy; John, Esther M.; Southey, Melissa; Goldgar, David; Singer, Christian F.; tea, Muy-Kheng Maria; Gschwantler-Kaulich, Daphne; Fink-Retter, Anneliese; Hansen, Thomas V. O.; Ejlertsen, Bent; Johannsson, Oskar T.; Offit, Kenneth; Sarrel, Kara; Gaudet, Mia M.; Vijai, Joseph; Robson, Mark; Piedmonte, Marion R.; Andrews, Lesley; Cohn, David; DeMars, Leslie R.; DiSilvestro, Paul; Rodriguez, Gustavo; Toland, Amanda Ewart; Montagna, Marco; Agata, Simona; Imyanitov, Evgeny; Isaacs, Claudine; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Ignacio; Ramus, Susan J.; Sucheston, Lara; Karlan, Beth Y.; Gross, Jenny; Ganz, Patricia A.; Beattie, Mary S.; Schmutzler, Rita K.; Wappenschmidt, Barbara; Meindl, Alfons; Arnold, Norbert; Niederacher, Dieter; Preisler-Adams, Sabine; Gadzicki, Dorotehea; Varon-Mateeva, Raymonda; Deissler, Helmut; Gehrig, Andrea; Sutter, Christian; Kast, Karin; Nevanlinna, Heli; Aittomäki, Kristiina; Simard, Jacques; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Tomlinson, Gail E.; Weitzel, Jeffrey; Garber, Judy E.; Olopade, Olufunmilayo I.; Rubinstein, Wendy S.; Tung, Nadine; Blum, Joanne L.; Narod, Steven A.; Brummel, Sean; Gillen, Daniel L.; Lindor, Noralane; Fredericksen, Zachary; Pankratz, Vernon S.; Couch, Fergus J.; Radice, Paolo; Peterlongo, Paolo; Greene, Mark H.; Loud, Jennifer T.; Mai, Phuong L.; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Gerdes, Anne-Marie; Thomassen, Mads; Jensen, Uffe Birk; Skytte, Anne-Bine; Caligo, Maria A.; Lee, Andrew; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Neuhausen, Susan L.

2012-01-01

Background: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were

A Nonsynonymous Polymorphism in IRS1 Modifies Risk of Developing Breast and Ovarian Cancers in BRCA1 and Ovarian Cancer in BRCA2 Mutation Carriers.

NARCIS (Netherlands)

Ding, Y.C.; McGuffog, L.; Healey, S.; Friedman, E.; Laitman, Y.; Paluch-Shimon, S.; Kaufman, B.; Liljegren, A.; Lindblom, A.; Olsson, H.; Kristoffersson, U.; Stenmark-Askmalm, M.; Melin, B.; Domchek, S.M.; Nathanson, K.L.; Rebbeck, T.R.; Jakubowska, A.; Lubinski, J.; Jaworska, K.; Durda, K.; Gronwald, J.; Huzarski, T.; Cybulski, C.; Byrski, T.; Osorio, A.; Cajal, T.R.; Stavropoulou, A.V.; Benitez, J.; Hamann, U.; Rookus, M.; Aalfs, C.M.; Lange, J.L. de; Meijers-Heijboer, H.E.; Oosterwijk, J.C.; Asperen, C.J. van; Gomez Garcia, E.B.; Hoogerbrugge, N.; Jager, A.; Luijt, R.B. van der; Easton, D.F.; Peock, S.; Frost, D.; Ellis, S.D.; Platte, R.; Fineberg, E.; Evans, D.G.; Lalloo, F.; Izatt, L.; Eeles, R.; Adlard, J.; Davidson, R.; Eccles, D.; Cole, T.; Cook, J.; Brewer, C.; Tischkowitz, M.; Godwin, A.K.; Pathak, H.; Stoppa-Lyonnet, D.; Sinilnikova, O.M.; Mazoyer, S.; Barjhoux, L.; Leone, M.; Gauthier-Villars, M.; Caux-Moncoutier, V.; Pauw, A. de; Hardouin, A.; Berthet, P.; Dreyfus, H.; Ferrer, S.F.; Collonge-Rame, M.A.; Sokolowska, J.; Buys, S.; Daly, M.; Miron, A.; Terry, M.B.; Chung, W.; John, E.M.; Southey, M.; Goldgar, D.; Singer, C.F.; Tea, M.K.; Gschwantler-Kaulich, D.; Fink-Retter, A.; Hansen, T.V.; Ejlertsen, B.; Johannsson, O.T.; Offit, K.; Sarrel, K.; Gaudet, M.M.; Vijai, J.; Robson, M.; Piedmonte, M.R.; Andrews, L.; Cohn, D.; Demars, L.R.; Disilvestro, P.; Rodriguez, G.; Toland, A.E.; Montagna, M.; Agata, S.; Imyanitov, E.; Isaacs, C.; Janavicius, R.; Lazaro, C.; Blanco, I.; Ramus, S.J.; Sucheston, L.; Karlan, B.Y.; Gross, J.; Ganz, P.A.; Beattie, M.S.; Schmutzler, R.K.; Wappenschmidt, B.; Meindl, A.; Arnold, N.; Niederacher, D.; Preisler-Adams, S.; Gadzicki, D.; Varon-Mateeva, R.; Deissler, H.; Gehrig, A.; Sutter, C.; Kast, K.; Nevanlinna, H.; Aittomaki, K.; Simard, J.; Spurdle, A.B.; Beesley, J.; Chen, X.; Tomlinson, G.E.; Weitzel, J.; Garber, J.E.; Olopade, O.I.; Rubinstein, W.S.; Tung, N.; Blum, J.L.; Narod, S.A.; Brummel, S.; Gillen, D.L.; Lindor, N.; Fredericksen, Z.; Pankratz, V.S.; Couch, F.J.; Radice, P.; Peterlongo, P.; Greene, M.H.; Loud, J.T.; Mai, P.L.; Andrulis, I.L.; Glendon, G.; Ozcelik, H.; Gerdes, A.M.; Thomassen, M.; Jensen, U.B.; Skytte, A.B.; Caligo, M.A.; Lee, A.; Chenevix-Trench, G.; Antoniou, A.C.; Neuhausen, S.L.

2012-01-01

BACKGROUND: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were

A Nonsynonymous Polymorphism in IRS1 Modifies Risk of Developing Breast and Ovarian Cancers in BRCA1 and Ovarian Cancer in BRCA2 Mutation Carriers

NARCIS (Netherlands)

Ding, Yuan C.; McGuffog, Lesley; Healey, Sue; Friedman, Eitan; Laitman, Yael; Shani-Paluch-Shimon, [No Value; Kaufman, Bella; Liljegren, Annelie; Lindblom, Annika; Olsson, Hakan; Kristoffersson, Ulf; Stenmark-Askmalm, Marie; Melin, Beatrice; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Gronwald, Jacek; Huzarski, Tomasz; Cybulski, Cezary; Byrski, Tomasz; Osorio, Ana; Ramony Cajal, Teresa; Stavropoulou, Alexandra V.; Benitez, Javier; Hamann, Ute; Rookus, Matti; Aalfs, Cora M.; de Lange, Judith L.; Meijers-Heijboer, Hanne E. J.; Oosterwijk, Jan C.; van Asperen, Christi J.; Garcia, Encarna B. Gomez; Hoogerbrugge, Nicoline; Jager, Agnes; van der Luijt, Rob B.; Easton, Douglas F.; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; Evans, D. Gareth; Lalloo, Fiona; Izatt, Louise; Eeles, Ros; Adlard, Julian

Background: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were

A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers

NARCIS (Netherlands)

Y.C. Ding (Yuan); L. McGuffog (Lesley); S. Healey (Sue); E. Friedman (Eitan); Y. Laitman (Yael); S.-P. Shimon (Shani-Paluch); B. Kaufman (Bella); A. Liljegren (Annelie); A. Lindblom (Annika); H. Olsson; U. Kristoffersson (Ulf); M. Stenmark-Askmalm (M.); B. Melin (Beatrice); S.M. Domchek (Susan); K.L. Nathanson (Katherine); R. Rebbeck (Timothy); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska (Katarzyna); K. Durda (Katarzyna); J. Gronwald (Jacek); T. Huzarski (Tomasz); C. Cybulski (Cezary); T. Byrski (Tomasz); A. Osorio (Ana); T.R. Cajal; A. Stavropoulou (Alexandra); J. Benítez (Javier); U. Hamann (Ute); M.A. Rookus (Matti); C.M. Aalfs (Cora); J.L. de Lange (J.); E.J. Meijers-Heijboer (Hanne); J.C. Oosterwijk (Jan); C.J. van Asperen (Christi); E.B. Gómez García (Encarna); N. Hoogerbrugge (Nicoline); A. Jager (Agnes); R.B. van der Luijt (Rob); D.F. Easton (Douglas); S. Peock (Susan); D. Frost (Debra); S.D. Ellis (Steve); R. Platte (Radka); E. Fineberg (Elena); D.G. Evans (Gareth); F. Lalloo (Fiona); L. Izatt (Louise); R. Eeles (Rosalind); J.W. Adlard (Julian); R. Davidson (Rosemarie); D. Eccles (Diana); T.J. Cole (Trevor); J. Cook (Jackie); C. Brewer (Carole); M. Tischkowitz (Marc); A.K. Godwin (Andrew); S.S. Pathak; D. Stoppa-Lyonnet (Dominique); O. Sinilnikova (Olga); S. Mazoyer (Sylvie); L. Barjhoux (Laure); M. Léone (Mélanie); M. Gauthier-Villars (Marion); V. Caux-Moncoutier (Virginie); A. de Pauw (Antoine); A. Hardouin (Agnès); P. Berthet (Pascaline); H. Dreyfus (Hélène); S.F. Ferrer; M.-A. Collonge-Rame; J. Sokolowska (Johanna); S.S. Buys (Saundra); M.B. Daly (Mary); A. Miron (Alexander); M.-B. Terry (Mary-Beth); W. Chung (Wendy); E.M. John (Esther); M.C. Southey (Melissa); D. Goldgar (David); C.F. Singer (Christian); M.-K. Tea; D. Gschwantler-Kaulich (Daphne); A. Fink-Retter (Anneliese); T.V.O. Hansen (Thomas); B. Ejlertsen (Bent); O.T. Johannson (Oskar); K. Offit (Kenneth); K. Sarrel (Kara); M.M. Gaudet (Mia); J. Vijai (Joseph); M. Robson (Mark); M. Piedmonte (Marion); L. Andrews (Lesley); D.E. Cohn (David); L.R. DeMars (Leslie); P. DiSilvestro (Paul); G.C. Rodriguez (Gustavo); A.E. Toland (Amanda); M. Montagna (Marco); S. Agata (Simona); E.N. Imyanitov (Evgeny); C. Isaacs (Claudine); R. Janavicius (Ramunas); C. Lazaro (Conxi); I. Blanco (Ignacio); S.J. Ramus (Susan); L. Sucheston (Lara); B.Y. Karlan (Beth); J. Gross (Jenny); P.A. Ganz (Patricia); M.S. Beattie (Mary); R.K. Schmutzler (Rita); B. Wapenschmidt (Barbara); A. Meindl (Alfons); N. Arnold (Norbert); D. Niederacher (Dieter); S. Preisler-Adams (Sabine); D. Gadzicki (Dorothea); R. Varon-Mateeva (Raymonda); H. Deissler (Helmut); P.A. Gehrig (Paola A.); C. Sutter (Christian); K. Kast (Karin); H. Nevanlinna (Heli); K. Aittomäki (Kristiina); J. Simard (Jacques); A.B. Spurdle (Amanda); J. Beesley (Jonathan); X. Chen (Xiaoqing); G. Tomlinson (Gail); J.N. Weitzel (Jeffrey); J. Garber; O.I. Olopade (Olofunmilayo); W.S. Rubinstein (Wendy); N. Tung (Nadine); J.L. Blum (Joanne); S. Narod (Steven); S. Brummel (Sean); D.L. Gillen (Daniel); N.M. Lindor (Noralane); Z. Fredericksen (Zachary); V.S. Pankratz (Shane); F.J. Couch (Fergus); P. Radice (Paolo); P. Peterlongo (Paolo); M.H. Greene (Mark); J.T. Loud (Jennifer); P.L. Mai (Phuong); I.L. Andrulis (Irene); G. Glendon (Gord); H. Ozcelik (Hilmi); A-M. Gerdes (Anne-Marie); M. Thomassen (Mads); U.B. Jensen; A.-B. Skytte (Anne-Bine); M.A. Caligo (Maria); A. Lee (Andrew); G. Chenevix-Trench (Georgia); A.C. Antoniou (Antonis); S.L. Neuhausen (Susan)

2012-01-01

textabstractBackground: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk inwomen carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and

TIA: algorithms for development of identity-linked SNP islands for analysis by massively parallel DNA sequencing.

Science.gov (United States)

Farris, M Heath; Scott, Andrew R; Texter, Pamela A; Bartlett, Marta; Coleman, Patricia; Masters, David

2018-04-11

Single nucleotide polymorphisms (SNPs) located within the human genome have been shown to have utility as markers of identity in the differentiation of DNA from individual contributors. Massively parallel DNA sequencing (MPS) technologies and human genome SNP databases allow for the design of suites of identity-linked target regions, amenable to sequencing in a multiplexed and massively parallel manner. Therefore, tools are needed for leveraging the genotypic information found within SNP databases for the discovery of genomic targets that can be evaluated on MPS platforms. The SNP island target identification algorithm (TIA) was developed as a user-tunable system to leverage SNP information within databases. Using data within the 1000 Genomes Project SNP database, human genome regions were identified that contain globally ubiquitous identity-linked SNPs and that were responsive to targeted resequencing on MPS platforms. Algorithmic filters were used to exclude target regions that did not conform to user-tunable SNP island target characteristics. To validate the accuracy of TIA for discovering these identity-linked SNP islands within the human genome, SNP island target regions were amplified from 70 contributor genomic DNA samples using the polymerase chain reaction. Multiplexed amplicons were sequenced using the Illumina MiSeq platform, and the resulting sequences were analyzed for SNP variations. 166 putative identity-linked SNPs were targeted in the identified genomic regions. Of the 309 SNPs that provided discerning power across individual SNP profiles, 74 previously undefined SNPs were identified during evaluation of targets from individual genomes. Overall, DNA samples of 70 individuals were uniquely identified using a subset of the suite of identity-linked SNP islands. TIA offers a tunable genome search tool for the discovery of targeted genomic regions that are scalable in the population frequency and numbers of SNPs contained within the SNP island regions

Synthesis of 1-Substituted-4-(Pyridin-4-yl) [1,2,4] Triazolo [4,3-a ...

African Journals Online (AJOL)

Methods: The synthesized compounds were characterized by Infrared spectroscopy (IR), proton nuclear magnetic .... sodium hydroxide (1.2 mL, 20 molar) was added drop by drop ... carbonate (100 mg) was added and refluxed for. 18 h.

Quantification of within-sample genetic heterogeneity from SNP-array data

DEFF Research Database (Denmark)

Martinez, Pierre; Kimberley, Christopher; Birkbak, Nicolai Juul

2017-01-01

Intra-tumour genetic heterogeneity (ITH) fosters drug resistance and is a critical hurdle to clinical treatment. ITH can be well-measured using multi-region sampling but this is costly and challenging to implement. There is therefore a need for tools to estimate ITH in individual samples, using...... standard genomic data such as SNP-arrays, that could be implemented routinely. We designed two novel scores S and R, respectively based on the Shannon diversity index and Ripley's L statistic of spatial homogeneity, to quantify ITH in single SNP-array samples. We created in-silico and in-vitro mixtures...... sequencing data but heterogeneity in the fraction of tumour cells present across samples hampered accurate quantification. The prognostic potential of both scores was moderate but significantly predictive of survival in several tumour types (corrected p = 0.03). Our work thus shows how individual SNP...

Prolonged activation of S6K1 does not suppress IRS or PI-3 kinase signaling during muscle cell differentiation

Directory of Open Access Journals (Sweden)

MacKenzie Matthew G

2010-05-01

Full Text Available Abstract Background Myogenesis in C2C12 cells requires the activation of the PI3K/mTOR signaling pathways. Since mTOR signaling can feedback through S6K1 to inhibit the activation of PI3K, the aim of this work was to assess whether feedback from S6K1 played a role in myogenesis and determine whether siRNA mediated knockdown of S6K1 would lead to an increased rate of myotube formation. Results S6K1 activity increased in a linear fashion following plating and was more than 3-fold higher after Day 3 of differentiation (subconfluent = 11.09 ± 3.05, Day 3 = 29.34 ± 3.58. IRS-1 levels tended to increase upon serum withdrawal but decreased approximately 2-fold (subconfluent = 0.88 ± 0.10, Day 3 = 0.42 ± 0.06 3 days following differentiation whereas IRS-2 protein remained stable. IRS-1 associated p85 was significantly reduced upon serum withdrawal (subconfluent = 0.86 ± 0.07, Day 0 = 0.31 ± 0.05, remaining low through day 1. IRS-2 associated p85 decreased following serum withdrawal (subconfluent = 0.96 ± 0.05, Day 1 = 0.56 ± 0.08 and remained suppressed up to Day 3 following differentiation (0.56 ± 0.05. Phospho-tyrosine associated p85 increased significantly from subconfluent to Day 0 and remained elevated throughout differentiation. siRNA directed against S6K1 and S6K2 did not result in changes in IRS-1 levels after either 48 or 96 hrs. Furthermore, neither 48 nor 96 hrs of S6K1 knockdown caused a change in myotube formation. Conclusions Even though S6K1 activity increases throughout muscle cell differentiation and IRS-1 levels decrease over this period, siRNA suggests that S6K1 is not mediating the decrease in IRS-1. The decrease in IRS-1/2 associated p85 together with the increase in phospho-tyrosine associated p85 suggests that PI3K associates primarily with scaffolds other than IRS-1/2 during muscle cell differentiation.

SNP genetic polymorphisms of MDR-1, CYP1A2 and CYPB11 genes in four canine breeds upon toxicological evaluation.

Science.gov (United States)

Gagliardi, Rosa; Llambí, Silvia; Arruga, M Victoria

2015-01-01

The fields of pharmacogenetics and pharmacogenomics have become increasingly promising regarding the clinical application of genetic data to aid in prevention of adverse reactions. Specific screening tests can predict which animals express modified proteins or genetic sequences responsible for adverse effects associated with a drug. Among the genetic variations that have been investigated in dogs, the multidrug resistance gene (MDR) is the best studied. However, other genes such as CYP1A2 and CYP2B11 control the protein syntheses involved in the metabolism of many drugs. In the present study, the MDR-1, CYP1A2 and CYP2B11 genes were examined to identify SNP polymorphisms associated with these genes in the following four canine breeds: Uruguayan Cimarron, Border Collie, Labrador Retriever and German Shepherd. The results revealed that several SNPs of the CYP1A2 and CYP2B11 genes are potential targets for drug sensitivity investigations.

J3Gen: A PRNG for Low-Cost Passive RFID

Directory of Open Access Journals (Sweden)

Jordi Herrera-Joancomartí

2013-03-01

Full Text Available Pseudorandom number generation (PRNG is the main security tool in low-cost passive radio-frequency identification (RFID technologies, such as EPC Gen2. We present a lightweight PRNG design for low-cost passive RFID tags, named J3Gen. J3Gen is based on a linear feedback shift register (LFSR configured with multiple feedback polynomials. The polynomials are alternated during the generation of sequences via a physical source of randomness. J3Gen successfully handles the inherent linearity of LFSR based PRNGs and satisfies the statistical requirements imposed by the EPC Gen2 standard. A hardware implementation of J3Gen is presented and evaluated with regard to different design parameters, defining the key-equivalence security and nonlinearity of the design. The results of a SPICE simulation confirm the power-consumption suitability of the proposal.

Role of IRS-2 in insulin and cytokine signalling.

Science.gov (United States)

Sun, X J; Wang, L M; Zhang, Y; Yenush, L; Myers, M G; Glasheen, E; Lane, W S; Pierce, J H; White, M F

1995-09-14

The protein IRS-1 acts as an interface between signalling proteins with Src-homology-2 domains (SH2 proteins) and the receptors for insulin, IGF-1, growth hormone, several interleukins (IL-4, IL-9, IL-13) and other cytokines. It regulates gene expression and stimulates mitogenesis, and appears to mediate insulin/IGF-1-stimulated glucose transport. Thus, survival of the IRS-1-/- mouse with only mild resistance to insulin was surprising. This dilemma is provisionally resolved with our discovery of a second IRS-signalling protein. We purified and cloned a likely candidate called 4PS from myeloid progenitor cells and, because of its resemblance to IRS-1, we designate it IRS-2. Alignment of the sequences of IRS-2 and IRS-1 revealed a highly conserved amino terminus containing a pleckstrin-homology domain and a phosphotyrosine-binding domain, and a poorly conserved carboxy terminus containing several tyrosine phosphorylation motifs. IRS-2 is expressed in many cells, including tissues from IRS-1-/- mice, and may be essential for signalling by several receptor systems.

Overexpression of the essential Sis1 chaperone reduces TDP-43 effects on toxicity and proteolysis

Science.gov (United States)

Park, Sei-Kyoung; Hong, Joo Y.; Arslan, Fatih; Tietsort, Alex; Tank, Elizabeth M. H.; Li, Xingli

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by selective loss of motor neurons with inclusions frequently containing the RNA/DNA binding protein TDP-43. Using a yeast model of ALS exhibiting TDP-43 dependent toxicity, we now show that TDP-43 overexpression dramatically alters cell shape and reduces ubiquitin dependent proteolysis of a reporter construct. Furthermore, we show that an excess of the Hsp40 chaperone, Sis1, reduced TDP-43’s effect on toxicity, cell shape and proteolysis. The strength of these effects was influenced by the presence of the endogenous yeast prion, [PIN+]. Although overexpression of Sis1 altered the TDP-43 aggregation pattern, we did not detect physical association of Sis1 with TDP-43, suggesting the possibility of indirect effects on TDP-43 aggregation. Furthermore, overexpression of the mammalian Sis1 homologue, DNAJB1, relieves TDP-43 mediated toxicity in primary rodent cortical neurons, suggesting that Sis1 and its homologues may have neuroprotective effects in ALS. PMID:28531192

Measurements of the neutron electric to magnetic form-factor ratio GEn/GMn via the 2H((rvec e), e(prime)(rvec n)) 1H reaction to Q2 = 1.45-(GeV/c)2

International Nuclear Information System (INIS)

Bradley Plaster; A.Yu. Semenov; A. Aghalaryan; Erick Crouse; Glen MacLachlan; Shigeyuki Tajima; William Tireman; Abdellah Ahmidouch; Brian Anderson; Hartmuth Arenhovel; Razmik Asaturyan; O. Baker; Alan Baldwin; David Barkhuff; Herbert Breuer; Roger Carlini; Michael Christy; Steve Churchwell; Leon Cole; Samuel Danagoulian; Donal Day; T. Eden; Mostafa Elaasar; Rolf Ent; Manouchehr Farkhondeh; Howard Fenker; John Finn; Liping Gan; Ashot Gasparian; Kenneth Garrow; Paul Gueye; Calvin Howell; Bitao Hu; Mark Jones; James Kelly; Cynthia Keppel; Mahbubul Khandaker; Wooyoung Kim; Stanley Kowalski; Allison Lung; David Mack; Richard Madey; D. Manley; Pete Markowitz; Joseph Mitchell; Hamlet Mkrtchyan; Allena Opper; Charles Perdrisat; Vina Punjabi; Brian Raue; Tilmann Reichelt; Joerg Reinhold; Julie Roche; Yoshinori Sato; Nikolai Savvinov; Irina Semenova; Wonick Seo; Neven Simicevic; Gregory Smith; Stepan Stepanyan; Vardan Tadevosyan; Liguang Tang; Shawn Taylor; Paul Ulmer; William Vulcan; John Watson; Steven Wells; Frank Wesselmann; Stephen Wood; Seunghoon Yang; Lulin Yuan; Wei-Ming Zhang; Hong Guo Zhu; Xiaofeng Zhu

2006-01-01

We report values for the neutron electric to magnetic form factor ratio, G En /G Mn , deduced from measurements of the neutron's recoil polarization in the quasielastic 2 H((rvec e), e(prime)(rvec n)) 1 H reaction, at three Q 2 values of 0.45, 1.13, and 1.45 (GeV/c) 2 . The data at Q 2 = 1.13 and 1.45 (GeV/c) 2 are the first direct experimental measurements of GEn employing polarization degrees of freedom in the Q 2 > 1 (GeV/c) 2 region and stand as the most precise determinations of GEn for all values of Q 2

A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers

DEFF Research Database (Denmark)

Ding, Yuan C; McGuffog, Lesley; Healey, Sue

2012-01-01

We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated wit...

O impacto da genética na asma infantil

OpenAIRE

Pinto,Leonardo A.; Stein,Renato T.; Kabesch,Michael

2008-01-01

OBJETIVO: Apresentar os resultados dos estudos mais importantes e recentes sobre a genética da asma. Estes dados devem auxiliar os clínicos gerais a compreender o impacto da genética sobre este distúrbio complexo e como os genes e polimorfismos influenciam a asma e a atopia. FONTES DOS DADOS: Os dados foram coletados do banco de dados MEDLINE. Os estudos de associação genética foram selecionados do Genetic Association Database, um repositório de estudos de associação genética de doenças e dis...

ABCB1-Gen-Polymorphismus in einer polnischen Kohorte ist mit Risiko für bullöses Pemphigoid assoziiert.

Science.gov (United States)

Rychlik-Sych, Mariola; Barańska, Małgorzata; Dudarewicz, Michał; Skrętkowicz, Jadwiga; Żebrowska, Agnieszka; Owczarek, Jacek; Waszczykowska, Elżbieta

2017-05-01

Polymorphismen im ABCB1-Gen, das für das P-Glykoprotein kodiert, können die intrazelluläre Konzentration von Xenobiotika beeinflussen und so zur Entwicklung von Autoimmunerkrankungen, einschließlich des bullösen Pemphigoids (BP), beitragen. In der vorliegenden Studie sollte untersucht werden, ob in einer polnischen Kohorte die C3435T- und G2677T/A-Polymorphismen im ABCB1-Gen mit dem Risiko für ein BP assoziiert sind. Die Studie umfasste 71 Patienten mit BP und 156 gesunde Probanden. Der C3435T-Polymorphismus wurde mittels PCR-RFLP bestimmt und der G2677T/A-Polymorphismus mittels Allel-spezifischer PCR. Es gab zwar keine Korrelation zwischen dem C3435-Polymorphismus und dem BP-Risiko, aber wir konnten eine derartige Assoziation hinsichtlich des G2677T/A-Polymorphismus nachweisen. Das relative Risiko eines BP war bei Personen mit dem 2677TA-Genotyp um mehr als den Faktor fünf erhöht (OR = 5,52; p = 0,0063) und bei Trägern des 2677TT-Genotyps mehr als verdoppelt (OR = 2,40; p = 0,0076). Mit 2,40 (p = 0,000018) war die OR bei Trägern des 2677T-Allels ebenfalls erhöht. Die höhere Prävalenz des 2677GG-Genotyps und des 2677G-Allels bei der Kontrollgruppe sowie eine OR < 1,0 (0,22 beziehungsweise 0,33) legen eine Schutzfunktion des 2677G-Allels hinsichtlich der Ausbildung eines BP nahe. Die Ergebnisse der vorliegenden Studie zeigen, dass der G2677T/A-Polymorphismus im ABCB1-Gen das Risiko für die Entstehung eines BP beeinflussen könnte. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Alkali-developable silicone-based negative photoresist (SNP) for deep UV, electron beam, and X-ray lithographies

International Nuclear Information System (INIS)

Ban, Hiroshi; Tanaka, Akinobu; Kawai, Yoshio; Deguchi, Kimiyoshi

1989-01-01

A new silicone-based negative photoresist (SNP) developable with alkaline aqueous solutions is prepared. SNP composed of acetylated phenylsilsesquioxane oligomer and azidopyrene is applied to deep UV, electron beam (EB), and X-ray lithographies. SNP slightly swells in alkaline developers, thus exhibiting exceptionally high resolution characteristics for a negative resist. The resistance of SNP to oxygen reactive ion etching is approximately 30 times greater than that of conventional novolac resists. (author)

Gas phase UV and IR absorption spectra of CxF2x+1CHO (x=1-4)

DEFF Research Database (Denmark)

Hashikawa, Y; Kawasaki, M; Waterland, RL

2004-01-01

The UV and IR spectra of CxF2x+1 CHO (x = 1-4) were investigated using computational and experimental techniques. CxF2x+1CHO (x = 1-4) have broad UV absorption features centered at 300-310 nm. The maximum absorption cross-section increases significantly and shifts slightly to the red with increased...

Impulsive IR-multiphoton dissociation of acrolein: observation of non-statistical product vibrational excitation in CO ( v=1-12) by time resolved IR fluorescence spectroscopy

Science.gov (United States)

Chowdhury, P. K.

2000-10-01

On IR-multiphoton excitation, vibrationally highly excited acrolein molecules undergo concerted dissociation generating CO and ethylene. The vibrationally excited products, CO and ethylene, are detected immediately following the CO 2 laser pulse by observing IR fluorescence at 4.7 and 3.2 μm, respectively. The nascent CO is formed with significant vibrational excitation, with a Boltzmann population distribution for v=1-12 levels corresponding to T v=12 950±50 K. The average vibrational energy in the product CO is found to be 26 kcal mol -1, in contrast to its statistical share of 5 kcal mol -1, available from the product energy distribution. The nascent vibrationally excited ethylene either dissociates by absorbing further infrared laser photons from the tail of the CO 2 laser pulse or relaxes by collisional deactivation. Ethylene IR-fluorescence excitation spectrum showed a structure in the quasi-continuum, with a facile resonance at 10.53 μm corresponding to the 10P(14) CO 2 laser line, which explains the higher acetylene yield observed at a higher pressure. A hydrogen atom transfer mechanism followed by C-C impulsive break in the acrolein transition state may be responsible for such non-statistical product energy distribution.

A procedure for the detection of linkage with high density SNP arrays in a large pedigree with colorectal cancer

International Nuclear Information System (INIS)

Middeldorp, Anneke; Wijnen, Juul T; Wezel, Tom van; Jagmohan-Changur, Shantie; Helmer, Quinta; Klift, Heleen M van der; Tops, Carli MJ; Vasen, Hans FA; Devilee, Peter; Morreau, Hans; Houwing-Duistermaat, Jeanine J

2007-01-01

The apparent dominant model of colorectal cancer (CRC) inheritance in several large families, without mutations in known CRC susceptibility genes, suggests the presence of so far unidentified genes with strong or moderate effect on the development of CRC. Linkage analysis could lead to identification of susceptibility genes in such families. In comparison to classical linkage analysis with multi-allelic markers, single nucleotide polymorphism (SNP) arrays have increased information content and can be processed with higher throughput. Therefore, SNP arrays can be excellent tools for linkage analysis. However, the vast number of SNPs on the SNP arrays, combined with large informative pedigrees (e.g. >35–40 bits), presents us with a computational complexity that is challenging for existing statistical packages or even exceeds their capacity. We therefore setup a procedure for linkage analysis in large pedigrees and validated the method by genotyping using SNP arrays of a colorectal cancer family with a known MLH1 germ line mutation. Quality control of the genotype data was performed in Alohomora, Mega2 and SimWalk2, with removal of uninformative SNPs, Mendelian inconsistencies and Mendelian consistent errors, respectively. Linkage disequilibrium was measured by SNPLINK and Merlin. Parametric linkage analysis using two flanking markers was performed using MENDEL. For multipoint parametric linkage analysis and haplotype analysis, SimWalk2 was used. On chromosome 3, in the MLH1-region, a LOD score of 1.9 was found by parametric linkage analysis using two flanking markers. On chromosome 11 a small region with LOD 1.1 was also detected. Upon linkage disequilibrium removal, multipoint linkage analysis yielded a LOD score of 2.1 in the MLH1 region, whereas the LOD score dropped to negative values in the region on chromosome 11. Subsequent haplotype analysis in the MLH1 region perfectly matched the mutation status of the family members. We developed a workflow for linkage

IRS-1 serine phosphorylation and insulin resistance in skeletal muscle from pancreas tranplant recipient

DEFF Research Database (Denmark)

Bouzakri, K; Karlsson, HRK; Vestergaard, Henrik

2006-01-01

Insulin-dependent diabetic recipients of successful pancreas allografts achieve self-regulatory insulin secretion and discontinue exogenous insulin therapy; however, chronic hyperinsulinemia and impaired insulin sensitivity generally develop. To determine whether insulin resistance is accompanied...... by altered signal transduction, skeletal muscle biopsies were obtained from pancreas-kidney transplant recipients (n = 4), nondiabetic kidney transplant recipients (receiving the same immunosuppressive drugs; n = 5), and healthy subjects (n = 6) before and during a euglycemic-hyperinsulinemic clamp. Basal...... insulin receptor substrate (IRS)-1 Ser (312) and Ser (616) phosphorylation, IRS-1-associated phosphatidylinositol 3-kinase activity, and extracellular signal-regulated kinase (ERK)-1/2 phosphorylation were elevated in pancreas-kidney transplant recipients, coincident with fasting hyperinsulinemia. Basal...

IRS-1 serine phosphorylation and insulin resistance in skeletal muscle from pancreas transplant recipients

DEFF Research Database (Denmark)

Bouzakri, Karim; Karlsson, Håkan K R; Vestergaard, Henrik

2006-01-01

Insulin-dependent diabetic recipients of successful pancreas allografts achieve self-regulatory insulin secretion and discontinue exogenous insulin therapy; however, chronic hyperinsulinemia and impaired insulin sensitivity generally develop. To determine whether insulin resistance is accompanied...... by altered signal transduction, skeletal muscle biopsies were obtained from pancreas-kidney transplant recipients (n = 4), nondiabetic kidney transplant recipients (receiving the same immunosuppressive drugs; n = 5), and healthy subjects (n = 6) before and during a euglycemic-hyperinsulinemic clamp. Basal...... insulin receptor substrate (IRS)-1 Ser (312) and Ser (616) phosphorylation, IRS-1-associated phosphatidylinositol 3-kinase activity, and extracellular signal-regulated kinase (ERK)-1/2 phosphorylation were elevated in pancreas-kidney transplant recipients, coincident with fasting hyperinsulinemia. Basal...

c-Jun N-terminal kinase mediates AML1-ETO protein-induced connexin-43 expression

International Nuclear Information System (INIS)

Gao Fenghou; Wang Qiong; Wu Yingli; Li Xi; Zhao Kewen; Chen Guoqiang

2007-01-01

AML1-ETO fusion protein, a product of leukemia-related chromosomal translocation t(8;21), was reported to upregulate expression of connexin-43 (Cx43), a member of gap junction-constituted connexin family. However, its mechanism(s) remains unclear. By bioinformatic analysis, here we showed that there are two putative AML1-binding consensus sequences followed by two activated protein (AP)1 sites in the 5'-flanking region upstream to Cx43 gene. AML1-ETO could directly bind to these two AML1-binding sites in electrophoretic mobility shift assay, but luciferase reporter assay revealed that the AML1 binding sites were not indispensable for Cx43 induction by AML1-ETO protein. Conversely, AP1 sites exerted an important role in this event. In agreement, AML1-ETO overexpression in leukemic U937 cells activated c-Jun N-terminal kinase (JNK), while its specific inhibitor SP600125 effectively abrogated AML1-ETO-induced Cx43 expression, indicating that JNK signaling pathway contributes to AML1-ETO induced Cx43 expression. These results would shed new insights for understanding mechanisms of AML1-ETO-associated leukemogenesis

MID-IR LUMINOSITIES AND UV/OPTICAL STAR FORMATION RATES AT z < 1.4

International Nuclear Information System (INIS)

Salim, Samir; Dickinson, Mark; Michael Rich, R.; Charlot, Stephane; Lee, Janice C.; Schiminovich, David; Perez-Gonzalez, Pablo G.; Ashby, Matthew L. N.; Noeske, Kai; Papovich, Casey; Weiner, Benjamin J.; Faber, S. M.; Ivison, Rob J.; Frayer, David T.; Walton, Josiah M.; Chary, Ranga-Ram; Bundy, Kevin; Koekemoer, Anton M.

2009-01-01

Ultraviolet (UV) nonionizing continuum and mid-infrared (IR) emission constitute the basis of two widely used star formation (SF) indicators at intermediate and high redshifts. We study 2430 galaxies with z 10 -10 12 L sun ). We show that the IR luminosity can be estimated from the UV and optical photometry to within a factor of 2, implying that most z IR >10 11 L sun , yet with little current SF. For them a reasonable amount of dust absorption of stellar light (but presumably higher than in nearby early-type galaxies) is sufficient to produce the observed levels of IR, which includes a large contribution from intermediate and old stellar populations. In our sample, which contains very few ultraluminous IR galaxies, optical and X-ray active galactic nuclei do not contribute on average more than ∼50% to the mid-IR luminosity, and we see no evidence for a large population of 'IR excess' galaxies.

Oceanographic profile temperature, salinity and other measurements collected using bottle from the SNP-1 in the Coastal South Pacific and South Pacific in 1976 (NODC Accession 0001483)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Temperature profile, nutrients, and meteorological data were collected using bottle casts from the SNP-1 in the South Pacific Ocean. Data were collected from 24...

Genomewide high-density SNP linkage analysis of non-BRCA1/2 breast cancer families identifies various candidate regions and has greater power than microsatellite studies

NARCIS (Netherlands)

A. González-Neira (Anna); J.M. Rosa-Rosa; A. Osorio (Ana); E. Gonzalez (Emilio); M.C. Southey (Melissa); O. Sinilnikova (Olga); H. Lynch (Henry); R.A. Oldenburg (Rogier); C.J. van Asperen (Christi); N. Hoogerbrugge (Nicoline); G. Pita (Guillermo); P. Devilee (Peter); D. Goldgar (David); J. Benítez (Javier)

2007-01-01

textabstractBackground: The recent development of new high-throughput technologies for SNP genotyping has opened the possibility of taking a genome-wide linkage approach to the search for new candidate genes involved in heredity diseases. The two major breast cancer susceptibility genes BRCA1 and

BOOTES-IR: near IR follow-up GRB observations by a robotic system

International Nuclear Information System (INIS)

Castro-Tirado, A.J.; Postrigo, A. de Ugarte; Jelinek, M.

2005-01-01

BOOTES-IR is the extension of the BOOTES experiment, which operates in Southern Spain since 1998, to the near IR (NIR). The goal is to follow up the early stage of the gamma ray burst (GRB) afterglow emission in the NIR, alike BOOTES does already at optical wavelengths. The scientific case that drives the BOOTES-IR performance is the study of GRBs with the support of spacecraft like INTEGRAL, SWIFT and GLAST. Given that the afterglow emission in both, the NIR and the optical, in the instances immediately following a GRB, is extremely bright (reached V = 8.9 in one case), it should be possible to detect this prompt emission at NIR wavelengths too. The combined observations by BOOTES-IR and BOOTES-1 and BOOTES-2 will allow for real time identification of trustworthy candidates to have a high redshift (z > 5). It is expected that, few minutes after a GRB, the IR magnitudes be H ∼ 7-10, hence very high quality spectra can be obtained for objects as far as z = 10 by larger instruments

Identification of Pit-1 Gen Using PCR-RFLP of Padjadjaran Sheep and Evaluate of Growth Rate

Science.gov (United States)

Prajoga, S. B. K.; Andriani, L.; Subhandiana, H.

2018-02-01

The objectives of this research were to evaluate variation of Pit-1 gen of Padjadjaran Sheep and evaluate of their growth rate. The data comprised of 15 lambs female and 15 lambs male records of 0 - 12 mouths old lambs. Variation of Padjadjaran Sheep PIT-1 gen was analyzed using PCR-RFLP and used primer by 5’-GAGGGATAATTACAAATGGTCC-3’ and 5’-TGTTAACAGCTGTGGGACACAC-3’, length fragment analyse using HinfI restriction enzyme. Presence or absence of deference bands in a PCR fragment of the result can be distinguished by differences in the electrophoretic migration of the fragment. The result showed that the variation Pit1 gene showed that there was in the position 345 bp, 137 bp and 115 bp. In this experiment the difference migration did occur in all samples (monomorphic), that was amplificated with reverse and forward primer. The average male birth weight (BW), weaning weight (WN) and Yearling Weight (YW) was 2.29 ±0.42kg 8.96 ±1,89 kg and 30.12 ±5,65 kg. The average female birth weight (BW), weaning weight (WN) and Yearling Weight (YW) was 2.33 ±0.49 kg; 8.23 ±1.99 kg and 26.11 ±5.50 kg. Correlation value between age and body weight was 0,99 for female and 0,97 for male. The highest body weight gain per month was 2.85 kg for female at the age of six months and 3.4 kg for male at the age of one year. The best equition of growth rate was Ŷ = 1,862 + 0,127X1 0,076X2

SNP calling using genotype model selection on high-throughput sequencing data

KAUST Repository

You, Na

2012-01-16

Motivation: A review of the available single nucleotide polymorphism (SNP) calling procedures for Illumina high-throughput sequencing (HTS) platform data reveals that most rely mainly on base-calling and mapping qualities as sources of error when calling SNPs. Thus, errors not involved in base-calling or alignment, such as those in genomic sample preparation, are not accounted for.Results: A novel method of consensus and SNP calling, Genotype Model Selection (GeMS), is given which accounts for the errors that occur during the preparation of the genomic sample. Simulations and real data analyses indicate that GeMS has the best performance balance of sensitivity and positive predictive value among the tested SNP callers. © The Author 2012. Published by Oxford University Press. All rights reserved.

Variabilidade genética e estimativas de herdabilidade para o caráter germinação em matrizes de Albizia lebbeck Genetic variability and heritability estimates for the germination trait in Albizia lebbeck parent trees

Directory of Open Access Journals (Sweden)

Flávio Luiz Hilário Rego

2005-10-01

Full Text Available Em áreas rurais, buscam-se espécies arbóreas que apresentem rápido crescimento, habilidade para fixar nitrogênio e melhorar a estrutura do solo, especialmente em locais degradados, tendo usos múltiplos e facilidade para consórcio com culturas agrícolas. A Albizia lebbeck apresenta essas características. O presente estudo avaliou a variabilidade genética e estimou parâmetros genéticos em progênies de albizia para o caráter germinação. Sementes de 26 matrizes da espécie foram coletadas no município de Campo Grande, MS. Os testes de superação da dormência e germinação foram realizados no laboratório de Botânica da Universidade Católica Dom Bosco. O delineamento experimental foi o de blocos ao acaso, com cinco repetições e 15 plantas. As estimativas de herdabilidade no sentido amplo foram de 0,43 para indivíduos e 0,79 para média de matrizes, sugerindo expressivo controle genético. A seleção das 10 melhores matrizes proporcionou ganho genético de, pelo menos, 8,1%. Este germoplasma pode ser usado em programa de melhoramento genético para a espécie.Fast growing and nitrogen fixing forest trees species play an important role in rural areas, mainly in degraded lands, where they provide multiple purposes and facilities for intercropping with other crops. Albizia lebbeck is one of such species. This paper aimed at estimating the genetic variability for germination in a progeny test of this species. Seeds from 26 parent trees were collected in a site located at Campo Grande, MS. The germination tests were performed in the UCDB University under a randomised complete block design with five replications and 15 plants per plot. The broad sense heritability estimates were 0.43 and 0.79 at individual and parent tree mean levels, respectively, which denotes a moderate to high genetic control. Selection of the best 10 parents provided a genetic gain of 8.1%. This genetic resource can be used in a genetic improvement program for

The clinical application of single-sperm-based SNP haplotyping for PGD of osteogenesis imperfecta.

Science.gov (United States)

Chen, Linjun; Diao, Zhenyu; Xu, Zhipeng; Zhou, Jianjun; Yan, Guijun; Sun, Haixiang

2018-05-15

Osteogenesis imperfecta (OI) is a genetically heterogeneous disorder, presenting either autosomal dominant, autosomal recessive or X-linked inheritance patterns. The majority of OI cases are autosomal dominant and are caused by heterozygous mutations in either the COL1A1 or COL1A2 gene. In these dominant disorders, allele dropout (ADO) can lead to misdiagnosis in preimplantation genetic diagnosis (PGD). Polymorphic markers linked to the mutated genes have been used to establish haplotypes for identifying ADO and ensuring the accuracy of PGD. However, the haplotype of male patients cannot be determined without data from affected relatives. Here, we developed a method for single-sperm-based single-nucleotide polymorphism (SNP) haplotyping via next-generation sequencing (NGS) for the PGD of OI. After NGS, 10 informative polymorphic SNP markers located upstream and downstream of the COL1A1 gene and its pathogenic mutation site were linked to individual alleles in a single sperm from an affected male. After haplotyping, a normal blastocyst was transferred to the uterus for a subsequent frozen embryo transfer cycle. The accuracy of PGD was confirmed by amniocentesis at 19 weeks of gestation. A healthy infant weighing 4,250 g was born via vaginal delivery at the 40th week of gestation. Single-sperm-based SNP haplotyping can be applied for PGD of any monogenic disorders or de novo mutations in males in whom the haplotype of paternal mutations cannot be determined due to a lack of affected relatives. ADO: allele dropout; DI: dentinogenesis imperfect; ESHRE: European Society of Human Reproduction and Embryology; FET: frozen embryo transfer; gDNA: genomic DNA; ICSI: intracytoplasmic sperm injection; IVF: in vitro fertilization; MDA: multiple displacement amplification; NGS: next-generation sequencing; OI: osteogenesis imperfect; PBS: phosphate buffer saline; PCR: polymerase chain reaction; PGD: preimplantation genetic diagnosis; SNP: single-nucleotide polymorphism; STR

Calmodulin-like protein 3 is an estrogen receptor alpha coregulator for gene expression and drug response in a SNP, estrogen, and SERM-dependent fashion.

Science.gov (United States)

Qin, Sisi; Ingle, James N; Liu, Mohan; Yu, Jia; Wickerham, D Lawrence; Kubo, Michiaki; Weinshilboum, Richard M; Wang, Liewei

2017-08-18

We previously performed a case-control genome-wide association study in women treated with selective estrogen receptor modulators (SERMs) for breast cancer prevention and identified single nucleotide polymorphisms (SNPs) in ZNF423 as potential biomarkers for response to SERM therapy. The ZNF423rs9940645 SNP, which is approximately 200 bp away from the estrogen response elements, resulted in the SNP, estrogen, and SERM-dependent regulation of ZNF423 expression and, "downstream", that of BRCA1. Electrophoretic mobility shift assay-mass spectrometry was performed to identify proteins binding to the ZNF423 SNP and coordinating with estrogen receptor alpha (ERα). Clustered, regularly interspaced short palindromic repeats (CRISPR)/Cas9 genome editing was applied to generate ZR75-1 breast cancer cells with different ZNF423 SNP genotypes. Both cultured cells and mouse xenograft models with different ZNF423 SNP genotypes were used to study the cellular responses to SERMs and poly(ADP-ribose) polymerase (PARP) inhibitors. We identified calmodulin-like protein 3 (CALML3) as a key sensor of this SNP and a coregulator of ERα, which contributes to differential gene transcription regulation in an estrogen and SERM-dependent fashion. Furthermore, using CRISPR/Cas9-engineered ZR75-1 breast cancer cells with different ZNF423 SNP genotypes, striking differences in cellular responses to SERMs and PARP inhibitors, alone or in combination, were observed not only in cells but also in a mouse xenograft model. Our results have demonstrated the mechanism by which the ZNF423 rs9940645 SNP might regulate gene expression and drug response as well as its potential role in achieving more highly individualized breast cancer therapy.

Vascular endothelial growth factor gene polymorphisms in patients with colorectal cancer Polimorfismos del gen del factor de crecimiento vascular endotelial en pacientes con cáncer colorrectal

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M. Vidaurreta

2010-01-01

Full Text Available Background: angiogenesis plays an important role in tumor progression. The vascular endothelial growth factor (VEGF is an important regulator of angiogenesis. In the present study we evaluated single nucleotide polymorphisms (SNPs -2578C > A, -1154G > A, and +936C > T in the VEGF gene, and their prognostic value for patients operated on for colorectal cancer (CRC. Patients and method: VEGF polymorphisms have been analyzed in 177 patients who had undergone surgical resection at Hospital Clínico San Carlos. The analysis of these polymorphisms was performed with specific probes for each nucleotide in a multiplex reaction using real-time PCR. Results: we only found a statistically significant relationship for one of these three polymorphisms, +936C > T, with gender and tumor location; 10.7% of patients heterozygotes for this SNP had tumors located in proximal colon, 35.2% in distal segment and 54.1% in rectum (p = 0.03. Patients with the +936T/T genotype had 100% overall survival (OS. Conclusion: patients with a +936T/T genotype showed increased survival, therefore the +936C > T SNP could be a useful marker in the follow-up and clinical management of patients with colorectal cancer.Introducción: la angiogénesis juega un papel importante en la progresión de los tumores. El factor de crecimiento endotelial vascular (VEGF es un importante regulador de la angiogénesis. En este trabajo se han analizado los polimorfismos de único nucleó-tido (SNP -2578C > A, -1154G > A y +936C > T del gen VEGF en pacientes intervenidos de carcinoma colorrectal, así como su posible implicación pronóstica. Pacientes y método: el estudio de estos SNP se ha realizado en 177 pacientes intervenidos quirúrgicamente de carcinoma colorrectal (CCR en el Hospital Clínico San Carlos. El análisis de los polimorfismos se realizó con sondas específicas para cada nucleótido y se determinó mediante una reacción multiplex mediante real time PCR. Resultados: de los 3

Actividad del Sistema Renina-Angiotensina en relación con sus polimorfismos genéticos

OpenAIRE

Morcillo Hidalgo, Luis

2015-01-01

La realización del presente estudio sobre sujetos jóvenes y sanos no hipertensos tiene dos objetivos primordiales: El primero es analizar la relación de los polimorfismos de los genes del Sistema Renina-Angiotensina, el M235T del gen del angiotensinógeno, el Inserción/Delección del gen de la ECA y el A1166C del gen del receptor AT1 para la angiotensina II, con los niveles en plasma de angiotensina I, angiotensina II y angiotensina-(1-7), todas sustancias peptídicas activas del sistema E...

BRCA1 is expressed in uterine serous carcinoma (USC) and controls insulin-like growth factor I receptor (IGF-IR) gene expression in USC cell lines.

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Amichay, Keren; Kidron, Debora; Attias-Geva, Zohar; Schayek, Hagit; Sarfstein, Rive; Fishman, Ami; Werner, Haim; Bruchim, Ilan

2012-06-01

The insulin-like growth factor I receptor (IGF-IR) and BRCA1 affect cell growth and apoptosis. Little information is available about BRCA1 activity on the IGF signaling pathway. This study evaluated the effect of BRCA1 on IGF-IR expression. BRCA1 and IGF-IR immunohistochemistry on archival tissues (35 uterine serous carcinomas [USCs] and 17 metastases) were performed. USPC1 and USPC2 cell lines were transiently cotransfected with an IGF-IR promoter construct driving a luciferase reporter gene and a BRCA1 expression plasmid. Endogenous IGF-IR levels were evaluated by Western immunoblotting. We found high BRCA1 and IGF-IR protein expression in primary and metastatic USC tumors. All samples were immunostained for BRCA1-71% strongly stained; and 33/35 (94%) were stained positive for IGF-IR-2 (6%) strongly stained. No difference in BRCA1 and IGF-IR staining intensity was noted between BRCA1/2 mutation carriers and noncarriers. Metastatic tumors stained more intensely for BRCA1 than did the primary tumor site (P = 0.041) and with borderline significance for IGF-IR (P = 0.069). BRCA1 and IGF-IR staining did not correlate to survival. BRCA1 expression led to 35% and 54% reduction in IGF-IR promoter activity in the USPC1 and USCP2 cell lines, respectively. Western immunoblotting showed a decline in phosphorylated IGF-IR and phosphorylated AKT in both transiently and stably transfected cells. BRCA1 and IGF-IR are highly expressed in USC tumors. BRCA1 suppresses IGF-IR gene expression and activity. These findings suggest a possible biological link between the BRCA1 and the IGF-I signaling pathways in USC. The clinical implications of this association need to be explored.

A SNP resource for Douglas-fir: de novo transcriptome assembly and SNP detection and validation.

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Howe, Glenn T; Yu, Jianbin; Knaus, Brian; Cronn, Richard; Kolpak, Scott; Dolan, Peter; Lorenz, W Walter; Dean, Jeffrey F D

2013-02-28

Douglas-fir (Pseudotsuga menziesii), one of the most economically and ecologically important tree species in the world, also has one of the largest tree breeding programs. Although the coastal and interior varieties of Douglas-fir (vars. menziesii and glauca) are native to North America, the coastal variety is also widely planted for timber production in Europe, New Zealand, Australia, and Chile. Our main goal was to develop a SNP resource large enough to facilitate genomic selection in Douglas-fir breeding programs. To accomplish this, we developed a 454-based reference transcriptome for coastal Douglas-fir, annotated and evaluated the quality of the reference, identified putative SNPs, and then validated a sample of those SNPs using the Illumina Infinium genotyping platform. We assembled a reference transcriptome consisting of 25,002 isogroups (unique gene models) and 102,623 singletons from 2.76 million 454 and Sanger cDNA sequences from coastal Douglas-fir. We identified 278,979 unique SNPs by mapping the 454 and Sanger sequences to the reference, and by mapping four datasets of Illumina cDNA sequences from multiple seed sources, genotypes, and tissues. The Illumina datasets represented coastal Douglas-fir (64.00 and 13.41 million reads), interior Douglas-fir (80.45 million reads), and a Yakima population similar to interior Douglas-fir (8.99 million reads). We assayed 8067 SNPs on 260 trees using an Illumina Infinium SNP genotyping array. Of these SNPs, 5847 (72.5%) were called successfully and were polymorphic. Based on our validation efficiency, our SNP database may contain as many as ~200,000 true SNPs, and as many as ~69,000 SNPs that could be genotyped at ~20,000 gene loci using an Infinium II array-more SNPs than are needed to use genomic selection in tree breeding programs. Ultimately, these genomic resources will enhance Douglas-fir breeding and allow us to better understand landscape-scale patterns of genetic variation and potential responses to

Índices HOMA1-IR e HOMA2-IR para identificação de resistência à insulina e síndrome metabólica: Estudo Brasileiro de Síndrome Metabólica (BRAMS)

OpenAIRE

Geloneze, Bruno; Vasques, Ana Carolina Junqueira; Stabe, Christiane França Camargo; Pareja, José Carlos; Rosado, Lina Enriqueta Frandsen Paez de Lima; Queiroz, Elaine Cristina de; Tambascia, Marcos Antonio

2009-01-01

OBJECTIVE: To investigate cut-off values for HOMA1-IR and HOMA2-IR to identify insulin resistance (IR) and metabolic syndrome (MS), and to assess the association of the indexes with components of the MS. METHODS: Nondiabetic subjects from the Brazilian Metabolic Syndrome Study were studied (n = 1,203, 18 to 78 years). The cut-off values for IR were determined from the 90th percentile in the healthy group (n = 297) and, for MS, a ROC curve was generated for the total sample. RESULTS: In the he...

A novel approach to analyzing fMRI and SNP data via parallel independent component analysis

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Liu, Jingyu; Pearlson, Godfrey; Calhoun, Vince; Windemuth, Andreas

2007-03-01

There is current interest in understanding genetic influences on brain function in both the healthy and the disordered brain. Parallel independent component analysis, a new method for analyzing multimodal data, is proposed in this paper and applied to functional magnetic resonance imaging (fMRI) and a single nucleotide polymorphism (SNP) array. The method aims to identify the independent components of each modality and the relationship between the two modalities. We analyzed 92 participants, including 29 schizophrenia (SZ) patients, 13 unaffected SZ relatives, and 50 healthy controls. We found a correlation of 0.79 between one fMRI component and one SNP component. The fMRI component consists of activations in cingulate gyrus, multiple frontal gyri, and superior temporal gyrus. The related SNP component is contributed to significantly by 9 SNPs located in sets of genes, including those coding for apolipoprotein A-I, and C-III, malate dehydrogenase 1 and the gamma-aminobutyric acid alpha-2 receptor. A significant difference in the presences of this SNP component is found between the SZ group (SZ patients and their relatives) and the control group. In summary, we constructed a framework to identify the interactions between brain functional and genetic information; our findings provide new insight into understanding genetic influences on brain function in a common mental disorder.

A large-scale chromosome-specific SNP discovery guideline.

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Akpinar, Bala Ani; Lucas, Stuart; Budak, Hikmet

2017-01-01

Single-nucleotide polymorphisms (SNPs) are the most prevalent type of variation in genomes that are increasingly being used as molecular markers in diversity analyses, mapping and cloning of genes, and germplasm characterization. However, only a few studies reported large-scale SNP discovery in Aegilops tauschii, restricting their potential use as markers for the low-polymorphic D genome. Here, we report 68,592 SNPs found on the gene-related sequences of the 5D chromosome of Ae. tauschii genotype MvGB589 using genomic and transcriptomic sequences from seven Ae. tauschii accessions, including AL8/78, the only genotype for which a draft genome sequence is available at present. We also suggest a workflow to compare SNP positions in homologous regions on the 5D chromosome of Triticum aestivum, bread wheat, to mark single nucleotide variations between these closely related species. Overall, the identified SNPs define a density of 4.49 SNPs per kilobyte, among the highest reported for the genic regions of Ae. tauschii so far. To our knowledge, this study also presents the first chromosome-specific SNP catalog in Ae. tauschii that should facilitate the association of these SNPs with morphological traits on chromosome 5D to be ultimately targeted for wheat improvement.

Association test based on SNP set: logistic kernel machine based test vs. principal component analysis.

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Yang Zhao

Full Text Available GWAS has facilitated greatly the discovery of risk SNPs associated with complex diseases. Traditional methods analyze SNP individually and are limited by low power and reproducibility since correction for multiple comparisons is necessary. Several methods have been proposed based on grouping SNPs into SNP sets using biological knowledge and/or genomic features. In this article, we compare the linear kernel machine based test (LKM and principal components analysis based approach (PCA using simulated datasets under the scenarios of 0 to 3 causal SNPs, as well as simple and complex linkage disequilibrium (LD structures of the simulated regions. Our simulation study demonstrates that both LKM and PCA can control the type I error at the significance level of 0.05. If the causal SNP is in strong LD with the genotyped SNPs, both the PCA with a small number of principal components (PCs and the LKM with kernel of linear or identical-by-state function are valid tests. However, if the LD structure is complex, such as several LD blocks in the SNP set, or when the causal SNP is not in the LD block in which most of the genotyped SNPs reside, more PCs should be included to capture the information of the causal SNP. Simulation studies also demonstrate the ability of LKM and PCA to combine information from multiple causal SNPs and to provide increased power over individual SNP analysis. We also apply LKM and PCA to analyze two SNP sets extracted from an actual GWAS dataset on non-small cell lung cancer.

Casein SNP in Norwegian goats: additive and dominance effects on milk composition and quality

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2011-01-01

Background The four casein proteins in goat milk are encoded by four closely linked casein loci (CSN1S1, CSN2, CSN1S2 and CSN3) within 250 kb on caprine chromosome 6. A deletion in exon 12 of CSN1S1, so far reported only in Norwegian goats, has been found at high frequency (0.73). Such a high frequency is difficult to explain because the national breeding goal selects against the variant's effect. Methods In this study, 575 goats were genotyped for 38 Single Nucleotide Polymorphisms (SNP) located within the four casein genes. Milk production records of these goats were obtained from the Norwegian Dairy Goat Control. Test-day mixed models with additive and dominance fixed effects of single SNP were fitted in a model including polygenic effects. Results Significant additive effects of single SNP within CSN1S1 and CSN3 were found for fat % and protein %, milk yield and milk taste. The allele with the deletion showed additive and dominance effects on protein % and fat %, and overdominance effects on milk quantity (kg) and lactose %. At its current frequency, the observed dominance (overdominance) effects of the deletion allele reduced its substitution effect (and additive genetic variance available for selection) in the population substantially. Conclusions The selection pressure of conventional breeding on the allele with the deletion is limited due to the observed dominance (overdominance) effects. Inclusion of molecular information in the national breeding scheme will reduce the frequency of this deletion in the population. PMID:21864407

Polygenic analysis of genome-wide SNP data identifies common variants on allergic rhinitis

DEFF Research Database (Denmark)

Mohammadnejad, Afsaneh; Brasch-Andersen, Charlotte; Haagerup, Annette

Background: Allergic Rhinitis (AR) is a complex disorder that affects many people around the world. There is a high genetic contribution to the development of the AR, as twins and family studies have estimated heritability of more than 33%. Due to the complex nature of the disease, single SNP...... analysis has limited power in identifying the genetic variations for AR. We combined genome-wide association analysis (GWAS) with polygenic risk score (PRS) in exploring the genetic basis underlying the disease. Methods: We collected clinical data on 631 Danish subjects with AR cases consisting of 434...... sibling pairs and unrelated individuals and control subjects of 197 unrelated individuals. SNP genotyping was done by Affymetrix Genome-Wide Human SNP Array 5.0. SNP imputation was performed using "IMPUTE2". Using additive effect model, GWAS was conducted in discovery sample, the genotypes...

Mining and Analysis of SNP in Response to Salinity Stress in Upland Cotton (Gossypium hirsutum L.).

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Wang, Xiaoge; Lu, Xuke; Wang, Junjuan; Wang, Delong; Yin, Zujun; Fan, Weili; Wang, Shuai; Ye, Wuwei

2016-01-01

Salinity stress is a major abiotic factor that affects crop output, and as a pioneer crop in saline and alkaline land, salt tolerance study of cotton is particularly important. In our experiment, four salt-tolerance varieties with different salt tolerance indexes including CRI35 (65.04%), Kanghuanwei164 (56.19%), Zhong9807 (55.20%) and CRI44 (50.50%), as well as four salt-sensitive cotton varieties including Hengmian3 (48.21%), GK50 (40.20%), Xinyan96-48 (34.90%), ZhongS9612 (24.80%) were used as the materials. These materials were divided into salt-tolerant group (ST) and salt-sensitive group (SS). Illumina Cotton SNP 70K Chip was used to detect SNP in different cotton varieties. SNPv (SNP variation of the same seedling pre- and after- salt stress) in different varieties were screened; polymorphic SNP and SNPr (SNP related to salt tolerance) were obtained. Annotation and analysis of these SNPs showed that (1) the induction efficiency of salinity stress on SNPv of cotton materials with different salt tolerance index was different, in which the induction efficiency on salt-sensitive materials was significantly higher than that on salt-tolerant materials. The induction of salt stress on SNPv was obviously biased. (2) SNPv induced by salt stress may be related to the methylation changes under salt stress. (3) SNPr may influence salt tolerance of plants by affecting the expression of salt-tolerance related genes.

Synthesis and antimicrobial activity of 1-benzhydryl-sulfonyl-4-(3-(piperidin-4-yl) propyl)piperidine derivatives against pathogens of Lycopersicon esculentum: a structure-activity evaluation study.

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Vinaya, K; Kavitha, R; Ananda Kumar, C S; Benaka Prasad, S B; Chandrappa, S; Deepak, S A; Nanjunda Swamy, S; Umesha, S; Rangappa, K S

2009-01-01

Several 1-benzhydryl-sulfonyl-4-(3-(piperidin-4-yl)propyl)piperidine derivatives 8(a-j) were prepared by the treatment of substituted benzhydryl chlorides with 4-(3-(piperidin-4-yl)propyl)piperidine followed by N-sulfonation with sulfonyl chlorides in the presence of dry methylene dichloride and triethyl amine. The synthesized compounds were characterized by (1)H-NMR, IR, and elemental analysis. All the synthesized compounds were evaluated in vitro for their efficacy as antimicrobial agents by artificial inoculation technique against standard strains of two important bacterial viz., Xanthomonas axonopodis pv. vesicatoria and Ralstonia solanacearum as well as and two fungal pathogens namely Alternaria solani and Fusarium solani of tomato plants. We have briefly investigated the structure-activity relation studies and reveal that the nature of substitutions on benzhydryl ring and sulfonamide ring influences the antibacterial activity. Among the synthesized new compounds 8b, 8d, 8g, 8h, 8i, and 8j were showed significant potent antimicrobial activities compared to the standard drugs chloramphenicol, mancozeb.

Development of Cytoplasmic Male Sterile IR24 and IR64 Using CW-CMS/Rf17 System.

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Toriyama, Kinya; Kazama, Tomohiko

2016-12-01

A wild-abortive-type (WA) cytoplasmic male sterility (CMS) has been almost exclusively used for breeding three-line hybrid rice. Many indica cultivars are known to carry restorer genes for WA-CMS lines and cannot be used as maintainer lines. Especially elite indica cultivars IR24 and IR64 are known to be restorer lines for WA-CMS lines, and are used as male parents for hybrid seed production. If we develop CMS IR24 and CMS IR64, the combination of F1 pairs in hybrid rice breeding programs will be greatly broadened. For production of CMS lines and restorer lines of IR24 and IR64, we employed Chinese wild rice (CW)-type CMS/Restorer of fertility 17 (Rf17) system, in which fertility is restored by a single nuclear gene, Rf17. Successive backcrossing and marker-assisted selection of Rf17 succeeded to produce completely male sterile CMS lines and fully restored restorer lines of IR24 and IR64. CW-cytoplasm did not affect agronomic characteristics. Since IR64 is one of the most popular mega-varieties and used for breeding of many modern varieties, the CW-CMS line of IR64 will be useful for hybrid rice breeding.

HLA-C -35kb expression SNP is associated with differential control of β-HPV infection in squamous cell carcinoma cases and controls.

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Karin A Vineretsky

Full Text Available A single nucleotide polymorphism (SNP 35 kb upstream of the HLA-C gene is associated with HLA-C expression, and the high expressing genotype (CC has been associated with HIV-I control. HLA-C is unique among the classical MHC class I molecules for its role in the control of viral infections and recognition of abnormal or missing self. This immunosurveillance is central to the pathogenesis of non-melanoma skin cancer (NMSC, and of squamous cell carcinoma (SCC in particular. While sun exposure is a major risk factor for these cancers, cutaneous infections with genus β-HPV have been implicated in the development of SCC. We hypothesized that the high expression HLA-C genotype is associated with β-HPV infections. Therefore, we investigated the association between β-HPV serology and the -35 kb SNP (rs9264942 in a population-based case-control study of 510 SCC cases and 608 controls. Among controls, the high expression -35 kb SNP genotype (CC reduced the likelihood of positive serology for multiple (≥2 β-HPV infections (OR = 0.49, 95% CI: 0.25-0.97, and β-HPV species 2 infection (OR = 0.43, 95% CI: 0.23-0.79. However, no association with β-HPV status was observed among SCC cases. Our findings suggest that underlying immunogenotype plays an important role in differential control of β-HPV in SCC cases and controls.

High-throughput SNP genotyping in the highly heterozygous genome of Eucalyptus: assay success, polymorphism and transferability across species

Science.gov (United States)

2011-01-01

Background High-throughput SNP genotyping has become an essential requirement for molecular breeding and population genomics studies in plant species. Large scale SNP developments have been reported for several mainstream crops. A growing interest now exists to expand the speed and resolution of genetic analysis to outbred species with highly heterozygous genomes. When nucleotide diversity is high, a refined diagnosis of the target SNP sequence context is needed to convert queried SNPs into high-quality genotypes using the Golden Gate Genotyping Technology (GGGT). This issue becomes exacerbated when attempting to transfer SNPs across species, a scarcely explored topic in plants, and likely to become significant for population genomics and inter specific breeding applications in less domesticated and less funded plant genera. Results We have successfully developed the first set of 768 SNPs assayed by the GGGT for the highly heterozygous genome of Eucalyptus from a mixed Sanger/454 database with 1,164,695 ESTs and the preliminary 4.5X draft genome sequence for E. grandis. A systematic assessment of in silico SNP filtering requirements showed that stringent constraints on the SNP surrounding sequences have a significant impact on SNP genotyping performance and polymorphism. SNP assay success was high for the 288 SNPs selected with more rigorous in silico constraints; 93% of them provided high quality genotype calls and 71% of them were polymorphic in a diverse panel of 96 individuals of five different species. SNP reliability was high across nine Eucalyptus species belonging to three sections within subgenus Symphomyrtus and still satisfactory across species of two additional subgenera, although polymorphism declined as phylogenetic distance increased. Conclusions This study indicates that the GGGT performs well both within and across species of Eucalyptus notwithstanding its nucleotide diversity ≥2%. The development of a much larger array of informative SNPs across

A high resolution photoemission study of surface core-level shifts in clean and oxygen-covered Ir(2 1 0) surfaces

Energy Technology Data Exchange (ETDEWEB)

Gladys, M.J.; Ermanoski, I.; Jackson, G.; Quinton, J.S.; Rowe, J.E.; Madey, T.E. E-mail: madey@physics.rutgers.edu

2004-04-01

High resolution soft X-ray photoemission electron spectroscopy (SXPS), using synchrotron radiation, is employed to investigate 4f core-level features of four differently-prepared Ir(2 1 0) surfaces: clean planar, oxygen-covered planar, oxygen-induced faceted, and clean faceted surfaces. Surface and bulk peak identifications are supported by measurements at different photon energies (thus probing different electron escape depths) and variable emission angles. Iridium 4f{sub 7/2} photoemission spectra are fitted with Doniach-Sunjic lineshapes. The surface components are identified with core levels positioned at lower binding energies than the bulk components, in contrast to previous reports of binding energy inversion on Ir(1 0 0) (1x1) and (5x1) surfaces. For clean planar Ir(2 1 0) three surface Ir 4f{sub 7/2} features are observed with core-level shifts of -765, -529, and -281 meV, with respect to the bulk; these are associated with the first, second and third layers of atoms, respectively, for atomically rough Ir(2 1 0). Adsorption of oxygen onto the planar Ir(2 1 0) surface is found to cause a suppression and shift of the surface features to higher binding energies. Annealing at T{>=}600 K in oxygen produces a faceted surface as verified by low energy electron diffraction (LEED). A comparison of planar and faceted oxygen-covered surfaces reveals minor differences in the normal emission SXPS spectra, while grazing emission spectra exhibit differences. The SXPS spectrum of the clean, faceted Ir(2 1 0) exhibits small differences in comparison to the clean planar case, with surface features having binding energy shifts of -710, -450, and -230 meV.