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See detailGenetic and kinetic characterization of the novel AmpC beta-lactamases DHA-6 and DHA-7.
Perez-Llarena, Francisco Jose; Zamorano, Laura; Kerff, Frédéric ULg et al

in Antimicrobial agents and chemotherapy (2014)

During a Spanish surveillance study, two natural variants of DHA beta-lactamases, DHA-6 and DHA-7 were found, with the replacements Ala226Thr and Phe322Ser respect to DHA-1, respectively. The enzymes were ... [more ▼]

During a Spanish surveillance study, two natural variants of DHA beta-lactamases, DHA-6 and DHA-7 were found, with the replacements Ala226Thr and Phe322Ser respect to DHA-1, respectively. The enzymes were isolated from Escherichia coli and Enterobacter cloacae clinical isolates, respectively. The aim of the study was the genetic, microbiological and biochemical characterization of the DHA-6 and DHA-7 beta-lactamases. The blaDHA-6 andblaDHA-7 genes were located in I1 and HI2 incompatibility group plasmids of 87.3 and 310.4 kb, respectively. The gene context of both blaDHA-6 andblaDHA-7 was similar to that already described for blaDHA-1 gene and included the qnrB4 and aadA genes. The MICs for cephalothin, aztreonam, cefotaxime and ceftazidime were 8 to 30 fold lower for the DHA-6 than for DHA-1 and DHA-7 expressed in the same isogenic E.coli TG1 strain. Interestingly the MIC for cefoxitin was higher in DHA-6 expressing transformant compared to DHA-1 and DHA-7. Biochemical studies with pure beta-lactamases revealed a slightly lower catalytic efficiency of DHA-6 against cephalothin, ceftazidime and cefotaxime compared to DHA-1 and DHA-7. To understand this behavior, stability experiments were carried out and showed that the DHA-6 protein displayed a significantly higher stability than DHA-1 and DHA-7 enzymes. The proximity of Thr226 to the N-terminal in the tertiary protein structure in DHA-6 may promote this stabilization and consequently could induce a slight reduction of the dynamic of this enzyme primarily affecting the hydrolysis of some of the bulkiest antibiotics. [less ▲]

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See detailGenetic and microbial factors modulating the ubiquitin proteasome system in inflammatory bowel disease.
Cleynen, Isabelle; Vazeille, Emilie; Artieda, Marta et al

in Gut (2013)

OBJECTIVE: Altered microbiota composition, changes in immune responses and impaired intestinal barrier functions are observed in IBD. Most of these features are controlled by proteases and their ... [more ▼]

OBJECTIVE: Altered microbiota composition, changes in immune responses and impaired intestinal barrier functions are observed in IBD. Most of these features are controlled by proteases and their inhibitors to maintain gut homeostasis. Unrestrained or excessive proteolysis can lead to pathological gastrointestinal conditions. The aim was to validate the identified protease IBD candidates from a previously performed systematic review through a genetic association study and functional follow-up. DESIGN: We performed a genetic association study in a large multicentre cohort of patients with Crohn's disease (CD) and UC from five European IBD referral centres in a total of 2320 CD patients, 2112 UC patients and 1796 healthy controls. Subsequently, we did an extensive functional assessment of the candidate genes to explore their causality in IBD pathogenesis. RESULTS: Ten single nucleotide polymorphisms (SNPs) in four genes were significantly associated with CD: CYLD, USP40, APEH and USP3. CYLD was the most significant gene with the intronically located rs12324931 the strongest associated SNP (pFDR=1.74e-17, OR=2.24 (1.83 to 2.74)). Five SNPs in four genes were significantly associated with UC: USP40, APEH, DAG1 and USP3. CYLD, as well as some of the other associated genes, is part of the ubiquitin proteasome system (UPS). We therefore determined if the IBD-associated adherent-invasive Escherichia coli (AIEC) can modulate the UPS functioning. Infection of intestinal epithelial cells with the AIEC LF82 reference strain modulated the UPS turnover by reducing poly-ubiquitin conjugate accumulation, increasing 26S proteasome activities and decreasing protein levels of the NF-kappaB regulator CYLD. This resulted in IkappaB-alpha degradation and NF-kappaB activation. This activity was very important for the pathogenicity of AIEC since decreased CYLD resulted in increased ability of AIEC LF82 to replicate intracellularly. CONCLUSIONS: Our results reveal the UPS, and CYLD specifically, as an important contributor to IBD pathogenesis, which is favoured by both genetic and microbial factors. [less ▲]

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See detailGenetic and non genetic effects on growth traits of West African Dwarf sheep in Benin (West Africa)
Gbangboche, A. B.; Abiola, F. A.; Alimi, S. et al

in Livestock Production Science (2008)

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See detailGenetic and splice variations of Bos taurus CD46 shift cell permissivity to BVDV, the bovine pestivirus.
Zezafoun, Hussein ULg; Decreux, Annabelle; Desmecht, Daniel ULg

in Veterinary Microbiology (2011), 152(3-4), 315-27

The pestivirus bovine viral diarrhea virus (BVDV) is known to bind to the CD46 molecule, which subsequently promotes entry of the virus. Mapping of the BVD-virion-binding site has shown that two peptides ... [more ▼]

The pestivirus bovine viral diarrhea virus (BVDV) is known to bind to the CD46 molecule, which subsequently promotes entry of the virus. Mapping of the BVD-virion-binding site has shown that two peptides, 66EQIV69 and 82GQVLAL87, located on antiparallel beta sheets in the most distal complement control protein module (CCP1), provide the attachment platform. In the present study, we reveal the existence of ten distinct allelic versions of the CCP1 module, varying significantly in frequency among taurine and indicine races. A complex mRNA splicing pattern was also evidenced for bovine CD46, generating three different serine-threonine-proline segments and five different cytoplasmic domains. The four most frequent allelic variants and the six splice variants were then expressed in BVDV-nonpermissive porcine cells and the quantity of progeny virions generated by each cell preparation was measured 48 h post-infection. As expected, ectopic expression of the 10 bovine CD46 isoforms rendered the PK15 cells permissive to BVDV, as attested by the 100,000-fold greater recovery of virions from these cells than from non-transfected cells. This permissivity increase was significantly lower (-33%, P<0.001) when the canonical CCP1 was replaced with the variant most frequent in zebus, suggesting positive or negative selection of this allele in the latter and in the former, respectively. The predicted secondary structure of this variant suggests that the measured loss of function is due to the disappearance of one of the two beta sheets constituting the BVDV attachment platform. On the other hand we showed that for a given CCP1, the titer recovered at 48 hpi also depended on the nature of the CD46 cytoplasmic domain (P<0.001). This result implies that virus binding generates a cytoplasmic-tail-dependent outside-in signal that determines permissivity to BVDV. [less ▲]

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See detailGenetic aspects of abdominal aortic aneurysm.
VERLOES, Alain ULg; SakalihasanN, Natzi ULg; Limet, Raymond ULg et al

in Annals of the New York Academy of Sciences (1996), 800

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See detailGenetic association and functional role of Crohn disease risk alleles involved in microbial sensing, autophagy, and endoplasmic reticulum (ER) stress.
Hoefkens, Eveline; Nys, Kris; John, Jestinah M. et al

in Autophagy (2013), 9(12), 2046-55

Genome-wide association studies have identified several genes implicated in autophagy (ATG16L1, IRGM, ULK1, LRRK2, and MTMR3), intracellular bacterial sensing (NOD2), and endoplasmic reticulum (ER) stress ... [more ▼]

Genome-wide association studies have identified several genes implicated in autophagy (ATG16L1, IRGM, ULK1, LRRK2, and MTMR3), intracellular bacterial sensing (NOD2), and endoplasmic reticulum (ER) stress (XBP1 and ORMDL3) to be associated with Crohn disease (CD). We studied the known CD-associated variants in these genes in a large cohort of 3451 individuals (1744 CD patients, 793 ulcerative colitis (UC) patients and 914 healthy controls). We also investigated the functional phenotype linked to these genetic variants. Association with CD was confirmed for NOD2, ATG16L1, IRGM, MTMR3, and ORMDL3. The risk for developing CD increased with an increasing number of risk alleles for these genes (P<0.001, OR 1.26 [1.20 to 1.32]). Three times as many (34.8%) CD patients carried a risk allele in all three pathways, in contrast to 13.3% of the controls (P<0.0001, OR = 3.46 [2.77 to 4.32]). For UC, no significant association for one single nucleotide polymorphism (SNP) was found, but the risk for development of UC increased with an increasing total number of risk alleles (P = 0.001, OR = 1.10 [1.04 to 1.17]). We found a genetic interaction between reference SNP (rs)2241880 (ATG16L1) and rs10065172 (IRGM) in CD. Functional experiments hinted toward an association between an increased genetic risk and an augmented inflammatory status, highlighting the relevance of the genetic findings. [less ▲]

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See detailGenetic basis of congenital erythrocytosis: mutation update and online databases.
Bento, Celeste; Percy, Melanie J.; Gardie, Betty et al

in Human mutation (2014), 35(1), 15-26

Congenital erythrocytosis (CE), or congenital polycythemia, represents a rare and heterogeneous clinical entity. It is caused by deregulated red blood cell production where erythrocyte overproduction ... [more ▼]

Congenital erythrocytosis (CE), or congenital polycythemia, represents a rare and heterogeneous clinical entity. It is caused by deregulated red blood cell production where erythrocyte overproduction results in elevated hemoglobin and hematocrit levels. Primary congenital familial erythrocytosis is associated with low erythropoietin (Epo) levels and results from mutations in the Epo receptor gene (EPOR). Secondary CE arises from conditions causing tissue hypoxia and results in increased Epo production. These include hemoglobin variants with increased affinity for oxygen (HBB, HBA mutations), decreased production of 2,3-bisphosphoglycerate due to BPGM mutations, or mutations in the genes involved in the hypoxia sensing pathway (VHL, EPAS1, and EGLN1). Depending on the affected gene, CE can be inherited either in an autosomal dominant or recessive mode, with sporadic cases arising de novo. Despite recent important discoveries in the molecular pathogenesis of CE, the molecular causes remain to be identified in about 70% of the patients. With the objective of collecting all the published and unpublished cases of CE the COST action MPN&MPNr-Euronet developed a comprehensive Internet-based database focusing on the registration of clinical history, hematological, biochemical, and molecular data (http://www.erythrocytosis.org/). In addition, unreported mutations are also curated in the corresponding Leiden Open Variation Database. [less ▲]

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See detailGénétic causes : Awareness, who and how to screen
Beckers, Albert ULg

Scientific conference (2007, September 28)

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See detailGenetic causes of familial pituitary adenomas
Vandeva, Silvia; Zacharieva, S.; Daly, Adrian ULg et al

in Growth Hormone Related Diseases and Therapy - Contemporary Endocrinology (2011)

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See detailGenetic Causes of Pituitary Adenmas; Focus on the Roe of AIF Status in Multiple Tumor Types
Ansaneli Naves, L.; Ferreira Azevedo, M.; Faria de Castro, L. et al

in ENDO 2008: 90th Annual Meeting of the Endocrine Society - Abstract book (2008)

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See detailGenetic causes of pituitary diseases
Beckers, Albert ULg

Scientific conference (2010, October)

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See detailGenetic characterization of the Indian cattle breeds, Ongole and Deoni (Bos indicus), using microsatellite markers - a preliminary study.
Metta, Muralidhar ULg; Kanginakudru, Sriramana; Gudiseva, Narasimharao et al

in BMC Genetics (2004), 5

BACKGROUND: Molecular characterization of cattle breeds is important for the prevention of germplasm erosion by cross breeding. The Indian zebu cattle have their significant role in evolution of present ... [more ▼]

BACKGROUND: Molecular characterization of cattle breeds is important for the prevention of germplasm erosion by cross breeding. The Indian zebu cattle have their significant role in evolution of present day cattle breeds and development of some of the exotic breeds. Microsatellites are the best available molecular tools for characterization of cattle breeds. The present study was carried out to characterize two Indian cattle breeds, Ongole and Deoni, using microsatellite markers. RESULTS: Using 5 di- and 5 tri-nucleotide repeat loci, 17 Ongole and 13 Deoni unrelated individuals were studied. Of the ten loci, eight revealed polymorphism in both the breeds. The di-nucleotide repeat loci were found to be more polymorphic (100%) than tri-nucleotide repeat loci (60%). A total of 39 polymorphic alleles were obtained at 4.5 alleles per locus in Ongole and 4.1 in Deoni. The average expected heterozygosity was 0.46 (+/-0.1) and 0.50 (+/-0.1) in Ongole and Deoni breeds, respectively. The PIC values of the polymorphic loci ranged from 0.15 to 0.79 in Ongole and 0.13 to 0.80 in Deoni breeds. Six Ongole specific and three Deoni specific alleles were identified. The two breeds showed a moderate genetic relationship between themselves with a FST value of 0.117 (P = 0.01). CONCLUSIONS: This preliminary study shows that microsatellite markers are useful in distinguishing the two zebu breeds namely, Ongole and Deoni. Further studies of other zebu breeds using many microsatellite loci with larger sample sizes can reveal the genetic relationships of Indian breeds. [less ▲]

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See detailGenetic Characterization Of The Yeast Pichia Anomala (Strain K), An Antagonist Of Postharvest Diseases Of Apple
Friel, D.; Vandenbol, Micheline ULg; Jijakli, Mohamed ULg

in Journal of Applied Microbiology (2005), 98(3),

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See detailGenetic control of flowering time in maize
Périlleux, Claire ULg; Colasanti, J.; Irish, E.

in Prioul, J.-L.; Thévenot, C.; Molnar, T. (Eds.) Advances in Maize (2011)

Flowering in temperate maize occurs largely autonomously after the plant has accumulated a given amount of vegetative growth. Mutants affected in leaf initiation rate or in phyllotaxy however indicate ... [more ▼]

Flowering in temperate maize occurs largely autonomously after the plant has accumulated a given amount of vegetative growth. Mutants affected in leaf initiation rate or in phyllotaxy however indicate that total leaf number can vary independently of flowering time, e.g. in relation with cytokinin signalling. By contrast, heterochronic mutants in which juvenile-to-adult and/or adult vegetative-to-reproductive phase changes are abnormal aided in the identification of key regulators of endogenous developmental timing in maize. These regulators include gibberellins and micro-RNAs, such as miR156 and miR172, which have been identified more recently. Progress towards unravelling the maize flowering time genetic network is also emerging from comparison with other species. Although maize expansion beyond domestication centres implied reduction in photoperiod sensitivity, molecular genetic studies indicated conservation of genes which, in Arabidopsis or rice, act in a signalling cascade whereby flowering is controlled by photoperiod. Several gene sequences are now available to assess functionality of such a pathway in maize and evaluate its contribution to flowering time control. [less ▲]

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See detailGenetic control of isozymes in the primary gene pool Phaseolus lunatus L.
Bi, Irié Zoro; Maquet, Alain; Wathelet, Bernard ULg et al

in Biotechnologie, Agronomie, Société et Environnement = Biotechnology, Agronomy, Society and Environment [=BASE] (1999)

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See detailGenetic correlations among body condition score, yield and fertility in multiparous cows using random regression models
Bastin, Catherine ULg; Gillon, Alain ULg; Massart, Xavier et al

in Proceedings of the 9th World Congress on Genetics Applied to Livestock Production (2010, August)

Genetic correlations between body condition score (BCS) in lactation 1 to 3 and four economically important traits (days open, 305-days milk, fat, and protein yields recorded in the first 3 lactations ... [more ▼]

Genetic correlations between body condition score (BCS) in lactation 1 to 3 and four economically important traits (days open, 305-days milk, fat, and protein yields recorded in the first 3 lactations) were estimated on about 12,500 Walloon Holstein cows using 4-trait random regression models. Results indicated moderate favorable genetic correlations between BCS and days open (from -0.46 to -0.62) and suggested the use of BCS for indirect selection on fertility. However, unfavorable genetic correlations between BCS and yields (from -0.16 to -0.71) indicated that selection on BCS would have deleterious effects on milk, fat, and protein yields, especially in lactation greater than 1. [less ▲]

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See detailGenetic correlations of days open with production traits and contents in milk of major fatty acids predicted by mid-infrared spectrometry.
Bastin, Catherine ULg; Berry, D. P.; Soyeurt, Hélène ULg et al

in Journal of Dairy Science (2012), 95(10), 6113-21

The objective of this study was to estimate the genetic relationships between days open (DO) and both milk production traits and fatty acid (FA) content in milk predicted by mid-infrared spectrometry. The ... [more ▼]

The objective of this study was to estimate the genetic relationships between days open (DO) and both milk production traits and fatty acid (FA) content in milk predicted by mid-infrared spectrometry. The edited data set included 143,332 FA and production test-day records and 29,792 DO records from 29,792 cows in 1,170 herds. (Co)variances were estimated using a series of 2-trait models that included a random regression for milk production and FA traits. In contrast to the genetic correlations with fat content, those between DO and FA content in milk changed considerably over the lactation. The genetic correlations with DO for unsaturated FA, monounsaturated FA, long-chain FA, C18:0, and C18:1 cis-9 were positive in early lactation but negative after 100 d in milk. For the other FA, genetic correlations with DO were negative across the whole lactation. At 5 d in milk, the genetic correlation between DO and C18:1 cis-9 was 0.39, whereas the genetic correlations between DO and C6:0 to C16:0 FA ranged from -0.37 to -0.23. These results substantiated the known relationship between fertility and energy balance status, explained by the release of long-chain FA in early lactation, from the mobilization of body fat reserves, and the consequent inhibition of de novo FA synthesis in the mammary gland. At 200 d in milk, the genetic correlations between DO and FA content ranged from -0.38 for C18:1 cis-9 to -0.03 for C6:0. This research indicates an opportunity to use FA content in milk as an indicator trait to supplement the prediction of genetic merit for fertility. [less ▲]

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