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Sample records for functional variants meat

  1. Improving functional value of meat products.

    Science.gov (United States)

    Zhang, Wangang; Xiao, Shan; Samaraweera, Himali; Lee, Eun Joo; Ahn, Dong U

    2010-09-01

    In recent years, much attention has been paid to develop meat and meat products with physiological functions to promote health conditions and prevent the risk of diseases. This review focuses on strategies to improve the functional value of meat and meat products. Value improvement can be realized by adding functional compounds including conjugated linoneleic acid, vitamin E, n3 fatty acids and selenium in animal diets to improve animal production, carcass composition and fresh meat quality. In addition, functional ingredients such as vegetable proteins, dietary fibers, herbs and spices, and lactic acid bacteria can be directly incorporated into meat products during processing to improve their functional value for consumers. Functional compounds, especially peptides, can also be generated from meat and meat products during processing such as fermentation, curing and aging, and enzymatic hydrolysis. This review further discusses the current status, consumer acceptance, and market for functional foods from the global viewpoints. Future prospects for functional meat and meat products are also discussed.

  2. Functional Meat and Meat Products: An Overview

    OpenAIRE

    Arun Kumar; Satish Kumar; B.D. Sharma; S.K. Mendiratta; Om Prakash Verma; Arun Kumar Patel

    2012-01-01

    A food can be regarded as functional if it is satisfactorily demonstrated to beneficially affect one or more target functions in the body, beyond adequate nutritional effects, in a way that is relevant to either improved health or well-being and/or to a reduction in the risk of disease. They are very important for health and are classified on various basis such as Supplementation of functional ingredients in diets of animals which includes Conjugated linoleic acid, Vitamin E, Omega-3 (ω3) fat...

  3. Bioactive Compounds in Functional Meat Products

    Directory of Open Access Journals (Sweden)

    Ewelina Pogorzelska-Nowicka

    2018-01-01

    Full Text Available Meat and meat products are a good source of bioactive compounds with positive effect on human health such as vitamins, minerals, peptides or fatty acids. Growing food consumer awareness and intensified global meat producers competition puts pressure on creating new healthier meat products. In order to meet these expectations, producers use supplements with functional properties for animal diet and as direct additives for meat products. In the presented work seven groups of key functional constituents were chosen: (i fatty acids; (ii minerals; (iii vitamins; (iv plant antioxidants; (v dietary fibers; (vi probiotics and (vii bioactive peptides. Each of them is discussed in term of their impact on human health as well as some quality attributes of the final products.

  4. Perspectives in production of functional meat products

    Science.gov (United States)

    Vasilev, D.; Glišić, M.; Janković, V.; Dimitrijević, M.; Karabasil, N.; Suvajdžić, B.; Teodorović, V.

    2017-09-01

    The meat industry has met new challenges since the World Health Organization classified processed meat in carcinogenic Group 1. In relation to this, the functional food concept in meat processing has gained importance, especially in reducing carcinogenic N-nitroso compounds and polycyclic aromatic hydrocarbons (PAHs) as an additional imperative, apart from the usual fat and salt reduction and product enrichment with functional ingredients. PAH reduction relies on control of the smoking process, but there is also a possibility they could be degraded by means of probiotic microorganisms or spices. The reduction of N-nitroso compounds could be provided by lowering the amount of added nitrite/nitrate, using substitutes for these chemicals, and/or by preventing conditions for the creation of N-nitroso compounds. Nevertheless, fat and salt reductions still remain topical, and rely mostly on the use of functional ingredients as their substitutes.

  5. Development and assessment of healthy properties of meat and meat products designed as functional foods.

    Science.gov (United States)

    Olmedilla-Alonso, Begoña; Jiménez-Colmenero, Francisco; Sánchez-Muniz, Francisco J

    2013-12-01

    This review deals with the two major aspects to be considered in the context of meat-based functional foods and human health. One involves the different strategies used to improve (increase or reduce) the presence of bioactive (healthy and unhealthy) compounds in meat and meat products in order to develop potential meat-based functional foods; these strategies are basically concerned with animal production practices, meat processing and storage, distribution and consumption conditions. Since the link between the consumption of those foods and their potentially beneficial effects (improving health and/or reducing the risk of several chronic diseases) needs to be demonstrated scientifically, the second aspect considered is related to intervention studies to examine the functional capacity of meat-based potentially functional foods in humans, discussing how the functionality of a food can be assessed in terms of its effects on health in relation to both target body functions and risk factors. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Genome-wide characterization of genetic variants and putative regions under selection in meat and egg-type chicken lines.

    Science.gov (United States)

    Boschiero, Clarissa; Moreira, Gabriel Costa Monteiro; Gheyas, Almas Ara; Godoy, Thaís Fernanda; Gasparin, Gustavo; Mariani, Pilar Drummond Sampaio Corrêa; Paduan, Marcela; Cesar, Aline Silva Mello; Ledur, Mônica Corrêa; Coutinho, Luiz Lehmann

    2018-01-25

    Meat and egg-type chickens have been selected for several generations for different traits. Artificial and natural selection for different phenotypes can change frequency of genetic variants, leaving particular genomic footprints throghtout the genome. Thus, the aims of this study were to sequence 28 chickens from two Brazilian lines (meat and white egg-type) and use this information to characterize genome-wide genetic variations, identify putative regions under selection using Fst method, and find putative pathways under selection. A total of 13.93 million SNPs and 1.36 million INDELs were identified, with more variants detected from the broiler (meat-type) line. Although most were located in non-coding regions, we identified 7255 intolerant non-synonymous SNPs, 512 stopgain/loss SNPs, 1381 frameshift and 1094 non-frameshift INDELs that may alter protein functions. Genes harboring intolerant non-synonymous SNPs affected metabolic pathways related mainly to reproduction and endocrine systems in the white-egg layer line, and lipid metabolism and metabolic diseases in the broiler line. Fst analysis in sliding windows, using SNPs and INDELs separately, identified over 300 putative regions of selection overlapping with more than 250 genes. For the first time in chicken, INDEL variants were considered for selection signature analysis, showing high level of correlation in results between SNP and INDEL data. The putative regions of selection signatures revealed interesting candidate genes and pathways related to important phenotypic traits in chicken, such as lipid metabolism, growth, reproduction, and cardiac development. In this study, Fst method was applied to identify high confidence putative regions under selection, providing novel insights into selection footprints that can help elucidate the functional mechanisms underlying different phenotypic traits relevant to meat and egg-type chicken lines. In addition, we generated a large catalog of line-specific and common

  7. The role of rabbit meat as functional food.

    Science.gov (United States)

    Dalle Zotte, Antonella; Szendro, Zsolt

    2011-07-01

    Increasing consumer knowledge of the link between diet and health has raised the awareness and demand for functional food ingredients. Meat and its derivatives may be considered functional foods to the extent that they contain numerous compounds thought to be functional. This review will attempt to outline the excellent nutritional and dietetic properties of rabbit meat and offer an overview of the studies performed on the strategies adopted to improve the functional value of rabbit meat. Dietary manipulation has been seen to be very effective in increasing the levels of essential FA, EPA, DHA, CLA, branched chain FA, vitamin E, and selenium in rabbit meat. Dietary fortification with vitamin E or natural products such as oregano essential oil, chia seed oil, and Spirulina platensis microalga seem promising in improving the oxidative stability of rabbit meat while also adding functional ingredients. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Vegetable fats and oils as functional ingredients in meat products

    Directory of Open Access Journals (Sweden)

    Alfonso Totosaus

    2011-12-01

    Full Text Available Sausages are a widely consumed food in México, and due to their low fat content (ca. 10% they can be employed to enrich diet by including functional or nutraceutic ingredients as vegetable fats and oils. The replace or incorporation of vegetable fats or oils in cooked sausages is a way to improve their nutritional profile to offer functional meat products.

  9. A combination of two variants in PRKAG3 is needed for a positive effect on meat quality in pigs.

    Science.gov (United States)

    Uimari, Pekka; Sironen, Anu

    2014-02-28

    Color and pH of meat measured 24 h post mortem are common selection objectives in pig breeding programs. Several amino acid substitutions in PRKAG3 have been associated with various meat quality traits. In our previous study ASGA0070625, a SNP next to PRKAG3, had the most significant association with meat quality traits in the Finnish Yorkshire. However, the known amino acid substitutions, including I199V, did not show any association. The aims of this study were to characterize further variation in PRKAG3 and its promoter region, and to test the association between these variants and the pH and color of pork meat. The data comprised of 220 Finnish Landrace and 230 Finnish Yorkshire artificial insemination boars with progeny information. We sequenced the coding and promoter region of PRKAG3 in these and in three additional wild boars. Genotypes from our previous genome-wide scans were also included in the data. Association between SNPs or haplotypes and meat quality traits (deregressed estimates of breeding values from Finnish national breeding value estimation for pH, color lightness and redness measured from loin or ham) was tested using a linear regression model. Sequencing revealed several novel amino acid substitutions in PRKAG3, including K24E, I41V, K131R, and P134L. Linkage disequilibrium was strong among the novel variants, SNPs in the promoter region and ASGA0070625, especially for the Yorkshire. The strongest associations were observed between ASGA0070625 and the SNPs in the promoter region and pH measured from loin in the Yorkshire and between I199V and pH measured from ham in the Landrace. In contrast, ASGA0070625 was not significantly associated with meat quality traits in the Landrace and I199V not in the Yorkshire. Haplotype analysis showed a significant association between a haplotype consisting of 199I and 24E alleles (or g.-157C or g.-58A alleles in the promoter region) and pH measured from loin and ham in both breeds (P-values varied from 1.72

  10. Association analysis of CAPN1 gene variants with carcass and meat ...

    African Journals Online (AJOL)

    ajl yemi

    2011-11-28

    Nov 28, 2011 ... the cattle industry. Key words: Bovine, CAPN1 gene, Carcass and meat quality traits, SNPs. INTRODUCTION. Carcass and meat quality traits, which are influenced by multiple ... value assessment of beef cattle industry. Selection of ..... tenderness marker test to include cattle of Bos indicus, Bos taurus,.

  11. Assessment of Functional Effects of Unclassified Genetic Variants

    NARCIS (Netherlands)

    Couch, Fergus J.; Rasmussen, Lene Juel; Hofstra, Robert; Monteiro, Alvaro N. A.; Greenblatt, Marc S.; de Wind, Niels

    2008-01-01

    Inherited predisposition to disease is often linked to reduced activity of a disease associated gene product. Thus, quantitation of the influence of inherited variants on gene function can potentially be used to predict the disease relevance of these variants. While many disease genes have been

  12. Gain-of-function HCN2 variants in genetic epilepsy.

    Science.gov (United States)

    Li, Melody; Maljevic, Snezana; Phillips, A Marie; Petrovski, Slave; Hildebrand, Michael S; Burgess, Rosemary; Mount, Therese; Zara, Federico; Striano, Pasquale; Schubert, Julian; Thiele, Holger; Nürnberg, Peter; Wong, Michael; Weisenberg, Judith L; Thio, Liu Lin; Lerche, Holger; Scheffer, Ingrid E; Berkovic, Samuel F; Petrou, Steven; Reid, Christopher A

    2018-02-01

    Genetic generalized epilepsy (GGE) is a common epilepsy syndrome that encompasses seizure disorders characterized by spike-and-wave discharges (SWDs). Pacemaker hyperpolarization-activated cyclic nucleotide-gated channels (HCN) are considered integral to SWD genesis, making them an ideal gene candidate for GGE. We identified HCN2 missense variants from a large cohort of 585 GGE patients, recruited by the Epilepsy Phenome-Genome Project (EPGP), and performed functional analysis using two-electrode voltage clamp recordings from Xenopus oocytes. The p.S632W variant was identified in a patient with idiopathic photosensitive occipital epilepsy and segregated in the family. This variant was also independently identified in an unrelated patient with childhood absence seizures from a European cohort of 238 familial GGE cases. The p.V246M variant was identified in a patient with photo-sensitive GGE and his father diagnosed with juvenile myoclonic epilepsy. Functional studies revealed that both p.S632W and p.V246M had an identical functional impact including a depolarizing shift in the voltage dependence of activation that is consistent with a gain-of-function. In contrast, no biophysical changes resulted from the introduction of common population variants, p.E280K and p.A705T, and the p.R756C variant from EPGP that did not segregate with disease. Our data suggest that HCN2 variants can confer susceptibility to GGE via a gain-of-function mechanism. © 2017 Wiley Periodicals, Inc.

  13. Association analysis of CAPN1 gene variants with carcass and meat ...

    African Journals Online (AJOL)

    In this study, two single nucleotide polymorphisms (SNPs) A3717G and A3854G of bovine CAPN1 gene were predicted and identified by bioinformatics and DNA sequencing methods. Furthermore, the association between the genetic polymorphisms of SNPs and meat quality characteristics of beef was analyzed. Statistical ...

  14. Association of MC4R gene variants with carcass and meat quality ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-08-04

    Aug 4, 2009 ... meat tenderness (MT). DNA samples were extracted from leu- kocytes and tissue samples according to Mullenbach et al. (1989). SNP identification and genotyping. According to the sequence of bovine the MC4R gene (GenBank accession No. NW_001494269.1), three pairs of primers were de- signed to ...

  15. Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants.

    Directory of Open Access Journals (Sweden)

    Mengmeng Du

    Full Text Available Genome-wide association studies (GWAS have identified many common single nucleotide polymorphisms (SNPs associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs. We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33. We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s.

  16. Genetic variants associated with lung function

    DEFF Research Database (Denmark)

    Thyagarajan, Bharat; Wojczynski, Mary; Minster, Ryan L

    2014-01-01

    ) associated with FEV1/FVC, none of which were replicated in the CHARGE/SpiroMeta consortia. Using linkage analysis, we identified a novel linkage peak in chromosome 2 at 219 cM for FEV1/FVC (LOD: 3.29) and confirmed a previously reported linkage peak in chromosome 6 at 28 cM (LOD: 3.33) for FEV1. CONCLUSION......: Future studies need to identify the rare genetic variants underlying the linkage peak in chromosome 6 for FEV1....

  17. A Functional Assay for Sick Sinus Syndrome Genetic Variants

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    Chuanchau J. Jou

    2017-08-01

    Full Text Available Background/Aims: Congenital Sick Sinus Syndrome (SSS is a disorder associated with sudden cardiac death due to severe bradycardia and prolonged pauses. Mutations in HCN4, the gene encoding inward Na+/K+ current (If, have been described as a cause of congenital SSS. The objective of this study is to develop an SSS model in embryonic zebrafish, and use zebrafish as a moderate-throughput assay to functionally characterize HCN4 variants. Methods: To determine the function of hcn4 in zebrafish, embryos were either bathed in the If -specific blocker (ZD-7288, or endogenous hcn4 expression was knocked down using splice-blocking morpholinos. To assess whether the zebrafish model discriminates benign from pathogenic variants, we tested four HCN4 mutations known to cause human SSS and four variants of unknown significance (VUS. Results: Pharmacological blockade and knockdown of hcn4 in zebrafish phenocopied human SSS, displaying bradycardia and cardiac pauses in intact embryos and explanted hearts. The zebrafish assay correctly identified all disease-causing variants. Of the VUS, the assay predicted 2 as benign and 2 as hypomorphic variants. Conclusions: We conclude that our embryonic zebrafish assay is a novel and effective tool to functionally characterize human HCN4 variants, which can be translated into important clinical prognostic information.

  18. Functionally Significant, Rare Transcription Factor Variants in Tetralogy of Fallot

    Science.gov (United States)

    Töpf, Ana; Griffin, Helen R.; Glen, Elise; Soemedi, Rachel; Brown, Danielle L.; Hall, Darroch; Rahman, Thahira J.; Eloranta, Jyrki J.; Jüngst, Christoph; Stuart, A. Graham; O'Sullivan, John; Keavney, Bernard D.; Goodship, Judith A.

    2014-01-01

    Objective Rare variants in certain transcription factors involved in cardiac development cause Mendelian forms of congenital heart disease. The purpose of this study was to systematically assess the frequency of rare transcription factor variants in sporadic patients with the cardiac outflow tract malformation tetralogy of Fallot (TOF). Methods and Results We sequenced the coding, 5′UTR, and 3′UTR regions of twelve transcription factor genes implicated in cardiac outflow tract development (NKX2.5, GATA4, ISL1, TBX20, MEF2C, BOP/SMYD1, HAND2, FOXC1, FOXC2, FOXH, FOXA2 and TBX1) in 93 non-syndromic, non-Mendelian TOF cases. We also analysed Illumina Human 660W-Quad SNP Array data for copy number variants in these genes; none were detected. Four of the rare variants detected have previously been shown to affect transactivation in in vitro reporter assays: FOXC1 p.P297S, FOXC2 p.Q444R, FOXH1 p.S113T and TBX1 p.P43_G61del PPPPRYDPCAAAAPGAPGP. Two further rare variants, HAND2 p.A25_A26insAA and FOXC1 p.G378_G380delGGG, A488_491delAAAA, affected transactivation in in vitro reporter assays. Each of these six functionally significant variants was present in a single patient in the heterozygous state; each of the four for which parental samples were available were maternally inherited. Thus in the 93 TOF cases we identified six functionally significant mutations in the secondary heart field transcriptional network. Significance This study indicates that rare genetic variants in the secondary heart field transcriptional network with functional effects on protein function occur in 3–13% of patients with TOF. This is the first report of a functionally significant HAND2 mutation in a patient with congenital heart disease. PMID:25093829

  19. Functionally significant, rare transcription factor variants in tetralogy of Fallot.

    Directory of Open Access Journals (Sweden)

    Ana Töpf

    Full Text Available Rare variants in certain transcription factors involved in cardiac development cause Mendelian forms of congenital heart disease. The purpose of this study was to systematically assess the frequency of rare transcription factor variants in sporadic patients with the cardiac outflow tract malformation tetralogy of Fallot (TOF.We sequenced the coding, 5'UTR, and 3'UTR regions of twelve transcription factor genes implicated in cardiac outflow tract development (NKX2.5, GATA4, ISL1, TBX20, MEF2C, BOP/SMYD1, HAND2, FOXC1, FOXC2, FOXH, FOXA2 and TBX1 in 93 non-syndromic, non-Mendelian TOF cases. We also analysed Illumina Human 660W-Quad SNP Array data for copy number variants in these genes; none were detected. Four of the rare variants detected have previously been shown to affect transactivation in in vitro reporter assays: FOXC1 p.P297S, FOXC2 p.Q444R, FOXH1 p.S113T and TBX1 p.P43_G61del PPPPRYDPCAAAAPGAPGP. Two further rare variants, HAND2 p.A25_A26insAA and FOXC1 p.G378_G380delGGG, A488_491delAAAA, affected transactivation in in vitro reporter assays. Each of these six functionally significant variants was present in a single patient in the heterozygous state; each of the four for which parental samples were available were maternally inherited. Thus in the 93 TOF cases we identified six functionally significant mutations in the secondary heart field transcriptional network.This study indicates that rare genetic variants in the secondary heart field transcriptional network with functional effects on protein function occur in 3-13% of patients with TOF. This is the first report of a functionally significant HAND2 mutation in a patient with congenital heart disease.

  20. Diverse Functional Properties of Wilson Disease ATP7B Variants

    Science.gov (United States)

    Huster, Dominik; Kühne, Angelika; Bhattacharjee, Ashima; Raines, Lily; Jantsch, Vanessa; Noe, Johannes; Schirrmeister, Wiebke; Sommerer, Ines; Sabri, Osama; Berr, Frieder; Mössner, Joachim; Stieger, Bruno; Caca, Karel; Lutsenko, Svetlana

    2012-01-01

    BACKGROUND & AIMS Wilson disease is a severe disorder of copper metabolism caused by mutations in ATP7B, which encodes a copper-transporting adenosine triphosphatase. The disease presents with a variable phenotype that complicates the diagnostic process and treatment. Little is known about the mechanisms that contribute to the different phenotypes of the disease. METHODS We analyzed 28 variants of ATP7B from patients with Wilson disease that affected different functional domains; the gene products were expressed using the baculovirus expression system in Sf9 cells. Protein function was analyzed by measuring catalytic activity and copper (64Cu) transport into vesicles. We studied intracellular localization of variants of ATP7B that had measurable transport activities and were tagged with green fluorescent protein in mammalian cells using confocal laser scanning microscopy. RESULTS Properties of ATP7B variants with pathogenic amino-acid substitution varied greatly even if substitutions were in the same functional domain. Some variants had complete loss of catalytic and transport activity, whereas others lost transport activity but retained phosphor-intermediate formation or had partial losses of activity. In mammalian cells, transport-competent variants differed in stability and subcellular localization. CONCLUSIONS Variants in ATP7B associated with Wilson disease disrupt the protein’s transport activity, result in its mislocalization, and reduce its stability. Single assays are insufficient to accurately predict the effects of ATP7B variants the function of its product and development of Wilson disease. These findings will contribute to our understanding of genotype–phenotype correlation and mechanisms of disease pathogenesis. PMID:22240481

  1. Functional characterization of rare FOXP2 variants in neurodevelopmental disorder.

    Science.gov (United States)

    Estruch, Sara B; Graham, Sarah A; Chinnappa, Swathi M; Deriziotis, Pelagia; Fisher, Simon E

    2016-01-01

    Heterozygous disruption of FOXP2 causes a rare form of speech and language impairment. Screens of the FOXP2 sequence in individuals with speech/language-related disorders have identified several rare protein-altering variants, but their phenotypic relevance is often unclear. FOXP2 encodes a transcription factor with a forkhead box DNA-binding domain, but little is known about the functions of protein regions outside this domain. We performed detailed functional analyses of seven rare FOXP2 variants found in affected cases, including three which have not been previously characterized, testing intracellular localization, transcriptional regulation, dimerization, and interaction with other proteins. To shed further light on molecular functions of FOXP2, we characterized the interaction between this transcription factor and co-repressor proteins of the C-terminal binding protein (CTBP) family. Finally, we analysed the functional significance of the polyglutamine tracts in FOXP2, since tract length variations have been reported in cases of neurodevelopmental disorder. We confirmed etiological roles of multiple FOXP2 variants. Of three variants that have been suggested to cause speech/language disorder, but never before been characterized, only one showed functional effects. For the other two, we found no effects on protein function in any assays, suggesting that they are incidental to the phenotype. We identified a CTBP-binding region within the N-terminal portion of FOXP2. This region includes two amino acid substitutions that occurred on the human lineage following the split from chimpanzees. However, we did not observe any effects of these amino acid changes on CTBP binding or other core aspects of FOXP2 function. Finally, we found that FOXP2 variants with reduced polyglutamine tracts did not exhibit altered behaviour in cellular assays, indicating that such tracts are non-essential for core aspects of FOXP2 function, and that tract variation is unlikely to be a

  2. Implications of domestic food practices for the presence of bioactive components in meats with special reference to meat-based functional foods.

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    Jiménez-Colmenero, Francisco; Cofrades, Susana; Herrero, Ana M; Ruiz-Capillas, Claudia

    2017-06-14

    Although an essential component of the diet, the consumption of meat is in question. Meat is a major source of beneficial compounds but it also contains other substances with negative health implications. Functional foods, which are leading trends in the food industry, constitute an excellent opportunity for the meat sector to improve healthier meat options. Most studies on meat-based functional foods have focused mainly on the application of different strategies (animal production practices and meat transformation systems) to improve (increase/reduce) the presence of bioactive (healthy/unhealthy) compounds; these have led to the development of numerous products, many of them by the meat industry. However, like other foods, after purchase meats undergo certain processes before they are consumed, and these affect their composition. Although domestic handling practices can significantly alter the make-up of the marketed product in terms of healthy/unhealthy compounds, there are very few studies on their consequences. This paper provides an overview of the influence of different domestic practices (from shopping to eating) habitually followed by consumers on the presence of, and consequently on the levels of exposure to, (healthy and unhealthy) food components associated with the consumption of meats, with special reference to meat-based functional foods.

  3. Bioactive Components in The Meat and Their Functional Properties: A Literature Study

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    Khothibul Umam Al Awwaly

    2017-03-01

    Full Text Available Consumer awareness in meat and meat products is generally recognized as a good source of food, with high biological value protein, B group vitamins, minerals and minor elements like several other bioactive compounds that are beneficial to the human body. But in many cases, a processing error is affecting the bioactive compounds of functional foods and consumer impression are relatively negative to some levels of substances in meat such as fat, cholesterol, saturated fatty acids, salt and other substances, which however also involves a diseases of western society such as cardiovascular diseases, respiratory, carcinogenesis, obesity, impaired immune system and accelerate the aging process. Hence there is a need for adequate information related to favorable nutritional value of meat that has not been widely disclosed. Bioactive components in the meat can be anserin, karnosin and bioactive peptides. The generation of bioactive components in the meat in the form of bioactive peptides can be done in three ways: (1 aging or storage of meat, (2 meat fermentation, and (3 the enzyme treatment. Functional properties of bioactive components in meat varies greatly as an antioxidant, antihypertensive, antimicrobial, anticancer and immunomodulatory.

  4. Melanoma risk associated with MC1R gene variants in Latvia and the functional analysis of rare variants.

    Science.gov (United States)

    Ozola, Aija; Azarjana, Kristīne; Doniņa, Simona; Proboka, Guna; Mandrika, Ilona; Petrovska, Ramona; Cēma, Ingrīda; Heisele, Olita; Eņģele, Ludmila; Streinerte, Baiba; Pjanova, Dace

    2013-03-01

    To evaluate the association of melanocortin 1 receptor gene (MC1R) variants with melanoma risk in a Latvian population, the MC1R gene was sequenced in 200 melanoma patients and 200 control persons. A functional study of previously uncharacterized, rare MC1R variants was also performed. In total, 26 different MC1R variants, including two novel variants Val165Ile and Val188Ile, were detected. The highest risk of melanoma was associated with the Arg151Cys variant (odds ratio (OR) 4.47, 95% confidence interval (CI) 2.19-9.14, PLatvia. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Flavonoids in the development of functional meat products: A review

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    Pramod K. Singh

    2013-06-01

    Full Text Available Flavonoids or bioflavonoids are unique low molecular weight ubiquitous polyphenolic compounds produced by plants during their metabolic activities as a secondary metabolites and responsible for major organoleptic characteristics and health benefits of plant derived foods. The flavonoids are potent antioxidants agents and protect the cells by scavenging and inhibiting the production and initiation of free radicals, superoxide anions and lipid peroxy radicals. Besides potent antioxidant capacity, flavonoids also shows antimicrobial, antimutagenic, antidiabetic, antithrombosis, antirheumatic, antiatherosclerotic, antiallergic, anti-inflammatory, antiulcers and hepatoprotectives and better termed as neutraceuticals. The antioxidant capacity of meat is very low and this can be increased by adding flavonoids in meat during processing in the form of plant parts rich in flavonoids such as seeds, fruit skin or peel, bark and flower as raw or in extract form without comprising the sensory attributes of meat and meat products. [Vet World 2013; 6(8.000: 573-578

  6. Functional consequences of a novel variant of PCSK1.

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    Lindsay A Pickett

    Full Text Available Common single nucleotide polymorphisms (SNPs in proprotein convertase subtilisin/kexin type 1 with modest effects on PC1/3 in vitro have been associated with obesity in five genome-wide association studies and with diabetes in one genome-wide association study. We here present a novel SNP and compare its biosynthesis, secretion and catalytic activity to wild-type enzyme and to SNPs that have been linked to obesity.A novel PC1/3 variant introducing an Arg to Gln amino acid substitution at residue 80 (within the secondary cleavage site of the prodomain (rs1799904 was studied. This novel variant was selected for analysis from the 1000 Genomes sequencing project based on its predicted deleterious effect on enzyme function and its comparatively more frequent allele frequency. The actual existence of the R80Q (rs1799904 variant was verified by Sanger sequencing. The effects of this novel variant on the biosynthesis, secretion, and catalytic activity were determined; the previously-described obesity risk SNPs N221D (rs6232, Q665E/S690T (rs6234/rs6235, and the Q665E and S690T SNPs (analyzed separately were included for comparative purposes. The novel R80Q (rs1799904 variant described in this study resulted in significantly detrimental effects on both the maturation and in vitro catalytic activity of PC1/3.Our findings that this novel R80Q (rs1799904 variant both exhibits adverse effects on PC1/3 activity and is prevalent in the population suggests that further biochemical and genetic analysis to assess its contribution to the risk of metabolic disease within the general population is warranted.

  7. Hydroxytyrosol: Health Benefits and Use as Functional Ingredient in Meat

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    Lorena Martínez

    2018-01-01

    Full Text Available Hydroxytyrosol (HXT is a phenolic compound drawn from the olive tree and its leaves as a by-product obtained from the manufacturing of olive oil. It is considered the most powerful antioxidant compound after gallic acid and one of the most powerful antioxidant compounds between phenolic compounds from olive tree followed by oleuropein, caffeic and tyrosol. Due to its molecular structure, its regular consumption has several beneficial effects such as antioxidant, anti-inflammatory, anticancer, and as a protector of skin and eyes, etc. For these reasons, the use of HXT extract is a good strategy for use in meat products to replace synthetics additives. However, this extract has a strong odour and flavour, so it is necessary to previously treat this compound in order to not alter the organoleptic quality of the meat product when is added as ingredient. The present review exposes the health benefits provided by HXT consumption and the latest research about its use on meat. In addition, new trends about the application of HXT in the list of ingredients of healthier meat products will be discussed.

  8. Red meat intake, insulin resistance, and markers of endothelial function among Iranian women.

    Science.gov (United States)

    Barak, Farzaneh; Falahi, Ebrahim; Keshteli, Ammar Hassanzadeh; Yazdannik, Ahmadreza; Saneei, Parvane; Esmaillzadeh, Ahmad

    2015-02-01

    Few data, with conflicting findings, are available linking red meat consumption to indicators of insulin resistance and endothelial dysfunction. This study aimed to investigate the association of red meat consumption with insulin resistance and endothelial dysfunction among a sample of female nurses in Isfahan, Iran. This cross-sectional study was carried out among 420 female nurses who were selected by a multistage cluster random sampling method. Usual dietary intakes were assessed using a validated food frequency questionnaire. Red meat intake was calculated by summing up the consumption of all kinds of red meat in foods and processed meat in sausages and fast foods. To measure serum concentrations of adhesion molecules and glycemic indexes, a fasting blood sample was taken. After adjustment for potential confounders, high red meat intake was significantly associated with higher fasting plasma glucose, homeostasis model assessment of insulin resistance, and lower quantitative insulin sensitivity check index. Although high red meat intake was significantly associated with higher serum insulin levels and lower homeostasis model assessment of beta-cell function in the crude model, after controlling for BMI, the association was no longer significant. Red meat consumption was associated with high concentrations of E-selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble intercellular adhesion molecule-1 (sICAM-1) after adjustment for different potential confounders. We found that increased red meat intake was associated with high concentrations of plasma endothelial dysfunction biomarkers and abnormal glucose homeostasis among Iranian women. Prospective studies are required to confirm these findings. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Functional consequences of AXL sequence variants in hypogonadotropic hypogonadism.

    Science.gov (United States)

    Salian-Mehta, S; Xu, M; Knox, A J; Plummer, L; Slavov, D; Taylor, M; Bevers, S; Hodges, R S; Crowley, W F; Wierman, M E

    2014-04-01

    Prior studies showed that Axl /Tyro3 null mice have delayed first estrus and abnormal cyclicity due to developmental defects in GnRH neuron migration and survival. The objective of the study was to test whether the absence of Axl would alter reproductive function in mice and that mutations in AXL are present in patients with Kallmann syndrome (KS) or normosmic idiopathic hypogonadotropic hypogonadism (nIHH). The sexual maturation of Axl null mice was examined. The coding region of AXL was sequenced in 104 unrelated, carefully phenotyped KS or nIHH subjects. Frequency of mutations was compared with other causes of GnRH deficiency. Functional assays were performed on the detected mutations. Axl null mice demonstrated delay in first estrus and the interval between vaginal opening and first estrus. Three missense AXL mutations (p.L50F, p.S202C, and p.Q361P) and one intronic variant 6 bp upstream from the start of exon 5 (c.586-6 C>T) were identified in two KS and 2 two nIHH subjects. Comparison of the frequencies of AXL mutations with other putative causes of idiopathic hypogonadotropic hypogonadism confirmed they are rare variants. Testing of the c.586-6 C>T mutation revealed no abnormal splicing. Surface plasmon resonance analysis of the p.L50F, p.S202C, and p.Q361P mutations showed no altered Gas6 ligand binding. In contrast, GT1-7 GnRH neuronal cells expressing p.S202C or p.Q361P demonstrated defective ligand dependent receptor processing and importantly aberrant neuronal migration. In addition, the p.Q361P showed defective ligand independent chemotaxis. Functional consequences of AXL sequence variants in patients with idiopathic hypogonadotropic hypogonadism support the importance of AXL and the Tyro3, Axl, Mer (TAM) family in reproductive development.

  10. Reduced functionality of PSE-like chicken breast meat batter resulting from alterations in protein conformation.

    Science.gov (United States)

    Li, K; Zhao, Y Y; Kang, Z L; Wang, P; Han, M Y; Xu, X L; Zhou, G H

    2015-01-01

    The objectives of this study were to evaluate protein thermal stability, water-protein interaction, microstructure, and protein conformation between PSE-like and normal chicken breast meat batters. Sixty pale, soft, and exudative (PSE)-like (L*>53, pH24 hbatters were formulated to 14% meat protein and 2% salt, and they were analyzed for the protein changes and the microstructure using differential scanning calorimetry, low-field (LF)-NMR, SEM, and Raman spectroscopy. PSE-like meat batter had lower gel strength, water-holding capacity, and salt-soluble protein extraction (Pbatter formed an aggregated gel matrix, while normal meat batter produced a compact gel network with fine, cross-linked strands by many protein filaments. LF-NMR revealed an increase in the water mobility in heated PSE-like meat batter with an increasing amount of loosely bound water (Pbatter had less unfolded α-helix and β-sheet structure formation, reduced exposure of hydrophobic and tyrosine residues (P<0.05), and changes in the microenvironment of aliphatic residues and tryptophan, which affected salt-soluble protein extraction, gel properties, and water-holding capacity. In conclusion, the inferior functional properties of PSE-like meat were attributed to not only myosin denaturation, but also actin denaturation after salt addition and different protein structural states. © 2015 Poultry Science Association Inc.

  11. Functional relevance for associations between osteoporosis and genetic variants.

    Science.gov (United States)

    Liu, Kun; Tan, Li-Jun; Wang, Peng; Chen, Xiang-Ding; Zhu, Li-Hua; Zeng, Qin; Hu, Yuan; Deng, Hong-Wen

    2017-01-01

    Osteoporosis is characterized by increased bone loss and deterioration of bone microarchitecture, which will lead to reduced bone strength and increased risk of fragility fractures. Previous studies have identified many genetic loci associated with osteoporosis, but functional mechanisms underlying the associations have rarely been explored. In order to explore the potential molecular functional mechanisms underlying the associations for osteoporosis, we performed integrative analyses by using the publically available datasets and resources. We searched 128 identified osteoporosis associated SNPs (PLRP5 rs3736228) were confirmed to impact the expression of 3 genes (RPL31, CPT1A and MTL5) that were differentially expressed between human subjects of high BMD group and low BMD group. All of the functional evidence suggested the important functional mechanisms underlying the associations of the 2 SNPs (rs2278729 and rs3736228) and 3 genes (RPL31, CPT1A and MTL5) with osteoporosis. This study may provide novel insights into the functional mechanisms underlying the osteoporosis associated genetic variants, which will help us to comprehend the potential mechanisms underlying the genetic association for osteoporosis.

  12. Functional relevance for associations between osteoporosis and genetic variants.

    Directory of Open Access Journals (Sweden)

    Kun Liu

    Full Text Available Osteoporosis is characterized by increased bone loss and deterioration of bone microarchitecture, which will lead to reduced bone strength and increased risk of fragility fractures. Previous studies have identified many genetic loci associated with osteoporosis, but functional mechanisms underlying the associations have rarely been explored. In order to explore the potential molecular functional mechanisms underlying the associations for osteoporosis, we performed integrative analyses by using the publically available datasets and resources. We searched 128 identified osteoporosis associated SNPs (P<10-6, and 8 SNPs exert cis-regulation effects on 11 eQTL target genes. Among the 8 SNPs, 2 SNPs (RPL31 rs2278729 and LRP5 rs3736228 were confirmed to impact the expression of 3 genes (RPL31, CPT1A and MTL5 that were differentially expressed between human subjects of high BMD group and low BMD group. All of the functional evidence suggested the important functional mechanisms underlying the associations of the 2 SNPs (rs2278729 and rs3736228 and 3 genes (RPL31, CPT1A and MTL5 with osteoporosis. This study may provide novel insights into the functional mechanisms underlying the osteoporosis associated genetic variants, which will help us to comprehend the potential mechanisms underlying the genetic association for osteoporosis.

  13. Functional and rheological properties of proteins in frozen turkey breast meat with different ultimate pH.

    Science.gov (United States)

    Chan, J T Y; Omana, D A; Betti, M

    2011-05-01

    Functional and rheological properties of proteins from frozen turkey breast meat with different ultimate pH at 24 h postmortem (pH(24)) have been studied. Sixteen breast fillets from Hybrid Tom turkeys were initially selected based on lightness (L*) values for each color group (pale, normal, and dark), with a total of 48 breast fillets. Further selection of 8 breast samples was made within each class of meat according to the pH(24). The average L* and pH values of the samples were within the following range: pale (L* >52; pH ≤5.7), normal (46 meat, respectively. Ultimate pH did not cause major changes in the emulsifying and foaming properties of the extracted sarcoplasmic and myofibrillar proteins. An SDS-PAGE profile of proteins from low and normal pH meat was similar, which revealed that the extent of protein denaturation was the same. Low pH meat had the lowest water-holding capacity compared with normal and high pH meat as shown by the increase in cooking loss, which can be explained by factors other than protein denaturation. Gel strength analysis and folding test revealed that gel-forming ability was better for high pH meat compared with low and normal pH meat.Dynamic viscoelastic behavior showed that myosin denaturation temperature was independent of pH(24). Normal and high pH meat had similar hardness, springiness, and chewiness values as revealed by texture profile analysis. The results from this study indicate that high pH meat had similar or better functional properties than normal pH meat. Therefore, high pH meat is suitable for further processed products, whereas low pH meat may need additional treatment or ingredient formulations to improve its functionality.

  14. Functional properties of PSE (Pale, Soft, Exudative broiler meat in the production of mortadella

    Directory of Open Access Journals (Sweden)

    Cassiana Kissel

    2009-11-01

    Full Text Available This work was carried out in order to evaluate whether the functional properties of broiler meat are affected by the factors that lead to PSE (Pale, Soft, Exudative. PSE meat was characterized by pH and L* values, and mortadella formulations consisted of isolated soy protein, sodium tripolyphosphate, and cassava starch in addition to PSE and normal meats. The functionality of the meat was evaluated by examining the water holding capacity (WHC, texture profile, emulsion stability (ES and color of the final products. The results show that in mortadella prepared with PSE meat, the protein denaturation affected the ES. Additives are necessary to enhance the functional properties of PSE meat.Este trabalho foi realizado para avaliar o efeito dos fatores que conduzem à formação das carnes PSE (Pale, Soft, Exudative sobre as propriedades funcionais da carne de frango. Carnes PSE foram caracterizadas pelos valores de pH e L* e as formulações da mortadela consistiram de proteina isolada de soja, trifosfato de sódio, amido de mandioca e a adição das carnes normal e PSE. A funcionalidade da carne foi avaliada medindo a capacidade de retenção de água (CRA, perfil de textura, estabilidade de emulsão (EE, e cor dos produtos finais. Os resultados mostraram que na mortadela preparada com carnes PSE, as proteinas desnaturadas afetaram a EE. Aditivos são necessários para potencializar as propriedades funcionais da carne PSE.

  15. Quality function deployment in the organic animal food sector: application to poultry meat

    Directory of Open Access Journals (Sweden)

    Simona Naspetti

    2015-09-01

    Full Text Available This study presents the results of an Italian investigation into the development of food quality for poultry meat in the organic sector, using the quality function deployment technique. The results show that among the characteristics of poultry, meat consumers assign greater importance to those that are strictly related to animal welfare issues. Price and product appearance (i.e., colour, presence of fat come in second. To meet these needs, producers can effectively operate along the supply chain by acting on poultry housing type, genotype lines, and stocking density. Information about these issues should then be shared with the consumers (i.e., clear product labelling.

  16. Modelling Meat Quality Attributes.

    OpenAIRE

    Farrell, Terence C.

    2001-01-01

    Recent meat demand models incorporate demand functions for cuts of meat rather than whole carcasses. However, parameters for “meat quality” are seldom included in such models. Modelling difficulty arises as meat cuts are heterogeneous in their quality attributes. Meat quality may be assessed by measurement of attributes including tenderness, juiciness and flavour. Cooking method and cooking time are the two primary factors that affect meat-eating quality. The purpose of this paper is to show ...

  17. Identification of Pleiotropic Cancer Susceptibility Variants from Genome-Wide Association Studies Reveals Functional Characteristics.

    Science.gov (United States)

    Wu, Yi-Hsuan; Graff, Rebecca E; Passarelli, Michael N; Hoffman, Joshua D; Ziv, Elad; Hoffmann, Thomas J; Witte, John S

    2018-01-01

    Background: There exists compelling evidence that some genetic variants are associated with the risk of multiple cancer sites (i.e., pleiotropy). However, the biological mechanisms through which the pleiotropic variants operate are unclear. Methods: We obtained all cancer risk associations from the National Human Genome Research Institute-European Bioinformatics Institute GWAS Catalog, and correlated cancer risk variants were clustered into groups. Pleiotropic variant groups and genes were functionally annotated. Associations of pleiotropic cancer risk variants with noncancer traits were also obtained. Results: We identified 1,431 associations between variants and cancer risk, comprised of 989 unique variants associated with 27 unique cancer sites. We found 20 pleiotropic variant groups (2.1%) composed of 33 variants (3.3%), including novel pleiotropic variants rs3777204 and rs56219066 located in the ELL2 gene. Relative to single-cancer risk variants, pleiotropic variants were more likely to be in genes (89.0% vs. 65.3%, P = 2.2 × 10 -16 ), and to have somewhat larger risk allele frequencies (median RAF = 0.49 versus 0.39, P = 0.046). The 27 genes to which the pleiotropic variants mapped were suggestive for enrichment in response to radiation and hypoxia, alpha-linolenic acid metabolism, cell cycle, and extension of telomeres. In addition, we observed that 8 of 33 pleiotropic cancer risk variants were associated with 16 traits other than cancer. Conclusions: This study identified and functionally characterized genetic variants showing pleiotropy for cancer risk. Impact: Our findings suggest biological pathways common to different cancers and other diseases, and provide a basis for the study of genetic testing for multiple cancers and repurposing cancer treatments. Cancer Epidemiol Biomarkers Prev; 27(1); 75-85. ©2017 AACR . ©2017 American Association for Cancer Research.

  18. A functional variant in ERAP1 predisposes to multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Franca Rosa Guerini

    Full Text Available The ERAP1 gene encodes an aminopeptidase involved in antigen processing. A functional polymorphism in the gene (rs30187, Arg528Lys associates with susceptibility to ankylosying spondylitis (AS, whereas a SNP in the interacting ERAP2 gene increases susceptibility to another inflammatory autoimmune disorder, Crohn's disease (CD. We analysed rs30187 in 572 Italian patients with CD and in 517 subjects suffering from multiple sclerosis (MS; for each cohort, an independent sex- and age-matched control group was genotyped. The frequency of the 528Arg allele was significantly higher in both disease cohorts compared to the respective control population (for CD, OR = 1.20 95%CI: 1.01-1.43, p = 0.036; for RRMS, OR = 1.26; 95%CI: 1.04-1.51, p = 0.01. Meta-analysis with the Wellcome Trust Cases Control Consortium GWAS data confirmed the association with MS (p(meta = 0.005, but not with CD. In AS, the rs30187 variant has a predisposing effect only in an HLA-B27 allelic background. It remains to be evaluated whether interaction between ERAP1 and distinct HLA class I alleles also affects the predisposition to MS, and explains the failure to provide definitive evidence for a role of rs30187 in CD. Results herein support the emerging concept that a subset of master-regulatory genes underlay the pathogenesis of autoimmunity.

  19. [Functional meat products; development and evaluation of their health-promoting properties].

    Science.gov (United States)

    Olmedilla-Alonso, Begoña; Jiménez-Colmenero, Francisco

    2014-06-01

    For a number of reasons, meat products are an exceptionally adequate means for introducing different bioactive compounds into the diet without modifying eating habits. In recent years, there has been a notable development of meat products designed as potentially functional foods. Within the framework of the functional food, this article provides a general view of the reasons that motivate and justify their formulation, with special emphasis on: a) aspects to be considered in their design in order to be able to make nutrition claims and statements concerning their health-promoting properties; b) the strategies employed to optimize the presence of functional ingredients, favoring the presence of beneficial bioactive compounds and limiting others with negative consequences for our health, and c) the procedures for demonstrating a relationship between the consumption of potentially functional meat products with beneficial effects on health and the way in which these studies are reflected in the literature. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  20. Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes

    DEFF Research Database (Denmark)

    Grarup, Niels; Moltke, Ida; Andersen, Mette K

    2018-01-01

    We have identified a variant in ADCY3 (encoding adenylate cyclase 3) associated with markedly increased risk of obesity and type 2 diabetes in the Greenlandic population. The variant disrupts a splice acceptor site, and carriers have decreased ADCY3 RNA expression. Additionally, we observe...... an enrichment of rare ADCY3 loss-of-function variants among individuals with type 2 diabetes in trans-ancestry cohorts. These findings provide new information on disease etiology relevant for future treatment strategies....

  1. A systematic survey of loss-of-function variants in human protein-coding genes

    NARCIS (Netherlands)

    MacArthur, D.G.; Balasubramanian, S.; Frankish, A.; Huang, N.; Morris, J.; Walter, K.; Jostins, L.; Habegger, L.; Pickrell, J.K.; Montgomery, S.B.; Albers, C.A.; Zhang, Z.D.; Conrad, D.F.; Lunter, G.; Zheng, H.; Ayub, Q.; DePristo, M.A.; Banks, E.; Hu, M.; Handsaker, R.E.; Rosenfeld, J.A.; Fromer, M.; Jin, M.; Mu, X.J.; Khurana, E.; Ye, K.; Kay, M.; Saunders, G.I.; Suner, M.M.; Hunt, T.; Barnes, I.H.; Amid, C.; Carvalho-Silva, D.R.; Bignell, A.H.; Snow, C.; Yngvadottir, B.; Bumpstead, S.; Cooper, D.N.; Xue, Y.; Romero, I.G.; Genomes Project, C.; Wang, J; Li, Y.; Gibbs, R.A.; McCarroll, S.A.; Dermitzakis, E.T.; Pritchard, J.K.; Barrett, J.C.; Harrow, J.; Hurles, M.E.; Gerstein, M.B.; Tyler-Smith, C.

    2012-01-01

    Genome-sequencing studies indicate that all humans carry many genetic variants predicted to cause loss of function (LoF) of protein-coding genes, suggesting unexpected redundancy in the human genome. Here we apply stringent filters to 2951 putative LoF variants obtained from 185 human genomes to

  2. In silico functional pathway annotation of 86 established prostate cancer risk variants.

    Directory of Open Access Journals (Sweden)

    Lenora W M Loo

    Full Text Available Heritability is one of the strongest risk factors of prostate cancer, emphasizing the importance of the genetic contribution towards prostate cancer risk. To date, 86 established prostate cancer risk variants have been identified by genome-wide association studies (GWAS. To determine if these risk variants are located near genes that interact together in biological networks or pathways contributing to prostate cancer initiation or progression, we generated gene sets based on proximity to the 86 prostate cancer risk variants. We took two approaches to generate gene lists. The first strategy included all immediate flanking genes, up- and downstream of the risk variant, regardless of distance from the index variant, and the second strategy included genes closest to the index GWAS marker and to variants in high LD (r2 ≥0.8 in Europeans with the index variant, within a 100 kb window up- and downstream. Pathway mapping of the two gene sets supported the importance of the androgen receptor-mediated signaling in prostate cancer biology. In addition, the hedgehog and Wnt/β-catenin signaling pathways were identified in pathway mapping for the flanking gene set. We also used the HaploReg resource to examine the 86 risk loci and variants high LD (r2 ≥0.8 for functional elements. We found that there was a 12.8 fold (p = 2.9 x 10-4 enrichment for enhancer motifs in a stem cell line and a 4.4 fold (p = 1.1 x 10-3 enrichment of DNase hypersensitivity in a prostate adenocarcinoma cell line, indicating that the risk and correlated variants are enriched for transcriptional regulatory motifs. Our pathway-based functional annotation of the prostate cancer risk variants highlights the potential regulatory function that GWAS risk markers, and their highly correlated variants, exert on genes. Our study also shows that these genes may function cooperatively in key signaling pathways in prostate cancer biology.

  3. m6ASNP: a tool for annotating genetic variants by m6A function.

    Science.gov (United States)

    Jiang, Shuai; Xie, Yubin; He, Zhihao; Zhang, Ya; Zhao, Yuli; Chen, Li; Zheng, Yueyuan; Miao, Yanyan; Zuo, Zhixiang; Ren, Jian

    2018-04-02

    Large-scale genome sequencing projects have identified many genetic variants for diverse diseases. A major goal of these projects is to characterize these genetic variants to provide insight into their function and roles in diseases. N6-methyladenosine (m6A) is one of the most abundant RNA modifications in eukaryotes. Recent studies have revealed that aberrant m6A modifications are involved in many diseases. In this study, we present a user-friendly web server called "m6ASNP" that is dedicated to the identification of genetic variants targeting m6A modification sites. A random forest model was implemented in m6ASNP to predict whether the methylation status of a m6A site is altered by the variants surrounding the site. In m6ASNP, genetic variants in a standard VCF format are accepted as the input data, and the output includes an interactive table containing the genetic variants annotated by m6A function. In addition, statistical diagrams and a genome browser are provided to visualize the characteristics and annotate the genetic variants. We believe that m6ASNP is a highly convenient tool that can be used to boost further functional studies investigating genetic variants. The web server "m6ASNP" is implemented in JAVA and PHP and is freely available at http://m6asnp.renlab.org.

  4. Impact of white striping on functionality attributes of broiler breast meat1.

    Science.gov (United States)

    Bowker, B; Zhuang, H

    2016-08-01

    The influence of white striping (WS) on the water-holding capacity (WHC) and protein functionality attributes of broiler breast meat was investigated. Boneless breast fillets (Pectoralis major) were collected from the deboning line of a commercial processing plant and categorized by WS score (normal, moderate, severe). The physical (weight, pH, CIE-color values), water-holding capacity (salt-induced water uptake, cook loss, final yield), protein functionality (solubility, emulsifying activity), and protein composition (SDS-PAGE) characteristics of the fillets were measured in three experiments. Breast meat with WS exhibited greater fillet weights, higher pH, and similar color values (L*a*b*) to normal fillets. In experiment 1, fillets were frozen-thawed prior to analysis. The WS condition reduced thaw loss, sarcoplasmic protein solubility, and the emulsifying activity of the myofibrillar proteins, but did not significantly affect salt-induced water uptake, cook loss, final yield, or myofibrillar protein solubility. In experiment 2, breast meat was analyzed fresh and after a freeze-thaw cycle. Freezing samples prior to analysis negatively influenced WHC and reduced sarcoplasmic protein solubility in both WS and normal fillets. In fresh and frozen-thawed meat, the WS condition decreased sarcoplasmic protein solubility but did not significantly alter WHC or myofibrillar protein solubility. For experiment 3, fillets were portioned into 3 sections (Location A, cranial end-ventral surface; Location B, cranial end-dorsal surface; Location C, caudal end). The effects of WS on WHC and protein solubility were dependent upon breast fillet sampling location. Fillets with WS exhibited lower salt-induced water uptake, greater cook loss, and lower sarcoplasmic protein solubility than normal fillets when sampled from location A. SDS-PAGE analysis indicated that differences in the composition of sarcoplasmic and myofibrillar protein fractions between WS and normal fillets were

  5. Modeling production functions and economic weights in intensive meat production of guinea pigs.

    Science.gov (United States)

    Pascual, Mariam; Cruz, Danny Julio; Blasco, Agustín

    2017-10-01

    A profit function for a typical commercial farm of intensive guinea pig production was designed. The simulated farm contained 86 cages with a ratio of 7:1 females/males, with continuous mating. Kits were weaned at 15 days of age and slaughtered for meat production at 90 days of age. The absolute (EW) and relative economic weights of the main traits were calculated. The highest EW were kits produced per kindling (US$25), kits weaned per kindling (US$22), kits born alive per kindling (US$20), and the number of kindlings per female and year (US$12). Profit, returns, and costs per female and year were US$15, 68, and 53, respectively. Returns came from the production of young guinea pigs and discarded reproductive adults for meat production, 90 and 10% of the total returns. The highest costs were feeding and labor, 44 and 23% of the total cost. The EW and profit did not substantially change when simulating variations of ±20% in the prices of kilograms of fattening feed and kilograms of live weight of guinea pig, showing their robustness to future variations in market prices or to variations in prices between countries. The results obtained highlight the importance of the feeding costs in the guinea pig meat production.

  6. Functional diversity of human protein kinase splice variants marks significant expansion of human kinome

    Directory of Open Access Journals (Sweden)

    Anamika Krishanpal

    2009-12-01

    Full Text Available Abstract Background Protein kinases are involved in diverse spectrum of cellular processes. Availability of draft version of the human genomic data in the year 2001 enabled recognition of repertoire of protein kinases. However, over the years the human genomic data is being refined and the current release of human genomic data has helped us to recognize a larger repertoire of over 900 human protein kinases represented mainly by splice variants. Results Many of these identified protein kinases are alternatively spliced products. Interestingly, some of the human kinase splice variants appear to be significantly diverged in terms of their functional properties as represented by incorporation or absence of one or more domains. Many sets of protein kinase splice variants have substantially different domain organization and in a few sets of splice variants kinase domains belong to different subfamilies of kinases suggesting potential participation in different signal transduction pathways. Conclusions Addition or deletion of a domain between splice variants of multi-domain kinases appears to be a means of generating differences in the functional features of otherwise similar kinases. It is intriguing that marked sequence diversity within the catalytic regions of some of the splice variant kinases result in kinases belonging to different subfamilies. These human kinase splice variants with different functions might contribute to diversity of eukaryotic cellular signaling.

  7. Genetic Load of Loss-of-Function Polymorphic Variants in Great Apes.

    Science.gov (United States)

    de Valles-Ibáñez, Guillem; Hernandez-Rodriguez, Jessica; Prado-Martinez, Javier; Luisi, Pierre; Marquès-Bonet, Tomàs; Casals, Ferran

    2016-03-26

    Loss of function (LoF) genetic variants are predicted to disrupt gene function, and are therefore expected to substantially reduce individual's viability. Knowing the genetic burden of LoF variants in endangered species is of interest for a better understanding of the effects of declining population sizes on species viability. In this study, we have estimated the number of LoF polymorphic variants in six great ape populations, based on whole-genome sequencing data in 79 individuals. Our results show that although the number of functional variants per individual is conditioned by the effective population size, the number of variants with a drastic phenotypic effect is very similar across species. We hypothesize that for those variants with high selection coefficients, differences in effective population size are not important enough to affect the efficiency of natural selection to remove them. We also describe that mostly CpG LoF mutations are shared across species, and an accumulation of LoF variants at olfactory receptor genes in agreement with its pseudogenization in humans and other primate species. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  8. Computational approaches to identify functional genetic variants in cancer genomes

    DEFF Research Database (Denmark)

    Gonzalez-Perez, Abel; Mustonen, Ville; Reva, Boris

    2013-01-01

    The International Cancer Genome Consortium (ICGC) aims to catalog genomic abnormalities in tumors from 50 different cancer types. Genome sequencing reveals hundreds to thousands of somatic mutations in each tumor but only a minority of these drive tumor progression. We present the result of discu...... of discussions within the ICGC on how to address the challenge of identifying mutations that contribute to oncogenesis, tumor maintenance or response to therapy, and recommend computational techniques to annotate somatic variants and predict their impact on cancer phenotype....

  9. Functional genetic variants in the vesicular monoamine transporter 1 (VMAT1) modulate emotion processing

    Science.gov (United States)

    Lohoff, Falk W.; Hodge, Rachel; Narasimhan, Sneha; Nall, Aleksandra; Ferraro, Thomas N.; Mickey, Brian J.; Heitzeg, Mary M.; Langenecker, Scott A.; Zubieta, Jon-Kar; Bogdan, Ryan; Nikolova, Yuliya S.; Drabant, Emily; Hariri, Ahmad R.; Bevilacqua, Laura; Goldman, David; Doyle, Glenn A.

    2012-01-01

    SUMMARY Emotional behavior is in part heritable and often disrupted in psychopathology. Identification of specific genetic variants that drive this heritability may provide important new insight into molecular and neurobiological mechanisms involved in emotionality. Our results demonstrate that the presynaptic vesicular monoamine transporter 1 (VMAT1) Thr136Ile (rs1390938) polymorphism is functional in vitro, with the Ile allele leading to increased monoamine transport into presynaptic vesicles. Moreover, we show that the Thr136Ile variant predicts differential responses in emotional brain circuits consistent with its effects in vitro. Lastly, deep sequencing of bipolar disorder (BPD) patients and controls identified several rare novel VMAT1 variants. The variant Phe84Ser was only present in individuals with BPD and leads to marked increase monoamine transport in vitro. Taken together, our data show that VMAT1 polymorphisms influence monoamine signaling, the functional response of emotional brain circuits, and risk for psychopathology. PMID:23337945

  10. Distribution and medical impact of loss-of-function variants in the Finnish founder population.

    Directory of Open Access Journals (Sweden)

    Elaine T Lim

    2014-07-01

    Full Text Available Exome sequencing studies in complex diseases are challenged by the allelic heterogeneity, large number and modest effect sizes of associated variants on disease risk and the presence of large numbers of neutral variants, even in phenotypically relevant genes. Isolated populations with recent bottlenecks offer advantages for studying rare variants in complex diseases as they have deleterious variants that are present at higher frequencies as well as a substantial reduction in rare neutral variation. To explore the potential of the Finnish founder population for studying low-frequency (0.5-5% variants in complex diseases, we compared exome sequence data on 3,000 Finns to the same number of non-Finnish Europeans and discovered that, despite having fewer variable sites overall, the average Finn has more low-frequency loss-of-function variants and complete gene knockouts. We then used several well-characterized Finnish population cohorts to study the phenotypic effects of 83 enriched loss-of-function variants across 60 phenotypes in 36,262 Finns. Using a deep set of quantitative traits collected on these cohorts, we show 5 associations (p<5×10⁻⁸ including splice variants in LPA that lowered plasma lipoprotein(a levels (P = 1.5×10⁻¹¹⁷. Through accessing the national medical records of these participants, we evaluate the LPA finding via Mendelian randomization and confirm that these splice variants confer protection from cardiovascular disease (OR = 0.84, P = 3×10⁻⁴, demonstrating for the first time the correlation between very low levels of LPA in humans with potential therapeutic implications for cardiovascular diseases. More generally, this study articulates substantial advantages for studying the role of rare variation in complex phenotypes in founder populations like the Finns and by combining a unique population genetic history with data from large population cohorts and centralized research access to National Health

  11. Characterization and functional analysis of four HYH splicing variants in Arabidopsis hypocotyl elongation.

    Science.gov (United States)

    Li, Chen; Zheng, Lanlan; Zhang, Jingxuan; Lv, Yanxia; Liu, Jianping; Wang, Xuanbin; Palfalvi, Gergo; Wang, Guodong; Zhang, Yonghong

    2017-07-01

    Arabidopsis thaliana LONG HYPOCOTYL5 (HY5) is a positive regulator of the light signaling pathway. The hy5 mutant has an elongated hypocotyl in all light conditions, whereas the hy5 homolog (hyh) mutant has a very weak phenotype, but only in blue light. However, overexpression of HYH rescues the elongated hypocotyl phenotype in the hy5 null mutant. Here, we report the identification of four HYH splicing variants in Arabidopsis. Alternative splicing in the 5' region of the HYH gene occurred such that the proteins encoded by all four HYH variants retained their bZIP domain. In hypocotyl tissue, transcript levels of HYH.2, HYH.3, and HYH.4 were higher than those of HYH.1. Like HY5, all HYH variants were induced by light. Functional analysis of the four HYH variants, based on their abilities to complement the hy5 mutant, indicated that they have similar roles in hypocotyl development, and may function redundantly with HY5. Our results indicate that the bZIP domain in HYH is critical for the function of four variants in the compensation of hy5 mutant in hypocotyl development. Additionally, while HY5/HYH is found in plant species ranging from green algae to flowering plants, the potential alternative splicing events are distinct in different species, with certain HYH variants found with greater frequency in some species than others. Copyright © 2017. Published by Elsevier B.V.

  12. Functional assays for analysis of variants of uncertain significance in BRCA2

    DEFF Research Database (Denmark)

    Guidugli, Lucia; Carreira, Aura; Caputo, Sandrine M

    2014-01-01

    Missense variants in the BRCA2 gene are routinely detected during clinical screening for pathogenic mutations in patients with a family history of breast and ovarian cancer. These subtle changes frequently remain of unknown clinical significance because of the lack of genetic information that may...... help establish a direct correlation with cancer predisposition. Therefore, alternative ways of predicting the pathogenicity of these variants are urgently needed. Since BRCA2 is a protein involved in important cellular mechanisms such as DNA repair, replication, and cell cycle control, functional...... of uncertain significance analyzed, and describe a validation set of (genetically) proven pathogenic and neutral missense variants to serve as a golden standard for the validation of each assay. Guidelines are proposed to enable implementation of laboratory-based methods to assess the impact of the variant...

  13. Runs of homozygosity and distribution of functional variants in cattle genome

    DEFF Research Database (Denmark)

    Zhang, Qianqian; Guldbrandtsen, Bernt; Bosse, Mirte

    Runs of homozygosity (ROH) are identified in four dairy cattle breeds using NGS data. Cattle populations have been exposed to strong artificial selection for some generations. Genomic regions under selection will show increased levels of ROH. By investigating the relationship between ROH and dist......Runs of homozygosity (ROH) are identified in four dairy cattle breeds using NGS data. Cattle populations have been exposed to strong artificial selection for some generations. Genomic regions under selection will show increased levels of ROH. By investigating the relationship between ROH...... and distribution of predicted deleterious and tolerated variants, we can gain insight into how selection shapes the distribution of functional variants in inbred regions. We observe that predicted deleterious variants are more enriched in ROHs than predicted tolerated variants. Moreover, increase of enrichment...

  14. Associations of Filaggrin Gene Loss-of-Function Variants with Urinary Phthalate Metabolites and Testicular Function in Young Danish Men

    DEFF Research Database (Denmark)

    Joensen, Ulla Nordström; Jørgensen, Niels; Meldgaard, Michael

    2014-01-01

    variants in a cross-sectional study of 861 young men from the general Danish population. METHODS: All men were genotyped for FLG R501X, 2282del4, and R2447X loss-of-function variants. We measured urinary concentrations of 14 phthalate metabolites and serum levels of reproductive hormones. We also evaluated...... not significantly associated with reproductive hormones or semen quality parameters. CONCLUSION: This study provides evidence that carriers of FLG loss-of-function alleles may have higher internal exposure to phthalates, possibly due to increased transepidermal absorption. FLG loss-of-function variants may indicate......BACKGROUND: Filaggrin is an epidermal protein that is crucial for skin barrier function. Up to 10% of Europeans and 5% of Asians carry at least one null allele in the filaggrin gene (FLG). Reduced expression of filaggrin in carriers of the null allele is associated with facilitated transfer...

  15. Effects of broccoli stem and leaf meal on broiler performance, skin pigmentation, antioxidant function, and meat quality.

    Science.gov (United States)

    Hu, C H; Wang, D G; Pan, H Y; Zheng, W B; Zuo, A Y; Liu, J X

    2012-09-01

    Three hundred sixty 1-d-old Ross 308 male broilers were used to study the effects of broccoli stem and leaf meal (BSLM) on growth performance, skin pigmentation, antioxidant function, and meat quality. The chicks were fed 4 diets containing different levels (0, 4.0, 8.0, and 12.0%) of BSLM as partial replacement for corn and soybean meal for a period of 42 d. The results showed that dietary supplementation of BSLM had no effect (P > 0.05) on growth performance. As compared with control, dietary 4%, 8%, and 12% BSLM increased (P poultry products quality with the more skin pigmentation and the less drip loss percentage of breast meat. The more skin pigmentation mainly related to the high amount of xanthophylls in BSLM. The decreased meat drip loss fed BSLM may be caused by the antioxidative function of BSLM.

  16. Contribution of High-Pressure-Induced Protein Modifications to the Microenvironment and Functional Properties of Rabbit Meat Sausages.

    Science.gov (United States)

    Xue, Siwen; Yu, Xiaobo; Yang, Huijuan; Xu, Xinglian; Ma, Hanjun; Zhou, Guanghong

    2017-06-01

    Rabbit meat batters were subjected to high pressure (HP, 100 to 300 MPa for 3, 9, or 15 min) to elucidate their effects on proteins structures, the microenvironment, and the resulting functionalities of the subsequently heated products. To determine these effects, we investigated structural and microenvironmental changes using Raman spectroscopy and also expressible moisture content, textural characteristics, and dynamic rheological properties of batters during heating (20 to 80 °C). Untreated samples served as controls. Analysis of specific Raman spectral regions demonstrated that applications of HP to rabbit meat batters tended to induce the transformation of the all-gauche S-S conformation to gauche-gauche-trans in the batter system. HP treatment higher than 100 MPa for 9 min promoted secondary structural rearrangements, and molecular polarity enhancement in the proteins prior to cooking. Also, increases of O-H stretching intensities of rabbit meat sausages were obtained by HP treatment, denoting the strengthening of water-holding capacity. These HP-induced alterations resulted in improved texture and, perhaps, improved juiciness of rabbit meat sausages (P < 0.05), however they had relatively poorer rheological properties than the controls. Nevertheless, HP treatment, especially 200 MPa for 9 or 15 min, was an effective technique for improving the functionalities of gel-type products through modification of meat proteins. © 2017 Institute of Food Technologists®.

  17. Identification and characterization of two functional variants in the human longevity gene FOXO3

    DEFF Research Database (Denmark)

    Flachsbart, Friederike; Dose, Janina; Gentschew, Liljana

    2017-01-01

    FOXO3 is consistently annotated as a human longevity gene. However, functional variants and underlying mechanisms for the association remain unknown. Here, we perform resequencing of the FOXO3 locus and single-nucleotide variant (SNV) genotyping in three European populations. We find two FOXO3 SNVs......, rs12206094 and rs4946935, to be most significantly associated with longevity and further characterize them functionally. We experimentally validate the in silico predicted allele-dependent binding of transcription factors (CTCF, SRF) to the SNVs. Specifically, in luciferase reporter assays...

  18. Cloning and characterization of functional subtype A HIV-1 envelope variants transmitted through breastfeeding.

    Science.gov (United States)

    Rainwater, Stephanie M J; Wu, Xueling; Nduati, Ruth; Nedellec, Rebecca; Mosier, Donald; John-Stewart, Grace; Mbori-Ngacha, Dorothy; Overbaugh, Julie

    2007-03-01

    Previous studies of HIV-1 variants transmitted from mother-to-infant have focused primarily on computational analyses of partial envelope gene sequences, rather than analyses of functional envelope variants. There are very few examples of well-characterized functional envelope clones from mother-infant pairs, especially from envelope variants representing the most prevalent subtypes worldwide. To address this, we amplified the envelope variants present in 4 mother-infant transmission pairs, all of whom were infected with subtype A and three of whom presumably transmitted HIV-1 during the breastfeeding period. Functional envelope clones were constructed, either encoding full-length envelope sequences from the mother and baby or by making chimeric envelope clones in a common backbone sequence. The infant envelope sequences were genetically homogeneous compared to the maternal viruses, and pseudoviruses bearing these envelopes all used CCR5 as a coreceptor. The infant viruses were generally resistant to neutralization by maternal antibodies present near the time of transmission. There were no notable differences in sensitivity of the mother and infant envelope variants to neutralization by heterologous plasma or monoclonal antibodies 2G12 and b12, or to inhibition by sCD4, PSC-RANTES or TAK779. This collection of viral envelopes, which can be used for making pseudotyped viruses, may be useful for examining the efficacy of interventions to block mother-infant transmission, including sera from vaccine candidates, purified antibodies under consideration for passive immunization and viral entry inhibitors.

  19. Waste utilization of apple pomace as a source of functional ingredient in buffalo meat sausage

    Directory of Open Access Journals (Sweden)

    Kaiser Younis

    2015-12-01

    Full Text Available Apple pomace was analyzed for its proximate analysis which showed protein content of 4.50% and total dietary fiber of 62.67%. Its functional properties were also carried out which showed high water- and oil-holding capacity of 3.89 gH2O g−1 Solid and 1.92 ml g−1, respectively. Its antimicrobial activity was also found against S. aureus, P. aeruginosa, and L. monocytogenes. Further, it has shown lower in vitro glucose retardation index. Buffalo meat sausages incorporated with apple pomace powder showed high cooking yield and emulsion stability of 94.46% and 74.70, respectively, as compared to control sausage. Additionally, the dietary fiber content got enhanced with the incorporation of apple pomace powder as expected.

  20. GRIN2B encephalopathy: novel findings on phenotype, variant clustering, functional consequences and treatment aspects.

    Science.gov (United States)

    Platzer, Konrad; Yuan, Hongjie; Schütz, Hannah; Winschel, Alexander; Chen, Wenjuan; Hu, Chun; Kusumoto, Hirofumi; Heyne, Henrike O; Helbig, Katherine L; Tang, Sha; Willing, Marcia C; Tinkle, Brad T; Adams, Darius J; Depienne, Christel; Keren, Boris; Mignot, Cyril; Frengen, Eirik; Strømme, Petter; Biskup, Saskia; Döcker, Dennis; Strom, Tim M; Mefford, Heather C; Myers, Candace T; Muir, Alison M; LaCroix, Amy; Sadleir, Lynette; Scheffer, Ingrid E; Brilstra, Eva; van Haelst, Mieke M; van der Smagt, Jasper J; Bok, Levinus A; Møller, Rikke S; Jensen, Uffe B; Millichap, John J; Berg, Anne T; Goldberg, Ethan M; De Bie, Isabelle; Fox, Stephanie; Major, Philippe; Jones, Julie R; Zackai, Elaine H; Abou Jamra, Rami; Rolfs, Arndt; Leventer, Richard J; Lawson, John A; Roscioli, Tony; Jansen, Floor E; Ranza, Emmanuelle; Korff, Christian M; Lehesjoki, Anna-Elina; Courage, Carolina; Linnankivi, Tarja; Smith, Douglas R; Stanley, Christine; Mintz, Mark; McKnight, Dianalee; Decker, Amy; Tan, Wen-Hann; Tarnopolsky, Mark A; Brady, Lauren I; Wolff, Markus; Dondit, Lutz; Pedro, Helio F; Parisotto, Sarah E; Jones, Kelly L; Patel, Anup D; Franz, David N; Vanzo, Rena; Marco, Elysa; Ranells, Judith D; Di Donato, Nataliya; Dobyns, William B; Laube, Bodo; Traynelis, Stephen F; Lemke, Johannes R

    2017-07-01

    We aimed for a comprehensive delineation of genetic, functional and phenotypic aspects of GRIN2B encephalopathy and explored potential prospects of personalised medicine. Data of 48 individuals with de novo GRIN2B variants were collected from several diagnostic and research cohorts, as well as from 43 patients from the literature. Functional consequences and response to memantine treatment were investigated in vitro and eventually translated into patient care. Overall, de novo variants in 86 patients were classified as pathogenic/likely pathogenic. Patients presented with neurodevelopmental disorders and a spectrum of hypotonia, movement disorder, cortical visual impairment, cerebral volume loss and epilepsy. Six patients presented with a consistent malformation of cortical development (MCD) intermediate between tubulinopathies and polymicrogyria. Missense variants cluster in transmembrane segments and ligand-binding sites. Functional consequences of variants were diverse, revealing various potential gain-of-function and loss-of-function mechanisms and a retained sensitivity to the use-dependent blocker memantine. However, an objectifiable beneficial treatment response in the respective patients still remains to be demonstrated. In addition to previously known features of intellectual disability, epilepsy and autism, we found evidence that GRIN2B encephalopathy is also frequently associated with movement disorder, cortical visual impairment and MCD revealing novel phenotypic consequences of channelopathies. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. Predicting the Functional Impact of KCNQ1 Variants of Unknown Significance.

    Science.gov (United States)

    Li, Bian; Mendenhall, Jeffrey L; Kroncke, Brett M; Taylor, Keenan C; Huang, Hui; Smith, Derek K; Vanoye, Carlos G; Blume, Jeffrey D; George, Alfred L; Sanders, Charles R; Meiler, Jens

    2017-10-01

    An emerging standard-of-care for long-QT syndrome uses clinical genetic testing to identify genetic variants of the KCNQ1 potassium channel. However, interpreting results from genetic testing is confounded by the presence of variants of unknown significance for which there is inadequate evidence of pathogenicity. In this study, we curated from the literature a high-quality set of 107 functionally characterized KCNQ1 variants. Based on this data set, we completed a detailed quantitative analysis on the sequence conservation patterns of subdomains of KCNQ1 and the distribution of pathogenic variants therein. We found that conserved subdomains generally are critical for channel function and are enriched with dysfunctional variants. Using this experimentally validated data set, we trained a neural network, designated Q1VarPred, specifically for predicting the functional impact of KCNQ1 variants of unknown significance. The estimated predictive performance of Q1VarPred in terms of Matthew's correlation coefficient and area under the receiver operating characteristic curve were 0.581 and 0.884, respectively, superior to the performance of 8 previous methods tested in parallel. Q1VarPred is publicly available as a web server at http://meilerlab.org/q1varpred. Although a plethora of tools are available for making pathogenicity predictions over a genome-wide scale, previous tools fail to perform in a robust manner when applied to KCNQ1. The contrasting and favorable results for Q1VarPred suggest a promising approach, where a machine-learning algorithm is tailored to a specific protein target and trained with a functionally validated data set to calibrate informatics tools. © 2017 American Heart Association, Inc.

  2. Valorization of functional properties of extract and powder of olive leaves in raw and cooked minced beef meat.

    Science.gov (United States)

    Aouidi, Fathia; Okba, Aicha; Hamdi, Moktar

    2017-08-01

    Olive leaves (OL), available in huge amounts from pruning, are known to be a useful source of biologically active compounds. This study investigated the potential application of OL as a supplement to minced beef meat in order to develop a functional product. The effect of OL extract or powder (100 and 150 µg phenols g -1 meat) on the quality and stability of raw and cooked meat during refrigerated storage was examined. Microwave drying at 600 W gave OL with the highest antioxidant quality (evaluated by TEAC/[phenols] (mg mg -1 ) and DPPH/[phenols] (mg mg -1 )) compared with other methods. OL showed an ability to inhibit (P production was 43-65% in control samples and 14-35% in treated samples). OL also improved the technological quality of the meat, decreasing (P meat products of good technological quality that remain stable during storage. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  3. A genetic variant in COL11A1 is functionally associated with lumbar ...

    Indian Academy of Sciences (India)

    This study aimed to explore whether the genetic variant of COL11A1 is functionally associated with the development of lumbar disc herniation (LDH) in Chinese population. SNP rs1676486 of COL11A1 was genotyped in 647 patients and 532 healthy controls. The differences of genotype and allele distributions between ...

  4. CAUSEL: an epigenome- and genome-editing pipeline for establishing function of noncoding GWAS variants

    DEFF Research Database (Denmark)

    Spisák, Sándor; Lawrenson, Kate; Fu, Yanfang

    2015-01-01

    The vast majority of disease-associated single-nucleotide polymorphisms (SNPs) mapped by genome-wide association studies (GWASs) are located in the non-protein-coding genome, but establishing the functional and mechanistic roles of these sequence variants has proven challenging. Here we describe ...

  5. A genetic variant in COL11A1 is functionally associated with lumbar ...

    Indian Academy of Sciences (India)

    WENJUN LIU

    2017-12-14

    Dec 14, 2017 ... Abstract. This study aimed to explore whether the genetic variant of COL11A1 is functionally associated with the development of lumbar disc herniation (LDH) in Chinese population. SNP rs1676486 of COL11A1 was genotyped in 647 patients and 532 healthy controls. The differences of genotype and ...

  6. GRIN2B encephalopathy : Novel findings on phenotype, variant clustering, functional consequences and treatment aspects

    NARCIS (Netherlands)

    Platzer, Konrad; Yuan, Hongjie; Schütz, Hannah; Winschel, Alexander; Chen, Wenjuan; Hu, Chun; Kusumoto, Hirofumi; Heyne, Henrike O; Helbig, Katherine L; Tang, Sha; Willing, Marcia C; Tinkle, Brad T; Adams, Darius J; Depienne, Christel; Keren, Boris; Mignot, Cyril; Frengen, Eirik; Strømme, Petter; Biskup, Saskia; Döcker, Dennis; Strom, Tim M.; Mefford, Heather C.; Myers, Candace T.; Muir, Alison M; LaCroix, Amy; Sadleir, Lynette G.; Scheffer, Ingrid E.; Brilstra, Eva; van Haelst, Mieke M.; van der Smagt, Jasper J.; Bok, Levinus A; Møller, Rikke S.; Jensen, Uffe Birk; Millichap, John J; Berg, Anne T; Goldberg, Ethan M; De Bie, Isabelle; Fox, Stephanie; Major, Philippe; Jones, Julie R; Zackai, Elaine H.; Abou Jamra, Rami; Rolfs, Arndt; Leventer, Richard J; Lawson, John A; Roscioli, Tony; Jansen, Floor E.; Ranza, Emmanuelle; Korff, Christian M; Lehesjoki, Anna-Elina; Courage, Carolina; Linnankivi, Tarja; Smith, Douglas R; Stanley, Christine; Mintz, Mark; McKnight, Dianalee; Decker, Amy; Tan, Wen-Hann; Tarnopolsky, Mark A; Brady, Lauren I; Wolff, Markus; Dondit, Lutz; Pedro, Helio F; Parisotto, Sarah E; Jones, Kelly L; Patel, Anup D; Franz, David N; Vanzo, Rena; Marco, Elysa; Ranells, Judith D; Di Donato, Nataliya; Dobyns, William B.; Laube, Bodo; Traynelis, Stephen F; Lemke, Johannes R.

    2017-01-01

    Background: We aimed for a comprehensive delineation of genetic, functional and phenotypic aspects of GRIN2B encephalopathy and explored potential prospects of personalised medicine. Methods: Data of 48 individuals with de novo GRIN2B variants were collected from several diagnostic and research

  7. Functional and clinical relevance of novel and known PCSK1 variants for childhood obesity and glucose metabolism

    Directory of Open Access Journals (Sweden)

    Dennis Löffler

    2017-03-01

    Conclusions: We identified and functionally characterized two rare novel PCSK1 variants of which c.1095 + 1G > A caused complete loss of protein function. In addition to confirming rs6232 and rs6234 in PCSK1 as polygenic risk variants for childhood obesity, we describe an association of rs725522 with insulin metabolism. Our results support the contribution of PCSK1 variants to obesity predisposition in children.

  8. IRF4 rs12203592 functional variant and melanoma survival.

    Science.gov (United States)

    Potrony, Miriam; Rebollo-Morell, Aida; Giménez-Xavier, Pol; Zimmer, Lisa; Puig-Butille, Joan Anton; Tell-Marti, Gemma; Sucker, Antje; Badenas, Celia; Carrera, Cristina; Malvehy, Josep; Schadendorf, Dirk; Puig, Susana

    2017-04-15

    Inherited genetic factors may modulate clinical outcome in melanoma. Some low-to-medium risk genes in melanoma susceptibility play a role in melanoma outcome. Our aim was to assess the role of the functional IRF4 SNP rs12203592 in melanoma prognosis in two independent sets (Barcelona, N = 493 and Essen, N = 438). Genotype association analyses showed that the IRF4 rs12203592 T allele increased the risk of dying from melanoma in both sets (Barcelona: odds ratio [OR] = 6.53, 95% CI 1.38-30.87, Adj p = 0.032; Essen: OR = 1.68, 95% CI 1.04-2.72, Adj p = 0.035). Survival analyses only showed significance for the Barcelona set (hazard ratio = 4.58, 95% CI 1.11-18.92, Adj p = 0.036). This SNP was also associated with tumour localization, increasing the risk of developing melanoma in head or neck (OR = 1.79, 95% CI 1.07-2.98, Adj p = 0.032) and protecting from developing melanoma in the trunk (OR = 0.59, 95% CI 0.41-0.85, Adj p = 0.004). These findings suggest for the first time that IRF4 rs12203592 plays a role in the modulation of melanoma outcome and confirms its contribution to the localization of the primary tumour. © 2017 UICC.

  9. Identification and functional characterization of de novo FOXP1 variants provides novel insights into the etiology of neurodevelopmental disorder.

    Science.gov (United States)

    Sollis, Elliot; Graham, Sarah A; Vino, Arianna; Froehlich, Henning; Vreeburg, Maaike; Dimitropoulou, Danai; Gilissen, Christian; Pfundt, Rolph; Rappold, Gudrun A; Brunner, Han G; Deriziotis, Pelagia; Fisher, Simon E

    2016-02-01

    De novo disruptions of the neural transcription factor FOXP1 are a recently discovered, rare cause of sporadic intellectual disability (ID). We report three new cases of FOXP1-related disorder identified through clinical whole-exome sequencing. Detailed phenotypic assessment confirmed that global developmental delay, autistic features, speech/language deficits, hypotonia and mild dysmorphic features are core features of the disorder. We expand the phenotypic spectrum to include sensory integration disorder and hypertelorism. Notably, the etiological variants in these cases include two missense variants within the DNA-binding domain of FOXP1. Only one such variant has been reported previously. The third patient carries a stop-gain variant. We performed functional characterization of the three missense variants alongside our stop-gain and two previously described truncating/frameshift variants. All variants severely disrupted multiple aspects of protein function. Strikingly, the missense variants had similarly severe effects on protein function as the truncating/frameshift variants. Our findings indicate that a loss of transcriptional repression activity of FOXP1 underlies the neurodevelopmental phenotype in FOXP1-related disorder. Interestingly, the three novel variants retained the ability to interact with wild-type FOXP1, suggesting these variants could exert a dominant-negative effect by interfering with the normal FOXP1 protein. These variants also retained the ability to interact with FOXP2, a paralogous transcription factor disrupted in rare cases of speech and language disorder. Thus, speech/language deficits in these individuals might be worsened through deleterious effects on FOXP2 function. Our findings highlight that de novo FOXP1 variants are a cause of sporadic ID and emphasize the importance of this transcription factor in neurodevelopment. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email

  10. Suspected Lynch syndrome associated MSH6 variants: A functional assay to determine their pathogenicity.

    Directory of Open Access Journals (Sweden)

    Hellen Houlleberghs

    2017-05-01

    Full Text Available Lynch syndrome (LS is a hereditary cancer predisposition caused by inactivating mutations in DNA mismatch repair (MMR genes. Mutations in the MSH6 DNA MMR gene account for approximately 18% of LS cases. Many LS-associated sequence variants are nonsense and frameshift mutations that clearly abrogate MMR activity. However, missense mutations whose functional implications are unclear are also frequently seen in suspected-LS patients. To conclusively diagnose LS and enroll patients in appropriate surveillance programs to reduce morbidity as well as mortality, the functional consequences of these variants of uncertain clinical significance (VUS must be defined. We present an oligonucleotide-directed mutagenesis screen for the identification of pathogenic MSH6 VUS. In the screen, the MSH6 variant of interest is introduced into mouse embryonic stem cells by site-directed mutagenesis. Subsequent selection for MMR-deficient cells using the DNA damaging agent 6-thioguanine (6TG allows the identification of MMR abrogating VUS because solely MMR-deficient cells survive 6TG exposure. We demonstrate the efficacy of the genetic screen, investigate the phenotype of 26 MSH6 VUS and compare our screening results to clinical data from suspected-LS patients carrying these variant alleles.

  11. Functional study of DAND5 variant in patients with Congenital Heart Disease and laterality defects.

    Science.gov (United States)

    Cristo, Fernando; Inácio, José M; de Almeida, Salomé; Mendes, Patrícia; Martins, Duarte Saraiva; Maio, José; Anjos, Rui; Belo, José A

    2017-07-24

    Perturbations on the Left-Right axis establishment lead to laterality defects, with frequently associated Congenital Heart Diseases (CHDs). Indeed, in the last decade, it has been reported that the etiology of isolated cases of CHDs or cases of laterality defects with associated CHDs is linked with variants of genes involved in the Nodal signaling pathway. With this in mind, we analyzed a cohort of 38 unrelated patients with Congenital Heart Defects that can arise from initial perturbations in the formation of the Left-Right axis and 40 unrelated ethnically matched healthy individuals as a control population. Genomic DNA was extracted from buccal epithelial cells, and variants screening was performed by PCR and direct sequencing. A Nodal-dependent luciferase assay was conducted in order to determine the functional effect of the variant found. In this work, we report two patients with a DAND5 heterozygous non-synonymous variant (c.455G > A) in the functional domain of the DAND5 protein (p.R152H), a master regulator of Nodal signaling. Patient 1 presents left isomerism, ventricular septal defect with overriding aorta and pulmonary atresia, while patient 2 presents ventricular septal defect with overriding aorta, right ventricular hypertrophy and pulmonary atresia (a case of extreme tetralogy of Fallot phenotype). The functional analysis assay showed a significant decrease in the activity of this variant protein when compared to its wild-type counterpart. Altogether, our results provide new insight into the molecular mechanism of the laterality defects and related CHDs, priming for the first time DAND5 as one of multiple candidate determinants for CHDs in humans.

  12. Genetic variants affecting cross-sectional lung function in adults show little or no effect on longitudinal lung function decline

    DEFF Research Database (Denmark)

    John, Catherine; Soler Artigas, María; Hui, Jennie

    2017-01-01

    across eight time points). A mixed model was fitted and weighted risk scores were calculated for the joint effect of 26 known regions on baseline and longitudinal changes in FEV1 and FEV1/FVC. Potential additional regions of interest were identified and followed up in two independent cohorts. RESULTS......: The 26 regions previously associated with cross-sectional lung function jointly showed a strong effect on baseline lung function (p=4.44×10-16 for FEV1/FVC) but no effect on longitudinal decline (p=0.160 for FEV1/FVC). This was replicated in an independent cohort. 39 additional regions of interest (48...... variants) were identified; these associations were not replicated in two further cohorts. CONCLUSIONS: Previously identified genetic variants jointly have a strong effect on cross-sectional lung function in adults but little or no effect on the rate of decline of lung function. It is possible...

  13. BRCA1 R1699Q variant displaying ambiguous functional abrogation confers intermediate breast and ovarian cancer risk

    DEFF Research Database (Denmark)

    Spurdle, Amanda B; Whiley, Phillip J; Thompson, Bryony

    2012-01-01

    Clinical classification of rare sequence changes identified in the breast cancer susceptibility genes BRCA1 and BRCA2 is essential for appropriate genetic counselling of individuals carrying these variants. We previously showed that variant BRCA1 c.5096G>A p.Arg1699Gln in the BRCA1 transcriptional...... transactivation domain demonstrated equivocal results from a series of functional assays, and proposed that this variant may confer low to moderate risk of cancer....

  14. Emerging applications of genome-editing technology to examine functionality of GWAS-associated variants for complex traits.

    Science.gov (United States)

    Smith, Andrew J P; Deloukas, Panos; Munroe, Patricia B

    2018-04-13

    Over the last decade, genome-wide association studies (GWAS) have propelled the discovery of thousands of loci associated with complex diseases. The focus is now turning towards the function of these association signals, determining the causal variant(s) amongst those in strong linkage disequilibrium, and identifying their underlying mechanisms, such as long-range gene regulation. Genome-editing techniques utilising zinc-finger nucleases (ZFN), transcription activator-like effector nucleases (TALENs) and clustered regularly-interspaced short palindromic repeats with Cas9 nuclease (CRISPR-Cas9), are becoming the tools of choice to establish functionality for these variants, due to the ability to assess effects of single variants in vivo. This review will discuss examples of how these technologies have begun to aid functional analysis of GWAS loci for complex traits such as cardiovascular disease, type 2 diabetes, cancer, obesity and autoimmune disease. We focus on analysis of variants occurring within non-coding genomic regions, as these comprise the majority of GWAS variants, providing the greatest challenges to determining functionality, and compare editing strategies that provide different levels of evidence for variant functionality. The review describes molecular insights into some of these potentially causal variants, and how these may relate to the pathology of the trait, and look towards future directions for these technologies in post-GWAS analysis, such as base-editing.

  15. Reliable and rapid characterization of functional FCN2 gene variants reveals diverse geographical patterns

    Directory of Open Access Journals (Sweden)

    Ojurongbe Olusola

    2012-05-01

    Full Text Available Abstract Background Ficolin-2 coded by FCN2 gene is a soluble serum protein and an innate immune recognition element of the complement system. FCN2 gene polymorphisms reveal distinct geographical patterns and are documented to alter serum ficolin levels and modulate disease susceptibility. Methods We employed a real-time PCR based on Fluorescence Resonance Energy Transfer (FRET method to genotype four functional SNPs including -986 G > A (#rs3124952, -602 G > A (#rs3124953, -4A > G (#rs17514136 and +6424 G > T (#rs7851696 in the ficolin-2 (FCN2 gene. We characterized the FCN2 variants in individuals representing Brazilian (n = 176, Nigerian (n = 180, Vietnamese (n = 172 and European Caucasian ethnicity (n = 165. Results We observed that the genotype distribution of three functional SNP variants (−986 G > A, -602 G > A and -4A > G differ significantly between the populations investigated (p p  Conclusions The observed distribution of the FCN2 functional SNP variants may likely contribute to altered serum ficolin levels and this may depend on the different disease settings in world populations. To conclude, the use of FRET based real-time PCR especially for FCN2 gene will benefit a larger scientific community who extensively depend on rapid, reliable method for FCN2 genotyping.

  16. The Effect of Antioxidant Activity of Liquid Smoke in Feed Supplement Block on Meat Functional of Muscle Longissimus dorsi

    Science.gov (United States)

    Abustam, E.; Said, M. I.; Yusuf, M.

    2018-02-01

    This study aims to look at the role of liquid smoke as an antioxidant added in feed supplement block and administered to cattle for 45 days on the functional properties of meat. The level of liquid smoke in the feed and the time of maturation in Muscle Longissimus dorsi after slaughtering cattle were the two treatment factors observed for the functional properties of meat. The study used a complete randomized design in which factor 1 was a 10% smoke level in the feed (0, 1, 2%) and factor 2 was maturation time (0, 2, 4, 6, 8 days). The parameters observed were water holding capacity (WHC), raw meat shear force (RMSF), fat oxidation rate (thiobarbituric acid reactive substance) and antioxidant activity (DPPH). The results showed that liquid smoke levels lowered the WHC, RMSF more or less the same, increased fat oxidation rate, and antioxidant activity more or less the same. While maturation tends to increase WHC, increase RMSF, fat oxidation rate, and antioxidant activity. It can be concluded that liquid smoke as an antioxidant in the diet of block supplements can maintain the functional properties of Muscle Longissimus dorsi of Bali cattle during maturation.

  17. Genetic Variants in KLOTHO Associate With Cognitive Function in the Oldest Old Group

    DEFF Research Database (Denmark)

    Mengel-From, Jonas; Sørensen, Mette; Nygaard, Marianne

    2016-01-01

    Decline in cognitive abilities is a major concern in aging individuals. A potential important factor for functioning of the central nervous system in late-life stages is the KLOTHO (KL) gene. KL is expressed in various organs including the brain and is involved in multiple biological processes......, for example, growth factor signaling. In the present study, 19 tagging gene variants in KL were studied in relation to 2 measures of cognitive function, a 5-item cognitive composite score and the Mini Mental State Examination, in 1,480 Danes 92-100 years of age. We found that heterozygotes for the previously...

  18. Significance of functional disease-causal/susceptible variants identified by whole-genome analyses for the understanding of human diseases.

    Science.gov (United States)

    Hitomi, Yuki; Tokunaga, Katsushi

    2017-01-01

    Human genome variation may cause differences in traits and disease risks. Disease-causal/susceptible genes and variants for both common and rare diseases can be detected by comprehensive whole-genome analyses, such as whole-genome sequencing (WGS), using next-generation sequencing (NGS) technology and genome-wide association studies (GWAS). Here, in addition to the application of an NGS as a whole-genome analysis method, we summarize approaches for the identification of functional disease-causal/susceptible variants from abundant genetic variants in the human genome and methods for evaluating their functional effects in human diseases, using an NGS and in silico and in vitro functional analyses. We also discuss the clinical applications of the functional disease causal/susceptible variants to personalized medicine.

  19. Functional variants of the melanocortin-4 receptor associated with the Odontoceti and Mysticeti suborders of cetaceans.

    Science.gov (United States)

    Zhao, Liyuan; Zhou, Xiaofan; Rokas, Antonis; Cone, Roger D

    2017-07-18

    Cetaceans, a group of mammals adapted to the aquatic environment that descended from terrestrial artiodactyls, exhibit tremendous interspecific differences in a number of phenotypes, including feeding behavior, such as filter feeding in the Mysticeti vs prey-hunting Odontoceti, and size, with the smallest cetacean, the vaquita, at 1.4 meters and the largest, the blue whale, reaching 33 meters. The Melanocortin-4 receptor (MC4R) regulates food intake, energy balance, and somatic growth in both mammals and teleosts. In this study, we examined allelic variants of the MC4R in cetaceans. We sequenced the MC4R from 20 cetaceans, and pharmacologically characterized 17 of these protein products. Results identified a single variation at amino acid 156 in the MC4R from representative species of major cetacean lineages uniquely associated with the toothed whales or Odontoceti (arginine at 156) and baleen whales or Mysticeti (glutamine at 156). The Q156 receptor variant found in the larger baleen whales was functionally less responsive to its endogenous anorexigenic ligand, α-MSH. Furthermore, the R156 receptor variant showed greater constitutive activity and a higher affinity for ligand. These data suggest that the MC4R may be one gene involved in the evolution of feeding ecology, energy balance, and body size in cetaceans.

  20. Gauge-fixing parameter dependence of two-point gauge-variant correlation functions

    International Nuclear Information System (INIS)

    Zhai, C.

    1996-01-01

    The gauge-fixing parameter ξ dependence of two-point gauge-variant correlation functions is studied for QED and QCD. We show that, in three Euclidean dimensions, or for four-dimensional thermal gauge theories, the usual procedure of getting a general covariant gauge-fixing term by averaging over a class of covariant gauge-fixing conditions leads to a nontrivial gauge-fixing parameter dependence in gauge-variant two-point correlation functions (e.g., fermion propagators). This nontrivial gauge-fixing parameter dependence modifies the large-distance behavior of the two-point correlation functions by introducing additional exponentially decaying factors. These factors are the origin of the gauge dependence encountered in some perturbative evaluations of the damping rates and the static chromoelectric screening length in a general covariant gauge. To avoid this modification of the long-distance behavior introduced by performing the average over a class of covariant gauge-fixing conditions, one can either choose a vanishing gauge-fixing parameter or apply an unphysical infrared cutoff. copyright 1996 The American Physical Society

  1. Variants of asthma and chronic obstructive pulmonary disease genes and lung function decline in aging.

    Science.gov (United States)

    Poon, Audrey H; Houseman, E Andres; Ryan, Louise; Sparrow, David; Vokonas, Pantel S; Litonjua, Augusto A

    2014-07-01

    A substantial proportion of the general population has low lung function, and lung function is known to decrease as we age. Low lung function is a feature of several pulmonary disorders, such as uncontrolled asthma and chronic obstructive pulmonary disease. The objective of this study is to investigate the association of polymorphisms in asthma and chronic obstructive pulmonary disease candidate genes with rates of lung function decline in a general population sample of aging men. We analyzed data from a cohort of 1,047 Caucasian men without known lung disease, who had a mean of 25 years of lung function data, and on whom DNA was available. The cohort was randomly divided into two groups, and we tested a total of 940 single-nucleotide polymorphisms in 44 asthma and chronic obstructive pulmonary disease candidate genes in the first group (testing cohort, n = 545) for association with change in forced expiratory volume in 1 second over time. One hundred nineteen single-nucleotide polymorphisms that showed nominal associations in the testing cohort were then genotyped and tested in the second group (replication cohort, n = 502). Evidence for association from the testing and replication cohorts were combined, and after adjustment for multiple testing, seven variants of three genes (DPP10, NPSR1, and ADAM33) remained significantly associated with change in forced expiratory volume in 1 second over time. Our findings that genetic variants of genes involved in asthma and chronic obstructive pulmonary disease are associated with lung function decline in normal aging participants suggest that similar genetic mechanisms may underlie lung function decline in both disease and normal aging processes. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Postnatally-transmitted HIV-1 Envelope variants have similar neutralization-sensitivity and function to that of nontransmitted breast milk variants

    Science.gov (United States)

    2013-01-01

    Background Breastfeeding is a leading cause of infant HIV-1 infection in the developing world, yet only a minority of infants exposed to HIV-1 via breastfeeding become infected. As a genetic bottleneck severely restricts the number of postnatally-transmitted variants, genetic or phenotypic properties of the virus Envelope (Env) could be important for the establishment of infant infection. We examined the efficiency of virologic functions required for initiation of infection in the gastrointestinal tract and the neutralization sensitivity of HIV-1 Env variants isolated from milk of three postnatally-transmitting mothers (n=13 viruses), five clinically-matched nontransmitting mothers (n=16 viruses), and seven postnatally-infected infants (n = 7 postnatally-transmitted/founder (T/F) viruses). Results There was no difference in the efficiency of epithelial cell interactions between Env virus variants from the breast milk of transmitting and nontransmitting mothers. Moreover, there was similar efficiency of DC-mediated trans-infection, CCR5-usage, target cell fusion, and infectivity between HIV-1 Env-pseudoviruses from nontransmitting mothers and postnatal T/F viruses. Milk Env-pseudoviruses were generally sensitive to neutralization by autologous maternal plasma and resistant to breast milk neutralization. Infant T/F Env-pseudoviruses were equally sensitive to neutralization by broadly-neutralizing monoclonal and polyclonal antibodies as compared to nontransmitted breast milk Env variants. Conclusion Postnatally-T/F Env variants do not appear to possess a superior ability to interact with and cross a mucosal barrier or an exceptional resistance to neutralization that define their capability to initiate infection across the infant gastrointestinal tract in the setting of preexisting maternal antibodies. PMID:23305422

  3. Integrative analysis of functional genomic annotations and sequencing data to identify rare causal variants via hierarchical modeling

    Directory of Open Access Journals (Sweden)

    Marinela eCapanu

    2015-05-01

    Full Text Available Identifying the small number of rare causal variants contributing to disease has beena major focus of investigation in recent years, but represents a formidable statisticalchallenge due to the rare frequencies with which these variants are observed. In thiscommentary we draw attention to a formal statistical framework, namely hierarchicalmodeling, to combine functional genomic annotations with sequencing data with theobjective of enhancing our ability to identify rare causal variants. Using simulations weshow that in all configurations studied, the hierarchical modeling approach has superiordiscriminatory ability compared to a recently proposed aggregate measure of deleteriousness,the Combined Annotation-Dependent Depletion (CADD score, supportingour premise that aggregate functional genomic measures can more accurately identifycausal variants when used in conjunction with sequencing data through a hierarchicalmodeling approach

  4. The genomic distribution and function of histone variant HTZ-1 during C. elegans embryogenesis.

    Directory of Open Access Journals (Sweden)

    Christina M Whittle

    2008-09-01

    Full Text Available In all eukaryotes, histone variants are incorporated into a subset of nucleosomes to create functionally specialized regions of chromatin. One such variant, H2A.Z, replaces histone H2A and is required for development and viability in all animals tested to date. However, the function of H2A.Z in development remains unclear. Here, we use ChIP-chip, genetic mutation, RNAi, and immunofluorescence microscopy to interrogate the function of H2A.Z (HTZ-1 during embryogenesis in Caenorhabditis elegans, a key model of metazoan development. We find that HTZ-1 is expressed in every cell of the developing embryo and is essential for normal development. The sites of HTZ-1 incorporation during embryogenesis reveal a genome wrought by developmental processes. HTZ-1 is incorporated upstream of 23% of C. elegans genes. While these genes tend to be required for development and occupied by RNA polymerase II, HTZ-1 incorporation does not specify a stereotypic transcription program. The data also provide evidence for unexpectedly widespread independent regulation of genes within operons during development; in 37% of operons, HTZ-1 is incorporated upstream of internally encoded genes. Fewer sites of HTZ-1 incorporation occur on the X chromosome relative to autosomes, which our data suggest is due to a paucity of developmentally important genes on X, rather than a direct function for HTZ-1 in dosage compensation. Our experiments indicate that HTZ-1 functions in establishing or maintaining an essential chromatin state at promoters regulated dynamically during C. elegans embryogenesis.

  5. Optimization of Membership Functions for the Fuzzy Controllers of the Water Tank and Inverted Pendulum with Differents PSO Variants

    Directory of Open Access Journals (Sweden)

    Patricia Melin

    2013-11-01

    Full Text Available In this paper the Particle Swarm Optimization metaheuristic and two of its variants (inertia weight and constriction coefficient are used as an optimization strategy for the design of optimal membership functions of fuzzy control systems for the water tank and inverted pendulum benchmark problems. Each variant has its own advantages in the algorithm, allowing the exploration and exploitation in different ways and this allows finding the optimal solution in a better way.

  6. Identification and functional activity of a staphylocoagulase type XI variant originating from staphylococcal food poisoning isolates.

    Science.gov (United States)

    Suzuki, Y; Matsushita, S; Kubota, H; Kobayashi, M; Murauchi, K; Higuchi, Y; Kato, R; Hirai, A; Sadamasu, K

    2016-09-01

    Staphylocoagulase, an extracellular protein secreted by Staphylococcus aureus, has been used as an epidemiological marker. At least 12 serotypes and 24 genotypes subdivided on the basis of nucleotide sequence have been reported to date. In this study, we identified a novel staphylocoagulase nucleotide sequence, coa310, from staphylococcal food poisoning isolates that had the ability to coagulate plasma, but could not be typed using the conventional method. The protein encoded by coa310 contained the six fundamental conserved domains of staphylocoagulase. The full-length nucleotide sequence of coa310 shared the highest similarity (77·5%) with that of staphylocoagulase-type (SCT) XIa. The sequence of the D1 region, which would be responsible for the determination of SCT, shared the highest similarity (91·8%) with that of SCT XIa. These results suggest that coa310 is a novel variant of SCT XI. Moreover, we demonstrated that coa310 encodes a functioning coagulase, by confirming the coagulating activity of the recombinant protein expressed from coa310. This is the first study to directly demonstrate that Coa310, a putative SCT XI, has coagulating activity. These findings may be useful for the improvement of the staphylocoagulase-typing method, including serotyping and genotyping. This is the first study to identify a novel variant of staphylocoagulase type XI based on its nucleotide sequence and to demonstrate coagulating activity in the variant using a recombinant protein. Elucidation of the variety of staphylocoagulases will provide suggestions for further improvement of the staphylocoagulase-typing method and contribute to our understanding of the epidemiologic characterization of Staphylococcus aureus. © 2016 The Society for Applied Microbiology.

  7. European consumer attitudes on the associated health benefits of neutraceutical-containing processed meats using Co-enzyme Q10 as a sample functional ingredient.

    Science.gov (United States)

    Tobin, Brian D; O'Sullivan, Maurice G; Hamill, Ruth; Kerry, Joseph P

    2014-06-01

    This study accumulated European consumer attitudes towards processed meats and their use as a functional food. A survey was set up using an online web-application to gather information on consumer perception of processed meats as well as neutraceutical-containing processed meats. 548 responses were obtained and statistical analysis was carried out using a statistical software package. Data was summarized as frequencies for each question and statistical differences analyzed using the Chi-Square statistical test with a significance level of 5% (Pmeat indicate that they are unhealthy products. Most believe that processed meats contain large quantities of harmful chemicals, fat and salt. Consumers were found to be very pro-bioactive compounds in yogurt style products but unsure of their feelings in meat based products, which is likely due to the lack of familiarity to these products. Many of the respondents were willing to consume meat based functional foods but were not willing to pay more for them. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Biallelic loss-of-function variants in DOCK3 cause muscle hypotonia, ataxia, and intellectual disability.

    Science.gov (United States)

    Helbig, K L; Mroske, C; Moorthy, D; Sajan, S A; Velinov, M

    2017-10-01

    DOCK3 encodes the dedicator of cytokinesis 3 protein, a member of the DOCK180 family of proteins that are characterized by guanine-nucleotide exchange factor activity. DOCK3 is expressed exclusively in the central nervous system and plays an important role in axonal outgrowth and cytoskeleton reorganization. Dock3 knockout mice exhibit motor deficiencies with abnormal ataxic gait and impaired learning. We report 2 siblings with biallelic loss-of-function variants in DOCK3. Diagnostic whole-exome sequencing (WES) and chromosomal microarray were performed on a proband with severe developmental disability, hypotonia, and ataxic gait. Testing was also performed on the proband's similarly affected brother. A paternally inherited 458 kb deletion in chromosomal region 3p21.2 disrupting the DOCK3 gene was identified in both affected siblings. WES identified a nonsense variant c.382C>G (p.Gln128*) in the DOCK3 gene (NM_004947) on the maternal allele in both siblings. Common features in both affected individuals include severe developmental disability, ataxic gait, and severe hypotonia, which recapitulates the Dock3 knockout mouse phenotype. We show that complete DOCK3 deficiency in humans leads to developmental disability with significant hypotonia and gait ataxia, probably due to abnormal axonal development. © 2017 The Authors. Clinical Genetics published by John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Association study of functional genetic variants of innate immunity related genes in celiac disease

    Directory of Open Access Journals (Sweden)

    Martín J

    2005-08-01

    Full Text Available Abstract Background Recent evidence suggest that the innate immune system is implicated in the early events of celiac disease (CD pathogenesis. In this work for the first time we have assessed the relevance of different proinflammatory mediators typically related to innate immunity in CD predisposition. Methods We performed a familial study in which 105 celiac families characterized by the presence of an affected child with CD were genotyped for functional polymorphisms located at regulatory regions of IL-1α, IL-1β, IL-1RN, IL-18, RANTES and MCP-1 genes. Familial data was analysed with a transmission disequilibrium test (TDT that revealed no statistically significant differences in the transmission pattern of the different genetic markers considered. Results The TDT analysis for IL-1α, IL-1β, IL-1RN, IL-18, and MCP-1 genes genetic variants did not reveal biased transmission to the affected offspring. Only a borderline association of RANTES promoter genetic variants with CD predisposition was observed. Conclusion Our results suggest that the analysed polymorphisms of IL-1α, IL-1β, IL-1RN, IL-18, RANTES and MCP-1 genes do not seem to play a major role in CD genetic predisposition in our population.

  10. Rare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Johanna Jakobsdottir

    2016-10-01

    Full Text Available We performed an exome-wide association analysis in 1393 late-onset Alzheimer's disease (LOAD cases and 8141 controls from the CHARGE consortium. We found that a rare variant (P155L in TM2D3 was enriched in Icelanders (~0.5% versus <0.05% in other European populations. In 433 LOAD cases and 3903 controls from the Icelandic AGES sub-study, P155L was associated with increased risk and earlier onset of LOAD [odds ratio (95% CI = 7.5 (3.5-15.9, p = 6.6x10-9]. Mutation in the Drosophila TM2D3 homolog, almondex, causes a phenotype similar to loss of Notch/Presenilin signaling. Human TM2D3 is capable of rescuing these phenotypes, but this activity is abolished by P155L, establishing it as a functionally damaging allele. Our results establish a rare TM2D3 variant in association with LOAD susceptibility, and together with prior work suggests possible links to the β-amyloid cascade.

  11. VAT: a computational framework to functionally annotate variants in personal genomes within a cloud-computing environment.

    Science.gov (United States)

    Habegger, Lukas; Balasubramanian, Suganthi; Chen, David Z; Khurana, Ekta; Sboner, Andrea; Harmanci, Arif; Rozowsky, Joel; Clarke, Declan; Snyder, Michael; Gerstein, Mark

    2012-09-01

    The functional annotation of variants obtained through sequencing projects is generally assumed to be a simple intersection of genomic coordinates with genomic features. However, complexities arise for several reasons, including the differential effects of a variant on alternatively spliced transcripts, as well as the difficulty in assessing the impact of small insertions/deletions and large structural variants. Taking these factors into consideration, we developed the Variant Annotation Tool (VAT) to functionally annotate variants from multiple personal genomes at the transcript level as well as obtain summary statistics across genes and individuals. VAT also allows visualization of the effects of different variants, integrates allele frequencies and genotype data from the underlying individuals and facilitates comparative analysis between different groups of individuals. VAT can either be run through a command-line interface or as a web application. Finally, in order to enable on-demand access and to minimize unnecessary transfers of large data files, VAT can be run as a virtual machine in a cloud-computing environment. VAT is implemented in C and PHP. The VAT web service, Amazon Machine Image, source code and detailed documentation are available at vat.gersteinlab.org.

  12. Determining the functional significance of mismatch repair gene missense variants using biochemical and cellular assays

    DEFF Research Database (Denmark)

    Heinen, Christopher D; Juel Rasmussen, Lene

    2012-01-01

    ABSTRACT: With the discovery that the hereditary cancer susceptibility disease Lynch syndrome (LS) is caused by deleterious germline mutations in the DNA mismatch repair (MMR) genes nearly 20 years ago, genetic testing can now be used to diagnose this disorder in patients. A definitive diagnosis...... of LS can direct how clinicians manage the disease as well as prevent future cancers for the patient and their families. A challenge emerges, however, when a germline missense variant is identified in a MMR gene in a suspected LS patient. The significance of a single amino acid change in these large...... some of these assays along with the challenges of using such assays to determine the functional consequences of MMR VUS which, in turn, can provide valuable insight into their clinical significance. With increased gene sequencing in patients, the number of identified VUS has expanded dramatically...

  13. Association of ABCB1 genetic variants with renal function in Africans and in Caucasians

    Directory of Open Access Journals (Sweden)

    Elston Robert C

    2008-06-01

    Full Text Available Abstract Background The P-glycoprotein, encoded by the ABCB1 gene, is expressed in human endothelial and mesangial cells, which contribute to control renal plasma flow and glomerular filtration rate. We investigated the association of ABCB1 variants with renal function in African and Caucasian subjects. Methods In Africans (290 subjects from 62 pedigrees, we genotyped the 2677G>T and 3435 C>T ABCB1 polymorphisms. Glomerular filtration rate (GFR was measured using inulin clearance and effective renal plasma flow (ERPF using para-aminohippurate clearance. In Caucasians (5382 unrelated subjects, we analyzed 30 SNPs located within and around ABCB1, using data from the Affymetrix 500 K chip. GFR was estimated using the simplified Modification of the Diet in Renal Disease (MDRD and Cockcroft-Gault equations. Results In Africans, compared to the reference genotype (GG or CC, each copy of the 2677T and 3435T allele was associated, respectively, with: GFR higher by 10.6 ± 2.9 (P P = 0.06 mL/min; ERPF higher by 47.5 ± 11.6 (P P = 0.007 mL/min; and renal resistances lower by 0.016 ± 0.004 (P P = 0.004 mm Hg/mL/min. In Caucasians, we identified 3 polymorphisms in the ABCB1 gene that were strongly associated with all estimates of GFR (smallest P value = 0.0006, overall P = 0.014 after multiple testing correction. Conclusion Variants of the ABCB1 gene were associated with renal function in both Africans and Caucasians and may therefore confer susceptibility to nephropathy in humans. If confirmed in other studies, these results point toward a new candidate gene for nephropathy in humans.

  14. Meiotic Interactors of a Mitotic Gene TAO3 Revealed by Functional Analysis of its Rare Variant.

    Science.gov (United States)

    Gupta, Saumya; Radhakrishnan, Aparna; Nitin, Rachana; Raharja-Liu, Pandu; Lin, Gen; Steinmetz, Lars M; Gagneur, Julien; Sinha, Himanshu

    2016-08-09

    Studying the molecular consequences of rare genetic variants has the potential to identify novel and hitherto uncharacterized pathways causally contributing to phenotypic variation. Here, we characterize the functional consequences of a rare coding variant of TAO3, previously reported to contribute significantly to sporulation efficiency variation in Saccharomyces cerevisiae During mitosis, the common TAO3 allele interacts with CBK1-a conserved NDR kinase. Both TAO3 and CBK1 are components of the RAM signaling network that regulates cell separation and polarization during mitosis. We demonstrate that the role of the rare allele TAO3(4477C) in meiosis is distinct from its role in mitosis by being independent of ACE2-a RAM network target gene. By quantitatively measuring cell morphological dynamics, and expressing the TAO3(4477C) allele conditionally during sporulation, we show that TAO3 has an early role in meiosis. This early role of TAO3 coincides with entry of cells into meiotic division. Time-resolved transcriptome analyses during early sporulation identified regulators of carbon and lipid metabolic pathways as candidate mediators. We show experimentally that, during sporulation, the TAO3(4477C) allele interacts genetically with ERT1 and PIP2, regulators of the tricarboxylic acid cycle and gluconeogenesis metabolic pathways, respectively. We thus uncover a meiotic functional role for TAO3, and identify ERT1 and PIP2 as novel regulators of sporulation efficiency. Our results demonstrate that studying the causal effects of genetic variation on the underlying molecular network has the potential to provide a more extensive understanding of the pathways driving a complex trait. Copyright © 2016 Gupta et al.

  15. Effect of ultrasound treatment on functional properties of reduced-salt chicken breast meat batter.

    Science.gov (United States)

    Li, Ke; Kang, Zhuang-Li; Zou, Yu-Feng; Xu, Xing-Lian; Zhou, Guang-Hong

    2015-05-01

    The effect of ultrasound treatments (40 kHz, 300 W) for different times (10, 20, 30 and 40 min) combined with different salt contents (1.0 %, 1.5 % and 2.0 %) on gel properties and water holding capacity (WHC) of chicken breast meat batter were investigated. Results showed salt level significantly (p  0.05) on texture, cooking loss or WHC. However, longer ultrasound (40 min) treatment resulted in a decrease in hardness, G' value and WHC. Microstructural analysis revealed that gels treated with ultrasound for 20 min had a compact structure whereas those treated for 40 min contained more protein aggregations and more cavities. Low-field nuclear magnetic resonance (LF-NMR) indicated that ultrasound treatment for 20 min lowered the values of spin-spin relaxation time (T2) and increased the proportion of myofibillar water. Overall, high power ultrasound technology is a promising process which can improve the gelation properties and thereby allowing for a partial reduction in the salt levels in chicken meat gels.

  16. Pectoralis major muscle of turkey displays divergent function as correlated with meat quality.

    Science.gov (United States)

    Patterson, B A; Matarneh, S K; Stufft, K M; England, E M; Scheffler, T L; Preisser, R H; Shi, H; Stewart, E C; Eilert, S; Gerrard, D E

    2017-05-01

    Fresh turkey meat color is determined by many factors that include muscle fiber type composition and heme protein concentrations. These factors either are affected by or influence biochemical events occurring postmortem. Deviations in the processing environment also can result in aberrant fresh meat quality and may ultimately change the quality characteristics of further processed products. Our objective was to describe the underlying cause and significance of the two-toning color defect in fresh turkey breast. In the first experiment, pectoralis major muscles were collected, classified as single- or two-toned, and analyzed using image processing to characterize fresh turkey color. Samples from the large and small lobes of the pectoralis major muscle were collected for pH, glycolytic intermediates, protein abundance, mRNA expression, and quality characteristics. In the second experiment, time from stun to exsanguination was tested as a promoter of fresh turkey color. Results from the first experiment showed that the turkey breast possesses two distinct lobes. The large lobe had greater (P turkey color by mitigating the differences between the two lobes. Our results also showed that birds exsanguinated first had greater (P turkey color. © 2016 Poultry Science Association Inc.

  17. Pain modality- and sex-specific effects of COMT genetic functional variants

    Science.gov (United States)

    Belfer, Inna; Segall, Samantha K.; Lariviere, William R.; Smith, Shad B.; Dai, Feng; Slade, Gary G.; Rashid, Naim U.; Mogil, Jeffrey S.; Campbell, Claudia; Edwards, Robert; Liu, Qian; Bair, Eric; Maixner, William; Diatchenko, Luda

    2013-01-01

    The enzyme catechol-O-methyltransferase (COMT) metabolizes catecholamine neurotransmitters involved in a number of physiological functions including pain perception. Both human and mouse COMT genes possess functional polymorphisms contributing to inter-individual variability in pain phenotypes such as sensitivity to noxious stimuli, severity of clinical pain and response to pain treatment. In this study, we found that the effects of Comt functional variation in mice are modality-specific. Spontaneous inflammatory nociception and thermal nociception behaviors were correlated the most with the presence of the B2 SINE transposon insertion residing in the 3’UTR mRNA region. Similarly, in humans, COMT functional haplotypes were associated with thermal pain perception and with capsaicin-induced pain. Furthermore, COMT genetic variations contributed to pain behaviors in mice and pain ratings in humans in a sex-specific manner. The ancestral Comt variant, without a B2 SINE insertion, was more strongly associated with sensitivity to capsaicin in female versus male mice. In humans, the haplotype coding for low COMT activity increased capsaicin-induced pain perception in women, but not men. These findings reemphasize the fundamental contribution of COMT to pain processes, and provide a fine-grained resolution of this contribution at the genetic level that can be used to guide future studies in the area of pain genetics. PMID:23701723

  18. Discovery and functional assessment of gene variants in the vascular endothelial growth factor pathway.

    Science.gov (United States)

    Paré-Brunet, Laia; Glubb, Dylan; Evans, Patrick; Berenguer-Llergo, Antoni; Etheridge, Amy S; Skol, Andrew D; Di Rienzo, Anna; Duan, Shiwei; Gamazon, Eric R; Innocenti, Federico

    2014-02-01

    Angiogenesis is a host-mediated mechanism in disease pathophysiology. The vascular endothelial growth factor (VEGF) pathway is a major determinant of angiogenesis, and a comprehensive annotation of the functional variation in this pathway is essential to understand the genetic basis of angiogenesis-related diseases. We assessed the allelic heterogeneity of gene expression, population specificity of cis expression quantitative trait loci (eQTLs), and eQTL function in luciferase assays in CEU and Yoruba people of Ibadan, Nigeria (YRI) HapMap lymphoblastoid cell lines in 23 resequenced genes. Among 356 cis-eQTLs, 155 and 174 were unique to CEU and YRI, respectively, and 27 were shared between CEU and YRI. Two cis-eQTLs provided mechanistic evidence for two genome-wide association study findings. Five eQTLs were tested for function in luciferase assays and the effect of two KRAS variants was concordant with the eQTL effect. Two eQTLs found in each of PRKCE, PIK3C2A, and MAP2K6 could predict 44%, 37%, and 45% of the variance in gene expression, respectively. This is the first analysis focusing on the pattern of functional genetic variation of the VEGF pathway genes in CEU and YRI populations and providing mechanistic evidence for genetic association studies of diseases for which angiogenesis plays a pathophysiologic role. © 2013 WILEY PERIODICALS, INC.

  19. Co-Expression of Wild-Type P2X7R with Gln460Arg Variant Alters Receptor Function.

    Directory of Open Access Journals (Sweden)

    Fernando Aprile-Garcia

    Full Text Available The P2X7 receptor is a member of the P2X family of ligand-gated ion channels. A single-nucleotide polymorphism leading to a glutamine (Gln by arginine (Arg substitution at codon 460 of the purinergic P2X7 receptor (P2X7R has been associated with mood disorders. No change in function (loss or gain has been described for this SNP so far. Here we show that although the P2X7R-Gln460Arg variant per se is not compromised in its function, co-expression of wild-type P2X7R with P2X7R-Gln460Arg impairs receptor function with respect to calcium influx, channel currents and intracellular signaling in vitro. Moreover, co-immunoprecipitation and FRET studies show that the P2X7R-Gln460Arg variant physically interacts with P2X7R-WT. Specific silencing of either the normal or polymorphic variant rescues the heterozygous loss of function phenotype and restores normal function. The described loss of function due to co-expression, unique for mutations in the P2RX7 gene so far, explains the mechanism by which the P2X7R-Gln460Arg variant affects the normal function of the channel and may represent a mechanism of action for other mutations.

  20. Co-Expression of Wild-Type P2X7R with Gln460Arg Variant Alters Receptor Function.

    Science.gov (United States)

    Aprile-Garcia, Fernando; Metzger, Michael W; Paez-Pereda, Marcelo; Stadler, Herbert; Acuña, Matías; Liberman, Ana C; Senin, Sergio A; Gerez, Juan; Hoijman, Esteban; Refojo, Damian; Mitkovski, Mišo; Panhuysen, Markus; Stühmer, Walter; Holsboer, Florian; Deussing, Jan M; Arzt, Eduardo

    2016-01-01

    The P2X7 receptor is a member of the P2X family of ligand-gated ion channels. A single-nucleotide polymorphism leading to a glutamine (Gln) by arginine (Arg) substitution at codon 460 of the purinergic P2X7 receptor (P2X7R) has been associated with mood disorders. No change in function (loss or gain) has been described for this SNP so far. Here we show that although the P2X7R-Gln460Arg variant per se is not compromised in its function, co-expression of wild-type P2X7R with P2X7R-Gln460Arg impairs receptor function with respect to calcium influx, channel currents and intracellular signaling in vitro. Moreover, co-immunoprecipitation and FRET studies show that the P2X7R-Gln460Arg variant physically interacts with P2X7R-WT. Specific silencing of either the normal or polymorphic variant rescues the heterozygous loss of function phenotype and restores normal function. The described loss of function due to co-expression, unique for mutations in the P2RX7 gene so far, explains the mechanism by which the P2X7R-Gln460Arg variant affects the normal function of the channel and may represent a mechanism of action for other mutations.

  1. Targeted resequencing of regulatory regions at schizophrenia risk loci: Role of rare functional variants at chromatin repressive states.

    Science.gov (United States)

    González-Peñas, Javier; Amigo, Jorge; Santomé, Luis; Sobrino, Beatriz; Brenlla, Julio; Agra, Santiago; Paz, Eduardo; Páramo, Mario; Carracedo, Ángel; Arrojo, Manuel; Costas, Javier

    2016-07-01

    There is mounting evidence that regulatory variation plays an important role in genetic risk for schizophrenia. Here, we specifically search for regulatory variants at risk by sequencing promoter regions of twenty-three genes implied in schizophrenia by copy number variant or genome-wide association studies. After strict quality control, a total of 55,206bp per sample were analyzed in 526 schizophrenia cases and 516 controls from Galicia, NW Spain, using the Applied Biosystems SOLiD System. Variants were filtered based on frequency from public databases, chromatin states from the RoadMap Epigenomics Consortium at tissues relevant for schizophrenia, such as fetal brain, mid-frontal lobe, and angular gyrus, and prediction of functionality from RegulomeDB. The proportion of rare variants at polycomb repressive chromatin state at relevant tissues was higher in cases than in controls. The proportion of rare variants with predicted regulatory role was significantly higher in cases than in controls (P=0.0028, OR=1.93, 95% C.I.=1.23-3.04). Combination of information from both sources led to the identification of an excess of carriers of rare variants with predicted regulatory role located at polycomb repressive chromatin state at relevant tissues in cases versus controls (P=0.0016, OR=19.34, 95% C.I.=2.45-2495.26). The variants are located at two genes affected by the 17q12 copy number variant, LHX1 and HNF1B. These data strongly suggest that a specific epigenetic mechanism, chromatin remodeling by histone modification during early development, may be impaired in a subset of schizophrenia patients, in agreement with previous data. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Identification of functional DNA variants in the constitutive promoter region of MDM2

    Directory of Open Access Journals (Sweden)

    Lalonde Marie-Eve

    2012-09-01

    Full Text Available Abstract Although mutations in the oncoprotein murine double minute 2 (MDM2 are rare, MDM2 gene overexpression has been observed in several human tumors. Given that even modest changes in MDM2 levels might influence the p53 tumor suppressor signaling pathway, we postulated that sequence variation in the promoter region of MDM2 could lead to disregulated expression and variation in gene dosage. Two promoters have been reported for MDM2; an internal promoter (P2, which is located near the end of intron 1 and is p53-responsive, and an upstream constitutive promoter (P1, which is p53-independent. Both promoter regions contain DNA variants that could influence the expression levels of MDM2, including the well-studied single nucleotide polymorphism (SNP SNP309, which is located in the promoter P2; i.e., upstream of exon 2. In this report, we screened the promoter P1 for DNA variants and assessed the functional impact of the corresponding SNPs. Using the dbSNP database and genotyping validation in individuals of European descent, we identified three common SNPs (−1494 G > A; indel 40 bp; and −182 C > G. Three major promoter haplotypes were inferred by using these three promoter SNPs together with rs2279744 (SNP309. Following subcloning into a gene reporter system, we found that two of the haplotypes significantly influenced MDM2 promoter activity in a haplotype-specific manner. Site-directed mutagenesis experiments indicated that the 40 bp insertion/deletion variation is causing the observed allelic promoter activity. This study suggests that part of the variability in the MDM2 expression levels could be explained by allelic p53-independent P1 promoter activity.

  3. Functionally Equivalent Variants in a Non-standard Variety and Their Implications for Universal Grammar: A Spontaneous Speech Corpus

    Directory of Open Access Journals (Sweden)

    Evelina Leivada

    2017-07-01

    Full Text Available Findings from the field of experimental linguistics have shown that a native speaker may judge a variant that is part of her grammar as unacceptable, but still use it productively in spontaneous speech. The process of eliciting acceptability judgments from speakers of non-standard languages is sometimes clouded by factors akin to prescriptive notions of grammatical correctness. It has been argued that standardization enhances the ability to make clear-cut judgments, while non-standardization may result to grammatical hybridity, often manifested in the form of functionally equivalent variants in the repertoire of a single speaker. Recognizing the importance of working with corpora of spontaneous speech, this work investigates patterns of variation in the spontaneous production of five neurotypical, adult speakers of a non-standard variety in terms of three variants, each targeting one level of linguistic analysis: syntax, morphology, and phonology. The results reveal the existence of functionally equivalent variants across speakers and levels of analysis. We first discuss these findings in relation to the notions of competing, mixed, and fused grammars, and then we flesh out the implications that different values of the same variant carry for parametric approaches to Universal Grammar. We observe that intraspeaker realizations of different values of the same variant within the same syntactic environment are incompatible with the ‘triggering-a-single-value’ approach of parametric models, but we argue that they are compatible with the concept of Universal Grammar itself. Since the analysis of these variants is ultimately a way of investigating the status of Universal Grammar primitives, we conclude that claims about the alleged unfalsifiability of (the contents of Universal Grammar are unfounded.

  4. Functionally Equivalent Variants in a Non-standard Variety and Their Implications for Universal Grammar: A Spontaneous Speech Corpus.

    Science.gov (United States)

    Leivada, Evelina; Papadopoulou, Elena; Pavlou, Natalia

    2017-01-01

    Findings from the field of experimental linguistics have shown that a native speaker may judge a variant that is part of her grammar as unacceptable, but still use it productively in spontaneous speech. The process of eliciting acceptability judgments from speakers of non-standard languages is sometimes clouded by factors akin to prescriptive notions of grammatical correctness. It has been argued that standardization enhances the ability to make clear-cut judgments, while non-standardization may result to grammatical hybridity, often manifested in the form of functionally equivalent variants in the repertoire of a single speaker. Recognizing the importance of working with corpora of spontaneous speech, this work investigates patterns of variation in the spontaneous production of five neurotypical, adult speakers of a non-standard variety in terms of three variants, each targeting one level of linguistic analysis: syntax, morphology, and phonology. The results reveal the existence of functionally equivalent variants across speakers and levels of analysis. We first discuss these findings in relation to the notions of competing, mixed, and fused grammars, and then we flesh out the implications that different values of the same variant carry for parametric approaches to Universal Grammar. We observe that intraspeaker realizations of different values of the same variant within the same syntactic environment are incompatible with the 'triggering-a-single-value' approach of parametric models, but we argue that they are compatible with the concept of Universal Grammar itself. Since the analysis of these variants is ultimately a way of investigating the status of Universal Grammar primitives, we conclude that claims about the alleged unfalsifiability of (the contents of) Universal Grammar are unfounded.

  5. Characterization of functional methylomes by next-generation capture sequencing identifies novel disease-associated variants.

    Science.gov (United States)

    Allum, Fiona; Shao, Xiaojian; Guénard, Frédéric; Simon, Marie-Michelle; Busche, Stephan; Caron, Maxime; Lambourne, John; Lessard, Julie; Tandre, Karolina; Hedman, Åsa K; Kwan, Tony; Ge, Bing; Rönnblom, Lars; McCarthy, Mark I; Deloukas, Panos; Richmond, Todd; Burgess, Daniel; Spector, Timothy D; Tchernof, André; Marceau, Simon; Lathrop, Mark; Vohl, Marie-Claude; Pastinen, Tomi; Grundberg, Elin

    2015-05-29

    Most genome-wide methylation studies (EWAS) of multifactorial disease traits use targeted arrays or enrichment methodologies preferentially covering CpG-dense regions, to characterize sufficiently large samples. To overcome this limitation, we present here a new customizable, cost-effective approach, methylC-capture sequencing (MCC-Seq), for sequencing functional methylomes, while simultaneously providing genetic variation information. To illustrate MCC-Seq, we use whole-genome bisulfite sequencing on adipose tissue (AT) samples and public databases to design AT-specific panels. We establish its efficiency for high-density interrogation of methylome variability by systematic comparisons with other approaches and demonstrate its applicability by identifying novel methylation variation within enhancers strongly correlated to plasma triglyceride and HDL-cholesterol, including at CD36. Our more comprehensive AT panel assesses tissue methylation and genotypes in parallel at ∼4 and ∼3 M sites, respectively. Our study demonstrates that MCC-Seq provides comparable accuracy to alternative approaches but enables more efficient cataloguing of functional and disease-relevant epigenetic and genetic variants for large-scale EWAS.

  6. A role for coding functional variants in HNF4A in type 2 diabetes susceptibility

    DEFF Research Database (Denmark)

    Jafar-Mohammadi, B; Groves, C J; Gjesing, A P

    2011-01-01

    Rare mutations in the gene HNF4A, encoding the transcription factor hepatocyte nuclear factor 4α (HNF-4A), account for ~5% of cases of MODY and more frequent variants in this gene may be involved in multifactorial forms of diabetes. Two low-frequency, non-synonymous variants in HNF4A (V255M, mino...

  7. Distribution and medical impact of loss-of-function variants in the Finnish founder population

    NARCIS (Netherlands)

    Lim, Elaine T.; Würtz, Peter; Havulinna, Aki S.; Palta, Priit; Tukiainen, Taru; Rehnström, Karola; Esko, Tõnu; Mägi, Reedik; Inouye, Michael; Lappalainen, Tuuli; Chan, Yingleong; Salem, Rany M.; Lek, Monkol; Flannick, Jason; Sim, Xueling; Manning, Alisa; Ladenvall, Claes; Bumpstead, Suzannah; Hämäläinen, Eija; Aalto, Kristiina; Maksimow, Mikael; Salmi, Marko; Blankenberg, Stefan; Ardissino, Diego; Shah, Svati; Horne, Benjamin; McPherson, Ruth; Hovingh, Gerald K.; Reilly, Muredach P.; Watkins, Hugh; Goel, Anuj; Farrall, Martin; Girelli, Domenico; Reiner, Alex P.; Stitziel, Nathan O.; Kathiresan, Sekar; Gabriel, Stacey; Barrett, Jeffrey C.; Lehtimäki, Terho; Laakso, Markku; Groop, Leif; Kaprio, Jaakko; Perola, Markus; McCarthy, Mark I.; Boehnke, Michael; Altshuler, David M.; Lindgren, Cecilia M.; Hirschhorn, Joel N.; Metspalu, Andres; Freimer, Nelson B.; Zeller, Tanja; Jalkanen, Sirpa; Koskinen, Seppo; Raitakari, Olli; Durbin, Richard; MacArthur, Daniel G.; Salomaa, Veikko; Ripatti, Samuli; Daly, Mark J.; Palotie, Aarno

    2014-01-01

    Exome sequencing studies in complex diseases are challenged by the allelic heterogeneity, large number and modest effect sizes of associated variants on disease risk and the presence of large numbers of neutral variants, even in phenotypically relevant genes. Isolated populations with recent

  8. The A and B variants of the alpha 3 integrin subunit: tissue distribution and functional characterization

    NARCIS (Netherlands)

    de Melker, A. A.; Sterk, L. M.; Delwel, G. O.; Fles, D. L.; Daams, H.; Weening, J. J.; Sonnenberg, A.

    1997-01-01

    The alpha subunits of the laminin-binding integrins alpha 3 beta 1, alpha 6 beta 1, and alpha 7 beta 1 have homologous sequences and are similar in structure. Two cytoplasmic variants, A and B, have been identified for each of these alpha subunits, although the alpha 3B splice variant has been

  9. Can common functional gene variants affect visual discrimination in metacontrast masking?

    Science.gov (United States)

    Maksimov, Margus; Vaht, Mariliis; Harro, Jaanus; Bachmann, Talis

    2013-01-01

    Mechanisms of visual perception should be robustly fast and provide veridical information about environmental objects in order to facilitate survival and successful coping. Because species-specific brain mechanisms for fast vision must have evolved under heavy pressure for efficiency, it has been held that different human individuals see the physical world in the same way and produce psychophysical functions of visual discrimination that are qualitatively the same. For many years, this assumption has been implicitly accepted in vision research studying extremely fast, basic visual processes, including studies of visual masking. However, in recent studies of metacontrast masking surprisingly robust individual differences in the qualitative aspects of subjects' performance have been found. As the basic species-specific visual functions very likely are based on universal brain mechanisms of vision, these differences probably are the outcome of variability in ontogenetic development (i.e., formation of idiosyncrasic skills of perception). Such developmental differences can be brought about by variants of genes that are differentially expressed in the course of CNS development. The objective of this study was to assess whether visual discrimination in metacontrast masking is related to three widely studied genetic polymorphisms implicated in brain function and used here as independent variables. The findings suggest no main effects of BDNF Val66Met, NRG1/rs6994992, or 5-HTTLPR polymorphisms on metacontrast performance, but several notable interactions of genetic variables with gender, stage of the sequence of experimental trials, perceptual strategies, and target/mask shape congruence were found. Thus, basic behavioral functions of fast vision may be influenced by common genetic variability. Also, when left uncontrolled, genetic factors may seriously confound variables in vision research using masking, obscure clear theoretical interpretation, lead to unexplicable inter

  10. Can common functional gene variants affect visual discrimination in metacontrast masking?

    Directory of Open Access Journals (Sweden)

    Margus Maksimov

    Full Text Available Mechanisms of visual perception should be robustly fast and provide veridical information about environmental objects in order to facilitate survival and successful coping. Because species-specific brain mechanisms for fast vision must have evolved under heavy pressure for efficiency, it has been held that different human individuals see the physical world in the same way and produce psychophysical functions of visual discrimination that are qualitatively the same. For many years, this assumption has been implicitly accepted in vision research studying extremely fast, basic visual processes, including studies of visual masking. However, in recent studies of metacontrast masking surprisingly robust individual differences in the qualitative aspects of subjects' performance have been found. As the basic species-specific visual functions very likely are based on universal brain mechanisms of vision, these differences probably are the outcome of variability in ontogenetic development (i.e., formation of idiosyncrasic skills of perception. Such developmental differences can be brought about by variants of genes that are differentially expressed in the course of CNS development. The objective of this study was to assess whether visual discrimination in metacontrast masking is related to three widely studied genetic polymorphisms implicated in brain function and used here as independent variables. The findings suggest no main effects of BDNF Val66Met, NRG1/rs6994992, or 5-HTTLPR polymorphisms on metacontrast performance, but several notable interactions of genetic variables with gender, stage of the sequence of experimental trials, perceptual strategies, and target/mask shape congruence were found. Thus, basic behavioral functions of fast vision may be influenced by common genetic variability. Also, when left uncontrolled, genetic factors may seriously confound variables in vision research using masking, obscure clear theoretical interpretation, lead to

  11. Molecular and genetic characterization of natural HIV-1 Tat Exon-1 variants from North India and their functional implications.

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    Larance Ronsard

    Full Text Available BACKGROUND: Designing an ideal vaccine against HIV-1 has been difficult due to enormous genetic variability as a result of high replication rate and lack of proofreading activity of reverse transcriptase leading to emergence of genetic variants and recombinants. Tat transactivates HIV-1 LTR, resulting in a remarkable increase in viral gene expression, and plays a vital role in pathogenesis. The aim of this study was to characterize the genetic variations of Tat exon-1 from HIV-1 infected patients from North India. METHODS: Genomic DNA was isolated from PBMCs and Tat exon-1 was PCR amplified with specific primers followed by cloning, sequencing and sequence analyses using bioinformatic tools for predicting HIV-1 subtypes, recombination events, conservation of domains and phosphorylation sites, and LTR transactivation by luciferase assay. RESULTS: Phylogenetic analysis of Tat exon-1 variants (n = 120 revealed sequence similarity with South African Tat C sequences and distinct geographical relationships were observed for B/C recombinants. Bootscan analysis of our variants showed 90% homology to Tat C and 10% to B/C recombinants with a precise breakpoint. Natural substitutions were observed with high allelic frequencies which may be beneficial for virus. High amino acid conservation was observed in Tat among Anti Retroviral Therapy (ART recipients. Barring few changes, most of the functional domains, predicted motifs and phosphorylation sites were well conserved in most of Tat variants. dN/dS analysis revealed purifying selection, implying the importance of functional conservation of Tat exon-1. Our Indian Tat C variants and B/C recombinants showed differential LTR transactivation. CONCLUSIONS: The possible role of Tat exon-1 variants in shaping the current HIV-1 epidemic in North India was highlighted. Natural substitutions across conserved functional domains were observed and provided evidence for the emergence of B/C recombinants within the

  12. Molecular and genetic characterization of natural HIV-1 Tat Exon-1 variants from North India and their functional implications.

    Science.gov (United States)

    Ronsard, Larance; Lata, Sneh; Singh, Jyotsna; Ramachandran, Vishnampettai G; Das, Shukla; Banerjea, Akhil C

    2014-01-01

    Designing an ideal vaccine against HIV-1 has been difficult due to enormous genetic variability as a result of high replication rate and lack of proofreading activity of reverse transcriptase leading to emergence of genetic variants and recombinants. Tat transactivates HIV-1 LTR, resulting in a remarkable increase in viral gene expression, and plays a vital role in pathogenesis. The aim of this study was to characterize the genetic variations of Tat exon-1 from HIV-1 infected patients from North India. Genomic DNA was isolated from PBMCs and Tat exon-1 was PCR amplified with specific primers followed by cloning, sequencing and sequence analyses using bioinformatic tools for predicting HIV-1 subtypes, recombination events, conservation of domains and phosphorylation sites, and LTR transactivation by luciferase assay. Phylogenetic analysis of Tat exon-1 variants (n = 120) revealed sequence similarity with South African Tat C sequences and distinct geographical relationships were observed for B/C recombinants. Bootscan analysis of our variants showed 90% homology to Tat C and 10% to B/C recombinants with a precise breakpoint. Natural substitutions were observed with high allelic frequencies which may be beneficial for virus. High amino acid conservation was observed in Tat among Anti Retroviral Therapy (ART) recipients. Barring few changes, most of the functional domains, predicted motifs and phosphorylation sites were well conserved in most of Tat variants. dN/dS analysis revealed purifying selection, implying the importance of functional conservation of Tat exon-1. Our Indian Tat C variants and B/C recombinants showed differential LTR transactivation. The possible role of Tat exon-1 variants in shaping the current HIV-1 epidemic in North India was highlighted. Natural substitutions across conserved functional domains were observed and provided evidence for the emergence of B/C recombinants within the ORF of Tat exon-1. These events are likely to have

  13. Functional Studies and In Silico Analyses to Evaluate Non-Coding Variants in Inherited Cardiomyopathies

    Directory of Open Access Journals (Sweden)

    Giulia Frisso

    2016-11-01

    Full Text Available Point mutations are the most common cause of inherited diseases. Bioinformatics tools can help to predict the pathogenicity of mutations found during genetic screening, but they may work less well in determining the effect of point mutations in non-coding regions. In silico analysis of intronic variants can reveal their impact on the splicing process, but the consequence of a given substitution is generally not predictable. The aim of this study was to functionally test five intronic variants (MYBPC3-c.506-2A>C, MYBPC3-c.906-7G>T, MYBPC3-c.2308+3G>C, SCN5A-c.393-5C>A, and ACTC1-c.617-7T>C found in five patients affected by inherited cardiomyopathies in the attempt to verify their pathogenic role. Analysis of the MYBPC3-c.506-2A>C mutation in mRNA from the peripheral blood of one of the patients affected by hypertrophic cardiac myopathy revealed the loss of the canonical splice site and the use of an alternative splicing site, which caused the loss of the first seven nucleotides of exon 5 (MYBPC3-G169AfsX14. In the other four patients, we generated minigene constructs and transfected them in HEK-293 cells. This minigene approach showed that MYBPC3-c.2308+3G>C and SCN5A-c.393-5C>A altered pre-mRNA processing, thus resulting in the skipping of one exon. No alterations were found in either MYBPC3-c.906-7G>T or ACTC1-c.617-7T>C. In conclusion, functional in vitro analysis of the effects of potential splicing mutations can confirm or otherwise the putative pathogenicity of non-coding mutations, and thus help to guide the patient's clinical management and improve genetic counseling in affected families.

  14. Meet meat

    NARCIS (Netherlands)

    Bekker, Gerben A.; Tobi, Hilde; Fischer, Arnout R.H.

    2017-01-01

    In this cross-cultural study we investigated how study participants from China, Ethiopia and the Netherlands operationalize the concept of meat and to what extent cultured meat fits or does not fit into this operationalization. We argue that combining the conceptual approaches symbolic boundaries

  15. Advancements in meat packaging.

    Science.gov (United States)

    McMillin, Kenneth W

    2017-10-01

    Packaging of meat provides the same or similar benefits for raw chilled and processed meats as other types of food packaging. Although air-permeable packaging is most prevalent for raw chilled red meat, vacuum and modified atmosphere packaging offer longer shelf life. The major advancements in meat packaging have been in the widely used plastic polymers while biobased materials and their integration into composite packaging are receiving much attention for functionality and sustainability. At this time, active and intelligent packaging are not widely used for antioxidant, antimicrobial, and other functions to stabilize and enhance meat properties although many options are being developed and investigated. The advances being made in nanotechnology will be incorporated into food packaging and presumably into meat packaging when appropriate and useful. Intelligent packaging using sensors for transmission of desired information and prompting of subsequent changes in packaging materials, environments or the products to maintain safety and quality are still in developmental stages. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. [Comparative analysis of conventional pulmonary function test results in children with asthma or cough variant asthma].

    Science.gov (United States)

    Yuan, Jie; An, Shu-Hua; Gao, Wen-Jie; Du, Wen-Jin; Sun, Jun-Feng; Zhang, Man; Yao, Cong-Zhuo

    2013-03-01

    To compare the conventional pulmonary function test results of children with asthma or cough variant asthma (CVA). A total of 140 children, who were diagnosed with asthma or CVA from May 2010 to May 2011, were divided into acute asthma attack (n=50), asthma remission (n=50) and CVA groups (n=40); 30 healthy children were included as a control group. The forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), forced expiratory flow after 25% of vital capacity has been expelled (FEF25), forced expiratory flow after 50% of vital capacity has been expelled (FEF50), forced expiratory flow after 75% of vital capacity has been expelled (FEF75) and maximal midexpiratory flow (MMEF75/25) were measured. The mean percent predicted values of all the above indices were lower than 80% in the acute asthma attack group, with FEF50, FEF75 and MMEF75/25 declining markedly; the mean percent predicted values of FEF75 and MMEF75/25 were lower than 80% in the CVA group. All the pulmonary function indices in the acute asthma attack group were lower than those in the control group. The mean percent predicted values of FVC, FEV1, FEF25 and MMEF75/25 in the asthma remission and CVA groups were lower than in the control group. All the pulmonary function indices in the acute asthma attack group were lower than in the asthma remission and CVA groups, but there were no significant differences between the asthma remission and CVA groups. There is small and large airway dysfunction, particularly small airway dysfunction, in children with acute asthma attack. Children with CVA present mainly with mild small airway dysfunction, as do those with asthma in remission.

  17. Novel variants of major drug-metabolising enzyme genes in diverse African populations and their predicted functional effects

    Directory of Open Access Journals (Sweden)

    Matimba Alice

    2009-01-01

    Full Text Available Abstract Pharmacogenetics enables personalised therapy based on genetic profiling and is increasingly applied in drug discovery. Medicines are developed and used together with pharmacodiagnostic tools to achieve desired drug efficacy and safety margins. Genetic polymorphism of drug-metabolising enzymes such as cytochrome P450s (CYPs and N-acetyltransferases (NATs has been widely studied in Caucasian and Asian populations, yet studies on African variants have been less extensive. The aim of the present study was to search for novel variants of CYP2C9, CYP2C19, CYP2D6 and NAT2 genes in Africans, with a particular focus on their prevalence in different populations, their relevance to enzyme functionality and their potential for personalised therapy. Blood samples from various ethnic groups were obtained from the AiBST Biobank of African Populations. The nine exons and exon-intron junctions of the CYP genes and exon 2 of NAT2 were analysed by direct DNA sequencing. Computational tools were used for the identification, haplotype analysis and prediction of functional effects of novel single nucleotide polymorphisms (SNPs. Novel SNPs were discovered in all four genes, grouped to existing haplotypes or assigned new allele names, if possible. The functional effects of non-synonymous SNPs were predicted and known African-specific variants were confirmed, but no significant differences were found in the frequencies of SNPs between African ethnicities. The low prevalence of our novel variants and most known functional alleles is consistent with the generally high level of diversity in gene loci of African populations. This indicates that profiles of rare variants reflecting interindividual variability might become the most relevant pharmacodiagnostic tools explaining Africans' diversity in drug response.

  18. Alternative splicing variations in mouse CAPS2: differential expression and functional properties of splicing variants

    Directory of Open Access Journals (Sweden)

    Furuichi Teiichi

    2007-04-01

    Full Text Available Abstract Background Ca2+-dependent activator protein 2 (CAPS2/CADPS2 is a secretory vesicle-associated protein involved in the release of neurotrophin. We recently reported that an aberrant, alternatively spliced CAPS2 mRNA that lacks exon 3 (CAPS2Δexon3 is detected in some patients with autism. Splicing variations in mouse CAPS2 and their expression and functions remain unclear. Results In this study, we defined 31 exons in the mouse CAPS2 gene and identified six alternative splicing variants, CAPS2a-f. CAPS2a is an isoform lacking exons 22 and 25, which encode part of the Munc13-1-homologous domain (MHD. CAPS2b lacks exon 25. CAPS2c lacks exons 11 and 22. CAPS2d, 2e, and 2f have C-terminal deletions from exon 14, exon 12, and exon 5, respectively. On the other hand, a mouse counterpart of CAPS2Δexon3 was not detected in the mouse tissues tested. CAPS2b was expressed exclusively in the brain, and the other isoforms were highly expressed in the brain, but also in some non-neural tissues. In the brain, all isoforms showed predominant expression patterns in the cerebellum. In the developing cerebellum, CAPS2b showed an up-regulated expression pattern, whereas the other isoforms exhibited transiently peaked expression patterns. CAPS2 proteins were mostly recovered in soluble fractions, but some were present in membrane fractions, except for CAPS2c and 2f, both of which lack the PH domain, suggesting that the PH domain is important for membrane association. In contrast to CAPS2a and 2b, CAPS2c showed slightly decreased BDNF-releasing activity, which is likely due to the C-terminal truncation of the PH domain in CAPS2c. Conclusion This study indicates that, in mouse, there are six splicing variants of CAPS2 (CAPS2a-f, and that these are subdivided into two groups: a long form containing the C-terminal MHD and a short form lacking the C-terminal MHD. These results demonstrate that the splicing variations correlate with their expression patterns and

  19. Effects of dietary functional ingredients and packaging methods on sensory characteristics and consumer acceptance of irradiated turkey breast meat.

    Science.gov (United States)

    Yan, H J; Lee, E J; Nam, K C; Min, B R; Ahn, D U

    2006-08-01

    Raw and cooked breast patties from turkeys fed 8 different diets [control; 200 IU/kg of vitamin E (VE); 0.3 mg/kg of Se; 2.5% conjugated linoleic acids (CLA); 200 IU/kg of VE + 0.3 mg/kg of Se; 200 IU/kg of VE + 2.5% CLA; 0.3 mg/kg of Se + 2.5% CLA; and 200 IU/kg of VE + 0.3 mg/kg of Se + 2.5% CLA] were treated with 2 irradiation doses (0 and 1.5 kGy) and 2 packaging methods (vacuum and aerobic). Raw and cooked samples from 32 treatments were tested by 8 trained sensory panelists for turkey aroma and irradiation off-aroma. Based on the sensory scores, the 3 dietary treatments producing the most and the least off-aroma were selected and used for a consumer acceptance study. Sensory results of raw meat showed that turkey aroma was intense in aerobically packaged meat, whereas irradiation off-aroma was intense with vacuum packaging. Raw meats from dietary treatments containing CLA (CLA, VE + CLA, Se + CLA, VE + Se + CLA) had greater turkey aroma scores, whereas those containing VE (VE and VE + Se) had lower scores than the control. Dietary treatments containing VE (VE, VE + Se, VE + Se + CLA) significantly lowered (P turkey breast meat, whereas CLA increased it, especially when the meats were packaged aerobically. In cooked meat, however, irradiation and packaging had no effect on turkey meat aroma and irradiation off-aroma. Cooked meat from turkeys supplemented with VE (VE and VE + Se) had less (P meat, which could not be reduced, even when VE and Se were combined in the diet. Irradiation off-aroma of raw meat was not pleasant for most consumers, and dietary supplementation of VE and VE + Se improved consumer acceptance of irradiated raw meat. For cooked meat samples, consumers preferred both color and flavor of irradiated meat to nonirradiated meat.

  20. A platform for functional assessment of large variant libraries in mammalian cells

    Science.gov (United States)

    Stephany, Jason J.

    2017-01-01

    Abstract Sequencing-based, massively parallel genetic assays have revolutionized our ability to quantify the relationship between many genotypes and a phenotype of interest. Unfortunately, variant library expression platforms in mammalian cells are far from ideal, hindering the study of human gene variants in their physiologically relevant cellular contexts. Here, we describe a platform for phenotyping variant libraries in transfectable mammalian cell lines in two steps. First, a landing pad cell line with a genomically integrated, Tet-inducible cassette containing a Bxb1 recombination site is created. Second, a single variant from a library of transfected, promoter-less plasmids is recombined into the landing pad in each cell. Thus, every cell in the recombined pool expresses a single variant, allowing for parallel, sequencing-based assessment of variant effect. We describe a method for incorporating a single landing pad into a defined site of a cell line of interest, and show that our approach can be used generate more than 20 000 recombinant cells in a single experiment. Finally, we use our platform in combination with a sequencing-based assay to explore the N-end rule by simultaneously measuring the effects of all possible N-terminal amino acids on protein expression. PMID:28335006

  1. The Effect of PCSK9 Loss-of-Function Variants on the Postprandial Lipid and ApoB-Lipoprotein Response.

    Science.gov (United States)

    Ooi, Teik Chye; Krysa, Jacqueline A; Chaker, Seham; Abujrad, Hussein; Mayne, Janice; Henry, Kathy; Cousins, Marion; Raymond, Angela; Favreau, Colette; Taljaard, Monica; Chrétien, Michel; Mbikay, Majambu; Proctor, Spencer D; Vine, Donna F

    2017-09-01

    Proprotein convertase subtilisin kexin 9 (PCSK9) mediates degradation of the low-density lipoprotein receptor (LDLR), thereby increasing plasma low-density lipoprotein cholesterol (LDL-C). Variations in the PCSK9 gene associated with loss of function (LOF) of PCSK9 result in greater expression of hepatic LDLR, lower concentrations of LDL-C, and protection from cardiovascular disease (CVD). Apolipoprotein-B (apoB) remnants also contribute to CVD risk and are similarly cleared by the LDLR. We hypothesized that PCSK9-LOF carriers would have lower fasting and postprandial remnant lipoproteins on top of lower LDL-C. To compare fasting and postprandial concentrations of triglycerides (TGs), total apoB, and apoB48 as indicators of remnant lipoprotein metabolism in PCSK9-LOF carriers with those with no PCSK9 variants. Case-control, metabolic study. Clinical Research Center of The Ottawa Hospital. Persons with one or more copies of the L10ins/A53V and/or I474V and/or R46L PCSK9 variant and persons with no PCSK9 variants. Oral fat tolerance test. Fasting and postprandial plasma TG, apoB48, total apoB, total cholesterol, and PCSK9 were measured at 0, 2, 4, and 6 hours after an oral fat load. Participants with PCSK9-LOF variants (n = 22) had reduced fasting LDL-C (-14%) as well as lower fasting TG (-21%) compared with noncarrier controls (n = 23). LOF variants also had reduced postprandial total apoB (-17%), apoB48 (-23%), and TG (-18%). Postprandial PCSK9 declined in both groups (-24% vs -16%, respectively). Participants carrying PCSK9-LOF variants had attenuated levels of fasting and postprandial TG, apoB48, and total apoB. This may confer protection from CVD and further validate the use of PCSK9 inhibitors to lower CVD risk. Copyright © 2017 Endocrine Society

  2. Mechanisms of CFTR functional variants that impair regulated bicarbonate permeation and increase risk for pancreatitis but not for cystic fibrosis.

    Science.gov (United States)

    LaRusch, Jessica; Jung, Jinsei; General, Ignacio J; Lewis, Michele D; Park, Hyun Woo; Brand, Randall E; Gelrud, Andres; Anderson, Michelle A; Banks, Peter A; Conwell, Darwin; Lawrence, Christopher; Romagnuolo, Joseph; Baillie, John; Alkaade, Samer; Cote, Gregory; Gardner, Timothy B; Amann, Stephen T; Slivka, Adam; Sandhu, Bimaljit; Aloe, Amy; Kienholz, Michelle L; Yadav, Dhiraj; Barmada, M Michael; Bahar, Ivet; Lee, Min Goo; Whitcomb, David C

    2014-07-01

    CFTR is a dynamically regulated anion channel. Intracellular WNK1-SPAK activation causes CFTR to change permeability and conductance characteristics from a chloride-preferring to bicarbonate-preferring channel through unknown mechanisms. Two severe CFTR mutations (CFTRsev) cause complete loss of CFTR function and result in cystic fibrosis (CF), a severe genetic disorder affecting sweat glands, nasal sinuses, lungs, pancreas, liver, intestines, and male reproductive system. We hypothesize that those CFTR mutations that disrupt the WNK1-SPAK activation mechanisms cause a selective, bicarbonate defect in channel function (CFTRBD) affecting organs that utilize CFTR for bicarbonate secretion (e.g. the pancreas, nasal sinus, vas deferens) but do not cause typical CF. To understand the structural and functional requirements of the CFTR bicarbonate-preferring channel, we (a) screened 984 well-phenotyped pancreatitis cases for candidate CFTRBD mutations from among 81 previously described CFTR variants; (b) conducted electrophysiology studies on clones of variants found in pancreatitis but not CF; (c) computationally constructed a new, complete structural model of CFTR for molecular dynamics simulation of wild-type and mutant variants; and (d) tested the newly defined CFTRBD variants for disease in non-pancreas organs utilizing CFTR for bicarbonate secretion. Nine variants (CFTR R74Q, R75Q, R117H, R170H, L967S, L997F, D1152H, S1235R, and D1270N) not associated with typical CF were associated with pancreatitis (OR 1.5, p = 0.002). Clones expressed in HEK 293T cells had normal chloride but not bicarbonate permeability and conductance with WNK1-SPAK activation. Molecular dynamics simulations suggest physical restriction of the CFTR channel and altered dynamic channel regulation. Comparing pancreatitis patients and controls, CFTRBD increased risk for rhinosinusitis (OR 2.3, p<0.005) and male infertility (OR 395, p<0.0001). WNK1-SPAK pathway-activated increases in CFTR

  3. Mechanisms of CFTR functional variants that impair regulated bicarbonate permeation and increase risk for pancreatitis but not for cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Jessica LaRusch

    2014-07-01

    Full Text Available CFTR is a dynamically regulated anion channel. Intracellular WNK1-SPAK activation causes CFTR to change permeability and conductance characteristics from a chloride-preferring to bicarbonate-preferring channel through unknown mechanisms. Two severe CFTR mutations (CFTRsev cause complete loss of CFTR function and result in cystic fibrosis (CF, a severe genetic disorder affecting sweat glands, nasal sinuses, lungs, pancreas, liver, intestines, and male reproductive system. We hypothesize that those CFTR mutations that disrupt the WNK1-SPAK activation mechanisms cause a selective, bicarbonate defect in channel function (CFTRBD affecting organs that utilize CFTR for bicarbonate secretion (e.g. the pancreas, nasal sinus, vas deferens but do not cause typical CF. To understand the structural and functional requirements of the CFTR bicarbonate-preferring channel, we (a screened 984 well-phenotyped pancreatitis cases for candidate CFTRBD mutations from among 81 previously described CFTR variants; (b conducted electrophysiology studies on clones of variants found in pancreatitis but not CF; (c computationally constructed a new, complete structural model of CFTR for molecular dynamics simulation of wild-type and mutant variants; and (d tested the newly defined CFTRBD variants for disease in non-pancreas organs utilizing CFTR for bicarbonate secretion. Nine variants (CFTR R74Q, R75Q, R117H, R170H, L967S, L997F, D1152H, S1235R, and D1270N not associated with typical CF were associated with pancreatitis (OR 1.5, p = 0.002. Clones expressed in HEK 293T cells had normal chloride but not bicarbonate permeability and conductance with WNK1-SPAK activation. Molecular dynamics simulations suggest physical restriction of the CFTR channel and altered dynamic channel regulation. Comparing pancreatitis patients and controls, CFTRBD increased risk for rhinosinusitis (OR 2.3, p<0.005 and male infertility (OR 395, p<<0.0001. WNK1-SPAK pathway-activated increases in

  4. Effect of acid- and alkaline-aided extractions on functional and rheological properties of proteins recovered from mechanically separated turkey meat (MSTM).

    Science.gov (United States)

    Hrynets, Yuliya; Omana, Dileep A; Xu, Yan; Betti, Mirko

    2010-09-01

    Functional and rheological characteristics of acid- and alkali-extracted proteins from mechanically separated turkey meat (MSTM) have been investigated. Extractions were carried out at 4 pH values (2.5, 3.5, 10.5, and 11.5). The study demonstrated that alkali and acid extractions resulted in significant (P 0.05) by different extraction pH. The protein extracted at pH 3.5 formed a highly viscoelastic gel network as evidenced by storage modulus (G') values, whereas the gel formed from proteins extracted at pH 10.5 was found to be the weakest. The work also revealed that acid treatments were more effective for removal of total heme pigments from MSTM. Color characteristics of protein isolates were markedly improved compared to the initial material and tended to be better when subjected to acid extractions. Mechanically separated meat is one of the cheapest sources of protein obtained by grinding meat and bones together and forcing the mixture through a perforated drum. The use of mechanically separated turkey meat (MSTM) for the production of further processed poultry products is limited due to its undesirable color and textural properties. Recovery of proteins from MSTM using pH shifting process will help the poultry processors to get better returns and also create opportunity to produce functional food ingredients.

  5. Functional Analysis of Cancer-Associated DNA Polymerase ε Variants in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Stephanie R. Barbari

    2018-03-01

    Full Text Available DNA replication fidelity relies on base selectivity of the replicative DNA polymerases, exonucleolytic proofreading, and postreplicative DNA mismatch repair (MMR. Ultramutated human cancers without MMR defects carry alterations in the exonuclease domain of DNA polymerase ε (Polε. They have been hypothesized to result from defective proofreading. However, modeling of the most common variant, Polε-P286R, in yeast produced an unexpectedly strong mutator effect that exceeded the effect of proofreading deficiency by two orders of magnitude and indicated the involvement of other infidelity factors. The in vivo consequences of many additional Polε mutations reported in cancers remain poorly understood. Here, we genetically characterized 13 cancer-associated Polε variants in the yeast system. Only variants directly altering the DNA binding cleft in the exonuclease domain elevated the mutation rate. Among these, frequently recurring variants were stronger mutators than rare variants, in agreement with the idea that mutator phenotype has a causative role in tumorigenesis. In nearly all cases, the mutator effects exceeded those of an exonuclease-null allele, suggesting that mechanisms distinct from loss of proofreading may drive the genome instability in most ultramutated tumors. All mutator alleles were semidominant, supporting the view that heterozygosity for the polymerase mutations is sufficient for tumor development. In contrast to the DNA binding cleft alterations, peripherally located variants, including a highly recurrent V411L, did not significantly elevate mutagenesis. Finally, the analysis of Polε variants found in MMR-deficient tumors suggested that the majority cause no mutator phenotype alone but some can synergize with MMR deficiency to increase the mutation rate.

  6. Discovery and functional annotation of SIX6 variants in primary open-angle glaucoma.

    Directory of Open Access Journals (Sweden)

    Megan Ulmer Carnes

    Full Text Available Glaucoma is a leading cause of blindness worldwide. Primary open-angle glaucoma (POAG is the most common subtype and is a complex trait with multigenic inheritance. Genome-wide association studies have previously identified a significant association between POAG and the SIX6 locus (rs10483727, odds ratio (OR = 1.32, p = 3.87×10(-11. SIX6 plays a role in ocular development and has been associated with the morphology of the optic nerve. We sequenced the SIX6 coding and regulatory regions in 262 POAG cases and 256 controls and identified six nonsynonymous coding variants, including five rare and one common variant, Asn141His (rs33912345, which was associated significantly with POAG (OR = 1.27, p = 4.2×10(-10 in the NEIGHBOR/GLAUGEN datasets. These variants were tested in an in vivo Danio rerio (zebrafish complementation assay to evaluate ocular metrics such as eye size and optic nerve structure. Five variants, found primarily in POAG cases, were hypomorphic or null, while the sixth variant, found only in controls, was benign. One variant in the SIX6 enhancer increased expression of SIX6 and disrupted its regulation. Finally, to our knowledge for the first time, we have identified a clinical feature in POAG patients that appears to be dependent upon SIX6 genotype: patients who are homozygous for the SIX6 risk allele (His141 have a statistically thinner retinal nerve fiber layer than patients homozygous for the SIX6 non-risk allele (Asn141. Our results, in combination with previous SIX6 work, lead us to hypothesize that SIX6 risk variants disrupt the development of the neural retina, leading to a reduced number of retinal ganglion cells, thereby increasing the risk of glaucoma-associated vision loss.

  7. Functional analysis of human cytochrome P450 21A2 variants involved in congenital adrenal hyperplasia

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Chunxue; Pallan, Pradeep S.; Zhang, Wei; Lei, Li; Yoshimoto, Francis K.; Waterman, Michael R.; Egli, Martin; Guengerich, F. Peter (Vanderbilt-MED)

    2017-05-24

    Cytochrome P450 (P450, CYP) 21A2 is the major steroid 21-hydroxylase, converting progesterone to 11-deoxycorticosterone and 17α-hydroxyprogesterone (17α-OH-progesterone) to 11-deoxycortisol. More than 100 CYP21A2 variants give rise to congenital adrenal hyperplasia (CAH). We previously reported a structure of WT human P450 21A2 with bound progesterone and now present a structure bound to the other substrate (17α-OH-progesterone). We found that the 17α-OH-progesterone- and progesterone-bound complex structures are highly similar, with only some minor differences in surface loop regions. Twelve P450 21A2 variants associated with either salt-wasting or nonclassical forms of CAH were expressed, purified, and analyzed. The catalytic activities of these 12 variants ranged from 0.00009% to 30% of WT P450 21A2 and the extent of heme incorporation from 10% to 95% of the WT. Substrate dissociation constants (Ks) for four variants were 37–13,000-fold higher than for WT P450 21A2. Cytochrome b5, which augments several P450 activities, inhibited P450 21A2 activity. Similar to the WT enzyme, high noncompetitive intermolecular kinetic deuterium isotope effects (≥ 5.5) were observed for all six P450 21A2 variants examined for 21-hydroxylation of 21-d3-progesterone, indicating that C–H bond breaking is a rate-limiting step over a 104-fold range of catalytic efficiency. Using UV-visible and CD spectroscopy, we found that P450 21A2 thermal stability assessed in bacterial cells and with purified enzymes differed among salt-wasting- and nonclassical-associated variants, but these differences did not correlate with catalytic activity. Our in-depth investigation of CAH-associated P450 21A2 variants reveals critical insight into the effects of disease-causing mutations on this important enzyme.

  8. Meat flavour

    International Nuclear Information System (INIS)

    Rosset, R.; Liger, P.; Roussel-Ciquard, N.

    1978-01-01

    For the consumer, meat is characterized by a certain number of organoleptic qualities; among them, flavour -that is to say the association of both odour and taste- plays a leading part. This property is based upon a great number of chemical components: some volatile components are responsible for the aroma and some non-volatile ones for the taste. These substances are either made or released during the heating of the meat on account of components called precursors which are produced during the aging of the meat. The two main reactions which preside over the elaboration of flavour are: the Maillard's reaction and the autooxidation reactions. Meat flavour is associated with the animal characteristics; it is influenced by the ante- and post mortem treatments as well as by the technological treatments for storing it. The use of synthetical flavours is to be considered as possible in the future [fr

  9. Neonatal nonepileptic myoclonus is a prominent clinical feature of KCNQ2 gain-of-function variants R201C and R201H

    DEFF Research Database (Denmark)

    Mulkey, Sarah B; Ben-Zeev, Bruria; Nicolai, Joost

    2017-01-01

    patients had encephalopathy from birth and presented with prominent startle-like myoclonus, which could be triggered by sound or touch. In seven patients, electroencephalography (EEG) was performed in the neonatal period and showed a burst-suppression pattern. However, myoclonus did not have an EEG......-of-function variants, supporting the value of in vitro functional screening. These findings suggest that gain-of-function and loss-of-function variants need different targeted therapeutic approaches....

  10. The functional influences of common ABCB1 genetic variants on the inhibition of P-glycoprotein by Antrodia cinnamomea extracts.

    Directory of Open Access Journals (Sweden)

    Ming-Jyh Sheu

    Full Text Available Antrodia cinnamomea is a traditional healthy food that has been demonstrated to possess anti-inflammatory, antioxidative, and anticacer effects. The purpose of this study was to evaluate whether the ethanolic extract of A. cinnamomea (EEAC can affect the efflux function of P-glycoprotein (P-gp and the effect of ABCB1 genetic variants on the interaction between EEAC and P-gp. To investigate the mechanism of this interaction, Flp-In™-293 cells stably transfected with various genotypes of human P-gp were established and the expression of P-gp was confirmed by Western blot. The results of the rhodamine 123 efflux assay demonstrated that EEAC efficiently inhibited wild-type P-gp function at an IC50 concentration of 1.51 ± 0.08 µg/mL through non-competitive inhibition. The IC50 concentrations for variant-type 1236T-2677T-3435T P-gp and variant-type 1236T-2677A-3435T P-gp were 5.56 ± 0.49 µg/mL and 3.33±0.67 µg/mL, respectively. In addition, the inhibition kinetics of EEAC also changed to uncompetitive inhibition in variant-type 1236T-2677A-3435T P-gp. The ATPase assay revealed that EEAC was an ATPase stimulator and was capable of reducing verapamil-induced ATPase levels. These results indicate that EEAC may be a potent P-gp inhibitor and higher dosages may be required in subjects carrying variant-types P-gp. Further studies are required to translate this basic knowledge into clinical applications.

  11. Functional variants of POC5 identified in patients with idiopathic scoliosis.

    Science.gov (United States)

    Patten, Shunmoogum A; Margaritte-Jeannin, Patricia; Bernard, Jean-Claude; Alix, Eudeline; Labalme, Audrey; Besson, Alicia; Girard, Simon L; Fendri, Khaled; Fraisse, Nicolas; Biot, Bernard; Poizat, Coline; Campan-Fournier, Amandine; Abelin-Genevois, Kariman; Cunin, Vincent; Zaouter, Charlotte; Liao, Meijiang; Lamy, Raphaelle; Lesca, Gaetan; Menassa, Rita; Marcaillou, Charles; Letexier, Melanie; Sanlaville, Damien; Berard, Jerome; Rouleau, Guy A; Clerget-Darpoux, Françoise; Drapeau, Pierre; Moldovan, Florina; Edery, Patrick

    2015-03-02

    Idiopathic scoliosis (IS) is a spine deformity that affects approximately 3% of the population. The underlying causes of IS are not well understood, although there is clear evidence that there is a genetic component to the disease. Genetic mapping studies suggest high genetic heterogeneity, but no IS disease-causing gene has yet been identified. Here, genetic linkage analyses combined with exome sequencing identified a rare missense variant (p.A446T) in the centriolar protein gene POC5 that cosegregated with the disease in a large family with multiple members affected with IS. Subsequently, the p.A446T variant was found in an additional set of families with IS and in an additional 3 cases of IS. Moreover, POC5 variant p.A455P was present and linked to IS in one family and another rare POC5 variant (p.A429V) was identified in an additional 5 cases of IS. In a zebrafish model, expression of any of the 3 human IS-associated POC5 variant mRNAs resulted in spine deformity, without affecting other skeletal structures. Together, these findings indicate that mutations in the POC5 gene contribute to the occurrence of IS.

  12. DNM1L Variant Alters Baseline Mitochondrial Function and Response to Stress in a Patient with Severe Neurological Dysfunction.

    Science.gov (United States)

    Hogarth, Kaley A; Costford, Sheila R; Yoon, Grace; Sondheimer, Neal; Maynes, Jason T

    2018-04-01

    Mitochondria play vital roles in brain development and neuronal activity, and mitochondrial dynamics (fission and fusion) maintain organelle function through the removal of damaged components. Dynamin-like protein-1 (DRP-1), encoded by DNM1L, is an evolutionarily conserved GTPase that mediates mitochondrial fission by surrounding the scission site in concentric ring-like structures via self-oligomerization, followed by GTPase-dependant constriction. Here, we describe the clinical characteristics and cellular phenotype of a patient with severe neurological dysfunction, possessing a homozygous DNM1L variant c.305C>T (p.T115M) in the GTPase domain. For comparative analysis, we also describe a previously identified heterozygous variant demonstrating a rapidly fatal neurocognitive phenotype (c.261dup/c.385:386del, p.W88M*9/E129K*6). Using patient-generated fibroblasts, we demonstrated both DNM1L variants undergo adverse alterations to mitochondrial structure and function, including impaired mitochondrial fission, reduced membrane potential, and lower oxidative capacity including an increased cellular level of reactive oxygen species (ROS) and dsDNA breaks. Mutation of DNM1L was also associated with impaired responses to oxidative stress, as treatment with hydrogen peroxide dramatically increased cellular ROS, with minimal exacerbation of already impaired mitochondrial function. Taken together, our observations indicate that homozygous p.T115M variant of DNM1L produces a neurological and neurodevelopmental phenotype, consistent with impaired mitochondrial architecture and function, through a diminished ability to oligomerize, which was most prevalent under oxidative stress.

  13. Neonatal nonepileptic myoclonus is a prominent clinical feature of KCNQ2 gain-of-function variants R201C and R201H

    NARCIS (Netherlands)

    Mulkey, S.B.; Ben-Zeev, B.; Nicolai, J.; Carroll, J.L.; Gronborg, S.; Jiang, Y.H.; Joshi, N.; Kelly, M.; Koolen, D.A.; Mikati, M.A.; Park, K.; Pearl, P.L.; Scheffer, I.E.; Spillmann, R.C.; Taglialatela, M.; Vieker, S.; Weckhuysen, S.; Cooper, E.C.; Cilio, M.R.

    2017-01-01

    OBJECTIVE: To analyze whether KCNQ2 R201C and R201H variants, which show atypical gain-of-function electrophysiologic properties in vitro, have a distinct clinical presentation and outcome. METHODS: Ten children with heterozygous, de novo KCNQ2 R201C or R201H variants were identified worldwide,

  14. Gain-of-function Prolactin Receptor Variants Are Not Associated With Breast Cancer and Multiple Fibroadenoma Risk.

    Science.gov (United States)

    Chakhtoura, Zeina; Laki, Fatima; Bernadet, Marie; Cherifi, Ibtissem; Chiche, Aurélie; Pigat, Natascha; Bernichtein, Sophie; Courtillot, Carine; Boutillon, Florence; Bièche, Ivan; Vacher, Sophie; Tanguy, Marie-Laure; Bissery, Anne; Grouthier, Virginie; Camparo, Philippe; Foretz, Marc; Do Cruzeiro, Marcio; Pierre, Rémi; Rakotozafy, Fabienne; Tichet, Jean; Tejedor, Isabelle; Guidotti, Jacques-Emmanuel; Sigal-Zafrani, Brigitte; Goffin, Vincent; Touraine, Philippe

    2016-11-01

    In a cohort of 95 women with multiple breast fibroadenomas (MFAs), we recently identified patients harboring germline heterozygous variants of the prolactin receptor (PRLR) exhibiting constitutive activity (PRLR I146L and PRLR I176V ). This study sought to better delineate the potential role of PRLR gain-of-function variants in benign and malignant mammary tumorigenesis. This was an observational study and transgenic mouse model analysis. The study took place at the Department of Endocrinology, Reproductive Disorders and Rare Gynecologic Diseases, Pitié Salpêtrière, Paris, and Inserm Unit 1151, Paris. We generated a second MFA cohort (n = 71) as well as a group of control subjects (n = 496) and a cohort of women with breast cancer (n = 119). We also generated two transgenic mouse models carrying the coding sequences of human PRLR I146L or PRLR WT . We aimed to determine the prevalence of PRLR variants in these three populations and to uncover any association of the latter with specific tumor pattern, especially in patients with breast cancer. This study did not highlight a higher prevalence of PRLR variants in the MFA group and in the breast cancer group compared with control subjects. Transgenic mice expressing PRLR I146L exhibited very mild histological mammary phenotype but tumors were never observed. PRLR I146L and PRLR I176V variants are not associated with breast cancer or MFA risk. However, one cannot exclude that low but sustained PRLR signaling may facilitate or contribute to pathological development driven by oncogenic pathways. Long-term patient follow-up should help to address this issue.

  15. A guide for functional analysis of BRCA1 variants of uncertain significance

    DEFF Research Database (Denmark)

    Millot, Gaël A; Carvalho, Marcelo A; Caputo, Sandrine M

    2012-01-01

    Germline mutations in the tumor suppressor gene BRCA1 confer an estimated lifetime risk of 56-80% for breast cancer and 15-60% for ovarian cancer. Since the mid 1990s when BRCA1 was identified, genetic testing has revealed over 1,500 unique germline variants. However, for a significant number of ...

  16. Rare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease

    NARCIS (Netherlands)

    M. Jakobsdottir (Margret); S.J. van der Lee (Sven); J.C. Bis (Joshua); V. Chouraki (Vincent); Li-Kroeger, D. (David); Yamamoto, S. (Shinya); M.L. Grove (Megan); A.C. Naj (Adam); M. Vronskaya; Salazar, J.L. (Jose L.); A.L. DeStefano (Anita); J. Brody (Jennifer); A.V. Smith (Albert Vernon); N. Amin (Najaf); R. Sims (Rebecca); C.A. Ibrahim-Verbaas (Carla); S.-H. Choi (Seung-Hoan); C.L. Satizabal (Claudia L.); O.L. Lopez (Oscar L.); A. Beiser (Alexa); M.K. Ikram (Kamran); M.E. Garcia (M.); C. Hayward (Caroline); T.V. Varga (Tibor V.); S. Ripatti (Samuli); P.W. Franks (Paul); G. Hallmans (Göran); O. Rolandsson (Olov); Jansson, J.-H. (Jan-Håkon); D.J. Porteous (David J.); V. Salomaa (Veikko); G. Eiriksdottir (Gudny); K.M. Rice (Kenneth); Bellen, H.J. (Hugo J.); D. Levy (Daniel); A.G. Uitterlinden (André); V. Emilsson (Valur); Rotter, J.I. (Jerome I.); T. Aspelund (Thor); C.J. Ódonnell (Christopher); A.L. Fitzpatrick (Annette); L.J. Launer (Lenore); A. Hofman (Albert); L. Wang (Liang); J. Williams (Julie); G.D. Schellenberg (Gerard D.); E.A. Boerwinkle (Eric); B.M. Psaty (Bruce); S. Seshadri (Sudha); L. Shulman (Lee); V. Gudnason (Vilmundur); C.M. van Duijn (Cornelia)

    2016-01-01

    textabstractWe performed an exome-wide association analysis in 1393 late-onset Alzheimer’s disease (LOAD) cases and 8141 controls from the CHARGE consortium. We found that a rare variant (P155L) in TM2D3 was enriched in Icelanders (~0.5% versus <0.05% in other European populations). In 433 LOAD

  17. FunSAV: predicting the functional effect of single amino acid variants using a two-stage random forest model.

    Directory of Open Access Journals (Sweden)

    Mingjun Wang

    Full Text Available Single amino acid variants (SAVs are the most abundant form of known genetic variations associated with human disease. Successful prediction of the functional impact of SAVs from sequences can thus lead to an improved understanding of the underlying mechanisms of why a SAV may be associated with certain disease. In this work, we constructed a high-quality structural dataset that contained 679 high-quality protein structures with 2,048 SAVs by collecting the human genetic variant data from multiple resources and dividing them into two categories, i.e., disease-associated and neutral variants. We built a two-stage random forest (RF model, termed as FunSAV, to predict the functional effect of SAVs by combining sequence, structure and residue-contact network features with other additional features that were not explored in previous studies. Importantly, a two-step feature selection procedure was proposed to select the most important and informative features that contribute to the prediction of disease association of SAVs. In cross-validation experiments on the benchmark dataset, FunSAV achieved a good prediction performance with the area under the curve (AUC of 0.882, which is competitive with and in some cases better than other existing tools including SIFT, SNAP, Polyphen2, PANTHER, nsSNPAnalyzer and PhD-SNP. The sourcecodes of FunSAV and the datasets can be downloaded at http://sunflower.kuicr.kyoto-u.ac.jp/sjn/FunSAV.

  18. Differential expression and functional characterization of luteinizing hormone receptor splice variants in human luteal cells: implications for luteolysis.

    Science.gov (United States)

    Dickinson, Rachel E; Stewart, Alan J; Myers, Michelle; Millar, Robert P; Duncan, W Colin

    2009-06-01

    The human LH receptor (LHR) plays a key role in luteal function and the establishment of pregnancy through its interaction with the gonadotropins LH and human chorionic gonadotropin. We previously identified four splice variants of the LHR in human luteinized granulosa cells (LGCs) and corpora lutea (CL). Real-time quantitative PCR revealed that expression of the full-length LHR (LHRa) and the most truncated form (LHRd) changed significantly in CL harvested at different stages of the ovarian cycle (P < 0.01, ANOVA). LHRa expression was reduced in the late luteal CL (P < 0.05). Conversely, an increase in LHRd expression was observed in the late luteal CL (P < 0.01). Chronic manipulation of human chorionic gonadotropin in LGC primary cultures supported the in vivo findings. LHRd encodes a protein lacking the transmembrane and carboxyl terminal domains. COS-7 cells expressing LHRd were unable to produce cAMP in response to LH stimulation. COS-7 cells coexpressing LHRd and LHRa also failed to generate cAMP in response to LH, suggesting that this truncated form has a negative effect on the signaling of LHRa. Immunofluorescence staining of LGC and COS-7 cells implied that there is a reduction in cell surface expression of LHRa when LHRd is present. Overall, these results imply expression of LHR splice variants is regulated in the human CL. Furthermore, during functional luteolysis a truncated variant could modulate the cell surface expression and activity of full-length LHR.

  19. Two functional variants of IRF5 influence the development of macular edema in patients with non-anterior uveitis.

    Directory of Open Access Journals (Sweden)

    Ana Márquez

    Full Text Available OBJECTIVE: Interferon (IFN signaling plays a crucial role in autoimmunity. Genetic variation in interferon regulatory factor 5 (IRF5, a major regulator of the type I interferon induction, has been associated with risk of developing several autoimmune diseases. In the current study we aimed to evaluate whether three sets of correlated IRF5 genetic variants, independently associated with SLE and with different functional roles, are involved in uveitis susceptibility and its clinical subphenotypes. METHODS: Three IRF5 polymorphisms, rs2004640, rs2070197 and rs10954213, representative of each group, were genotyped using TaqMan® allelic discrimination assays in a total of 263 non-anterior uveitis patients and 724 healthy controls of Spanish origin. RESULTS: A clear association between two of the three analyzed genetic variants, rs2004640 and rs10954213, and the absence of macular edema was observed in the case/control analysis (P FDR =5.07E-03, OR=1.48, CI 95%=1.14-1.92 and P FDR =3.37E-03, OR=1.54, CI 95%=1.19-2.01, respectively. Consistently, the subphenotype analysis accordingly with the presence/absence of this clinical condition also reached statistical significance (rs2004640: P=0.037, OR=0.69, CI 95%=0.48-0.98; rs10954213: P=0.030, OR=0.67, CI 95%=0.47-0.96, thus suggesting that both IRF5 genetic variants are specifically associated with the lack of macular edema in uveitis patients. CONCLUSION: Our results clearly showed for the first time that two functional genetic variants of IRF5 may play a role in the development of macular edema in non-anterior uveitis patients. Identifying genetic markers for macular edema could lead to the possibility of developing novel treatments or preventive therapies.

  20. Two Functional Variants of IRF5 Influence the Development of Macular Edema in Patients with Non-Anterior Uveitis

    Science.gov (United States)

    Cordero-Coma, Miguel; Ortego-Centeno, Norberto; Adán, Alfredo; Fonollosa, Alejandro; Díaz Valle, David; Pato, Esperanza; Blanco, Ricardo; Cañal, Joaquín; Díaz-Llopis, Manuel; de Ramón, Enrique; del Rio, María José; García Serrano, José Luis; Artaraz, Joseba; Martín-Villa, José Manuel; Llorenç, Víctor; Gorroño-Echebarría, Marina Begoña; Martín, Javier

    2013-01-01

    Objective Interferon (IFN) signaling plays a crucial role in autoimmunity. Genetic variation in interferon regulatory factor 5 (IRF5), a major regulator of the type I interferon induction, has been associated with risk of developing several autoimmune diseases. In the current study we aimed to evaluate whether three sets of correlated IRF5 genetic variants, independently associated with SLE and with different functional roles, are involved in uveitis susceptibility and its clinical subphenotypes. Methods Three IRF5 polymorphisms, rs2004640, rs2070197 and rs10954213, representative of each group, were genotyped using TaqMan® allelic discrimination assays in a total of 263 non-anterior uveitis patients and 724 healthy controls of Spanish origin. Results A clear association between two of the three analyzed genetic variants, rs2004640 and rs10954213, and the absence of macular edema was observed in the case/control analysis (P FDR=5.07E-03, OR=1.48, CI 95%=1.14-1.92 and P FDR=3.37E-03, OR=1.54, CI 95%=1.19-2.01, respectively). Consistently, the subphenotype analysis accordingly with the presence/absence of this clinical condition also reached statistical significance (rs2004640: P=0.037, OR=0.69, CI 95%=0.48-0.98; rs10954213: P=0.030, OR=0.67, CI 95%=0.47-0.96), thus suggesting that both IRF5 genetic variants are specifically associated with the lack of macular edema in uveitis patients. Conclusion Our results clearly showed for the first time that two functional genetic variants of IRF5 may play a role in the development of macular edema in non-anterior uveitis patients. Identifying genetic markers for macular edema could lead to the possibility of developing novel treatments or preventive therapies. PMID:24116155

  1. A functional variant at a prostate cancer predisposition locus at 8q24 is associated with PVT1 expression.

    Directory of Open Access Journals (Sweden)

    Kerstin B Meyer

    2011-07-01

    Full Text Available Genetic mapping studies have identified multiple cancer susceptibility regions at chromosome 8q24, upstream of the MYC oncogene. MYC has been widely presumed as the regulated target gene, but definitive evidence functionally linking these cancer regions with MYC has been difficult to obtain. Here we examined candidate functional variants of a haplotype block at 8q24 encompassing the two independent risk alleles for prostate and breast cancer, rs620861 and rs13281615. We used the mapping of DNase I hypersensitive sites as a tool to prioritise regions for further functional analysis. This approach identified rs378854, which is in complete linkage disequilibrium (LD with rs620861, as a novel functional prostate cancer-specific genetic variant. We demonstrate that the risk allele (G of rs378854 reduces binding of the transcription factor YY1 in vitro. This factor is known to repress global transcription in prostate cancer and is a candidate tumour suppressor. Additional experiments showed that the YY1 binding site is occupied in vivo in prostate cancer, but not breast cancer cells, consistent with the observed cancer-specific effects of this single nucleotide polymorphism (SNP. Using chromatin conformation capture (3C experiments, we found that the region surrounding rs378854 interacts with the MYC and PVT1 promoters. Moreover, expression of the PVT1 oncogene in normal prostate tissue increased with the presence of the risk allele of rs378854, while expression of MYC was not affected. In conclusion, we identified a new functional prostate cancer risk variant at the 8q24 locus, rs378854 allele G, that reduces binding of the YY1 protein and is associated with increased expression of PVT1 located 0.5 Mb downstream.

  2. Splice variants of the SWR1-type nucleosome remodeling factor Domino have distinct functions during Drosophila melanogaster oogenesis.

    Science.gov (United States)

    Börner, Kenneth; Becker, Peter B

    2016-09-01

    SWR1-type nucleosome remodeling factors replace histone H2A by variants to endow chromatin locally with specialized functionality. In Drosophila melanogaster a single H2A variant, H2A.V, combines functions of mammalian H2A.Z and H2A.X in transcription regulation and the DNA damage response. A major role in H2A.V incorporation for the only SWR1-like enzyme in flies, Domino, is assumed but not well documented in vivo. It is also unclear whether the two alternatively spliced isoforms, DOM-A and DOM-B, have redundant or specialized functions. Loss of both DOM isoforms compromises oogenesis, causing female sterility. We systematically explored roles of the two DOM isoforms during oogenesis using a cell type-specific knockdown approach. Despite their ubiquitous expression, DOM-A and DOM-B have non-redundant functions in germline and soma for egg formation. We show that chromatin incorporation of H2A.V in germline and somatic cells depends on DOM-B, whereas global incorporation in endoreplicating germline nurse cells appears to be independent of DOM. By contrast, DOM-A promotes the removal of H2A.V from stage 5 nurse cells. Remarkably, therefore, the two DOM isoforms have distinct functions in cell type-specific development and H2A.V exchange. © 2016. Published by The Company of Biologists Ltd.

  3. Identification of a Functional Risk Variant for Pemphigus Vulgaris in the ST18 Gene.

    Science.gov (United States)

    Vodo, Dan; Sarig, Ofer; Geller, Shamir; Ben-Asher, Edna; Olender, Tsviya; Bochner, Ron; Goldberg, Ilan; Nosgorodsky, Judith; Alkelai, Anna; Tatarskyy, Pavel; Peled, Alon; Baum, Sharon; Barzilai, Aviv; Ibrahim, Saleh M; Zillikens, Detlef; Lancet, Doron; Sprecher, Eli

    2016-05-01

    Pemphigus vulgaris (PV) is a life-threatening autoimmune mucocutaneous blistering disease caused by disruption of intercellular adhesion due to auto-antibodies directed against epithelial components. Treatment is limited to immunosuppressive agents, which are associated with serious adverse effects. The propensity to develop the disease is in part genetically determined. We therefore reasoned that the delineation of PV genetic basis may point to novel therapeutic strategies. Using a genome-wide association approach, we recently found that genetic variants in the vicinity of the ST18 gene confer a significant risk for the disease. Here, using targeted deep sequencing, we identified a PV-associated variant residing within the ST18 promoter region (p<0.0002; odds ratio = 2.03). This variant was found to drive increased gene transcription in a p53/p63-dependent manner, which may explain the fact that ST18 is up-regulated in the skin of PV patients. We then discovered that when overexpressed, ST18 stimulates PV serum-induced secretion of key inflammatory molecules and contributes to PV serum-induced disruption of keratinocyte cell-cell adhesion, two processes previously implicated in the pathogenesis of PV. Thus, the present findings indicate that ST18 may play a direct role in PV and consequently represents a potential target for the treatment of this disease.

  4. Expression of long non-coding RNAs in autoimmunity and linkage to enhancer function and autoimmune disease risk genetic variants.

    Science.gov (United States)

    Aune, T M; Crooke, P S; Patrick, A E; Tossberg, J T; Olsen, N J; Spurlock, C F

    2017-07-01

    Genome-wide association studies have identified numerous genetic variants conferring autoimmune disease risk. Most of these genetic variants lie outside protein-coding genes hampering mechanistic explorations. Numerous mRNAs are also differentially expressed in autoimmune disease but their regulation is also unclear. The majority of the human genome is transcribed yet its biologic significance is incompletely understood. We performed whole genome RNA-sequencing [RNA-seq] to categorize expression of mRNAs, known and novel long non-coding RNAs [lncRNAs] in leukocytes from subjects with autoimmune disease and identified annotated and novel lncRNAs differentially expressed across multiple disorders. We found that loci transcribing novel lncRNAs were not randomly distributed across the genome but co-localized with leukocyte transcriptional enhancers, especially super-enhancers, and near genetic variants associated with autoimmune disease risk. We propose that alterations in enhancer function, including lncRNA expression, produced by genetics and environment, change cellular phenotypes contributing to disease risk and pathogenesis and represent attractive therapeutic targets. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Kinetic and sequence-structure-function analysis of known LinA variants with different hexachlorocyclohexane isomers.

    Directory of Open Access Journals (Sweden)

    Pooja Sharma

    Full Text Available BACKGROUND: Here we report specific activities of all seven naturally occurring LinA variants towards three different isomers, α, γ and δ, of a priority persistent pollutant, hexachlorocyclohexane (HCH. Sequence-structure-function differences contributing to the differences in their stereospecificity for α-, γ-, and δ-HCH and enantiospecificity for (+- and (--α -HCH are also discussed. METHODOLOGY/PRINCIPAL FINDINGS: Enzyme kinetic studies were performed with purified LinA variants. Models of LinA2(B90A A110T, A111C, A110T/A111C and LinA1(B90A were constructed using the FoldX computer algorithm. Turnover rates (min(-1 showed that the LinAs exhibited differential substrate affinity amongst the four HCH isomers tested. α-HCH was found to be the most preferred substrate by all LinA's, followed by the γ and then δ isomer. CONCLUSIONS/SIGNIFICANCE: The kinetic observations suggest that LinA-γ1-7 is the best variant for developing an enzyme-based bioremediation technology for HCH. The majority of the sequence variation in the various linA genes that have been isolated is not neutral, but alters the enantio- and stereoselectivity of the encoded proteins.

  6. Studies of the associations between functional beta2-adrenergic receptor variants and obesity, hypertension and type 2 diabetes in 7,808 white subjects

    DEFF Research Database (Denmark)

    Gjesing, A P; Andersen, G; Burgdorf, K S

    2007-01-01

    Functional and common Arg16Gly and Gln27Glu polymorphisms have been identified in ADRB2, the gene encoding the beta2-adrenergic receptor. These variants have previously been examined for association with obesity, hypertension and diabetes with inconclusive results.......Functional and common Arg16Gly and Gln27Glu polymorphisms have been identified in ADRB2, the gene encoding the beta2-adrenergic receptor. These variants have previously been examined for association with obesity, hypertension and diabetes with inconclusive results....

  7. The MTHFD1 p.Arg653Gln variant alters enzyme function and increases risk for congenital heart defects.

    Science.gov (United States)

    Christensen, Karen E; Rohlicek, Charles V; Andelfinger, Gregor U; Michaud, Jacques; Bigras, Jean-Luc; Richter, Andrea; Mackenzie, Robert E; Rozen, Rima

    2009-02-01

    Methylenetetrahydrofolate dehydrogenase)methenyltetrahydrofolate cyclohydrolase)formyltetrahydrofolate synthetase (MTHFD1) is a trifunctional enzyme that interconverts tetrahydrofolate (THF) derivatives for nucleotide synthesis. A common variant in MTHFD1, p.Arg653Gln (c.1958G>A), may increase the risk for neural tube defects (NTD). To examine the biological impact of this variant on MTHFD1 function, we measured enzyme activity and stability in vitro and assessed substrate flux in transfected mammalian cells. The purified Arg653Gln enzyme has normal substrate affinity but a 36% reduction in half)life at 42 degrees C. Thermolability is reduced by magnesium adenosine triphosphate and eliminated by the substrate analog folate pentaglutamate, suggesting that folate status may modulate impact of the variant. The mutation reduces the metabolic activity of MTHFD1 within cells: formate incorporation into DNA in murine Mthfd1 knockout cells transfected with Arg653Gln is reduced by 26%+/-7.7% (Pcells transfected with wild)type protein, indicating a disruption of de novo purine synthesis. We assessed the impact of the variant on risk for congenital heart defects (CHD) in a cohort of Quebec children (158 cases, 110 controls) and mothers of children with heart defects (199 cases, 105 controls). The 653QQ genotype in children is associated with increased risk for heart defects (odds ratio [OR], 2.11; 95% confidence interval [CI], 1.01-4.42), particularly Tetralogy of Fallot (OR, 3.60; 95% CI, 1.38-9.42) and aortic stenosis (OR, 3.13; 95% CI, 1.13-8.66). There was no effect of maternal genotype. Our results indicate that the Arg653Gln polymorphism decreases enzyme stability and increases risk for CHD. Further evaluation of this polymorphism in folate)related disorders and its potential interaction with folate status is warranted. (c) 2008 Wiley-Liss, Inc.

  8. Evaluation of quality characteristics and functional properties of mechanically deboned chicken meats treated with different dose rates of ionizing radiation and use of antioxidants

    International Nuclear Information System (INIS)

    Brito, Poliana de Paula

    2012-01-01

    The Mechanically Deboned chicken meat (MDCM) is used in traditional meat products, in greater proportion in those emulsified, replacing meat raw materials more expensive. The raw material can have high MDCM the microbial load, as a result of contamination during processing or failure during the evisceration. The irradiation process is accepted as one of the most effective technologies when compared to conventional techniques of preservation, to reduce contamination of pathogens and spoilage. However, little information is available about the use and effects of different dose rates of ionizing radiation processing. Irradiation causes chemical changes in food, a major cause of deterioration of quality of raw or cooked meat products during refrigerated storage, frozen. The objective of this study was to evaluate the effects of different dose rates of ionizing radiation on the production of Thiobarbituric Acid Reactive Substances (TBARS), color, microbiological and sensory characteristics of mechanically deboned chicken added or without added antioxidants, during the cold storage and evaluation of functional properties. The results showed that among the tested dose rates using cobalt-60 source, dose rate of 4.04 kGy.h-1 was the best for processing MDCM. Furthermore, the use of the combination of rosemary antioxidant and α-tocopherol were able to reduce lipid oxidation generated by irradiation of the samples, showed a synergistic effect to the processing with ionizing radiation in reduction of psychrotrophic bacteria count and contributed to a better sensory quality. The use of radiation in the processing FDMI did not adversely affect the functional properties studied. (author)

  9. Functional Impact of ABCB1 Variants on Interactions between P-Glycoprotein and Methadone

    Science.gov (United States)

    Hung, Chin-Chuan; Chiou, Mu-Han; Teng, Yu-Ning; Hsieh, Yow-Wen; Huang, Chieh-Liang; Lane, Hsien-Yuan

    2013-01-01

    Methadone is a widely used substitution therapy for opioid addiction. Large inter-individual variability has been observed in methadone maintenance dosages and P-glycoprotein (P-gp) was considered to be one of the major contributors. To investigate the mechanism of P-gp’s interaction with methadone, as well as the effect of genetic variants on the interaction, Flp-In™-293 cells stably transfected with various genotypes of human P-gp were established in the present study. The RNA and protein expression levels of human P-gp were confirmed by real-time quantitative RT-PCR and western blot, respectively. Utilizing rhodamine 123 efflux assay and calcein-AM uptake study, methadone was demonstrated to be an inhibitor of wild-type human P-gp via non-competitive kinetic (IC50 = 2.17±0.10 µM), while the variant-type human P-gp, P-gp with 1236T-2677T-3435T genotype and P-gp with 1236T-2677A-3435T genotype, showed less inhibition potency (IC50 = 2.97±0.09 µM and 4.43±1.10 µM, respectively) via uncompetitive kinetics. Methadone also stimulated P-gp ATPase and inhibited verapamil-stimulated P-gp ATPase activity under therapeutic concentrations. These results may provide a possible explanation for higher methadone dosage requirements in patients carrying variant-type of P-gp and revealed the possible drug-drug interactions in patients who receive concomitant drugs which are also P-gp substrates. PMID:23527191

  10. Chondroitin sulfate A-adhering Plasmodium falciparum-infected erythrocytes express functionally important antibody epitopes shared by multiple variants

    DEFF Research Database (Denmark)

    Barfod, Lea; Dobrilovic, Tina; Magistrado, Pamela

    2010-01-01

    Acquired protection from Plasmodium falciparum placental malaria, a major cause of maternal, fetal, and infant morbidity, is mediated by IgG specific for the P. falciparum erythrocyte membrane protein 1 variant VAR2CSA. This protein enables adhesion of P. falciparum-infected erythrocytes...... monoclonal IgG Abs from affinity-matured memory B cells of P. falciparum-exposed women to study interclonal variation and functional importance of Ab epitopes among placental and peripheral parasites from East and West Africa. Most placental P. falciparum isolates were labeled by several mAbs, whereas...

  11. A Multilevel Functional Study of a SNAP25 At-Risk Variant for Bipolar Disorder and Schizophrenia.

    Science.gov (United States)

    Houenou, Josselin; Boisgontier, Jennifer; Henrion, Annabelle; d'Albis, Marc-Antoine; Dumaine, Anne; Linke, Julia; Wessa, Michèle; Daban, Claire; Hamdani, Nora; Delavest, Marine; Llorca, Pierre-Michel; Lançon, Christophe; Schürhoff, Franck; Szöke, Andrei; Le Corvoisier, Philippe; Barau, Caroline; Poupon, Cyril; Etain, Bruno; Leboyer, Marion; Jamain, Stéphane

    2017-10-25

    The synaptosomal-associated protein SNAP25 is a key player in synaptic vesicle docking and fusion and has been associated with multiple psychiatric conditions, including schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder. We recently identified a promoter variant in SNAP25 , rs6039769 , that is associated with early-onset bipolar disorder and a higher gene expression level in human prefrontal cortex. In the current study, we showed that this variant was associated both in males and females with schizophrenia in two independent cohorts. We then combined in vitro and in vivo approaches in humans to understand the functional impact of the at-risk allele. Thus, we showed in vitro that the rs6039769 C allele was sufficient to increase the SNAP25 transcription level. In a postmortem expression analysis of 33 individuals affected with schizophrenia and 30 unaffected control subjects, we showed that the SNAP25b / SNAP25a ratio was increased in schizophrenic patients carrying the rs6039769 at-risk allele. Last, using genetics imaging in a cohort of 71 subjects, we showed that male risk carriers had an increased amygdala-ventromedial prefrontal cortex functional connectivity and a larger amygdala than non-risk carriers. The latter association has been replicated in an independent cohort of 121 independent subjects. Altogether, results from these multilevel functional studies are bringing strong evidence for the functional consequences of this allelic variation of SNAP25 on modulating the development and plasticity of the prefrontal-limbic network, which therefore may increase the vulnerability to both early-onset bipolar disorder and schizophrenia. SIGNIFICANCE STATEMENT Functional characterization of disease-associated variants is a key challenge in understanding neuropsychiatric disorders and will open an avenue in the development of personalized treatments. Recent studies have accumulated evidence that the SNARE complex, and more specifically

  12. A functional variant in the OAS1 gene is associated with Sjögren's syndrome complicated with HBV infection.

    Science.gov (United States)

    Liu, Xianjun; Xing, Hongcun; Gao, Wenjing; Yu, Di; Zhao, Yuming; Shi, Xiaoju; Zhang, Kun; Li, Pingya; Yu, Jiaao; Xu, Wei; Shan, Hongli; Zhang, Kaiyu; Bao, Wanguo; Fu, Xueqi; Yang, Sirui; Wang, Shafeng

    2017-12-14

    Hepatitis B virus (HBV) has been suspected to contribute to several autoimmune diseases, including Sjögren's syndrome (SS), although the exact mechanism is unknown. The 2'-5' oligoadenylate synthetase (OAS1) is one of the most important components of the immune system and has significant antiviral functions. We studied a polymorphism rs10774671 of OAS1 gene in Han Chinese descent. The minor allele G was significantly associated with a decreased risk for SS, anti-SSA-positive SS, and anti-SSA-positive SS complicated with HBV infection, which have not been seen in anti-SSA-negative SS and HBcAb-negative SS patients. Gene expression analysis showed that the risk-conferring A allele was correlated with lower expression of p46 and increased expression of p42, p48, and p44. A functional study of enzymatic activities revealed that the p42, p44, and p48 isoforms display a reduced capacity to inhibit HBV replication in HepG2 cells compared to the normal p46 isoform. Our data demonstrated that the functional variant, rs10774671, is associated with HBV infection and anti-SSA antibody-positive SS. The SAS variant switches the primary p46 isoform to three alternatives with decreased capacities to inhibit HBV replication. These data indicated that individuals harboring the risk allele might be susceptible to hepatitis B infection and SS development.

  13. Developmental profile of speech-language and communicative functions in an individual with the preserved speech variant of Rett syndrome.

    Science.gov (United States)

    Marschik, Peter B; Vollmann, Ralf; Bartl-Pokorny, Katrin D; Green, Vanessa A; van der Meer, Larah; Wolin, Thomas; Einspieler, Christa

    2014-08-01

    We assessed various aspects of speech-language and communicative functions of an individual with the preserved speech variant of Rett syndrome (RTT) to describe her developmental profile over a period of 11 years. For this study, we incorporated the following data resources and methods to assess speech-language and communicative functions during pre-, peri- and post-regressional development: retrospective video analyses, medical history data, parental checklists and diaries, standardized tests on vocabulary and grammar, spontaneous speech samples and picture stories to elicit narrative competences. Despite achieving speech-language milestones, atypical behaviours were present at all times. We observed a unique developmental speech-language trajectory (including the RTT typical regression) affecting all linguistic and socio-communicative sub-domains in the receptive as well as the expressive modality. Future research should take into consideration a potentially considerable discordance between formal and functional language use by interpreting communicative acts on a more cautionary note.

  14. Admixture mapping in lupus identifies multiple functional variants within IFIH1 associated with apoptosis, inflammation, and autoantibody production.

    Directory of Open Access Journals (Sweden)

    Julio E Molineros

    Full Text Available Systemic lupus erythematosus (SLE is an inflammatory autoimmune disease with a strong genetic component. African-Americans (AA are at increased risk of SLE, but the genetic basis of this risk is largely unknown. To identify causal variants in SLE loci in AA, we performed admixture mapping followed by fine mapping in AA and European-Americans (EA. Through genome-wide admixture mapping in AA, we identified a strong SLE susceptibility locus at 2q22-24 (LOD=6.28, and the admixture signal is associated with the European ancestry (ancestry risk ratio ~1.5. Large-scale genotypic analysis on 19,726 individuals of African and European ancestry revealed three independently associated variants in the IFIH1 gene: an intronic variant, rs13023380 [P(meta = 5.20×10(-14; odds ratio, 95% confidence interval = 0.82 (0.78-0.87], and two missense variants, rs1990760 (Ala946Thr [P(meta = 3.08×10(-7; 0.88 (0.84-0.93] and rs10930046 (Arg460His [P(dom = 1.16×10(-8; 0.70 (0.62-0.79]. Both missense variants produced dramatic phenotypic changes in apoptosis and inflammation-related gene expression. We experimentally validated function of the intronic SNP by DNA electrophoresis, protein identification, and in vitro protein binding assays. DNA carrying the intronic risk allele rs13023380 showed reduced binding efficiency to a cellular protein complex including nucleolin and lupus autoantigen Ku70/80, and showed reduced transcriptional activity in vivo. Thus, in SLE patients, genetic susceptibility could create a biochemical imbalance that dysregulates nucleolin, Ku70/80, or other nucleic acid regulatory proteins. This could promote antibody hypermutation and auto-antibody generation, further destabilizing the cellular network. Together with molecular modeling, our results establish a distinct role for IFIH1 in apoptosis, inflammation, and autoantibody production, and explain the molecular basis of these three risk alleles for SLE pathogenesis.

  15. Identification and functional analysis of variant haplotypes in the 5'-flanking region of protein phosphatase 2A-Bδ gene.

    Directory of Open Access Journals (Sweden)

    Hui-Feng Chen

    suggest that functional genetic variants and their haplotypes in the 5'-flanking region of PPP2R2D are critical for transcriptional regulation of PP2A-Bδ.

  16. Dietary Patterns High in Red Meat, Potato, Gravy, and Butter Are Associated with Poor Cognitive Functioning but Not with Rate of Cognitive Decline in Very Old Adults1234

    Science.gov (United States)

    Davies, Karen; Adamson, Ashley; Kirkwood, Thomas; Hill, Tom R; Siervo, Mario; Mathers, John C; Jagger, Carol

    2016-01-01

    Background: Healthy dietary patterns (DPs) have been linked to better cognition and reduced risk of dementia in older adults, but their role in cognitive functioning and decline in the very old (aged ≥85 y) is unknown. Objective: We investigated the association between previously established DPs from the Newcastle 85+ Study and global and attention-specific cognition over 5 y. Methods: We followed up with 302 men and 489 women (1921 birth cohort from Northeast United Kingdom) for change in global cognition [measured by the Standardized Mini-Mental State Examination (SMMSE)] over 5 y and attention (assessed by the cognitive drug research attention battery) over 3 y. We used 2-step clustering to derive DPs and mixed models to determine the relation between DPs and cognition in the presence of the dementia susceptibility gene. Results: Previously, we characterized 3 DPs that differed in intake of red meat, potato, gravy, and butter and varied with key health measures. When compared with participants in DP1 (high red meat) and DP3 (high butter), participants in DP2 (low meat) had higher SMMSE scores at baseline (P butter (DP3) were associated with poor cognition but not with the rate of cognitive decline in very old adults. PMID:26740685

  17. Dietary Patterns High in Red Meat, Potato, Gravy, and Butter Are Associated with Poor Cognitive Functioning but Not with Rate of Cognitive Decline in Very Old Adults.

    Science.gov (United States)

    Granic, Antoneta; Davies, Karen; Adamson, Ashley; Kirkwood, Thomas; Hill, Tom R; Siervo, Mario; Mathers, John C; Jagger, Carol

    2016-02-01

    Healthy dietary patterns (DPs) have been linked to better cognition and reduced risk of dementia in older adults, but their role in cognitive functioning and decline in the very old (aged ≥85 y) is unknown. We investigated the association between previously established DPs from the Newcastle 85+ Study and global and attention-specific cognition over 5 y. We followed up with 302 men and 489 women (1921 birth cohort from Northeast United Kingdom) for change in global cognition [measured by the Standardized Mini-Mental State Examination (SMMSE)] over 5 y and attention (assessed by the cognitive drug research attention battery) over 3 y. We used 2-step clustering to derive DPs and mixed models to determine the relation between DPs and cognition in the presence of the dementia susceptibility gene. Previously, we characterized 3 DPs that differed in intake of red meat, potato, gravy, and butter and varied with key health measures. When compared with participants in DP1 (high red meat) and DP3 (high butter), participants in DP2 (low meat) had higher SMMSE scores at baseline (P butter (DP3) were associated with poor cognition but not with the rate of cognitive decline in very old adults.

  18. KCNQ1 gene variants in the risk for type 2 diabetes and impaired renal function in the Spanish Renastur cohort.

    Science.gov (United States)

    Riobello, Cristina; Gómez, Juan; Gil-Peña, Helena; Tranche, Salvador; Reguero, Julián R; de la Hera, Jesús M; Delgado, Elías; Calvo, David; Morís, César; Santos, Fernando; Coto-Segura, Pablo; Iglesias, Sara; Alonso, Belén; Alvarez, Victoria; Coto, Eliecer

    2016-05-15

    Several common KCNQ1 gene polymorphisms have been associated with the risk of type 2 diabetes (T2DM) and diabetic nephropathy. This effect is explained by the role of the kcnq1 protein as a potassium channel that in the pancreatic beta-cells drives an electrical signal that facilitates glucose-stimulated insulin secretion. The KCNQ1 gene is also expressed in the kidney, and could thus be implicated in the risk of developing impaired renal function. To test this hypothesis, we genotyped six common KCNQ1 gene variants (three single nucleotide polymorphisms, rs2237892, rs2237895, and rs231362, and three intronic indels) in 681 healthy elderly individuals (>65 years old) from the Spanish Renastur cohort. None of the six variants was associated with T2DM (180 diabetics vs. 581 non-diabetics). The intron 12 insertion allele was associated with a reduced estimated glomerular filtration rate (eGFRKCNQ1 gene in 100 individuals with the extreme eGFR values. We found two rare amino acid changes (p.K393N and p.P408A) and the 393 Asn variant was found only among diabetics (n = 4; p = 0.05). The two rare alleles were present in the two eGFR groups. Our results suggest that a common KCNQ1 intron 12 indel polymorphism is a risk factor for impaired renal function independent of T2DM. If this association is confirmed by others, further research to determine the mechanism that drives this association would be warranted. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Excessive signal transduction of gain-of-function variants of the calcium-sensing receptor (CaSR are associated with increased ER to cytosol calcium gradient.

    Directory of Open Access Journals (Sweden)

    Marianna Ranieri

    Full Text Available In humans, gain-of-function mutations of the calcium-sensing receptor (CASR gene are the cause of autosomal dominant hypocalcemia or type 5 Bartter syndrome characterized by an abnormality of calcium metabolism with low parathyroid hormone levels and excessive renal calcium excretion. Functional characterization of CaSR activating variants has been so far limited at demonstrating an increased sensitivity to external calcium leading to lower Ca-EC50. Here we combine high resolution fluorescence based techniques and provide evidence that for the efficiency of calcium signaling system, cells expressing gain-of-function variants of CaSR monitor cytosolic and ER calcium levels increasing the expression of the Sarco-Endoplasmic Reticulum Calcium-ATPase (SERCA and reducing expression of Plasma Membrane Calcium-ATPase (PMCA. Wild-type CaSR (hCaSR-wt and its gain-of-function (hCaSR-R990G; hCaSR-N124K variants were transiently transfected in HEK-293 cells. Basal intracellular calcium concentration was significantly lower in cells expressing hCaSR-wt and its gain of function variants compared to mock. In line, FRET studies using the D1ER probe, which detects [Ca2+]ER directly, demonstrated significantly higher calcium accumulation in cells expressing the gain of function CaSR variants compared to hCaSR-wt. Consistently, cells expressing activating CaSR variants showed a significant increase in SERCA activity and expression and a reduced PMCA expression. This combined parallel regulation in protein expression increases the ER to cytosol calcium gradient explaining the higher sensitivity of CaSR gain-of-function variants to external calcium. This control principle provides a general explanation of how cells reliably connect (and exacerbate receptor inputs to cell function.

  20. Genetic evaluation and selection response for growth in meat-type quail through random regression models using B-spline functions and Legendre polynomials.

    Science.gov (United States)

    Mota, L F M; Martins, P G M A; Littiere, T O; Abreu, L R A; Silva, M A; Bonafé, C M

    2018-04-01

    The objective was to estimate (co)variance functions using random regression models (RRM) with Legendre polynomials, B-spline function and multi-trait models aimed at evaluating genetic parameters of growth traits in meat-type quail. A database containing the complete pedigree information of 7000 meat-type quail was utilized. The models included the fixed effects of contemporary group and generation. Direct additive genetic and permanent environmental effects, considered as random, were modeled using B-spline functions considering quadratic and cubic polynomials for each individual segment, and Legendre polynomials for age. Residual variances were grouped in four age classes. Direct additive genetic and permanent environmental effects were modeled using 2 to 4 segments and were modeled by Legendre polynomial with orders of fit ranging from 2 to 4. The model with quadratic B-spline adjustment, using four segments for direct additive genetic and permanent environmental effects, was the most appropriate and parsimonious to describe the covariance structure of the data. The RRM using Legendre polynomials presented an underestimation of the residual variance. Lesser heritability estimates were observed for multi-trait models in comparison with RRM for the evaluated ages. In general, the genetic correlations between measures of BW from hatching to 35 days of age decreased as the range between the evaluated ages increased. Genetic trend for BW was positive and significant along the selection generations. The genetic response to selection for BW in the evaluated ages presented greater values for RRM compared with multi-trait models. In summary, RRM using B-spline functions with four residual variance classes and segments were the best fit for genetic evaluation of growth traits in meat-type quail. In conclusion, RRM should be considered in genetic evaluation of breeding programs.

  1. Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Kozyrev, Sergey V; Abelson, Anna-Karin; Wojcik, Jerome

    2008-01-01

    -cell scaffold protein with ankyrin repeats gene, BANK1. We replicated the association in four independent case-control sets (combined P = 3.7 x 10(-10); OR = 1.38). We analyzed BANK1 cDNA and found two isoforms, one full-length and the other alternatively spliced and lacking exon 2 (Delta2), encoding a protein...... without a putative IP3R-binding domain. The transcripts were differentially expressed depending on a branch point-site SNP, rs17266594, in strong linkage disequilibrium (LD) with rs10516487. A third associated variant was found in the ankyrin domain (rs3733197, A383T). Our findings implicate BANK1...

  2. Functional variant disrupts insulin induction of USF1: mechanism for USF1-associated dyslipidemias

    DEFF Research Database (Denmark)

    Naukkarinen, J.; Nilsson, E.; Koistinen, H.A.

    2009-01-01

    BACKGROUND: The upstream transcription factor 1 (USF1) gene is associated with familial combined hyperlipidemia, the most common genetic dyslipidemia in humans, as well as with various dyslipidemic changes in numerous other studies. Typical of complex disease-associated genes, neither the explicit...... in USF1 is involved in the development of dyslipidemia. The effects of the risk variant on gene expression were studied in 2 relevant human tissues, fat and muscle. Global transcript profiles of 47 fat biopsies ascertained for carriership of the risk allele were tested for differential expression......, a defective response of USF1 to insulin results in the suboptimal response of relevant target genes that contributes to the enhanced risk of developing dyslipidemia and coronary heart disease Udgivelsesdato: 2009/10...

  3. Hereditary heat-labile hexosaminidase B: a variant whose homozygotes synthesize a functional HEX A.

    Science.gov (United States)

    Navon, R; Kopel, R; Nutman, J; Frisch, A; Conzelmann, E; Sandhoff, K; Adam, A

    1985-01-01

    Homozygosity for a mutant allele at the beta-chain locus of hexosaminidase (HEX), resulting in a variant of heat-labile HEX B, is reported for the first time in two healthy children. HEX activity in their sera, leukocytes, and cultured skin fibroblasts is severely deficient when measured on the synthetic substrate 4-MU-GLcNAc. However, their cultured skin fibroblasts synthesize and process both alpha and beta chains of HEX, and their lymphoid cells hydrolyze normally the natural ganglioside GM2. This mutation is, therefore, different from at least one of the beta-chain mutations found in previously published families with heat-labile HEX B. Images Fig. 2 PMID:3156493

  4. Dissecting the role of the mitochondrial chaperone mortalin in Parkinson's disease: functional impact of disease-related variants on mitochondrial homeostasis

    Science.gov (United States)

    Burbulla, Lena F.; Schelling, Carina; Kato, Hiroki; Rapaport, Doron; Woitalla, Dirk; Schiesling, Carola; Schulte, Claudia; Sharma, Manu; Illig, Thomas; Bauer, Peter; Jung, Stephan; Nordheim, Alfred; Schöls, Ludger; Riess, Olaf; Krüger, Rejko

    2010-01-01

    The mitochondrial chaperone mortalin has been linked to neurodegeneration in Parkinson's disease (PD) based on reduced protein levels in affected brain regions of PD patients and its interaction with the PD-associated protein DJ-1. Recently, two amino acid exchanges in the ATPase domain (R126W) and the substrate-binding domain (P509S) of mortalin were identified in Spanish PD patients. Here, we identified a separate and novel variant (A476T) in the substrate-binding domain of mortalin in German PD patients. To define a potential role as a susceptibility factor in PD, we characterized the functions of all three variants in different cellular models. In vitro import assays revealed normal targeting of all mortalin variants. In neuronal and non-neuronal human cell lines, the disease-associated variants caused a mitochondrial phenotype of increased reactive oxygen species and reduced mitochondrial membrane potential, which were exacerbated upon proteolytic stress. These functional impairments correspond with characteristic alterations of the mitochondrial network in cells overexpressing mutant mortalin compared with wild-type (wt), which were confirmed in fibroblasts from a carrier of the A476T variant. In line with a loss of function hypothesis, knockdown of mortalin in human cells caused impaired mitochondrial function that was rescued by wt mortalin, but not by the variants. Our genetic and functional studies of novel disease-associated variants in the mortalin gene define a loss of mortalin function, which causes impaired mitochondrial function and dynamics. Our results support the role of this mitochondrial chaperone in neurodegeneration and underscore the concept of impaired mitochondrial protein quality control in PD. PMID:20817635

  5. Large-scale studies of the functional K variant of the butyrylcholinesterase gene in relation to Type 2 diabetes and insulin secretion

    DEFF Research Database (Denmark)

    Johansen, A; Nielsen, E-M D; Andersen, G

    2004-01-01

    Polymorphisms of the butyrylcholinesterase gene (BCHE) are reported to associate with Alzheimer's disease and a recent study found a significant association of the BCHE K variant (G1615A/Ala539Thr) with Type 2 diabetes. The objectives of our study were to examine whether the BCHE K variant...... is associated with Type 2 diabetes or estimates of pancreatic beta cell function in large-scale populations of glucose-tolerant Caucasians....

  6. Effect of functional chitosan coating and gamma irradiation on the shelf-life of chicken meat during refrigerated storage

    Science.gov (United States)

    Hassanzadeh, Parviz; Tajik, Hossein; Rohani, Seyed Mehdi Razavi; Moradi, Mehran; Hashemi, Mohammad; Aliakbarlu, Javad

    2017-12-01

    The present study was conducted to evaluate the combined effect of low-dose gamma irradiation (2.5 kGy) and chitosan edible coating (2%) containing grape seed extract (GSE) (0.1%) on the microbial, chemical and sensorial quality of chicken breast meat during 21 days of storage at 4 °C. The samples were periodically analyzed for microbiological (aerobic mesophilic and psychrotrophic counts), chemical (TBA, pH, aw) and sensorial (odor, appearance, and overall acceptability) characteristics. Results indicated that irradiation and the active coating had significant (P ≤ 0.05) effects on reduction of bacterial growth with at least a 14-day extension of shelf life. Results represented the protective effect of chitosan coating containing GSE against induced lipid oxidation by irradiation. All chitosan-coated samples showed lower TBA and pH values than other treatments during storage, and no significant (P > 0.05) difference was observed due to irradiation in TBA values. Results also indicated that the application of chitosan coating significantly improved the sensorial quality of the samples, and none of the evaluated sensorial attributes was significantly affected by irradiation. Based on the results obtained in this study, the application of low-dose gamma irradiation and chitosan coating containing GSE was effective in preserving the quality of fresh chicken meats and is recommended in meat products.

  7. An abundance of rare functional variants in 202 drug target genes sequenced in 14.002 people

    DEFF Research Database (Denmark)

    Nelson, Matthew R.; Wegmann, Daniel; Ehm, Margaret G.

    2012-01-01

    Rare genetic variants contribute to complex disease risk; however, the abundance of rare variants in human populations remains unknown. We explored this spectrum of variation by sequencing 202 genes encoding drug targets in 14,002 individuals. We find rare variants are abundant (1 every 17 bases)...

  8. Association Between Variants of PRDM1 and NDP52 and Crohn's Disease, Based on Exome Sequencing and Functional Studies

    DEFF Research Database (Denmark)

    Ellinghaus, David; Zhang, Hu; Zeissig, Sebastian

    2013-01-01

    BACKGROUND & AIMS: Genome-wide association studies (GWAS) have identified 140 Crohn's disease (CD) susceptibility loci. For most loci, the variants that cause disease are not known and the genes affected by these variants have not been identified. We aimed to identify variants that cause CD throu...

  9. Association Between Variants of PRDM1 and NDP52 and Crohn's Disease, Based on Exome Sequencing and Functional Studies

    NARCIS (Netherlands)

    Ellinghaus, David; Zhang, Hu; Zeissig, Sebastian; Lipinski, Simone; Till, Andreas; Jiang, Tao; Stade, Bjoern; Bromberg, Yana; Ellinghaus, Eva; Keller, Andreas; Rivas, Manuel A.; Skieceviciene, Jurgita; Doncheva, Nadezhda T.; Liu, Xiao; Liu, Qing; Jiang, Fuman; Forster, Michael; Mayr, Gabriele; Albrecht, Mario; Haesler, Robert; Boehm, Bernhard O.; Goodall, Jane; Berzuini, Carlo R.; Lee, James; Andersen, Vibeke; Vogel, Ulla; Kupcinskas, Limas; Kayser, Manfred; Krawczak, Michael; Nikolaus, Susanna; Weersma, Rinse K.; Ponsioen, Cyriel Y.; Sans, Miquel; Wijmenga, Cisca; Strachan, David P.; McAardle, Wendy L.; Vermeire, Severine; Rutgeerts, Paul; Sanderson, Jeremy D.; Mathew, Christopher G.; Vatn, Morten H.; Wang, Jun; Noethen, Markus M.; Duerr, Richard H.; Buening, Carsten; Brand, Stephan; Glas, Juergen; Winkelmann, Juliane; Illig, Thomas; Latiano, Anna; Annese, Vito; Halfvarson, Jonas; D'Amato, Mauro; Daly, Mark J.; Nothnagel, Michael; Karlsen, Tom H.; Subramani, Suresh; Rosenstiel, Philip; Schreiber, Stefan; Parkes, Miles; Franke, Andre

    BACKGROUND & AIMS: Genome-wide association studies (GWAS) have identified 140 Crohn's disease (CD) susceptibility loci. For most loci, the variants that cause disease are not known and the genes affected by these variants have not been identified. We aimed to identify variants that cause CD through

  10. Association Between Variants of PRDM1 and NDP52 and Crohn's Disease, Based on Exome Sequencing and Functional Studies

    NARCIS (Netherlands)

    Ellinghaus, David; Zhang, Hu; Zeissig, Sebastian; Lipinski, Simone; Till, Andreas; Jiang, Tao; Stade, Björn; Bromberg, Yana; Ellinghaus, Eva; Keller, Andreas; Rivas, Manuel A.; Skieceviciene, Jurgita; Doncheva, Nadezhda T.; Liu, Xiao; Liu, Qing; Jiang, Fuman; Forster, Michael; Mayr, Gabriele; Albrecht, Mario; Häsler, Robert; Boehm, Bernhard O.; Goodall, Jane; Berzuini, Carlo R.; Lee, James; Andersen, Vibeke; Vogel, Ulla; Kupcinskas, Limas; Kayser, Manfred; Krawczak, Michael; Nikolaus, Susanna; Weersma, Rinse K.; Ponsioen, Cyriel Y.; Sans, Miquel; Wijmenga, Cisca; Strachan, David P.; McArdle, Wendy L.; Vermeire, Séverine; Rutgeerts, Paul; Sanderson, Jeremy D.; Mathew, Christopher G.; Vatn, Morten H.; Wang, Jun; Nöthen, Markus M.; Duerr, Richard H.; Büning, Carsten; Brand, Stephan; Glas, Jürgen; Winkelmann, Juliane; Illig, Thomas; Latiano, Anna; Annese, Vito; Halfvarson, Jonas; D'Amato, Mauro; Daly, Mark J.; Nothnagel, Michael; Karlsen, Tom H.; Subramani, Suresh; Rosenstiel, Philip; Schreiber, Stefan; Parkes, Miles; Franke, Andre

    2013-01-01

    Genome-wide association studies (GWAS) have identified 140 Crohn's disease (CD) susceptibility loci. For most loci, the variants that cause disease are not known and the genes affected by these variants have not been identified. We aimed to identify variants that cause CD through detailed

  11. Loss-of-Function KCNE2 Variants: True Monogenic Culprits of Long-QT Syndrome or Proarrhythmic Variants Requiring Secondary Provocation?

    Science.gov (United States)

    Roberts, Jason D; Krahn, Andrew D; Ackerman, Michael J; Rohatgi, Ram K; Moss, Arthur J; Nazer, Babak; Tadros, Rafik; Gerull, Brenda; Sanatani, Shubhayan; Wijeyeratne, Yanushi D; Baruteau, Alban-Elouen; Muir, Alison R; Pang, Benjamin; Cadrin-Tourigny, Julia; Talajic, Mario; Rivard, Lena; Tester, David J; Liu, Taylor; Whitman, Isaac R; Wojciak, Julianne; Conacher, Susan; Gula, Lorne J; Leong-Sit, Peter; Manlucu, Jaimie; Green, Martin S; Hamilton, Robert; Healey, Jeff S; Lopes, Coeli M; Behr, Elijah R; Wilde, Arthur A; Gollob, Michael H; Scheinman, Melvin M

    2017-08-01

    Insight into type 6 long-QT syndrome (LQT6), stemming from mutations in the KCNE2 -encoded voltage-gated channel β-subunit, is limited. We sought to further characterize its clinical phenotype. Individuals with reported pathogenic KCNE2 mutations identified during arrhythmia evaluation were collected from inherited arrhythmia clinics and the Rochester long-QT syndrome (LQTS) registry. Previously reported LQT6 cases were identified through a search of the MEDLINE database. Clinical features were assessed, while reported KCNE2 mutations were evaluated for genotype-phenotype segregation and classified according to the contemporary American College of Medical Genetics guidelines. Twenty-seven probands possessed reported pathogenic KCNE2 mutations, while a MEDLINE search identified 17 additional LQT6 cases providing clinical and genetic data. Sixteen probands had normal resting QTc values and only developed QT prolongation and malignant arrhythmias after exposure to QT-prolonging stressors, 10 had other LQTS pathogenic mutations, and 10 did not have an LQTS phenotype. Although the remaining 8 subjects had an LQTS phenotype, evidence suggested that the KCNE2 variant was not the underlying culprit. The collective frequency of KCNE2 variants implicated in LQT6 in the Exome Aggregation Consortium database was 1.4%, in comparison with a 0.0005% estimated clinical prevalence for LQT6. On the basis of clinical phenotype, the high allelic frequencies of LQT6 mutations in the Exome Aggregation Consortium database, and absence of previous documentation of genotype-phenotype segregation, our findings suggest that many KCNE2 variants, and perhaps all, have been erroneously designated as LQTS-causative mutations. Instead, KCNE2 variants may confer proarrhythmic susceptibility when provoked by additional environmental/acquired or genetic factors, or both. © 2017 American Heart Association, Inc.

  12. Clinical and Functional Characterization of a Missense ELF2 Variant in a CANVAS Family.

    Science.gov (United States)

    Ahmad, Hena; Requena, Teresa; Frejo, Lidia; Cobo, Marien; Gallego-Martinez, Alvaro; Martin, Francisco; Lopez-Escamez, Jose A; Bronstein, Adolfo M

    2018-01-01

    Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS) is a rare disorder with an unknown etiology. We present a British family with presumed autosomal dominant CANVAS with incomplete penetrance and variable expressivity. Exome sequencing identified a rare missense variant in the ELF2 gene at chr4:g.140058846 C > T, c.10G > A, p.A4T which segregated in all affected patients. By using transduced BE (2)-M17 cells, we found that the mutated ELF2 (mt-ELF2) gene increased ATXN2 and reduced ELOVL5 gene expression, the causal genes of type 2 and type 38 spinocerebellar ataxias. Both, western blot and confocal microscopy confirmed an increase of ataxin-2 in BE(2)-M17 cells transduced with lentivirus expressing mt-ELF2 (CEE-mt- ELF2 ), which was not observed in cells transduced with lentivirus expressing wt-ELF2 (CEE-wt-ELF2). Moreover, we observed a significant decrease in the number and size of lipid droplets in the CEE-mt- ELF2 -transduced BE (2)-M17 cells, but not in the CEE-wt-ELF2-transduced BE (2)-M17. Furthermore, changes in the expression of ELOVL5 could be related with the reduction of lipid droplets in BE (2)-M17 cells. This work supports that ELF2 gene regulates the expression of ATXN2 and ELOVL5 genes, and defines new molecular links in the pathophysiology of cerebellar ataxias.

  13. The expression of the rare caveolin-3 variant T78M alters cardiac ion channels function and membrane excitability

    Science.gov (United States)

    Campostrini, Giulia; Bonzanni, Mattia; Lissoni, Alessio; Bazzini, Claudia; Milanesi, Raffaella; Vezzoli, Elena; Francolini, Maura; Baruscotti, Mirko; Bucchi, Annalisa; Rivolta, Ilaria; Fantini, Matteo; Severi, Stefano; Cappato, Riccardo; Crotti, Lia; J. Schwartz, Peter; DiFrancesco, Dario; Barbuti, Andrea

    2017-01-01

    Abstract Aims Caveolinopathies are a family of genetic disorders arising from alterations of the caveolin-3 (cav-3) gene. The T78M cav-3 variant has been associated with both skeletal and cardiac muscle pathologies but its functional contribution, especially to cardiac diseases, is still controversial. Here, we evaluated the effect of the T78M cav-3 variant on cardiac ion channel function and membrane excitability. Methods and results We transfected either the wild type (WT) or T78M cav-3 in caveolin-1 knock-out mouse embryonic fibroblasts and found by immunofluorescence and electron microscopy that both are expressed at the plasma membrane and form caveolae. Two ion channels known to interact and co-immunoprecipitate with the cav-3, hKv1.5 and hHCN4, interact also with T78M cav-3 and reside in lipid rafts. Electrophysiological analysis showed that the T78M cav-3 causes hKv1.5 channels to activate and inactivate at more hyperpolarized potentials and the hHCN4 channels to activate at more depolarized potentials, in a dominant way. In spontaneously beating neonatal cardiomyocytes, the expression of the T78M cav-3 significantly increased action potential peak-to-peak variability without altering neither the mean rate nor the maximum diastolic potential. We also found that in a small cohort of patients with supraventricular arrhythmias, the T78M cav-3 variant is more frequent than in the general population. Finally, in silico analysis of both sinoatrial and atrial cell models confirmed that the T78M-dependent changes are compatible with a pro-arrhythmic effect. Conclusion This study demonstrates that the T78M cav-3 induces complex modifications in ion channel function that ultimately alter membrane excitability. The presence of the T78M cav-3 can thus generate a susceptible substrate that, in concert with other structural alterations and/or genetic mutations, may become arrhythmogenic. PMID:28898996

  14. Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus

    Science.gov (United States)

    Mahajan, Anubha; Sim, Xueling; Ng, Hui Jin; Manning, Alisa; Rivas, Manuel A.; Highland, Heather M.; Locke, Adam E.; Grarup, Niels; Im, Hae Kyung; Cingolani, Pablo; Flannick, Jason; Fontanillas, Pierre; Fuchsberger, Christian; Gaulton, Kyle J.; Teslovich, Tanya M.; Rayner, N. William; Robertson, Neil R.; Beer, Nicola L.; Rundle, Jana K.; Bork-Jensen, Jette; Ladenvall, Claes; Blancher, Christine; Buck, David; Buck, Gemma; Burtt, Noël P.; Gabriel, Stacey; Gjesing, Anette P.; Groves, Christopher J.; Hollensted, Mette; Huyghe, Jeroen R.; Jackson, Anne U.; Jun, Goo; Justesen, Johanne Marie; Mangino, Massimo; Murphy, Jacquelyn; Neville, Matt; Onofrio, Robert; Small, Kerrin S.; Stringham, Heather M.; Syvänen, Ann-Christine; Trakalo, Joseph; Abecasis, Goncalo; Bell, Graeme I.; Blangero, John; Cox, Nancy J.; Duggirala, Ravindranath; Hanis, Craig L.; Seielstad, Mark; Wilson, James G.; Christensen, Cramer; Brandslund, Ivan; Rauramaa, Rainer; Surdulescu, Gabriela L.; Doney, Alex S. F.; Lannfelt, Lars; Linneberg, Allan; Isomaa, Bo; Tuomi, Tiinamaija; Jørgensen, Marit E.; Jørgensen, Torben; Kuusisto, Johanna; Uusitupa, Matti; Salomaa, Veikko; Spector, Timothy D.; Morris, Andrew D.; Palmer, Colin N. A.; Collins, Francis S.; Mohlke, Karen L.; Bergman, Richard N.; Ingelsson, Erik; Lind, Lars; Tuomilehto, Jaakko; Hansen, Torben; Watanabe, Richard M.; Prokopenko, Inga; Dupuis, Josee; Karpe, Fredrik; Groop, Leif; Laakso, Markku; Pedersen, Oluf; Florez, Jose C.; Morris, Andrew P.; Altshuler, David; Meigs, James B.; Boehnke, Michael; McCarthy, Mark I.; Lindgren, Cecilia M.; Gloyn, Anna L.

    2015-01-01

    Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights. PMID:25625282

  15. Identification and functional characterization of G6PC2 coding variants influencing glycemic traits define an effector transcript at the G6PC2-ABCB11 locus.

    Directory of Open Access Journals (Sweden)

    Anubha Mahajan

    2015-01-01

    Full Text Available Genome wide association studies (GWAS for fasting glucose (FG and insulin (FI have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7 evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF=1.5% influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1% influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D, the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights.

  16. Uncovering the Rare Variants of DLC1 Isoform 1 and Their Functional Effects in a Chinese Sporadic Congenital Heart Disease Cohort

    Science.gov (United States)

    Wang, Zhen; Tan, Huilian; Kong, Xianghua; Shu, Yang; Zhang, Yuchao; Huang, Yun; Zhu, Yufei; Xu, Heng; Wang, Zhiqiang; Wang, Ping; Ning, Guang; Kong, Xiangyin; Hu, Guohong; Hu, Landian

    2014-01-01

    Congenital heart disease (CHD) is the most common birth defect affecting the structure and function of fetal hearts. Despite decades of extensive studies, the genetic mechanism of sporadic CHD remains obscure. Deleted in liver cancer 1 (DLC1) gene, encoding a GTPase-activating protein, is highly expressed in heart and essential for heart development according to the knowledge of Dlc1-deficient mice. To determine whether DLC1 is a susceptibility gene for sporadic CHD, we sequenced the coding region of DLC1 isoform 1 in 151 sporadic CHD patients and identified 13 non-synonymous rare variants (including 6 private variants) in the case cohort. Importantly, these rare variants (8/13) were enriched in the N-terminal region of the DLC1 isoform 1 protein. Seven of eight amino acids at the N-terminal variant positions were conserved among the primates. Among the 9 rare variants that were predicted as “damaging”, five were located at the N-terminal region. Ensuing in vitro functional assays showed that three private variants (Met360Lys, Glu418Lys and Asp554Val) impaired the ability of DLC1 to inhibit cell migration or altered the subcellular location of the protein compared to wild-type DLC1 isoform 1. These data suggest that DLC1 might act as a CHD-associated gene in addition to its role as a tumor suppressor in cancer. PMID:24587289

  17. The NOS1 variant rs6490121 is associated with variation in prefrontal function and grey matter density in healthy individuals.

    LENUS (Irish Health Repository)

    Rose, Emma J

    2012-03-01

    A common polymorphism within the nitric oxide sythanse-1 (NOS1) gene (rs6490121), initially identified as risk variant for schizophrenia, has been associated with variation in working memory and IQ. Here we investigated how this variation might be mediated at the level of brain structure and function. In healthy individuals (N=157), voxel based morphometry was used to compare grey matter (GM) volume between homozygous and heterozygous carriers of the \\'G\\' allele (i.e. the allele associated with impaired cognition and schizophrenia risk) and homozygous carriers of the non-risk \\'A\\' allele. Functional brain imaging data were also acquired from 48 participants during performance of a spatial working memory (SWM) task, and analysed to determine any effect of NOS1 risk status. An a priori region-of-interest analysis identified a significant reduction in ventromedial prefrontal GM volume in \\'G\\' allele carriers. Risk carriers also exhibited altered patterns of activation in the prefrontal cortex, caudate, and superior parietal lobe, which were characteristic of abnormal increases in activation in frontoparietal working memory networks and a failure to disengage regions of the default mode network. These functional changes suggest a NOS1-mediated processing inefficiency, which may contribute to cognitive dysfunction in schizophrenia. While the mechanisms by which NOS1 may influence brain structure and\\/or function have not yet been well delineated, these data provide further evidence for a role of NOS1 in risk for schizophrenia via an impact upon cognitive function.

  18. Functional assessment of allelic variants in the SLC26A4 gene involved in Pendred syndrome and nonsyndromic EVA

    Science.gov (United States)

    Pera, Alejandra; Dossena, Silvia; Rodighiero, Simona; Gandía, Marta; Bottà, Guido; Meyer, Giuliano; Moreno, Felipe; Nofziger, Charity; Hernández-Chico, Concepción; Paulmichl, Markus

    2008-01-01

    Pendred syndrome is an autosomal recessive disorder characterized by sensorineural hearing loss, with malformations of the inner ear, ranging from enlarged vestibular aqueduct (EVA) to Mondini malformation, and deficient iodide organification in the thyroid gland. Nonsyndromic EVA (ns-EVA) is a separate type of sensorineural hearing loss showing normal thyroid function. Both Pendred syndrome and ns-EVA seem to be linked to the malfunction of pendrin (SLC26A4), a membrane transporter able to exchange anions between the cytosol and extracellular fluid. In the past, the pathogenicity of SLC26A4 missense mutations were assumed if the mutations fulfilled two criteria: low incidence of the mutation in the control population and substitution of evolutionary conserved amino acids. Here we show that these criteria are insufficient to make meaningful predictions about the effect of these SLC26A4 variants on the pendrin-induced ion transport. Furthermore, we functionally characterized 10 missense mutations within the SLC26A4 ORF, and consistently found that on the protein level, an addition or omission of a proline or a charged amino acid in the SLC26A4 sequence is detrimental to its function. These types of changes may be adequate for predicting SLC26A4 functionality in the absence of direct functional tests. PMID:19017801

  19. Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome

    Science.gov (United States)

    Kuechler, Alma; Zink, Alexander M; Wieland, Thomas; Lüdecke, Hermann-Josef; Cremer, Kirsten; Salviati, Leonardo; Magini, Pamela; Najafi, Kimia; Zweier, Christiane; Czeschik, Johanna Christina; Aretz, Stefan; Endele, Sabine; Tamburrino, Federica; Pinato, Claudia; Clementi, Maurizio; Gundlach, Jasmin; Maylahn, Carina; Mazzanti, Laura; Wohlleber, Eva; Schwarzmayr, Thomas; Kariminejad, Roxana; Schlessinger, Avner; Wieczorek, Dagmar; Strom, Tim M; Novarino, Gaia; Engels, Hartmut

    2015-01-01

    Intellectual disability (ID) has an estimated prevalence of 2–3%. Due to its extreme heterogeneity, the genetic basis of ID remains elusive in many cases. Recently, whole exome sequencing (WES) studies revealed that a large proportion of sporadic cases are caused by de novo gene variants. To identify further genes involved in ID, we performed WES in 250 patients with unexplained ID and their unaffected parents and included exomes of 51 previously sequenced child–parents trios in the analysis. Exome analysis revealed de novo intragenic variants in SET domain-containing 5 (SETD5) in two patients. One patient carried a nonsense variant, and the other an 81 bp deletion located across a splice-donor site. Chromosomal microarray diagnostics further identified four de novo non-recurrent microdeletions encompassing SETD5. CRISPR/Cas9 mutation modelling of the two intragenic variants demonstrated nonsense-mediated decay of the resulting transcripts, pointing to a loss-of-function (LoF) and haploinsufficiency as the common disease-causing mechanism of intragenic SETD5 sequence variants and SETD5-containing microdeletions. In silico domain prediction of SETD5, a predicted SET domain-containing histone methyltransferase (HMT), substantiated the presence of a SET domain and identified a novel putative PHD domain, strengthening a functional link to well-known histone-modifying ID genes. All six patients presented with ID and certain facial dysmorphisms, suggesting that SETD5 sequence variants contribute substantially to the microdeletion 3p25.3 phenotype. The present report of two SETD5 LoF variants in 301 patients demonstrates a prevalence of 0.7% and thus SETD5 variants as a relatively frequent cause of ID. PMID:25138099

  20. Two new splice variants in porcine PPARGC1A

    Directory of Open Access Journals (Sweden)

    Peelman Luc J

    2008-12-01

    Full Text Available Abstract Background Peroxisome proliferator-activated receptor γ coactivator 1α (PPARGC1A is a coactivator with a vital and central role in fat and energy metabolism. It is considered to be a candidate gene for meat quality in pigs and is involved in the development of obesity and diabetes in humans. How its many functions are regulated, is however still largely unclear. Therefore a transcription profile of PPARGC1A in 32 tissues and 4 embryonic developmental stages in the pig was constructed by screening its cDNA for possible splice variants with exon-spanning primers. Findings This led to the discovery of 2 new splice variants in the pig, which were subsequently also detected in human tissues. In these variants, exon 8 was either completely or partly (the last 66 bp were conserved spliced out, potentially coding for a much shorter protein of respectively 337 and 359 amino acids (aa, of which the first 291 aa would be the same compared to the complete protein (796 aa. Conclusion Considering the functional domains of the PPARGC1A protein, it is very likely these splice variants considerably affect the function of the protein and alternative splicing could be one of the mechanisms by which the diverse functions of PPARGC1A are regulated.

  1. A functional genetic variant in fragile-site gene FATS modulates the risk of breast cancer in triparous women

    International Nuclear Information System (INIS)

    Song, Fangfang; Zhang, Jun; Qiu, Li; Zhao, Yawen; Xing, Pan; Lu, Jiachun; Chen, Kexin; Li, Zheng

    2015-01-01

    The fragile-site associated tumor suppressor (FATS, formerly known as C10orf90), a regulator of p53-p21 pathway has been involved in the onset of breast cancer. Recent data support the idea that the crosstalk between FATS and p53 may be of physiological importance for reproduction during evolution. The aim of the current study was to test the hypothesis that FATS genetic polymorphism can influence the risk of breast cancer. We conducted population-based studies in two independent cohorts comprising 1 532 cases and 1 573 controls in Tianjin of North China, and 804 cases and 835 controls in Guangzhou of South China, coupled with functional validation methods, to investigate the role of FATS genetic variant in breast cancer risk. We identified a functional variant rs11245007 (905C > T, 262D/N) in fragile-site gene FATS that modulates p53 activation. FATS-262 N exhibited stronger E3 activity to polyubiquitinate p53 than did FATS-262D, leading to the stronger transcriptional activity of p53 and more pronounced stabilization of p53 protein and its activation in response to DNA damage. Case–control studies found that CT or TT genotype was significantly associated with a protective effect on breast cancer risk in women with parity ≥ 3, which was not affected by family history. Our findings suggest the role of FATS-p53 signaling cascade in suppressing pregnancy-related carcinogenesis and potential application of FATS genotyping in breast cancer prevention. The online version of this article (doi:10.1186/s12885-015-1570-9) contains supplementary material, which is available to authorized users

  2. Evidence that multiple genetic variants of MC4R play a functional role in the regulation of energy expenditure and appetite in Hispanic children1234

    Science.gov (United States)

    Cole, Shelley A; Voruganti, V Saroja; Cai, Guowen; Haack, Karin; Kent, Jack W; Blangero, John; Comuzzie, Anthony G; McPherson, John D; Gibbs, Richard A

    2010-01-01

    Background: Melanocortin-4-receptor (MC4R) haploinsufficiency is the most common form of monogenic obesity; however, the frequency of MC4R variants and their functional effects in general populations remain uncertain. Objective: The aim was to identify and characterize the effects of MC4R variants in Hispanic children. Design: MC4R was resequenced in 376 parents, and the identified single nucleotide polymorphisms (SNPs) were genotyped in 613 parents and 1016 children from the Viva la Familia cohort. Measured genotype analysis (MGA) tested associations between SNPs and phenotypes. Bayesian quantitative trait nucleotide (BQTN) analysis was used to infer the most likely functional polymorphisms influencing obesity-related traits. Results: Seven rare SNPs in coding and 18 SNPs in flanking regions of MC4R were identified. MGA showed suggestive associations between MC4R variants and body size, adiposity, glucose, insulin, leptin, ghrelin, energy expenditure, physical activity, and food intake. BQTN analysis identified SNP 1704 in a predicted micro-RNA target sequence in the downstream flanking region of MC4R as a strong, probable functional variant influencing total, sedentary, and moderate activities with posterior probabilities of 1.0. SNP 2132 was identified as a variant with a high probability (1.0) of exerting a functional effect on total energy expenditure and sleeping metabolic rate. SNP rs34114122 was selected as having likely functional effects on the appetite hormone ghrelin, with a posterior probability of 0.81. Conclusion: This comprehensive investigation provides strong evidence that MC4R genetic variants are likely to play a functional role in the regulation of weight, not only through energy intake but through energy expenditure. PMID:19889825

  3. Functional characterization of the ABCG2 5' non-coding exon variants: Stem cell specificity, translation efficiency and the influence of drug selection.

    Science.gov (United States)

    Sándor, Sára; Jordanidisz, Theodora; Schamberger, Anita; Várady, György; Erdei, Zsuzsa; Apáti, Ágota; Sarkadi, Balázs; Orbán, Tamás I

    2016-07-01

    ABCG2 is a multidrug transporter with wide substrate specificity, and is believed to protect several cell types from various xenobiotics and endobiotics. This "guardian" function is important in numerous cell types and tissue barriers but becomes disadvantageous by being responsible for the multidrug resistance phenotype in certain tumor cells. ABCG2 regulation at the protein level has already been extensively studied, however, regulation at the mRNA level, especially the functional role of the various 5' untranslated exon variants (5' UTRs) has been elusive. In the present work, we describe a comprehensive characterization of four ABCG2 mRNA variants with different exon 1 sequences, investigate drug inducibility, stem cell specificity, mRNA stability, and translation efficiency. Although certain variants (E1B and E1C) are considered as "constitutive" mRNA isoforms, we show that chemotoxic drugs significantly alter the expression pattern of distinct ABCG2 mRNA isoforms. When examining human embryonic stem cell lines, we provide evidence that variant E1A has an expression pattern coupled to undifferentiated stem cell stage, as its transcript level is regulated parallel to mRNAs of Oct4 and Nanog pluripotency marker genes. When characterizing the four exon 1 variants we found no significant differences in terms of mRNA stabilities and half-lives of the isoforms. In contrast, variant E1U showed markedly lower translation efficiency both at the total protein level or regarding the functional presence in the plasma membrane. Taken together, these results indicate that the different 5' UTR variants play an important role in cell type specific regulation and fine tuning of ABCG2 expression. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Molecular epidemiology and functional assessment of novel allelic variants of SLC26A4 in non-syndromic hearing loss patients with enlarged vestibular aqueduct in China.

    Directory of Open Access Journals (Sweden)

    Yongyi Yuan

    Full Text Available Mutations in SLC26A4, which encodes pendrin, are a common cause of deafness. SLC26A4 mutations are responsible for Pendred syndrome and non-syndromic enlarged vestibular aqueduct (EVA. The mutation spectrum of SLC26A4 varies widely among ethnic groups. To investigate the incidence of EVA in Chinese population and to provide appropriate genetic testing and counseling to patients with SLC26A4 variants, we conducted a large-scale molecular epidemiological survey of SLC26A4.A total of 2352 unrelated non-syndromic hearing loss patients from 27 different regions of China were included. Hot spot regions of SLC26A4, exons 8, 10 and 19 were sequenced. For patients with one allelic variant in the hot spot regions, the other exons were sequenced one by one until two mutant alleles had been identified. Patients with SLC26A4 variants were then examined by temporal bone computed tomography scan for radiological diagnosis of EVA. Ten SLC26A4 variants were cloned for functional study. Confocal microscopy and radioisotope techniques were used to examine the membrane expression of pendrin and transporter function.Of the 86 types of variants found, 47 have never been reported. The ratio of EVA in the Chinese deaf population was at least 11%, and that in patients of Han ethnicity reached at least 13%. The mutational spectrum and mutation detection rate of SLC26A4 are distinct among both ethnicities and regions of Mainland China. Most of the variants caused retention of pendrin in the intracellular region. All the mutant pendrins showed significantly reduced transport capability.An overall description of the molecular epidemiological findings of SLC26A4 in China is provided. The functional assessment procedure can be applied to identification of pathogenicity of variants. These findings are valuable for genetic diagnosis, genetic counseling, prenatal testing and pre-implantation diagnosis in EVA families.

  5. Functional relevance for associations between genetic variants and systemic lupus erythematosus.

    Directory of Open Access Journals (Sweden)

    Fei-Yan Deng

    Full Text Available Systemic lupus erythematosus (SLE is a serious prototype autoimmune disease characterized by chronic inflammation, auto-antibody production and multi-organ damage. Recent association studies have identified a long list of loci that were associated with SLE with relatively high statistical power. However, most of them only established the statistical associations of genetic markers and SLE at the DNA level without supporting evidence of functional relevance. Here, using publically available datasets, we performed integrative analyses (gene relationship across implicated loci analysis, differential gene expression analysis and functional annotation clustering analysis and combined with expression quantitative trait loci (eQTLs results to dissect functional mechanisms underlying the associations for SLE. We found that 14 SNPs, which were significantly associated with SLE in previous studies, have cis-regulation effects on four eQTL genes (HLA-DQA1, HLA-DQB1, HLA-DQB2, and IRF5 that were also differentially expressed in SLE-related cell groups. The functional evidence, taken together, suggested the functional mechanisms underlying the associations of 14 SNPs and SLE. The study may serve as an example of mining publically available datasets and results in validation of significant disease-association results. Utilization of public data resources for integrative analyses may provide novel insights into the molecular genetic mechanisms underlying human diseases.

  6. Algorithm for finding partitionings of hard variants of boolean satisfiability problem with application to inversion of some cryptographic functions.

    Science.gov (United States)

    Semenov, Alexander; Zaikin, Oleg

    2016-01-01

    In this paper we propose an approach for constructing partitionings of hard variants of the Boolean satisfiability problem (SAT). Such partitionings can be used for solving corresponding SAT instances in parallel. For the same SAT instance one can construct different partitionings, each of them is a set of simplified versions of the original SAT instance. The effectiveness of an arbitrary partitioning is determined by the total time of solving of all SAT instances from it. We suggest the approach, based on the Monte Carlo method, for estimating time of processing of an arbitrary partitioning. With each partitioning we associate a point in the special finite search space. The estimation of effectiveness of the particular partitioning is the value of predictive function in the corresponding point of this space. The problem of search for an effective partitioning can be formulated as a problem of optimization of the predictive function. We use metaheuristic algorithms (simulated annealing and tabu search) to move from point to point in the search space. In our computational experiments we found partitionings for SAT instances encoding problems of inversion of some cryptographic functions. Several of these SAT instances with realistic predicted solving time were successfully solved on a computing cluster and in the volunteer computing project SAT@home. The solving time agrees well with estimations obtained by the proposed method.

  7. In Silico survey of functional coding variants in human AEG-1 gene ...

    African Journals Online (AJOL)

    Background and aims: Non-synonymous (ns)SNPs represent typical genetic variations that may potentially affect the structure or function of expressed proteins and therefore could have an impact on complex disorders. A computational-based (In Silico) analysis has been done to evaluate the phenotypic effect of nsSNPs in ...

  8. A New Hybrid MGBPSO-GSA Variant for Improving Function Optimization Solution in Search Space

    Directory of Open Access Journals (Sweden)

    Narinder Singh

    2017-03-01

    Full Text Available In this article, a newly hybrid nature-inspired approach (MGBPSO-GSA is developed with a combination of Mean Gbest Particle Swarm Optimization (MGBPSO and Gravitational Search Algorithm (GSA. The basic inspiration is to integrate the ability of exploitation in MGBPSO with the ability of exploration in GSA to synthesize the strength of both approaches. As a result, the presented approach has the automatic balance capability between local and global searching abilities. The performance of the hybrid approach is tested on a variety of classical functions, ie, unimodal, multimodal, and fixed-dimension multimodal functions. Furthermore, Iris data set, Heart data set, and economic dispatch problems are used to compare the hybrid approach with several metaheuristics. Experimental statistical solutions prove empirically that the new hybrid approach outperforms significantly a number of metaheuristics in terms of solution stability, solution quality, capability of local and global optimum, and convergence speed.

  9. The Gain-of-Function Integrin β3 Pro33 Variant Alters the Serotonin System in the Mouse Brain.

    Science.gov (United States)

    Dohn, Michael R; Kooker, Christopher G; Bastarache, Lisa; Jessen, Tammy; Rinaldi, Capria; Varney, Seth; Mazalouskas, Matthew D; Pan, Hope; Oliver, Kendra H; Velez Edwards, Digna R; Sutcliffe, James S; Denny, Joshua C; Carneiro, Ana M D

    2017-11-15

    Engagement of integrins by the extracellular matrix initiates signaling cascades that drive a variety of cellular functions, including neuronal migration and axonal pathfinding in the brain. Multiple lines of evidence link the ITGB3 gene encoding the integrin β3 subunit with the serotonin (5-HT) system, likely via its modulation of the 5-HT transporter (SERT). The ITGB3 coding polymorphism Leu33Pro (rs5918, Pl A2 ) produces hyperactive αvβ3 receptors that influence whole-blood 5-HT levels and may influence the risk for autism spectrum disorder (ASD). Using a phenome-wide scan of psychiatric diagnoses, we found significant, male-specific associations between the Pro33 allele and attention-deficit hyperactivity disorder and ASDs. Here, we used knock-in (KI) mice expressing an Itgb3 variant that phenocopies the human Pro33 variant to elucidate the consequences of constitutively enhanced αvβ3 signaling to the 5-HT system in the brain. KI mice displayed deficits in multiple behaviors, including anxiety, repetitive, and social behaviors. Anatomical studies revealed a significant decrease in 5-HT synapses in the midbrain, accompanied by decreases in SERT activity and reduced localization of SERTs to integrin adhesion complexes in synapses of KI mice. Inhibition of focal adhesion kinase (FAK) rescued SERT function in synapses of KI mice, demonstrating that constitutive active FAK signaling downstream of the Pro32Pro33 integrin αvβ3 suppresses SERT activity. Our studies identify a complex regulation of 5-HT homeostasis and behaviors by integrin αvβ3, revealing an important role for integrins in modulating risk for neuropsychiatric disorders. SIGNIFICANCE STATEMENT The integrin β3 Leu33Pro coding polymorphism has been associated with autism spectrum disorders (ASDs) within a subgroup of patients with elevated blood 5-HT levels, linking integrin β3, 5-HT, and ASD risk. We capitalized on these interactions to demonstrate that the Pro33 coding variation in the murine

  10. CLOCK 3111T/C genetic variant influences the daily rhythm of autonomic nervous function: relevance to body weight control.

    Science.gov (United States)

    Lo, M-T; Bandin, C; Yang, H-W; Scheer, F A J L; Hu, K; Garaulet, M

    2018-02-01

    Humans carrying the genetic risk variant C at the circadian CLOCK (Circadian Locomotor Output Cycles Kaput) 3111T/C have been shown to have more difficulties to achieve desired weight loss than TT carriers. We tested the hypothesis that the daily rhythm of autonomic nervous function differs in CLOCK 3111C carriers, leading to reduced effectiveness in weight control. We recruited 40 overweight/obese Caucasian women (body mass index>25), 20 carrying CLOCK 3111C (CC and TC) and 20 non-carriers with matched age and body mass index who participated in a dietary obesity treatment program of up to 30 weeks. Following the treatment, ambulatory electrocardiography was continuously monitored for up to 3.5 days when subjects underwent their normal daily activities. To assess autonomic function, heart rate variability analysis (HRV) was performed hourly to obtain mean inter-beat interval between two consecutive R waves (mean RR) and s.d. of normal-to-normal heartbeat intervals (SDNN), and two parasympathetic measures, namely, proportion of differences between adjacent NN intervals that are >50 ms (pNN50), and high-frequency (HF: 0.15-0.4 Hz) power. In the TT carriers, all tested HRV indices showed significant daily rhythms (all P-values CLOCK variation on body weight control.

  11. Analysis of PGC-1α variants Gly482Ser and Thr612Met concerning their PPARγ2-coactivation function

    International Nuclear Information System (INIS)

    Nitz, Inke; Ewert, Agnes; Klapper, Maja; Doering, Frank

    2007-01-01

    Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a cofactor involved in adaptive thermogenesis, fatty acid oxidation, and gluconeogenesis. Dysfunctions of this protein are likely to contribute to the development of obesity and the metabolic syndrome. This is in part but not definitely confirmed by results of population studies. The aim of this study was to investigate if common genetic variants rs8192678 (Gly482Ser) and rs3736265 (Thr612Met) in the PGC-1α gene lead to a functional consequence in cofactor activity using peroxisome proliferator-activated receptor-γ 2 (PPARγ2) as interacting transcription factor. Reporter gene assays in HepG2 cells with wildtype and mutant proteins of both PGC1α and PPARγ2 (Pro12Ala, rs1801282) using the acyl-CoA-binding protein (ACBP) promoter showed no difference in coactivator activity. This is First study implicating that the Gly482Ser and Thr612Met polymorphisms in PGC-1α and Pro12Ala polymorphism in PPARγ2 do not affect the functional integrity of these proteins

  12. Effect of pasture availability and genotype on welfare, immune function, performance and meat characteristics of growing rabbits

    Directory of Open Access Journals (Sweden)

    Cecilia Mugnai

    2014-03-01

    Full Text Available To analyse the effect of pasture availability and genotype on innate immunological status,morphological organisation of lymphoid follicles, behaviour, performance and carcass and meat characteristics, 80 growing rabbits (40 Leprino of Viterbo and 40 New Zealand White, NZW were reared in bicellular standard cages (control or in a wired pen, provided with an external grass pasture (pasture. Blood samples and behaviour observations (10 rabbits per group were performed at different ages (weaning, 49 and 89 d. At the end of the trial, 10 rabbits per group were slaughtered to study meat quality/composition and vermiform appendix structure. Leprino rabbits showed higher serum lysozyme values than NZW for all ages and rearing systems. Leprino rabbits showed the highest values in caged animals (29.6 and 32.4 mg/mL, respectively at 49 and 89 d of age, while NZW animals did so in the pen (2.2 and 0.00 g/mL, respectively at 49 and 89 d of age. Haemolytic Complement Assay increased with age in Leprino (43.7 vs. 48.6 and 51.2 μg/mL, respectively for cage and pen, but decreased in NZW (68.6 vs. 25.8 and 41.1 μg/mL, respectively for cage and pen. Plasma TBARs was always higher in Leprino rabbits (16.0 vs. 7.0 μmol malondialdehyde/L at 29 d of age; 17.9 vs. 8.0 μmol malondialdehyde/L at 49 d of age; 20.0 vs. 11.4 μmol malondialdehyde/L at 89 d of age, whereas plasma tocopherol showed an inverse trend (32.9 vs. 46.6 mg/L at 29 d of age; 32.5 vs. 44.4 mg/L at 49 d of age; 31.2 vs. 42.4 mg/L at 89 d of age. Mortality rate of Leprino rabbits was highest in the cage system, while mortality was highest in NZW housed in the pen. Productive performance, carcass traits and fatty acid composition of meat were strongly affected by genotype and rearing system. Regarding genotype effect, Leprino showed lower daily gains (31.9 and 29.6 vs. 44.2 and 40.0 g, respectively for cage and pen system, live (2563 and 2418 vs. 2902 and 2650, respectively for cage and pen system

  13. Tubulopathy and pancytopaenia with normal pancreatic function: a variant of Pearson syndrome.

    Science.gov (United States)

    Atale, Agnès; Bonneau-Amati, Patrizia; Rötig, Agnès; Fischer, Alain; Perez-Martin, Stéphanie; de Lonlay, Pascale; Niaudet, Patrick; De Parscau, L; Mousson, C; Thauvin-Robinet, C; Munnich, A; Huet, F; Faivre, L

    2009-01-01

    Out of a series of 30 French patients with Pearson syndrome, we report on two patients with an atypical presentation, which include growth deficiency, pancytopaenia, tubulopathy and absence of exocrine pancreas dysfunction. Patient 1, a 4-year-old boy with a past history of pancytopaenia and transient metabolic acidosis at 13 months of age, presented at 2(1/2) years of age with severe tubulopathy of de Toni-Debré-Fanconi type, growth retardation, metabolic lactic acidosis and mild cytolysis. Despite normal exocrine pancreatic function, study of mitochondrial DNA revealed a 3.5 kb deletion. Patient 2 had a personal history of pancytopaenia requiring blood transfusions at 11 months of age and presented with severe intractable proximal and distal tubulopathy at 2 years of age. Exocrine pancreatic deficiency could not be evidenced and post-mortem studies revealed a 4.9 kb deletion of the mitochondrial DNA. A review of the literature revealed three patients presenting with Pearson syndrome and tubulopathy with normal pancreatic function and highlights delay in diagnosis in those three patients. The series of 30 French patients with Pearson syndrome also revealed that tubulopathy was present in 7/30 cases (23%), with variable outcome. In conclusion, Pearson syndrome should be screened for in children presenting with the association of growth retardation, anaemia/pancytopaenia, lactic acidosis and tubulopathy, even in the absence of exocrine pancreatic deficiency.

  14. Conformational and functional variants of CD44-targeted protein nanoparticles bio-produced in bacteria

    International Nuclear Information System (INIS)

    Pesarrodona, Mireia; Conchillo-Solé, Oscar; Unzueta, Ugutz; Xu, Zhikun; Ferrer-Miralles, Neus; Daura, Xavier; Vázquez, Esther; Villaverde, Antonio; Fernández, Yolanda; Foradada, Laia; Schwartz, Simó Jr; Abasolo, Ibane; Sánchez-Chardi, Alejandro; Roldán, Mónica; Villegas, Sandra; Rinas, Ursula

    2016-01-01

    Biofabrication is attracting interest as a means to produce nanostructured functional materials because of its operational versatility and full scalability. Materials based on proteins are especially appealing, as the structure and functionality of proteins can be adapted by genetic engineering. Furthermore, strategies and tools for protein production have been developed and refined steadily for more than 30 years. However, protein conformation and therefore activity might be sensitive to production conditions. Here, we have explored whether the downstream strategy influences the structure and biological activities, in vitro and in vivo, of a self-assembling, CD44-targeted protein-only nanoparticle produced in Escherichia coli. This has been performed through the comparative analysis of particles built from soluble protein species or protein versions obtained by in vitro protein extraction from inclusion bodies, through mild, non-denaturing procedures. These methods have been developed recently as a convenient alternative to the use of toxic chaotropic agents for protein resolubilization from protein aggregates. The results indicate that the resulting material shows substantial differences in its physicochemical properties and its biological performance at the systems level, and that its building blocks are sensitive to the particular protein source. (paper)

  15. Analyses of germline variants associated with ovarian cancer survival identify functional candidates at the 1q22 and 19p12 outcome loci

    DEFF Research Database (Denmark)

    Glubb, Dylan M; Johnatty, Sharon E; Quinn, Michael C J

    2017-01-01

    We previously identified associations with ovarian cancer outcome at five genetic loci. To identify putatively causal genetic variants and target genes, we prioritized two ovarian outcome loci (1q22 and 19p12) for further study. Bioinformatic and functional genetic analyses indicated that MEF2D a...

  16. Effect of Common Genetic Variants Associated with Type 2 Diabetes and Glycemic Traits on α- and β-cell Function and Insulin Action in Man

    DEFF Research Database (Denmark)

    Jonsson, Anna Elisabet; Ladenvall, Claes; Ahluwalia, Tarun Veer Singh

    2013-01-01

    Although meta-analyses of genome-wide association studies have identified more than 60 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes and/or glycemic traits, there is little information whether these variants also affect α-cell function. The aim of the present study was to...

  17. Effect of Common Genetic Variants Associated with Type 2 Diabetes and Glycemic Traits on a- and ß-cell Function and Insulin Action in Man

    DEFF Research Database (Denmark)

    Jonsson, Anna; Ladenvall, Claes; Ahluwalia, Tarun Veer Singh

    2013-01-01

    Although meta-analyses of genome-wide association studies have identified more than 60 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes and/or glycemic traits, there is little information whether these variants also affect a-cell function. The aim of the present study was to...

  18. Wholesomeness of gamma-radicidated poultry meat

    International Nuclear Information System (INIS)

    Tencheva, S.; Katsareva, Ts.

    1987-01-01

    Wholesomeness of radicidated with 6 kGy poultry meat was studied on mice. Evaluation of two consecutive generations was performed on the base of the following medicobiological parameters: generative function, anatomical studies and hemathological analysis. The results obtained do not show any deviation from the normal values for both investigated groups fed with irradiated and non-irradiated poultry meat

  19. Functional analysis of promoter variants in the microsomal triglyceride transfer protein (MTTP) gene.

    Science.gov (United States)

    Rubin, Diana; Schneider-Muntau, Alexandra; Klapper, Maja; Nitz, Inke; Helwig, Ulf; Fölsch, Ulrich R; Schrezenmeir, Jürgen; Döring, Frank

    2008-01-01

    The microsomal triglyceride transfer protein (MTTP) is required for the assembly and secretion of apolipoprotein B (apoB)-containing lipoproteins from the intestine and liver. According to this function, polymorphic sites in the MTTP gene showed associations to low-density lipoprotein (LDL) cholesterol and related traits of the metabolic syndrome. Here we studied the functional impact of common MTTP promoter polymorphisms rs1800804:T>C (-164T>C), rs1800803:A>T (-400A>T), and rs1800591:G>T (-493G>T) using gene-reporter assays in intestinal Caco-2 and liver Huh-7 cells. Significant results were obtained in Huh-7 cells. The common MTTP promoter haplotype -164T/-400A/-493G showed about two-fold lower activity than the rare haplotype -164C/-400T/-493T. MTTP promoter mutant constructs -164T/-400A/-493T and -164T/-400T/-493T exhibited similar activity than the common haplotype. Activities of mutants -164C/-400A/-493G and -164C/-400A/-493T resembled the rare MTTP promoter haplotype. Electrophoretic mobility shift assays (EMSAs) revealed higher binding capacity of the transcriptional factor Sterol regulatory element binding protein1a (SREBP1a) to the -164T probe in comparison to the -164C probe. In conclusion, our study indicates that the polymorphism -164T>C mediates different activities of common MTTP promoter haplotypes via SREBP1a. This suggested that the already described SREBP-dependent modulation of MTTP expression by diet is more effective in -164T than in -164C carriers. (c) 2007 Wiley-Liss, Inc.

  20. Functional characterization of a constitutively active kinase variant of Arabidopsis phototropin 1.

    Science.gov (United States)

    Petersen, Jan; Inoue, Shin-Ichiro; Kelly, Sharon M; Sullivan, Stuart; Kinoshita, Toshinori; Christie, John M

    2017-08-18

    Phototropins (phots) are plasma membrane-associated serine/threonine kinases that coordinate a range of processes linked to optimizing photosynthetic efficiency in plants. These photoreceptors contain two light-, oxygen-, or voltage-sensing (LOV) domains within their N terminus, with each binding one molecule of flavin mononucleotide as a UV/blue light-absorbing chromophore. Although phots contain two LOV domains, light-induced activation of the C-terminal kinase domain and subsequent receptor autophosphorylation is controlled primarily by the A'α-LOV2-Jα photosensory module. Mutations that disrupt interactions between the LOV2 core and its flanking helical segments can uncouple this mode of light regulation. However, the impact of these mutations on phot function in Arabidopsis has not been explored. Here we report that histidine substitution of Arg-472 located within the A'α-helix of Arabidopsis phot1 constitutively activates phot1 kinase activity in vitro without affecting LOV2 photochemistry. Expression analysis of phot1 R472H in the phot-deficient mutant confirmed that it is autophosphorylated in darkness in vivo but unable to initiate phot1 signaling in the absence of light. Instead, we found that phot1 R472H is poorly functional under low-light conditions but can restore phototropism, chloroplast accumulation, stomatal opening, and leaf positioning and expansion at higher light intensities. Our findings suggest that Arabidopsis can adapt to the elevated phosphorylation status of the phot1 R472H mutant in part by reducing its stability, whereas the activity of the mutant under high-light conditions can be attributed to additional increases in LOV2-mediated photoreceptor autophosphorylation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. AAV vectors expressing LDLR gain-of-function variants demonstrate increased efficacy in mouse models of familial hypercholesterolemia.

    Science.gov (United States)

    Somanathan, Suryanarayan; Jacobs, Frank; Wang, Qiang; Hanlon, Alexandra L; Wilson, James M; Rader, Daniel J

    2014-08-29

    Familial hypercholesterolemia is a genetic disorder that arises because of loss-of-function mutations in the low-density lipoprotein receptor (LDLR) and homozygous familial hypercholesterolemia is a candidate for gene therapy using adeno-associated viral vectors. Proprotein convertase subtilisin/kexin type 9 (PCSK9) and inducible degrader of LDLR (IDOL) negatively regulate LDLR protein and could dampen adeno-associated viral vector encoded LDLR expression. We sought to create vectors expressing gain-of-function human LDLR variants that are resistant to degradation by human PCSK9 (hPCSK9) and IDOL and thereby enhance hepatic LDLR protein abundance and plasma LDL cholesterol reduction. Amino acid substitutions were introduced into the coding sequence of human LDLR cDNA to reduce interaction with hPCSK9 and human IDOL. A panel of mutant human LDLRs was initially screened in vitro for escape from PCSK9. The variant human LDLR-L318D was further evaluated using a mouse model of homozygous familial hypercholesterolemia lacking endogenous LDLR and apolipoprotein B mRNA editing enzyme catalytic, APOBEC-1 (double knockout). Administration of wild-type human LDLR to double knockout mice, expressing hPCSK9, led to diminished LDLR activity. However, LDLR-L318D was resistant to hPCSK9-mediated degradation and effectively reduced cholesterol levels. Similarly, the LDLR-K809R\\C818A construct avoided human IDOL regulation and achieved stable reductions in serum cholesterol. An adeno-associated viral vector serotype 8.LDLR-L318D\\K809R\\C818A vector that carried all 3 amino acid substitutions conferred partial resistance to both hPCSK9- and human IDOL-mediated degradation. Amino acid substitutions in the human LDLR confer partial resistance to PCSK9 and IDOL regulatory pathways with improved reduction in cholesterol levels and improve on a potential gene therapeutic approach to treat homozygous familial hypercholesterolemia subjects. © 2014 American Heart Association, Inc.

  2. Structural and Functional Characterization of Two Alternative Splicing Variants of Mouse Endothelial Cell-Specific Chemotaxis Regulator (ECSCR

    Directory of Open Access Journals (Sweden)

    Yongchang Chang

    2012-04-01

    Full Text Available Endothelial cells (ECs that line the lumen of blood vessels are important players in blood vessel formation, and EC migration is a key component of the angiogenic process. Thus, identification of genes that are specifically or preferentially expressed in vascular ECs and in-depth understanding of their biological functions may lead to discovery of new therapeutic targets. We have previously reported molecular characterization of human endothelial cell-specific molecule 2 (ECSM2/endothelial cell-specific chemotaxis regulator (ECSCR. In the present study, we cloned two mouse full-length cDNAs by RT-PCR, which encode two putative ECSCR isoform precursors with considerable homology to the human ECSCR. Nucleotide sequence and exon-intron junction analyses suggested that they are alternative splicing variants (ECSCR isoform-1 and -2, differing from each other in the first and second exons. Quantitative RT-PCR results revealed that isoform-2 is the predominant form, which was most abundant in heart, lung, and muscles, and moderately abundant in uterus and testis. In contrast, the expression of isoform-1 seemed to be more enriched in testis. To further explore their potential cellular functions, we expressed GFP- and FLAG-tagged ECSCR isoforms, respectively, in an ECSCR deficient cell line (HEK293. Interestingly, the actual sizes of either ECSCR-GFP or -FLAG fusion proteins detected by immunoblotting are much larger than their predicted sizes, suggesting that both isoforms are glycoproteins. Fluorescence microscopy revealed that both ECSCR isoforms are localized at the cell surface, which is consistent with the structural prediction. Finally, we performed cell migration assays using mouse endothelial MS1 cells overexpressing GFP alone, isoform-1-GFP, and isoform-2-GFP, respectively. Our results showed that both isoforms significantly inhibited vascular epidermal growth factor (VEGF-induced cell migration. Taken together, we have provided several lines

  3. In Vitro Functional Analyses of Infrequent Nucleotide Variants in the Lactase Enhancer Reveal Different Molecular Routes to Increased Lactase Promoter Activity and Lactase Persistence

    DEFF Research Database (Denmark)

    Liebert, A.; Jones, B.L.; Danielsen, Erik Thomas

    2016-01-01

    The genetic trait that allows intestinal lactase to persist into adulthood in some 35% of humans worldwide operates at the level of transcription, the effect being caused by cis-acting nucleotide changes upstream of the lactase gene (LCT). A single nucleotide substitution, -13910 C>T, the first...... causal variant to be identified, accounts for lactase persistence over most of Europe. Located in a region shown to have enhancer function in vitro, it causes increased activity of the LCT promoter in Caco-2 cells, and altered transcription factor binding. Three other variants in close proximity, -13907...

  4. Chemical and biotechnological processing of collagen-containing raw materials into functional components of feed suitable for production of high-quality meat from farm animals

    Science.gov (United States)

    Baburina, M. I.; Ivankin, A. N.; Stanovova, I. A.

    2017-09-01

    The process of chemical biotechnological processing of collagen-containing raw materials into functional components of feeds for effective pig rearing was studied. Protein components of feeds were obtained as a result of hydrolysis in the presence of lactic acid of the animal collagen from secondary raw materials, which comprised subcutaneous collagen (cuticle), skin and veined mass with tendons from cattle. For comparison, a method is described for preparing protein components of feeds by cultivating Lactobacillus plantarum. Analysis of the kinetic data of the conversion of a high-molecular collagen protein to an aminolyte polypeptide mixture showed the advantage of microbiological synthesis in obtaining a protein for feeds. Feed formulations have been developed to include the components obtained, and which result in high quality pork suitable for the production of quality meat products.

  5. A Variant of GJD2, Encoding for Connexin 36, Alters the Function of Insulin Producing β-Cells.

    Directory of Open Access Journals (Sweden)

    Valentina Cigliola

    Full Text Available Signalling through gap junctions contributes to control insulin secretion and, thus, blood glucose levels. Gap junctions of the insulin-producing β-cells are made of connexin 36 (Cx36, which is encoded by the GJD2 gene. Cx36-null mice feature alterations mimicking those observed in type 2 diabetes (T2D. GJD2 is also expressed in neurons, which share a number of common features with pancreatic β-cells. Given that a synonymous exonic single nucleotide polymorphism of human Cx36 (SNP rs3743123 associates with altered function of central neurons in a subset of epileptic patients, we investigated whether this SNP also caused alterations of β-cell function. Transfection of rs3743123 cDNA in connexin-lacking HeLa cells resulted in altered formation of gap junction plaques and cell coupling, as compared to those induced by wild type (WT GJD2 cDNA. Transgenic mice expressing the very same cDNAs under an insulin promoter revealed that SNP rs3743123 expression consistently lead to a post-natal reduction of islet Cx36 levels and β-cell survival, resulting in hyperglycemia in selected lines. These changes were not observed in sex- and age-matched controls expressing WT hCx36. The variant GJD2 only marginally associated to heterogeneous populations of diabetic patients. The data document that a silent polymorphism of GJD2 is associated with altered β-cell function, presumably contributing to T2D pathogenesis.

  6. A Modified Reading the Mind in the Eyes Test Predicts Behavioral Variant Frontotemporal Dementia Better Than Executive Function Tests

    Directory of Open Access Journals (Sweden)

    Matthias L. Schroeter

    2018-01-01

    Full Text Available Behavioral variant frontotemporal dementia (bvFTD is characterized by deep alterations in behavior and personality. Although revised diagnostic criteria agree for executive dysfunction as most characteristic, impairments in social cognition are also suggested. The study aimed at identifying those neuropsychological and behavioral parameters best discriminating between bvFTD and healthy controls. Eighty six patients were diagnosed with possible or probable bvFTD according to Rascovsky et al. (2011 and compared with 43 healthy age-matched controls. Neuropsychological performance was assessed with a modified Reading the Mind in the Eyes Test (RMET, Stroop task, Trail Making Test (TMT, Hamasch-Five-Point Test (H5PT, and semantic and phonemic verbal fluency tasks. Behavior was assessed with the Apathy Evaluation Scale, Frontal Systems Behavioral Scale, and Bayer Activities of Daily Living Scale. Each test’s discriminatory power was investigated by Receiver Operating Characteristic curves calculating the area under the curve (AUC. bvFTD patients performed significantly worse than healthy controls in all neuropsychological tests. Discriminatory power (AUC was highest in behavioral questionnaires, high in verbal fluency tasks and the RMET, and lower in executive function tests such as the Stroop task, TMT and H5PT. As fluency tasks depend on several cognitive functions, not only executive functions, results suggest that the RMET discriminated better between bvFTD and control subjects than other executive tests. Social cognition should be incorporated into diagnostic criteria for bvFTD in the future, such as in the International Classification of Diseases (ICD-11, as already suggested in the Diagnostic and Statistical Manual for Mental Disorders (DSM-5.

  7. Identification and characterization of functional risk variants for colorectal cancer mapping to chromosome 11q23.1

    Science.gov (United States)

    Biancolella, Michela; Fortini, Barbara K.; Tring, Stephanie; Plummer, Sarah J.; Mendoza-Fandino, Gustavo A.; Hartiala, Jaana; Hitchler, Michael J.; Yan, Chunli; Schumacher, Fredrick R.; Conti, David V.; Edlund, Christopher K.; Noushmehr, Houtan; Coetzee, Simon G.; Bresalier, Robert S.; Ahnen, Dennis J.; Barry, Elizabeth L.; Berman, Benjamin P.; Rice, Judd C.; Coetzee, Gerhard A.; Casey, Graham

    2014-01-01

    Genome-wide association studies of colorectal cancer (CRC) have identified a number of common variants associated with modest risk, including rs3802842 at chromosome 11q23.1. Several genes map to this region but rs3802842 does not map to any known transcribed or regulatory sequences. We reasoned, therefore, that rs3802842 is not the functional single-nucleotide polymorphism (SNP), but is in linkage disequilibrium (LD) with a functional SNP(s). We performed ChIP-seq for histone modifications in SW480 and HCT-116 CRC cells, and incorporated ChIP-seq and DNase I hypersensitivity data available through ENCODE within a 137-kb genomic region containing rs3802842 on 11q23.1. We identified SNP rs10891246 in LD with rs3802842 that mapped within a bidirectional promoter region of genes C11orf92 and C11orf93. Following mutagenesis to the risk allele, the promoter demonstrated lower levels of reporter gene expression. A second SNP rs7130173 was identified in LD with rs3802842 that mapped to a candidate enhancer region, which showed strong unidirectional activity in both HCT-116 and SW480 CRC cells. The risk allele of rs7130173 demonstrated reduced enhancer activity compared with the common allele, and reduced nuclear protein binding affinity in electromobility shift assays compared with the common allele suggesting differential transcription factor (TF) binding. SNPs rs10891246 and rs7130173 are on the same haplotype, and expression quantitative trait loci (eQTL) analyses of neighboring genes implicate C11orf53, C11orf92 and C11orf93 as candidate target genes. These data imply that rs10891246 and rs7130173 are functional SNPs mapping to 11q23.1 and that C11orf53, C11orf92 and C11orf93 represent novel candidate target genes involved in CRC etiology. PMID:24256810

  8. Analysis of ancestral and functionally relevant CD5 variants in systemic lupus erythematosus patients.

    Directory of Open Access Journals (Sweden)

    Maria Carmen Cenit

    Full Text Available CD5 plays a crucial role in autoimmunity and is a well-established genetic risk factor of developing RA. Recently, evidence of positive selection has been provided for the CD5 Pro224-Val471 haplotype in East Asian populations. The aim of the present work was to further analyze the functional relevance of non-synonymous CD5 polymorphisms conforming the ancestral and the newly derived haplotypes (Pro224-Ala471 and Pro224-Val471, respectively as well as to investigate the potential role of CD5 on the development of SLE and/or SLE nephritis.The CD5 SNPs rs2241002 (C/T; Pro224Leu and rs2229177 (C/T; Ala471Val were genotyped using TaqMan allelic discrimination assays in a total of 1,324 controls and 681 SLE patients of Spanish origin. In vitro analysis of CD3-mediated T cell proliferative and cytokine response profiles of healthy volunteers homozygous for the above mentioned CD5 haplotypes were also analyzed.T-cell proliferation and cytokine release were significantly increased showing a bias towards to a Th2 profile after CD3 cross-linking of peripheral mononuclear cells from healthy individuals homozygous for the ancestral Pro224-Ala471 (CC haplotype, compared to the more recently derived Pro224-Val471 (CT. The same allelic combination was statistically associated with Lupus nephritis.The ancestral Ala471 CD5 allele confers lymphocyte hyper-responsiveness to TCR/CD3 cross-linking and is associated with nephritis in SLE patients.

  9. Research on the Sensorial Quality and Economic Efficiency in Obtaining of a certain Raw Meat Product - Mici Paste

    Directory of Open Access Journals (Sweden)

    Claudiu-Dan Salagean

    2013-11-01

    Full Text Available Research aimed the sensorial quality connected with the economic efficiency to obtain a certain raw meat product (mici paste in 4 experimental variants: 1 and 3 variants, with animal raw materials (meat + bacon and mix of natural spices - fine grinding variant (1 and coarse grinding variant (3 - chopping at the volf through the sieve of 3-4 mm; 2 and 4 variants, with animal raw materials (meat + bacon + vegetable protein supplements (textured soy protein + binder (protein + fiber + additive mix - fine grinding variant (2 and coarse grinding variant (4 - chopping at the volf through the sieve of 3 - 4 mm. In this respect organoleptic analyzes were performed on appearance (exterior and section, color, smell, texture and taste of the finished product (after roasting, the results highlighting that, in terms of organoleptic, sample 1 obtained the highest score (on a scale of 1-poor to 5-very good quality (average 21.83, followed by sample 3 (average 19.22, the very small difference in the case of sample 2 (average 19.19 and finally, sample 4 (average 18.75. It was noted that sample 1 obtained the highest score (average of all analyzed organoleptic indicators: appearance (4.33, color (4.39, smell (4.67, texture (4.33 and taste (4.11 being favorite by all volunteer subjects who participated at the analysis. The same thing was found in sensory analysis of mici paste in fresh/chilled condition: 65% of subjects preferred variant 1 followed by variant 3 (19.2%, variant 2 (11.5% and finally, variant 4 (3.8%. In terms of economic the highest efficiency was found in 2 (specific consumption 0.73 and 4 (specific consumption 0.77 variants compared to 1 (specific consumption 0.80 and 3 (specific consumption 0.82 variants, which translates into a reduction in the cost of products manufactured in the variants 2 and 4 (with protein supplements and additive mix by about 25-20% (with importance for the manufacturer. Also, thermal processing (roasting revealed the

  10. Thirteen new patients with guanidinoacetate methyltransferase deficiency and functional characterization of nineteen novel missense variants in the GAMT gene

    DEFF Research Database (Denmark)

    Mercimek-Mahmutoglu, Saadet; Ndika, Joseph; Kanhai, Warsha

    2014-01-01

    Guanidinoacetate methyltransferase deficiency (GAMT-D) is an autosomal recessively inherited disorder of creatine biosynthesis. Creatine deficiency on cranial proton magnetic resonance spectroscopy, and elevated guanidinoacetate levels in body fluids are the biomarkers of GAMT-D. In 74 patients 50...... and 20% a mild phenotype. The effect of these variants on GAMT enzyme activity was overexpressed using primary GAMT-D fibroblasts: 17 variants retained no significant activity and are therefore considered pathogenic. Two additional variants, c.22C>A (p.Pro8Thr) and c.79T>C (p.Tyr27His) (the latter...

  11. The BRCA1 variant p.Ser36Tyr abrogates BRCA1 protein function and potentially confers a moderate risk of breast cancer.

    Science.gov (United States)

    Christou, Charita M; Hadjisavvas, Andreas; Kyratzi, Maria; Flouri, Christina; Neophytou, Ioanna; Anastasiadou, Violetta; Loizidou, Maria A; Kyriacou, Kyriacos

    2014-01-01

    The identification of variants of unknown clinical significance (VUS) in the BRCA1 gene complicates genetic counselling and causes additional anxiety to carriers. In silico approaches currently used for VUS pathogenicity assessment are predictive and often produce conflicting data. Furthermore, functional assays are either domain or function specific, thus they do not examine the entire spectrum of BRCA1 functions and interpretation of individual assay results can be misleading. PolyPhen algorithm predicted that the BRCA1 p.Ser36Tyr VUS identified in the Cypriot population was damaging, whereas Align-GVGD predicted that it was possibly of no significance. In addition the BRCA1 p.Ser36Tyr variant was found to be associated with increased risk (OR = 3.47, 95% CI 1.13-10.67, P = 0.02) in a single case-control series of 1174 cases and 1109 controls. We describe a cellular system for examining the function of exogenous full-length BRCA1 and for classifying VUS. We achieved strong protein expression of full-length BRCA1 in transiently transfected HEK293T cells. The p.Ser36Tyr VUS exhibited low protein expression similar to the known pathogenic variant p.Cys61Gly. Co-precipitation analysis further demonstrated that it has a reduced ability to interact with BARD1. Further, co-precipitation analysis of nuclear and cytosolic extracts as well as immunofluorescence studies showed that a high proportion of the p.Ser36Tyr variant is withheld in the cytoplasm contrary to wild type protein. In addition the ability of p.Ser36Tyr to co-localize with conjugated ubiquitin foci in the nuclei of S-phase synchronized cells following genotoxic stress with hydroxyurea is impaired at more pronounced levels than that of the p.Cys61Gly pathogenic variant. The p.Ser36Tyr variant demonstrates abrogated function, and based on epidemiological, genetic, and clinical data we conclude that the p.Ser36Tyr variant is probably associated with a moderate breast cancer risk.

  12. The BRCA1 variant p.Ser36Tyr abrogates BRCA1 protein function and potentially confers a moderate risk of breast cancer.

    Directory of Open Access Journals (Sweden)

    Charita M Christou

    Full Text Available The identification of variants of unknown clinical significance (VUS in the BRCA1 gene complicates genetic counselling and causes additional anxiety to carriers. In silico approaches currently used for VUS pathogenicity assessment are predictive and often produce conflicting data. Furthermore, functional assays are either domain or function specific, thus they do not examine the entire spectrum of BRCA1 functions and interpretation of individual assay results can be misleading. PolyPhen algorithm predicted that the BRCA1 p.Ser36Tyr VUS identified in the Cypriot population was damaging, whereas Align-GVGD predicted that it was possibly of no significance. In addition the BRCA1 p.Ser36Tyr variant was found to be associated with increased risk (OR = 3.47, 95% CI 1.13-10.67, P = 0.02 in a single case-control series of 1174 cases and 1109 controls. We describe a cellular system for examining the function of exogenous full-length BRCA1 and for classifying VUS. We achieved strong protein expression of full-length BRCA1 in transiently transfected HEK293T cells. The p.Ser36Tyr VUS exhibited low protein expression similar to the known pathogenic variant p.Cys61Gly. Co-precipitation analysis further demonstrated that it has a reduced ability to interact with BARD1. Further, co-precipitation analysis of nuclear and cytosolic extracts as well as immunofluorescence studies showed that a high proportion of the p.Ser36Tyr variant is withheld in the cytoplasm contrary to wild type protein. In addition the ability of p.Ser36Tyr to co-localize with conjugated ubiquitin foci in the nuclei of S-phase synchronized cells following genotoxic stress with hydroxyurea is impaired at more pronounced levels than that of the p.Cys61Gly pathogenic variant. The p.Ser36Tyr variant demonstrates abrogated function, and based on epidemiological, genetic, and clinical data we conclude that the p.Ser36Tyr variant is probably associated with a moderate breast cancer risk.

  13. Identification of a loss-of-function inducible degrader of the low-density lipoprotein receptor variant in individuals with low circulating low-density lipoprotein.

    Science.gov (United States)

    Sorrentino, Vincenzo; Fouchier, Sigrid W; Motazacker, Mohammad M; Nelson, Jessica K; Defesche, Joep C; Dallinga-Thie, Geesje M; Kastelein, John J P; Kees Hovingh, G; Zelcer, Noam

    2013-05-01

    Recent genome-wide association studies suggest that IDOL (also known as MYLIP) contributes to variation in circulating levels of low-density lipoprotein cholesterol (LDL-C). IDOL, an E3-ubiquitin ligase, is a recently identified post-transcriptional regulator of LDLR abundance. Briefly, IDOL promotes degradation of the LDLR thereby limiting LDL uptake. Yet the exact role of IDOL in human lipoprotein metabolism is unclear. Therefore, this study aimed at identifying and functionally characterizing IDOL variants in the Dutch population and to assess their contribution to circulating levels of LDL-C. We sequenced the IDOL coding region in 677 individuals with LDL-C above the 95th percentile adjusted for age and gender (high-LDL-C cohort) in which no mutations in the LDLR, APOB, and PCSK9 could be identified. In addition, IDOL was sequenced in 560 individuals with baseline LDL-C levels below the 20th percentile adjusted for age and gender (low-LDL-C cohort). We identified a total of 14 IDOL variants (5 synonymous, 8 non-synonymous, and 1 non-sense). Functional characterization of these variants demonstrated that the p.Arg266X variant represents a complete loss of IDOL function unable to promote ubiquitylation and subsequent degradation of the LDLR. Consistent with loss of IDOL function, this variant was identified in individuals with low circulating LDL-C. Our results support the notion that IDOL contributes to variation in circulating levels of LDL-C. Strategies to inhibit IDOL activity may therefore provide a novel therapeutic venue to treating dyslipidaemia.

  14. Functional properties of bicarbonates and lactic acid on chicken breast retail display properties and cooked meat quality.

    Science.gov (United States)

    Lee, Nakia; Sharma, Vijendra; Brown, Nettie; Mohan, Anand

    2015-02-01

    Whole chicken breast was injected with potassium bicarbonate (PB), sodium bicarbonate (SB), and potassium lactate (K-lactate) and salt, alone or in combination at different concentration levels. The objectives were to 1) investigate the effects of different concentration of PB, SB, and PL on instrumental color, water-holding capacity (WHC), objective tenderness, expressible moisture, and moisture content and 2) evaluate whether sodium-containing ingredients can be replaced with potassium as a potential strategy to reduce total sodium content in the finished product. Results showed that chicken breast tissue marinated with SB and PB had greater moisture retention, display characteristics, and cooked product qualities than chicken breast tissue injected with water and the nonmarinated control. The L* values (lightness) did not change over the period of retail display and were not different compared to the control (P>0.05). The chicken breast enhanced with SB, PB, and K-lactate retained better retail display color than the controls (marinated with water and nonmarinated). Increasing the potassium bicarbonate concentration from 0.5 to 1.5% significantly improved the water-holding capacity (82.17 to 92.61%; Pretail display and cooked meat quality than SB. This study suggests that chicken breast tissue can be marinated with KB as a healthier alternative to phosphate or SB. © 2015 Poultry Science Association Inc.

  15. High frequency of rare copy number variants affecting functionally related genes in patients with structural brain malformations

    DEFF Research Database (Denmark)

    Kariminejad, Roxana; Lind-Thomsen, Allan; Tümer, Zeynep

    2011-01-01

    ) to investigate copy number variants (CNVs) in a cohort of 169 patients with various structural brain malformations including lissencephaly, polymicrogyria, focal cortical dysplasia, and corpus callosum agenesis. The majority of the patients had intellectual disabilities (ID) and suffered from symptomatic...

  16. Mutations of Glucose-6-Phosphate Dehydrogenase Durham, Santa-Maria and A+ Variants Are Associated with Loss Functional and Structural Stability of the Protein

    Directory of Open Access Journals (Sweden)

    Saúl Gómez-Manzo

    2015-12-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD deficiency is the most common enzymopathy in the world. More than 160 mutations causing the disease have been identified, but only 10% of these variants have been studied at biochemical and biophysical levels. In this study we report on the functional and structural characterization of three naturally occurring variants corresponding to different classes of disease severity: Class I G6PD Durham, Class II G6PD Santa Maria, and Class III G6PD A+. The results showed that the G6PD Durham (severe deficiency, and the G6PD Santa Maria and A+ (less severe deficiency (Class I, II and III, respectively affect the catalytic efficiency of these enzymes, are more sensitive to temperature denaturing, and affect the stability of the overall protein when compared to the wild type WT-G6PD. In the variants, the exposure of more and buried hydrophobic pockets was induced and monitored with 8-Anilinonaphthalene-1-sulfonic acid (ANS fluorescence, directly affecting the compaction of structure at different levels and probably reducing the stability of the protein. The degree of functional and structural perturbation by each variant correlates with the clinical severity reported in different patients.

  17. Mutations of Glucose-6-Phosphate Dehydrogenase Durham, Santa-Maria and A+ Variants Are Associated with Loss Functional and Structural Stability of the Protein

    Science.gov (United States)

    Gómez-Manzo, Saúl; Marcial-Quino, Jaime; Vanoye-Carlo, America; Enríquez-Flores, Sergio; De la Mora-De la Mora, Ignacio; González-Valdez, Abigail; García-Torres, Itzhel; Martínez-Rosas, Víctor; Sierra-Palacios, Edgar; Lazcano-Pérez, Fernando; Rodríguez-Bustamante, Eduardo; Arreguin-Espinosa, Roberto

    2015-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy in the world. More than 160 mutations causing the disease have been identified, but only 10% of these variants have been studied at biochemical and biophysical levels. In this study we report on the functional and structural characterization of three naturally occurring variants corresponding to different classes of disease severity: Class I G6PD Durham, Class II G6PD Santa Maria, and Class III G6PD A+. The results showed that the G6PD Durham (severe deficiency), and the G6PD Santa Maria and A+ (less severe deficiency) (Class I, II and III, respectively) affect the catalytic efficiency of these enzymes, are more sensitive to temperature denaturing, and affect the stability of the overall protein when compared to the wild type WT-G6PD. In the variants, the exposure of more and buried hydrophobic pockets was induced and monitored with 8-Anilinonaphthalene-1-sulfonic acid (ANS) fluorescence, directly affecting the compaction of structure at different levels and probably reducing the stability of the protein. The degree of functional and structural perturbation by each variant correlates with the clinical severity reported in different patients. PMID:26633385

  18. Intracellular lipid dysregulation interferes with leukocyte function in the ovaries of meat-type hens under unrestricted feed intake.

    Science.gov (United States)

    Liu, Zu-Chen; Su, Chia-Ming; Xie, Yi-Lun; Chang, Chai-Ju; Chen, Jiang-Young; Wu, Shu-Wei; Chen, Yu-Hui; Walzem, Rosemary L; Huang, San-Yuan; Chen, Shuen-Ei

    2016-04-01

    Meat-type Red-feather country hens fed ad libitum (AD-hens) exhibit obesity-associated morbidities and a number of ovarian irregularities. Leukocyte participations in ovarian activities are unstudied in AD-hens. In contrast to feed-restricted hens (R-hens), ovulatory process of the F1 follicle appeared delayed in AD-hens in association with reduced F1 follicle progesterone content, gelatinase A (MMP-2) and collagenase-3 (MMP-13) activities coincident with elevated IL-1β and no production (Pcultures of granulosa cells with increasing numbers of leukocytes from either AD-hens or R-hens exhibited dose dependent reductions in progesterone production and increases in cell death. AD-hen leukocytes were less proapoptotic than their R counterparts (Pcultures with heterophils or monocytes in a dose-dependent manner (Pcultures than their respective counterparts (P<0.05). Both basal and LPS-induced IL-1β secretion and MMP-22 or MMP-2 activities in freshly isolated AD-hen leukocytes were reduced (P<0.05). Exposure of AD or R leukocytes to 0.5mM palmitate impaired IL-1β secretion and MMP-22 or MMP-2 activity. Inhibition of ceramide synthesis with FB1 and ROS production with n-MPG scavenging rescued MMP activity and IL-1β production in palmitate treated heterophils, but exacerbated monocyte suppression. These latter findings suggest that intracellular lipid dysregulation in leukocytes contributes to ovarian dysfunction in AD-hens. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Heterozygosity for the Mood Disorder-Associated Variant Gln460Arg Alters P2X7 Receptor Function and Sleep Quality.

    Science.gov (United States)

    Metzger, Michael W; Walser, Sandra M; Dedic, Nina; Aprile-Garcia, Fernando; Jakubcakova, Vladimira; Adamczyk, Marek; Webb, Katharine J; Uhr, Manfred; Refojo, Damian; Schmidt, Mathias V; Friess, Elisabeth; Steiger, Axel; Kimura, Mayumi; Chen, Alon; Holsboer, Florian; Arzt, Eduardo; Wurst, Wolfgang; Deussing, Jan M

    2017-11-29

    A single nucleotide polymorphism substitution from glutamine (Gln, Q) to arginine (Arg, R) at codon 460 of the purinergic P2X7 receptor (P2X7R) has repeatedly been associated with mood disorders. The P2X7R-Gln460Arg variant per se is not compromised in its function. However, heterologous expression of P2X7R-Gln460Arg together with wild-type P2X7R has recently been demonstrated to impair receptor function. Here we show that this also applies to humanized mice coexpressing both human P2X7R variants. Primary hippocampal cells derived from heterozygous mice showed an attenuated calcium uptake upon agonist stimulation. While humanized mice were unaffected in their behavioral repertoire under basal housing conditions, mice that harbor both P2X7R variants showed alterations in their sleep quality resembling signs of a prodromal disease stage. Also healthy heterozygous human subjects showed mild changes in sleep parameters. These results indicate that heterozygosity for the wild-type P2X7R and its mood disorder-associated variant P2X7R-Gln460Arg represents a genetic risk factor, which is potentially able to convey susceptibility to mood disorders. SIGNIFICANCE STATEMENT Depression and bipolar disorder are the most common mood disorders. The P2X7 receptor (P2X7R) regulates many cellular functions. Its polymorphic variant Gln460Arg has repeatedly been associated with mood disorders. Genetically engineered mice, with human P2X7R, revealed that heterozygous mice (i.e., they coexpress the disease-associated Gln460Arg variant together with its normal version) have impaired receptor function and showed sleep disturbances. Human participants with the heterozygote genotype also had subtle alterations in their sleep profile. Our findings suggest that altered P2X7R function in heterozygote individuals disturbs sleep and might increase the risk for developing mood disorders. Copyright © 2017 the authors 0270-6474/17/3711688-13$15.00/0.

  20. Scavengers for bacteria: Rainbow trout have two functional variants of MARCO that bind to gram-negative and -positive bacteria.

    Science.gov (United States)

    Poynter, Sarah J; Monjo, Andrea L; Micheli, Gabriella; DeWitte-Orr, Stephanie J

    2017-12-01

    Class A scavenger receptors (SR-As) are a family of surface-expressed receptors who bind a wide range of polyanionic ligands including bacterial components and nucleic acids and play a role in innate immunity. Macrophage receptor with collagenous structure (MARCO) is a SR-A family member that has been studied in mammals largely for its role in binding bacteria. To date there is little information about SR-As in general and MARCO specifically in fish, particularly what ligands individual SR-A family members bind remains largely unknown. In the present study two novel rainbow trout MARCO transcript variants have been identified and their sequence and putative protein domains have been analyzed. When overexpressed in CHSE-214, a cell line that appears to lack functional scavenger receptors, GFP-tagged rtMARCO-1 and rtMARCO-2 were able to bind gram-positive, and gram-negative bacteria of both mammalian and aquatic sources. rtMARCO appears to bind bacteria via its scavenger receptor cysteine-rich (SRCR) domain, because SRCR deleted rtMARCO-1 and -2 were unable to bind bacteria. rtMARCO did not show any binding to the yeast cell wall component zymosan or to double-stranded (ds)RNA. This is the first time rainbow trout MARCO sequences have been identified and the first in-depth study exploring their ligand binding profile. This study provides novel insight into the role of rainbow trout MARCO in bacterial innate immunity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. The region of XRCC1 which harbours the three most common nonsynonymous polymorphic variants, is essential for the scaffolding function of XRCC1

    DEFF Research Database (Denmark)

    Hanssen-Bauer, Audun; Solvang-Garten, Karin; Gilljam, Karin Margaretha

    2012-01-01

    for recruitment of XRCC1 to sites of DNA damage and DNA replication. Also, we found that ectopic expression of the region from residue 166-436 partially rescued the methyl methanesulfonate (MMS) hypersensitivity of XRCC1-deficient EM9 cells, suggesting a key role for this region in mediating DNA repair. The three...... most common amino acid variants of XRCC1, Arg194Trp, Arg280His and Arg399Gln, are located within the region comprising the NLS and BRCT1 domains, and these variants may be associated with increased incidence of specific types of cancer. While we could not detect differences in the intra......XRCC1 functions as a non-enzymatic, scaffold protein in single strand break repair (SSBR) and base excision repair (BER). Here, we examine different regions of XRCC1 for their contribution to the scaffolding functions of the protein. We found that the central BRCT1 domain is essential...

  2. Molecular and functional identification of cyclic AMP-sensitive BKCa potassium channels (ZERO variant) and L-type voltage-dependent calcium channels in single rat juxtaglomerular cells

    DEFF Research Database (Denmark)

    Friis, Ulla G; Jørgensen, Finn; Andreasen, Ditte

    2003-01-01

    This study aimed at identifying the type and functional significance of potassium channels and voltage-dependent calcium channels (Ca(v)) in single rat JG cells using whole-cell patch clamp. Single JG cells displayed outward rectification at positive membrane potentials and limited net currents......, respectively. Double immunofluorescence confirmed the presence of BKCa and renin in the same cell. cAMP increased the outward current by 1.6-fold, and this was inhibited by 74% with iberiotoxin. Expression of the cAMP-sensitive splice variant (ZERO) of BKCa was confirmed in single-sampled JG cells by RT...... no effect. We conclude that JG cells express functional cAMP-sensitive BKCa channels (the ZERO splice variant) and voltage-dependent L-type Ca2+ channels....

  3. Possible involvement of the glucocorticoid receptor (NR3C1) and selected NR3C1 gene variants in regulation of human testicular function

    DEFF Research Database (Denmark)

    Nordkap, L; Almstrup, K; Nielsen, J E

    2017-01-01

    Perceived stress has been associated with decreased semen quality but the mechanisms have not been elucidated. It is not known whether cortisol, the major stress hormone in humans, can act directly via receptors in the testis, and whether variants in the gene encoding the glucocorticoid receptor...... is limited, the results substantiate a suggested link between stress and testicular function. Hence this investigation should be regarded as a discovery study generating hypotheses for future studies....

  4. Allele variants in functional MicroRNA target sites of the neurotrophin-3 receptor gene (NTRK3) as susceptibility factors for anxiety disorders

    OpenAIRE

    Muiños Gimeno, Margarita; Guidi, Mònica; Kagerbauer, Birgit; Martín Santos, Rocío; Navinés, Ricard; Alonso, Pino; Menchón, José M.; Gratacós Mayora, Mònica; Estivill, Xavier, 1955-; Espinosa Parrilla, Yolanda

    2009-01-01

    Genetic and functional data indicate that variation in the expression of the neurotrophin-3 receptor gene (NTRK3) may have an impact on neuronal plasticity, suggesting a role for NTRK3 in the pathophysiology of anxiety disorders. MicroRNA (miRNA) posttranscriptional gene regulators act by base-pairing to specific sequence sites, usually at the 3'UTR of the target mRNA. Variants at these sites might result in gene expression changes contributing to disease susceptibility. We investigated genet...

  5. Use of an isoelectric solubilization/precipitation process to modify the functional properties of PSE (pale, soft, exudative)-like chicken meat protein: A mechanistic approach.

    Science.gov (United States)

    Zhao, Xue; Bai, Yun; Xing, Tong; Xu, Xing-Lian; Zhou, Guanghong

    2018-05-15

    The functionality of pale, soft, exudative (PSE)-like chicken protein was improved by isoelectric solubilization/precipitation (ISP) treatment. PSE-like chicken proteins were solubilized at an acidic pH 3.5 or an alkaline pH 11.0, followed by precipitating at pH 5.5 and 6.2. PSE-like meat paste was treated as control (CON). Precipitated at pH 6.2 led to a more elastic gel than at pH 5.5. Water distribution of ISP-isolated protein was affected by precipitation pH. More tryptophan residues exposed and -SH was partially oxidized to disulfide bond after ISP treatment, which led to large aggregates formation and higher viscosity of ISP isolated proteins than of CON. Absolute zeta potential of alkali-treated protein was higher than other counterparts, indicating stronger electric repulsion. ISP treatments could convert α-helix structure to relatively irregular structures. Overall, solubilizing at pH 11.0, combined with a precipitation pH 6.2 ISP treatment offers a potential for enhanced functionality of PSE-like chicken protein. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Effects of heat stress and probiotic supplementation on protein functionality and oxidative stability of ground chicken leg meat during display storage.

    Science.gov (United States)

    Kim, Hyun-Wook; Kim, Ji-Han; Yan, Feifei; Cheng, Heng-Wei; Brad Kim, Yuan H

    2017-12-01

    The present study aimed to evaluate the effects of heat stress and probiotic supplementation on protein functionality and oxidative stability of ground chicken leg during display storage. Two hundred and forty, 1-day-old male chicks (5 birds per pen) were subjected to four treatments in a 2 (thermoneutral condition at 21 °C and cyclic heat stress at 32-21-32 °C for 10 h day -1 ) × 2 (regular diet with 0 or 0.25 g kg -1 Bacillus subtilis) factorial design. Chickens were harvested at day 46, and pairs of whole legs were collected at 1 day postmortem. The chicken legs were deboned, ground, tray-packaged with oxygen-permeable film, and displayed for 3 days. Heat stress and probiotic supplementation had no impact on pH, water-holding capacity, color, protein functionality, lipid lipolysis and lipid/protein oxidation stability (P > 0.05). Display storage increased the pH and lipid oxidation of ground chicken legs (P chicken leg meat. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  7. Technological characteristics of meat - viscosity

    OpenAIRE

    DIBĎÁK, Tomáš

    2012-01-01

    This bachelor thesis is focused on the technological characteristics of meat, mainly viscosity of meat. At the beginning I dealt with construction of meat and various types of meat: beef, veal, pork, mutton, rabbit, poultry and venison. Then I described basic chemical composition of meat and it?s characteristic. In detail I dealt with viscosity of meat. Viscosity is the ability of meat to bind water both own and added. I mentioned influences, which effects viscosity and I presented the possib...

  8. Clostridium difficile in poultry and poultry meat.

    Science.gov (United States)

    Harvey, Roger B; Norman, Keri N; Andrews, Kathleen; Hume, Michael E; Scanlan, Charles M; Callaway, Todd R; Anderson, Robin C; Nisbet, David J

    2011-12-01

    The incidence and severity of disease associated with toxigenic Clostridium difficile have increased in hospitals in North America from the emergence of newer, more virulent strains. Toxigenic C. difficile has been isolated from food animals and retail meat with potential implications of transfer to human beings. The objective of the present study was to determine the prevalence of toxigenic C. difficile in chickens and retail poultry meat in Texas. Seven C. difficile isolates were detected in fecal samples of 300 (2.3%) broiler chickens. Three cultivation procedures were evaluated for isolation of C. difficile from poultry meat and detected 1/32 (3.1%), 2/32 (6.2%), and 4/32 (12.5%) for the three procedures, respectively. Chicken and poultry meat isolates were characterized as toxinotype V and pulsed-field gel electrophoresis gel type-NAP7 or NAP7-variant. Susceptibilities to 11 antimicrobial agents in the current study suggested somewhat reduced resistance than reported for other meat or animal toxinotype V isolates.

  9. Identification of a functional variant in the KIF5A-CYP27B1-METTL1-FAM119B locus associated with multiple sclerosis

    Science.gov (United States)

    Alcina, Antonio; Fedetz, Maria; Fernández, Óscar; Saiz, Albert; Izquierdo, Guillermo; Lucas, Miguel; Leyva, Laura; García-León, Juan-Antonio; Abad-Grau, María del Mar; Alloza, Iraide; Antigüedad, Alfredo; Garcia-Barcina, María J; Vandenbroeck, Koen; Varadé, Jezabel; de la Hera, Belén; Arroyo, Rafael; Comabella, Manuel; Montalban, Xavier; Petit-Marty, Natalia; Navarro, Arcadi; Otaegui, David; Olascoaga, Javier; Blanco, Yolanda; Urcelay, Elena; Matesanz, Fuencisla

    2013-01-01

    Background and aim Several studies have highlighted the association of the 12q13.3–12q14.1 region with coeliac disease, type 1 diabetes, rheumatoid arthritis and multiple sclerosis (MS); however, the causal variants underlying diseases are still unclear. The authors sought to identify the functional variant of this region associated with MS. Methods Tag-single nucleotide polymorphism (SNP) analysis of the associated region encoding 15 genes was performed in 2876 MS patients and 2910 healthy Caucasian controls together with expression regulation analyses. Results rs6581155, which tagged 18 variants within a region where 9 genes map, was sufficient to model the association. This SNP was in total linkage disequilibrium (LD) with other polymorphisms that associated with the expression levels of FAM119B, AVIL, TSFM, TSPAN31 and CYP27B1 genes in different expression quantitative trait loci studies. Functional annotations from Encyclopedia of DNA Elements (ENCODE) showed that six out of these rs6581155-tagged-SNPs were located in regions with regulatory potential and only one of them, rs10877013, exhibited allele-dependent (ratio A/G=9.5-fold) and orientation-dependent (forward/reverse=2.7-fold) enhancer activity as determined by luciferase reporter assays. This enhancer is located in a region where a long-range chromatin interaction among the promoters and promoter-enhancer of several genes has been described, possibly affecting their expression simultaneously. Conclusions This study determines a functional variant which alters the enhancer activity of a regulatory element in the locus affecting the expression of several genes and explains the association of the 12q13.3–12q14.1 region with MS. PMID:23160276

  10. The incorporation of the novel histone variant H2AL2 confers unusual structural and functional properties of the nucleosome

    Czech Academy of Sciences Publication Activity Database

    Syed, S.H.; Boulard, M.; Shukla, M.S.; Gautier, T.; Travers, A.; Bednár, Jan; Faivre-Moskalenko, C.; Dimitrov, S.; Angelov, D.

    2009-01-01

    Roč. 37, č. 14 (2009), s. 4684-4695 ISSN 0305-1048 Grant - others:GA MŠk(CZ) LC535; GA ČR(CZ) GA304/05/2168 Program:LC Institutional research plan: CEZ:AV0Z50110509 Keywords : nucleosome * histone * variant Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.479, year: 2009

  11. Functional modulation of the glutamate transporter variant GLT1b by the PDZ domain protein PICK1

    DEFF Research Database (Denmark)

    Søgaard, Rikke; Borre, Lars; Braunstein, Thomas H

    2013-01-01

    The dominant glutamate transporter isoform in the mammalian brain, GLT1, exists as at least three splice variants, GLT1a, GLT1b, and GLT1c. GLT1b interacts with the scaffold protein PICK1 (protein interacting with kinase C1), which is implicated in glutamatergic neurotransmission via its regulato...

  12. Identification, expression and functional characterization of M4L, a muscarinic acetylcholine M4 receptor splice variant.

    Directory of Open Access Journals (Sweden)

    Douglas A Schober

    Full Text Available Rodent genomic alignment sequences support a 2-exon model for muscarinic M4 receptor. Using this model a novel N-terminal extension was discovered in the human muscarinic acetylcholine M4 receptor. An open reading frame was discovered in the human, mouse and rat with a common ATG (methionine start codon that extended the N-terminus of the muscarinic acetylcholine M4 receptor subtype by 155 amino acids resulting in a longer variant. Transcriptional evidence for this splice variant was confirmed by RNA-Seq and RT-PCR experiments performed from human donor brain prefrontal cortices. We detected a human upstream exon indicating the translation of the mature longer M4 receptor transcript. The predicted size for the longer two-exon M4 receptor splice variant with the additional 155 amino acid N-terminal extension, designated M4L is 69.7 kDa compared to the 53 kDa canonical single exon M4 receptor (M4S. Western blot analysis from a mammalian overexpression system, and saturation radioligand binding with [3H]-NMS (N-methyl-scopolamine demonstrated the expression of this new splice variant. Comparative pharmacological characterization between the M4L and M4S receptors revealed that both the orthosteric and allosteric binding sites for both receptors were very similar despite the addition of an N-terminal extension.

  13. Identification, expression and functional characterization of M4L, a muscarinic acetylcholine M4 receptor splice variant.

    Science.gov (United States)

    Schober, Douglas A; Croy, Carrie H; Ruble, Cara L; Tao, Ran; Felder, Christian C

    2017-01-01

    Rodent genomic alignment sequences support a 2-exon model for muscarinic M4 receptor. Using this model a novel N-terminal extension was discovered in the human muscarinic acetylcholine M4 receptor. An open reading frame was discovered in the human, mouse and rat with a common ATG (methionine start codon) that extended the N-terminus of the muscarinic acetylcholine M4 receptor subtype by 155 amino acids resulting in a longer variant. Transcriptional evidence for this splice variant was confirmed by RNA-Seq and RT-PCR experiments performed from human donor brain prefrontal cortices. We detected a human upstream exon indicating the translation of the mature longer M4 receptor transcript. The predicted size for the longer two-exon M4 receptor splice variant with the additional 155 amino acid N-terminal extension, designated M4L is 69.7 kDa compared to the 53 kDa canonical single exon M4 receptor (M4S). Western blot analysis from a mammalian overexpression system, and saturation radioligand binding with [3H]-NMS (N-methyl-scopolamine) demonstrated the expression of this new splice variant. Comparative pharmacological characterization between the M4L and M4S receptors revealed that both the orthosteric and allosteric binding sites for both receptors were very similar despite the addition of an N-terminal extension.

  14. Meat analogues: Health promising sustainable meat substitutes.

    Science.gov (United States)

    Kumar, Pavan; Chatli, M K; Mehta, Nitin; Singh, Parminder; Malav, O P; Verma, Akhilesh K

    2017-03-24

    There is a scarcity of protein of high biological value due to rapid increase in the world population and limited natural resources. Meat is a good source of protein of high biological value but converting the vegetable protein into animal protein is not economical. There is a trend of production of healthy and delicious meat free food for satisfaction of vegetarian and personal well beings. This resulted in increasing use of low cost vegetable protein such as textured soy protein, mushroom, wheat gluten, pulses etc as a substitute for animal-protein. These simulated meat-like products, with similar texture, flavor, color, and nutritive value can be substituted directly for meat to all sections of the society.

  15. Analysis of functional germline variants in APOBEC3 and driver genes on breast cancer risk in Moroccan study population

    International Nuclear Information System (INIS)

    Marouf, Chaymaa; Göhler, Stella; Filho, Miguel Inacio Da Silva; Hajji, Omar; Hemminki, Kari; Nadifi, Sellama; Försti, Asta

    2016-01-01

    Breast cancer (BC) is the most prevalent cancer in women and a major public health problem in Morocco. Several Moroccan studies have focused on studying this disease, but more are needed, especially at the genetic and molecular levels. Therefore, we investigated the potential association of several functional germline variants in the genes commonly mutated in sporadic breast cancer. In this case–control study, we examined 36 single nucleotide polymorphisms (SNPs) in 13 genes (APOBEC3A, APOBEC3B, ARID1B, ATR, MAP3K1, MLL2, MLL3, NCOR1, RUNX1, SF3B1, SMAD4, TBX3, TTN), which were located in the core promoter, 5’-and 3’UTR or which were nonsynonymous SNPs to assess their potential association with inherited predisposition to breast cancer development. Additionally, we identified a ~29.5-kb deletion polymorphism between APOBEC3A and APOBEC3B and explored possible associations with BC. A total of 226 Moroccan breast cancer cases and 200 matched healthy controls were included in this study. The analysis showed that12 SNPs in 8 driver genes, 4 SNPs in APOBEC3B gene and 1 SNP in APOBEC3A gene were associated with BC risk and/or clinical outcome at P ≤ 0.05 level. RUNX1-rs8130963 (odds ratio (OR) = 2.25; 95 % CI 1.42-3.56; P = 0.0005; dominant model), TBX3-rs8853 (OR = 2.04; 95 % CI 1.38-3.01; P = 0.0003; dominant model), TBX3-rs1061651 (OR = 2.14; 95 % CI1.43-3.18; P = 0.0002; dominant model), TTN-rs12465459 (OR = 2.02; 95 % confidence interval 1.33-3.07; P = 0.0009; dominant model), were the most significantly associated SNPs with BC risk. A strong association with clinical outcome were detected for the genes SMAD4 -rs3819122 with tumor size (OR = 0.45; 95 % CI 0.25-0.82; P = 0.009) and TTN-rs2244492 with estrogen receptor (OR = 0.45; 95 % CI 0.25-0.82; P = 0.009). Our results suggest that genetic variations in driver and APOBEC3 genes were associated with the risk of BC and may have impact on clinical outcome. However, the reported association between the

  16. Genetic association of marbling score with intragenic nucleotide variants at selection signals of the bovine genome.

    Science.gov (United States)

    Ryu, J; Lee, C

    2016-04-01

    Selection signals of Korean cattle might be attributed largely to artificial selection for meat quality. Rapidly increased intragenic markers of newly annotated genes in the bovine genome would help overcome limited findings of genetic markers associated with meat quality at the selection signals in a previous study. The present study examined genetic associations of marbling score (MS) with intragenic nucleotide variants at selection signals of Korean cattle. A total of 39 092 nucleotide variants of 407 Korean cattle were utilized in the association analysis. A total of 129 variants were selected within newly annotated genes in the bovine genome. Their genetic associations were analyzed using the mixed model with random polygenic effects based on identical-by-state genetic relationships among animals in order to control for spurious associations produced by population structure. Genetic associations of MS were found (P<3.88×10-4) with six intragenic nucleotide variants on bovine autosomes 3 (cache domain containing 1, CACHD1), 5 (like-glycosyltransferase, LARGE), 16 (cell division cycle 42 binding protein kinase alpha, CDC42BPA) and 21 (snurportin 1, SNUPN; protein tyrosine phosphatase, non-receptor type 9, PTPN9; chondroitin sulfate proteoglycan 4, CSPG4). In particular, the genetic associations with CDC42BPA and LARGE were confirmed using an independent data set of Korean cattle. The results implied that allele frequencies of functional variants and their proximity variants have been augmented by directional selection for greater MS and remain selection signals in the bovine genome. Further studies of fine mapping would be useful to incorporate favorable alleles in marker-assisted selection for MS of Korean cattle.

  17. The Functional Roles of the MDM2 Splice Variants P2-MDM2-10 and MDM2-∆5 in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Johanna Huun

    2017-10-01

    Full Text Available BACKGROUND: MDM2 is a negative regulator of p53 and is upregulated in numerous human cancers. While different MDM2 splice variants have been observed in both normal tissues and malignant cells, their functions are poorly understood. METHODS: We evaluated the effect of MDM2 splice variants by overexpression in MCF-7 cells and analyses of expression of downstream genes (qPCR and Western blot, subcellular localization (immunofluorescence, cell cycle assays (Nucleocounter3000, apoptosis analysis (Annexin V detection, and induction of senescence (β-galactosidase analysis. RESULTS: In a screen for MDM2 splice variants in MCF-7 breast cancer cells, extended with data from healthy leukocytes, we found P2-MDM2-10 and MDM2-Δ5 to be the splice variants expressed at highest levels. Contrasting MDM2 full-length protein, we found normal tissue expression levels of P2-MDM2-10 and MDM2-Δ5 to be highest in individuals harboring the promoter SNP309TT genotype. While we detected no protein product coded for by MDM2-Δ5, the P2-MDM2-10 variant generated a protein markedly more stable than MDM2-FL. Both splice variants were significantly upregulated in stressed cells (P = 4.3 × 10−4 and P = 7.1 × 10−4, respectively. Notably, chemotherapy treatment and overexpression of P2-MDM2-10 or MDM2-Δ5 both lead to increased mRNA levels of the endogenous MDM2-FL (P = .039 and P = .070, respectively but also the proapoptotic gene PUMA (P = .010 and P = .033, respectively, accompanied by induction of apoptosis and repression of senescence. CONCLUSION: We found P2-MDM2-10 and MDM2-Δ5 to have distinct biological functions in breast cancer cells. GENERAL SIGNIFICANCE: Alternative splicing may influence the oncogenic effects of the MDM2 gene.

  18. Biogenic amines in meat and meat products.

    Science.gov (United States)

    Ruiz-Capillas, Claudia; Jiménez-Colmenero, Francisco

    2004-01-01

    It has been recognized for some time that biogenic amines occur in a wide range of foods, among them meat and meat products. Meat is an important component of the diet in developed countries. The presence of these amines in food is of interest for two reasons: firstly, for toxicological reasons, in the sense that high levels of dietary biogenic amines can be toxic for certain consumers, and secondly, for their role as possible quality indicators. Based on these two premises, the present article offers a new analysis on aspects of toxicology and on the use of biogenic amines as a quality control method, as well as on their presence in meat and meat products. The article focuses particularly on factors affecting the production of biogenic amines, with reference to various parameters relating to microorganisms, meat raw materials, and processing conditions. A better understanding of the factors determining their formation (i.e., microorganisms, raw materials used, and technological processes applied) and their effects could lead to ways of controlling their production, limiting their presence in the end product, and hence, rendering them less toxic.

  19. Novel trends in development of dietary fiber rich meat products—a critical review

    OpenAIRE

    Mehta, Nitin; Ahlawat, S. S.; Sharma, D. P.; Dabur, R. S.

    2013-01-01

    Meat and meat products are generally recognized as good sources of high biological value proteins, fat-soluble vitamins, minerals, trace elements and bioactive compounds. Changes in socioeconomic factors in recent years have increased the consumer’s preference for ready to eat foods including meat products. The processing of meat and meat products leads to generation of many functional compounds beneficial to human health but most of those foods are rich in fat, added salts but deficient in c...

  20. Association of COMT and PRODH gene variants with intelligence quotient (IQ) and executive functions in 22q11.2DS subjects.

    Science.gov (United States)

    Carmel, Miri; Zarchi, Omer; Michaelovsky, Elena; Frisch, Amos; Patya, Miriam; Green, Tamar; Gothelf, Doron; Weizman, Abraham

    2014-09-01

    The 22q11.2 deletion syndrome (22q11.2DS) carries the highest genetic risk factor for the development of schizophrenia. We investigated the association of genetic variants in two schizophrenia candidate genes with executive function (EF) and IQ in 22q11.2DS individuals. Ninety two individuals with 22q11.2 deletion were studied for the genetic association between COMT and PRODH variants and EF and IQ. Subjects were divided into children (under 12 years old), adolescents (between 12 and 18 years old) and adults (older than 18 years), and genotyped for the COMT Val158Met (rs4680) and PRODH Arg185Trp (rs4819756) polymorphisms. The participants underwent psychiatric evaluation and EF assessment. Our main finding is a significant influence of the COMT Val158Met polymorphism on both IQ and EF performance. Specifically, 22q11.2DS subjects with Met allele displayed higher IQ scores in all age groups compared to Val carriers, reaching significance in both adolescents and adults. The Met allele carriers performed better than Val carriers in EF tasks, being statistically significant in the adult group. PRODH Arg185Trp variant did not affect IQ or EF in our 22q11.2DS cohort. In conclusion, functional COMT variant, but not PRODH, affects IQ and EF in 22q11.2DS subjects during neurodevelopment with a maximal effect at adulthood. Future studies should monitor the cognitive performance of the same individuals from childhood to old age. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Molecular dynamics and docking simulation of a natural variant of Activated Protein C with impaired protease activity: implications for integrin-mediated antiseptic function.

    Science.gov (United States)

    D'Ursi, Pasqualina; Orro, Alessandro; Morra, Giulia; Moscatelli, Marco; Trombetti, Gabriele; Milanesi, Luciano; Rovida, Ermanna

    2015-01-01

    Activated Protein C (APC) is a multifunctional serine protease, primarily known for its anticoagulant function in the coagulation system. Several studies have already elucidated its role in counteracting apoptosis and inflammation in cells, while significant effort is still ongoing for defining its involvement in sepsis. Earlier literature has shown that the antiseptic function of APC is mediated by its binding to leukocyte integrins, which is due to the presence of the integrin binding motif Arg-Gly-Asp at the N-terminus of the APC catalytic chain. Many natural mutants have been identified in patients with Protein C deficiency diagnosis including a variant of specificity pocket (Gly216Asp). In this work, we present a molecular model of the complex of APC with αVβ3 integrin obtained by protein-protein docking approach. A computational analysis of this variant is hereby presented, based on molecular dynamics and docking simulations, aiming at investigating the effects of the Gly216Asp mutation on the protein conformation and inferring its functional implications. Our study shows that such mutation is likely to impair the protease activity while preserving the overall protein fold. Moreover, superposition of the integrin binding motifs in wild-type and mutant forms suggests that the interaction with integrin can still occur and thus the mutant is likely to retain its antiseptic function related to the neutrophyl integrin binding. Therapeutic applications could result in this APC mutant which retains antiseptic function without anticoagulant side effects.

  2. A Loss-of-Function Splice Acceptor Variant in IGF2 Is Protective for Type 2 Diabetes.

    Science.gov (United States)

    Mercader, Josep M; Liao, Rachel G; Bell, Avery D; Dymek, Zachary; Estrada, Karol; Tukiainen, Taru; Huerta-Chagoya, Alicia; Moreno-Macías, Hortensia; Jablonski, Kathleen A; Hanson, Robert L; Walford, Geoffrey A; Moran, Ignasi; Chen, Ling; Agarwala, Vineeta; Ordoñez-Sánchez, María Luisa; Rodríguez-Guillen, Rosario; Rodríguez-Torres, Maribel; Segura-Kato, Yayoi; García-Ortiz, Humberto; Centeno-Cruz, Federico; Barajas-Olmos, Francisco; Caulkins, Lizz; Puppala, Sobha; Fontanillas, Pierre; Williams, Amy L; Bonàs-Guarch, Sílvia; Hartl, Chris; Ripke, Stephan; Tooley, Katherine; Lane, Jacqueline; Zerrweck, Carlos; Martínez-Hernández, Angélica; Córdova, Emilio J; Mendoza-Caamal, Elvia; Contreras-Cubas, Cecilia; González-Villalpando, María E; Cruz-Bautista, Ivette; Muñoz-Hernández, Liliana; Gómez-Velasco, Donaji; Alvirde, Ulises; Henderson, Brian E; Wilkens, Lynne R; Le Marchand, Loic; Arellano-Campos, Olimpia; Riba, Laura; Harden, Maegan; Gabriel, Stacey; Abboud, Hanna E; Cortes, Maria L; Revilla-Monsalve, Cristina; Islas-Andrade, Sergio; Soberon, Xavier; Curran, Joanne E; Jenkinson, Christopher P; DeFronzo, Ralph A; Lehman, Donna M; Hanis, Craig L; Bell, Graeme I; Boehnke, Michael; Blangero, John; Duggirala, Ravindranath; Saxena, Richa; MacArthur, Daniel; Ferrer, Jorge; McCarroll, Steven A; Torrents, David; Knowler, William C; Baier, Leslie J; Burtt, Noel; González-Villalpando, Clicerio; Haiman, Christopher A; Aguilar-Salinas, Carlos A; Tusié-Luna, Teresa; Flannick, Jason; Jacobs, Suzanne B R; Orozco, Lorena; Altshuler, David; Florez, Jose C

    2017-11-01

    Type 2 diabetes (T2D) affects more than 415 million people worldwide, and its costs to the health care system continue to rise. To identify common or rare genetic variation with potential therapeutic implications for T2D, we analyzed and replicated genome-wide protein coding variation in a total of 8,227 individuals with T2D and 12,966 individuals without T2D of Latino descent. We identified a novel genetic variant in the IGF2 gene associated with ∼20% reduced risk for T2D. This variant, which has an allele frequency of 17% in the Mexican population but is rare in Europe, prevents splicing between IGF2 exons 1 and 2. We show in vitro and in human liver and adipose tissue that the variant is associated with a specific, allele-dosage-dependent reduction in the expression of IGF2 isoform 2. In individuals who do not carry the protective allele, expression of IGF2 isoform 2 in adipose is positively correlated with both incidence of T2D and increased plasma glycated hemoglobin in individuals without T2D, providing support that the protective effects are mediated by reductions in IGF2 isoform 2. Broad phenotypic examination of carriers of the protective variant revealed no association with other disease states or impaired reproductive health. These findings suggest that reducing IGF2 isoform 2 expression in relevant tissues has potential as a new therapeutic strategy for T2D, even beyond the Latin American population, with no major adverse effects on health or reproduction. © 2017 by the American Diabetes Association.

  3. Functionally Equivalent Variants in a Non-standard Variety and Their Implications for Universal Grammar: A Spontaneous Speech Corpus

    OpenAIRE

    Evelina Leivada; Evelina Leivada; Elena Papadopoulou; Elena Papadopoulou; Natalia Pavlou

    2017-01-01

    Findings from the field of experimental linguistics have shown that a native speaker may judge a variant that is part of her grammar as unacceptable, but still use it productively in spontaneous speech. The process of eliciting acceptability judgments from speakers of non-standard languages is sometimes clouded by factors akin to prescriptive notions of grammatical correctness. It has been argued that standardization enhances the ability to make clear-cut judgments, while non-standardization ...

  4. Incorporating Functional Genomic Information to Enhance Polygenic Signal and Identify Variants Involved in Gene-by-Environment Interaction for Young Adult Alcohol Problems.

    Science.gov (United States)

    Salvatore, Jessica E; Savage, Jeanne E; Barr, Peter; Wolen, Aaron R; Aliev, Fazil; Vuoksimaa, Eero; Latvala, Antti; Pulkkinen, Lea; Rose, Richard J; Kaprio, Jaakko; Dick, Danielle M

    2018-02-01

    Characterizing aggregate genetic risk for alcohol misuse and identifying variants involved in gene-by-environment (G × E) interaction effects has so far been a major challenge. We hypothesized that functional genomic information could be used to enhance detection of polygenic signal underlying alcohol misuse and to prioritize identification of single nucleotide polymorphisms (SNPs) most likely to exhibit G × E effects. We examined these questions in the young adult FinnTwin12 sample (n = 1,170). We used genomewide association estimates from an independent sample to derive 2 types of polygenic scores for alcohol problems in FinnTwin12. Genomewide polygenic scores included all SNPs surpassing a designated p-value threshold. DNase polygenic scores were a subset of the genomewide polygenic scores including only variants in DNase I hypersensitive sites (DHSs), which are open chromatin marks likely to index regions with a regulatory function. We conducted parallel analyses using height as a nonpsychiatric model phenotype to evaluate the consistency of effects. For the G × E analyses, we examined whether SNPs in DHSs were overrepresented among SNPs demonstrating significant G × E effects in an interaction between romantic relationship status and intoxication frequency. Contrary to our expectations, we found that DNase polygenic scores were not more strongly predictive of alcohol problems than conventional polygenic scores. However, variants in DNase polygenic scores had per-SNP effects that were up to 1.4 times larger than variants in conventional polygenic scores. This same pattern of effects was also observed in supplementary analyses with height. In G × E models, SNPs in DHSs were modestly overrepresented among SNPs with significant interaction effects for intoxication frequency. These findings highlight the potential utility of integrating functional genomic annotation information to increase the signal-to-noise ratio in polygenic scores and identify

  5. Meat Managers' Expectations Regarding Marketing of Irradiated Red Meats

    OpenAIRE

    Gaynor, Joe; Jensen, Kimberly L.; Jaenicke, Edward C.

    2003-01-01

    The objective of this study is to assess meat managers' expectations about impact of the recent regulatory approval of irradiated raw meat and meat products on marketing decisions and plans by supermarkets and grocery meat retailers. Forty managers of meat departments were interviewed in person to obtain the information for the study. While many of the meat managers believed that irradiation would help increase shelf life and reduce spoilage, they were less optimistic about consumers being wi...

  6. Optical Properties Of Polymeric Films Of Bacteriorhodopsin And Its Functional Variants: New Materials For Optical Information Processing

    Science.gov (United States)

    Hampp, Norbert; Braeuchle, Christoph R.; Oesterhelt, Dieter

    1990-01-01

    Purple membrane (PM) from Halobacterium halobium consists of a two-dimensional crystal of the photochromic retinal protein bacteriorhodopsin (BR). Purple membrane embedded in inert polymer matrices can be used as reversible recording medium in holography. The thermal and photochemical stability (at least 100.000 recording cycles at room temperature), the high quantum yield (70%), the high resolution (~ 5000 lines/mm) and the wide spectral range (400-680 nm) of these films are promising features for any possible technical application. The variability of this material was restricted to chemical modifications of the chromophoric group for a long time. new class of BR based recording media is introduced by the availability of variants of BR with a modified amino acid sequence. After generation of a mutant strain PM variants can be easily produced by the same cultivation and purification procedures as the PM of the wildtype and therefore are available in virtually unlimited amounts, too. As an example the properties of PM-films containing the variant BR-326, which differs from the wildtype by a single amino acid, are reported here. The improved diffraction efficiency (~ 2-fold) and increased sensitivity (~ 50%) of films containing BR-326 give an impression of the new possibilities for optimizing reversible recording media by biochemical and gentechnological methods as an alternative or an addition to conventional chemical methods.

  7. Meat science research tendencies

    Directory of Open Access Journals (Sweden)

    José Arturo García Macías

    2010-12-01

    Full Text Available Meat is a high quality food due its higher protein content, besides to provide energy, vitamins particularly B complex, water and minerals, resulting in an appreciated food for humans. Even in same country, consumers search for different stuffs, since north consumers looks for meat cuts with fat and bone, whereas center-south consumers prefers fatless debones meat cuts. Modern consumers demand excellent appearance, color, taste and flavor in foods, microbiologically safe, minimal processed and curing salts, very nutritive and cheap. All these together in one single product are a hard challenge in the meat products area.

  8. Update on meat irradiation

    International Nuclear Information System (INIS)

    Olson, D.G.

    1997-01-01

    The irradiation of meat and poultry in the United States is intended to eliminate pathogenic bacteria from raw product, preferably after packaging to prevent recontamination. Irradiation will also increase the shelf life of raw meat and poultry products approximately two to three times the normal shelf life. Current clearances in the United States are for poultry (fresh or frozen) at doses from 1.5 to 3.0 kGy and for fresh pork at doses from 0.3 to 1.0 kGy. A petition for the clearance of all red meat was submitted to the Food and Drug Administration (FDA) in July 1994. The petition is for clearances of fresh meat at doses from 1.5 to 4.5 kGy and for frozen meat at ∼2.5 to 7.5 kGy. Clearance for red meat is expected before the end of 1997. There are 28 countries that have food irradiation clearances, of which 18 countries have clearances for meat or poultry. However, there are no uniform categories or approved doses for meat and poultry among the countries that could hamper international trade of irradiated meat and poultry

  9. INFLUENCE OF AUTOLYTIC TRANSFORMATIONS ON ELECTROPHYSICAL PROPERTIES OF GOAT MEAT

    Directory of Open Access Journals (Sweden)

    L. V. Antipova

    2014-01-01

    Full Text Available Functional foods represented an important element of a balanced, healthy diet. They play an important role in improving the structure of the diet of the population, are a means of prevention, correction and prevention of early transition premorbid conditions and various diseases. Meat and meat products based on it can be considered as a promising raw material for functional foods. Goat has certain dietary properties and can be used in manufacturing, but the production of high-grade products from goat meat, capable of long-term storage is not well developed. The chemical composition of the new raw meat - goat meat, on the example of the longissimus muscle of back is rich in protein, moisture, ash, and low-fat compared with other types of raw meat, which lets you create based on goat meat sector wide functional meat products. Therefore investigated the possibility of using goat meat in the production technology of functional foods. Showing the prospects for the development of goat in Russia. Investigated character of autolysis goat meat electro-physical methods and histological analysis. In the process of autolysis of goat meat are changing the electrical properties of raw meat, which are correlated with the morphological characteristics. Basic autolytic changes occurring in muscle tissue in the early stages of ripening, were reduced to a small extent the political process involving varying degrees of muscle structure in the early stages. In the later stages of maturation revealed changing widespread. Revealed that autolysis has characteristic periods and develops within 12 hours, further changes are irreversible. Shows the change in pH, carbohydrate fractions in the longissimus muscle of back goat. Results of the study of dynamics of change in pH, carbohydrate fractions in the longissimus muscle of back goat show compliance with the laws of classical autolysis noted in other sources, but differ in the time period. Defined stages of autolysis in

  10. Impact of functional germline variants and a deletion polymorphism in APOBEC3A and APOBEC3B on breast cancer risk and survival in a Swedish study population.

    Science.gov (United States)

    Göhler, Stella; Da Silva Filho, Miguel Inacio; Johansson, Robert; Enquist-Olsson, Kerstin; Henriksson, Roger; Hemminki, Kari; Lenner, Per; Försti, Asta

    2016-01-01

    The C → T mutation signature caused by APOBEC family members contributes to the development of breast cancer (BC). Also overexpression of APOBEC3B and a ~29.5-kb deletion polymorphism between APOBEC3A and APOBEC3B have been associated with increased BC risk. We investigated in a population-based study, with 782 Swedish BC cases and 1559 controls, associations between potentially functional germline variants in APOBEC3A or APOBEC3B gene and BC risk and survival. Additionally, we identified deletion polymorphism carriers and explored possible associations with BC. No evidence of association between any germline variant, including the deletion polymorphism, and BC risk or survival was observed. Only APOBEC3A promoter polymorphism rs5757402 was associated with low stage (OR = 0.69, 95 % CI 0.50-0.96, dominant model). The reported association between the deletion polymorphism and BC risk was not confirmed in the Swedish population, nor did any genotyped germline variant show any association with BC risk or survival.

  11. Crystal structure of the S187F variant of human liver alanine: Aminotransferase associated with primary hyperoxaluria type I and its functional implications

    Science.gov (United States)

    Oppici, Elisa; Fodor, Krisztian; Paiardini, Alessandro; Williams, Chris; Voltattorni, Carla Borri; Wilmanns, Matthias; Cellini, Barbara

    2013-01-01

    The substitution of Ser187, a residue located far from the active site of human liver peroxisomal alanine:glyoxylate aminotransferase (AGT), by Phe gives rise to a variant associated with primary hyperoxaluria type I. Unexpectedly, previous studies revealed that the recombinant form of S187F exhibits a remarkable loss of catalytic activity, an increased pyridoxal 5′-phosphate (PLP) binding affinity and a different coenzyme binding mode compared with normal AGT. To shed light on the structural elements responsible for these defects, we solved the crystal structure of the variant to a resolution of 2.9 Å. Although the overall conformation of the variant is similar to that of normal AGT, we noticed: (i) a displacement of the PLP-binding Lys209 and Val185, located on the re and si side of PLP, respectively, and (ii) slight conformational changes of other active site residues, in particular Trp108, the base stacking residue with the pyridine cofactor moiety. This active site perturbation results in a mispositioning of the AGT-pyridoxamine 5′-phosphate (PMP) complex and of the external aldimine, as predicted by molecular modeling studies. Taken together, both predicted and observed movements caused by the S187F mutation are consistent with the following functional properties of the variant: (i) a 300- to 500-fold decrease in both the rate constant of L-alanine half-transamination and the kcat of the overall transamination, (ii) a different PMP binding mode and affinity, and (iii) a different microenvironment of the external aldimine. Proposals for the treatment of patients bearing S187F mutation are discussed on the basis of these results. Proteins 2013; 81:1457–1465. © 2013 Wiley Periodicals, Inc. PMID:23589421

  12. Analyzing structure–function relationships of artificial and cancer-associated PARP1 variants by reconstituting TALEN-generated HeLa PARP1 knock-out cells

    Science.gov (United States)

    Rank, Lisa; Veith, Sebastian; Gwosch, Eva C.; Demgenski, Janine; Ganz, Magdalena; Jongmans, Marjolijn C.; Vogel, Christopher; Fischbach, Arthur; Buerger, Stefanie; Fischer, Jan M.F.; Zubel, Tabea; Stier, Anna; Renner, Christina; Schmalz, Michael; Beneke, Sascha; Groettrup, Marcus; Kuiper, Roland P.; Bürkle, Alexander; Ferrando-May, Elisa; Mangerich, Aswin

    2016-01-01

    Genotoxic stress activates PARP1, resulting in the post-translational modification of proteins with poly(ADP-ribose) (PAR). We genetically deleted PARP1 in one of the most widely used human cell systems, i.e. HeLa cells, via TALEN-mediated gene targeting. After comprehensive characterization of these cells during genotoxic stress, we analyzed structure–function relationships of PARP1 by reconstituting PARP1 KO cells with a series of PARP1 variants. Firstly, we verified that the PARP1\\E988K mutant exhibits mono-ADP-ribosylation activity and we demonstrate that the PARP1\\L713F mutant is constitutively active in cells. Secondly, both mutants exhibit distinct recruitment kinetics to sites of laser-induced DNA damage, which can potentially be attributed to non-covalent PARP1–PAR interaction via several PAR binding motifs. Thirdly, both mutants had distinct functional consequences in cellular patho-physiology, i.e. PARP1\\L713F expression triggered apoptosis, whereas PARP1\\E988K reconstitution caused a DNA-damage-induced G2 arrest. Importantly, both effects could be rescued by PARP inhibitor treatment, indicating distinct cellular consequences of constitutive PARylation and mono(ADP-ribosyl)ation. Finally, we demonstrate that the cancer-associated PARP1 SNP variant (V762A) as well as a newly identified inherited PARP1 mutation (F304L\\V762A) present in a patient with pediatric colorectal carcinoma exhibit altered biochemical and cellular properties, thereby potentially supporting human carcinogenesis. Together, we establish a novel cellular model for PARylation research, by revealing strong structure–function relationships of natural and artificial PARP1 variants. PMID:27694308

  13. Volatile compounds in meat and meat products

    Directory of Open Access Journals (Sweden)

    Monika KOSOWSKA

    Full Text Available Abstract Meaty flavor is composed of a few hundreds of volatile compounds, only minor part of which are responsible for the characteristic odor. It is developed as a result of multi-directional reactions proceeding between non-volatile precursors contained in raw meat under the influence of temperature. The volatile compounds are generated upon: Maillard reactions, lipid oxidation, interactions between Maillard reaction products and lipid oxidation products as well as upon thiamine degradation. The developed flavor is determined by many factors associated with: raw material (breed, sex, diet and age of animal, conditions and process of slaughter, duration and conditions of meat storage, type of muscle, additives applied and the course of the technological process. The objective of this review article is to draw attention to the issue of volatile compounds characteristic for meat products and factors that affect their synthesis.

  14. A targeted genotyping approach enhances identification of variants in taste receptor and appetite/reward genes of potential functional importance for obesity-related porcine traits

    DEFF Research Database (Denmark)

    Cirera, S.; Clop, A.; Jacobsen, M. J.

    2018-01-01

    Taste receptors (TASRs) and appetite and reward (AR) mechanisms influence eating behaviour, which in turn affects food intake and risk of obesity. In a previous study, we used next generation sequencing to identify potentially functional mutations in TASR and AR genes and found indications...... for genetic associations between identified variants and growth and fat deposition in a subgroup of animals (n = 38) from the UNIK resource pig population. This population was created for studying obesity and obesity-related diseases. In the present study we validated results from our previous study...

  15. Expression of insulin receptor spliced variants and their functional correlates in muscle from patients with non-insulin-dependent diabetes mellitus

    DEFF Research Database (Denmark)

    Hansen, Torben; Bjørbaek, C; Vestergaard, H

    1993-01-01

    Due to alternative splicing of exon 11 of the receptor gene, the human insulin receptor exists in two forms, that have distinct tissue-specific expression and are functionally different. Needle biopsies obtained from vastus lateralis muscle from 20 patients with noninsulin-dependent diabetes...... mellitus (NIDDM) and 20 normal control subjects were analyzed for the relative expression of insulin receptor mRNA variants in a novel assay using fluorescence-labeled primers and subsequent analysis on an automated DNA sequencer. In subgroups of patients and control subjects, insulin binding and tyrosine...

  16. an intermediate moisture meat

    African Journals Online (AJOL)

    Bunmi

    Matured leaves of Ocimum gratissimum were harvested and the extracts used to cure. Suya (an intermediate moisture meat). O. gratissimum leaves were collected from. Oyo state south west region of Nigeria, rinsed in distilled water and squeezed to extract the fluid. The meat used was Semi membranosus muscle from beef ...

  17. Functional analysis in mouse embryonic stem cells reveals wild-type activity for three MSH6 variants found in suspected Lynch syndrome patients.

    Directory of Open Access Journals (Sweden)

    Eva A L Wielders

    Full Text Available Lynch syndrome confers an increased risk to various types of cancer, in particular early onset colorectal and endometrial cancer. Mutations in mismatch repair (MMR genes underlie Lynch syndrome, with the majority of mutations found in MLH1 and MSH2. Mutations in MSH6 have also been found but these do not always cause a clear cancer predisposition phenotype and MSH6-defective tumors often do not show the standard characteristics of MMR deficiency, such as microsatellite instability. In particular, the consequences of MSH6 missense mutations are challenging to predict, which further complicates genetic counseling. We have previously developed a method for functional characterization of MSH2 missense mutations of unknown significance. This method is based on endogenous gene modification in mouse embryonic stem cells using oligonucleotide-directed gene targeting, followed by a series of functional assays addressing the MMR functions. Here we have adapted this method for the characterization of MSH6 missense mutations. We recreated three MSH6 variants found in suspected Lynch syndrome families, MSH6-P1087R, MSH6-R1095H and MSH6-L1354Q, and found all three to behave like wild type MSH6. Thus, despite suspicion for pathogenicity from clinical observations, our approach indicates these variants are not disease causing. This has important implications for counseling of mutation carriers.

  18. Functional Analysis of a Carotid Intima-Media Thickness Locus Implicates BCAR1 and Suggests a Causal Variant

    DEFF Research Database (Denmark)

    Boardman-Pretty, Freya; Smith, Andrew J. P.; Cooper, Jackie

    2015-01-01

    Carotid intima-media thickness (IMT) is a marker of subclinical atherosclerosis that can predict cardiovascular disease events over traditional risk factors. This study examined the BCAR1-CFDP1-TMEM170A locus on chromosome 16, associated with carotid IMT and coronary artery disease in the IMT...... with slower IMT progression in women (P=0.04) but not in men. Meta-analysis of 5 cohort studies also supported a protective effect of the A allele on common carotid IMT in women only (women: β=-0.0047, P=1.63×10-4; men: β=-0.0029, P=0.0678). Two hundred fourteen noncoding variants in strong linkage...... associations of rs4888378 with BCAR1 in vascular tissues. Molecular studies suggest the lead SNP as a potentially causal SNP at the BCAR1-CFDP1-TMEM170A locus, and expression quantitative trait loci studies implicate BCAR1 as the causal gene. This variant showed stronger effects on common carotid IMT in women...

  19. Qualitative analysis of meat and meat products by multiplex ...

    African Journals Online (AJOL)

    ... fish, pork and ruminant, respectively. The optimized M-PCR assay was applied to 93 commercial meat products and it showed the presence of poultry meat in red meat analyzed, although, it was not indicated on the label. Key words: Multiplex polymerase chain reaction (M-PCR), meat products, food, salami, sausage.

  20. Prevalence and antibiotic resistance of Salmonella spp. in meat products, meat preparations and minced meat

    Science.gov (United States)

    Rašeta, M.; Mrdović, B.; Janković, V.; Bečkei, Z.; Lakićević, B.; Vidanović, D.; Polaček, V.

    2017-09-01

    This study aimed to determine Salmonella spp. prevalence in meat products, meat preparations and minced meat. Over a period of three years, a total of 300 samples were taken (100 RTE meat products, 100 meat preparations and 100 minced meat) and examined for the presence of Salmonella spp. Sampling was carried out at the warehouses of the food manufacturers. Salmonella spp. were not detected in RTE meat products, while 7% of semi-finished meat products (fresh sausages, grill meat formed and unformed) contained Salmonella, as did 18% of minced meats (minced pork II category, minced beef II category, mixed minced meat). The 25 Salmonella isolates obtained were examined for antibiotic resistance by the disk diffusion test, according to the NCCLS and CLSI guidelines. Isolates showed resistance to ampicillin and nalidixic acid (80%), tetracycline (72%), cefotaxime/clavulanic acid (48%), but not to gentamicin (8%) or trimethoprim/sulfamethoxazole (0%).

  1. Functional and Biochemical Analysis of Glucose-6-Phosphate Dehydrogenase (G6PD Variants: Elucidating the Molecular Basis of G6PD Deficiency

    Directory of Open Access Journals (Sweden)

    Saúl Gómez-Manzo

    2017-05-01

    Full Text Available G6PD deficiency is the most common enzymopathy, leading to alterations in the first step of the pentose phosphate pathway, which interferes with the protection of the erythrocyte against oxidative stress and causes a wide range of clinical symptoms of which hemolysis is one of the most severe. The G6PD deficiency causes several abnormalities that range from asymptomatic individuals to more severe manifestations that can lead to death. Nowadays, only 9.2% of all recognized variants have been related to clinical manifestations. It is important to understand the molecular basis of G6PD deficiency to understand how gene mutations can impact structure, stability, and enzymatic function. In this work, we reviewed and compared the functional and structural data generated through the characterization of 20 G6PD variants using different approaches. These studies showed that severe clinical manifestations of G6PD deficiency were related to mutations that affected the catalytic and structural nicotinamide adenine dinucleotide phosphate (NADPH binding sites, and suggests that the misfolding or instability of the 3D structure of the protein could compromise the half-life of the protein in the erythrocyte and its activity.

  2. A variant at 9p21.3 functionally implicates CDKN2B in paediatric B-cell precursor acute lymphoblastic leukaemia aetiology.

    Science.gov (United States)

    Hungate, Eric A; Vora, Sapana R; Gamazon, Eric R; Moriyama, Takaya; Best, Timothy; Hulur, Imge; Lee, Younghee; Evans, Tiffany-Jane; Ellinghaus, Eva; Stanulla, Martin; Rudant, Jéremie; Orsi, Laurent; Clavel, Jacqueline; Milne, Elizabeth; Scott, Rodney J; Pui, Ching-Hon; Cox, Nancy J; Loh, Mignon L; Yang, Jun J; Skol, Andrew D; Onel, Kenan

    2016-02-12

    Paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) is the most common cancer of childhood, yet little is known about BCP-ALL predisposition. In this study, in 2,187 cases of European ancestry and 5,543 controls, we discover and replicate a locus indexed by rs77728904 at 9p21.3 associated with BCP-ALL susceptibility (Pcombined=3.32 × 10(-15), OR=1.72) and independent from rs3731217, the previously reported ALL-associated variant in this region. Of correlated SNPs tagged by this locus, only rs662463 is significant in African Americans, suggesting it is a plausible causative variant. Functional analysis shows that rs662463 is a cis-eQTL for CDKN2B, with the risk allele associated with lower expression, and suggests that rs662463 influences BCP-ALL risk by regulating CDKN2B expression through CEBPB signalling. Functional analysis of rs3731217 suggests it is associated with BCP-ALL by acting within a splicing regulatory element determining CDKN2A exon 3 usage (P=0.01). These findings provide new insights into the critical role of the CDKN2 locus in BCP-ALL aetiology.

  3. Assosiations of functional candidate genes derived from gene expression profiles of prenatal porcine muscle issue with meat quality and carcass traits

    NARCIS (Netherlands)

    Wimmers, K.; Murani, E.; Pas, te M.F.W.; Chang, K.C.; Davoli, R.; Merks, J.W.M.; Henne, H.; Costa, da N.; Harlizius, B.; Schellander, K.; Braglia, S.; Wit, de A.A.C.; Cagnazzo, M.; Fontanesi, L.; Prins, D.; Ponsuksili, S.

    2007-01-01

    Ten genes (ANK1, bR10D1, CA3, EPOR, HMGA2, MYPN, NME1, PDGFRA, ERC1, TTN), whose candidacy for meat-quality and carcass traits arises from their differential expression in prenatal muscle development, were examined for association in 1700 performance-tested fattening pigs of commercial purebred and

  4. Prevalence and risk of psychiatric disorders as a function of variant rape histories: results from a national survey of women.

    Science.gov (United States)

    Zinzow, Heidi M; Resnick, Heidi S; McCauley, Jenna L; Amstadter, Ananda B; Ruggiero, Kenneth J; Kilpatrick, Dean G

    2012-06-01

    Rape is an established risk factor for mental health disorders, such as posttraumatic stress disorder (PTSD), major depressive episodes (MDE), and substance use disorders. The majority of studies have not differentiated substance-involved rape or examined comorbid diagnoses among victims. Therefore, the aim of the present study was to estimate the prevalence of common trauma-related psychiatric disorders (and their comorbidity) in a national sample of women, with an emphasis on distinguishing between rape tactics. A secondary objective was to estimate the risk for psychiatric disorders among victims of variant rape tactics, in comparison to non-victims. A nationally representative population-based sample of 3,001 non-institutionalized, civilian, English or Spanish speaking women (aged 18-86 years) participated in a structured telephone interview assessing rape history and DSM-IV criteria for PTSD, MDE, alcohol abuse (AA), and drug abuse (DA). Descriptive statistics and multivariate logistic regression analyses were employed. Women with rape histories involving both substance facilitation and forcible tactics reported the highest current prevalence of PTSD (36%), MDE (36%), and AA (20%). Multivariate models demonstrated that this victim group was also at highest risk for psychiatric disorders, after controlling for demographics and childhood and multiple victimization history. Women with substance-facilitated rapes reported higher prevalence of substance abuse in comparison to women with forcible rape histories. Comorbidity between PTSD and other psychiatric disorders was higher among rape victims in comparison to non-rape victims. Researchers and clinicians should assess substance-facilitated rape tactics and attend to comorbidity among rape victims. Empirically supported treatments are needed to address the complex presentations observed among women with variant rape histories.

  5. Muscle growth and poultry meat quality issues.

    Science.gov (United States)

    Petracci, Massimiliano; Cavani, Claudio

    2012-01-01

    Over the past 50 years the worldwide growing demand of poultry meat has resulted in pressure on breeders, nutritionists and growers to increase the growth rate of birds, feed efficiency, size of breast muscle and reduction in abdominal fatness. Moreover, the shift toward further processed products has emphasized the necessity for higher standards in poultry meat to improve sensory characteristics and functional properties. It is believed that genetic progress has put more stress on the growing bird and it has resulted in histological and biochemical modifications of the muscle tissue by impairing some meat quality traits. The most current poultry meat quality concerns are associated with deep pectoral muscle disease and white striping which impair product appearance, and increased occurrence of problems related with the meat's poor ability to hold water during processing and storage (PSE-like condition) as well as poor toughness and cohesiveness related to immaturity of intramuscular connective tissue. This paper is aimed at making a general statement of recent studies focusing on the relationship between muscle growth and meat quality issues in poultry.

  6. Novel aspects of health promoting compounds in meat.

    Science.gov (United States)

    Young, J F; Therkildsen, M; Ekstrand, B; Che, B N; Larsen, M K; Oksbjerg, N; Stagsted, J

    2013-12-01

    Meat is an integral part of the human diet. Besides essential amino acids and nutritive factors of high quality and availability, meat provides often overlooked components of importance for human health. These are amino acids and bioactive compounds that may be very important in i) preventing muscle wasting diseases, such as in sarcopenia, ii) reducing food and caloric intake to prevent metabolic syndrome, iii) blood pressure homeostasis via ACE-inhibitory components from connective tissue, and iv) maintaining functional gut environment through meat-derived nucleotides and nucleosides. In addition, meat could be an important source of phytanic acid, conjugated linoleic acids and antioxidants. Further, it becomes increasingly apparent that design of in vitro meat will be possible, and that this development may lead to improved health benefits from commercially viable and sustainable meat products. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. The Importance of Taurine Meat in Human Alimentation

    Directory of Open Access Journals (Sweden)

    Marian Daniel Usturoi

    2015-11-01

    Full Text Available Meat is an important ingredient in the proper functioning of the human body. Thinking out of a trophic-biological point of view, meat represents the main aliment with plastic and energetic roles. The protein substances that the meat contains have a high biological value, due to the fact that they have all the necessary amino acids needed to maintain a healthy azote balance within the body. The production of meat is quite a complex operation, that is based not only on the market needs (which is mostly based on price and income, but also a multitude of social and economic influences.

  8. A Functional Toll-Interacting Protein Variant Is Associated with Bacillus Calmette-Guérin-Specific Immune Responses and Tuberculosis.

    Science.gov (United States)

    Shah, Javeed A; Musvosvi, Munyaradzi; Shey, Muki; Horne, David J; Wells, Richard D; Peterson, Glenna J; Cox, Jeffery S; Daya, Michelle; Hoal, Eileen G; Lin, Lin; Gottardo, Raphael; Hanekom, Willem A; Scriba, Thomas J; Hatherill, Mark; Hawn, Thomas R

    2017-08-15

    The molecular mechanisms that regulate tuberculosis susceptibility and bacillus Calmette-Guérin (BCG)-induced immunity are mostly unknown. However, induction of the adaptive immune response is a critical step in host control of Mycobacterium tuberculosis. Toll-interacting protein (TOLLIP) is a ubiquitin-binding protein that regulates innate immune responses, including Toll-like receptor signaling, which initiate adaptive immunity. TOLLIP variation is associated with susceptibility to tuberculosis, but the mechanism by which it regulates tuberculosis immunity is poorly understood. To identify functional TOLLIP variants and evaluate the role of TOLLIP variation on innate and adaptive immune responses to mycobacteria and susceptibility to tuberculosis. We used human cellular immunology approaches to characterize the role of a functional TOLLIP variant on monocyte mRNA expression and M. tuberculosis-induced monocyte immune functions. We also examined the association of TOLLIP variation with BCG-induced T-cell responses and susceptibility to latent tuberculosis infection. We identified a functional TOLLIP promoter region single-nucleotide polymorphism, rs5743854, which was associated with decreased TOLLIP mRNA expression in infant monocytes. After M. tuberculosis infection, TOLLIP-deficient monocytes demonstrated increased IL-6, increased nitrite, and decreased bacterial replication. The TOLLIP-deficiency G/G genotype was associated with decreased BCG-specific IL-2 + CD4 + T-cell frequency and proliferation. This genotype was also associated with increased susceptibility to latent tuberculosis infection. TOLLIP deficiency is associated with decreased BCG-specific T-cell responses and increased susceptibility to tuberculosis. We hypothesize that the heightened antibacterial monocyte responses after vaccination of TOLLIP-deficient infants are responsible for decreased BCG-specific T-cell responses. Activating TOLLIP may provide a novel adjuvant strategy for BCG

  9. Study on Influence of Different Types of Meat on the Quality of Meat Products

    Directory of Open Access Journals (Sweden)

    Melinda Nagy

    2015-11-01

    Full Text Available Meat species in processed food products have been gaining an increasing interest mainly due to public health, economic and legal concerns, but also due to religious reasons. In the recent years there was an increasing demand for healthier meat products. Formulation of healthier meat products based on processing strategies is one of the most important current approaches to the development of potential meat-based functional foods. The main objective of the study was to characterize different type of meat and to use that to obtain a meat product-smoked sausage. The physico-chemical analyses highlighted the moisture content (drying-oven at 105 ºC, protein (Kjeldahl method and fat (Soxhlet method content and sodium chloride content (Mohr method of the meat and the final product. Sensory analyses of the samples as well as control sample were evaluated by 17 untrained panellists using a 9 point hedonic scale. Following this study, it was noted an improvement of organoleptic characteristics (texture and appearance as well as physico-chemical and sensorial properties of the new product compared with the limits stipulated.

  10. Factors that predict consumer acceptance of enriched processed meats.

    Science.gov (United States)

    Shan, Liran C; Henchion, Maeve; De Brún, Aoife; Murrin, Celine; Wall, Patrick G; Monahan, Frank J

    2017-11-01

    The study aimed to understand predictors of consumers' purchase intention towards processed meat based functional foods (i.e. enriched processed meat). A cross-sectional survey was conducted with 486 processed meat consumers in spring 2016. Results showed that processed meats were perceived differently in healthiness, with sausage-type products perceived less healthy than cured meat products. Consumers were in general more uncertain than positive about enriched processed meat but differences existed in terms of the attitudes and purchase intention. Following regression analysis, consumers' purchase intention towards enriched processed meat was primarily driven by their attitudes towards the product concept. Perceived healthiness of existing products and eating frequency of processed meat were also positively associated with the purchase intention. Other factors such as general food choice motives, socio-demographic characteristics, consumer health and the consumption of functional foods and dietary supplements in general, were not significant predictors of the purchase intention for enriched processed meat. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. The Meat City

    DEFF Research Database (Denmark)

    Thelle, Mikkel

    2017-01-01

    This article investigates the emergence of the Copenhagen slaughterhouse, called the Meat City, during the late nineteenth century. This slaughterhouse was a product of a number of heterogeneous components: industrialization and new infrastructures were important, but hygiene and the significance...... of Danish bacon exports also played a key role. In the Meat City, this created a distinction between rising production and consumption on the one hand, and the isolation and closure of the slaughtering facility on the other. This friction mirrored an ambivalent attitude towards meat in the urban space: one...... where consumers demanded more meat than ever before, while animals were being removed from the public eye. These contradictions, it is argued, illustrate and underline the change of the city towards a ‘post-domestic’ culture. The article employs a variety of sources, but primarily the Copenhagen...

  12. Meat and Appetite Regulation

    DEFF Research Database (Denmark)

    Kehlet, Ursula Nana

    D thesis was to investigate the effects of fiber addition to meatballs and the effects of cooking methods of pork on appetite regulation. The PhD thesis is based on three human meal test studies and one analytical study related to the characteristics of fiber meat products. In paper I, the objective...... pork products are also characterized as high fat products containing more than 10 g fat per 100 g. In this context, the Danish meat industry puts a lot of effort into developing meat products with a healthier nutritional profile. Thus, it is relevant to provide scientific evidence of the satiating...... effects of new formulations of pork products. Different strategies can be applied to potentially enhance the satiating properties of pork. Processed meat products such as meatballs can serve as a matrix for the addition of fiber ingredients. Based on their high protein and fiber contents, high...

  13. The Meat City

    DEFF Research Database (Denmark)

    Thelle, Mikkel

    2017-01-01

    where consumers demanded more meat than ever before, while animals were being removed from the public eye. These contradictions, it is argued, illustrate and underline the change of the city towards a ‘post-domestic’ culture. The article employs a variety of sources, but primarily the Copenhagen......This article investigates the emergence of the Copenhagen slaughterhouse, called the Meat City, during the late nineteenth century. This slaughterhouse was a product of a number of heterogeneous components: industrialization and new infrastructures were important, but hygiene and the significance...... of Danish bacon exports also played a key role. In the Meat City, this created a distinction between rising production and consumption on the one hand, and the isolation and closure of the slaughtering facility on the other. This friction mirrored an ambivalent attitude towards meat in the urban space: one...

  14. Contribution of ARLTS1 Cys148Arg (T442C variant with prostate cancer risk and ARLTS1 function in prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Sanna Siltanen

    Full Text Available ARLTS1 is a recently characterized tumor suppressor gene at 13q14.3, a region frequently deleted in both sporadic and hereditary prostate cancer (PCa. ARLTS1 variants, especially Cys148Arg (T442C, increase susceptibility to different cancers, including PCa. In this study the role of Cys148Arg substitution was investigated as a risk factor for PCa using both genetic and functional analysis. Cys148Arg genotypes and expression of the ARLTS1 were explored in a large set of familial and unselected PCa cases, clinical tumor samples, xenografts, prostate cancer cell lines and benign prostatic hyperplasia (BPH samples. The frequency of the variant genotype CC was significantly higher in familial (OR = 1.67, 95% CI = 1.08-2.56, P = 0.019 and unselected patients (OR = 1.52, 95% CI = 1.18-1.97, P = 0.001 and the overall risk was increased (OR = 1.54, 95% CI = 1.20-1.98, P = 0.0007. Additional analysis with clinicopathological data revealed an association with an aggressive disease (OR = 1.28, 95% CI = 1.05-∞, P = 0.02. The CC genotype of the Cys148Arg variant was also contributing to the lowered ARLTS1 expression status in lymphoblastoid cells from familial patients. In addition significantly lowered ARLTS1 expression was observed in clinical tumor samples compared to BPH samples (P = 0.01. The ARLTS1 co-expression signature based on previously published microarray data was generated from 1587 cancer samples confirming the low expression of ARLTS1 in PCa and showed that ARLTS1 expression was strongly associated with immune processes. This study provides strong confirmation of the important role of ARLTS1 Cys148Arg variant as a contributor in PCa predisposition and a potential marker for aggressive disease outcome.

  15. Allelic variants from Dahlia variabilis encode flavonoid 3'-hydroxylases with functional differences in chalcone 3-hydroxylase activity.

    Science.gov (United States)

    Schlangen, Karin; Miosic, Silvija; Halbwirth, Heidi

    2010-02-01

    In the petals of Dahlia variabilis, hydroxylation of chalcones at position 3 can be detected, except the well-known flavonoid 3'-hydroxylation. Although the reaction is well characterized at the enzymatic level, it remained unclear whether it is catalyzed by a flavonoid 3'-hydroxylase (F3'H, EC1.14.13.21, CYP75B) with broad substrate specificity. Two novel allelic variants of F3'H were cloned from D. variabilis, which differ only in three amino acids within their 508 residues. The corresponding recombinant enzymes show significant differences in their chalcone 3-hydroxylase (CH3H) activity. A substitution of alanine at position 425 with valine enables CH3H activity, whereas the reciprocal substitution leads to a loss of CH3H activity. Interaction of the valine at position 425 with not yet identified structural properties seems to be decisive for chalcone acceptance. This is the first identification of an F3'H which is able to catalyze chalcone 3-hydroxylation to a physiologically relevant extent from any plant species. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  16. Consumer sensory evaluation of meat from South African goat ...

    African Journals Online (AJOL)

    Administrator

    2011-05-23

    May 23, 2011 ... and BOR goats, the aroma intensity scores of the fried meat were significantly higher than the cooked meat. Female respondents gave ... assessments of food products can correspond with that of consumers. Consumers ..... to excel in functional roles such as flavor development, tenderness and juiciness of ...

  17. Research into poultry meat quality.

    Science.gov (United States)

    Grashorn, M A

    2010-08-01

    1. Research in the field of poultry meat quality has become more varied during the last 50 years. Besides meat content and microbial condition, animal welfare issues during the slaughter process, muscle morphology, physiology of meat ripening, impact of slaughter process on meat quality, sensory attributes of meat and meat processing have come into focus. 2. The present review summarizes findings and developments in the fields of muscle physiology, meat ripening and meat quality aberrations (like PSE), nutrient composition and sensory qualities, effect of the slaughter process on carcass and meat quality, hygienic conditions and product safety during slaughtering, all based on selected papers published in British Poultry Science during the last 50 years. 3. Some special findings and conclusions are lifted out of the whole results presented in the papers to indicate their importance and to show their contribution to the development of knowledge in the respective field.

  18. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis

    DEFF Research Database (Denmark)

    Palmer, Colin N A; Irvine, Alan D; Terron-Kwiatkowski, Ana

    2006-01-01

    most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated. Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Here we show that two independent loss-of-function genetic...... dermatitis. This work establishes a key role for impaired skin barrier function in the development of atopic disease....

  19. A functional variant in microRNA-146a promoter modulates its expression and confers disease risk for systemic lupus erythematosus.

    Directory of Open Access Journals (Sweden)

    Xiaobing Luo

    2011-06-01

    Full Text Available Systemic lupus erythematosus (SLE is a complex autoimmune disease with a strong genetic predisposition, characterized by an upregulated type I interferon pathway. MicroRNAs are important regulators of immune homeostasis, and aberrant microRNA expression has been demonstrated in patients with autoimmune diseases. We recently identified miR-146a as a negative regulator of the interferon pathway and linked the abnormal activation of this pathway to the underexpression of miR-146a in SLE patients. To explore why the expression of miR-146a is reduced in SLE patients, we conducted short parallel sequencing of potentially regulatory regions of miR-146a and identified a novel genetic variant (rs57095329 in the promoter region exhibiting evidence for association with SLE that was replicated independently in 7,182 Asians (P(meta = 2.74×10(-8, odds ratio = 1.29 [1.18-1.40]. The risk-associated G allele was linked to reduced expression of miR-146a in the peripheral blood leukocytes of the controls. Combined functional assays showed that the risk-associated G allele reduced the protein-binding affinity and activity of the promoter compared with those of the promoter containing the protective A allele. Transcription factor Ets-1, encoded by the lupus-susceptibility gene ETS1, identified in recent genome-wide association studies, binds near this variant. The manipulation of Ets-1 levels strongly affected miR-146a promoter activity in vitro; and the knockdown of Ets-1, mimicking its reduced expression in SLE, directly impaired the induction of miR-146a. We also observed additive effects of the risk alleles of miR-146a and ETS1. Our data identified and confirmed an association between a functional promoter variant of miR-146a and SLE. This risk allele had decreased binding to transcription factor Ets-1, contributing to reduced levels of miR-146a in SLE patients.

  20. Replacement of Pork Meat with Pork Head Meat for Frankfurters

    Science.gov (United States)

    Choi, Yun-Sang; Hwang, Ko-Eun; Kim, Hyun-Wook; Song, Dong-Heon; Jeon, Ki-Hong; Park, Jong-Dae; Sung, Jung-Min; Kim, Young-Boong; Kim, Cheon-Jei

    2016-01-01

    The effect of reducing pork meat concentrations from 50% to 30% and replacing it with up to 20% pork head meat on chemical composition, cooking characteristics, physicochemical and textural properties, apparent viscosity, and sensory characteristics of frankfurters was determined. The highest moisture content in frankfurters was found in the control and T1 (frankfurter with 45% pork meat + 5% pork head). Protein and fat contents in frankfurters with pork head meat added were significantly (ppork head meat was increased from 0% to 20%, cooking loss, total expressible fluid separation, fat separation, and pH of frankfurters were increased, while the lightness, redness, yellowness, and apparent viscosity of frankfurters were decreased. Ash contents, cohesiveness, color, and tenderness of sensory characteristics of frankfurters added with different amounts of pork meat or pork head meat were not significantly (p>0.05) different from those of the control or there treatments. Frankfurters in T4 (frankfurter with 30% pork meat + 20% pork head) had the lowest (p0.05) from that in the control. Frankfurters with higher pork head meat concentrations had lower flavor, juiciness, and overall acceptability scores. Therefore, replacing pork meat with pork head meat in the formulation could successfully produce results similar to those of control frankfurters. The best results were obtained when 10% pork head meat was used to replace pork meat. PMID:27621683

  1. Nanotechnology in meat processing and packaging: potential applications - a review.

    Science.gov (United States)

    Ramachandraiah, Karna; Han, Sung Gu; Chin, Koo Bok

    2015-02-01

    Growing demand for sustainable production, increasing competition and consideration of health concerns have led the meat industries on a path to innovation. Meat industries across the world are focusing on the development of novel meat products and processes to meet consumer demand. Hence, a process innovation, like nanotechnology, can have a significant impact on the meat processing industry through the development of not only novel functional meat products, but also novel packaging for the products. The potential benefits of utilizing nanomaterials in food are improved bioavailability, antimicrobial effects, enhanced sensory acceptance and targeted delivery of bioactive compounds. However, challenges exist in the application of nanomaterials due to knowledge gaps in the production of ingredients such as nanopowders, stability of delivery systems in meat products and health risks caused by the same properties which also offer the benefits. For the success of nanotechnology in meat products, challenges in public acceptance, economics and the regulation of food processed with nanomaterials which may have the potential to persist, accumulate and lead to toxicity need to be addressed. So far, the most promising area for nanotechnology application seems to be in meat packaging, but the long term effects on human health and environment due to migration of the nanomaterials from the packaging needs to be studied further. The future of nanotechnology in meat products depends on the roles played by governments, regulatory agencies and manufacturers in addressing the challenges related to the application of nanomaterials in food.

  2. A Functional Variant at the miR-214 Binding Site in the Methylenetetrahydrofolatereductase Gene Alters Susceptibility to Gastric Cancer in a Chinese Han Population

    Directory of Open Access Journals (Sweden)

    Qiaoyun Chen

    2015-05-01

    Full Text Available Background and Aims: Single nucleotide polymorphisms in miRNA binding sites, which are located in mRNA 3' untranslated regions (3'-UTRs, were recently found to influence microRNA-target interactions. Specifically, such polymorphisms can modulatebinding affinity or create or destroy miRNA-binding sites; such variants have also been found to be associated with cancer risk. In this study, we explored the effect of a functional variant at the miR-214 binding site in the methylenetetrahydrofolate reductase gene (rs114673809 on gastric cancer (GC risk in a hospital-based case-control study in a Chinese Han population. Methods and Results: We genotyped the rs114673809 polymorphism in 345 gastric cancer patients and 376 cancer-free controls using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP technique. The functions of rs114673809 were investigated using a luciferase activity assay and validated by immunoblotting. We found that participants carrying the rs114673809 AA genotype or A allele had a significantly increased risk of gastric cancer (OR = 1.667, 95% CI = 1.044-2.660, P = 0.034; OR = 1.261, 95% CI = 1.017-1.563, P = 0.037, respectively compared to those carrying the GG genotype and G allele. In addition, rs114673809 modified the binding of hsa-miR-214 to MTHFR as well as MTHFR protein levels in gastric cancer patients. Conclusion: Our data suggested that rs114673809, which is located at the miR-214 binding site in the 3'-UTR of MTHFR, may play an important role in the development of gastric cancer in a Chinese Han population.

  3. Functional promoter -308G>A variant in tumor necrosis factor α gene is associated with risk and progression of gastric cancer in a Chinese population.

    Directory of Open Access Journals (Sweden)

    Yan Hong

    Full Text Available BACKGROUND: Tumor necrosis factor-α (TNF-α plays a crucial role in the development and progression of gastric cancer. A functional polymorphism, -308 G>A (rs1800629, which is located in the promoter of TNFA gene, has been suggested to alter the production of TNF-α and influence cancer risk. In the present study, we sought to investigate whether this polymorphism has effects on the risk and progression of gastric cancer in a Chinese population. METHODS: We genotyped the TNFA -308 G>A polymorphism using the TaqMan method in a two-stage case-control study comprising a total of 1686 gastric cancer patients and 1895 cancer-free subjects. The logistic regression was used to assess the genetic associations with occurrence and progression of gastric cancer. RESULTS: We found a significant association between the variant genotypes and increased risk of gastric cancer [P = 0.034, odds ratio (OR = 1.39, 95% confidence interval (CI = 1.01-1.67, GA/AA vs. GG]. Similar results were observed in the follow-up replication study. When combined the data from the two studies, we found a more significant association (P = 0.001, OR = 1.34, 95%CI = 1.13-1.59, especially for older subjects (>65 years. Furthermore, the patients carrying the variant genotypes had a significantly greater prevalence of T4 stage of disease (P = 0.001, OR = 2.19, 95%CI = 1.39-3.47 and distant metastasis (P = 0.013, OR = 1.61, 95%CI = 1.10-2.35. CONCLUSIONS: Our results suggest that the functional promoter -308 G>A polymorphism in TNFA influence the susceptibility and progression of gastric cancer in the Chinese population.

  4. THE DEMAND FOR MEAT PRODUCTS IN THE UNITED STATES: AN EMPIRICAL ANALYSIS

    OpenAIRE

    Olowolayemo, Surajudeen O.; Martin, Neil R., Jr.; Raymond, Jennie E.

    1993-01-01

    Given the importance of meat consumption, and the proportion of consumers' income spent on meat, this study estimates the demand for eight meat categories using two different functional forms. An inverse almost ideal demand system (IAIDS), and linear double-log price dependent demand models are specified. In most cases, flexibilities obtained from both methods are comparable and show that the demand for meat products is price inflexible. In addition, there are regional as well as seasonal var...

  5. Biochemical function of typical and variant Arabidopsis thaliana U-box E3 ubiquitin-protein ligases

    DEFF Research Database (Denmark)

    Wiborg, Jakob; O'Shea, Charlotte; Skriver, Karen

    2008-01-01

    respectively, but no productive interaction was observed with the UBC15 E2 tested. The activity of AtPUB54 [Arabidopsis thaliana (thale cress) plant U-box 54 protein] was dependent on Trp(266) in the E2-binding cleft, and the E2 selectivity was changed by substitution of this position. The function...... of the distant U-box protein, AtPUB49, representing a large family of eukaryotic proteins containing a U-box linked to a cyclophilin-like peptidyl-prolyl cis-trans isomerase domain, was characterized biochemically. AtPUB49 functioned both as a prolyl isomerase and a chaperone by catalysing cis.......g. co-existence or interactions with additional domains. The biochemical functions of AtPUB49 suggest that the protein can be involved in folding or degradation of protein substrates. Similar functions can also be retained within a protein complex with separate chaperone and U-box proteins....

  6. Novel loss-of-function PCSK9 variant is associated with low plasma LDL cholesterol in a French-Canadian family and with impaired processing and secretion in cell culture.

    Science.gov (United States)

    Mayne, Janice; Dewpura, Thilina; Raymond, Angela; Bernier, Lise; Cousins, Marion; Ooi, Teik Chye; Davignon, Jean; Seidah, Nabil G; Mbikay, Majambu; Chrétien, Michel

    2011-10-01

    PCSK9 (proprotein convertase subtilisin/kexin type 9) is a polymorphic gene whose protein product regulates plasma LDL cholesterol (LDLC) concentrations by shuttling liver LDL receptors (LDLRs) for degradation. PCSK9 variants that cause a gain or loss of PCSK9 function are associated with hyper- or hypocholesterolemia, which increases or reduces the risk of cardiovascular disease, respectively. We studied the clinical and molecular characteristics of a novel PCSK9 loss-of-function sequence variant in a white French-Canadian family. In vivo plasma and ex vivo secreted PCSK9 concentrations were measured with a commercial ELISA. We sequenced the PCSK9 exons for 15 members of a family, the proband of which exhibited very low plasma PCSK9 and LDLC concentrations. We then conducted a structure/function analysis of the novel PCSK9 variant in cell culture to identify its phenotypic basis. We identified a PCSK9 sequence variant in the French-Canadian family that produced the PCSK9 Q152H substitution. Family members carrying this variant had mean decreases in circulating PCSK9 and LDLC concentrations of 79% and 48%, respectively, compared with unrelated noncarriers (n=210). In cell culture, the proPCSK9-Q152H variant did not undergo efficient autocatalytic cleavage and was not secreted. Cells transiently transfected with PCSK9-Q152H cDNA had LDLR concentrations that were significantly higher than those of cells overproducing wild-type PCSK9 (PCSK9-WT). Cotransfection of PCSK9-Q152H and PCSK9-WT cDNAs produced a 78% decrease in the secreted PCSK9-WT protein compared with control cells. Collectively, our results demonstrate that the PCSK9-Q152H variant markedly lowers plasma PCSK9 and LDLC concentrations in heterozygous carriers via decreased autocatalytic processing and secretion, and hence, inactivity on the LDLR.

  7. Meat and meat products as a source of bioactive peptides

    Directory of Open Access Journals (Sweden)

    Alfonso Totosaus

    2016-12-01

    Full Text Available Meat is a high protein content food, with great nutritional and biological value. Meat protein hydrolysis begins with the muscle to meat conversion, during meat ageing. After slaughter, endogen enzymes are responsible of meat softening since myofibrillar anchorage proteins are degraded. Protein hydrolysis continues during food preparation. When meat reaches the stomach, pepsin is the first enzyme to interact. As the food travel trough out gastrointestinal tract, pancreatic enzymes degraded the remained protein and the peptidases made the final proteolysis process. The small proteins or peptides are the absorbed to the circulatory system and distributed to the rest of the body. Bioactive peptides activity of meat and meat products is anti-hypertensive mainly, where histidine, carnosine and anserine are the main peptides identified. Another peptide with anti-oxidant activity is glutathione. The content depends on animal species.

  8. Replacement of Pork Meat with Pork Head Meat for Frankfurters

    OpenAIRE

    Choi, Yun-Sang; Hwang, Ko-Eun; Kim, Hyun-Wook; Song, Dong-Heon; Jeon, Ki-Hong; Park, Jong-Dae; Sung, Jung-Min; Kim, Young-Boong; Kim, Cheon-Jei

    2016-01-01

    The effect of reducing pork meat concentrations from 50% to 30% and replacing it with up to 20% pork head meat on chemical composition, cooking characteristics, physicochemical and textural properties, apparent viscosity, and sensory characteristics of frankfurters was determined. The highest moisture content in frankfurters was found in the control and T1 (frankfurter with 45% pork meat + 5% pork head). Protein and fat contents in frankfurters with pork head meat added were significantly (p0...

  9. Decarbonising meat : Exploring greenhouse gas emissions in the meat sector

    NARCIS (Netherlands)

    Aan Den Toorn, S. I.; Van Den Broek, M. A.; Worrell, E.

    Consumption of meat is an important source of global greenhouse gas (GHG) emission and deep decarbonisation of the whole meat production chain is required to be able to meet global climate change (CC) mitigation goals. Emissions happen in different stages of meat production ranging from agricultural

  10. A functional genetic variant (N521D in natriuretic peptide receptor 3 is associated with diastolic dysfunction: the prevalence of asymptomatic ventricular dysfunction study.

    Directory of Open Access Journals (Sweden)

    Naveen L Pereira

    Full Text Available To evaluate the impact of a functional genetic variant in the natriuretic peptide clearance receptor, NPR3, on circulating natriuretic peptides (NPs and myocardial structure and function in the general community.NPR3 plays an important role in the clearance of NPs and through direct signaling mechanisms modulates smooth muscle cell function and cardiac fibroblast proliferation. A NPR3 nonsynonymous single nucleotide polymorphism (SNP rs2270915, resulting in a N521D substitution in the intracellular catalytic domain that interacts with Gi could affect receptor function. Whether this SNP is associated with alterations in NPs levels and altered cardiac structure and function is unknown.DNA samples of 1931 randomly selected residents of Olmsted County, Minnesota were genotyped. Plasma NT-proANP1-98, ANP1-28, proBNP1-108, NT-proBNP1-76, BNP1-32 and BNP3-32 levels were measured. All subjects underwent comprehensive echocardiography.Genotype frequencies for rs2270915 were as follows: (A/A 60%, A/G 36%, G/G 4%. All analyses performed were for homozygotes G/G versus wild type A/A plus the heterozygotes A/G. Diastolic dysfunction was significantly more common (p = 0.007 in the homozygotes G/G (43% than the A/A+A/G (28% group. Multivariate regression adjusted for age, sex, body mass index and hypertension demonstrated rs2270915 to be independently associated with diastolic dysfunction (odds ratio 1.94, p = 0.03. There was no significant difference in NPs levels between the 2 groups suggesting that the clearance function of the receptor was not affected.A nonsynonymous NPR3 SNP is independently associated with diastolic dysfunction and this association does not appear to be related to alterations in circulating levels of natriuretic peptides.

  11. Muscle Growth and Poultry Meat Quality Issues

    Directory of Open Access Journals (Sweden)

    Massimiliano Petracci

    2011-12-01

    Full Text Available Over the past 50 years the worldwide growing demand of poultry meat has resulted in pressure on breeders, nutritionists and growers to increase the growth rate of birds, feed efficiency, size of breast muscle and reduction in abdominal fatness. Moreover, the shift toward further processed products has emphasized the necessity for higher standards in poultry meat to improve sensory characteristics and functional properties. It is believed that genetic progress has put more stress on the growing bird and it has resulted in histological and biochemical modifications of the muscle tissue by impairing some meat quality traits. The most current poultry meat quality concerns are associated with deep pectoral muscle disease and white striping which impair product appearance, and increased occurrence of problems related with the meat’s poor ability to hold water during processing and storage (PSE-like condition as well as poor toughness and cohesiveness related to immaturity of intramuscular connective tissue. This paper is aimed at making a general statement of recent studies focusing on the relationship between muscle growth and meat quality issues in poultry.

  12. Rationalizing meat consumption. The 4Ns.

    Science.gov (United States)

    Piazza, Jared; Ruby, Matthew B; Loughnan, Steve; Luong, Mischel; Kulik, Juliana; Watkins, Hanne M; Seigerman, Mirra

    2015-08-01

    Recent theorizing suggests that the 4Ns - that is, the belief that eating meat is natural, normal, necessary, and nice - are common rationalizations people use to defend their choice of eating meat. However, such theorizing has yet to be subjected to empirical testing. Six studies were conducted on the 4Ns. Studies 1a and 1b demonstrated that the 4N classification captures the vast majority (83%-91%) of justifications people naturally offer in defense of eating meat. In Study 2, individuals who endorsed the 4Ns tended also to objectify (dementalize) animals and included fewer animals in their circle of moral concern, and this was true independent of social dominance orientation. Subsequent studies (Studies 3-5) showed that individuals who endorsed the 4Ns tend not to be motivated by ethical concerns when making food choices, are less involved in animal-welfare advocacy, less driven to restrict animal products from their diet, less proud of their animal-product decisions, tend to endorse Speciesist attitudes, tend to consume meat and animal products more frequently, and are highly committed to eating meat. Furthermore, omnivores who strongly endorsed the 4Ns tended to experience less guilt about their animal-product decisions, highlighting the guilt-alleviating function of the 4Ns. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Fine-scale mapping of the FGFR2 breast cancer risk locus: putative functional variants differentially bind FOXA1 and E2F1.

    Science.gov (United States)

    Meyer, Kerstin B; O'Reilly, Martin; Michailidou, Kyriaki; Carlebur, Saskia; Edwards, Stacey L; French, Juliet D; Prathalingham, Radhika; Dennis, Joe; Bolla, Manjeet K; Wang, Qin; de Santiago, Ines; Hopper, John L; Tsimiklis, Helen; Apicella, Carmel; Southey, Melissa C; Schmidt, Marjanka K; Broeks, Annegien; Van 't Veer, Laura J; Hogervorst, Frans B; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Fasching, Peter A; Lux, Michael P; Ekici, Arif B; Beckmann, Matthias W; Peto, Julian; Dos Santos Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Menegaux, Florence; Bojesen, Stig E; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Zamora, M Pilar; Arias, Jose I; Benitez, Javier; Neuhausen, Susan; Anton-Culver, Hoda; Ziogas, Argyrios; Dur, Christina C; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Schmutzler, Rita K; Engel, Christoph; Ditsch, Nina; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Dörk, Thilo; Helbig, Sonja; Bogdanova, Natalia V; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Chenevix-Trench, Georgia; Wu, Anna H; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Lambrechts, Diether; Thienpont, Bernard; Christiaens, Marie-Rose; Smeets, Ann; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Bonanni, Bernardo; Bernard, Loris; Couch, Fergus J; Olson, Janet E; Wang, Xianshu; Purrington, Kristen; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; McLean, Catriona; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Teo, Soo-Hwang; Yip, Cheng-Har; Phuah, Sze-Yee; Kristensen, Vessela; Grenaker Alnæs, Grethe; Børresen-Dale, Anne-Lise; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha; Long, Jirong; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline M; García-Closas, Montserrat; Figueroa, Jonine; Chanock, Stephen J; Lissowska, Jolanta; Czene, Kamila; Darabi, Hartef; Eriksson, Kimael; Hooning, Maartje J; Martens, John W M; van den Ouweland, Ans M W; van Deurzen, Carolien H M; Hall, Per; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cox, Angela; Reed, Malcolm W R; Blot, William; Signorello, Lisa B; Cai, Qiuyin; Pharoah, Paul D P; Ghoussaini, Maya; Harrington, Patricia; Tyrer, Jonathan; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K; Noh, Dong-Young; Hartman, Mikael; Hui, Miao; Lim, Wei-Yen; Buhari, Shaik A; Hamann, Ute; Försti, Asta; Rüdiger, Thomas; Ulmer, Hans-Ulrich; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Vachon, Celine; Slager, Susan; Fostira, Florentia; Pilarski, Robert; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Hou, Ming-Feng; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk J; Ponder, Bruce A J; Dunning, Alison M; Easton, Douglas F

    2013-12-05

    The 10q26 locus in the second intron of FGFR2 is the locus most strongly associated with estrogen-receptor-positive breast cancer in genome-wide association studies. We conducted fine-scale mapping in case-control studies genotyped with a custom chip (iCOGS), comprising 41 studies (n = 89,050) of European ancestry, 9 Asian ancestry studies (n = 13,983), and 2 African ancestry studies (n = 2,028) from the Breast Cancer Association Consortium. We identified three statistically independent risk signals within the locus. Within risk signals 1 and 3, genetic analysis identified five and two variants, respectively, highly correlated with the most strongly associated SNPs. By using a combination of genetic fine mapping, data on DNase hypersensitivity, and electrophoretic mobility shift assays to study protein-DNA binding, we identified rs35054928, rs2981578, and rs45631563 as putative functional SNPs. Chromatin immunoprecipitation showed that FOXA1 preferentially bound to the risk-associated allele (C) of rs2981578 and was able to recruit ERα to this site in an allele-specific manner, whereas E2F1 preferentially bound the risk variant of rs35054928. The risk alleles were preferentially found in open chromatin and bound by Ser5 phosphorylated RNA polymerase II, suggesting that the risk alleles are associated with changes in transcription. Chromatin conformation capture demonstrated that the risk region was able to interact with the promoter of FGFR2, the likely target gene of this risk region. A role for FOXA1 in mediating breast cancer susceptibility at this locus is consistent with the finding that the FGFR2 risk locus primarily predisposes to estrogen-receptor-positive disease. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  14. Evaluation of association of common variants in HTR1A and HTR5A with schizophrenia and executive function.

    Science.gov (United States)

    Guan, Fanglin; Lin, Huali; Chen, Gang; Li, Lu; Chen, Teng; Liu, Xinshe; Han, Jiuqiang; Li, Tao

    2016-11-29

    The 5-HT1A receptor (HTR1A) and the 5-HT5A receptor (HTR5A) are key 5-HT receptors with distinct inhibitory functions. Studies have been conducted to investigate the association of a few HTR1A polymorphisms with schizophrenia, producing conflicting results, and the relationship between HTR5A and schizophrenia has not yet been well investigated. We aimed to examine the association of HTR1A and HTR5A with schizophrenia and executive function. The study included a discovery stage with 1,115 patients and 2,289 controls and a replication stage with 2,128 patients and 3,865 controls. A total of 30 common SNPs in HTR1A and HTR5A were genotyped in the discovery stage, and significantly associated SNPs were genotyped in the replication stage. We identified that two SNPs (rs878567 in HTR1A and rs1800883 in HTR5A) were significantly associated with schizophrenia in both datasets, and similar results were observed in imputation and haplotype association analyses. Moreover, we found that SNP rs1800883 significantly interacted with executive function when processing the perseverative error of Wisconsin Card Sorting Test in patients. Our results provide further supportive evidence of the effect of HTR1A and HTR5A on the etiology of schizophrenia and suggest that the selected genetic variations in HTR5A may be involved in impaired executive function.

  15. Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy

    NARCIS (Netherlands)

    Brown, Sara J.; Asai, Yuka; Cordell, Heather J.; Campbell, Linda E.; Zhao, Yiwei; Liao, Haihui; Northstone, Kate; Henderson, John; Alizadehfar, Reza; Ben-Shoshan, Moshe; Morgan, Kenneth; Roberts, Graham; Masthoff, Laury J. N.; Pasmans, Suzanne G. M. A.; van den Akker, Peter C.; Wijmenga, Cisca; Hourihane, Jonathan O'B.; Palmer, Colin N. A.; Lack, Gideon; Clarke, Ann; Hull, Peter R.; Irvine, Alan D.; McLean, W. H. Irwin

    Background: IgE-mediated peanut allergy is a complex trait with strong heritability, but its genetic basis is currently unknown. Loss-of-function mutations within the filaggrin gene are associated with atopic dermatitis and other atopic diseases; therefore, filaggrin is a candidate gene in the

  16. Role of transcription factor KLF11 and its diabetes-associated gene variants in pancreatic beta cell function

    DEFF Research Database (Denmark)

    Neve, Bernadette; Fernandez-Zapico, Martin E; Ashkenazi-Katalan, Vered

    2005-01-01

    KLF11 (TIEG2) is a pancreas-enriched transcription factor that has elicited significant attention because of its role as negative regulator of exocrine cell growth in vitro and in vivo. However, its functional role in the endocrine pancreas remains to be established. Here, we report, for the first...

  17. B97-3c: A revised low-cost variant of the B97-D density functional method

    Science.gov (United States)

    Brandenburg, Jan Gerit; Bannwarth, Christoph; Hansen, Andreas; Grimme, Stefan

    2018-02-01

    A revised version of the well-established B97-D density functional approximation with general applicability for chemical properties of large systems is proposed. Like B97-D, it is based on Becke's power-series ansatz from 1997 and is explicitly parametrized by including the standard D3 semi-classical dispersion correction. The orbitals are expanded in a modified valence triple-zeta Gaussian basis set, which is available for all elements up to Rn. Remaining basis set errors are mostly absorbed in the modified B97 parametrization, while an established atom-pairwise short-range potential is applied to correct for the systematically too long bonds of main group elements which are typical for most semi-local density functionals. The new composite scheme (termed B97-3c) completes the hierarchy of "low-cost" electronic structure methods, which are all mainly free of basis set superposition error and account for most interactions in a physically sound and asymptotically correct manner. B97-3c yields excellent molecular and condensed phase geometries, similar to most hybrid functionals evaluated in a larger basis set expansion. Results on the comprehensive GMTKN55 energy database demonstrate its good performance for main group thermochemistry, kinetics, and non-covalent interactions, when compared to functionals of the same class. This also transfers to metal-organic reactions, which is a major area of applicability for semi-local functionals. B97-3c can be routinely applied to hundreds of atoms on a single processor and we suggest it as a robust computational tool, in particular, for more strongly correlated systems where our previously published "3c" schemes might be problematic.

  18. Association of LXRA gene variants with carcass and meat quality ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-10-20

    Oct 20, 2008 ... 2Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100094, China. Accepted 28 July, 2008. LXRA is an important regulator of genes involved in lipid, fatty acid and glucose metabolism in liver, and adipose tissue as well as in skeletal muscle. In this study, we discovered and ...

  19. Mechanisms of CFTR Functional Variants That Impair Regulated Bicarbonate Permeation and Increase Risk for Pancreatitis but Not for Cystic Fibrosis

    OpenAIRE

    LaRusch, Jessica; Jung, Jinsei; General, Ignacio J.; Lewis, Michele D.; Park, Hyun Woo; Brand, Randall E.; Gelrud, Andres; Anderson, Michelle A.; Banks, Peter A.; Conwell, Darwin; Lawrence, Christopher; Romagnuolo, Joseph; Baillie, John; Alkaade, Samer; Cote, Gregory

    2014-01-01

    CFTR is a dynamically regulated anion channel. Intracellular WNK1-SPAK activation causes CFTR to change permeability and conductance characteristics from a chloride-preferring to bicarbonate-preferring channel through unknown mechanisms. Two severe CFTR mutations (CFTRsev ) cause complete loss of CFTR function and result in cystic fibrosis (CF), a severe genetic disorder affecting sweat glands, nasal sinuses, lungs, pancreas, liver, intestines, and male reproductive system. We hypothesize tha...

  20. Lack of association between a functional variant of the BRCA-1 related associated protein (BRAP) gene and ischemic stroke

    OpenAIRE

    Liao, Yi-Chu; Lin, Hsiu-Fen; Guo, Yuh-Cherng; Chen, Chung-Hung; Huang, Zhi-Zhang; Juo, Suh-Hang Hank; Lin, Ruey-Tay

    2013-01-01

    Abstract Background Atherosclerosis shares common pathogenic features with myocardial infarction (MI) and ischemic stroke. BRCA-1 associated protein (BRAP), a newly identified risk gene for MI, aggravates the inflammatory response in atherosclerosis. The aim of this study was to test the association between the BRAP gene and stroke in a Taiwanese population. Methods A total of 1,074 stroke patients and 1,936 controls were genotyped for the functional SNP rs11066001. In our previous studies, t...

  1. Color of Meat and Poultry

    Science.gov (United States)

    ... JSR 286) Actions ${title} Loading... The Color of Meat and Poultry I've just opened a package of fresh ... Poultry Hotline concerning the color of meat and poultry. Color is important when meat and poultry are purchased, stored, and cooked. Often ...

  2. THE EFFECTS OF HORSE MEAT SCANDAL ON ROMANIAN MEAT MARKET

    Directory of Open Access Journals (Sweden)

    Silvius STANCIU

    2013-06-01

    Full Text Available Sustainable business in the domestic production of meat must meet both the usual Requirements regarding quality, safety for customer and New Challenges in the European meat market. The Romanian food industry must meet the challenge of recent suspicions regarding the substitution of beef meat with horse meat. The modern applicable to meat traceability systems and authentication procedures can be considered as new ways to support fair trade and transparency, THUS, removing suspicions that appeared lately. Lack of safety measures in the field can affect business continuity critically, creating significant losses.

  3. Market Driving to Develop Rabbit Meat Products in Indonesia

    Directory of Open Access Journals (Sweden)

    Atien Priyanti

    2012-09-01

    Full Text Available Rabbit meat is a nutritional food containing high protein and low cholesterol, fat and sodium. Current research in rabbit production is aimed for developing production strategies to increase the nutritional and economic values of rabbit meat products as functional food. Nowadays, producing rabbit is a popular farming activity in many parts of Indonesia as a small and medium scale operation for food security and cash income. Rabbit farming is to produce meat, skin and hides, fur, organic fertilizers and pet or fancy animals. Consumption of rabbit meat is considered very low, due partly to low meat supply and inavailability of marketing. In some tourist areas, such as Lembang (West Java, Tawangmangu (Central Java, Sarangan and Batu (East Java rabbit meat is a specific food. Attempt to create and drive rabbit markets will simultaneously increase meat production to fulfill the demand and meet economic scale of farming. Hence, this will give significant impact to the farmers’ welfare. Availability of good quality meat, dissemination and diversification of meat products, production efficiency toward competitive price along with its proper marketing strategy will drive consumers’ preferences to consume more rabbit meat. Market driving needs to be created in order to promote rabbit meat products by establishing food outlets. This program has been developed by a farmers group in Magelang, Central Java. During the period of 2006 – 2007 the food outlets had increased to 5 outlets, and in 2012 become 9 outlets. This market driving will also have an impact on changing orientation of rabbit farming from traditional to a small and medium economic scale that will influence the production efficiency.

  4. Functional dissociation between anterior temporal lobe and inferior frontal gyrus in the processing of dynamic body expressions: Insights from behavioral variant frontotemporal dementia.

    Science.gov (United States)

    Jastorff, Jan; De Winter, Francois-Laurent; Van den Stock, Jan; Vandenberghe, Rik; Giese, Martin A; Vandenbulcke, Mathieu

    2016-12-01

    Several brain regions are involved in the processing of emotional stimuli, however, the contribution of specific regions to emotion perception is still under debate. To investigate this issue, we combined behavioral testing, structural and resting state imaging in patients diagnosed with behavioral variant frontotemporal dementia (bvFTD) and age matched controls, with task-based functional imaging in young, healthy volunteers. As expected, bvFTD patients were impaired in emotion detection as well as emotion categorization tasks, testing dynamic emotional body expressions as stimuli. Interestingly, their performance in the two tasks correlated with gray matter volume in two distinct brain regions, the left anterior temporal lobe for emotion detection and the left inferior frontal gyrus (IFG) for emotion categorization. Confirming this observation, multivoxel pattern analysis in healthy volunteers demonstrated that both ROIs contained information for emotion detection, but that emotion categorization was only possible from the pattern in the IFG. Furthermore, functional connectivity analysis showed reduced connectivity between the two regions in bvFTD patients. Our results illustrate that the mentalizing network and the action observation network perform distinct tasks during emotion processing. In bvFTD, communication between the networks is reduced, indicating one possible cause underlying the behavioral symptoms. Hum Brain Mapp 37:4472-4486, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Neuronal AChE splice variants and their non-hydrolytic functions: redefining a target of AChE inhibitors?

    OpenAIRE

    Zimmermann, M

    2013-01-01

    AChE enzymatic inhibition is a core focus of pharmacological intervention in Alzheimer's disease (AD). Yet, AChE has also been ascribed non-hydrolytic functions, which seem related to its appearance in various isoforms. Neuronal AChE presents as a tailed form (AChE-T) predominantly found on the neuronal synapse, and a facultatively expressed readthough form (AChE-R), which exerts short to medium-term protective effects. Notably, this latter form is also found in the periphery. While these non...

  6. an intermediate moisture meat

    African Journals Online (AJOL)

    STORAGESEVER

    2008-07-04

    Jul 4, 2008 ... thereby increasing their animal protein intake, this experiment therefore become imperative. Meat from the semimembranosus (SM), biceps .... most critical eating quality that determines whether consumers are repeat buyer. It is however worthy of note that as a result of the heat treatment and the use of.

  7. Thermodynamics of meat proteins

    NARCIS (Netherlands)

    Sman, van der R.G.M.

    2012-01-01

    We describe the water activity of meat, being a mixture of proteins, salts and water, by the Free-Volume-Flory–Huggins (FVFH) theory augmented with the equation. Earlier, the FVFH theory is successfully applied to describe the thermodynamics to glucose homopolymers like starch, dextrans and

  8. Detecting variants with Metabolic Design, a new software tool to design probes for explorative functional DNA microarray development

    Directory of Open Access Journals (Sweden)

    Gravelat Fabrice

    2010-09-01

    Full Text Available Abstract Background Microorganisms display vast diversity, and each one has its own set of genes, cell components and metabolic reactions. To assess their huge unexploited metabolic potential in different ecosystems, we need high throughput tools, such as functional microarrays, that allow the simultaneous analysis of thousands of genes. However, most classical functional microarrays use specific probes that monitor only known sequences, and so fail to cover the full microbial gene diversity present in complex environments. We have thus developed an algorithm, implemented in the user-friendly program Metabolic Design, to design efficient explorative probes. Results First we have validated our approach by studying eight enzymes involved in the degradation of polycyclic aromatic hydrocarbons from the model strain Sphingomonas paucimobilis sp. EPA505 using a designed microarray of 8,048 probes. As expected, microarray assays identified the targeted set of genes induced during biodegradation kinetics experiments with various pollutants. We have then confirmed the identity of these new genes by sequencing, and corroborated the quantitative discrimination of our microarray by quantitative real-time PCR. Finally, we have assessed metabolic capacities of microbial communities in soil contaminated with aromatic hydrocarbons. Results show that our probe design (sensitivity and explorative quality can be used to study a complex environment efficiently. Conclusions We successfully use our microarray to detect gene expression encoding enzymes involved in polycyclic aromatic hydrocarbon degradation for the model strain. In addition, DNA microarray experiments performed on soil polluted by organic pollutants without prior sequence assumptions demonstrate high specificity and sensitivity for gene detection. Metabolic Design is thus a powerful, efficient tool that can be used to design explorative probes and monitor metabolic pathways in complex environments

  9. Functional analysis of two PLA2G2A variants associated with secretory phospholipase A2-IIA levels.

    Directory of Open Access Journals (Sweden)

    Holly J Exeter

    Full Text Available Secretory phospholipase A2 group IIA (sPLA2-IIA has been identified as a biomarker of atherosclerosis in observational and animal studies. The protein is encoded by the PLA2G2A gene and the aim of this study was to test the functionality of two PLA2G2A non-coding SNPs, rs11573156 C>G and rs3767221 T>G where the rare alleles have been previously associated with higher and lower sPLA2-IIA levels respectively.Luciferase assays, electrophoretic mobility shift assays (EMSA, and RNA expression by RT-PCR were used to examine allelic differences. For rs3767221 the G allele showed ∼55% lower luciferase activity compared to the T allele (T = 62.1 (95% CI 59.1 to 65.1 G = 27.8 (95% CI 25.0 to 30.6, p = 1.22×10⁻³⁵, and stronger EMSA binding of a nuclear protein compared to the T-allele. For rs11573156 C >G there were no luciferase or EMSA allelic differences seen. In lymphocyte cell RNA, from individuals of known rs11573156 genotype, there was no allelic RNA expression difference for exons 5 and 6, but G allele carriers (n = 7 showed a trend to lower exon 1-2 expression compared to CC individuals. To take this further, in the ASAP study (n = 223, an rs11573156 proxy (r² = 0.91 showed ∼25% higher liver expression of PLA2G2A (1.67×10⁻¹⁷ associated with the G allele. However, considering exon specific expression, the association was greatly reduced for exon 2 (4.5×10⁻⁵ compared to exons 3-6 (10⁻¹⁰ to 10⁻²⁰, suggesting rs11573156 G allele-specific exon 2 skipping.Both SNPs are functional and provide useful tools for Mendelian Randomisation to determine whether the relationship between sPLA2-IIA and coronary heart disease is causal.

  10. Functional variant in complement C3 gene promoter and genetic susceptibility to temporal lobe epilepsy and febrile seizures.

    Directory of Open Access Journals (Sweden)

    Sarah Jamali

    Full Text Available BACKGROUND: Human mesial temporal lobe epilepsies (MTLE represent the most frequent form of partial epilepsies and are frequently preceded by febrile seizures (FS in infancy and early childhood. Genetic associations of several complement genes including its central component C3 with disorders of the central nervous system, and the existence of C3 dysregulation in the epilepsies and in the MTLE particularly, make it the C3 gene a good candidate for human MTLE. METHODOLOGY/PRINCIPAL FINDINGS: A case-control association study of the C3 gene was performed in a first series of 122 patients with MTLE and 196 controls. Four haplotypes (HAP1 to 4 comprising GF100472, a newly discovered dinucleotide repeat polymorphism [(CA8 to (CA15] in the C3 promoter region showed significant association after Bonferroni correction, in the subgroup of MTLE patients having a personal history of FS (MTLE-FS+. Replication analysis in independent patients and controls confirmed that the rare HAP4 haplotype comprising the minimal length allele of GF100472 [(CA8], protected against MTLE-FS+. A fifth haplotype (HAP5 with medium-size (CA11 allele of GF100472 displayed four times higher frequency in controls than in the first cohort of MTLE-FS+ and showed a protective effect against FS through a high statistical significance in an independent population of 97 pure FS. Consistently, (CA11 allele by its own protected against pure FS in a second group of 148 FS patients. Reporter gene assays showed that GF100472 significantly influenced C3 promoter activity (the higher the number of repeats, the lower the transcriptional activity. Taken together, the consistent genetic data and the functional analysis presented here indicate that a newly-identified and functional polymorphism in the promoter of the complement C3 gene might participate in the genetic susceptibility to human MTLE with a history of FS, and to pure FS. CONCLUSIONS/SIGNIFICANCE: The present study provides important

  11. Functional Characterization of NIPBL Physiological Splice Variants and Eight Splicing Mutations in Patients with Cornelia de Lange Syndrome

    Directory of Open Access Journals (Sweden)

    María E. Teresa-Rodrigo

    2014-06-01

    Full Text Available Cornelia de Lange syndrome (CdLS is a congenital developmental disorder characterized by distinctive craniofacial features, growth retardation, cognitive impairment, limb defects, hirsutism, and multisystem involvement. Mutations in five genes encoding structural components (SMC1A, SMC3, RAD21 or functionally associated factors (NIPBL, HDAC8 of the cohesin complex have been found in patients with CdLS. In about 60% of the patients, mutations in NIPBL could be identified. Interestingly, 17% of them are predicted to change normal splicing, however, detailed molecular investigations are often missing. Here, we report the first systematic study of the physiological splicing of the NIPBL gene, that would reveal the identification of four new splicing isoforms ΔE10, ΔE12, ΔE33,34, and B’. Furthermore, we have investigated nine mutations affecting splice-sites in the NIPBL gene identified in twelve CdLS patients. All mutations have been examined on the DNA and RNA level, as well as by in silico analyses. Although patients with mutations affecting NIPBL splicing show a broad clinical variability, the more severe phenotypes seem to be associated with aberrant transcripts resulting in a shift of the reading frame.

  12. Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus

    DEFF Research Database (Denmark)

    Mahajan, Anubha; Sim, Xueling; Ng, Hui Jin

    2015-01-01

    . To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels...... and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent......Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance...

  13. The functional Pro129Thr variant of the FAAH gene is not associated with various fat accumulation phenotypes in a population-based cohort of 5,801 whites

    DEFF Research Database (Denmark)

    Jensen, Dorit P; Andersen, Mette K; Hansen, Lars

    2007-01-01

    Food intake and weight gain are influenced by endocannabinoids whose actions are regulated by the fatty acid amide hydrolase (FAAH) enzyme. The homozygous Thr/Thr genotype of the functional Pro129Thr variant (rs324420) in the gene encoding FAAH was recently reported to associate with overweight...... and obesity in white and black populations. We investigated the Pro129Thr variant in relation to overweight and obesity in a relatively large population-based study sample of Danish whites (n=5,801). In case-control studies of obesity, a borderline association with the major Pro allele was identified; however...... of an association of the Pro129Thr FAAH variant with overweight, obesity, and any related quantitative traits among the examined whites....

  14. Assuring eating quality of meat.

    Science.gov (United States)

    Dalen, G A

    1996-01-01

    The way of assuring quality has changed over the years, from inspection of end product to quality management systems and on-line process control. The latter concepts have had a great impact in many industries during the last decades. But the concept of Total Quality is continuos improvement so it is time to take advantage of the next generation of quality assurance tools: Quality by Design. This is the most powerful instrument in quality assurance today. Quality by design has been used with outstanding results in many industries as the automobile and the electronics industry. Maybe the meat industry will be the next? To succeed, the "eating quality attributes" that are most important to the customer must be brought into focus. The challenge to the meat research scientist is to design products and processes that take care of customer needs despite variation in the raw material and the consumer's rough handling. The Quality Management Standards are helpful in conducting the design and production process, but to focus on the right aspects, there also are need for suitable methods as Quality Function Deployment. Customer needs change and new research changes old 'truths'. This require an organisation, a quality system and a culture which can handle rapid changes and a diversity of customer needs.

  15. Alanine-scanning mutagenesis of human signal transducer and activator of transcription 1 to estimate loss- or gain-of-function variants.

    Science.gov (United States)

    Kagawa, Reiko; Fujiki, Ryoji; Tsumura, Miyuki; Sakata, Sonoko; Nishimura, Shiho; Itan, Yuval; Kong, Xiao-Fei; Kato, Zenichiro; Ohnishi, Hidenori; Hirata, Osamu; Saito, Satoshi; Ikeda, Maiko; El Baghdadi, Jamila; Bousfiha, Aziz; Fujiwara, Kaori; Oleastro, Matias; Yancoski, Judith; Perez, Laura; Danielian, Silvia; Ailal, Fatima; Takada, Hidetoshi; Hara, Toshiro; Puel, Anne; Boisson-Dupuis, Stéphanie; Bustamante, Jacinta; Casanova, Jean-Laurent; Ohara, Osamu; Okada, Satoshi; Kobayashi, Masao

    2017-07-01

    Germline heterozygous mutations in human signal transducer and activator of transcription 1 (STAT1) can cause loss of function (LOF), as in patients with Mendelian susceptibility to mycobacterial diseases, or gain of function (GOF), as in patients with chronic mucocutaneous candidiasis. LOF and GOF mutations are equally rare and can affect the same domains of STAT1, especially the coiled-coil domain (CCD) and DNA-binding domain (DBD). Moreover, 6% of patients with chronic mucocutaneous candidiasis with a GOF STAT1 mutation have mycobacterial disease, obscuring the functional significance of the identified STAT1 mutations. Current computational approaches, such as combined annotation-dependent depletion, do not distinguish LOF and GOF variants. We estimated variations in the CCD/DBD of STAT1. We mutagenized 342 individual wild-type amino acids in the CCD/DBD (45.6% of full-length STAT1) to alanine and tested the mutants for STAT1 transcriptional activity. Of these 342 mutants, 201 were neutral, 30 were LOF, and 111 were GOF mutations in a luciferase assay. This assay system correctly estimated all previously reported LOF mutations (100%) and slightly fewer GOF mutations (78.1%) in the CCD/DBD of STAT1. We found that GOF alanine mutants occurred at the interface of the antiparallel STAT1 dimer, suggesting that they destabilize this dimer. This assay also precisely predicted the effect of 2 hypomorphic and dominant negative mutations, E157K and G250E, in the CCD of STAT1 that we found in 2 unrelated patients with Mendelian susceptibility to mycobacterial diseases. The systematic alanine-scanning assay is a useful tool to estimate the GOF or LOF status and the effect of heterozygous missense mutations in STAT1 identified in patients with severe infectious diseases, including mycobacterial and fungal diseases. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  16. Post-genome wide association studies and functional analyses identify association of MPP7 gene variants with site-specific bone mineral density.

    Science.gov (United States)

    Xiao, Su-Mei; Kung, Annie Wai Chee; Gao, Yi; Lau, Kam-Shing; Ma, Alvin; Zhang, Zhen-Lin; Liu, Jian-Min; Xia, Wiebo; He, Jin-Wei; Zhao, Lin; Nie, Min; Fu, Wei-Zhen; Zhang, Min-Jia; Sun, Jing; Kwan, Johnny S H; Tso, Gloria Hoi Wan; Dai, Zhi-Jie; Cheung, Ching-Lung; Bow, Cora H; Leung, Anskar Yu Hung; Tan, Kathryn Choon Beng; Sham, Pak Chung

    2012-04-01

    Our previous genome-wide association study (GWAS) in a Hong Kong Southern Chinese population with extreme bone mineral density (BMD) scores revealed suggestive association with MPP7, which ranked second after JAG1 as a candidate gene for BMD. To follow-up this suggestive signal, we replicated the top single-nucleotide polymorphism rs4317882 of MPP7 in three additional independent Asian-descent samples (n= 2684). The association of rs4317882 reached the genome-wide significance in the meta-analysis of all available subjects (P(meta)= 4.58 × 10(-8), n= 4204). Site heterogeneity was observed, with a larger effect on spine than hip BMD. Further functional studies in a zebrafish model revealed that vertebral bone mass was lower in an mpp7 knock-down model compared with the wide-type (P= 9.64 × 10(-4), n= 21). In addition, MPP7 was found to have constitutive expression in human bone-derived cells during osteogenesis. Immunostaining of murine MC3T3-E1 cells revealed that the Mpp7 protein is localized in the plasma membrane and intracytoplasmic compartment of osteoblasts. In an assessment of the function of identified variants, an electrophoretic mobility shift assay demonstrated the binding of transcriptional factor GATA2 to the risk allele 'A' but not the 'G' allele of rs4317882. An mRNA expression study in human peripheral blood mononuclear cells confirmed that the low BMD-related allele 'A' of rs4317882 was associated with lower MPP7 expression (P= 9.07 × 10(-3), n= 135). Our data suggest a genetic and functional association of MPP7 with BMD variation.

  17. Lack of association between a functional variant of the BRCA-1 related associated protein (BRAP) gene and ischemic stroke.

    Science.gov (United States)

    Liao, Yi-Chu; Lin, Hsiu-Fen; Guo, Yuh-Cherng; Chen, Chung-Hung; Huang, Zhi-Zhang; Juo, Suh-Hang Hank; Lin, Ruey-Tay

    2013-01-28

    Atherosclerosis shares common pathogenic features with myocardial infarction (MI) and ischemic stroke. BRCA-1 associated protein (BRAP), a newly identified risk gene for MI, aggravates the inflammatory response in atherosclerosis. The aim of this study was to test the association between the BRAP gene and stroke in a Taiwanese population. A total of 1,074 stroke patients and 1,936 controls were genotyped for the functional SNP rs11066001. In our previous studies, the rare allele of this SNP has been repeatedly shown to exert a recessive effect. Therefore, in the current study, we tested for the same recessive model. First, the genotype distributions between all the controls and all the stroke cases were compared. Then to reduce heterogeneity, we explored several population subsets by selecting young stroke subjects (using 45 years of age as the cutoff point), age- and sex-comparable controls, plaque-free controls, and stroke subtypes. We did not find any significant association for the entire data set (OR = 0.94, p = 0.74) or for the subset analyses using age- and sex-comparable controls (p = 0.70) and plaque-free controls (p = 0.91). Analyses of the four stroke subtypes also failed to show any significant associations (p = 0.42 - 0.98). For both young and old subjects, the GG genotype of rs11066001 was similar in the stroke cases and unmatched controls (8.1% vs. 9.4% in young subjects and 8.0% vs. 7.8% in old subjects). Comparing stroke cases with plaque-free controls also failed to find any significant association. The BRAP polymorphism may not play an important role in ischemic stroke in the studied population.

  18. Lack of association between a functional variant of the BRCA-1 related associated protein (BRAP gene and ischemic stroke

    Directory of Open Access Journals (Sweden)

    Liao Yi-Chu

    2013-01-01

    Full Text Available Abstract Background Atherosclerosis shares common pathogenic features with myocardial infarction (MI and ischemic stroke. BRCA-1 associated protein (BRAP, a newly identified risk gene for MI, aggravates the inflammatory response in atherosclerosis. The aim of this study was to test the association between the BRAP gene and stroke in a Taiwanese population. Methods A total of 1,074 stroke patients and 1,936 controls were genotyped for the functional SNP rs11066001. In our previous studies, the rare allele of this SNP has been repeatedly shown to exert a recessive effect. Therefore, in the current study, we tested for the same recessive model. First, the genotype distributions between all the controls and all the stroke cases were compared. Then to reduce heterogeneity, we explored several population subsets by selecting young stroke subjects (using 45 years of age as the cutoff point, age- and sex-comparable controls, plaque-free controls, and stroke subtypes. Results We did not find any significant association for the entire data set (OR = 0.94, p = 0.74 or for the subset analyses using age- and sex-comparable controls (p = 0.70 and plaque-free controls (p = 0.91. Analyses of the four stroke subtypes also failed to show any significant associations (p = 0.42 – 0.98. For both young and old subjects, the GG genotype of rs11066001 was similar in the stroke cases and unmatched controls (8.1% vs. 9.4% in young subjects and 8.0% vs. 7.8% in old subjects. Comparing stroke cases with plaque-free controls also failed to find any significant association. Conclusions The BRAP polymorphism may not play an important role in ischemic stroke in the studied population.

  19. Gain-of-function variants in NLRP1 protect against the development of diabetic kidney disease: NLRP1 inflammasome role in metabolic stress sensing?

    Science.gov (United States)

    Soares, Jaine L S; Fernandes, Fernanda Pereira; Patente, Thiago Andrade; Monteiro, Maria B; Parisi, Maria C; Giannella-Neto, Daniel; Corrêa-Giannella, Maria L; Pontillo, Alessandra

    2018-02-01

    Although inflammasome plays a well-known role in animal models of renal injury, limited studies in humans are available, and its participation in diabetic kidney disease (DKD) remains unknown. Aim of this study was to elucidate the contribution of inflammasome genetics in the development of DKD in type-1 diabetes (T1D). The association of functional variants in inflammasome genes with DKD was assessed by multivariate analysis in a retrospective and in a prospective cohort. NLRP1 rs2670660 and rs11651270 polymorphisms were significantly associated with a decrease risk to develop DKD (p adj <0.01), and rs11651270 also with a lower risk of new renal events during follow-up (p adj =0.01). Supporting these findings, diabetes metabolites (glycated albumin and high glucose) were able to modulate NLRP1 expression. This study is the first to suggest a protective role of NLRP1 in DKD, highlighting an emerging role of NLRP1 as a homeostatic factor against metabolic stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Transgenic mouse lines expressing rat AH receptor variants - A new animal model for research on AH receptor function and dioxin toxicity mechanisms

    International Nuclear Information System (INIS)

    Pohjanvirta, Raimo

    2009-01-01

    Han/Wistar (Kuopio; H/W) rats are exceptionally resistant to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity mainly because of their mutated aryl hydrocarbon receptor (AHR) gene. In H/W rats, altered splicing of the AHR mRNA generates two AHR proteins: deletion (DEL) and insertion (INS) variants, with the INS isoform being predominantly expressed. To gain further insight into their functional properties, cDNAs of these and rat wild-type (rWT) isoform were transferred into C57BL/6J-derived mice by microinjection. The endogenous mouse AHR was eliminated by selective crossing with Ahr-null mice. A single mouse line was obtained for each of the three constructs. The AHR mRNA levels in tissues were generally close to those of C57BL/6 mice in INS and DEL mice and somewhat higher in rWT mice; in testis, however, all 3 constructs exhibited marked overexpression. The transgenic mouse lines were phenotypically normal except for increased testis weight. Induction of drug-metabolizing enzymes by TCDD occurred similarly to that in C57BL/6 mice, but there tended to be a correlation with AHR concentrations, especially in testis. In contrast to C57BL/6 mice, the transgenics did not display any major gender difference in susceptibility to the acute lethality and hepatotoxicity of TCDD; rWT mice were highly sensitive, DEL mice moderately resistant and INS mice highly resistant. Co-expression of mouse AHR and rWT resulted in augmented sensitivity to TCDD and abolished the natural resistance of female C57BL/6 mice, whereas mice co-expressing mouse AHR and INS were resistant. Thus, these transgenic mouse lines provide a novel promising tool for molecular studies on dioxin toxicity and AHR function.

  1. Identification of a functional genetic variant at 16q12.1 for breast cancer risk: results from the Asia Breast Cancer Consortium.

    Directory of Open Access Journals (Sweden)

    Jirong Long

    2010-06-01

    Full Text Available Genetic factors play an important role in the etiology of breast cancer. We carried out a multi-stage genome-wide association (GWA study in over 28,000 cases and controls recruited from 12 studies conducted in Asian and European American women to identify genetic susceptibility loci for breast cancer. After analyzing 684,457 SNPs in 2,073 cases and 2,084 controls in Chinese women, we evaluated 53 SNPs for fast-track replication in an independent set of 4,425 cases and 1,915 controls of Chinese origin. Four replicated SNPs were further investigated in an independent set of 6,173 cases and 6,340 controls from seven other studies conducted in Asian women. SNP rs4784227 was consistently associated with breast cancer risk across all studies with adjusted odds ratios (95% confidence intervals of 1.25 (1.20-1.31 per allele (P = 3.2 x 10(-25 in the pooled analysis of samples from all Asian samples. This SNP was also associated with breast cancer risk among European Americans (per allele OR = 1.19, 95% CI = 1.09-1.31, P = 1.3 x 10(-4, 2,797 cases and 2,662 controls. SNP rs4784227 is located at 16q12.1, a region identified previously for breast cancer risk among Europeans. The association of this SNP with breast cancer risk remained highly statistically significant in Asians after adjusting for previously-reported SNPs in this region. In vitro experiments using both luciferase reporter and electrophoretic mobility shift assays demonstrated functional significance of this SNP. These results provide strong evidence implicating rs4784227 as a functional causal variant for breast cancer in the locus 16q12.1 and demonstrate the utility of conducting genetic association studies in populations with different genetic architectures.

  2. Radurization of fowl meat

    International Nuclear Information System (INIS)

    Gel'fand, S.

    1974-01-01

    The effects of pre-slaughter adrenalization and of treatment with additives of semifinished poultry products were studied with a view to improving the storage quality of irradiated poultry. It was found that pre-slaughter adrenalization, pre-irradiation treatment with phosphates and, particularly, a combination of these two methods considerably delayed the formation of carbonyl compounds, the delay being somewhat greater in white meat. (E.T.)

  3. THE IMPORTANCE OF BACTERIOCINS IN MEAT AND MEAT PRODUCTS

    Directory of Open Access Journals (Sweden)

    Meltem SERDAROĞLU

    2000-03-01

    Full Text Available There is an increasing consumer demand for food products which are free of chemical additives, reduced in salt and processed as little as possible. These minimally processed foods require special application to assure their microbiological safety. The use of microorganisms and enzymes for food preservatives is called biopreservation. The most important group of microorganisms with antimicrobial effect used in the production of foods is the lactic acid bacteria. In meats although lactic acid bacteria constitue apart of the initial microflora, they become dominant during the processing of meats. In this research bacteriocins of lactic acid bacteria and their usage in meat and meat products for biopreservation are discussed.

  4. Natural antioxidants in meat and poultry products.

    Science.gov (United States)

    Karre, Liz; Lopez, Keyla; Getty, Kelly J K

    2013-06-01

    In response to recent claims that synthetic antioxidants have the potential to cause toxicological effects and consumers' increased interest in purchasing natural products, the meat and poultry industry has been seeking sources of natural antioxidants. Due to their high phenolic compound content, fruits and other plant materials provide a good alternative to conventional antioxidants. Plum, grape seed extract, cranberry, pomegranate, bearberry, pine bark extract, rosemary, oregano, and other spices functions as antioxidants in meat and poultry products. Pomegranate, pine bark extract, cinnamon, and cloves have exhibited stronger antioxidant properties than some synthetic options. Plum products, grape seed extract, pine bark extract, rosemary, and some spices all have been shown to affect the color of finished meat or poultry products; however, in some products such as pork sausage or uncured meats, an increase in red color may be desired. When selecting a natural antioxidant, sensory and quality impact on the product should be considered to achieve desired traits. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. A rare P2X7 variant Arg307Gln with absent pore formation function protects against neuroinflammation in multiple sclerosis.

    Science.gov (United States)

    Gu, Ben J; Field, Judith; Dutertre, Sébastien; Ou, Amber; Kilpatrick, Trevor J; Lechner-Scott, Jeannette; Scott, Rodney; Lea, Rodney; Taylor, Bruce V; Stankovich, Jim; Butzkueven, Helmut; Gresle, Melissa; Laws, Simon M; Petrou, Steven; Hoffjan, Sabine; Akkad, Denis A; Graham, Colin A; Hawkins, Stanley; Glaser, Anna; Bedri, Sahl Khalid; Hillert, Jan; Matute, Carlos; Antiguedad, Alfredo; Wiley, James S

    2015-10-01

    Multiple sclerosis (MS) is a chronic relapsing-remitting inflammatory disease of the central nervous system characterized by oligodendrocyte damage, demyelination and neuronal death. Genetic association studies have shown a 2-fold or greater prevalence of the HLA-DRB1*1501 allele in the MS population compared with normal Caucasians. In discovery cohorts of Australasian patients with MS (total 2941 patients and 3008 controls), we examined the associations of 12 functional polymorphisms of P2X7, a microglial/macrophage receptor with proinflammatory effects when activated by extracellular adenosine triphosphate (ATP). In discovery cohorts, rs28360457, coding for Arg307Gln was associated with MS and combined analysis showed a 2-fold lower minor allele frequency compared with controls (1.11% for MS and 2.15% for controls, P = 0.0000071). Replication analysis of four independent European MS case-control cohorts (total 2140 cases and 2634 controls) confirmed this association [odds ratio (OR) = 0.69, P = 0.026]. A meta-analysis of all Australasian and European cohorts indicated that Arg307Gln confers a 1.8-fold protective effect on MS risk (OR = 0.57, P = 0.0000024). Fresh human monocytes heterozygous for Arg307Gln have >85% loss of 'pore' function of the P2X7 receptor measured by ATP-induced ethidium uptake. Analysis shows Arg307Gln always occurred with 270His suggesting a single 307Gln-270His haplotype that confers dominant negative effects on P2X7 function and protection against MS. Modeling based on the homologous zP2X4 receptor showed Arg307 is located in a region rich in basic residues located only 12 Å from the ligand binding site. Our data show the protective effect against MS of a rare genetic variant of P2RX7 with heterozygotes showing near absent proinflammatory 'pore' function. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Data-variant kernel analysis

    CERN Document Server

    Motai, Yuichi

    2015-01-01

    Describes and discusses the variants of kernel analysis methods for data types that have been intensely studied in recent years This book covers kernel analysis topics ranging from the fundamental theory of kernel functions to its applications. The book surveys the current status, popular trends, and developments in kernel analysis studies. The author discusses multiple kernel learning algorithms and how to choose the appropriate kernels during the learning phase. Data-Variant Kernel Analysis is a new pattern analysis framework for different types of data configurations. The chapters include

  7. Dairy products, meat and sports performance.

    Science.gov (United States)

    Fogelholm, Mikael

    2003-01-01

    Creatine supplementation improves repetitive, short-term performance. It has not been shown that exclusion of meat from the diet would impair repetitive short-term performance. In contrast, reduction of protein intake and a concomitant increase of carbohydrate intake during a period of 3-5 days improves anaerobic (2-7 minutes) performance. The protein intake in a mixed or lacto-vegetarian diet is adequate even for elite athletes, providing that energy requirements are met. Many dietary supplements have been suggested to increase muscle mass and/or to decrease fat mass. Although the effects of conjugated linoleic acid on body composition in athletes are not clear, some positive findings in untrained, obese individuals call for more studies. Strenuous training may impair immune function and increase the susceptibility to infections. Exclusion of meat from the diet does not seem to have adverse effects on immune function. Glutamine supplementation (>3-6 g/day) may improve immune function, but more studies are needed. Similarly, more studies on the possible effects of whey protein and probiotic supplementation on immune function and performance in physically highly active individuals are warranted. Vitamin and mineral balance are not usually a problem among athletes. Notable exceptions may be calcium and iron in some females. Increased calcium intake in athletes with hormonal and menstrual disturbances could theoretically help in maintaining bone status; however, no data are available. A diet with meat may help in maintaining adequate iron stores.

  8. Red meat and colorectal cancer

    Directory of Open Access Journals (Sweden)

    Nuri Faruk Aykan

    2015-12-01

    Full Text Available Colorectal cancer (CRC is the third most common cancer in men and the second in women worldwide. More than half of cases occur in more developed countries. The consumption of red meat (beef, pork, lamb, veal, mutton is high in developed countries and accumulated evidence until today demonstrated a convincing association between the intake of red meat and especially processed meat and CRC risk. In this review, meta-analyses of prospective epidemiological studies addressed to this association, observed link of some subtypes of red meat with CRC risk, potential carcinogenic compounds, their mechanisms and actual recommendations of international guidelines are presented.

  9. PREDICTION OF MEAT PRODUCT QUALITY BY THE MATHEMATICAL PROGRAMMING METHODS

    Directory of Open Access Journals (Sweden)

    A. B. Lisitsyn

    2016-01-01

    Full Text Available Abstract Use of the prediction technologies is one of the directions of the research work carried out both in Russia and abroad. Meat processing is accompanied by the complex physico-chemical, biochemical and mechanical processes. To predict the behavior of meat raw material during the technological processing, a complex of physico-technological and structural-mechanical indicators, which objectively reflects its quality, is used. Among these indicators are pH value, water binding and fat holding capacities, water activity, adhesiveness, viscosity, plasticity and so on. The paper demonstrates the influence of animal proteins (beef and pork on the physico-chemical and functional properties before and after thermal treatment of minced meat made from meat raw material with different content of the connective and fat tissues. On the basis of the experimental data, the model (stochastic dependence parameters linking the quantitative resultant and factor variables were obtained using the regression analysis, and the degree of the correlation with the experimental data was assessed. The maximum allowable levels of meat raw material replacement with animal proteins (beef and pork were established by the methods of mathematical programming. Use of the information technologies will significantly reduce the costs of the experimental search and substantiation of the optimal level of replacement of meat raw material with animal proteins (beef, pork, and will also allow establishing a relationship of product quality indicators with quantity and quality of minced meat ingredients.

  10. Physicochemical properties of meat of ducks of mulberries in modern technologies of meat products

    Directory of Open Access Journals (Sweden)

    R. F. Galin

    2017-01-01

    Full Text Available The article presents the results of studying the chemical composition of mullards duck meat in comparison with the ducks of the Beijingg white breed and musk ducks. The chemical analysis results allow us to note the high moisture content for mullard duck meat. The low fat content for white and red mullard duck meat opens up wide opportunities for the development of an assortment of meat products with a functional orientation. The limited amino acids are determined. The total number of essential amino acids in the mullard duck meat is higher than in musk (by 1.02 g / 100 g protein and Beijingg (by 0.86 g / 100 g protein, which indicates a higher biological value. The limiting amino acid is methionine and cysteine. The article presents the results of the raw material aroma assessment using the "MAG 8" - "electronic nose" analyzer. The content of easily volatile compounds in the equilibrium gas phase for samples of muscle and fat tissue from ducks of different breeding was compared and evaluated. The most informative in the matrix are sensors with films of polydiethylene glycol succinate, polyvinylpyrrolidone, polyethylene glycol PEG-2000, 18-crown-6, trioctylphosphine oxidase, which show maximum sensitivity to polar and nitrogen-containing compounds, aromatic hydrocarbons. This is explained by the fact that the easily volatile fraction of both meat and fat of the samples under study is represented by a variety of organic compounds of different concentrations. Such a variety of substances can be perceived by tasters as "a noticeable smell, difficult". In accordance with the results obtained, we concluded that the aroma of muscle and fat tissue of mulard ducks is more intense, more saturated than the Beijingg duck. The obtained data on the chemical composition indicate possible dietary properties of meat of ducks of mullards. The rich, pronounced aroma of muscle and fatty tissue causes high organoleptic parameters of the finished product, which is

  11. Multiple functional variants at 13q14 risk locus for osteoporosis regulate RANKL expression through long-range super-enhancer.

    Science.gov (United States)

    Zhu, Dong-Li; Chen, Xiao-Feng; Hu, Wei-Xin; Dong, Shan-Shan; Lu, Bing-Jie; Rong, Yu; Chen, Yi-Xiao; Chen, Hao; Thynn, Hlaing Nwe; Wang, Nai-Ning; Guo, Yan; Yang, Tie-Lin

    2018-03-12

    RANKL is a key regulator involved in bone metabolism, and a drug target for osteoporosis. The clinical diagnosis and assessment of osteoporosis are mainly based on bone mineral density (BMD). Previous powerful genome-wide association studies (GWASs) have identified multiple intergenic single nucleotide polymorphisms (SNPs) located over 100 kb upstream of RANKL and 65 kb downstream of AKAP11 at 13q14.11 for osteoporosis. Whether these SNPs exert their roles on osteoporosis through RANKL is unknown. In this study, we conducted integrative analyses combining expression quantitative trait locus (eQTL), genomic chromatin interaction (Hi-C), epigenetic annotation and a series of functional assays. The eQTL analysis identified six potential functional SNPs (rs9533090, rs9594738, r8001611, rs9533094, rs9533095 and rs9594759) exclusively correlated with RANKL gene expression (P < 0.001) at 13q14.11. Co-localization analyses suggested that eQTL signal for RANKL and BMD-GWAS signal shared the same causal variants. Hi-C analysis and functional annotation further validated that the first 5 osteoporosis SNPs are located in a super-enhancer region to regulate the expression of RANKL via long-range chromosomal interaction. Particularly, dual-luciferase assay demonstrated that the region harboring rs9533090 in the super-enhancer has the strongest enhancer activity, and rs9533090 is an allele-specific regulatory SNP. Furthermore, deletion of the region harboring rs9533090 using CRISPR/Cas9 genome editing significantly reduced RANKL expression in both mRNA level and protein level. Finally, we found that the rs9533090-C robustly recruits transcription factor NFIC, which efficiently elevates the enhancer activity and increases the RANKL expression. In summary, we provided a feasible method to identify regulatory noncoding SNPs to distally regulate their target gene underlying the pathogenesis of osteoporosis by using bioinformatics data analyses and experimental validation. Our

  12. A robust variant of block Jacobi-Davidson for extracting a large number of eigenpairs: Application to grid-based real-space density functional theory.

    Science.gov (United States)

    Lee, M; Leiter, K; Eisner, C; Breuer, A; Wang, X

    2017-09-21

    In this work, we investigate a block Jacobi-Davidson (J-D) variant suitable for sparse symmetric eigenproblems where a substantial number of extremal eigenvalues are desired (e.g., ground-state real-space quantum chemistry). Most J-D algorithm variations tend to slow down as the number of desired eigenpairs increases due to frequent orthogonalization against a growing list of solved eigenvectors. In our specification of block J-D, all of the steps of the algorithm are performed in clusters, including the linear solves, which allows us to greatly reduce computational effort with blocked matrix-vector multiplies. In addition, we move orthogonalization against locked eigenvectors and working eigenvectors outside of the inner loop but retain the single Ritz vector projection corresponding to the index of the correction vector. Furthermore, we minimize the computational effort by constraining the working subspace to the current vectors being updated and the latest set of corresponding correction vectors. Finally, we incorporate accuracy thresholds based on the precision required by the Fermi-Dirac distribution. The net result is a significant reduction in the computational effort against most previous block J-D implementations, especially as the number of wanted eigenpairs grows. We compare our approach with another robust implementation of block J-D (JDQMR) and the state-of-the-art Chebyshev filter subspace (CheFSI) method for various real-space density functional theory systems. Versus CheFSI, for first-row elements, our method yields competitive timings for valence-only systems and 4-6× speedups for all-electron systems with up to 10× reduced matrix-vector multiplies. For all-electron calculations on larger elements (e.g., gold) where the wanted spectrum is quite narrow compared to the full spectrum, we observe 60× speedup with 200× fewer matrix-vector multiples vs. CheFSI.

  13. Social influence on associative learning: double dissociation in high-functioning autism, early-stage behavioural variant frontotemporal dementia and Alzheimer's disease.

    Science.gov (United States)

    Kéri, Szabolcs

    2014-05-01

    Most of our learning activity takes place in a social context. I examined how social interactions influence associative learning in neurodegenerative diseases and atypical neurodevelopmental conditions primarily characterised by social cognitive and memory dysfunctions. Participants were individuals with high-functioning autism (HFA, n = 18), early-stage behavioural variant frontotemporal dementia (bvFTD, n = 16) and Alzheimer's disease (AD, n = 20). The leading symptoms in HFA and bvFTD were social and behavioural dysfunctions, whereas AD was characterised by memory deficits. Participants received three versions of a paired associates learning task. In the game with boxes test, objects were hidden in six candy boxes placed in different locations on the computer screen. In the game with faces, each box was labelled by a photo of a person. In the real-life version of the game, participants played with real persons. Individuals with HFA and bvFTD performed well in the computer games, but failed on the task including real persons. In contrast, in patients with early-stage AD, social interactions boosted paired associates learning up to the level of healthy control volunteers. Worse performance in the real life game was associated with less successful recognition of complex emotions and mental states in the Reading the Mind in the Eyes Test. Spatial span did not affect the results. When social cognition is impaired, but memory systems are less compromised (HFA and bvFTD), real-life interactions disrupt associative learning; when disease process impairs memory systems but social cognition is relatively intact (early-stage AD), social interactions have a beneficial effect on learning and memory. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Bacterial spoilage of meat and cured meat products

    NARCIS (Netherlands)

    Borch, E.; Kant-Muermans, M.L.T.; Blixt, Y.

    1996-01-01

    The influence of environmental factors (product composition and storage conditions) on the selection, growth rate and metabolic activity of the bacterial flora is presented for meat (pork and beef) and cooked, cured meat products. The predominant bacteria associated with spoilage of refrigerated

  15. Qualitative analysis of meat and meat products by multiplex ...

    African Journals Online (AJOL)

    Jane

    2011-08-22

    Aug 22, 2011 ... acid; BLAST, Basic Local Alignment Search Tool; NCBI,. National Center for Biotechnology Information. ... Several workers have developed PCR methods to control the suitability, with labels of meat products. ..... The test could be useful in controlling and verifying the origin of the meat species, especially in ...

  16. Breast meat yield, muscle linear measurements and meat ...

    African Journals Online (AJOL)

    Breast meat yield, chemical composition, mineral profile and linear measurement of the resultant breast meat Supracoracoides and Pectoralis thoracicus of one hundred and eighty (28 days old BUT) male turkeys fed diet containing wheat or sorghum as sole cereal source were studied. One hundred and eighty 28-days old ...

  17. The meat grinder - Theoretical and practical limitations

    Science.gov (United States)

    Zucker, O.; Wyatt, J.; Lindner, K.

    1984-03-01

    The meat grinder (Zucker and Long, 1980) is shown to be a purely inductive energy transfer system whose opening switch problem is drastically reduced because of its reversibility. It is also shown that the number of switches is a function only of the desired overall efficiency, the coupling coefficient, and the desired current. The dynamic behavior of the voltage on the switches is demonstrated, and a calculation is made for a typical application.

  18. Improvement of turkey breast meat quality and cooked gel functionality using hot-boning, quarter sectioning, crust-freeze-air-chilling and cold-batter-mincing technologies.

    Science.gov (United States)

    Lee, H C; Erasmus, M A; Swanson, J C; Hong, H G; Kang, I

    2016-01-01

    The effect of rapid carcass chilling on breast meat quality was evaluated using commercial (COMM) and random-bred (RB) turkeys. Immediately after slaughter, 48 turkeys from COMM or RB line were randomly subjected to one of four chilling methods: 1) water-immersion chilling (WIC) of the carcasses at 0°C ice slurry, 2) WIC after temperature abuse (TA) of the carcasses at 40°C for 30 min (TA-WIC), 3) hot-boning, quarter sectioning, and crust-freeze-air-chilling (HB-(1)/4CFAC) of breast fillets at -12°C, and 4) HB-(1)/4CFAC of fillets after TA of carcasses (TA-HB-(1)/4CFAC). The TA increased carcass and fillet temperatures by ∼1.3 and ∼4.1°C, respectively, regardless of turkey line, whereas HB-(1)/4CFAC of fillets required 28 and 33% of carcass chilling time for COMM and RB, respectively. During chilling, COMM breast pH rapidly reduced from 6.04 to 5.82, resulting in a significantly lower pH than RB after chilling (P 0.05). Significantly higher L* value and cooking yield (P 0.05). Higher values of hardness, gumminess, and chewiness were found for RB, no TA, and HB-(1)/4CFAC gels than COMM, TA, and WIC, respectively. These results generally indicated that protein quality and textural properties of turkey fillets were improved, regardless of strains or temperature abuse, using HB-(1)/4CFAC technology. © 2015 Poultry Science Association Inc.

  19. Guidelines for investigating causality of sequence variants in human disease

    Science.gov (United States)

    MacArthur, D. G.; Manolio, T. A.; Dimmock, D. P.; Rehm, H. L.; Shendure, J.; Abecasis, G. R.; Adams, D. R.; Altman, R. B.; Antonarakis, S. E.; Ashley, E. A.; Barrett, J. C.; Biesecker, L. G.; Conrad, D. F.; Cooper, G. M.; Cox, N. J.; Daly, M. J.; Gerstein, M. B.; Goldstein, D. B.; Hirschhorn, J. N.; Leal, S. M.; Pennacchio, L. A.; Stamatoyannopoulos, J. A.; Sunyaev, S. R.; Valle, D.; Voight, B. F.; Winckler, W.; Gunter, C.

    2014-01-01

    The discovery of rare genetic variants is accelerating, and clear guidelines for distinguishing disease-causing sequence variants from the many potentially functional variants present in any human genome are urgently needed. Without rigorous standards we risk an acceleration of false-positive reports of causality, which would impede the translation of genomic research findings into the clinical diagnostic setting and hinder biological understanding of disease. Here we discuss the key challenges of assessing sequence variants in human disease, integrating both gene-level and variant-level support for causality. We propose guidelines for summarizing confidence in variant pathogenicity and highlight several areas that require further resource development. PMID:24759409

  20. Detection of Salmonella in Meat

    DEFF Research Database (Denmark)

    Löfström, Charlotta; Hansen, Flemming; Mansdal, Susanne

    2012-01-01

    Cost-effective and rapid monitoring of Salmonella in the meat production chain can contribute to food safety. The objective of this study was to validate an easy-to-use pre-PCR sample preparation method based on a simple boiling protocol for screening of Salmonella in meat and carcass swab samples...

  1. Cultured Meat in Islamic Perspective.

    Science.gov (United States)

    Hamdan, Mohammad Naqib; Post, Mark J; Ramli, Mohd Anuar; Mustafa, Amin Rukaini

    2017-04-29

    Cultured meat is a promising product that is derived through biotechnology that partially circumvents animal physiology, thereby being potentially more sustainable, environmentally friendly and animal friendly than traditional livestock meat. Such a novel technology that can impact many consumers evokes ethical, philosophical and religious discussions. For the Islamic community, the crucial question is whether cultured meat is halal, meaning compliant with Islamic laws. Since the culturing of meat is a new discovery, invention and innovation by scientists that has never been discussed by classical jurists (fuqaha'), an ijtihad by contemporary jurists must look for and provide answers for every technology introduced, whether it comply the requirements of Islamic law or not. So, this article will discuss an Islamic perspective on cultured meat based on the original scripture in the Qur'an and interpretations by authoritative Islamic jurists. The halal status of cultured meat can be resolve through identifying the source cell and culture medium used in culturing the meat. The halal cultured meat can be obtained if the stem cell is extracted from a (Halal) slaughtered animal, and no blood or serum is used in the process. The impact of this innovation will give positive results in the environmental and sustain the livestock industry.

  2. Iodine in meat in Macedonia

    International Nuclear Information System (INIS)

    Bogdanov, Bogdan; Gonev, Mihajlo; Tadzher, Isak

    2000-01-01

    Iodine deficiency in Macedonia still persists in a mild form. In 1999 the iodination of salt rose to 20 m gr iodine in Kg salt. The consumption of salt diminished after the last war from 20-30 gr salt per day to 10-20 gr salt daily. This shows that the problem of the elimination of iodine deficiency is being vigorously tackled. Since 1956 the iodine in salt in Macedonia rose to 10 m gr KI/Kg salt. The content of iodine in the Macedonian diet seems to be important. The amount of iodine in milk, eggs and bread is low as found by the investigation of MANU. The content of iodine in meat is low, compared to British meat is 10 times lower. The average iodine content in Macedonian meat is 95.15 micro gr per Kg, whereas in British meat it is 850-1510 micro gr iodine per k gr meat. (Original)

  3. Food safety and organic meats.

    Science.gov (United States)

    Van Loo, Ellen J; Alali, Walid; Ricke, Steven C

    2012-01-01

    The organic meat industry in the United States has grown substantially in the past decade in response to consumer demand for nonconventionally produced products. Consumers are often not aware that the United States Department of Agriculture (USDA) organic standards are based only on the methods used for production and processing of the product and not on the product's safety. Food safety hazards associated with organic meats remain unclear because of the limited research conducted to determine the safety of organic meat from farm-to-fork. The objective of this review is to provide an overview of the published results on the microbiological safety of organic meats. In addition, antimicrobial resistance of microbes in organic food animal production is addressed. Determining the food safety risks associated with organic meat production requires systematic longitudinal studies that quantify the risks of microbial and nonmicrobial hazards from farm-to-fork.

  4. Environmental costs of meat production

    DEFF Research Database (Denmark)

    Nguyen, T Lan T; Hermansen, John Erik; Mogensen, Lisbeth

    2012-01-01

    This paper aims to address two questions: First, what is the real cost of meat to society if taking into account the environmental costs arising throughout the product life cycle; and second, whether and how the environmental costs related to meat production can be reduced. In addressing the issues......, we use pig meat production in the EU as a case study. The environmental costs of meat are displayed first as characterized results at different midpoint categories e.g. global warming, nature occupation, acidification, eutrophication, ecotoxicity, etc., and then aggregated into a single score using...... conversion factors available from the Stepwise2006 method. Overall, the environmental costs of producing conventional pig meat are estimated to be 1.9 EUR per kg, which are of even larger size than the private costs of 1.4 EUR. In decreasing order of importance, nature occupation has been found...

  5. Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers

    DEFF Research Database (Denmark)

    French, Juliet D; Ghoussaini, Maya; Edwards, Stacey L

    2013-01-01

    Analysis of 4,405 variants in 89,050 European subjects from 41 case-control studies identified three independent association signals for estrogen-receptor-positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer element in which the G allele of the best candidate causative...

  6. High incidence of functional ion-channel abnormalities in a consecutive Long QT cohort with novel missense genetic variants of unknown significance

    DEFF Research Database (Denmark)

    Steffensen, Annette Buur; Refaat, Marwan M; David, Jens-Peter

    2015-01-01

    The Long QT syndrome (LQTS) is a disorder characterized by a prolongation of the QT interval and a propensity to ventricular tachyarrhythmias, which may lead to syncope, cardiac arrest, or sudden death. Our objective was to (1) determine the incidence of variants with unknown significance (VUS) i...

  7. Identification of Functional Variants for Cleft Lip with or without Cleft Palate in or near PAX7, FGFR2, and NOG by Targeted Sequencing of GWAS Loci

    DEFF Research Database (Denmark)

    Leslie, Elizabeth J; Taub, Margaret A; Liu, Huan

    2015-01-01

    Although genome-wide association studies (GWASs) for nonsyndromic orofacial clefts have identified multiple strongly associated regions, the causal variants are unknown. To address this, we selected 13 regions from GWASs and other studies, performed targeted sequencing in 1,409 Asian and European...... alleles for nonsyndromic clefting in humans....

  8. A functional ABCA1 gene variant is associated with low HDL-cholesterol levels and shows evidence of positive selection in Native Americans

    NARCIS (Netherlands)

    Acuña-Alonzo, Víctor; Flores-Dorantes, Teresa; Kruit, Janine K; Villarreal-Molina, Teresa; Arellano-Campos, Olimpia; Hünemeier, Tábita; Moreno-Estrada, Andrés; Ortiz-López, Ma Guadalupe; Villamil-Ramírez, Hugo; León-Mimila, Paola; Villalobos-Comparan, Marisela; Jacobo-Albavera, Leonor; Ramírez-Jiménez, Salvador; Sikora, Martin; Zhang, Lin-Hua; Pape, Terry D; Granados-Silvestre, Ma de Angeles; Montufar-Robles, Isela; Tito-Alvarez, Ana M; Zurita-Salinas, Camilo; Bustos-Arriaga, José; Cedillo-Barrón, Leticia; Gómez-Trejo, Celta; Barquera-Lozano, Rodrigo; Vieira-Filho, Joao P; Granados, Julio; Romero-Hidalgo, Sandra; Huertas-Vázquez, Adriana; González-Martín, Antonio; Gorostiza, Amaya; Bonatto, Sandro L; Rodríguez-Cruz, Maricela; Wang, Li; Tusié-Luna, Teresa; Aguilar-Salinas, Carlos A; Lisker, Ruben; Moises, Regina S; Menjivar, Marta; Salzano, Francisco M; Knowler, William C; Bortolini, M Cátira; Hayden, Michael R; Baier, Leslie J; Canizales-Quinteros, Samuel

    2010-01-01

    It has been suggested that the higher susceptibility of Hispanics to metabolic disease is related to their Native American heritage. A frequent cholesterol transporter ABCA1 (ATP-binding cassette transporter A1) gene variant (R230C, rs9282541) apparently exclusive to Native American individuals was

  9. PIGS BREEDING FOR THE PRODUCTION OF TRADITIONAL MEAT PRODUCTS

    Directory of Open Access Journals (Sweden)

    Đuro Senčić

    2014-06-01

    Full Text Available The fertile Slavonia is known for production of several types of cured meats: kulen, kulen sis, sausage, ham and bacon, and other pork products (“krvavica” - blood sausage, “švargl” - a type of brawn where chopped parts of head are stuffed inside the pig’s stomach, “čvarci” - a variant of pork crisps, fat. These products require “mature pigs” of adequate slaughter quality. Production of pigs intended for traditional meat products may take place in different production systems (open, closed, semi-open, “organic”. Each of these systems provides a specific quality of pigs for slaughter, reflecting on the quality of the final product. Production systems can have a significant impact on growth performance and carcass and meat quality of pigs. This effect arises from the interaction between housing conditions, the amount and composition of food and used pig genotype. The choice of a production system depends on local production conditions, pig genotype, consumer demand (market for a given product quality, and other factors. Due to their quality, the traditional Slavonian meat products can become a recognizable Croatian brand in both domestic and international markets. Production of standard quality products requires standard quality of pigs. Therefore this book is focused on such pigs production.

  10. Contributions of Function-Altering Variants in Genes Implicated in Pubertal Timing and Body Mass for Self-Limited Delayed Puberty.

    Science.gov (United States)

    Howard, Sasha R; Guasti, Leonardo; Poliandri, Ariel; David, Alessia; Cabrera, Claudia P; Barnes, Michael R; Wehkalampi, Karoliina; O'Rahilly, Stephen; Aiken, Catherine E; Coll, Anthony P; Ma, Marcella; Rimmington, Debra; Yeo, Giles S H; Dunkel, Leo

    2018-02-01

    Self-limited delayed puberty (DP) is often associated with a delay in physical maturation, but although highly heritable the causal genetic factors remain elusive. Genome-wide association studies of the timing of puberty have identified multiple loci for age at menarche in females and voice break in males, particularly in pathways controlling energy balance. We sought to assess the contribution of rare variants in such genes to the phenotype of familial DP. We performed whole-exome sequencing in 67 pedigrees (125 individuals with DP and 35 unaffected controls) from our unique cohort of familial self-limited DP. Using a whole-exome sequencing filtering pipeline one candidate gene [fat mass and obesity-associated gene (FTO)] was identified. In silico, in vitro, and mouse model studies were performed to investigate the pathogenicity of FTO variants and timing of puberty in FTO+/- mice. We identified potentially pathogenic, rare variants in genes in linkage disequilibrium with genome-wide association studies of age at menarche loci in 283 genes. Of these, five genes were implicated in the control of body mass. After filtering for segregation with trait, one candidate, FTO, was retained. Two FTO variants, found in 14 affected individuals from three families, were also associated with leanness in these patients with DP. One variant (p.Leu44Val) demonstrated altered demethylation activity of the mutant protein in vitro. Fto+/- mice displayed a significantly delayed timing of pubertal onset (P < 0.05). Mutations in genes implicated in body mass and timing of puberty in the general population may contribute to the pathogenesis of self-limited DP. Copyright © 2017 Endocrine Society

  11. Expression and functional characterization of the Agrobacterium VirB2 amino acid substitution variants in T-pilus biogenesis, virulence, and transient transformation efficiency.

    Science.gov (United States)

    Wu, Hung-Yi; Chen, Chao-Ying; Lai, Erh-Min

    2014-01-01

    Agrobacterium tumefaciens is a phytopathogenic bacterium that causes crown gall disease by transferring transferred DNA (T-DNA) into the plant genome. The translocation process is mediated by the type IV secretion system (T4SS) consisting of the VirD4 coupling protein and 11 VirB proteins (VirB1 to VirB11). All VirB proteins are required for the production of T-pilus, which consists of processed VirB2 (T-pilin) and VirB5 as major and minor subunits, respectively. VirB2 is an essential component of T4SS, but the roles of VirB2 and the assembled T-pilus in Agrobacterium virulence and the T-DNA transfer process remain unknown. Here, we generated 34 VirB2 amino acid substitution variants to study the functions of VirB2 involved in VirB2 stability, extracellular VirB2/T-pilus production and virulence of A. tumefaciens. From the capacity for extracellular VirB2 production (ExB2+ or ExB2-) and tumorigenesis on tomato stems (Vir+ or Vir-), the mutants could be classified into three groups: ExB2-/Vir-, ExB2-/Vir+, and ExB2+/Vir+. We also confirmed by electron microscopy that five ExB2-/Vir+ mutants exhibited a wild-type level of virulence with their deficiency in T-pilus formation. Interestingly, although the five T-pilus-/Vir+ uncoupling mutants retained a wild-type level of tumorigenesis efficiency on tomato stems and/or potato tuber discs, their transient transformation efficiency in Arabidopsis seedlings was highly attenuated. In conclusion, we have provided evidence for a role of T-pilus in Agrobacterium transformation process and have identified the domains and amino acid residues critical for VirB2 stability, T-pilus biogenesis, tumorigenesis, and transient transformation efficiency.

  12. Expression and functional characterization of the Agrobacterium VirB2 amino acid substitution variants in T-pilus biogenesis, virulence, and transient transformation efficiency.

    Directory of Open Access Journals (Sweden)

    Hung-Yi Wu

    Full Text Available Agrobacterium tumefaciens is a phytopathogenic bacterium that causes crown gall disease by transferring transferred DNA (T-DNA into the plant genome. The translocation process is mediated by the type IV secretion system (T4SS consisting of the VirD4 coupling protein and 11 VirB proteins (VirB1 to VirB11. All VirB proteins are required for the production of T-pilus, which consists of processed VirB2 (T-pilin and VirB5 as major and minor subunits, respectively. VirB2 is an essential component of T4SS, but the roles of VirB2 and the assembled T-pilus in Agrobacterium virulence and the T-DNA transfer process remain unknown. Here, we generated 34 VirB2 amino acid substitution variants to study the functions of VirB2 involved in VirB2 stability, extracellular VirB2/T-pilus production and virulence of A. tumefaciens. From the capacity for extracellular VirB2 production (ExB2+ or ExB2- and tumorigenesis on tomato stems (Vir+ or Vir-, the mutants could be classified into three groups: ExB2-/Vir-, ExB2-/Vir+, and ExB2+/Vir+. We also confirmed by electron microscopy that five ExB2-/Vir+ mutants exhibited a wild-type level of virulence with their deficiency in T-pilus formation. Interestingly, although the five T-pilus-/Vir+ uncoupling mutants retained a wild-type level of tumorigenesis efficiency on tomato stems and/or potato tuber discs, their transient transformation efficiency in Arabidopsis seedlings was highly attenuated. In conclusion, we have provided evidence for a role of T-pilus in Agrobacterium transformation process and have identified the domains and amino acid residues critical for VirB2 stability, T-pilus biogenesis, tumorigenesis, and transient transformation efficiency.

  13. 9 CFR 319.80 - Barbecued meats.

    Science.gov (United States)

    2010-01-01

    ... CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Cooked Meats § 319.80 Barbecued meats. Barbecued meats, such as product labeled “Beef Barbecue” or “Barbecued Pork,” shall be cooked by the direct... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Barbecued meats. 319.80 Section 319.80...

  14. GAME MEAT MARKET IN EASTERN CROATIA

    Directory of Open Access Journals (Sweden)

    Z. Tolušić

    2006-12-01

    Full Text Available In the Republic of Croatia, game meat is consumed far less than meat of domestic animals. Yearly game meat consumption amounts to only 0.55 kg per household member. Consumers prefer meat of domestic animals, because it is cheaper, not paying attention to specific nutritive advantages of game meat. A research on the game meat market and consumers’ preferences was carried out on 101 examinees, chosen among inhabitants of Slavonia and Baranja. The majority of questioned inhabitants did consume game meat (92%, of whom 66% consider game meat to be of better quality than meat of domestic animals. Significant number of examinees considers game meat as healthy food, being also convinced that game was healthier to consume if hunted in their natural environment, than if reared on specialized farms (90%. Irrespective of quality, only 22% of examinees buy game meat, and 51% think such meat is too expensive. This is the main reason why consumers have game meat only once a month (51%. Taking into consideration monthly income of their respective household, 58% of examinees can afford game meat only once a month, and, if having an opportunity, they would opt for meat of roe deer (55% and rabbit (25%. When asked what would stimulate the game meat market in Croatia, 56% of examinees believe this could be achieved by lowering of prices, 27% think the issue could be addressed by opening of specialty stores, and only 17% opted for more aggressive marketing activities.

  15. Whole genome QTL mapping for growth, meat quality and breast meat yield traits in turkey.

    Science.gov (United States)

    Aslam, Muhammad L; Bastiaansen, John W M; Crooijmans, Richard P M A; Vereijken, Addie; Groenen, Martien A M

    2011-07-11

    The turkey (Meleagris gallopavo) is an important agricultural species and is the second largest contributor to the world's poultry meat production. Demand of turkey meat is increasing very rapidly. Genetic markers linked to genes affecting quantitative traits can increase the selection response of animal breeding programs. The use of these molecular markers for the identification of quantitative trait loci, and subsequently fine-mapping of quantitative trait loci regions, allows for pinpointing of genes that underlie such economically important traits. The quantitative trait loci analyses of the growth curve, body weight, breast yield and the meat quality traits showed putative quantitative trait loci on 21 of the 27 turkey chromosomes covered by the linkage map. Forty-five quantitative trait loci were detected across all traits and these were found in 29 different regions on 21 chromosomes. Out of the 45 quantitative trait loci, twelve showed significant (pmeat quality and breast yield traits. A large number of quantitative trait loci were detected across the turkey genome, which affected growth, breast yield and meat quality traits. Pleiotropic effects or close linkages between quantitative trait loci were suggested for several of the chromosomal regions. The comparative analysis regarding the location of quantitative trait loci on different turkey, and on the syntenic chicken chromosomes, along with their phenotypic associations, revealed signs of functional conservation between these species. © 2011 Aslam et al; licensee BioMed Central Ltd.

  16. Identification of a PRPF4 loss-of-function variant that abrogates U4/U6.U5 tri-snRNP integration and is associated with retinitis pigmentosa.

    Directory of Open Access Journals (Sweden)

    Bastian Linder

    Full Text Available Pre-mRNA splicing by the spliceosome is an essential step in the maturation of nearly all human mRNAs. Mutations in six spliceosomal proteins, PRPF3, PRPF4, PRPF6, PRPF8, PRPF31 and SNRNP200, cause retinitis pigmentosa (RP, a disease characterized by progressive photoreceptor degeneration. All splicing factors linked to RP are constituents of the U4/U6.U5 tri-snRNP subunit of the spliceosome, suggesting that the compromised function of this particle may lead to RP. Here, we report the identification of the p.R192H variant of the tri-snRNP factor PRPF4 in a patient with RP. The mutation affects a highly conserved arginine residue that is crucial for PRPF4 function. Introduction of a corresponding mutation into the zebrafish homolog of PRPF4 resulted in a complete loss of function in vivo. A series of biochemical experiments suggested that p.R192H disrupts the binding interface between PRPF4 and its interactor PRPF3. This interferes with the ability of PRPF4 to integrate into the tri-snRNP, as shown in a human cell line and in zebrafish embryos. These data suggest that the p.R192H variant of PRPF4 represents a functional null allele. The resulting haploinsufficiency of PRPF4 compromises the function of the tri-snRNP, reinforcing the notion that this spliceosomal particle is of crucial importance in the physiology of the retina.

  17. Irradiation of meats and poultry

    International Nuclear Information System (INIS)

    Urbain, W.M.

    1978-01-01

    A number of beneficial effects can be achieved by irradiating meats and poultry under different conditions. It is possible, for example, to extend the market life of both fresh and processed meats by applying radiation doses sufficient to reduce the microbial population, thereby delaying onset of spoilage; higher doses aimed at destroying both spoilage and pathogenic microorganisms can also be applied to meats, packaged to prevent recontamination, resulting in a shelf-stable product; the objective may also be to inactivate pathogenic bacteria, parasites and viruses in order to obtain a product which is acceptable from the point of view of public health. (orig.) [de

  18. Adaptive ridge regression for rare variant detection.

    Directory of Open Access Journals (Sweden)

    Haimao Zhan

    Full Text Available It is widely believed that both common and rare variants contribute to the risks of common diseases or complex traits and the cumulative effects of multiple rare variants can explain a significant proportion of trait variances. Advances in high-throughput DNA sequencing technologies allow us to genotype rare causal variants and investigate the effects of such rare variants on complex traits. We developed an adaptive ridge regression method to analyze the collective effects of multiple variants in the same gene or the same functional unit. Our model focuses on continuous trait and incorporates covariate factors to remove potential confounding effects. The proposed method estimates and tests multiple rare variants collectively but does not depend on the assumption of same direction of each rare variant effect. Compared with the Bayesian hierarchical generalized linear model approach, the state-of-the-art method of rare variant detection, the proposed new method is easy to implement, yet it has higher statistical power. Application of the new method is demonstrated using the well-known data from the Dallas Heart Study.

  19. Adaptive ridge regression for rare variant detection.

    Science.gov (United States)

    Zhan, Haimao; Xu, Shizhong

    2012-01-01

    It is widely believed that both common and rare variants contribute to the risks of common diseases or complex traits and the cumulative effects of multiple rare variants can explain a significant proportion of trait variances. Advances in high-throughput DNA sequencing technologies allow us to genotype rare causal variants and investigate the effects of such rare variants on complex traits. We developed an adaptive ridge regression method to analyze the collective effects of multiple variants in the same gene or the same functional unit. Our model focuses on continuous trait and incorporates covariate factors to remove potential confounding effects. The proposed method estimates and tests multiple rare variants collectively but does not depend on the assumption of same direction of each rare variant effect. Compared with the Bayesian hierarchical generalized linear model approach, the state-of-the-art method of rare variant detection, the proposed new method is easy to implement, yet it has higher statistical power. Application of the new method is demonstrated using the well-known data from the Dallas Heart Study.

  20. Effect of a high protein meat diet on muscle and cognitive functions: A randomised controlled dietary intervention trial in healthy men

    DEFF Research Database (Denmark)

    Jakobsen, Lene H.; Kondrup, Jens; Zellner, Maria

    2011-01-01

    BackgroundRecommendations to use other criteria than N-balance for defining protein requirements have been proposed. However, little evidence to support other measures such as physiological functions is available. ObjectiveTo investigate the effects of a usual (UP) versus a high protein (HP) diet...... on muscle function, cognitive function, quality of life and biochemical regulators of protein metabolism. DesignA randomised intervention study was conducted with 23 healthy males (aged 19–31 yrs). All subjects consumed a Usual Protein (UP) diet (1.5 g protein/kg BW) for a 1-wk run-in period before...... the intervention period where they were assigned to either a UP or a High Protein (HP) diet (3.0 g protein/kg BW) for 3-wks with controlled intake of food and beverages. Blood and urine samples were taken along with measurements of physiological functions at baseline and at the end of the intervention period...

  1. A putative Lynch syndrome family carrying MSH2 and MSH6 variants of uncertain significance-functional analysis reveals the pathogenic one

    DEFF Research Database (Denmark)

    Kantelinen, Jukka; Hansen, Thomas V O; Kansikas, Minttu

    2011-01-01

    Inherited pathogenic mutations in the mismatch repair (MMR) genes, MSH2, MLH1, MSH6, and PMS2 predispose to Lynch syndrome (LS). However, the finding of a variant or variants of uncertain significance (VUS) in affected family members complicates the risk assessment. Here, we describe a putative LS...... and the tumor pathological data suggested that the missense variation in MSH2, the more common susceptibility gene in LS, would be the predisposing alteration. However, MSH2 VUS was surprisingly found to be MMR proficient in an in vitro MMR assay and a tolerant alteration in silico. By supplying evidence...... identified VUS before predictive gene testing and genetic counseling are offered to a family....

  2. NEW MEAT PRODUCTS WITH IMMUNOMODULATORY EFFECT CREATION METHOD

    Directory of Open Access Journals (Sweden)

    I. V. Kaltovich

    2016-01-01

    Full Text Available New meat products with immunomodulatory effect creation method reflecting differential characteristics of technological stages of manufacture of those types of meat products, including issues on the selection of primary and secondary raw materials, guidelines for development of formulations and production technologies, legislative requirements towards its labeling, etc, has been developed for the first time. A list of prospective meat raw materials for the manufacture of products with immunomodulatory effect was established: beef, pork, rabbit meat, broiler chicken meat, turkey, veal, ostrich meat, which have high content of protein (14,3– 21,7%, low content of fat (1,2–16,1%, excluding pork (33,3%, high levels of minimum amino-acid score (90,0–104,0%, protein quality indicator(0,91–1,64, essential amino acid index (1,16-1,25, coefficient of utility of amino acid content (0,72–0,86 and close to optimum fatty acid content, and also contain a great number of vitamins and minerals which play a significant role for immunity improvement. It was determined that the following functional ingredients are recommended to use: amino acids (valine, leucine, isoleucine, methionine, threonine, arginine, tryptophan, lysine, histidin, phenylalanyl, vitamins and provitamins (C,E, beta-carotene, B vitamins(Bc, B12, PP, etc., P(bioflavonoid complex, H, K, minerals (calcium, magnesium, iron, cuprum, zinc, manganese, selenium, polyunsaturated fatty acids omega-3 and omega-6, pseudo-vitamins (L-carnitin, coenzyme Q10, polysaccharides and peptides naturally occurring(squalen, B-Carotene, ginger, shiitake mushrooms, probiotics and prebiotics, glutathione, indole and lycopienes, bioflavonoids, L-arginine, N-acetylcysteine, gel from seaweed «Lamifaren». The use of the developed meat products with immunomodulatory effect creation method by process engineers of meat processing factories will allow them to form a single scientifically grounded approach during the

  3. Meat cooking shrinkage: Measurement of a new meat quality parameter.

    Science.gov (United States)

    Barbera, S; Tassone, S

    2006-07-01

    A parameter, meat cooking shrinkage (MCS), has been introduced based on investigations carried out on meat shrinkage caused by heat during cooking. MCS is the difference between the raw and cooked areas of the meat sample, expressed as a percentage of the raw area. The method uses a disk of meat (10mm thick and 55mm wide) measured before and after cooking in a hot air oven at 165°C for 10min, the meat having reached an internal temperature of 70°C. Video image analysis was used to measure the meat sample area. The proposed MCS protocol permits us to measure cooking loss and to reduce cost and variability, moreover it could be improved to obtain color and marbling measurements by developing the image analysis software. Analysing two or more parameters on the same sample, the correlations among them should improve analysis efficacy. A detailed description of the measurement protocol of MCS is reported as well as its application to beef and pork.

  4. Effect of lyophilized water extracts of Melissa officinalis on the stability of algae and linseed oil-in-water emulsion to be used as a functional ingredient in meat products.

    Science.gov (United States)

    de Ciriano, Mikel García-Iñiguez; Rehecho, Sheyla; Calvo, Maria Isabel; Cavero, Rita Yolanda; Navarro, Iñigo; Astiasarán, Iciar; Ansorena, Diana

    2010-06-01

    Previous work pointed out the possibility to enhance the nutritional value of meat products using long chain omega-3 PUFA enriched emulsions. Oil-in-water emulsions elaborated with a mixture of algae and linseed oils (15:10) in order to be used as functional ingredient were stabilized with BHA (butylhydroxyanisol) or with a lyophilized water extract of Melissa officinalis L. (Lemon balm). The lipid profile of the oil mixture showed a high amount of DHA (31.7%), oleic (25.4%) and alpha-linolenic acid (12.7%) resulting in a very low omega-6/omega-3 ratio (0.12). The lyophilized extract of M. officinalis showed a high antioxidant activity (being 62ppm of the lyophilized water extract of Melissa equivalent to 200ppm of BHA, using the DPPH assay as reference), and high total phenolic content. Studying the oxidation process in the emulsions during 15days at room temperature, it could be concluded that this extract was as efficient as BHA in order to control the thiobarbituric acid reactive substances (TBARS) formation. Copyright 2010 Elsevier Ltd. All rights reserved.

  5. 9 CFR 319.500 - Meat pies.

    Science.gov (United States)

    2010-01-01

    ... CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Meat Food Entree Products, Pies, and Turnovers § 319.500 Meat pies. Meat pies such as “Beef Pie,” “Veal Pie,” and “Pork Pie” shall contain meat... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Meat pies. 319.500 Section 319.500...

  6. The Ethics of Producing In Vitro Meat

    OpenAIRE

    Schaefer, G Owen; Savulescu, Julian

    2014-01-01

    The prospect of consumable meat produced in a laboratory setting without the need to raise and slaughter animals is both realistic and exciting. Not only could such in vitro meat become popular due to potential cost savings, but it also avoids many of the ethical and environmental problems with traditional meat productions. However, as with any new technology, in vitro meat is likely to face some detractors. We examine in detail three potential objections: 1) in vitro meat is disrespectful, e...

  7. Changes of meat colour during storage

    OpenAIRE

    Maria Bocian; Hanna Jankowiak; Wojciech Kapelański

    2015-01-01

    The study investigated a relation between objective colour measurement and standard meat quality traits together with changes of meat colour parameters (∆) during the 48 h storage time. Analysed meat derived from 30 market pigs F1 (plw × pl) originated from Kuyavian--Pomeranian voivodeship. In the samples taken from longissimus lumborum muscle at 48 h post mortem the pH48, visual colour intensity and meat heme pigment concentration, as well as meat holding capacity, drip loss and ...

  8. Impact of extruded flaxseed meal supplemented diet on growth performance, oxidative stability and quality of broiler meat and meat products.

    Science.gov (United States)

    Anjum, Faqir Muhammad; Haider, Muhammad Faizan; Khan, Muhammad Issa; Sohaib, Muhammad; Arshad, Muhammad Sajid

    2013-02-08

    This study was intended to explore the effect of extruded flaxseed meal supplemented diet on broiler growth performance, oxidative stability and organoleptic characteristics of broiler meat and meat products. 120 (day old) broiler chicks were randomly allotted to 12 experimental groups and fed on diets containing extruded flaxseed meal at 0, 5, 10 and 15%. The supplementation of extruded flaxseed in the diet decreases the body weight gain, feed intake and increased feed conversion ratio (FCR) values of broilers. The antioxidant enzymes were strongly influenced by different levels of extruded flaxseed supplementation among treatments. The TBARS assay revealed that maximum malondialdehyde were produced in T3 containing highest extruded flaxseed level (15%) and minimum malondialdehyde were produced in T0 treatment having no extruded flaxseed. The TBARS values ranged from 0.850-2.106 and 0.460-1.052 in leg and breast met respectively. The Free radical scavenging activity varied significantly and DPPH values of breast meat ranged from 20.70% to 39.09% and in leg meat 23.53% to 43.09% respectively. The sensory acceptability of broiler meat nuggets was decreased with the increase in the level of flaxseeds due to the lipid peroxidation of polyunsaturated fatty acids (PUFA) which generated off flavors and bad odors. Feeding extruded flaxseed to chicken through feed strongly inflated the quality and functional properties, fatty acid contents and reduced the oxidative stability of broiler meat and meat products. The present study concludes that up to 10% of flaxseed meal may be used in broiler diet to enhance the omega 3 fatty acids content in the broiler meat.

  9. Impact of extruded flaxseed meal supplemented diet on growth performance, oxidative stability and quality of broiler meat and meat products

    Directory of Open Access Journals (Sweden)

    Anjum Faqir Muhammad

    2013-02-01

    Full Text Available Abstract This study was intended to explore the effect of extruded flaxseed meal supplemented diet on broiler growth performance, oxidative stability and organoleptic characteristics of broiler meat and meat products. 120 (day old broiler chicks were randomly allotted to 12 experimental groups and fed on diets containing extruded flaxseed meal at 0, 5, 10 and 15%. The supplementation of extruded flaxseed in the diet decreases the body weight gain, feed intake and increased feed conversion ratio (FCR values of broilers. The antioxidant enzymes were strongly influenced by different levels of extruded flaxseed supplementation among treatments. The TBARS assay revealed that maximum malondialdehyde were produced in T3 containing highest extruded flaxseed level (15% and minimum malondialdehyde were produced in T0 treatment having no extruded flaxseed. The TBARS values ranged from 0.850-2.106 and 0.460-1.052 in leg and breast met respectively. The Free radical scavenging activity varied significantly and DPPH values of breast meat ranged from 20.70% to 39.09% and in leg meat 23.53% to 43.09% respectively. The sensory acceptability of broiler meat nuggets was decreased with the increase in the level of flaxseeds due to the lipid peroxidation of polyunsaturated fatty acids (PUFA which generated off flavors and bad odors. Feeding extruded flaxseed to chicken through feed strongly inflated the quality and functional properties, fatty acid contents and reduced the oxidative stability of broiler meat and meat products. The present study concludes that up to 10% of flaxseed meal may be used in broiler diet to enhance the omega 3 fatty acids content in the broiler meat.

  10. MODERN TECHNOLOGY OF FERMENTED MEAT PRODUCTS

    Directory of Open Access Journals (Sweden)

    L. V. Antipova

    2015-01-01

    Full Text Available Summary. New trends of meat industry development, on the example of sausages are shown. The detailed description of indicators of quality of meat raw materials, auxiliary materials and their influence on the processes of tissue and microbial fermentation in the process of ripening raw sausages. Measures for improving the quality control of meat raw materials, auxiliary materials, as well as the processing conditions in all stages of production of smoked products are suggested. The modern technology of production of raw sausages with starter cultures and complex products, allowing better standardization process is considered. Questions of chemistry of color formation, the formation of taste and flavor, textures and the suppression of undesired microflora in foods in general, and in particular the raw sausage are thoroughly covered. Ideas about factors affecting the formation of color in sausages are given. It is pointed out that the susceptibility to oxidation of nitrosilmioglobin is directly related to the fat oxidation in the whole redox potential. Trends in the market of raw sausages are shown. Requirements used in the meat industry to starting cultures are shown. Recommendations on the rational use of starter cultures, and other functional additives in technology of uncooked fermented products, which are used to improve the quality and ensure a high level of product safety are given. The characteristic of the innovative series of starter cultures Protect, its species belonging and qualitative composition, providing a unique protection system in the process of ripening and storage of smoked products is given. The properties are proved on the example of smoked poultry sausage.

  11. Single scan parameterization of space-variant point spread functions in image space via a printed array: the impact for two PET/CT scanners

    Energy Technology Data Exchange (ETDEWEB)

    Kotasidis, F A; Matthews, J C; Angelis, G I; Noonan, P J; Jackson, A [Imaging, Genomics and Proteomics, Wolfson Molecular Imaging Centre, MAHSC, University of Manchester, Manchester (United Kingdom); Price, P [Academic Department of Radiation Oncology, University of Manchester, Manchester (United Kingdom); Lionheart, W R [School of Mathematics, Alan Turing Building, University of Manchester, Manchester (United Kingdom); Reader, A J, E-mail: fotis.kotasidis@mmic.man.ac.uk [Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC (Canada)

    2011-05-21

    Incorporation of a resolution model during statistical image reconstruction often produces images of improved resolution and signal-to-noise ratio. A novel and practical methodology to rapidly and accurately determine the overall emission and detection blurring component of the system matrix using a printed point source array within a custom-made Perspex phantom is presented. The array was scanned at different positions and orientations within the field of view (FOV) to examine the feasibility of extrapolating the measured point source blurring to other locations in the FOV and the robustness of measurements from a single point source array scan. We measured the spatially-variant image-based blurring on two PET/CT scanners, the B-Hi-Rez and the TruePoint TrueV. These measured spatially-variant kernels and the spatially-invariant kernel at the FOV centre were then incorporated within an ordinary Poisson ordered subset expectation maximization (OP-OSEM) algorithm and compared to the manufacturer's implementation using projection space resolution modelling (RM). Comparisons were based on a point source array, the NEMA IEC image quality phantom, the Cologne resolution phantom and two clinical studies (carbon-11 labelled anti-sense oligonucleotide [{sup 11}C]-ASO and fluorine-18 labelled fluoro-l-thymidine [{sup 18}F]-FLT). Robust and accurate measurements of spatially-variant image blurring were successfully obtained from a single scan. Spatially-variant resolution modelling resulted in notable resolution improvements away from the centre of the FOV. Comparison between spatially-variant image-space methods and the projection-space approach (the first such report, using a range of studies) demonstrated very similar performance with our image-based implementation producing slightly better contrast recovery (CR) for the same level of image roughness (IR). These results demonstrate that image-based resolution modelling within reconstruction is a valid alternative to

  12. The Effect of Turmeric (Curcuma longa Extract on the Functionality of the Solute Carrier Protein 22 A4 (SLC22A4 and Interleukin-10 (IL-10 Variants Associated with Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Mark J. McCann

    2014-10-01

    Full Text Available Inflammatory bowel disease (IBD is a chronic relapsing disease. Genetic predisposition to the disease reduces an individual’s capacity to respond appropriately to environmental challenges in the intestine leading to inappropriate inflammation. IBD patients often modify their diet to mitigate or reduce the severity of inflammation. Turmeric (Curcuma longa L., Zingiberaceae has historically been used in Chinese, Hindu, and Ayurvedic medicine over several centuries to treat inflammatory disorders. To understand how turmeric may influence the consequences of a genetic predisposition to inappropriate inflammation, we used HEK293 cells to examine the in vitro capacity of turmeric extract and fractions to affect the functionality of two gene variants, solute carrier protein 22 A4 (SLC22A4, rs1050152 and interleukin-10 (IL-10, rs1800896 associated with IBD. We found that a turmeric extract and several chromatographically separated fractions beneficially affected the variants of SLC22A4 and IL-10 associated with IBD, by reducing inappropriate epithelial cell transport (SLC22A4, 503F and increasing anti-inflammatory cytokine gene promoter activity (IL-10, −1082A. The effect of turmeric on the IL-10 variant was strongly associated with the curcumin content of the extract and its fractions.

  13. The effect of turmeric (Curcuma longa) extract on the functionality of the solute carrier protein 22 A4 (SLC22A4) and interleukin-10 (IL-10) variants associated with inflammatory bowel disease.

    Science.gov (United States)

    McCann, Mark J; Johnston, Sarah; Reilly, Kerri; Men, Xuejing; Burgess, Elaine J; Perry, Nigel B; Roy, Nicole C

    2014-10-13

    Inflammatory bowel disease (IBD) is a chronic relapsing disease. Genetic predisposition to the disease reduces an individual's capacity to respond appropriately to environmental challenges in the intestine leading to inappropriate inflammation. IBD patients often modify their diet to mitigate or reduce the severity of inflammation. Turmeric (Curcuma longa L., Zingiberaceae) has historically been used in Chinese, Hindu, and Ayurvedic medicine over several centuries to treat inflammatory disorders. To understand how turmeric may influence the consequences of a genetic predisposition to inappropriate inflammation, we used HEK293 cells to examine the in vitro capacity of turmeric extract and fractions to affect the functionality of two gene variants, solute carrier protein 22 A4 (SLC22A4, rs1050152) and interleukin-10 (IL-10, rs1800896) associated with IBD. We found that a turmeric extract and several chromatographically separated fractions beneficially affected the variants of SLC22A4 and IL-10 associated with IBD, by reducing inappropriate epithelial cell transport (SLC22A4, 503F) and increasing anti-inflammatory cytokine gene promoter activity (IL-10, -1082A). The effect of turmeric on the IL-10 variant was strongly associated with the curcumin content of the extract and its fractions.

  14. The Effect of Turmeric (Curcuma longa) Extract on the Functionality of the Solute Carrier Protein 22 A4 (SLC22A4) and Interleukin-10 (IL-10) Variants Associated with Inflammatory Bowel Disease

    Science.gov (United States)

    McCann, Mark J.; Johnston, Sarah; Reilly, Kerri; Men, Xuejing; Burgess, Elaine J.; Perry, Nigel B.; Roy, Nicole C.

    2014-01-01

    Inflammatory bowel disease (IBD) is a chronic relapsing disease. Genetic predisposition to the disease reduces an individual’s capacity to respond appropriately to environmental challenges in the intestine leading to inappropriate inflammation. IBD patients often modify their diet to mitigate or reduce the severity of inflammation. Turmeric (Curcuma longa L., Zingiberaceae) has historically been used in Chinese, Hindu, and Ayurvedic medicine over several centuries to treat inflammatory disorders. To understand how turmeric may influence the consequences of a genetic predisposition to inappropriate inflammation, we used HEK293 cells to examine the in vitro capacity of turmeric extract and fractions to affect the functionality of two gene variants, solute carrier protein 22 A4 (SLC22A4, rs1050152) and interleukin-10 (IL-10, rs1800896) associated with IBD. We found that a turmeric extract and several chromatographically separated fractions beneficially affected the variants of SLC22A4 and IL-10 associated with IBD, by reducing inappropriate epithelial cell transport (SLC22A4, 503F) and increasing anti-inflammatory cytokine gene promoter activity (IL-10, −1082A). The effect of turmeric on the IL-10 variant was strongly associated with the curcumin content of the extract and its fractions. PMID:25314644

  15. Meat and Poultry Labeling Terms

    Science.gov (United States)

    ... Web Content Viewer (JSR 286) Actions ${title} Loading... Meat and Poultry Labeling Terms What does 'mechanically separated ... Top of Page ] NATURAL: A product containing no artificial ingredient or added color and is only minimally ...

  16. Meat production perspective in Yucatan

    Directory of Open Access Journals (Sweden)

    Victor M. Toledo-Lopez

    2011-12-01

    Full Text Available The evolution of meat production in Mexico during the last decade is the result of the complex interaction between different areas of livestock production and consumers’ preferences, being the former widely influenced by new tendencies and purchasing capacity. In Yucatan, there are two meat product processing plants. Yucatan’s research projects are basically focused to production, handling and genetics. This research is developed in Research Centers like Universidad Autonoma Yucatan’s Ciencias Biologicas Agropecuarias Campus, INIFAP Mococha, Instituto Tecnologico Conkal and Instituto Tecnologoco Merida. Many projects are inter-institutional and others by Cuerpos Academicos inside the institutions. Grants are provided by state, national or international dependencies. In the Instituto Tecnologico Merida research projects are on different animals’ meat quality and novel meat products.

  17. Variants of cellobiohydrolases

    Energy Technology Data Exchange (ETDEWEB)

    Bott, Richard R.; Foukaraki, Maria; Hommes, Ronaldus Wilhelmus; Kaper, Thijs; Kelemen, Bradley R.; Kralj, Slavko; Nikolaev, Igor; Sandgren, Mats; Van Lieshout, Johannes Franciscus Thomas; Van Stigt Thans, Sander

    2018-04-10

    Disclosed are a number of homologs and variants of Hypocrea jecorina Ce17A (formerly Trichoderma reesei cellobiohydrolase I or CBH1), nucleic acids encoding the same and methods for producing the same. The homologs and variant cellulases have the amino acid sequence of a glycosyl hydrolase of family 7A wherein one or more amino acid residues are substituted and/or deleted.

  18. Effect of a high protein meat diet on muscle and cognitive functions: a randomised controlled dietary intervention trial in healthy men.

    Science.gov (United States)

    Jakobsen, Lene H; Kondrup, Jens; Zellner, Maria; Tetens, Inge; Roth, Erich

    2011-06-01

    Recommendations to use other criteria than N-balance for defining protein requirements have been proposed. However, little evidence to support other measures such as physiological functions is available. To investigate the effects of a usual (UP) versus a high protein (HP) diet on muscle function, cognitive function, quality of life and biochemical regulators of protein metabolism. A randomised intervention study was conducted with 23 healthy males (aged 19-31 yrs). All subjects consumed a Usual Protein (UP) diet (1.5 g protein/kg BW) for a 1-wk run-in period before the intervention period where they were assigned to either a UP or a High Protein (HP) diet (3.0 g protein/kg BW) for 3-wks with controlled intake of food and beverages. Blood and urine samples were taken along with measurements of physiological functions at baseline and at the end of the intervention period. The HP group improved their reaction time significantly compared with the UP group. Branched chain amino acids and phenylalanine in plasma were significantly increased following the HP diet, which may explain the improved reaction time. Healthy young males fed a HP diet improved reaction time. No adverse effects of the HP diet were observed. This trial was registered at www.clinicaltrials.gov as NCT00621231. Copyright © 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  19. Prospects of achieving the world standards of meat consumption in Ukraine

    Directory of Open Access Journals (Sweden)

    Skrypnyk Andrii V.

    2014-01-01

    Full Text Available The article analyses possible variants of growth of the level of consumption of meat products (beef, pork, and poultry during the nearest 6 years. The article considers, as a basic variant, planned indicators provided by the Institute of Agrarian Economy and approved in “Strategy of Development of the Agrarian Sector for the Period until 2020”. Based on the time series of meat products consumption during 2000 – 2012, the article builds a forecast of consumption until 2020 using methods of econometric analysis. The article compares the obtained forecast indicators with official indicators, on the basis of which a conclusion is made with respect to groundlessness of planned indicators of beef consumption, for realisation of which the 15% annual growth is needed. In order to specify the level of meat products consumption depending on the level of income, the whole population was presented in the form of three groups: under-provided (40%, averagely provided (30% and well-provided (30%. Optimisation task for maximum of caloricity of the meat products basket, with availability of budget and production (built up on the forecast restrictions, was solved for each group. In the result an optimal ration, which differs significantly both in composition and caloricity, was obtained for each group. Moreover, the article shows that in order to achieve these meat products baskets, it is necessary to bring beef import up to 210 thousand tonnes and the unclaimed 190 thousand tonnes of pork and 210 tonnes of poultry could be exported.

  20. Meat production perspective in Yucatan

    OpenAIRE

    Victor M. Toledo-Lopez

    2011-01-01

    The evolution of meat production in Mexico during the last decade is the result of the complex interaction between different areas of livestock production and consumers’ preferences, being the former widely influenced by new tendencies and purchasing capacity. In Yucatan, there are two meat product processing plants. Yucatan’s research projects are basically focused to production, handling and genetics. This research is developed in Research Centers like Universidad Autonoma Yucatan’s Ciencia...

  1. Utilizing High Pressure Processing to Induce Structural Changes in Dairy and Meat Products

    DEFF Research Database (Denmark)

    Orlien, Vibeke

    2017-01-01

    . In this article the HP modification of milk and meat proteins is evaluated in relation to the changed molecular functionality and product texture. The underlying mechanisms of the pressure-induced molecular changes are surveyed and related to practical applications in the view of HP-produced milk and meat...

  2. Editor's Highlight: Modifying Role of Endothelial Function Gene Variants on the Association of Long-Term PM2.5 Exposure With Blood DNA Methylation Age: The VA Normative Aging Study.

    Science.gov (United States)

    Nwanaji-Enwerem, Jamaji C; Bind, Marie-Abele; Dai, Lingzhen; Oulhote, Youssef; Colicino, Elena; Di, Qian; Just, Allan C; Hou, Lifang; Vokonas, Pantel; Coull, Brent A; Weisskopf, Marc G; Baccarelli, Andrea A; Schwartz, Joel D

    2017-07-01

    Recent studies have reported robust associations of long-term PM2.5 exposure with DNA methylation-based measures of aging; yet, the molecular implications of these relationships remain poorly understood. We evaluated if genetic variation in 3 biological pathways implicated in PM2.5-related disease-oxidative stress, endothelial function, and metal processing-could modify the effect of PM2.5 on DNAm-age, one prominent DNA methylation-based measure of biological age. This analysis was based on 552 individuals from the Normative Aging Study with at least one visit between 2000 and 2011 (n = 940 visits). A genetic-score approach was used to calculate aging-risk variant scores for endothelial function, oxidative stress, and metal processing pathways. One-year PM2.5 and PM2.5 component (sulfate and ammonium) levels at participants' addresses were estimated using the GEOS-chem transport model. Blood DNAm-age was calculated using CpG sites on the Illumina HumanMethylation450 BeadChip. In fully-adjusted linear mixed-effects models, the effects of sulfate on DNAm-age (in years) were greater in individuals with high aging-risk endothelial function variant scores when compared with individuals with low aging-risk endothelial function variant scores (Pinteraction = 0.0007; βHigh = 1.09, 95% CIHigh: 0.70, 1.48; βLow = 0.40, 95% CILow: 0.14, 0.67). Similar trends were observed in fully adjusted models of ammonium and total PM2.5 alone. No effect modification was observed by oxidative stress and metal processing variant scores. Secondary analyses revealed significant associations of serum endothelial markers, intercellular adhesion molecule-1 (β = 0.01, 95% CI: 0.002, 0.012) and vascular cell adhesion molecule-1 (β = 0.002, 95% CI: 0.0005, 0.0026), with DNAm-age. Our results add novel evidence that endothelial physiology may be important to DNAm-age relationships, but further research is required to establish their generalizability. © The Author 2017. Published by

  3. Genetic association study of adiposity and melanocortin-4 receptor (MC4R common variants: replication and functional characterization of non-coding regions.

    Directory of Open Access Journals (Sweden)

    Daniel S Evans

    Full Text Available Common genetic variants 3' of MC4R within two large linkage disequilibrium (LD blocks spanning 288 kb have been associated with common and rare forms of obesity. This large association region has not been refined and the relevant DNA segments within the association region have not been identified. In this study, we investigated whether common variants in the MC4R gene region were associated with adiposity-related traits in a biracial population-based study. Single nucleotide polymorphisms (SNPs in the MC4R region were genotyped with a custom array and a genome-wide array and associations between SNPs and five adiposity-related traits were determined using race-stratified linear regression. Previously reported associations between lower BMI and the minor alleles of rs2229616/Val103Ile and rs52820871/Ile251Leu were replicated in white female participants. Among white participants, rs11152221 in a proximal 3' LD block (closer to MC4R was significantly associated with multiple adiposity traits, but SNPs in a distal 3' LD block (farther from MC4R were not. In a case-control study of severe obesity, rs11152221 was significantly associated. The association results directed our follow-up studies to the proximal LD block downstream of MC4R. By considering nucleotide conservation, the significance of association, and proximity to the MC4R gene, we identified a candidate MC4R regulatory region. This candidate region was sequenced in 20 individuals from a study of severe obesity in an attempt to identify additional variants, and the candidate region was tested for enhancer activity using in vivo enhancer assays in zebrafish and mice. Novel variants were not identified by sequencing and the candidate region did not drive reporter gene expression in zebrafish or mice. The identification of a putative insulator in this region could help to explain the challenges faced in this study and others to link SNPs associated with adiposity to altered MC4R expression.

  4. Muscle composition slightly affects in vitro digestion of aged and cooked meat: identification of associated proteomic markers.

    Science.gov (United States)

    Bax, M-L; Sayd, T; Aubry, L; Ferreira, C; Viala, D; Chambon, C; Rémond, D; Santé-Lhoutellier, V

    2013-02-15

    Meat is an appropriate source of proteins and minerals for human nutrition. Technological treatments modify the physical-chemical properties of proteins, making them liable to decrease the nutritional potential of meat. To counteract this damage, antioxidants and chaperone proteins in muscle cells can prevent oxidation, restore the function of denatured proteins, and thus prevent aggregation. This study aimed to explore the impact of indoor vs outdoor-reared meat protein composition on digestion and to associate protein markers to in vitro digestion parameters. Indoor-reared meat tended to show less oxidation and denaturation than outdoor-reared meat and was characterised by an overexpression of contractile and chaperone proteins. Outdoor-reared meat showed amplification of antioxidant and detoxification metabolism defending against oxidised compounds. Impacts on digestion remained minor. Several protein markers of in vitro digestion parameters were found for aged and cooked meat, linked to the detoxification process and to muscle contraction. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Splicing analysis of 14 BRCA1 missense variants classifies nine variants as pathogenic

    DEFF Research Database (Denmark)

    Ahlborn, Lise B; Dandanell, Mette; Steffensen, Ane Y

    2015-01-01

    Pathogenic germline mutations in the BRCA1 gene predispose carriers to early onset breast and ovarian cancer. Clinical genetic screening of BRCA1 often reveals variants with uncertain clinical significance, complicating patient and family management. Therefore, functional examinations are urgently...

  6. Significance of authenticity in meat and meat products in Iran

    Directory of Open Access Journals (Sweden)

    Tahereh Rezazadeh

    2014-06-01

    Full Text Available The Authenticity of meat products is very important for religious and health reasons in Iran. According to legislation in Iran, the consumption and importation of pork, horse, donkey and cat products should be banned. Therefore, the identification of meat products cannot be judged solely by its appearance. This issue led to the authenticity of bovine, sheep, pig, horse, donkey, chicken and soya (Glycine max in raw and processed meat products.In this study, specific primers were designed for the identification of pig ( base pair, donkey (325 base pair, chicken (391 base pair, sheep (499 base pair, horse (607 base pair, soya (707 base pair and bovine (853 base pair by Polymerase chain reaction. Following PCR, expected,, , 499,,  and  base pair fragments were detectable in pig, donkey, chicken, sheep, horse, soya and bovine, respectively. This protocol can be used for identification of raw and processed meat products in various animal species for replication to regulatory obligations for meat species safety in Iran.

  7. Nanotechnology in Meat Processing and Packaging: Potential Applications — A Review

    Directory of Open Access Journals (Sweden)

    Karna Ramachandraiah

    2015-02-01

    Full Text Available Growing demand for sustainable production, increasing competition and consideration of health concerns have led the meat industries on a path to innovation. Meat industries across the world are focusing on the development of novel meat products and processes to meet consumer demand. Hence, a process innovation, like nanotechnology, can have a significant impact on the meat processing industry through the development of not only novel functional meat products, but also novel packaging for the products. The potential benefits of utilizing nanomaterials in food are improved bioavailability, antimicrobial effects, enhanced sensory acceptance and targeted delivery of bioactive compounds. However, challenges exist in the application of nanomaterials due to knowledge gaps in the production of ingredients such as nanopowders, stability of delivery systems in meat products and health risks caused by the same properties which also offer the benefits. For the success of nanotechnology in meat products, challenges in public acceptance, economics and the regulation of food processed with nanomaterials which may have the potential to persist, accumulate and lead to toxicity need to be addressed. So far, the most promising area for nanotechnology application seems to be in meat packaging, but the long term effects on human health and environment due to migration of the nanomaterials from the packaging needs to be studied further. The future of nanotechnology in meat products depends on the roles played by governments, regulatory agencies and manufacturers in addressing the challenges related to the application of nanomaterials in food.

  8. Nanotechnology in Meat Processing and Packaging: Potential Applications — A Review

    Science.gov (United States)

    Ramachandraiah, Karna; Han, Sung Gu; Chin, Koo Bok

    2015-01-01

    Growing demand for sustainable production, increasing competition and consideration of health concerns have led the meat industries on a path to innovation. Meat industries across the world are focusing on the development of novel meat products and processes to meet consumer demand. Hence, a process innovation, like nanotechnology, can have a significant impact on the meat processing industry through the development of not only novel functional meat products, but also novel packaging for the products. The potential benefits of utilizing nanomaterials in food are improved bioavailability, antimicrobial effects, enhanced sensory acceptance and targeted delivery of bioactive compounds. However, challenges exist in the application of nanomaterials due to knowledge gaps in the production of ingredients such as nanopowders, stability of delivery systems in meat products and health risks caused by the same properties which also offer the benefits. For the success of nanotechnology in meat products, challenges in public acceptance, economics and the regulation of food processed with nanomaterials which may have the potential to persist, accumulate and lead to toxicity need to be addressed. So far, the most promising area for nanotechnology application seems to be in meat packaging, but the long term effects on human health and environment due to migration of the nanomaterials from the packaging needs to be studied further. The future of nanotechnology in meat products depends on the roles played by governments, regulatory agencies and manufacturers in addressing the challenges related to the application of nanomaterials in food. PMID:25557827

  9. Snail meat: Significance and consumption

    Directory of Open Access Journals (Sweden)

    Dragićević Olgica

    2005-01-01

    Full Text Available The consumption of snail meat goes back to prehistoric times. Different ancient nations had snails on their menu, but Helices culture as a productive activity was born as a Roman culture. Some of the most economically important edible species are: Helix aspersa (Mtiller Helixpomatia (Linne, Helix iucorum (Linne, Helix aperta (Born, Eobania vermiculata (Miiller. Together with its tasie, snail meat has several advantages over others: quite low lipid rate and calorie values versus rich mineral, essential amino acid and fatty acid content. The composition of snail meat is presented. In addition, the composition of different snail species and the part analyzed (pedal mass and visceral mass is presented. Also, the differences in composition according to the species (snail meat horse/chicken meat, beef, swine meat, fish meat are presented. The French are the world's leading consumers of snails. !n France snails come to market in a variety of ways. Estimated consumption of snails in France is around 40 000 tones/year. Total French imports account for 25% of world imports. France is also the leading exporter of prepared snails, mainly sold as preserved snails and prepared dishes. Snail imports have been much higher than exports (65 tones exported in 2002. vs. 2.700 tones imported. Despite the large consumption, only 3% of snails in France come from production (farming. Italy is in second place in the world consumption of snails, and Spain and Germany are in the third and fourth place. The development of snails consumption in Italy is followed with the same amount of production of snails in the whole biological circle. In 2001, from 24,700 tons, 9,350 tons (37.8% came from production, 6 00 tons (2.4% came from nature, and 14,750 tons (59.70% came from imports (frozen, fresh and prepared snails. In Serbia, at the beginning of 2005, we had over 400 registered farms for snail production.

  10. The potentiality of synbiotic minced meat production

    OpenAIRE

    Hoda Khavaninzade; Mahnaz Hashemiravan; Shila Berenji

    2016-01-01

    Consumption of veal and mutton with high protein and the most important iron source at growth age is of great importance. Red meat has high vitamin (B12), mineral (zinc) and pigments. To produce function food, various compounds as probiotics, prebiotics and diet fiber and secondary plant metabolites as phenol compound are added to food products. The present study applied the mixture of mutton and veal, 0.5% Inulin and three levels of microbial inoculation of lactobacillus plantarum1.5× 107 ...

  11. Effect of antioxidants on thiobarbituric acid reactive substances, psychrotrophic bacteria and functional properties of mechanically deboned chicken meat irradiated with Cobalto-60 and electron beam sources

    International Nuclear Information System (INIS)

    Brito, Poliana de Paula; Azevedo, Heliana de; Roque, Claudio Vitor; Pomarico Neto, Walter

    2013-01-01

    Samples of MDCM with skin were divided into three groups: control (without antioxidants), Antioxidant 1 (Sodium Polyphosphate and Sodium Ascorbate and Antioxidant 2 (Rosemary Extract and α-Tocopherol. The three batches of samples were divided into nine groups: no antioxidant and non-irradiated (C), with antioxidant A1 and non-irradiated (A1), with antioxidant A2 and non-irradiated (A2) without antioxidant and irradiated in Cobalt-60 source (Co), with antioxidant A1 irradiated in Cobalt 60 source (A1Co) with antioxidant A2 irradiated in Cobalt-60 source (A2Co) with antioxidant A1 irradiated in Electron beam (A1Eb) and with antioxidant A2 irradiated in Electron beam (A2Eb). The samples was conditioned in a transparent, low density frozen overnight at a temperature of -18 ± 1 deg C in a chamber, and irradiated in this state with a dose of 3.0 kGy, used two sources of radiation: Cobalt-60 (3.1 kGy/h) and electron beam (7.86 kGy/s). After this process, the samples were evaluated during the refrigeration period (2 ± 1 deg C) for 11 days for the following analysis: total psychrotrophic bacteria count and thiobarbituric acid reactive substances (TBARS) and the analysis of functional properties were performed after the irradiation process. The use of the combination of rosemary antioxidant and α-tocopherol were able to significantly decrease TBARS values caused by the irradiation of samples in MDCM cobalt-60 sources and electron beam, and show a synergetic effect to processing with ionizing radiation to reduce of psychrotrophic bacteria count. The use of irradiation processing of MDCM did not negatively affect the functional properties studied. (author)

  12. Polymorphisms in the xenobiotic transporter Multidrug Resistance 1 (MDR1) and interaction with meat intake in relation to risk of colorectal cancer in a Danish prospective case-cohort study

    International Nuclear Information System (INIS)

    Andersen, Vibeke; Østergaard, Mette; Christensen, Jane; Overvad, Kim; Tjønneland, Anne; Vogel, Ulla

    2009-01-01

    The xenobiotic transporters, Multidrug Resistance 1 (MDR1/ABCB1) and Breast Cancer Resistance Protein (BCRP/ABCG2) may restrict intestinal absorption of various carcinogens, including heterocyclic amines (HCA) and polycyclic aromatic hydrocarbons (PAH). Cyclooxygenase-2 (COX-2) derived prostaglandins promote gastrointestinal carcinogenesis, affecting angiogenesis, apoptosis, and invasiveness. The aim of this study was to investigate if polymorphisms in these genes were associated with risk of colorectal cancer (CRC), and to investigate possible interactions with lifestyle factors such as smoking, meat consumption, and NSAID use. The following polymorphisms were analyzed; a synonymous MDR1 C3435T (rs1045642) in exon26, G-rs3789243-A in intron3, the functional BCRP C421A (rs2231142), the two COX-2 A-1195G (rs689466) and G-765C (rs20417) in the promoter region, and the COX-2 T8473C (rs5275) polymorphisms in the 3'-untranslated region. The polymorphisms were assessed together with lifestyle factors in a nested case-cohort study of 359 cases and a random cohort sample of 765 participants from the Danish prospective Diet, Cancer and Health study. Carriers of the variant allele of MDR1 intron 3 polymorphism were at 1.52-fold higher risk of CRC than homozygous wild type allele carriers (Incidence rate ratio (IRR) = 1.52, 95% Confidence Interval (CI): 1.12-2.06). Carriers of the variant allele of MDR1 C3435T exon 26 had a lower risk of CRC than homozygous C-allele carriers (IRR = 0.71 (CI:0.50-1.00)). There was interaction between these MDR1 polymorphisms and intake of red and processed meat in relation to CRC risk. Homozygous MDR1 C3435T C-allele carriers were at 8% increased risk pr 25 gram meat per day (CI: 1.00-1.16) whereas variant allele carriers were not at increased risk (p for interaction = 0.02). COX-2 and BCRP polymorphisms were not associated with CRC risk. There was interaction between NSAID use and MDR1 C3435T and COX-2 T8473C (p-values for interaction 0

  13. Prostaglandin E₂ production in mice is reduced by consumption of range-fed sources of red meat.

    Science.gov (United States)

    Broughton, K Shane; Rule, Daniel C; Handrich, Eldon

    2011-12-01

    Many view bison as a healthful alternative to other red meat sources, and as a way to decrease health risks, they associate it with meat consumption. Using mice as a model for immune function, we hypothesized that consumption of meat from range-fed bison would decrease prostaglandin (PG) E₂ and alter prostacyclin (PGI₂) release upon immune challenge when compared with mice fed meat from grain-finished bison, range-fed beef, feedlot steers, free-ranging elk, or chicken breast. After 2 weeks on an experimental diet and inflammatory stimulation, mouse peritoneal macrophage was isolated and analyzed in 12 animals per diet. Peritoneal cell arachidonic acid increased in response to a chicken-based diet (P meat of range-fed beef, range-fed bison, and elk but was highest with meat of grain-finished beef and intermediate in mice fed chicken (P meat had the greatest PGI₂, whereas PGI₂ was decreased in mice fed meat of either range bison, range beef, or chicken (P meat of steers or bison finished in a feedlot. We conclude that consumption of meats characteristic of range-fed ruminants or wild ungulates supports reduced PGE₂ and greater PGI₂ synthesis, indicating potentially greater immune health and lower blood clotting potential than meat from grain-finished cattle or bison in this model system. Published by Elsevier Inc.

  14. Seaweed Polysaccharides (Laminarin and Fucoidan) as Functional Ingredients in Pork Meat: An Evaluation of Anti-Oxidative Potential, Thermal Stability and Bioaccessibility

    Science.gov (United States)

    Moroney, Natasha C.; O’Grady, Michael N.; Lordan, Sinéad; Stanton, Catherine; Kerry, Joseph P.

    2015-01-01

    The anti-oxidative potential of laminarin (L), fucoidan (F) and an L/F seaweed extract was measured using the DPPH free radical scavenging assay, in 25% pork (longissimus thoracis et lumborum (LTL)) homogenates (TBARS) (3 and 6 mg/mL) and in horse heart oxymyoglobin (OxyMb) (0.1 and 1 mg/mL). The DPPH activity of fresh and cooked minced LTL containing L (100 mg/g; L100), F100 and L/F100,300, and bioaccessibility post in vitro digestion (L/F300), was assessed. Theoretical cellular uptake of antioxidant compounds was measured in a transwell Caco-2 cell model. Laminarin displayed no activity and fucoidan reduced lipid oxidation but catalysed OxyMb oxidation. Fucoidan activity was lowered by cooking while the L/F extract displayed moderate thermal stability. A decrease in DPPH antioxidant activity of 44.15% and 36.63%, after 4 and 20 h respectively, indicated theoretical uptake of L/F antioxidant compounds. Results highlight the potential use of seaweed extracts as functional ingredients in pork. PMID:25903283

  15. Global antioxidant response of meat.

    Science.gov (United States)

    Carrillo, Celia; Barrio, Ángela; Del Mar Cavia, María; Alonso-Torre, Sara

    2017-06-01

    The global antioxidant response (GAR) method uses an enzymatic digestion to release antioxidants from foods. Owing to the importance of digestion for protein breakdown and subsequent release of bioactive compounds, the aim of the present study was to compare the GAR method for meat with the existing methodologies: the extraction-based method and QUENCHER. Seven fresh meats were analyzed using ABTS and FRAP assays. Our results indicated that the GAR of meat was higher than the total antioxidant capacity (TAC) assessed with the traditional extraction-based method. When evaluated with GAR, the thermal treatment led to an increase in the TAC of the soluble fraction, contrasting with a decreased TAC after cooking measured using the extraction-based method. The effect of thermal treatment on the TAC assessed by the QUENCHER method seemed to be dependent on the assay applied, since results from ABTS differed from FRAP. Our results allow us to hypothesize that the activation of latent bioactive peptides along the gastrointestinal tract should be taken into consideration when evaluating the TAC of meat. Therefore, we conclude that the GAR method may be more appropriate for assessing the TAC of meat than the existing, most commonly used methods. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  16. Development of industrial variant specification systems

    DEFF Research Database (Denmark)

    Hansen, Benjamin Loer

    acquisition and order fulfilment, i.e. the creation of drawings, bill-of-materials, routings, product descriptions, quote letters etc. The present thesis is rooted in the assumption that variant specification systems supporting the cross-functional processes of order acquisition and order fulfilment must...... be developed from a holistic and strategically anchored point of view. Another assumption is that this is a challenge for many industrial companies. Even though the literature presents many considerations on general issues covering new information technology, little work is found on the business perspectives...... to the four research tasks of the Ph.D. project: • Define and describe the variant specification system. • Create a procedure for the development of variant specification systems. • Create concepts, methods and tools to support the analysis and determination of the variant specification task. • Identify...

  17. Development of industrial variant specification systems

    DEFF Research Database (Denmark)

    Hansen, Benjamin Loer

    With globalisation and increased competition industrial companies must be prepared to satisfy individual customer needs and still stay competitive with regards to lead times, quality, and prices. These factors require companies to be better prepared to handle specification activities during order...... to the four research tasks of the Ph.D. project: • Define and describe the variant specification system. • Create a procedure for the development of variant specification systems. • Create concepts, methods and tools to support the analysis and determination of the variant specification task. • Identify...... are presented for analysing and determining the variant specification task. These are grouped in external and internal task variables. Additionally functional characteristics, which can be used for defining performance measures, are defined. Based in the concept of “focus” different levels of tasks...

  18. The influence of different stocking densities on biochemical composition of rainbow trout meat reared in a recirculating aquaculture system

    Directory of Open Access Journals (Sweden)

    Mirela Cretu

    2014-10-01

    Full Text Available The aim of this study is to evaluate the biochemical composition of rainbow trout meat, reared in a recirculating aquaculture system, at different stocking densities (DS1-2,64 kg/m3, DS2-5,16 kg/m3, DS3-7,12 kg/m3, DS4-9,42 kg/m3. The analyses were performed in the research laboratory of Aquaculture, Environmental Science and Cadastre Department – Faculty of Food Science and Engineering, from ,,Dunarea de Jos’’University of Galati. The content of meat proteins, fats, dry substance and ash was determined. After a 33 days experimental trial, the biochemical analysis of meat from all four experimental variants shows that protein content was higher in DS1 and DS4 variants, while the smallest amount of fats was quantified at DS1 and DS2 variants, without significant differences (p >0.05 for none of the biochemical compounds analyzed, at the mean comparison on experimental variants. Thus, it can be concluded that biochemical composition of rainbow trout meat was not influenced by the tested stocking densities.

  19. Evaluation of quality characteristics and functional properties of mechanically deboned chicken meats treated with different dose rates of ionizing radiation and use of antioxidants; Avaliacao de caracteristicas de qualidade e propriedades funcionais da carne mecanicamente separada de frango tratada com diferentes taxas de dose de radiacao ionizante e uso de antioxidantes

    Energy Technology Data Exchange (ETDEWEB)

    Brito, Poliana de Paula

    2012-07-01

    The Mechanically Deboned chicken meat (MDCM) is used in traditional meat products, in greater proportion in those emulsified, replacing meat raw materials more expensive. The raw material can have high MDCM the microbial load, as a result of contamination during processing or failure during the evisceration. The irradiation process is accepted as one of the most effective technologies when compared to conventional techniques of preservation, to reduce contamination of pathogens and spoilage. However, little information is available about the use and effects of different dose rates of ionizing radiation processing. Irradiation causes chemical changes in food, a major cause of deterioration of quality of raw or cooked meat products during refrigerated storage, frozen. The objective of this study was to evaluate the effects of different dose rates of ionizing radiation on the production of Thiobarbituric Acid Reactive Substances (TBARS), color, microbiological and sensory characteristics of mechanically deboned chicken added or without added antioxidants, during the cold storage and evaluation of functional properties. The results showed that among the tested dose rates using cobalt-60 source, dose rate of 4.04 kGy.h-1 was the best for processing MDCM. Furthermore, the use of the combination of rosemary antioxidant and α-tocopherol were able to reduce lipid oxidation generated by irradiation of the samples, showed a synergistic effect to the processing with ionizing radiation in reduction of psychrotrophic bacteria count and contributed to a better sensory quality. The use of radiation in the processing FDMI did not adversely affect the functional properties studied. (author)

  20. Genetic and functional identification of the likely causative variant for cholesterol gallstone disease at the ABCG5/8 lithogenic locus

    DEFF Research Database (Denmark)

    von Kampen, Oliver; Buch, Stephan; Nothnagel, Michael

    2013-01-01

    The sterolin locus (ABCG5/ABCG8) confers susceptibility for cholesterol gallstone disease in humans. Both the responsible variant and the molecular mechanism causing an increased incidence of gallstones in these patients have as yet not been identified. Genetic mapping utilized patient samples from...... Germany (2,808 cases, 2,089 controls), Chile (680 cases, 442 controls), Denmark (366 cases, 766 controls), India (247 cases, 224 controls), and China (280 cases, 244 controls). Analysis of allelic imbalance in complementary DNA (cDNA) samples from human liver (n = 22) was performed using pyrosequencing....... Transiently transfected HEK293 cells were used for [(3) H]-cholesterol export assays, analysis of protein expression, and localization of allelic constructs. Through fine mapping in German and Chilean samples, an ∼250 kB disease-associated interval could be defined for this locus. Lack of allelic imbalance...

  1. Lenalidomide enhances the function of chimeric antigen receptor T cells against the epidermal growth factor receptor variant III by enhancing immune synapses.

    Science.gov (United States)

    Kuramitsu, S; Ohno, M; Ohka, F; Shiina, S; Yamamichi, A; Kato, A; Tanahashi, K; Motomura, K; Kondo, G; Kurimoto, M; Senga, T; Wakabayashi, T; Natsume, A

    2015-10-01

    The epidermal growth factor receptor variant III (EGFRvIII) is exclusively expressed on the cell surface in ~50% of glioblastoma multiforme (GBM). This variant strongly and persistently activates the phosphatidylinositol 3-kinase-Akt signaling pathway in a ligand-independent manner resulting in enhanced tumorigenicity, cellular motility and resistance to chemoradiotherapy. Our group generated a recombinant single-chain variable fragment (scFv) antibody specific to the EGFRvIII, referred to as 3C10-scFv. In the current study, we constructed a lentiviral vector transducing the chimeric antigen receptor (CAR) that consisted of 3C10-scFv, CD3ζ, CD28 and 4-1BB (3C10-CAR). The 3C10-CAR-transduced peripheral blood mononuclear cells (PBMCs) and CD3(+) T cells specifically lysed the glioma cells that express EGFRvIII. Moreover, we demonstrated that CAR CD3(+) T cells migrated to the intracranial xenograft of GBM in the mice treated with 3C10-CAR PBMCs. An important and novel finding of our study was that a thalidomide derivative lenalidomide induced 3C10-CAR PBMC proliferation and enhanced the persistent antitumor effect of the cells in vivo. Lenalidomide also exhibited enhanced immunological synapses between the effector cells and the target cells as determined by CD11a and F-actin polymerization. Collectively, lentiviral-mediated transduction of CAR effectors targeting the EGFRvIII showed specific efficacy, and lenalidomide even intensified CAR cell therapy by enhanced formation of immunological synapses.

  2. Microsatellite Instability Use in Mismatch Repair Gene Sequence Variant Classification

    Directory of Open Access Journals (Sweden)

    Bryony A. Thompson

    2015-03-01

    Full Text Available Inherited mutations in the DNA mismatch repair genes (MMR can cause MMR deficiency and increased susceptibility to colorectal and endometrial cancer. Microsatellite instability (MSI is the defining molecular signature of MMR deficiency. The clinical classification of identified MMR gene sequence variants has a direct impact on the management of patients and their families. For a significant proportion of cases sequence variants of uncertain clinical significance (also known as unclassified variants are identified, constituting a challenge for genetic counselling and clinical management of families. The effect on protein function of these variants is difficult to interpret. The presence or absence of MSI in tumours can aid in determining the pathogenicity of associated unclassified MMR gene variants. However, there are some considerations that need to be taken into account when using MSI for variant interpretation. The use of MSI and other tumour characteristics in MMR gene sequence variant classification will be explored in this review.

  3. Bioactive Peptides from Muscle Sources: Meat and Fish

    Directory of Open Access Journals (Sweden)

    Catherine Stanton

    2011-08-01

    Full Text Available Bioactive peptides have been identified in a range of foods, including plant, milk and muscle, e.g., beef, chicken, pork and fish muscle proteins. Bioactive peptides from food proteins offer major potential for incorporation into functional foods and nutraceuticals. The aim of this paper is to present an outline of the bioactive peptides identified in the muscle protein of meat to date, with a focus on muscle protein from domestic animals and fish. The majority of research on bioactives from meat sources has focused on angiotensin-1-converting enzyme (ACE inhibitory and antioxidant peptides.

  4. High pressure processing of meat

    DEFF Research Database (Denmark)

    Grossi, Alberto; Christensen, Mette; Ertbjerg, Per

    Abstract Background: The research of high pressure (HP) processing of meat based foods needs to address how pressure affects protein interactions, aggregation and/or gelation. The understanding of the gel forming properties of myofibrillar components is fundamental for the development of muscle...... based products (Chapleau et al., 2004;Colmenero, 2002). Object: The aim was to study the rheological properties of pork meat emulsion exposed to HP and the effect of HP on the aggregation state of myofibrillar proteins. To address the role of cathepsin in myofibrillar protein degradation the changes...... in the myofibrillar protein pattern and HP-induced change in activity of cathepsin B and L were investigated. Results: In this study we showed that HP treatment of pork meat emulsion, ranging from 0.1 to 800 MPa, induced protein gel formation as shown by the increased Young’s modulus (Fig.1). Analysis of SDS...

  5. Will novel protein foods beat meat? : consumer acceptance of meat substitutes - a multidisciplinary research approach

    NARCIS (Netherlands)

    Hoek, A.C.

    2010-01-01

    Meat production places a heavy burden on the environment and therefore options are sought to reduce meat consumption. One option is to let new meat substitutes take the place of meat on the plate. This can only succeed when these products are acceptable to consumers. The thesis investigated which

  6. The Efficacy of the clay meat ball as a method of traditional meat ...

    African Journals Online (AJOL)

    Keywords: meat ball, protein, mineral content. This work was carried out to determine the effectiveness of the use of clay meat balls (an African traditional method of preserving meat) in extending the shelf life of meat over a period of months against microbial (bacterial and fungal) spoilage and contamination without ...

  7. The importance of wild meat in the Global South

    DEFF Research Database (Denmark)

    Nielsen, Martin R.; Meilby, Henrik; Smith-Hall, Carsten

    2018-01-01

    Information on the economic importance of wild meat to rural people is mainly based on small case studies conducted in limited geographical areas with high hunting intensities, which impede generalization of results. Through a one-year quarterly income survey of 7978 households in 24 countries...... is highest among the poorest households and inversely related to their reliance on domestic animal income. Seasonally, reliance on wild meat is inversely related to other incomes, suggesting a gap filling function. The fact that hunting is of low economic importance but widespread and mostly for subsistence...... suggests that wild meat is important in rural households’ diets. Through an approximated yield-effort curve estimation, we show that hunting appears economically sustainable in 78% of the observed communities although in most cases this might represent post-depletion sustainability. Our results imply...

  8. Meat production in developing countries.

    Science.gov (United States)

    Gill, M

    1999-05-01

    Developing countries have very diverse food consumption patterns and agricultural production systems. The proportion of meat in national diets varies from negligible in some countries in central Africa to 30-40% in some countries in Latin America and Mongolia. However, the demand for meat in developing countries is increasing rapidly (53%/year from 1982 to 1993), as the result of population growth and the trend for people to move to the cities. Growth rates in consumption are greatest in Asia, with China dominating the statistics, in view of the size of its population. Theoretically, livestock production can be increased to meet this demand, but the multiple roles of livestock in developing countries must be recognized if this is to be achieved in a sustainable manner. Resource-poor farmers who keep livestock may value more highly their contribution to livelihoods and to crop production, through provision of draught power and improvements in soil fertility through the recycling of manure, than the production of more meat. Recognition of the goals of the farmer and the wishes of the consumer regarding meat quality need to be reflected in the way in which opportunities for increasing meat production are identified and communicated to farmers. The impact of the global economy on cereal prices, for example, will also influence which interventions will be economically viable. Interpretation of information in an integral manner, using geographical information systems, mathematical models and/or simple spreadsheet models will be an important ingredient in turning scientific knowledge into increased meat production in developing countries.

  9. Clinical significance of CRNDE transcript variants in glioblastoma multiforme

    Directory of Open Access Journals (Sweden)

    Karrie M.Y. Kiang

    2017-06-01

    Full Text Available The long non-coding RNA CRNDE is an oncogene that promotes tumor growth in glioblastoma multiforme (GBM. At least five CRNDE transcript variants with possibly different functional roles have been described in recent studies. Here, we report our preliminary findings on the differential expressions of CRNDE transcript variants in GBM, and their prognostic significance. Our preliminary data suggest that different transcript variants of CRNDE might have different functions in GBM and should be further studied as potential biomarkers for clinical prognostication. Keywords: Long non-coding RNA, CRNDE, Transcript variant, Glioblastoma

  10. In the elderly, meat protein assimilation from rare meat is lower than that from meat that is well done.

    Science.gov (United States)

    Buffière, Caroline; Gaudichon, Claire; Hafnaoui, Noureddine; Migné, Carole; Scislowsky, Valérie; Khodorova, Nadezda; Mosoni, Laurent; Blot, Adeline; Boirie, Yves; Dardevet, Dominique; Santé-Lhoutellier, Véronique; Rémond, Didier

    2017-11-01

    Background: Meat cooking conditions in in vitro and in vivo models have been shown to influence the rate of protein digestion, which is known to affect postprandial protein metabolism in the elderly. Objective: The present study was conducted to demonstrate the effect of cooking conditions on meat protein assimilation in the elderly. We used a single-meal protocol to assess the meat protein absorption rate and estimate postprandial meat protein utilization in elderly subjects. Design: The study recruited 10 elderly volunteers aged 70-82 y. Each received, on 2 separate occasions, a test meal exclusively composed of intrinsically 15 N-labeled bovine meat (30 g protein), cooked at 55°C for 5 min [rare meat (RM)] or at 90°C for 30 min [fully cooked meat (FCM)], and minced. Whole-body fluxes of leucine, before and after the meal, were determined with the use of a [1- 13 C]leucine intravenous infusion. Meat protein absorption was recorded with the use of 15 N enrichment of amino acids. Results: Postprandial time course observations showed a lower concentration in the plasma of indispensable amino acids ( P meat leucine in the plasma ( P meat nitrogen to plasma amino acid nitrogen ( P meat amino acids with RM than with FCM. This was associated with decreased postprandial whole-body protein synthesis with RM than with FCM (40% compared with 56% of leucine intake, respectively; P meat cooking conditions have little effect on postprandial protein utilization in young adults, the present work showed that the bioavailability and assimilation of meat amino acids in the elderly is lower when meat is poorly cooked. In view to preventing sarcopenia, elderly subjects should be advised to favor the consumption of well-cooked meat. This trial was registered at clinicaltrials.gov as NCT02157805. © 2017 American Society for Nutrition.

  11. Meat consumption, diabetes and its complications

    NARCIS (Netherlands)

    Feskens, E.J.M.; Sluik, D.; Woudenbergh, van G.J.

    2013-01-01

    Several prospective studies have reported that risk of type 2 diabetes (T2DM) is elevated in meat consumers, especially when processed meats are consumed. Elevated risks of coronary heart disease (CHD) and stroke in meat consumers have also been reported. In this overview, the evidence regarding

  12. 9 CFR 319.260 - Luncheon meat.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Luncheon meat. 319.260 Section 319.260... ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Luncheon Meat, Loaves and Jellied Products...

  13. 9 CFR 319.261 - Meat loaf.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Meat loaf. 319.261 Section 319.261... ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Luncheon Meat, Loaves and Jellied Products...

  14. Variations in land requirements for meat production

    NARCIS (Netherlands)

    Elferink, E. V.; Nonhebel, S.

    2007-01-01

    Production of meat requires substantial amounts of feed grains which in turn require vast amounts of land. Future population growth and increase in consumption will raise the demand for meat and with it the land required for meat production. This paper analyses the various factors that affect land

  15. Breeding for meat quality in pigs

    NARCIS (Netherlands)

    Hovenier, R.

    1993-01-01

    The aim of this study was to investigate the possibilities of improving pig meat quality by selection. Therefore, literature is reviewed to determine the meat quality traits to be used and genetic parameters of those meat quality traits are calculated. A method is described to obtain

  16. 9 CFR 319.304 - Meat stews.

    Science.gov (United States)

    2010-01-01

    ... Products § 319.304 Meat stews. Meat stews such as “Beef Stew” or “Lamb Stew” shall contain not less than 25... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Meat stews. 319.304 Section 319.304 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY...

  17. Safer and healthier reduced nitrites turkey meat sausages using lyophilized Cystoseira barbata seaweed extract.

    Science.gov (United States)

    Sellimi, Sabrine; Benslima, Abdelkarim; Ksouda, Ghada; Montero, Veronique Barragan; Hajji, Mohamed; Nasri, Moncef

    2017-10-21

    Background Nitrite salts are still common additives in the meat industry. The present study provides a first approach on the employment of the lyophilized aqueous extract (WE) of the Tunisian seaweed Cystoseira barbata for the quality enhancement of turkey meat sausage. Methods WE was supplemented as a natural antioxidant agent to investigate its effectiveness in delaying lipid oxidation turkey meat sausages containing reduced amounts of sodium nitrites. Results On storage day 5, all concentrations of WE (0.01-0.4 %) reduced the meat lipid oxidation by approximately 36 %, as compared to the negative control containing only 80 mg/kg of meat of sodium nitrites as antioxidant. It was noted that within 15 days of refrigerated storage, a meat system containing 80 mg/kg of meat of sodium nitrites and 0.02 % and 0.04 % of WE had similar Thiobarbituric Acid Reactive Substances (TBARS) levels (19±1.32 and 17±1.12 µmol/kg of meat, respectively), which were comparable to the positive control containing sodium nitrites (150 mg/kg of meat) and 0.045 % vitamin C (18.46±1.27 µmol/kg of meat). In-depth, the metabolomic profiling using gas chromatography-mass spectrometry (GC/MS) and liquid chromatography-quadripole-time-of-flight-mass spectrometry (LC-QTOF-MS) analyses of the Tunisian seaweed C. barbata solvent extracts showed that the main active compounds were phenolic compounds, fatty acids and sterols. Conclusions Overall, the cold medium containing C. barbata lyophilized aqueous extrac, with strong antioxidant activity and antihypertensive properties, may open the way to the development of a natural quality enhancement strategy for new functional and ever healthier reduced nitrites meat sausages based on algae.

  18. Dietary supplementation of garlic and rosemary: effects on colour stability and lipid oxidation in lamb meat

    Directory of Open Access Journals (Sweden)

    M. Scafizzari

    2010-01-01

    Full Text Available The colour of fresh meat is an important criterion consumers take into consideration when purchasing meat. Meat colour depends on the occurrence of chemical and microbial deterioration processes. The role of vitamin E and other antioxidants on ruminant meat colour stability and prevention of lipid oxidation has been widely investigated (Macit et al., 2003; Realini et al., 2004. Many natural herbs and plant extracts exert antioxidant effects such as garlic (Yin and Cheng, 2003 and rosemary (Sánchez-Escalante et al., 2001. Their use as additives for animal feeding may be a valid alternative to synthetic antioxidants since they show beneficial effects also on animal welfare and other physiological functions (Tedesco, 2001. The aim of this study was to evaluate whether garlic and rosemary dietary supplementation as compared with vitamin E affects lamb meat colour and lipid stability during storage.

  19. Lactobacillus sakei: A Starter for Sausage Fermentation, a Protective Culture for Meat Products

    Directory of Open Access Journals (Sweden)

    Monique Zagorec

    2017-09-01

    Full Text Available Among lactic acid bacteria of meat products, Lactobacillus sakei is certainly the most studied species due to its role in the fermentation of sausage and its prevalence during cold storage of raw meat products. Consequently, the physiology of this bacterium regarding functions involved in growth, survival, and metabolism during meat storage and processing are well known. This species exhibits a wide genomic diversity that can be observed when studying different strains and on which probably rely its multiple facets in meat products: starter, spoiler, or protective culture. The emerging exploration of the microbial ecology of meat products also revealed the multiplicity of bacterial interactions L. sakei has to face and their various consequences on microbial quality and safety at the end of storage.

  20. Lactobacillus sakei: A Starter for Sausage Fermentation, a Protective Culture for Meat Products

    Science.gov (United States)

    Zagorec, Monique; Champomier-Vergès, Marie-Christine

    2017-01-01

    Among lactic acid bacteria of meat products, Lactobacillus sakei is certainly the most studied species due to its role in the fermentation of sausage and its prevalence during cold storage of raw meat products. Consequently, the physiology of this bacterium regarding functions involved in growth, survival, and metabolism during meat storage and processing are well known. This species exhibits a wide genomic diversity that can be observed when studying different strains and on which probably rely its multiple facets in meat products: starter, spoiler, or protective culture. The emerging exploration of the microbial ecology of meat products also revealed the multiplicity of bacterial interactions L. sakei has to face and their various consequences on microbial quality and safety at the end of storage. PMID:28878171

  1. TREM2 Variants in Alzheimer's Disease

    Science.gov (United States)

    Guerreiro, Rita; Wojtas, Aleksandra; Bras, Jose; Carrasquillo, Minerva; Rogaeva, Ekaterina; Majounie, Elisa; Cruchaga, Carlos; Sassi, Celeste; Kauwe, John S.K.; Younkin, Steven; Hazrati, Lilinaz; Collinge, John; Pocock, Jennifer; Lashley, Tammaryn; Williams, Julie; Lambert, Jean-Charles; Amouyel, Philippe; Goate, Alison; Rademakers, Rosa; Morgan, Kevin; Powell, John; St. George-Hyslop, Peter; Singleton, Andrew; Hardy, John

    2013-01-01

    BACKGROUND Homozygous loss-of-function mutations in TREM2, encoding the triggering receptor expressed on myeloid cells 2 protein, have previously been associated with an autosomal recessive form of early-onset dementia. METHODS We used genome, exome, and Sanger sequencing to analyze the genetic variability in TREM2 in a series of 1092 patients with Alzheimer's disease and 1107 controls (the discovery set). We then performed a meta-analysis on imputed data for the TREM2 variant rs75932628 (predicted to cause a R47H substitution) from three genomewide association studies of Alzheimer's disease and tested for the association of the variant with disease. We genotyped the R47H variant in an additional 1887 cases and 4061 controls. We then assayed the expression of TREM2 across different regions of the human brain and identified genes that are differentially expressed in a mouse model of Alzheimer's disease and in control mice. RESULTS We found significantly more variants in exon 2 of TREM2 in patients with Alzheimer's disease than in controls in the discovery set (P = 0.02). There were 22 variant alleles in 1092 patients with Alzheimer's disease and 5 variant alleles in 1107 controls (P<0.001). The most commonly associated variant, rs75932628 (encoding R47H), showed highly significant association with Alzheimer's disease (P<0.001). Meta-analysis of rs75932628 genotypes imputed from genomewide association studies confirmed this association (P = 0.002), as did direct genotyping of an additional series of 1887 patients with Alzheimer's disease and 4061 controls (P<0.001). Trem2 expression differed between control mice and a mouse model of Alzheimer's disease. CONCLUSIONS Heterozygous rare variants in TREM2 are associated with a significant increase in the risk of Alzheimer's disease. (Funded by Alzheimer's Research UK and others.) PMID:23150934

  2. Meat, dairy, and cancer1234

    Science.gov (United States)

    Abid, Zaynah; Cross, Amanda J; Sinha, Rashmi

    2014-01-01

    In 2007 the World Cancer Research Fund and American Institute for Cancer Research (WCRF/AICR) report judged that the evidence for an association between red and processed meat consumption and colorectal cancer was convincing. In addition, the effect of other animal products on cancer risk has been studied, and the WCRF/AICR report concluded that milk probably decreases the risk of colorectal cancer but diets high in calcium probably increase the risk of prostate cancer, whereas there was limited evidence for an association between milk and bladder cancer and insufficient evidence for other cancers. There are several potential mechanisms relating meat to cancer, including heterocyclic amines, polycyclic aromatic hydrocarbons, N-nitroso compounds, and heme iron. Although the evidence in favor of a link between red and processed meat and colorectal cancer is convincing, the relations with other cancers are unclear. In this review, we summarize cohort studies conducted by the National Cancer Institute on meat and dairy intake in relation to cancer since the 2007 WCRF/AICR report. We also report the findings of meta-analyses published since 2007. PMID:24847855

  3. Fetal programming in meat production.

    Science.gov (United States)

    Du, Min; Wang, Bo; Fu, Xing; Yang, Qiyuan; Zhu, Mei-Jun

    2015-11-01

    Nutrient fluctuations during the fetal stage affects fetal development, which has long-term impacts on the production efficiency and quality of meat. During the early development, a pool of mesenchymal progenitor cells proliferate and then diverge into either myogenic or adipogenic/fibrogenic lineages. Myogenic progenitor cells further develop into muscle fibers and satellite cells, while adipogenic/fibrogenic lineage cells develop into adipocytes, fibroblasts and resident fibro-adipogenic progenitor cells. Enhancing the proliferation and myogenic commitment of progenitor cells during fetal development enhances muscle growth and lean production in offspring. On the other hand, promoting the adipogenic differentiation of adipogenic/fibrogenic progenitor cells inside the muscle increases intramuscular adipocytes and reduces connective tissue, which improves meat marbling and tenderness. Available studies in mammalian livestock, including cattle, sheep and pigs, clearly show the link between maternal nutrition and the quantity and quality of meat production. Similarly, chicken muscle fibers develop before hatching and, thus, egg and yolk sizes and hatching temperature affect long-term growth performance and meat production of chicken. On the contrary, because fishes are able to generate new muscle fibers lifelong, the impact of early nutrition on fish growth performance is expected to be minor, which requires further studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Hemoglobin Variants in Mice

    Energy Technology Data Exchange (ETDEWEB)

    Popp, Raymond A.

    1965-04-22

    Variability among mammalian hemoglobins was observed many years ago (35). The chemical basis for differences among hemoglobins from different species of mammals has been studied by several investigators (5, 11, 18, 48). As well as interspecies differences, hemoglobin variants are frequently found within a species of mammals (2, 3, 7, 16) The inheritance of these intraspecies variants can be studied, and pedigrees indicate that the type of hemoglobin synthesized in an individual is genetically controlled (20). Several of the variant human hemoglobins are f'unctionally deficient (7, 16). Such hemoglobin anomalies are of basic interest to man because of the vital role of hemoglobin for transporting oxygen to all tissues of the body.

  5. Implications of white striping and spaghetti meat abnormalities on meat quality and histological features in broilers.

    Science.gov (United States)

    Baldi, G; Soglia, F; Mazzoni, M; Sirri, F; Canonico, L; Babini, E; Laghi, L; Cavani, C; Petracci, M

    2018-01-01

    During the past few years, there has been an increasing prevalence of broiler breast muscle abnormalities, such as white striping (WS) and wooden breast conditions. More recently, a new muscular abnormality termed as spaghetti meat (SM) because of the altered structural integrity of the Pectoralis major muscle often associated with WS has emerged. Thus, this study aimed at evaluating the effects of WS and SM conditions, occurring alone or combined within the same P. major muscle, on meat quality traits and muscle histology. In two replications, 96 P. major muscles were classified into four classes: normal (N), WS, SM and WS/SM. The whole fillet was used for weight assessment and morphometric measurements, then each sample was cut in order to separate the superficial layer from the deep one and used to evaluate proximate composition, histological features, nuclear magnetic resonance relaxation times, functional properties and both myofibrillar and sarcoplasmic proteins profile. Fillets affected by WS and SM abnormalities exhibited higher weights and increased thickness and length. SM condition was associated with a relevant decrease in protein content coupled with a significant increase in moisture level, whereas fat content was affected only by the simultaneous presence of WS. Histological evaluations revealed that abnormal samples were characterized by several degenerative aspects that almost completely concerned the superficial layer of the fillets. White striped fillets exhibited necrosis and lysis of fibers, fibrosis, lipidosis, loss of cross striation and vacuolar degeneration. Moreover, SM samples were characterized by poor fiber uniformity and a progressive rarefaction of the endo- and peri-mysial connective tissue, whereas WS/SM fillets showed intermediate histological features. Nuclear magnetic resonance relaxation analysis revealed a higher proportion of extra-myofibrillar water in the superficial section of all the abnormal fillets, especially in SM

  6. Studies of levels of biogenic amines in meat samples in relation to the content of additives.

    Science.gov (United States)

    Jastrzębska, Aneta; Kowalska, Sylwia; Szłyk, Edward

    2016-01-01

    The impact of meat additives on the concentration of biogenic amines and the quality of meat was studied. Fresh white and red meat samples were fortified with the following food additives: citric and lactic acids, disodium diphosphate, sodium nitrite, sodium metabisulphite, potassium sorbate, sodium chloride, ascorbic acid, α-tocopherol, propyl 3,4,5-trihydroxybenzoate (propyl gallate) and butylated hydroxyanisole. The content of spermine, spermidine, putrescine, cadaverine, histamine, tyramine, tryptamine and 2-phenylethylamine was determined by capillary isotachophoretic methods in meat samples (fresh and fortified) during four days of storage at 4°C. The results were applied to estimate the impact of the tested additives on the formation of biogenic amines in white and red meat. For all tested meats, sodium nitrite, sodium chloride and disodium diphosphate showed the best inhibition. However, cadaverine and putrescine were characterised by the biggest changes in concentration during the storage time of all the additives. Based on the presented data for the content of biogenic amines in meat samples analysed as a function of storage time and additives, we suggest that cadaverine and putrescine have a significant impact on meat quality.

  7. Use of artificial intelligence in the production of high quality minced meat

    Science.gov (United States)

    Kapovsky, B. R.; Pchelkina, V. A.; Plyasheshnik, P. I.; Dydykin, A. S.; Lazarev, A. A.

    2017-09-01

    A design for an automatic line for minced meat production according to new production technology based on an innovative meat milling method is proposed. This method allows the necessary degree of raw material comminution at the stage of raw material preparation to be obtained, which leads to production intensification due to the traditional meat mass comminution equipment being unnecessary. To ensure consistent quality of the product obtained, the use of on-line automatic control of the technological process for minced meat production is envisaged. This system has been developed using artificial intelligence methods and technologies. The system is trainable during the operation process, adapts to changes in processed raw material characteristics and to external impacts that affect the system operation, and manufactures meat shavings with minimal dispersion of the typical particle size. The control system includes equipment for express analysis of the chemical composition of the minced meat and its temperature after comminution. In this case, the minced meat production process can be controlled strictly as a function of time, which excludes subjective factors for assessing the degree of finished product readiness. This will allow finished meat products with consistent, targeted high quality to be produced.

  8. Physicochemical Properties of Meat Batter Added with Edible Silkworm Pupae (Bombyx mori) and Transglutaminase.

    Science.gov (United States)

    Park, Yoo-Sun; Choi, Yun-Sang; Hwang, Ko-Eun; Kim, Tae-Kyung; Lee, Cheol-Won; Shin, Dong-Min; Han, Sung Gu

    2017-01-01

    This study was conducted to investigate the physicochemical properties of meat batters prepared with fresh pork meat, back fat, water, and salt and formulated with three different amounts (5%, 10%, and 15%) of silkworm pupae ( Bombyx mori ) powder and transglutaminase (TG). Meat batters formulated with silkworm pupae powder showed significantly higher contents of protein and ash than control batter. Addition of silkworm pupae to batter also showed significantly lower cooking loss than the control. Moreover, meat batter containing 15% silkworm pupae showed no significant difference in redness value compared to the control. In addition, pH, viscosity, hardness, gumminess, and chewiness were improved after the addition of silkworm pupae. Furthermore, meat batter formulated with TG and silkworm pupae showed improved hardness, gumminess, chewiness and viscosity compared to control batter. Addition of 1% TG with 15% silkworm pupae to meat batter resulted in significantly higher pH, textures, and viscosity. Our data suggest that both silkworm pupae and TG can be added to meat batter to improve its physicochemical properties. Therefore, combination of silkworm pupae and TG could be a new nutritional and functional source for meat products.

  9. Environmental footprints in the meat chain

    Science.gov (United States)

    Đekić, I.; Tomašević, I.

    2017-09-01

    The objective of this paper was to present environmental performance of the meat chain and highlight main environmental footprints. The meat sector is recognized as one of the leading polluting sectors in the food industry. The meat chain was analyzed from a five-link perspective introducing the following actors: farm(er)s, slaughterhouses, meat processors, customers and consumers. Meat production needs natural resources (water and energy) resulting in waste and waste water discharge. As an outcome it has a high influence on climate change in respect to global warming, acidification and eutrophication potentials and ozone depletion substances.

  10. Regulations on Meat Hygiene in the USA

    Science.gov (United States)

    Seward, Robert (Skip) A.

    Regulations on meat hygiene in the United States of America (US) stem from the Federal Meat Inspection Act (FMIA, 21 USC §§ 601 et. seq.), promulgated in 1906, that gives the US Secretary of Agriculture (the Secretary) the power to oversee the conversion of livestock into meat products. The FMIA is reviewed herein to provide a background for discussion on how the US Department of Agriculture (USDA) and its departments, particularly the Food Safety and Inspection Service (FSIS), control and regulate the meat industry. This chapter discusses regulations that pertain to meat, herein meant to mean beef, veal, and pork, and does not specifically address poultry, although the regulations for poultry slaughter and processing are in many ways similar to those for meat and meat food products.

  11. Main Concerns of Pathogenic Microorganisms in Meat

    Science.gov (United States)

    Nørrung, Birgit; Andersen, Jens Kirk; Buncic, Sava

    Although various foods can serve as sources of foodborne illness, meat and meat products are important sources of human infections with a variety of foodborne pathogens, i.e. Salmonella spp., Campylobacter jejuni/coli, Yersinia enterocolitica, Verotoxigenic E. coli and, to some extent, Listeria monocytogenes. All these may be harboured in the gastrointestinal tract of food-producing animals. The most frequent chain of events leading to meat-borne illness involves food animals, which are healthy carriers of the pathogens that are subsequently transferred to humans through production, handling and consumption of meat and meat products. Occurrences of Salmonella spp., C. jejuni/coli, Y. enterocolitica and Verotoxigenic E. coli in fresh red meat vary relatively widely, although most often are between 1 and 10%, depending on a range of factors including the organism, geographical factors, farming and/or meat production practices.

  12. Identification of Splice Variants, Targeted MicroRNAs and Functional Single Nucleotide Polymorphisms of the BOLA-DQA2 Gene in Dairy Cattle

    Science.gov (United States)

    Hou, Qinlei; Huang, Jinming; Ju, Zhihua; Li, Qiuling; Li, Liming; Wang, Changfa; Sun, Tao; Wang, Lingling; Hou, Minghai

    2012-01-01

    Major histocompatibility complex, class II, DQ alpha 2, also named BOLA-DQA2, belongs to the Bovine Leukocyte Antigen (BOLA) class II genes which are involved in the immune response. To explore the variability of the BOLA-DQA2 gene and resistance to mastitis in cows, the splice variants (SV), targeted microRNAs (miRNAs), and single nucleotide polymorphisms (SNPs) were identified in this study. A new SV (BOLA-DQA2-SV1) lacking part of exon 3 (195 bp) and two 3′-untranslated regions (UTR) (52 bp+167 bp) of the BOLA-DQA2 gene was found in the healthy and mastitis-infected mammary gland tissues. Four of 13 new SNPs and multiple nucleotide polymorphisms resulted in amino acid changes in the protein and SNP (c. +1283 C>T) may affect the binding to the seed sequence of bta-miR-2318. Further, we detected the relative expressions of two BOLA-DQA2 transcripts and five candidated microRNAs binding to the 3′-UTR of two transcripts in the mammary gland tissues in dairy cattle by using the quantitative real-time polymerase chain reaction. The result showed that expression of the BOLA-DQA2-SV1 mRNA was significantly upregulated 2.67-fold (pmastitis-infected mammary tissues (n=5) compared with the healthy mammary gland mammary tissues (n=5). Except for bta-miR-1777a, miRNA expression (bta-miR-296, miR-2430, and miR-671) was upregulated 1.75 to 2.59-fold (pmastitis cows. Our findings reveal that BOLA-DQA2-SV1 may play an important role in the mastitis resistance in dairy cattle. Whether the SNPs affect the structure of the BOLA-DQA2 gene or association with mastitis resistance is unknown and warrants further investigation. PMID:22084936

  13. Identification of species origin of meat and meat products on the DNA basis: a review.

    Science.gov (United States)

    Kumar, Arun; Kumar, Rajiv Ranjan; Sharma, Brahm Deo; Gokulakrishnan, Palanisamy; Mendiratta, Sanjod Kumar; Sharma, Deepak

    2015-01-01

    The adulteration/substitution of meat has always been a concern for various reasons such as public health, religious factors, wholesomeness, and unhealthy competition in meat market. Consumer should be protected from these malicious practices of meat adulterations by quick, precise, and specific identification of meat animal species. Several analytical methodologies have been employed for meat speciation based on anatomical, histological, microscopic, organoleptic, chemical, electrophoretic, chromatographic, or immunological principles. However, by virtue of their inherent limitations, most of these techniques have been replaced by the recent DNA-based molecular techniques. In the last decades, several methods based on polymerase chain reaction have been proposed as useful means for identifying the species origin in meat and meat products, due to their high specificity and sensitivity, as well as rapid processing time and low cost. This review intends to provide an updated and extensive overview on the DNA-based methods for species identification in meat and meat products.

  14. The Use of Starter Cultures in Traditional Meat Products

    Directory of Open Access Journals (Sweden)

    Marta Laranjo

    2017-01-01

    Full Text Available Starter cultures could play an essential role in the manufacture of traditional cured meat products. In order to achieve objectives related to meat products’ quality and safety improvement, the selection of particular strains constituting a starter culture should be carried out in the context of its application, since its functionality will depend on the type of sausage and process conditions. Also, strain selection should comply with particular requirements to warrant safety. The aim of the current review is to update the knowledge on the use of starter cultures in traditional meat products, with focus on dry-fermented products. In this manuscript, we will try to give answers to some relevant questions: Which starter cultures are used and why? Why are LAB used? What are their role and their specific mode of action? Which other groups of microorganisms (bacteria and fungi are used as starter cultures and how do they act? A particular revision of omics approach regarding starter cultures is made since the use of these techniques allows rapid screening of promising wild strains with desirable functional characteristics, enabling the development of starter cultures better adapted to the meat matrix.

  15. Control of salmonella in meat and meat products by irradiation

    International Nuclear Information System (INIS)

    Dempster, J.F.

    1985-01-01

    This paper highlights the importance of food irradiation in the protection of the public against food poisoning from eating meat or meat products contaminated with salmonella. Salmonella infections are increasing at an alarming rate (2000 in 1952 to 12000 reported cases in 1982 in England and Wales alone). Dr. Dempster reports that 50% of the chicken carcasses examined by workers in America were found to be salmonella contaminated. Use of irradiation in conjunction with mild refrigeration can extend the shelf-life of vacuum packed chicken by a factor of three. Important legislation now under discussion in the U.S.A. is likely to extend the applicability of food irradiation rapidly in the near future

  16. Meat quality traits and proteome profile of woody broiler breast (pectoralis major) meat.

    Science.gov (United States)

    Cai, K; Shao, W; Chen, X; Campbell, Y L; Nair, M N; Suman, S P; Beach, C M; Guyton, M C; Schilling, M W

    2018-01-01

    Woody breast meat has recently become prevalent in the broiler industry in both the United States and European Union. Recent publications have described the meat quality characteristics of woody breast meat as having hardened areas and pale ridge-like bulges at both the caudal and cranial regions of the breast. The present study investigated the meat quality (pH, color, cooking loss, and shear force) and protein quality characteristics (protein and salt-soluble protein content) in woody breast meat as compared to normal breast meat. In addition, the differences in the muscle proteome profiles of woody and normal breast meat were characterized. Results indicated that woody breast meat had a greater average pH (P 0.05) in comparison to normal breast meat samples. The L*, a*, and b* values of woody breast fillets were greater than normal breast fillets (P < 0.0001 to L*; P = 0.002 to a*; P = 0.016 to b*). The woody breast meat had more fat (P < 0.0001) and moisture (P < 0.021) and less protein (P < 0.0001) and salt-soluble protein (P < 0.0001) when compared with normal breast fillets. Whole muscle proteome analysis indicated 8 proteins that were differentially expressed (P < 0.05) between normal and woody breast meat samples. The differences in muscle proteome between normal and woody breast meat indicated an increased oxidative stress in woody breast meat when compared to normal meat. In addition, the abundance of some glycolytic enzymes, which are critical to the regeneration of adenosine triphosphate (ATP) in postmortem muscles, was lower in woody breast meat than in normal breast meat. Proteomic differences provide additional information on the biochemical pathways and genetic variations that lead to woody breast meat. Further research should be conducted to elucidate the genetic and nutritional contributions to the proliferation of woody breast meat in the United States. © 2017 Poultry Science Association Inc.

  17. CONCENTRATION OF CADMIUM IN MEAT AND SELECTED MEATS PRODUCTS

    Directory of Open Access Journals (Sweden)

    Anetta Lukáčová

    2015-02-01

    Full Text Available The cadmium concentrations depend on the environmental conditions and food production methods. The monitoring of cadmium concentration in meat is important for human health. The concentrations of cadmium in meat and meat products collected from central Slovakia, in the central Europe region and from different countries of West Europe were assessed using by AA spectrometer with graphite furnace (PerkinElmer AAnalyst 80, MA, USA. Within starting materials we detected the highest values of cadmium in beef from foreign production (0.1101 ppm, followed by pork from foreign production (0.0901 ppm in Lovecka salama and pork thigh (0.0523 ppm in selected ham. In Lovecka salami we were found the highest concentration of cadmium in final samples from foreign starting materials, followed by homogenized samples from foreign starting materials, final samples from domestic starting materials and homogenized samples from domestic starting materials (0.3728, 0.3549, 0.2387, 0.2112 ppm, respectively. The highest concentration of cadmium in selected ham were found in final products from foreign starting materials, homogenized samples from foreign starting materials, final products from domestic starting materials and homogenized samples from domestic starting materials (0.1453, 0.1382,0.0810, 0.0734 ppm, respectively. The obtained results suggested that the concentrations of cadmium are higher in homogenized samples and final products in Lovecka salami and selected ham in comparison with to starting materials. Technological process of meat processing can create a potential source of heavy metals in final products.

  18. PENGARUH BERBAGAI KECAMBAH KACANG-KACANGAN LOKAL SEBAGAI BAHAN DASAR MEAT ANALOG TERHADAP SIFAT FISIK (TEKSTUR, KESUKAAN DAN RASIO ARGININ/LISIN

    Directory of Open Access Journals (Sweden)

    Bayu Kanetro

    2013-06-01

    Full Text Available The aims of this research were to determine the best of local legume sprout as raw material of meat analog, based on its texture, sensory (preference properties, and the ratio of arginine/lysine, compared to meat analog from soybean. Meat analogs were made of protein of local legumes sprout, which were velvet beans, cowpeas, and winged beans that had been germinated for 48, 36 and 24 hr respectively. The protein of velvet beans, cowpeas, and winged beans sprout for meat analog production were extracted at pH 9 and precipitated at pH 4, 5, and 5 respectively. Hence their products were analyzed the texture, the sensory properties (the hedonic scales of color, texture, odor, taste, and overall, and the ratio of arginine/lysine. The characteristics of meat analog from the legumes sprout were compared to meat analog from soybean for determination of the best legume sprout as raw material of meat analog. The result of this research showed the properties of meat analog from winged bean and cowpeas sprouts were better than velvet beans sprout. The meat analog from soybean was still better than meat analog from the local legumes sprout, especially its texture. The arginine content, that was known as  hypocholesterolemic and hypoglycemic component,  of meat analog from cowpeas sprout was lower than meat analog from soybean, but its ratio of arginie/lysine was not signifi cantly different. While the ratio of arginine/lysine of meat analog from the other legumes sprout were lower than meat analog from soybean. Therefore the meat analog from cowpeas sprout was chosen as the best product and was potential as functional food especially for reducing blood cholesterol. Keywords: Meat analog, sprout, local legumes, arginine/lysine ratio   ABSTRAK Tujuan penelitian ini adalah untuk menentukan jenis kecambah kacang-kacangan lokal terbaik sebagai bahan baku kedelai berdasarkan tekstur, sifat sensoris, dan rasio arginin/lisin dibandingkan meat analog dari biji

  19. Histone variants and lipid metabolism

    NARCIS (Netherlands)

    Borghesan, Michela; Mazzoccoli, Gianluigi; Sheedfar, Fareeba; Oben, Jude; Pazienza, Valerio; Vinciguerra, Manlio

    2014-01-01

    Within nucleosomes, canonical histones package the genome, but they can be opportunely replaced with histone variants. The incorporation of histone variants into the nucleosome is a chief cellular strategy to regulate transcription and cellular metabolism. In pathological terms, cellular steatosis

  20. Variants of Modeling Dwelling Market Value

    Directory of Open Access Journals (Sweden)

    Barańska Anna

    2014-10-01

    Full Text Available The object of this paper is to determine real estate market value on the basis of a multidimensional function model in different variants: A - directly from the model estimated on the basis of a big database, B - from the same model form, but estimated on the basis of a reduced database consisting of dwellings most similar to the estimated one, and C - based on modeled prices corrected by random correction, calculated from random deviations for dwellings most similar to the assessed one. In the framework of statistical inference procedures, the resulting comparison was carried out by parametric significance tests. They were applied to draw conclusions on the analyzed variants

  1. Prevalence of Campylobacter spp. in poultry meat and meat products imported in Republic of Macedonia

    Directory of Open Access Journals (Sweden)

    Kostova Sandra

    2008-11-01

    Full Text Available Campylobacter spp. is leading bacterial cause of diarrhea in human population in all parts of the world. In most of the cases infection with Campylobacter spp. in humans originate from contaminated poultry meat and poultry meat products. This study was designed to estimate prevalence of Campylobacter spp. in meat and meat products imported in Republic of Macedonia. During the period of 8 months (January-August 2008 we tested 56 samples of meat and meat products (poultry meat, MDM, pork meat, beef meat and smoked beef. Samples were submitted to analysis for detection of thermo-tolerant Campylobacter spp. according to ISO 10272:1995. We determined among the analyzed samples highest prevalence of Campylobacter spp. in MDM with 84% positive samples, poultry meat with 81,8%, pork meat with 10%. We didn.t detect any positive samples in beef meat and smoked beef. Overall prevalence of Campylobacter spp. in all tested samples was 55,36%. This study shows that the high prevalence of Campylobacter spp. in tested samples and in correlation with severe symptoms in humans are reasons good enough for the producing and processing poultry meat industry and food business operators so they should take in consideration Campylobacter spp. in their risk assessment and preparation of HACCP plan.

  2. Interaction between GPR120 p.R270H loss-of-function variant and dietary fat intake on incident type 2 diabetes risk in the D.E.S.I.R. study.

    Science.gov (United States)

    Lamri, A; Bonnefond, A; Meyre, D; Balkau, B; Roussel, R; Marre, M; Froguel, P; Fumeron, F

    2016-10-01

    GPR120 (encoded by FFAR4) is a lipid sensor that plays an important role in the control of energy balance. GPR120 is activated by long chain fatty acids (FAs) including omega-3 FAs. In humans, the loss of function p.R270H variant of the gene FFAR4 has been associated with a lower protein activity, an increased risk of obesity and higher fasting plasma glucose levels. The aim of this study was to investigate whether p.R270H interacts with dietary fat intake to modulate the risk of type 2 diabetes (T2D, 198 incident; 368 prevalent cases) and overweight (787 incident and 2891 prevalent cases) in the prospective D.E.S.I.R. study (n = 5,212, 9 years follow-up). The association of p.R270H with dietary fat and total calories was assessed by linear mixed models. The interaction between p.R270H and dietary fat on T2D and overweight was assessed by logistic regression analysis. The p.R270H variant had a minor allele frequency of 1.45% and was not significantly associated with total calories intake, fat intake or the total calories derived from fat (%). However, there was a significant interaction between p.R270H and dietary fat modulating the incidence of T2D (Pinteraction = 0.02) where the H-carriers had a higher risk of T2D than RR homozygotes in the low fat intake category only. The interaction between p.R270H and fat intake modulating the incidence and prevalence of overweight was not significant. The p.R270H variant of GPR120 modulates the risk of T2D in interaction with dietary fat intake in the D.E.S.I.R. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  3. Meat-based enteral nutrition

    Science.gov (United States)

    Derevitskay, O. K.; Dydykin, A. S.

    2017-09-01

    Enteral nutrition is widely used in hospitals as a means of nutritional support and therapy for different diseases. Enteral nutrition must fulfil the energy needs of the body, be balanced by the nutrient composition and meet patient’s nutritional needs. Meat is a source of full-value animal protein, vitamins and minerals. On the basis of this research, recipes and technology for a meat-based enteral nutrition product were developed. The product is a ready-to-eat sterilised mixture in the form of a liquid homogeneous mass, which is of full value in terms of composition and enriched with vitamins and minerals, consists of particles with a size of not more than 0.3 mm and has the modified fat composition and rheological characteristics that are necessary for passage through enteral feeding tubes. The study presents experimental data on the content of the main macro- and micro-nutrients in the developed product. The new product is characterised by a balanced fatty acid composition, which plays an important role in correction of lipid metabolism disorders and protein-energy deficiency, and it is capable of satisfying patients’ daily requirements for vitamins and the main macro- and microelements when consuming 1500-2000 ml. Meat-based enteral nutrition can be used in diets as a standard mixture for effective correction of the energy and anabolic requirements of the body and support of the nutritional status of patients, including those with operated stomach syndrome.

  4. Molecular identification and functional analysis of two variants of myeloid differentiation factor 88 (MyD88) from disk abalone (Haliotis discus discus).

    Science.gov (United States)

    Priyathilaka, Thanthrige Thiunuwan; Bathige, S D N K; Lee, Seongdo; Lee, Jehee

    2018-02-01

    Myeloid differentiation factor 88 (MyD88) is a crucial adaptor protein of the Toll-like receptor (TLR)- and interleukin 1 receptor-mediated signaling pathways and is involved in a diverse array of inflammatory responses via NF-κB activation. In the present study, two MyD88 variants were identified from disk abalone (Haliotis discus discus) and designated AbMyD88-2 and AbMyD88-X. The deduced AbMyD88-2 and AbMyD88-X comprised 433 and 354 amino acids with predicted molecular masses of 48.85 kDa and 40.17 kDa, respectively. AbMyD88-2 and AbMyD88-X possessed typical MyD88 domain structural features including an N-terminal death domain (DD) and C-terminal toll interleukin 1 receptor (TIR) domain similar to those in mammals. Expression analysis of AbMyD88-2 and AbMyD88-X mRNA at different early embryonic developmental stages of abalone by qPCR revealed that their constitutive expression at all developmental stages analyzed with the considerably higher values at the 16-cell (AbMyD88-2) and morula stages (AbMyD88-X). In unchallenged disk abalones, AbMyD88-2 was highly expressed in muscles, while AbMyD88-X mRNA was predominantly transcribed in hemocytes. Moreover, AbMyD88-2 and AbMyD88-X mRNA were differentially modulated in abalone hemocytes after a challenge with live bacteria (Vibrio parahaemolyticus, Listeria monocytogenes), virus (viral hemorrhagic septicemia virus), and pathogen-associated molecular patterns (lipopolysaccharides and Poly I:C). Overexpression of AbMyD88-2 and AbMyD88-X in HEK293T cells induced the activation of the NF-κB promoter. AbMyD88-2 and AbMyD88-X involvement in inflammatory responses was characterized by their overexpression in RAW264.7 murine macrophage cells. These results revealed comparatively higher NO (Nitric oxide) production, induction of inflammatory mediator genes (iNOS and COX2), and proinflammatory genes (IL1β, IL6 and TNFα) expression in abalone MyD88s-overexpressing cells than in mock control in the presence or absence of LPS

  5. Role of the functional MNS16A VNTR-243 variant of the human telomerase reverse transcriptase gene in progression and response to therapy of patients with non-Hodgkin's B-cell lymphomas.

    Science.gov (United States)

    Wysoczanska, B; Wrobel, T; Dobrzynska, O; Mazur, G; Bogunia-Kubik, K

    2015-04-01

    MNS16A is a functional polymorphic tandem repeat within the human telomerase reverse transcriptase (hTERT) gene. To investigate whether any of the MNS16A repeats represents a genetic risk factor for NHL susceptibility, progression of or response to therapy in 75 patients with non-Hodgkin's lymphomas (NHLs) and 126 healthy individuals were genotyped using the PCR-VNTR technique. A slightly higher frequency of the MNS16A VNTR-243 variant was detected among patients who did not respond to treatment (NR) as compared to patients with complete or partial remission (0.83 vs. 0.51, P = 0.055). NR patients more frequently developed aggressive than indolent type of the disease (0.92 vs. 0.41, P = 0.001). The VNTR-243 allele was more frequently detected among patients with an intermediate-high/high International Prognostic Index (IPI 3-4) score (P = 0.063), especially in patients with advanced age and IPI 3-4 (P = 0.040). In multivariate analysis, higher IPI 3-4 score (OR = 11.364, P = 0.051) and aggressive type of the disease (OR = 18.182, P = 0.012) were found to be independent genetic markers associated with nonresponse to treatment. Presence of the MNS16A VNTR-243 variant also strongly tended to affect the risk of a less favourable response to therapy and was more frequently present among nonresponders (OR = 5.848, P = 0.059). Genetic variation within the hTERT gene may affect the progression and treatment of lymphoproliferative disorders. © 2015 John Wiley & Sons Ltd.

  6. Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

    DEFF Research Database (Denmark)

    Zeng, Chenjie; Guo, Xingyi; Long, Jirong

    2016-01-01

    carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. RESULTS...

  7. Splicing variants of porcine synphilin-1

    DEFF Research Database (Denmark)

    Larsen, Knud Erik; Madsen, Lone Bruhn; Farajzadeh, Leila

    2015-01-01

    %) and to mouse (84%) synphilin-1. Three shorter transcript variants of the synphilin-1 gene were identified, all lacking one or more exons. SNCAIP transcripts were detected in most examined organs and tissues and the highest expression was found in brain tissues and lung. Conserved splicing variants and a novel...... splice form of synhilin-1 were found in this study. All synphilin-1 isoforms encoded by the identified transcript variants lack functional domains important for protein degradation....... with α-synuclein in LBs. The aim of this study was to isolate and characterize porcine synphilin-1 and isoforms hereof with the future perspective to use the pig as a model for Parkinson's disease. The porcine SNCAIP cDNA was cloned by reverse transcriptase PCR. The spatial expression of SNCAIP mRNA...

  8. Hemoglobin Variants: Biochemical Properties and Clinical Correlates

    Science.gov (United States)

    Thom, Christopher S.; Dickson, Claire F.; Gell, David A.; Weiss, Mitchell J.

    2013-01-01

    Diseases affecting hemoglobin synthesis and function are extremely common worldwide. More than 1000 naturally occurring human hemoglobin variants with single amino acid substitutions throughout the molecule have been discovered, mainly through their clinical and/or laboratory manifestations. These variants alter hemoglobin structure and biochemical properties with physiological effects ranging from insignificant to severe. Studies of these mutations in patients and in the laboratory have produced a wealth of information on hemoglobin biochemistry and biology with significant implications for hematology practice. More generally, landmark studies of hemoglobin performed over the past 60 years have established important paradigms for the disciplines of structural biology, genetics, biochemistry, and medicine. Here we review the major classes of hemoglobin variants, emphasizing general concepts and illustrative examples. PMID:23388674

  9. DEMAND FOR TURKEY MEAT: PRICE EFFECT OR SPENDING EFFECT

    Directory of Open Access Journals (Sweden)

    Miguel Angel Martinez Damian

    2016-08-01

    Full Text Available Turkey meat is a white meat demand in Mexico, however, its consumption is still low. In order to explore the convenience of expanding the market and foresee if the industry should compete in price or expenditure, the aim of this work is to study the demand for turkey meat as part of a protein basket; that consists of beef, chicken, pork and egg. Methodologically an almost ideal demand model was used, in an economic sense, this model allows an optimal assignment representation through budget share equations as a function of prices and real expenditure within the bundle. With statistical information from secondary sources, the results showed that the demand for turkey meat responds inelastically to price, and that the response on spending is almost one. With the estimates of price and expenditure growth rates, in terms of an expansion policy in the turkey market, results conclude that spending is the most relevant factor in demand, followed to a lesser extent by price.

  10. The Ethics of Producing In Vitro Meat.

    Science.gov (United States)

    Schaefer, G Owen; Savulescu, Julian

    2014-05-01

    The prospect of consumable meat produced in a laboratory setting without the need to raise and slaughter animals is both realistic and exciting. Not only could such in vitro meat become popular due to potential cost savings, but it also avoids many of the ethical and environmental problems with traditional meat productions. However, as with any new technology, in vitro meat is likely to face some detractors. We examine in detail three potential objections: 1) in vitro meat is disrespectful, either to nature or to animals; 2) it will reduce the number of happy animals in the world; and 3) it will open the door to cannibalism. While each objection has some attraction, we ultimately find that all can be overcome. The upshot is that in vitro meat production is generally permissible and, especially for ethical vegetarians, worth promoting.

  11. Chinese ethnic meat products: Continuity and development.

    Science.gov (United States)

    Zeng, Weicai; Wen, Wenting; Deng, Yue; Tian, Yuanyuan; Sun, Honghu; Sun, Qun

    2016-10-01

    With their distinctive sensory characterizations and unique processing technologies, Chinese ethnic meat products possess great potential for development and continuity in modern China's meat industry. Due to the greater demand for meat products and higher quality and safety concerns in economically fast growing China, the development and continuity of ethnic meat products face its own unique challenges. In this review, the classification of typical ethnic products and their characteristics, and the research progress on their quality and processing technologies are discussed. The application of innovative and green technologies to improve the safety and quality of ethnic meat products for greater industrialization and sustainable development is highlighted. Furthermore, the strategy for promoting the production of Chinese ethnic meat products during the next five years is presented. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Introducing the new meat. Problems and prospects

    Directory of Open Access Journals (Sweden)

    Stellan Welin

    2013-05-01

    Full Text Available Cultured meat, or in vitro meat, is one of the ideas that are being proposed to help solve the problems associated with the ever-growing global meat consumption. The prospect may bring benefit for the environment, climate, and animal ethics, but has also generated doubts and criticism. A discussion of the possible environmental benefit and of animal ethics issues in relation to cultured meat production will be given. A perceived 'unnaturalness' of cultured meat may be one of the strongest barriers for public acceptance. This will be discussed and rejected. As to our relations with nature and animals, it is plausible that cultured meat will lead to improvement rather than to deterioration. The issue of public acceptance and some of the problems of introducing this new product on the market will also be discussed.http://dx.doi.org/10.5324/eip.v7i1.1788

  13. Variants of glycoside hydrolases

    Energy Technology Data Exchange (ETDEWEB)

    Teter, Sarah; Ward, Connie; Cherry, Joel; Jones, Aubrey; Harris, Paul; Yi, Jung

    2017-07-11

    The present invention relates to variants of a parent glycoside hydrolase, comprising a substitution at one or more positions corresponding to positions 21, 94, 157, 205, 206, 247, 337, 350, 373, 383, 438, 455, 467, and 486 of amino acids 1 to 513 of SEQ ID NO: 2, and optionally further comprising a substitution at one or more positions corresponding to positions 8, 22, 41, 49, 57, 113, 193, 196, 226, 227, 246, 251, 255, 259, 301, 356, 371, 411, and 462 of amino acids 1 to 513 of SEQ ID NO: 2 a substitution at one or more positions corresponding to positions 8, 22, 41, 49, 57, 113, 193, 196, 226, 227, 246, 251, 255, 259, 301, 356, 371, 411, and 462 of amino acids 1 to 513 of SEQ ID NO: 2, wherein the variants have glycoside hydrolase activity. The present invention also relates to nucleotide sequences encoding the variant glycoside hydrolases and to nucleic acid constructs, vectors, and host cells comprising the nucleotide sequences.

  14. Variants of glycoside hydrolases

    Science.gov (United States)

    Teter, Sarah; Ward, Connie; Cherry, Joel; Jones, Aubrey; Harris, Paul; Yi, Jung

    2013-02-26

    The present invention relates to variants of a parent glycoside hydrolase, comprising a substitution at one or more positions corresponding to positions 21, 94, 157, 205, 206, 247, 337, 350, 373, 383, 438, 455, 467, and 486 of amino acids 1 to 513 of SEQ ID NO: 2, and optionally further comprising a substitution at one or more positions corresponding to positions 8, 22, 41, 49, 57, 113, 193, 196, 226, 227, 246, 251, 255, 259, 301, 356, 371, 411, and 462 of amino acids 1 to 513 of SEQ ID NO: 2 a substitution at one or more positions corresponding to positions 8, 22, 41, 49, 57, 113, 193, 196, 226, 227, 246, 251, 255, 259, 301, 356, 371, 411, and 462 of amino acids 1 to 513 of SEQ ID NO: 2, wherein the variants have glycoside hydrolase activity. The present invention also relates to nucleotide sequences encoding the variant glycoside hydrolases and to nucleic acid constructs, vectors, and host cells comprising the nucleotide sequences.

  15. Generation of a vector system facilitating cloning of DMBT1 variants and recombinant expression of functional full-length DMBT1

    DEFF Research Database (Denmark)

    End, Caroline; Lyer, Stefan; Renner, Marcus

    2005-01-01

    Deleted in malignant brain tumours 1 (DMBT1) codes for a approximately 340kDa glycoprotein with highly repetitive scavenger receptor cysteine-rich (SRCR) domains. DMBT1 was implicated in cancer, defence against viral and bacterial infections, and differentiation of epithelial cells. Recombinant...... expression and purification of DMBT1 is an essential step for systematic standardized functional research and towards the evaluation of its therapeutical potential. So far, DMBT1 is obtained from natural sources such as bronchioalveolar lavage or saliva, resulting in time consuming sample collection, low...... yields, and protein preparations which may substantially vary due to differential processing and genetic polymorphism, all of which impedes functional research on DMBT1. Cloning of DMBT1 cDNAs is hampered because of the size and the 13 highly homologous SRCR exons. In this study, we report on the setup...

  16. Benevolent technotopias and hitherto unimaginable meats: Tracing the promises of in vitro meat

    OpenAIRE

    Jönsson, Erik

    2016-01-01

    Today, in vitro (Latin: in glass) meat researchers strive to overhaul meat production technologies by producing meat outside animal bodies, primarily by culturing cells. In the process, meat should become healthier, more environmentally friendly and kinder to animals. In this article, I scrutinize (and problematize) this promissory discourse by examining the world that proponents envision alongside the world from which promises emerge. First, I trace the increasing number of publications stri...

  17. Structure and function of hemoglobin variants at an internal hydrophobic site: Consequences of mutations at the β 27 (B9) position

    International Nuclear Information System (INIS)

    Huang, Yue; Pagnier, J.; Magne, P.; Kister, J.; Poyart, C.; Baklouti, F.; Delaunay, J.; Fermi, G.; Perutz, M.F.

    1990-01-01

    The authors have studied the structure-function relationships in newly discovered hemoglobin (Hb) mutants with substitutions occurring at the tight and highly hydrophobic cluster between the B and G helices in the β chains, namely, Hb Knossos or β A27S and Hb Grange-Blanche or β A27V. The β A27S mutant has a 50% decrease in oxygen affinity relative to native human Hb A, while the β A27V mutant has an increased oxygen affinity. They have also engineered the artificial β A27T mutation through site-directed mutagenesis. This new mutant exhibits functional properties similar to those of Hb A. None of these mutants is unstable. X-ray analyses show that the substitution of Val for Ala may reduce the relative stability of the T structure of the molecule through packing effects in the β chains; for the β A27S mutant a new hydrogen bond between serine and the carbonyl O at β 23 (B5) Val is observed and is likely to increase the relative stability of the T structure in the mutant hemoglobin. However, no significant changes in the crystals were observed for these mutants between the quaternary R and T structures relative to native Hb A. They conclude that small tertiary structural changes in the tight hydrophobic B-G helix interface are sufficient to induce functional abnormalities resulting in either low or high intrinsic oxygen affinities

  18. Associations of filaggrin gene loss-of-function variants and human papillomavirus-related cancer and pre-cancer in Danish adults.

    Directory of Open Access Journals (Sweden)

    Tea Skaaby

    Full Text Available Filaggrin proteins are expressed in the skin, oral cavity, oesophagus, and cervical mucose. Loss-of-function mutations in the filaggrin gene (FLG reduce filaggrin expression and cause an impaired skin barrier function. We hypothesized that FLG mutation carriers would be more susceptible to human papillomavirus (HPV infection and thus a higher risk of HPV-related cancer and pre-cancer. We investigated the association of the FLG genotype with incidence of HPV-related cancer of cervix, vagina, vulva, penis, anus and head and neck, and pre-cancer of the cervix.We included 13,376 persons from four population-based studies conducted in the same background population in Copenhagen, Denmark. Participants were genotyped for the most common FLG mutations in Europeans. Information on cancer was obtained from The Danish Cancer Registry until 11 July 2011.There were 489 cases of prevalent and 97 cases of incident HPV-related cancer and pre-cancer (median follow-up 11.5 years. There was a statistically significant association between FLG genotype and incident HPV-related cancer and pre-cancer with a hazard ratio, HR = 2.1 (95% confidence intervals, CI: 1.2, 3.7 for FLG mutation carriers vs. wild types.FLG loss-of-function mutations were associated with higher incidence of HPV-related cancers and pre-cancers that are potentially screening and vaccine preventable.

  19. 9 CFR 311.38 - Meat and meat byproducts from livestock which have been exposed to radiation.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Meat and meat byproducts from... MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.38 Meat and meat byproducts from livestock which have been...

  20. Environmental impacts of cultured meat production.

    Science.gov (United States)

    Tuomisto, Hanna L; de Mattos, M Joost Teixeira

    2011-07-15

    Cultured meat (i.e., meat produced in vitro using tissue engineering techniques) is being developed as a potentially healthier and more efficient alternative to conventional meat. Life cycle assessment (LCA) research method was used for assessing environmental impacts of large-scale cultured meat production. Cyanobacteria hydrolysate was assumed to be used as the nutrient and energy source for muscle cell growth. The results showed that production of 1000 kg cultured meat requires 26-33 GJ energy, 367-521 m(3) water, 190-230 m(2) land, and emits 1900-2240 kg CO(2)-eq GHG emissions. In comparison to conventionally produced European meat, cultured meat involves approximately 7-45% lower energy use (only poultry has lower energy use), 78-96% lower GHG emissions, 99% lower land use, and 82-96% lower water use depending on the product compared. Despite high uncertainty, it is concluded that the overall environmental impacts of cultured meat production are substantially lower than those of conventionally produced meat.

  1. Campylobacter radicidation of poultry meat by means of low dose ionizing radiation

    International Nuclear Information System (INIS)

    Tarjan, Veronika

    1984-01-01

    The effect of ionizing radiation on the number of sprouts of pathogenic Campylobacter was studied in the function of time, storage temperature and radiation dose. Culture-media and minced poultry meat treated with isolated bacteria were irradiated by sup(60)Co up to a dose of 1 kGy. It would be established that low irradiation doses of 3-5 kGy used to eliminate Salmonella infection satisfactorily destroy Campylobacter in chilled meat. (V.N.)

  2. Development of Rabbit Meat Products Fortified With n-3 Polyunsaturated Fatty Acids

    Directory of Open Access Journals (Sweden)

    Massimiliano Petracci

    2009-10-01

    Full Text Available Rabbit meat is a highly digestible, tasty, low-calorie food, often recommended by nutritionists over other meats. Currently research in the rabbit sector is interested in developing feeding strategies aiming to further increase the nutritional value of rabbit meat as a “functional food” by including n-3 polyunsaturated fatty acids (n-3 PUFA, conjugated linoleic acid (CLA, vitamins and antioxidants in rabbit diets and assessing their effects on both raw and stored/processed meat quality properties. Our recent studies indicate that the dietary inclusion from 3 to 6% of linseed might be considered as a way to achieve the enrichment of the meat with α-linolenic acid and to guarantee satisfactory product stability during further processing and storage. Considering that 6% dietary linseed corresponds to a n-3 PUFA content of 8.5% of the total fatty acids and a lipid content of 4.7 g/100 g of leg meat, a content of 396 mg n-3 PUFA/100g meat can be estimated, which represents about 19% of the recommended daily allowance (RDA for n-3 PUFA.

  3. Dietary soy and meat proteins induce distinct physiological and gene expression changes in rats

    Science.gov (United States)

    Song, Shangxin; Hooiveld, Guido J.; Li, Mengjie; Zhao, Fan; Zhang, Wei; Xu, Xinglian; Muller, Michael; Li, Chunbao; Zhou, Guanghong

    2016-01-01

    This study reports on a comprehensive comparison of the effects of soy and meat proteins given at the recommended level on physiological markers of metabolic syndrome and the hepatic transcriptome. Male rats were fed semi-synthetic diets for 1 wk that differed only regarding protein source, with casein serving as reference. Body weight gain and adipose tissue mass were significantly reduced by soy but not meat proteins. The insulin resistance index was improved by soy, and to a lesser extent by meat proteins. Liver triacylglycerol contents were reduced by both protein sources, which coincided with increased plasma triacylglycerol concentrations. Both soy and meat proteins changed plasma amino acid patterns. The expression of 1571 and 1369 genes were altered by soy and meat proteins respectively. Functional classification revealed that lipid, energy and amino acid metabolic pathways, as well as insulin signaling pathways were regulated differently by soy and meat proteins. Several transcriptional regulators, including NFE2L2, ATF4, Srebf1 and Rictor were identified as potential key upstream regulators. These results suggest that soy and meat proteins induce distinct physiological and gene expression responses in rats and provide novel evidence and suggestions for the health effects of different protein sources in human diets. PMID:26857845

  4. Myoglobins: the link between discoloration and lipid oxidation in muscle and meat

    Directory of Open Access Journals (Sweden)

    Jens K. S. Møller

    2006-12-01

    Full Text Available Aerobic metabolism changes rapidly to glycolysis post-mortem resulting in a pH-decrease during the transformation of muscle in to meat affecting ligand binding and redox potential of the heme iron in myoglobin, the meat pigment. The "inorganic chemistry" of meat involves (i redox-cycling between iron(II, iron(III, and iron(IV/protein radicals; (ii ligand exchange processes; and (iii spin-equilibra with a change in coordination number for the heme iron. In addition to the function of myoglobin for oxygen storage, new physiological roles of myoglobin are currently being discovered, which notably find close parallels in the processes in fresh meat and nitrite-cured meat products. Myoglobin may be characterized as a bioreactor for small molecules like O2, NO, CO, CO2, H2O, and HNO with importance in bio-regulation and in protection against oxidative stress in vivo otherwise affecting lipids in membranes. Many of these processes may be recognised as colour changes in fresh meat and cured meat products under different atmospheric conditions, and could also be instructive for teaching purposes.

  5. Protein hydrolysate from turkey meat and optimization of its antioxidant potential by response surface methodology.

    Science.gov (United States)

    Wang, Daoying; Shahidi, Fereidoon

    2018-05-01

    The objective of this research was to optimize antioxidant potential of hydrolyzed protein using Flavourzyme assisted hydrolysis of turkey meat and compare the antioxidant activity of hydrolysates from turkey meat, chicken, and beef. Response surface methodology (RSM) was used to determine the optimal Flavourzyme hydrolysis conditions for preparation of hydrolysate from turkey meat, which were at a temperature of 50.09°C, pH of 5.42, and processing time of 1.08 hours. For comparison, antioxidant activities of the hydrolysate from turkey meat, chicken, and beef under the optimum conditions were determined using reducing power, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical cation, hydroxyl radical, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities. The antioxidant activity of turkey meat and chicken meat was significantly higher than that of beef (P turkey meat, indicating the potential use of it as a functional food ingredient with shelf-life extension purposes.

  6. 9 CFR 319.311 - Chow mein vegetables with meat, and chop suey vegetables with meat.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Chow mein vegetables with meat, and chop suey vegetables with meat. 319.311 Section 319.311 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY...

  7. Consumers' motivational associations favoring free-range meat or less meat

    NARCIS (Netherlands)

    de Boer, J.; Boersema, J.J.; Aiking, H.

    2009-01-01

    The present paper analyzed the motivational orientations of consumers who choose to eat (1) small portions of meat or (2) ethically distinctive meat, such as free-range meat, in relation to the motivational orientations of their opposites. Going beyond the conventional approach to consumer behavior,

  8. Longissimus muscle transcriptome profiles related to carcass and meat quality traits in fresh meat Pietrain carcasses

    NARCIS (Netherlands)

    Pas, te M.F.W.; Keuning, E.; Hulsegge, B.; Hoving-Bolink, A.H.; Evans, G.; Mulder, H.A.

    2010-01-01

    High quality pork is consumed as fresh meat while other carcasses are used in the processing industry. Meat quality is determined measuring technical muscle parameters. The objective of this research was to investigate the molecular regulatory mechanisms underlying meat quality differences of pork

  9. An Insight of Meat Industry in Pakistan with Special Reference to Halal Meat: A Comprehensive Review.

    Science.gov (United States)

    Sohaib, Muhammad; Jamil, Faraz

    2017-01-01

    Livestock is considered central component in agricultural sector of Pakistan, provides employment to more than 8 million families. Meat and meat products holds pivotal significance in meeting dietary requirements serving as major protein source and provide essential vitamins and minerals. Globally, consumer demand is increasing for healthy, hygienic and safe meat and meat products due to growing population, income level and food choices. As, food choices are mainly influenced by region, religion and economic level. However, religion is one of the major factor to influence the food choices. In this context, halal foods a growing trend, trade estimated to cross USD $ 3 trillion and among this, meat sector contribute about US$ 600 billion. Halal meat and allied products is requirement from Muslims but it is also accepted by non-Muslims due to safe and hygienic nature, nutritious value and superior quality. Pakistan meat industry is vibrant and has seen rigorous developments during last decade as government also showed interest to boost livestock production and processing facilities to meet increasing local and global demand. The industry has potential to grow owing to its natural animal rearing capability, muslim majority country (96% of total population), improvisation of market and consumer preference towards halal meat. Current review debates Pakistan meat industry scenario, production trend, global trade as well as future potential with respect to modernization, processing, distribution and trade. The data presented here is useful for meat producers, processors and people involved in export of Pakistani meat and meat based products.

  10. A unified phylogeny-based nomenclature for histone variants

    Directory of Open Access Journals (Sweden)

    Talbert Paul B

    2012-06-01

    Full Text Available Abstract Histone variants are non-allelic protein isoforms that play key roles in diversifying chromatin structure. The known number of such variants has greatly increased in recent years, but the lack of naming conventions for them has led to a variety of naming styles, multiple synonyms and misleading homographs that obscure variant relationships and complicate database searches. We propose here a unified nomenclature for variants of all five classes of histones that uses consistent but flexible naming conventions to produce names that are informative and readily searchable. The nomenclature builds on historical usage and incorporates phylogenetic relationships, which are strong predictors of structure and function. A key feature is the consistent use of punctuation to represent phylogenetic divergence, making explicit the relationships among variant subtypes that have previously been implicit or unclear. We recommend that by default new histone variants be named with organism-specific paralog-number suffixes that lack phylogenetic implication, while letter suffixes be reserved for structurally distinct clades of variants. For clarity and searchability, we encourage the use of descriptors that are separate from the phylogeny-based variant name to indicate developmental and other properties of variants that may be independent of structure.

  11. Trends in meat and meat products packaging – a review

    Directory of Open Access Journals (Sweden)

    Mia Kurek

    2010-01-01

    Full Text Available The aim of any packaging system for fresh muscle foods is to prevent or delay undesirable changes to the appearance, flavour, odour, and texture. Deterioration in these qualities can result in economic losses due to consumer rejection of the product. Therefore, a preservative packaging should ideally inhibit undesirable enzyme activities, but not interfere with, or inhibit, activities that are beneficial. The non-enzimatic reactions that affect the organoleptic qualities of raw meats are invariably undesirable, so these should preferably be slowed or prevented by a preservative packaging.

  12. The Functional Competence State of Patients with Rheumatic Arthritis and Different Variants of Polymorphic Site of 5-HTR2A T102C Gene or A-1438-G Depending on Sex

    Directory of Open Access Journals (Sweden)

    L. O. Protsiuk

    2016-03-01

    Full Text Available The state of functional competence in 100 patients with RA and different variants of polymorphic sites of serotonin receptor 5-HT2A T102C or A-1438-G gene was studied using the Health Assessment Questionnaire (HAQ. Polymorphic sites of T102C or A-1438-G gene were amplified with polymerase chain reaction. Anxiety level was assessed by Spielberger State-Trait Anxiety Scale (STAI. Depressive status and depression severity were evaluated by Hamilton Depression Rating Scale (HDRS. Results. In the study, we found that women with RA and TT and TC genotypes had significantly more frequent symptoms of fatigue, autonomic anxiety and depressive disorders (DS, high state, trait anxiety and symptoms of severe depression (p <0.001. Whereas women with CC genotype significantly more (p <0.05 often had mild symptoms of DS than women with GG genotype as compared with АG genotype women. According to HAQ findings women with TC, TT and GG genotype had decreased ability to perform minimal household physical activity as compared to male patients. Conclusions. Functional competence values proved to be considerably worse in female patients with TC and GG genotypes than in males. There was a tendency of more severe disorders in women with TT and AA genotypes. Positive relationship between HAQ index and anxiety depressive disorders in female patients with TC, CC, AA and GG genotypes were found while in patients with TT genotype this relationship was inverse.

  13. Functional Variants in Linc-ROR are Associated with mRNA Expression of Linc-ROR and Breast Cancer Susceptibility.

    Science.gov (United States)

    Luo, Chenglin; Cao, Jingjing; Peng, Rui; Guo, Qiaoyun; Ye, Hua; Wang, Peng; Wang, Kaijuan; Song, Chunhua

    2018-03-16

    Functional polymorphisms in Linc-ROR may change its ability of regulation by regulating Linc-ROR expression. However, these functional polymorphisms in Linc-ROR and their associations with breast cancer (BC) susceptibility were scarcely reported. In this molecular epidemiological study, four SNPs (rs6420545, rs4801078, rs1942348 and rs9636089) were selected in Linc-ROR by bioinformatics method. Unconditional logistic regression model was performed to analyze the associations between four SNPs and BC susceptibility adjusted for reproductive factors. Quantitative real-time (qRT) PCR was used to evaluate relative expression of Linc-ROR in plasma. The interactions of gene reproductive factors were assessed by Multifactor Dimensionality Reduction (MDR) method. A novel finding showed TT (OR: 1.79; 95%CI: 1.20-2.68) genotype of rs4801078 in Linc-ROR had a significant association with the higher risk of BC and the expression of Linc-ROR mRNA was closely related with the alleles of rs4801078. In addition, we found the interaction of rs4801078, number of pregnancy and menopausal status might increase BC risk (OR: 2.78; 95%CI: 2.74-3.61). Our results suggest that interactions of SNPs in Linc-ROR and reproductive factors might contribute to BC risk, and alleles of rs4801078 might affect Linc-ROR expression level.

  14. Radappertization of chicken and pork meat by irradiation

    International Nuclear Information System (INIS)

    Luna C, P.C.

    1992-05-01

    In this report the benefits that presents the irradiation process in the conservation of meat products, as the chicken, head meat and pig meat are analysed, also the implications that it brings in health and economical aspects. (Author)

  15. Fish, shellfish, and meat meals of the public in Singapore

    International Nuclear Information System (INIS)

    Burger, Joanna; Fleischer, Jennifer; Gochfeld, Michael

    2003-01-01

    Understanding different patterns of fish consumption is an important component of the assessment of risk from contaminants in fish. While there have been extensive studies of fish consumption in Western cultures, less attention has been devoted to the role of fish and meat in the diets of people in other cultures. A survey of 212 people living in Singapore was conducted to examine the relative importance of fish, shellfish, and other meat in their diets and to ascertain whether there were differences as a function of age, income, education or gender. As expected, fish and shellfish played an important role in their daily diets. On average, people ate fish in about 10 meals a week, chicken for eight meals, and shrimp and pork for about six meals each. While nearly 8% never ate fish, 18% ate fish at all 21 meals a week and over 20% ate shellfish for all 21 meals. Income explained about 14% of the variation in the number of fish meals consumed, and age explained about 8% of the variation in number of chicken meals per week. There were no gender differences in the number of meals of each type. People less than 26 years old ate significantly more pork, chicken, and other meat meals and fewer shellfish meals than older people. People with higher incomes ate significantly more fish meals than those with lower incomes. Chinese individuals ate significantly more meals of pork, chicken, and other meat than other ethnic groups, and they ate only 26% of their meals at home, while others ate 33% of their meals at home. The data indicate a great deal of variation in the number of meals of fish, shellfish, and other meats eaten by the people interviewed, making dietary and risk assessments challenging

  16. Immunofluorescence detection of milk protein in meat products

    Directory of Open Access Journals (Sweden)

    Michaela Petrášová

    2015-05-01

    Full Text Available Nowadays there are various vegetable protein additives intended for the manufacture of meat products in the food industry. These ingredients include both, plant-origin as well as animal-origin proteins. The most common vegetable additives include various types of flour, starch, fiber and plant protein. Among animal proteins, the most commonly used are plasma, collagen or milk protein. Milk protein is added to meat products due to its functional properties, such as emulsifying fats, improving the holding capacity of meat, improving juiciness, gel-forming capacity and affecting the taste of the product. Usage of these proteins, however, is currently limited by the effective legislation, not only in order to prevent consumer deception, but also because of their potential impact on consumers' health of. Thus, this issue has received considerable attention not only in the Czech Republic, but also globally. The main risk is the impossibility of selecting a suitable foodstuff for individuals with potential allergic reactions. The only option for allergic consumers to protect themselves is to strictly exclude the given allergen from their diet. Although the number of studies dealing with the reduction or loss of allergenicity is increasing, yet these practices are not common. Most of the population suffering from food allergies is thus still dependent on strict exclusion of foodstuffs causing adverse allergic reactions from their diet. Detection of allergens in foodstuffs is unfortunately quite difficult due to the fact that they occur in trace amounts and are often masked by different parts of the foodstuff. This research dealt with the detection of milk protein in meat products purchased in the market network of the Czech Republic, whereas declaration given by the manufacturer on the packaging for the small meat products purchased from the market was used to verify the detection of milk protein by the immunofluorescence method. 20 products were

  17. Meet meat: An explorative study on meat and cultured meat as seen by Chinese, Ethiopians and Dutch

    NARCIS (Netherlands)

    Bekker, G.A.; Tobi, H.; Fischer, A.R.

    2017-01-01

    In this cross-cultural study we investigated how study participants from China, Ethiopia and the Netherlands operationalize the concept of meat and to what extent cultured meat fits or does not fit into this operationalization. We argue that combining the conceptual approaches symbolic boundaries

  18. An APOA5 3' UTR variant associated with plasma triglycerides triggers APOA5 downregulation by creating a functional miR-485-5p binding site.

    Science.gov (United States)

    Caussy, Cyrielle; Charrière, Sybil; Marçais, Christophe; Di Filippo, Mathilde; Sassolas, Agnès; Delay, Mireille; Euthine, Vanessa; Jalabert, Audrey; Lefai, Etienne; Rome, Sophie; Moulin, Philippe

    2014-01-02

    APOA5 c.*158C>T (rs2266788), located in the 3' UTR, belongs to APOA5 haplotype 2 (APOA5*2), which is strongly associated with plasma triglyceride levels and modulates the occurrence of both moderate and severe hypertriglyceridemia. Individuals with APOA5*2 display reduced APOA5 expression at the posttranscriptional level. However, the functionality of this haplotype remains unclear. We hypothesized that the hypertriglyceridemic effects of APOA5*2 could involve miRNA regulation in the APOA5 3' UTR. Bioinformatic studies have identified the creation of a potential miRNA binding site for liver-expressed miR-485-5p (MIRN485-5p) in the mutant APOA5 3' UTR with the c.*158C allele. In human embryonic kidney 293T (HEK293T) cells cotransfected with an APOA5 3' UTR luciferase reporter vector and a miR485-5p precursor, c.*158C allele expression was significantly decreased. Moreover, in HuH-7 cells endogenously expressing miR-485-5p, we observed that luciferase activity was significantly lower in the presence of the c.*158C allele than in the presence of the c.*158T allele, which was completely reversed by a miR-485-5p inhibitor. We demonstrated that the rare c.*158C APOA5 allele creates a functional target site for liver-expressed miR-485-5p. Therefore, we propose that the well-documented hypertriglyceridemic effect of APOA5*2 involves an APOA5 posttranscriptional downregulation mediated by miR-485-5p. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  19. An APOA5 3′ UTR Variant Associated with Plasma Triglycerides Triggers APOA5 Downregulation by Creating a Functional miR-485-5p Binding Site

    Science.gov (United States)

    Caussy, Cyrielle; Charrière, Sybil; Marçais, Christophe; Di Filippo, Mathilde; Sassolas, Agnès; Delay, Mireille; Euthine, Vanessa; Jalabert, Audrey; Lefai, Etienne; Rome, Sophie; Moulin, Philippe

    2014-01-01

    APOA5 c.∗158C>T (rs2266788), located in the 3′ UTR, belongs to APOA5 haplotype 2 (APOA5∗2), which is strongly associated with plasma triglyceride levels and modulates the occurrence of both moderate and severe hypertriglyceridemia. Individuals with APOA5∗2 display reduced APOA5 expression at the posttranscriptional level. However, the functionality of this haplotype remains unclear. We hypothesized that the hypertriglyceridemic effects of APOA5∗2 could involve miRNA regulation in the APOA5 3′ UTR. Bioinformatic studies have identified the creation of a potential miRNA binding site for liver-expressed miR-485-5p (MIRN485-5p) in the mutant APOA5 3′ UTR with the c.∗158C allele. In human embryonic kidney 293T (HEK293T) cells cotransfected with an APOA5 3′ UTR luciferase reporter vector and a miR485-5p precursor, c.∗158C allele expression was significantly decreased. Moreover, in HuH-7 cells endogenously expressing miR-485-5p, we observed that luciferase activity was significantly lower in the presence of the c.∗158C allele than in the presence of the c.∗158T allele, which was completely reversed by a miR-485-5p inhibitor. We demonstrated that the rare c.∗158C APOA5 allele creates a functional target site for liver-expressed miR-485-5p. Therefore, we propose that the well-documented hypertriglyceridemic effect of APOA5∗2 involves an APOA5 posttranscriptional downregulation mediated by miR-485-5p. PMID:24387992

  20. A genetic variant in the IL-17 promoter is functionally associated with acute graft-versus-host disease after unrelated bone marrow transplantation.

    Directory of Open Access Journals (Sweden)

    J Luis Espinoza

    Full Text Available Interleukin IL-17 is a proinflammatory cytokine that has been implicated in the pathogenesis of various autoimmune diseases. The single nucleotide polymorphism (SNP, rs2275913, in the promoter region of the IL-17 gene is associated with susceptibility to ulcerative colitis. When we examined the impact of rs2275913 in a cohort consisting of 438 pairs of patients and their unrelated donors transplanted through the Japan Marrow Donor Program, the donor IL-17 197A allele was found to be associated with a higher risk of acute graft-versus-host disease (GVHD; hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.00 to 2.13; P = 0.05. Next, we investigated the functional relevance of the rs2275913 SNP. In vitro stimulated T cells from healthy individuals possessing the 197A allele produced significantly more IL-17 than those without the 197A allele. In a gene reporter assay, the 197A allele construct induced higher luciferase activity than the 197G allele, and the difference was higher in the presence of T cell receptor activation and was abrogated by cyclosporine treatment. Moreover, the 197A allele displayed a higher affinity for the nuclear factor activated T cells (NFAT, a critical transcription factor involved in IL-17 regulation. These findings substantiate the functional relevance of the rs2275913 polymorphism and indicate that the higher IL-17 secretion by individuals with the 197A allele likely accounts for their increased risk for acute GVHD and certain autoimmune diseases.

  1. Enantiospecific (+)- and (-)-germacrene D synthases, cloned from goldenrod, reveal a functionally active variant of the universal isoprenoid-biosynthesis aspartate-rich motif.

    Science.gov (United States)

    Prosser, Ian; Altug, Iris G; Phillips, Andy L; König, Wilfried A; Bouwmeester, Harro J; Beale, Michael H

    2004-12-15

    The naturally occurring, volatile sesquiterpene hydrocarbon germacrene D has strong effects on insect behaviour and genes encoding enzymes that produce this compound are of interest in the study of plant-insect interactions and in a number of biotechnological approaches to pest control. Goldenrod, Solidago canadensis, is unusual in that it produces both enantiomers of germacrene D. Two new sesquiterpene synthase cDNAs, designated Sc11 and Sc19, have been isolated from goldenrod and functional expression in Escherichia coli identified Sc11 as (+)-germacrene D synthase and Sc19 as (-)-germacrene D synthase. Thus, the enantiomers of germacrene D are the products of separate, but closely related (85% amino-acid identity), enzymes. Unlike other sesquiterpene synthases and the related monoterpene synthases and prenyl transferases, which contain the characteristic amino-acid motif DDXX(D,E), Sc11 is unusual in that this motif occurs as (303)NDTYD. Mutagenesis of this motif to (303)DDTYD gave rise to an enzyme that fully retained (+)-germacrene D synthase activity. The converse mutation in Sc19 (D303N) resulted in a less efficient but functional enzyme. Mutagenesis of position 303 to glutamate in both enzymes resulted in loss of activity. These results indicate that the magnesium ion-binding role of the first aspartate in the DDXXD motif may not be as critical as previously thought. Further amino-acid sequence comparisons and molecular modelling of the enzyme structures revealed that very subtle changes to the active site of this family of enzymes are required to alter the reaction pathway to form, in this case, different enantiomers from the same enzyme-bound carbocationic intermediate.

  2. Neurodevelopmental Disorders Caused by De Novo Variants in KCNB1 Genotypes and Phenotypes

    DEFF Research Database (Denmark)

    de Kovel, Carolien G F; Syrbe, Steffen; Brilstra, Eva H

    2017-01-01

    channel domain and loss-of-function variants in this domain and the C-terminal likely cause neurodevelopmental disorders with or without seizures. Patients with presumed pathogenic variants in KCNB1 have a variable phenotype. However, the type and position of the variants in the protein are (imperfectly...

  3. Novel trends in development of dietary fiber rich meat products-a critical review.

    Science.gov (United States)

    Mehta, Nitin; Ahlawat, S S; Sharma, D P; Dabur, R S

    2015-02-01

    Meat and meat products are generally recognized as good sources of high biological value proteins, fat-soluble vitamins, minerals, trace elements and bioactive compounds. Changes in socioeconomic factors in recent years have increased the consumer's preference for ready to eat foods including meat products. The processing of meat and meat products leads to generation of many functional compounds beneficial to human health but most of those foods are rich in fat, added salts but deficient in complex carbohydrates like dietary fiber and pose a health hazard that somehow is proved to be a predisposing factor for cardiovascular diseases, colon cancer, obesity including diabetes mellitus. With increasing consciousness among consumers about their nutrition and well being, there is a growing concern over nutritional diseases of affluence. Therefore an increase in dietary fiber inclusion in daily diet has been recommended. For adults, the recommended acceptable intakes of dietary fiber are 28-36 g/day, 70-80 % of which must be insoluble fiber. The insoluble fraction of dietary fiber has been related to intestinal regulation whereas soluble fiber is associated with decrease in cholesterol level and absorption of intestinal glucose. So incorporation of dietary fibers from different sources in meat products would help to enhance their desirability. Dietary fiber sources are generally agricultural byproducts that are comparatively cheap and incorporation in meat products reduces its overall cost. Whole grains and cereal brans are the rich source of insoluble fiber and pectins, gums, starch and other storage polysaccharides have high content of the soluble fraction. With this background, the effect of various dietary fibers on the quality attributes of meat and meat products with its physiological role has been reviewed here.

  4. ACTIVE PACKAGING SYSTEM FOR MEAT AND MEAT PRODUCTS

    Directory of Open Access Journals (Sweden)

    Adriana Pavelková

    2012-10-01

    Full Text Available In the recent past, food packaging was used to enable marketing of products and to provide passive protection against environmental contaminations or influences that affect the shelf life of the products. However, unlike traditional packaging, which must be totally inert, active packaging is designed to interact with the contents and/or the surrounding environment. Interest in the use of active packaging systems for meat and meat products has increased in recent years. Active packaging systems are developed with the goal of extending shelf life for foods and increasing the period of time that the food is high quality. Developments in active packaging have led to advances in many areas, including delayed oxidation and controlled respiration rate, microbial growth, and moisture migration. Active packaging technologies include some physical, chemical, or biological action which changes interactions between a package, product, and/or headspace of the package in order to get a desired outcome. Active packaging systems discussed include oxygen scavengers, carbon dioxide scavengers and emitters, moisture control agents, flavour/odour absorbers and releasers  and antimicrobial packaging technologies. Active packaging is typically found in two types of systems; sachets and pads which are placed inside of packages, and active ingredients that are incorporated directly into packaging materials.  Recognition of the benefits of active packaging technologies by the food industry, development of economically viable packaging systems and increased consumer acceptance is necessary for com