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Sample records for met allele load

  1. Effects of the BDNF Val66Met polymorphism and met allele load on declarative memory related neural networks

    Dodds, Chris M; Henson, Richard N; Suckling, John

    2013-01-01

    It has been suggested that the BDNF Val66Met polymorphism modulates episodic memory performance via effects on hippocampal neural circuitry. However, fMRI studies have yielded inconsistent results in this respect. Moreover, very few studies have examined the effect of met allele load on activatio...

  2. Effects of the BDNF Val66Met polymorphism and met allele load on declarative memory related neural networks.

    Dodds, Chris M; Henson, Richard N; Suckling, John; Miskowiak, Kamilla W; Ooi, Cinly; Tait, Roger; Soltesz, Fruzsina; Lawrence, Phil; Bentley, Graham; Maltby, Kay; Skeggs, Andrew; Miller, Sam R; McHugh, Simon; Bullmore, Edward T; Nathan, Pradeep J

    2013-01-01

    It has been suggested that the BDNF Val66Met polymorphism modulates episodic memory performance via effects on hippocampal neural circuitry. However, fMRI studies have yielded inconsistent results in this respect. Moreover, very few studies have examined the effect of met allele load on activation of memory circuitry. In the present study, we carried out a comprehensive analysis of the effects of the BDNF polymorphism on brain responses during episodic memory encoding and retrieval, including an investigation of the effect of met allele load on memory related activation in the medial temporal lobe. In contrast to previous studies, we found no evidence for an effect of BDNF genotype or met load during episodic memory encoding. Met allele carriers showed increased activation during successful retrieval in right hippocampus but this was contrast-specific and unaffected by met allele load. These results suggest that the BDNF Val66Met polymorphism does not, as previously claimed, exert an observable effect on neural systems underlying encoding of new information into episodic memory but may exert a subtle effect on the efficiency with which such information can be retrieved.

  3. Effects of the BDNF Val66Met polymorphism and met allele load on declarative memory related neural networks.

    Chris M Dodds

    Full Text Available It has been suggested that the BDNF Val66Met polymorphism modulates episodic memory performance via effects on hippocampal neural circuitry. However, fMRI studies have yielded inconsistent results in this respect. Moreover, very few studies have examined the effect of met allele load on activation of memory circuitry. In the present study, we carried out a comprehensive analysis of the effects of the BDNF polymorphism on brain responses during episodic memory encoding and retrieval, including an investigation of the effect of met allele load on memory related activation in the medial temporal lobe. In contrast to previous studies, we found no evidence for an effect of BDNF genotype or met load during episodic memory encoding. Met allele carriers showed increased activation during successful retrieval in right hippocampus but this was contrast-specific and unaffected by met allele load. These results suggest that the BDNF Val66Met polymorphism does not, as previously claimed, exert an observable effect on neural systems underlying encoding of new information into episodic memory but may exert a subtle effect on the efficiency with which such information can be retrieved.

  4. Effects of the BDNF Val66Met Polymorphism and Met Allele Load on Declarative Memory Related Neural Networks

    Dodds, Chris M.; Henson, Richard N.; Suckling, John; Miskowiak, Kamilla W.; Ooi, Cinly; Tait, Roger; Soltesz, Fruzsina; Lawrence, Phil; Bentley, Graham; Maltby, Kay; Skeggs, Andrew; Miller, Sam R.; McHugh, Simon; Bullmore, Edward T.; Nathan, Pradeep J.

    2013-01-01

    It has been suggested that the BDNF Val66Met polymorphism modulates episodic memory performance via effects on hippocampal neural circuitry. However, fMRI studies have yielded inconsistent results in this respect. Moreover, very few studies have examined the effect of met allele load on activation of memory circuitry. In the present study, we carried out a comprehensive analysis of the effects of the BDNF polymorphism on brain responses during episodic memory encoding and retrieval, including...

  5. Transmission of epi-alleles with MET1-dependent dense methylation in Arabidopsis thaliana.

    Michael Watson

    Full Text Available DNA methylation in plants targets cytosines in three sequence contexts, CG, CHG and CHH (H representing A, C or T. Each of these patterns has traditionally been associated with distinct DNA methylation pathways with CHH methylation being controlled by the RNA dependent DNA methylation (RdDM pathway employing small RNAs as a guide for the de novo DOMAINS REARRANGED METHYLTRANSFERASE (DRM2, and maintenance DNA METHYLTRANSFERASE1 (MET1 being responsible for faithful propagation of CG methylation. Here we report an unusual 'dense methylation' pattern under the control of MET1, with methylation in all three sequence contexts. We identified epi-alleles of dense methylation at a non coding RNA locus (At4g15242 in Arabidopsis ecotypes, with distinct dense methylation and expression characteristics, which are stably maintained and transmitted in genetic crosses and which can be heritably altered by depletion of MET1. This suggests that, in addition to its classical CG maintenance function, at certain loci MET1 plays a role in creating transcriptional diversity based on the generation of independent epi-alleles. Database inspection identified several other loci with MET1-dependent dense methylation patterns. Arabidopsis ecotypes contain distinct epi-alleles of these loci with expression patterns that inversely correlate with methylation density, predominantly within the transcribed region. In Arabidopsis, dense methylation appears to be an exception as it is only found at a small number of loci. Its presence does, however, highlight the potential for MET1 as a contributor to epigenetic diversity, and it will be interesting to investigate the representation of dense methylation in other plant species.

  6. Impaired cognitive flexibility during sleep deprivation among carriers of the Brain Derived Neurotrophic Factor (BDNF) Val66Met allele.

    Grant, Leilah K; Cain, Sean W; Chang, Anne-Marie; Saxena, Richa; Czeisler, Charles A; Anderson, Clare

    2018-02-15

    Accumulating evidence points to a genetic contribution to explain inter-individual vulnerability to sleep deprivation. A functional polymorphism in the BDNF gene, which causes a valine (Val) to methionine (Met) amino acid substitution at Codon 66, has been associated with cognitive impairment, particularly in populations with impaired frontal functioning. We hypothesised that sleep deprivation, which affects frontal function, may lead to cognitive dysfunction in Met allele carriers. To examine this, we investigated, in different BDNF genotypes, the effects of sleep deprivation on cognitive flexibility, as measured by response inhibition using the Stroop Color Naming Task. Thirty healthy, adults of European ancestry, including 12 heterozygous Met allele carriers and 18 Val/Val homozygotes, underwent 30-h of extended wakefulness under constant routine conditions. A computerised Stroop task was administered every 2h. Error rate and reaction times increased with time awake for all individuals. Participants with the Val/Met genotype made more errors on incongruent trials after 20h awake. While Val/Met participants also took significantly longer to respond when inhibiting a prepotent response irrespective of time awake, this was particularly evident during the biological night. Our study shows that carriers of the BDNF Met allele are more vulnerable to the impact of prolonged wakefulness and the biological night on a critical component of executive function, as measured by response inhibition on the Stroop task. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. The CFTR Met 470 allele is associated with lower birth rates in fertile men from a population isolate.

    Gülüm Kosova

    2010-06-01

    Full Text Available Although little is known about the role of the cystic fibrosis transmembrane regulator (CFTR gene in reproductive physiology, numerous variants in this gene have been implicated in etiology of male infertility due to congenital bilateral absence of the vas deferens (CBAVD. Here, we studied the fertility effects of three CBAVD-associated CFTR polymorphisms, the (TGm and polyT repeat polymorphisms in intron 8 and Met470Val in exon 10, in healthy men of European descent. Homozygosity for the Met470 allele was associated with lower birth rates, defined as the number of births per year of marriage (P = 0.0029. The Met470Val locus explained 4.36% of the phenotypic variance in birth rate, and men homozygous for the Met470 allele had 0.56 fewer children on average compared to Val470 carrier men. The derived Val470 allele occurs at high frequencies in non-African populations (allele frequency = 0.51 in HapMap CEU, whereas it is very rare in African population (Fst = 0.43 between HapMap CEU and YRI. In addition, haplotypes bearing Val470 show a lack of genetic diversity and are thus longer than haplotypes bearing Met470 (measured by an integrated haplotype score [iHS] of -1.93 in HapMap CEU. The fraction of SNPs in the HapMap Phase2 data set with more extreme Fst and iHS measures is 0.003, consistent with a selective sweep outside of Africa. The fertility advantage conferred by Val470 relative to Met470 may provide a selective mechanism for these population genetic observations.

  8. Preventing the Return of Fear Using Reconsolidation Update Mechanisms Depends on the Met-Allele of the Brain Derived Neurotrophic Factor Val66Met Polymorphism.

    Asthana, Manish Kumar; Brunhuber, Bettina; Mühlberger, Andreas; Reif, Andreas; Schneider, Simone; Herrmann, Martin J

    2016-06-01

    Memory reconsolidation is the direct effect of memory reactivation followed by stabilization of newly synthesized proteins. It has been well proven that neural encoding of both newly and reactivated memories requires synaptic plasticity. Brain derived neurotrophic factor (BDNF) has been extensively investigated regarding its role in the formation of synaptic plasticity and in the alteration of fear memories. However, its role in fear reconsolidation is still unclear; hence, the current study has been designed to investigate the role of the BDNF val66met polymorphism (rs6265) in fear memory reconsolidation in humans. An auditory fear-conditioning paradigm was conducted, which comprised of three stages (acquisition, reactivation, and spontaneous recovery). One day after fear acquisition, the experimental group underwent reactivation of fear memory followed by the extinction training (reminder group), whereas the control group (non-reminder group) underwent only extinction training. On day 3, both groups were subjected to spontaneous recovery of earlier learned fearful memories. The treat-elicited defensive response due to conditioned threat was measured by assessing the skin conductance response to the conditioned stimulus. All participants were genotyped for rs6265. The results indicate a diminishing effect of reminder on the persistence of fear memory only in the Met-allele carriers, suggesting a moderating effect of the BDNF polymorphism in fear memory reconsolidation. Our findings suggest a new role for BDNF gene variation in fear memory reconsolidation in humans. © The Author 2016. Published by Oxford University Press on behalf of CINP.

  9. The enzymatic activities of brain catechol-O-methyltransferase (COMT) and methionine sulphoxide reductase are correlated in a COMT Val/Met allele-dependent fashion.

    Moskovitz, Jackob; Walss-Bass, Consuelo; Cruz, Dianne A; Thompson, Peter M; Hairston, Jenaqua; Bortolato, Marco

    2015-12-01

    The enzyme catechol-O-methyltransferase (COMT) plays a primary role in the metabolism of catecholamine neurotransmitters and is implicated in the modulation of cognitive and emotional responses. The best characterized single nucleotide polymorphism (SNP) of the COMT gene consists of a valine (Val)-to-methionine (Met) substitution at codon 108/158. The Met-containing variant confers a marked reduction in COMT catalytic activity. We recently showed that the activity of recombinant COMT is positively regulated by the enzyme Met sulphoxide reductase (MSR), which counters the oxidation of Met residues of proteins. The current study was designed to assess whether brain COMT activity may be correlated to MSR in an allele-dependent fashion. COMT and MSR activities were measured from post-mortem samples of prefrontal cortices, striata and cerebella of 32 subjects by using catechol and dabsyl-Met sulphoxide as substrates, respectively. Allelic discrimination of COMT Val(108/185) Met SNP was performed using the Taqman 5'nuclease assay. Our studies revealed that, in homozygous carriers of Met, but not Val alleles, the activity of COMT and MSR was significantly correlated throughout all tested brain regions. These results suggest that the reduced enzymatic activity of Met-containing COMT may be secondary to Met sulphoxidation and point to MSR as a key molecular determinant for the modulation of COMT activity. © 2015 British Neuropathological Society.

  10. Cattle with the BoLA class II DRB3*0902 allele have significantly lower bovine leukemia proviral loads.

    Hayashi, Takumi; Mekata, Hirohisa; Sekiguchi, Satoshi; Kirino, Yumi; Mitoma, Shuya; Honkawa, Kazuyuki; Horii, Yoichiro; Norimine, Junzo

    2017-09-12

    The bovine MHC (BoLA) class II DRB3 alleles are associated with polyclonal expansion of lymphocytes caused by bovine leukemia virus (BLV) infection in cattle. To examine whether the DRB3*0902 allele, one of the resistance-associated alleles, is associated with the proviral load, we measured BLV proviral load of BLV-infected cattle and clarified their DRB3 alleles. Fifty-seven animals with DRB3*0902 were identified out of 835 BLV-infected cattle and had significantly lower proviral load (Pclass II DRA/DRB3*0902 molecule plays an important immunological role in suppressing viral replication, resulting in resistance to the disease progression.

  11. Lower baseline performance but greater plasticity of working memory for carriers of the val allele of the COMT Val¹⁵⁸Met polymorphism.

    Bellander, Martin; Bäckman, Lars; Liu, Tian; Schjeide, Brit-Maren M; Bertram, Lars; Schmiedek, Florian; Lindenberger, Ulman; Lövdén, Martin

    2015-03-01

    Little is known about genetic contributions to individual differences in cognitive plasticity. Given that the neurotransmitter dopamine is critical for cognition and associated with cognitive plasticity, we investigated the effects of 3 polymorphisms of dopamine-related genes (LMX1A, DRD2, COMT) on baseline performance and plasticity of working memory (WM), perceptual speed, and reasoning. One hundred one younger and 103 older adults underwent approximately 100 days of cognitive training, and extensive testing before and after training. We analyzed the baseline and posttest data using latent change score models. For working memory, carriers of the val allele of the COMT polymorphism had lower baseline performance and larger performance gains from training than carriers of the met allele. There was no significant effect of the other genes or on other cognitive domains. We relate this result to available evidence indicating that met carriers perform better than val carriers in WM tasks taxing maintenance, whereas val carriers perform better at updating tasks. We suggest that val carriers may show larger training gains because updating operations carry greater potential for plasticity than maintenance operations. PsycINFO Database Record (c) 2015 APA, all rights reserved.

  12. Headway Deviation Effects on Bus Passenger Loads : Analysis of Tri-Met's Archived AVL-APC Data

    2003-01-01

    In this paper we empirically analyze the relationship between transit service headway deviations and passenger loads, using archived data from Tri-Met's automatic vehicle location and automatic passenger counter systems. The analysis employs twostage...

  13. Interaction between BDNF rs6265 Met allele and low family cohesion is associated with smaller left hippocampal volume in pediatric bipolar disorder.

    Zeni, Cristian Patrick; Mwangi, Benson; Cao, Bo; Hasan, Khader M; Walss-Bass, Consuelo; Zunta-Soares, Giovana; Soares, Jair C

    2016-01-01

    Genetic and environmental factors are implicated in the onset and evolution of pediatric bipolar disorder, and may be associated to structural brain abnormalities. The aim of our study was to assess the impact of the interaction between the Brain-Derived Neurotrophic Factor (BDNF) rs6265 polymorphism and family functioning on hippocampal volumes of children and adolescents with bipolar disorder, and typically-developing controls. We evaluated the family functioning cohesion subscale using the Family Environment Scale-Revised, genotyped the BDNF rs6265 polymorphism, and performed structural brain imaging in 29 children and adolescents with bipolar disorder, and 22 healthy controls. We did not find significant differences between patients with BD or controls in left or right hippocampus volume (p=0.44, and p=0.71, respectively). However, we detected a significant interaction between low scores on the cohesion subscale and the presence of the Met allele at BNDF on left hippocampal volume of patients with bipolar disorder (F=3.4, p=0.043). None of the factors independently (BDNF Val66Met, cohesion scores) was significantly associated with hippocampal volume differences. small sample size, cross-sectional study. These results may lead to a better understanding of the impact of the interaction between genes and environment factors on brain structures associated to bipolar disorder and its manifestations. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Metabolic and haemodynamic effects of oral glucose loading in young healthy men carrying the 825T-allele of the G protein β3 subunit

    Wenzel Rene R

    2003-06-01

    Full Text Available Abstract Background A C825T polymorphism was recently identified in the gene encoding the β3 subunit of heterotrimeric G-proteins (GNB3. The T-allele is significantly associated with essential hypertension and obesity. In order to further explore a possible pathogenetic link between the T-allele and impaired glucose tolerance we studied metabolic and haemodynamic responses to oral glucose loading in young, healthy subjects with and without the 825T-allele. Methods Twelve subjects with and 10 without the 825T-allele were investigated at rest and following glucose ingestion (75 g. Blood glucose, serum insulin and haemodynamics were determined prior to and over 2 hours following glucose ingestion. We non-invasively measured stroke volume (SV, by impedance-cardiography, blood pressure (BP, heart rate (HR, and systolic-time-intervals. Cardiac output (CO was calculated from HR and SV. Total peripheral resistance was calculated from CO and BP. Metabolic and haemodynamic changes were quantified by maximal responses and by calculation of areas under the concentration time profile (AUC. Significances of differences between subjects with and without the T-allele were determined by unpaired two-tailed t-tests. A p Results Metabolic and haemodynamic parameters at baseline were very similar between both groups. The presence of the T-allele did not alter the response of any metabolic or haemodynamic parameter to glucose loading. Conclusions In conclusion, this study does not support the hypothesis that the C825T polymorphism may serve as a genetic marker of early impaired glucose tolerance.

  15. The minor C-allele of rs2014355 in ACADS is associated with reduced insulin release following an oral glucose load

    Hornbak, Malene; Banasik, Karina; Justesen, Johanne Marie

    2011-01-01

    -aged Danish individuals (nACADS=4,324; nACADM=4,337). The T2D-case-control study involved a total of ~8,300 Danish individuals (nACADS=8,313; nACADM=8,344). Results In glucose-tolerant individuals the minor C-allele of rs2014355 of ACADS associated with reduced measures of serum insulin at 30 min following...... an oral glucose load (per allele effect (beta)=-3.8% (-6.3%;-1.3%), P=0.003), reduced incremental area under the insulin curve (beta=-3.6% (-6.3%;-0.9%), P=0.009), reduced acute insulin response (beta=-2.2% (-4.2%;0.2%), P=0.03), and with increased insulin sensitivity ISIMatsuda (beta= 2.9% (0.5%;5.2%), P...

  16. Risk allelic load in Th2 and Th3 cytokines genes as biomarker of susceptibility to HPV-16 positive cervical cancer: a case control study

    Torres-Poveda, K.; Burguete-García, A. I.; Bahena-Román, M.; Méndez-Martínez, R.; Zurita-Díaz, M. A.; López-Estrada, G.; Delgado-Romero, K.; Peralta-Zaragoza, O.; Bermúdez-Morales, V. H.; Cantú, D.; García-Carrancá, A.; Madrid-Marina, V.

    2016-01-01

    Alterations in the host cellular immune response allow persistent infections with High-Risk Human Papillomavirus (HR-HPV) and development of premalignant cervical lesions and cervical cancer (CC). Variations of immunosuppressive cytokine levels in cervix are associated with the natural history of CC. To assess the potential role of genetic host immunity and cytokines serum levels in the risk of developing CC, we conducted a case–control study paired by age. Peripheral blood samples from patients with CC (n = 200) and hospital controls (n = 200), were used to evaluate nine biallelic SNPs of six cytokine genes of the adaptive immune system by allelic discrimination and cytokines serum levels by ELISA. After analyzing the SNP association by multivariate logistic regression adjusted by age, CC history and smoking history, three Th2 cytokines (IL-4, IL-6 and IL-10) and one Th3 (TGFB1) cytokine were significantly associated with CC. Individuals with at least one copy of the following risk alleles: T of SNP (−590C > T IL-4), C of SNP (−573G > C IL-6), A of SNP (−592C > A IL-10), T of SNP (−819C > T IL-10) and T of SNP (−509C > T TGFB1), had an adjusted odds ratio (OR) of 2.08 (95 % CI 1.475–2.934, p = 0.0001), an OR of 1.70 (95 % CI 1.208–2.404, p = 0.002), an OR of 1.87 (95 % CI 1.332–2.630, p = 0.0001), an OR of 1.67 (95 % CI 1.192–2.353, p = 0.003) and an OR of 1.91 (95 % CI 1.354–2.701, p = 0.0001), respectively, for CC. The burden of carrying two or more of these risk alleles was found to have an additive effect on the risk of CC (p trend = 0.0001). Finally, the serum levels of Th2 and Th3 cytokines were higher in CC cases than the controls; whereas IFNG levels, a Th1 cytokine, were higher in controls than CC cases. The significant associations of five SNPs with CC indicate that these polymorphisms are potential candidates for predicting the risk of development of CC, representing a risk allelic load for CC and can be used as a biomarker of

  17. The type 2 diabetes associated minor allele of rs2237895 KCNQ1 associates with reduced insulin release following an oral glucose load.

    Johan Holmkvist

    Full Text Available BACKGROUND: Polymorphisms in the potassium channel, voltage-gated, KQT-like subfamily, member 1 (KCNQ1 have recently been reported to associate with type 2 diabetes. The primary aim of the present study was to investigate the putative impact of these KCNQ1 polymorphisms (rs2283228, rs2237892, rs2237895, and rs2237897 on estimates of glucose stimulated insulin release. METHODOLOGY/PRINCIPAL FINDINGS: Genotypes were examined for associations with serum insulin levels following an oral glucose tolerance test (OGTT in a population-based sample of 6,039 middle-aged and treatment-naïve individuals. Insulin release indices estimated from the OGTT and the interplay between insulin sensitivity and insulin release were investigated using linear regression and Hotelling T2 analyses. Applying an additive genetic model the minor C-allele of rs2237895 was associated with reduced serum insulin levels 30 min (mean+/-SD: (CC 277+/-160 vs. (AC 280+/-164 vs. (AA 299+/-200 pmol/l, p = 0.008 after an oral glucose load, insulinogenic index (29.6+/-17.4 vs. 30.2+/-18.7vs. 32.2+/-22.1, p = 0.007, incremental area under the insulin curve (20,477+/-12,491 vs. 20,503+/-12,386 vs. 21,810+/-14,685, p = 0.02 among the 4,568 individuals who were glucose tolerant. Adjustment for the degree of insulin sensitivity had no effect on the measures of reduced insulin release. The rs2237895 genotype had a similar impact in the total sample of treatment-naïve individuals. No association with measures of insulin release were identified for the less common diabetes risk alleles of rs2237892, rs2237897, or rs2283228. CONCLUSION: The minor C-allele of rs2237895 of KCNQ1, which has a prevalence of about 42% among Caucasians was associated with reduced measures of insulin release following an oral glucose load suggesting that the increased risk of type 2 diabetes, previously reported for this variant, likely is mediated through an impaired beta cell function.

  18. The Type 2 Diabetes Associated Minor Allele of rs2237895 KCNQ1 Associates with Reduced Insulin Release Following an Oral Glucose Load

    Brunak, Søren; Holmkvist, J; Banasik, K

    2009-01-01

    , and rs2237897) on estimates of glucose stimulated insulin release. METHODOLOGY/PRINCIPAL FINDINGS: Genotypes were examined for associations with serum insulin levels following an oral glucose tolerance test (OGTT) in a population-based sample of 6,039 middle-aged and treatment-naïve individuals. Insulin...... release indices estimated from the OGTT and the interplay between insulin sensitivity and insulin release were investigated using linear regression and Hotelling T2 analyses. Applying an additive genetic model the minor C-allele of rs2237895 was associated with reduced serum insulin levels 30 min (mean......,568 individuals who were glucose tolerant. Adjustment for the degree of insulin sensitivity had no effect on the measures of reduced insulin release. The rs2237895 genotype had a similar impact in the total sample of treatment-naïve individuals. No association with measures of insulin release were identified...

  19. Sereniteit met een dip

    dr Ed de Jonge

    2015-01-01

    Boekbespreking van Serendipiteit. De ongezochte vondst. Het boek opent met een verzameling van citaten die direct of indirect met het onderwerp samenhangen. Daarna volgt een kort voorwoord van Hans Clevers, de toenmalige president van de KNAW, die een lans breekt voor serendipiteit in de biologie.

  20. Ervaringen met beeldverwerking.

    Meuleman, J.

    1989-01-01

    Verslag van een werkbezoek aan het Franse instituut Cemagref, met nadruk op beeldverwerking. Toepassingen van beeldverwerking zijn onder andere: een plukrobot voor appels; het detecteren van oppervlaktebeschadigingen bij appels; het detecteren van breuk in eieren; remote sensing

  1. Nisine geholpen met hordentechnologie

    Jong, de L.S.

    2001-01-01

    Een combinatie van nisine met carvacrol, thymol of carvon leidde tot een synergistische reductie van het aantal levensvatbare cellen van Listeria monocytogenes en Bacillus cereus. Verslag van een promotieonderzoek

  2. Autorijden met ADHD

    Fuermaier, Anselm B.M.; Tucha, Lara; de Vries, Stefanie M.; Koerts, Janneke; de Waard, Dick; Brookhuis, Karel; Tucha, Oliver

    Volwassenen met attention deficit hyperactivity disorder (ADHD) hebben uiteenlopende cognitieve beperkingen, die een aanzienlijke invloed kunnen hebben op verschillende aspecten van het dagelijks leven. Een van deze aspecten is het besturen van een auto. Autorijden is een belangrijke activiteit in

  3. When Historiography Met Epistemology

    Jean-François Stoffel

    2017-06-01

    Full Text Available Review of Bordoni, Stefano. When historiography met epistemology: Sophisticated histories and philosophies of science in French-speaking countries in the second half of the nineteenth century. Reviewed by Jean-François Stoffel.

  4. Jeugd met beperkingen

    Sjoerd Kooiker

    2006-01-01

    Voor kinderen en jongeren met een lichamelijke of verstandelijke beperking is 'gewoon meedoen' in de samenleving geen vanzelfsprekendheid.  Zij ervaren vaak meer obstakels bij het naar school gaan, het vinden van een baan en in hun vrijetijdsbesteding dan andere kinderen en jongeren. Ook

  5. Studeren met Hans Rosenberg

    Rutten, R.J.

    2001-01-01

    Hoe was het om in de jaren zestig te studeren? Laat ik een terugblik ophangen aan een studiemakker, Hans Rosenberg. We vormden samen de sterrekundejaar- gang 1961. Hans studeerde af in 1966 met hoofdvak wiskunde, promoveerde op radiostralingsprocessen in de zonnecorona in 1973, verliet de

  6. SPSS met syntax

    Grotenhuis, H.F. te; Visscher, C.A.M.

    2007-01-01

    Dit boekje wijkt af van de gebruikelijke statistiekboeken omdat het sec gaat over het bekende statistische computerprogramma SPSS, en dan alleen nog de oorspronkelijke variant waarin wordt gewerkt met syntax (intypen commando's -zoals bij DOS) i.p.v. de later ontwikkelde 'Windows-schil' (aanklikken

  7. Identification of BDNF sensitive electrophysiological markers of synaptic activity and their structural correlates in healthy subjects using a genetic approach utilizing the functional BDNF Val66Met polymorphism.

    Fruzsina Soltész

    Full Text Available Increasing evidence suggests that synaptic dysfunction is a core pathophysiological hallmark of neurodegenerative disorders. Brain-derived neurotropic factor (BDNF is key synaptogenic molecule and targeting synaptic repair through modulation of BDNF signalling has been suggested as a potential drug discovery strategy. The development of such "synaptogenic" therapies depend on the availability of BDNF sensitive markers of synaptic function that could be utilized as biomarkers for examining target engagement or drug efficacy in humans. Here we have utilized the BDNF Val66Met genetic polymorphism to examine the effect of the polymorphism and genetic load (i.e. Met allele load on electrophysiological (EEG markers of synaptic activity and their structural (MRI correlates. Sixty healthy adults were prospectively recruited into the three genetic groups (Val/Val, Val/Met, Met/Met. Subjects also underwent fMRI, tDCS/TMS, and cognitive assessments as part of a larger study. Overall, some of the EEG markers of synaptic activity and brain structure measured with MRI were the most sensitive markers of the polymorphism. Met carriers showed decreased oscillatory activity and synchrony in the neural network subserving error-processing, as measured during a flanker task (ERN; and showed increased slow-wave activity during resting. There was no evidence for a Met load effect on the EEG measures and the polymorphism had no effects on MMN and P300. Met carriers also showed reduced grey matter volume in the anterior cingulate and in the (left prefrontal cortex. Furthermore, anterior cingulate grey matter volume, and oscillatory EEG power during the flanker task predicted subsequent behavioural adaptation, indicating a BDNF dependent link between brain structure, function and behaviour associated with error processing and monitoring. These findings suggest that EEG markers such as ERN and resting EEG could be used as BDNF sensitive functional markers in early

  8. The catechol-O-methyltransferase (COMT) Val158Met genotype modulates working memory-related dorsolateral prefrontal response and performance in bipolar disorder

    Miskowiak, K. W.; Kjærstad, H. L.; Støttrup, M. M.

    2017-01-01

    prefrontal cortex (dlPFC) (P=.016). Exploratory whole-brain analysis revealed a bilateral decrease in working memory-related dlPFC activity in the ValVal group vs the ValMet group which was not associated with differences in working memory performance during fMRI. Outside the MRI scanner, Val carriers...... performed worse in the CANTAB Spatial Working Memory task than Met homozygotes (P≤.006), with deficits being most pronounced in Val homozygotes. CONCLUSIONS: The association between Val allelic load, dlPFC activity and WM impairment points to a putative role of aberrant PFC dopamine tonus in the cognitive......-O-methyltransferase (COMT) gene is associated with reduced prefrontal cortex dopamine and exaggerated working memory-related prefrontal activity. This functional magnetic resonance imaging (fMRI) study investigated for the first time whether the COMT Val158Met genotype modulates prefrontal activity during spatial working...

  9. Met kerse op met -konstruksies 1 : 'n Verwysingspuntperspektief ...

    Met kerse op met-konstruksies1: 'n Verwysingspuntperspektief. Johanna Messerschmidt, Luna Bergh. Abstract. This article analyses the usage of the Afrikaans preposition met ('with'). The analysis is done within the framework of Cognitive Linguistics and more specifically within the model proposed by Langacker (1993) ...

  10. The COMT val158met polymorphism and brain morphometry in healthy young adults

    Zinkstok, Janneke; Schmitz, Nicole; van Amelsvoort, Therese; de Win, Maartje; van den Brink, Wim; Baas, Frank; Linszen, Don

    2006-01-01

    Catechol-O-methyltransferase (COMT) is the most important mechanism for dopamine degradation in the prefrontal cortex and contains a functional polymorphism (val(158)met) influencing enzyme activity. The low-activity met allele has been associated with better performance on cognitive tasks relying

  11. COMT Val158Met genotype as a risk factor for problem behaviors in youth

    M.D. Albaugh (Matthew); V.S. Harder (Valerie); R.R. Althoff (Robert); D.C. Rettew (David); E.A. Ehli (Erik); T. Lengyel-Nelson (Timea); G.E. Davies (Gareth); L. Ayer (Lynsay); J. Sulman (Julie); C. Stanger (Catherine); J.J. Hudziak (James)

    2010-01-01

    textabstractObjective: To test the association between the catechol-O-methyltransferase (COMT) Val158Met polymorphism and both aggressive behavior and attention problems in youth. We hypothesized that youth carrying a Met allele would have greater average aggressive behavior scores, and that youth

  12. Allele coding in genomic evaluation

    Christensen Ole F

    2011-06-01

    Full Text Available Abstract Background Genomic data are used in animal breeding to assist genetic evaluation. Several models to estimate genomic breeding values have been studied. In general, two approaches have been used. One approach estimates the marker effects first and then, genomic breeding values are obtained by summing marker effects. In the second approach, genomic breeding values are estimated directly using an equivalent model with a genomic relationship matrix. Allele coding is the method chosen to assign values to the regression coefficients in the statistical model. A common allele coding is zero for the homozygous genotype of the first allele, one for the heterozygote, and two for the homozygous genotype for the other allele. Another common allele coding changes these regression coefficients by subtracting a value from each marker such that the mean of regression coefficients is zero within each marker. We call this centered allele coding. This study considered effects of different allele coding methods on inference. Both marker-based and equivalent models were considered, and restricted maximum likelihood and Bayesian methods were used in inference. Results Theoretical derivations showed that parameter estimates and estimated marker effects in marker-based models are the same irrespective of the allele coding, provided that the model has a fixed general mean. For the equivalent models, the same results hold, even though different allele coding methods lead to different genomic relationship matrices. Calculated genomic breeding values are independent of allele coding when the estimate of the general mean is included into the values. Reliabilities of estimated genomic breeding values calculated using elements of the inverse of the coefficient matrix depend on the allele coding because different allele coding methods imply different models. Finally, allele coding affects the mixing of Markov chain Monte Carlo algorithms, with the centered coding being

  13. Shot loading platform analysis

    Norman, B.F.

    1994-01-01

    This document provides the wind/seismic analysis and evaluation for the shot loading platform. Hand calculations were used for the analysis. AISC and UBC load factors were used in this evaluation. The results show that the actual loads are under the allowable loads and all requirements are met

  14. Allele coding in genomic evaluation

    Standen, Ismo; Christensen, Ole Fredslund

    2011-01-01

    Genomic data are used in animal breeding to assist genetic evaluation. Several models to estimate genomic breeding values have been studied. In general, two approaches have been used. One approach estimates the marker effects first and then, genomic breeding values are obtained by summing marker...... effects. In the second approach, genomic breeding values are estimated directly using an equivalent model with a genomic relationship matrix. Allele coding is the method chosen to assign values to the regression coefficients in the statistical model. A common allele coding is zero for the homozygous...... genotype of the first allele, one for the heterozygote, and two for the homozygous genotype for the other allele. Another common allele coding changes these regression coefficients by subtracting a value from each marker such that the mean of regression coefficients is zero within each marker. We call...

  15. Gezondheidsrisico's in verband met het werken met Pentachloorfenol : een onderzoek

    Geuskens, R.B.M.; Nossent, S.M.; Koëter, H.B.W.M.; Dreef-van der Meulen, H.C.; Stijkel, A.; Zielhuis, R.l.

    1989-01-01

    De gezondheidsrisico's i.v.m. het werken met pentachloorfenol (PCP) wordt geevalueerd. Het gebruik van PCP in Nederlandse arbeidssituaties neemt sterk af en is beperkt tot de formulering van emeltenkorrels en de, met name preventieve, houtverduurzaming. De totale risicopopulatie is niet omvangrijk

  16. Microbewerking met behulp van lasers

    Ezendam, M.M.M.

    1994-01-01

    Het bewerken van materialen met behulp van lasers staat momenteel enorm in de belangstelling, en terecht. De ontwikkeling van bestaande en nieuwe typen lasers staat alles behalve stil. Ontwikkelingen bevinden zich met name in het gebied van hogere vermogens, betere bundelkwaliteit en hogere

  17. D1S80 (pMCT118) allele frequencies in a Malay population sample from Malaysia.

    Koh, C L; Lim, M E; Ng, H S; Sam, C K

    1997-01-01

    The D1S80 allele frequencies in 124 unrelated Malays from the Malaysian population were determined and 51 genotypes and 19 alleles were encountered. The D1S80 frequency distribution met Hardy-Weinberg expectations. The observed heterozygosity was 0.80 and the power of discrimination was 0.96.

  18. Delimiting Allelic Imbalance of TYMS by Allele-Specific Analysis.

    Balboa-Beltrán, Emilia; Cruz, Raquel; Carracedo, Angel; Barros, Francisco

    2015-07-01

    Allelic imbalance of thymidylate synthase (TYMS) is attributed to polymorphisms in the 5'- and 3'-untranslated region (UTR). These polymorphisms have been related to the risk of suffering different cancers, for example leukemia, breast or gastric cancer, and response to different drugs, among which are methotrexate glutamates, stavudine, and specifically 5-fluorouracil (5-FU), as TYMS is its direct target. A vast literature has been published in relation to 5-FU, even suggesting the sole use of these polymorphisms to effectively manage 5-FU dosage. Estimates of the extent to which these polymorphisms influence in TYMS expression have in the past been based on functional analysis by luciferase assays and quantification of TYMS mRNA, but both these studies, as the association studies with cancer risk or with toxicity or response to 5-FU, are very contradictory. Regarding functional assays, the artificial genetic environment created in luciferase assay and the problems derived from quantitative polymerase chain reactions (qPCRs), for example the use of a reference gene, may have distorted the results. To avoid these sources of interference, we have analyzed the allelic imbalance of TYMS by allelic-specific analysis in peripheral blood mononuclear cells (PBMCs) from patients.Allelic imbalance in PBMCs, taken from 40 patients with suspected myeloproliferative haematological diseases, was determined by fluorescent fragment analysis (for the 3'-UTR polymorphism), Sanger sequencing and allelic-specific qPCR in multiplex (for the 5'-UTR polymorphisms).For neither the 3'- nor the 5'-UTR polymorphisms did the observed allelic imbalance exceed 1.5 fold. None of the TYMS polymorphisms is statistically associated with allelic imbalance.The results acquired allow us to deny the previously established assertion of an influence of 2 to 4 fold of the rs45445694 and rs2853542 polymorphisms in the expression of TYMS and narrow its allelic imbalance to 1.5 fold, in our population

  19. Gezondheidsrisico's in verband met het werken met Polychloorbifenylen : een onderzoek

    Geuskens, R.B.M.; Nossent, S.M.; Koëter, H.B.W.M.; Dreef-van der Meulen, H.C.; Stijkel, A.; Zielhuis, R.L.

    1989-01-01

    Met behulp van gegevens verkregen uit een werkplekinventarisatie naar gegevens over produktie/gebruik, risicopopulatie en (mogelijke) blootstelling aan polychloorbifenylen (PCB's), en een literatuurstudie naar mogelijke schadelijke eigenschappen van PCB's op het reproductiesysteem en/of nageslacht

  20. The effect of COMT Val158 Met genotype on decision-making and preliminary findings on its interaction with the 5-HTTLPR in healthy females.

    van den Bos, Ruud; Homberg, Judith; Gijsbers, Ellen; den Heijer, Esther; Cuppen, Edwin

    2009-02-01

    Poor decision-making is inherent to several psychiatric conditions for which a genetic basis may exist. We previously showed that healthy female volunteers homozygous for the short allele (s/s) of the serotonin transporter length polymorphic region (5-HTTLPR) chose more often cards from disadvantageous decks in the Iowa Gambling Task (IGT), which measures decision-making, than long (l) allele carriers. The 5-HTTLPR and catechol-O-methyltransferase (COMT) Val(158) Met polymorphism affect the same set of neuronal structures. Therefore, we explored the effect of the (COMT) Val(158) Met polymorphism on IGT performance and its interaction with the 5-HTTLPR in the same subjects in this study. We observed that subjects homozygous for methionine (Met/Met) chose more disadvantageously than subjects homozygous for valine (Val/Val). s/s-Met/Met-subjects appeared to show the poorest IGT performance of all possible combinations of 5-HTTLPR and COMT allelic variants. Using the Expectancy-Valence model, no differences were found for the three different 5-HTTLPR or COMT genotypes regarding (i) attention to wins versus losses, (ii) updating rate, or (iii) response consistency. However, subjects with at least one Met-allele were paying more attention to wins than subjects with no Met-alleles. We discuss whether a common neuronal mechanism relates to s- and Met-allele-related deficits in updating and/or processing of choice outcome to guide subsequent choices in this gamble-based test.

  1. Genetic contribution of catechol-O-methyltransferase polymorphism (Val158Met) in children with chronic tension-type headache.

    Fernández-de-las-Peñas, César; Ambite-Quesada, Silvia; Rivas-Martínez, Inés; Ortega-Santiago, Ricardo; de-la-Llave-Rincón, Ana Isabel; Fernández-Mayoralas, Daniel M; Pareja, Juan A

    2011-10-01

    Our aim was to investigate the relationship between Val158Met polymorphisms, headache, and pressure hypersensitivity in children with chronic tension-type headache (CTTH). A case-control study with blinded assessor was conducted. Seventy children with CTTH associated with pericranial tenderness and 70 healthy children participated. After amplifying Val158Met polymorphism by polymerase chain reactions, we assessed genotype frequencies and allele distributions. We classified children according to their Val158Met polymorphism: Val/Val, Val/Met, Met/Met. Pressure pain thresholds (PPT) were bilaterally assessed over the temporalis, upper trapezius, second metacarpal, and tibialis anterior muscles. The distribution of Val158Met genotypes was not significantly different (p = 0.335), between children with CTTH and healthy children, and between boys and girls (p = 0.872). Children with CTTH with the Met/Met genotype showed a longer headache history compared with those with Met/Val (p = 0.001) or Val/Val (p = 0.002) genotype. Children with CTTH with Met/Met genotype showed lower PPT over upper trapezius and temporalis muscles than children with CTTH with Met/Val or Val/Val genotype (p < 0.01). The Val158Met catechol-O-methyltransferase (COMT) polymorphism does not appear to be involved in predisposition to suffer from CTTH in children; nevertheless, this genetic factor may be involved in the phenotypic expression, as pressure hypersensitivity was greater in those CTTH children with the Met/Met genotype.

  2. Induction of epigenetic variation in Arabidopsis by over-expression of DNA METHYLTRANSFERASE1 (MET1.

    Samuel Brocklehurst

    Full Text Available Epigenetic marks such as DNA methylation and histone modification can vary among plant accessions creating epi-alleles with different levels of expression competence. Mutations in epigenetic pathway functions are powerful tools to induce epigenetic variation. As an alternative approach, we investigated the potential of over-expressing an epigenetic function, using DNA METHYLTRANSFERASE1 (MET1 for proof-of-concept. In Arabidopsis thaliana, MET1 controls maintenance of cytosine methylation at symmetrical CG positions. At some loci, which contain dense DNA methylation in CG- and non-CG context, loss of MET1 causes joint loss of all cytosines methylation marks. We find that over-expression of both catalytically active and inactive versions of MET1 stochastically generates new epi-alleles at loci encoding transposable elements, non-coding RNAs and proteins, which results for most loci in an increase in expression. Individual transformants share some common phenotypes and genes with altered gene expression. Altered expression states can be transmitted to the next generation, which does not require the continuous presence of the MET1 transgene. Long-term stability and epigenetic features differ for individual loci. Our data show that over-expression of MET1, and potentially of other genes encoding epigenetic factors, offers an alternative strategy to identify epigenetic target genes and to create novel epi-alleles.

  3. Brain-derived neurotrophic factor Val66Met genotype modulates amygdala habituation.

    Perez-Rodriguez, M Mercedes; New, Antonia S; Goldstein, Kim E; Rosell, Daniel; Yuan, Qiaoping; Zhou, Zhifeng; Hodgkinson, Colin; Goldman, David; Siever, Larry J; Hazlett, Erin A

    2017-05-30

    A deficit in amygdala habituation to repeated emotional stimuli may be an endophenotype of disorders characterized by emotion dysregulation, such as borderline personality disorder (BPD). Amygdala reactivity to emotional stimuli is genetically modulated by brain-derived neurotrophic factor (BDNF) variants. Whether amygdala habituation itself is also modulated by BDNF genotypes remains unknown. We used imaging-genetics to examine the effect of BDNF Val66Met genotypes on amygdala habituation to repeated emotional stimuli. We used functional magnetic resonance imaging (fMRI) in 57 subjects (19 BPD patients, 18 patients with schizotypal personality disorder [SPD] and 20 healthy controls [HC]) during a task involving viewing of unpleasant, neutral, and pleasant pictures, each presented twice to measure habituation. Amygdala responses across genotypes (Val66Met SNP Met allele-carriers vs. Non-Met carriers) and diagnoses (HC, BPD, SPD) were examined with ANOVA. The BDNF 66Met allele was significantly associated with a deficit in amygdala habituation, particularly for emotional pictures. The association of the 66Met allele with a deficit in habituation to unpleasant emotional pictures remained significant in the subsample of BPD patients. Using imaging-genetics, we found preliminary evidence that deficient amygdala habituation may be modulated by BDNF genotype. Copyright © 2017. Published by Elsevier B.V.

  4. Lack of neural compensatory mechanisms of BDNF val66met met carriers and APOE E4 carriers in healthy aging, mild cognitive impairment, and Alzheimer's disease.

    Gomar, Jesus J; Conejero-Goldberg, Concepcion; Huey, Edward D; Davies, Peter; Goldberg, Terry E

    2016-03-01

    Compromises in compensatory neurobiologic mechanisms due to aging and/or genetic factors (i.e., APOE gene) may influence brain-derived neurotrophic factor (BDNF) val66met polymorphism effects on temporal lobe morphometry and memory performance. We studied 2 cohorts from Alzheimer's Disease Neuroimaging Initiative: 175 healthy subjects and 222 with prodromal and established Alzheimer's disease. Yearly structural magnetic resonance imaging and cognitive performance assessments were carried out over 3 years of follow-up. Both cohorts had similar BDNF Val/Val and Met allele carriers' (including both Val/Met and Met/Met individuals) distribution. In healthy subjects, a significant trend for thinner posterior cingulate and precuneus cortices was detected in Met carriers compared to Val homozygotes in APOE E4 carriers, with large and medium effect sizes, respectively. The mild cognitive impairment/Alzheimer's disease cohort showed a longitudinal decline in entorhinal thickness in BDNF Met carriers compared to Val/Val in APOE E4 carriers, with effect sizes ranging from medium to large. In addition, an effect of BDNF genotype was found in APOE E4 carriers for episodic memory (logical memory and ADAS-Cog) and semantic fluency measures, with Met carriers performing worse in all cases. These findings suggest a lack of compensatory mechanisms in BDNF Met carriers and APOE E4 carriers in healthy and pathological aging. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. The BDNF Val66Met Polymorphism Influences Reading Ability and Patterns of Neural Activation in Children.

    Kaja K Jasińska

    Full Text Available Understanding how genes impact the brain's functional activation for learning and cognition during development remains limited. We asked whether a common genetic variant in the BDNF gene (the Val66Met polymorphism modulates neural activation in the young brain during a critical period for the emergence and maturation of the neural circuitry for reading. In animal models, the bdnf variation has been shown to be associated with the structure and function of the developing brain and in humans it has been associated with multiple aspects of cognition, particularly memory, which are relevant for the development of skilled reading. Yet, little is known about the impact of the Val66Met polymorphism on functional brain activation in development, either in animal models or in humans. Here, we examined whether the BDNF Val66Met polymorphism (dbSNP rs6265 is associated with children's (age 6-10 neural activation patterns during a reading task (n = 81 using functional magnetic resonance imaging (fMRI, genotyping, and standardized behavioral assessments of cognitive and reading development. Children homozygous for the Val allele at the SNP rs6265 of the BDNF gene outperformed Met allele carriers on reading comprehension and phonological memory, tasks that have a strong memory component. Consistent with these behavioral findings, Met allele carriers showed greater activation in reading-related brain regions including the fusiform gyrus, the left inferior frontal gyrus and left superior temporal gyrus as well as greater activation in the hippocampus during a word and pseudoword reading task. Increased engagement of memory and spoken language regions for Met allele carriers relative to Val/Val homozygotes during reading suggests that Met carriers have to exert greater effort required to retrieve phonological codes.

  6. The BDNF Val66Met Polymorphism Influences Reading Ability and Patterns of Neural Activation in Children.

    Jasińska, Kaja K; Molfese, Peter J; Kornilov, Sergey A; Mencl, W Einar; Frost, Stephen J; Lee, Maria; Pugh, Kenneth R; Grigorenko, Elena L; Landi, Nicole

    2016-01-01

    Understanding how genes impact the brain's functional activation for learning and cognition during development remains limited. We asked whether a common genetic variant in the BDNF gene (the Val66Met polymorphism) modulates neural activation in the young brain during a critical period for the emergence and maturation of the neural circuitry for reading. In animal models, the bdnf variation has been shown to be associated with the structure and function of the developing brain and in humans it has been associated with multiple aspects of cognition, particularly memory, which are relevant for the development of skilled reading. Yet, little is known about the impact of the Val66Met polymorphism on functional brain activation in development, either in animal models or in humans. Here, we examined whether the BDNF Val66Met polymorphism (dbSNP rs6265) is associated with children's (age 6-10) neural activation patterns during a reading task (n = 81) using functional magnetic resonance imaging (fMRI), genotyping, and standardized behavioral assessments of cognitive and reading development. Children homozygous for the Val allele at the SNP rs6265 of the BDNF gene outperformed Met allele carriers on reading comprehension and phonological memory, tasks that have a strong memory component. Consistent with these behavioral findings, Met allele carriers showed greater activation in reading-related brain regions including the fusiform gyrus, the left inferior frontal gyrus and left superior temporal gyrus as well as greater activation in the hippocampus during a word and pseudoword reading task. Increased engagement of memory and spoken language regions for Met allele carriers relative to Val/Val homozygotes during reading suggests that Met carriers have to exert greater effort required to retrieve phonological codes.

  7. La metáfora

    Agustin, Oscar Garcia

    2007-01-01

    2002 y principios de 2003, anteriores a la proclamación de las Juntas de Buen Gobierno. Nuestro objetivo es comprobar cómo las metáforas crean nuevas significaciones, que intentan deshacer una lógica comúnmente asumida, y promover otros modos de comprender la acción y la realidad político-social. Este...

  8. Assessment of the myostatin Q204X allele using an allelic discrimination assay

    Sifuentes-Rincón,Ana M.; Puentes-Montiel,Herlinda E.; Moreno-Medina,Víctor R.; Rosa-Reyna,Xóchitl F. de la

    2006-01-01

    An allelic discrimination assay was designed and used to determine the genotypic and allelic frequencies of the myostatin (MSTN) gene Q204X allele from two Mexican Full-French herds. The assay is a simple high throughput genotyping method that could be applied to investigate the effect of the Q204X allele on the Charolais breed.

  9. COMT Val158Met polymorphism, cognitive stability and cognitive flexibility: an experimental examination

    Rosa Elise C

    2010-09-01

    Full Text Available Abstract Background Dopamine in prefrontal cortex (PFC modulates core cognitive processes, notably working memory and executive control. Dopamine regulating genes and polymorphisms affecting PFC - including Catechol-O-Methyltransferase (COMT Val158Met - are crucial to understanding the molecular genetics of cognitive function and dysfunction. A mechanistic account of the COMT Val158Met effect associates the Met allele with increased tonic dopamine transmission underlying maintenance of relevant information, and the Val allele with increased phasic dopamine transmission underlying the flexibility of updating new information. Thus, consistent with some earlier work, we predicted that Val carriers would display poorer performance when the maintenance component was taxed, while Met carriers would be less efficient when rapid updating was required. Methods Using a Stroop task that manipulated level of required cognitive stability and flexibility, we examined reaction time performance of patients with schizophrenia (n = 67 and healthy controls (n = 186 genotyped for the Val/Met variation. Results In both groups we found a Met advantage for tasks requiring cognitive stability, but no COMT effect when a moderate level of cognitive flexibility was required, or when a conflict cost measure was calculated. Conclusions Our results do not support a simple stability/flexibility model of dopamine COMT Val/Met effects and suggest a somewhat different conceptualization and experimental operationalization of these cognitive components.

  10. The BDNF Val66Met Polymorphism Affects the Vulnerability of the Brain Structural Network

    Chang-hyun Park

    2017-08-01

    Full Text Available Val66Met, a naturally occurring polymorphism in the human brain-derived neurotrophic factor (BDNF gene resulting in a valine (Val to methionine (Met substitution at codon 66, plays an important role in neuroplasticity. While the effect of the BDNF Val66Met polymorphism on local brain structures has previously been examined, its impact on the configuration of the graph-based white matter structural networks is yet to be investigated. In the current study, we assessed the effect of the BDNF polymorphism on the network properties and robustness of the graph-based white matter structural networks. Graph theory was employed to investigate the structural connectivity derived from white matter tractography in two groups, Val homozygotes (n = 18 and Met-allele carriers (n = 55. Although there were no differences in the global network measures including global efficiency, local efficiency, and modularity between the two genotype groups, we found the effect of the BDNF Val66Met polymorphism on the robustness properties of the white matter structural networks. Specifically, the white matter structural networks of the Met-allele carrier group showed higher vulnerability to targeted removal of central nodes as compared with those of the Val homozygote group. These findings suggest that the central role of the BDNF Val66Met polymorphism in regards to neuroplasticity may be associated with inherent differences in the robustness of the white matter structural network according to the genetic variants. Furthermore, greater susceptibility to brain disorders in Met-allele carriers may be understood as being due to their limited stability in white matter structural connectivity.

  11. Association study between COMT 158Met and creativity scores in bipolar disorder and healthy controls

    Márcio Gerhardt Soeiro-de-Souza

    2014-03-01

    Full Text Available Background Bipolar disorder (BD patients have been reported to be associated higher creativity abilities, and recent data tend to support the hypothesis that dopaminergic system that could be associated with creativity. Catechol-O-methyltransferase (COMT is one of the major enzymes involved in the metabolic degradation of dopamine. The COMT gene polymorphism (rs4680 or Val158Met Met allele is reported to cause decreased activity of this enzyme in prefrontal cortex and improve performance in several cognitive domains. Objective The objective of this study was to evaluate the influence of Val158Met on creativity in BD type I and healthy controls. Methods Ninety-seven healthy volunteers and 120 BD type I were genotyped for COMT rs4680 and tested for creativity (Barrow Welsh Art Scale – BWAS and intelligence Wechsler Abbreviated Scale of Intelligence (WASI. Results COMT Met allele positively influenced creativity scores in healthy controls but not in BD subjects during mood episodes and euthymia. The presence of allele Met did not influence IQ scores. No influence of IQ total score on creativity was observed. Limitations control group presented higher IQ scores and euthymic group was under medication use. Discussion Our research suggests positive effect of COMT rs4680 (allele Met on creativity scores in healthy controls. One possible interpretation is that creativity is more likely to be associated with lesser degrees of bipolarity. The fact that the same results were not observed in BD may be associated to dysfunctions in the dopaminergic system that characterizes this disorder. Further studies with larger samples and other types of BD should explore the role of the dopaminergic system in creativity.

  12. The BDNF Val66Met polymorphism moderates the relationship between Posttraumatic Stress Disorder and fear extinction learning.

    Felmingham, Kim L; Zuj, Daniel V; Hsu, Ken Chia Ming; Nicholson, Emma; Palmer, Matthew A; Stuart, Kimberley; Vickers, James C; Malhi, Gin S; Bryant, Richard A

    2018-05-01

    The low expression Met allele of the BDNF Val66Met polymorphism is associated with impaired fear extinction in healthy controls, and poorer response to exposure therapy in patients with Posttraumatic Stress Disorder (PTSD). Given that fear extinction underlies exposure therapy, this raises the question of the impact of BDNFVal66Met polymorphism on fear extinction in PTSD, yet this question has not yet been examined. One hundred and six participants (22 PTSD, 46 trauma-exposed controls (TC) and 38 non-trauma exposed controls (NTC)) completed a fear conditioning and extinction task and saliva samples were taken for DNA extraction and genotyped for the BDNF Val66Met polymorphism. Moderation analyses using PROCESS examined whether BDNF genotype (Val-Val vs Met carriers) moderated the relationship between PTSD symptom severity (and diagnostic status) and skin conductance response (SCR) amplitude during fear extinction. The PTSD group displayed significantly slower fear extinction learning compared to TC and NTC in the early extinction phase. The BDNF Val66Met polymorphism moderated the relationship between PTSD and fear extinction learning, such that poorer fear extinction learning was associated with greater PTSD symptom severity (and PTSD diagnostic status) in individuals with the low-expression Met allele, but no relationship was demonstrated in individuals with the Val-Val allele. This study reveals that impaired fear extinction learning is particularly evident in individuals with PTSD who carry the low-expression BDNF Met allele and importantly not in those with the Val-Val allele. This provides novel evidence of a link between BDNF and impaired fear extinction learning in PTSD, which may contribute to poorer response to exposure therapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Progress in switching technology for METS systems

    Honig, E.M.; Swannack, C.E.; Warren, R.W.; Whitaker, D.H.

    1977-01-01

    Three distinct sets of switching requirements have emerged from design optimization studies of large superconducting magnetic energy storage systems, such as the METS system to power the adiabatic plasma compression field in the proposed theta-pinch SFTR. Extremely low joule loss cryogenic disconnects are required between storage coils in the liquid helium environment to allow charging the coils in series over a prolonged time, then to isolate the coils for parallel fast discharging into the load. Another switch must break the current in the series charging loop and absorb the energy from the stray inductance. This action will allow the subsequent opening of the cryogenic disconnects under near zero current condition. The current now has been transferred to the many paralleled circuits, each containing a high current, high voltage interrupter. The opening and arc commutation of the interrupter starts the energy transfer into the load. The primary activities associated with cryogenic disconnect have been testing and development of contact materials, configurations, and closing forces for carrying 26 kA with a resistance less than 40 nΩ, and development of an actuating system that is both reliable and fast acting in a liquid helium environment. The charging loop switch will include a continuous duty switch and a vacuum interrupter. The continuous duty switch resistance can be an order of magnitude larger than that of the cryogenic disconnect because it does not present a refrigeration load. The HVDC interrupter must break 26 kA and withstand 60 kV during the energy transfer time of 700 μs. Testing in progress already has shown successful interruption using single vacuum interrupters up to 31 kA and 66 kV

  14. Reactions of Met-Cars

    Castleman, A.W. Jr.; Guo, B.C.

    1993-01-01

    A new class of metal-carbon complexes, termed metallo-carbohedrenes (Met-Cars), have been discovered to form in a plasma reactor in which early transition metals are vaporized into a stream carrying small hydrocarbon molecules. The initial discovery involved the species Ti 8 c 12 + , while subsequent studies revealed the stability of the anion and, most importantly, the neutral species. Subsequent investigations show that similar molecules, predicted to have a pentagonal dodecahedral structure, can also be formed with vanadium, hafnium, and zirconium. In the case of the latter, more recent investigations have displaced an interesting growth pattern. In particular, pentagonal dodecahedrons with dangling carbon atoms can undergo further growth, adding at least a second and third cage. The latest results on the properties and reactivities of these new cage-like molecular clusters will be discussed

  15. Modification of depression by COMT val158met polymorphism in children exposed to early severe psychosocial deprivation

    Drury, Stacy S; Theall, Katherine P; Smyke, Anna T; Keats, Bronya JB; Egger, Helen L; Nelson, Charles A; Fox, Nathan A; Marshall, Peter J; Zeanah, Charles H

    2014-01-01

    Objective To examine the impact of the Catechol-O-Methyltransferase (COMT) val158met allele on depressive symptoms in young children exposed to early severe social deprivation as a result of being raised in institutions. Methods 136 children from the Bucharest Early Intervention Project (BEIP) were randomized before 31 months of age to either care as usual (CAU) in institutions or placement in newly created foster care (FCG). At 54 months of age, a psychiatric assessment using the Preschool Age Psychiatric Assessment (PAPA) was completed. DNA was collected and genotyped for the COMT val158met polymorphism. Multivariate analysis examined the relationship between COMT alleles and depressive symptoms. Results Mean level of depressive symptoms was lower among participants with the met allele compared to those with two copies of the val allele (p <0.05). Controlling for group and gender, the rate of depressive symptoms was significantly lower among participants with the met/met or the met/val genotype (adjusted relative risk (aRR) = 0.67, 95% CI = 0.45, 0.99) compared to participants with the val/val genotype, indicating an intermediate impact for heterozygotes consistent with the biological impact of this polymorphism. The impact of genotype within groups differed significantly. There was a significant protective effect of the met allele on depressive symptoms within the CAU group, however there was no relationship seen within the FCG group. Conclusions This is the first study, to our knowledge, to find evidence of a gene × environment interaction in the setting of early social deprivation. These results support the hypothesis that individual genetic differences may explain some of the variability in recovery amongst children exposed to early severe social deprivation. PMID:20403637

  16. Gender effects of the COMT Val 158 Met genotype on verbal fluency in healthy adults.

    Soeiro-De-Souza, Marcio Gerhardt; Bio, Danielle Soares; David, Denise Petresco; Missio, Giovani; Lima, Bruno; Fernandes, Fernando; Machado-Vieira, Rodrigo; Moreno, Ricardo Alberto

    2013-09-01

    Cognitive performance in healthy individuals is associated with gender differences in specific tests; a female advantage has been demonstrated in language tests, whereas a male advantage has been demonstrated in spatial relation examinations. The prefrontal cortex (PFC) mediates important cognitive domains and is influenced by dopamine (DA) activity. The single nucleotide polymorphism (SNP) rs4680 in the catechol‑O‑methyltransferase (COMT) gene results in an amino acid substitution from valine (Val) to methionine (Met). The Met allele has been demonstrated to decrease COMT enzyme activity and improve PFC cognitive function. COMT regulates DA activity in the PFC and exhibits gender effects. The aim of the present study was to investigate the gender‑specific effects of the COMT genotype on cognition in healthy young adults. Seventy‑six healthy subjects were genotyped for COMT rs4680 and submitted to an extensive range of neuropsychological tests assessing aspects of PFC function. The COMT Met allele influenced the performance of executive function. The results revealed gender effects of the COMT rs4680 Met allele on verbal fluency, with positive effects in males and negative effects in females. This suggested that DA activity affects cognitive function in different ways, according to gender.

  17. Proef met duurzaam watergebruik in de bollenstreek

    Fliegenthart, F.; Dik, P.E.; Groenendijk, P.

    2009-01-01

    In 2007 begon in de Wieringermeer een praktijkproef met alternatieve waterbeheersystemen voor de bollenteelt. Met drie verschillende teeltsystemen wordt onderzoek verricht naar zo optimaal mogelijk gebruik van zoet water door recirculatie en hergebruik. Ook loopt onderzoek naar de emissie van

  18. Impact of BDNF Val66Met and 5-HTTLPR polymorphism variants on neural substrates related to sadness and executive function.

    Wang, L; Ashley-Koch, A; Steffens, D C; Krishnan, K R R; Taylor, W D

    2012-04-01

    The brain-derived neurotrophic factor (BDNF) Val(66) Met allelic variation is linked to both the occurrence of mood disorders and antidepressant response. These findings are not universally observed, and the mechanism by which this variation results in increased risk for mood disorders is unclear. One possible explanation is an epistatic relationship with other neurotransmitter genes associated with depression risk, such as the serotonin-transporter-linked promotor region (5-HTTLPR). Further, it is unclear how the coexistence of the BDNF Met and 5-HTTLPR S variants affects the function of the affective and cognitive control systems. To address this question, we conducted a functional magnetic resonance imaging (fMRI) study in 38 older adults (20 healthy and 18 remitted from major depressive disorder). Subjects performed an emotional oddball task during the fMRI scan and provided blood samples for genotyping. Our analyses examined the relationship between genotypes and brain activation to sad distractors and attentional targets. We found that 5-HTTLPR S allele carriers exhibited stronger activation in the amygdala in response to sad distractors, whereas BDNF Met carriers exhibited increased activation to sad stimuli but decreased activation to attentional targets in the dorsolateral prefrontal and dorsomedial prefrontal cortices. In addition, subjects with both the S allele and Met allele genes exhibited increased activation to sad stimuli in the subgenual cingulate and posterior cingulate. Our results indicate that the Met allele alone or in combination with 5-HTTLPR S allele may increase reactivity to sad stimuli, which might represent a neural mechanism underlying increased depression vulnerability. © 2012 The Authors. Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

  19. Genotype distribution and allele frequencies of the genes associated with body composition and locomotion traits in Myanmar native horses.

    Okuda, Yu; Moe, Hla Hla; Moe, Kyaw Kyaw; Shimizu, Yuki; Nishioka, Kenji; Shimogiri, Takeshi; Mannen, Hideyuki; Kanemaki, Misao; Kunieda, Tetsuo

    2017-08-01

    Myanmar native horses are small horses used mainly for drafting carts or carriages in rural areas and packing loads in mountainy areas. In the present study, we investigated genotype distributions and allele frequencies of the LCORL/NCAPG, MSTN and DMRT3 genes, which are associated with body composition and locomotion traits of horses, in seven local populations of Myanmar native horses. The genotyping result of LCORL/NCAPG showed that allele frequencies of C allele associated with higher withers height ranged from 0.08 to 0.27, and 0.13 in average. For MSTN, allele frequencies of C allele associated with higher proportion of Type 2B muscular fiber ranged from 0.05 to 0.23, and 0.09 in average. For DMRT3, allele frequencies of A allele associated with ambling gait ranged from 0 to 0.04, and 0.01 in average. The presences of the minor alleles of these genes at low frequencies suggest a possibility that these horse populations have not been under strong selection pressure for particular locomotion traits and body composition. Our findings of the presence of these minor alleles in Southeast Asian native horses are also informative for considering the origins of these minor alleles associated with body composition and locomotion traits in horse populations. © 2016 Japanese Society of Animal Science.

  20. The BDNF Val66Met polymorphism: relation to familiar risk of affective disorder, BDNF levels and salivary cortisol.

    Vinberg, Maj; Trajkovska, Viktorija; Bennike, Bente; Knorr, Ulla; Knudsen, Gitte M; Kessing, Lars V

    2009-10-01

    Brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis are considered to play an important role in the pathophysiology of affective disorders. The aim of the present study was to investigate whether the BDNF Val66Met polymorphism is associated with a familiar risk of affective disorder and whether these genotypes affect whole blood BDNF level and salivary cortisol. In a high-risk study, healthy monozygotic and dizygotic twins with and without a co-twin (high- and low-risk twins, respectively) history of affective disorder were identified through nationwide registers. Familiar predisposition to unipolar and bipolar disorder was not associated with any specific genotype pattern of the BDNF Val66Met polymorphism, not in this sample of 124 val/val, 58 val/met and 8 met/met individuals. However, the combination of having a high familiar risk of affective disorder and the met allele was associated with a higher whole blood BDNF (p=0.02) and a higher evening cortisol level (p=0.01), but not with awakening cortisol. Individuals at high risk of affective disorders and who are carriers of the met allele of the Val66Met polymorphism may present with an enhanced stress response. The presence of a specific genotype alone may not enhance the risk of developing an affective episode. Rather, the altered stress response may be expressed only in combination with other risk variants through interactions with the environment.

  1. CYP3A4 allelic variants with amino acid substitutions in exons 7 and 12: evidence for an allelic variant with altered catalytic activity.

    Sata, F; Sapone, A; Elizondo, G; Stocker, P; Miller, V P; Zheng, W; Raunio, H; Crespi, C L; Gonzalez, F J

    2000-01-01

    To determine the existence of mutant and variant CgammaP3A4 alleles in three racial groups and to assess functions of the variant alleles by complementary deoxyribonucleic acid (cDNA) expression. A bacterial artificial chromosome that contains the complete CgammaP3A4 gene was isolated and the exons and surrounding introns were directly sequenced to develop primers to polymerase chain reaction (PCR) amplify and sequence the gene from lymphocyte DNA. DNA samples from Chinese, black, and white subjects were screened. Mutating the affected amino acid in the wild-type cDNA and expressing the variant enzyme with use of the baculovirus system was used to functionally evaluate the variant allele having a missense mutation. To investigate the existence of mutant and variant CgammaP3A4 alleles in humans, all 13 exons and the 5'-flanking region of the human CgammaP3A4 gene in three racial groups were sequenced and four alleles were identified. An A-->G point mutation in the 5'-flanking region of the human CgammaP3A4 gene, designated CgammaP3A4*1B, was found in the three different racial groups. The frequency of this allele in a white population was 4.2%, whereas it was 66.7% in black subjects. The CgammaP3A4*1B allele was not found in Chinese subjects. A second variant allele, designated CgammaP3A4*2, having a Ser222Pro change, was found at a frequency of 2.7% in the white population and was absent in the black subjects and Chinese subjects analyzed. Baculovirus-directed cDNA expression revealed that the CYP3A4*2 P450 had a lower intrinsic clearance for the CYP3A4 substrate nifedipine compared with the wild-type enzyme but was not significantly different from the wild-type enzyme for testosterone 6beta-hydroxylation. Another rare allele, designated CgammaP3A4*3, was found in a single Chinese subject who had a Met445Thr change in the conserved heme-binding region of the P450. These are the first examples of potential function polymorphisms resulting from missense mutations in

  2. Activating mutation in MET oncogene in familial colorectal cancer

    Schildkraut Joellen M

    2011-10-01

    Full Text Available Abstract Background In developed countries, the lifetime risk of developing colorectal cancer (CRC is 5%, and it is the second leading cause of death from cancer. The presence of family history is a well established risk factor with 25-35% of CRCs attributable to inherited and/or familial factors. The highly penetrant inherited colon cancer syndromes account for approximately 5%, leaving greater than 20% without clear genetic definition. Familial colorectal cancer has been linked to chromosome 7q31 by multiple affected relative pair studies. The MET proto-oncogene which resides in this chromosomal region is considered a candidate for genetic susceptibility. Methods MET exons were amplified by PCR from germline DNA of 148 affected sibling pairs with colorectal cancer. Amplicons with altered sequence were detected with high-resolution melt-curve analysis using a LightScanner (Idaho Technologies. Samples demonstrating alternative melt curves were sequenced. A TaqMan assay for the specific c.2975C >T change was used to confirm this mutation in a cohort of 299 colorectal cancer cases and to look for allelic amplification in tumors. Results Here we report a germline non-synonymous change in the MET proto-oncogene at amino acid position T992I (also reported as MET p.T1010I in 5.2% of a cohort of sibling pairs affected with CRC. This genetic variant was then confirmed in a second cohort of individuals diagnosed with CRC and having a first degree relative with CRC at prevalence of 4.1%. This mutation has been reported in cancer cells of multiple origins, including 2.5% of colon cancers, and in Conclusions Although the MET p.T992I genetic mutation is commonly found in somatic colorectal cancer tissues, this is the first report also implicating this MET genetic mutation as a germline inherited risk factor for familial colorectal cancer. Future studies on the cancer risks associated with this mutation and the prevalence in different at-risk populations will

  3. Differences in MetS marker prevalence between black African and ...

    Multiple linear regression analysis, independent of covariates, showed that the albumin:creatinine ratio is explained only by glucose in Africans. Conclusion: African women, as a group, present with few MetS risk factors, and glucose is associated with renal function risk in Africans. Keywords: MetS, metabolic syndrome, ...

  4. Modification of Depression by COMT val[superscript 158]Met Polymorphism in Children Exposed to Early Severe Psychosocial Deprivation

    Drury, Stacy S.; Theall, Katherine P.; Smyke, Anna T.; Keats, Bronya J. B.; Egger, Helen L.; Nelson, Charles A.; Fox, Nathan A.; Marshall, Peter J.; Zeanah, Charles H.

    2010-01-01

    Objective: To examine the impact of the catechol-O-methyltransferase (COMT) val[superscript 158]met allele on depressive symptoms in young children exposed to early severe social deprivation as a result of being raised in institutions. Methods: One hundred thirty six children from the Bucharest Early Intervention Project (BEIP) were randomized…

  5. Transcriptional regulation of the MET receptor tyrosine kinase gene by MeCP2 and sex-specific expression in autism and Rett syndrome.

    Plummer, J T; Evgrafov, O V; Bergman, M Y; Friez, M; Haiman, C A; Levitt, P; Aldinger, K A

    2013-10-22

    Single nucleotide variants (SNV) in the gene encoding the MET receptor tyrosine kinase have been associated with an increased risk for autism spectrum disorders (ASD). The MET promoter SNV rs1858830 C 'low activity' allele is enriched in ASD, associated with reduced protein expression, and impacts functional and structural circuit connectivity in humans. To gain insight into the transcriptional regulation of MET on ASD-risk etiology, we examined an interaction between the methyl CpG-binding protein 2 (MeCP2) and the MET 5' promoter region. Mutations in MeCP2 cause Rett syndrome (RTT), a predominantly female neurodevelopmental disorder sharing some ASD clinical symptoms. MeCP2 binds to a region of the MET promoter containing the ASD-risk SNV, and displays rs1858830 genotype-specific binding in human neural progenitor cells derived from the olfactory neuroepithelium. MeCP2 binding enhances MET expression in the presence of the rs1858830 C allele, but MET transcription is attenuated by RTT-specific mutations in MeCP2. In the postmortem temporal cortex, a region normally enriched in MET, gene expression is reduced dramatically in females with RTT, although not due to enrichment of the rs1858830 C 'low activity' allele. We newly identified a sex-based reduction in MET expression, with male ASD cases, but not female ASD cases compared with sex-matched controls. The experimental data reveal a prominent allele-specific regulation of MET transcription by MeCP2. The mechanisms underlying the pronounced reduction of MET in ASD and RTT temporal cortex are distinct and likely related to factors unique to each disorder, including a noted sex bias.

  6. Effects of the BDNF Val66Met polymorphism on neural responses to facial emotion.

    Mukherjee, Prerona; Whalley, Heather C; McKirdy, James W; McIntosh, Andrew M; Johnstone, Eve C; Lawrie, Stephen M; Hall, Jeremy

    2011-03-31

    The brain derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with affective disorders, but its role in emotion processing has not been fully established. Due to the clinically heterogeneous nature of these disorders, studying the effect of genetic variation in the BDNF gene on a common attribute such as fear processing may elucidate how the BDNF Val66Met polymorphism impacts brain function. Here we use functional magnetic resonance imaging examine the effect of the BDNF Val66Met genotype on neural activity for fear processing. Forty healthy participants performed an implicit fear task during scanning, where subjects made gender judgments from facial images with neutral or fearful emotion. Subjects were tested for facial emotion recognition post-scan. Functional connectivity was investigated using psycho-physiological interactions. Subjects were genotyped for the BDNF Val66Met polymorphism and the measures compared between genotype groups. Met carriers showed overactivation in the anterior cingulate cortex (ACC), brainstem and insula bilaterally for fear processing, along with reduced functional connectivity from the ACC to the left hippocampus, and impaired fear recognition ability. The results show that during fear processing, Met allele carriers show an increased neural response in regions previously implicated in mediating autonomic arousal. Further, the Met carriers show decreased functional connectivity with the hippocampus, which may reflect differential retrieval of emotional associations. Together, these effects show significant differences in the neural substrate for fear processing with genetic variation in BDNF. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  7. Catechol-O-methyltransferase val158met polymorphism predicts placebo effect in irritable bowel syndrome.

    Kathryn T Hall

    Full Text Available Identifying patients who are potential placebo responders has major implications for clinical practice and trial design. Catechol-O-methyltransferase (COMT, an important enzyme in dopamine catabolism plays a key role in processes associated with the placebo effect such as reward, pain, memory and learning. We hypothesized that the COMT functional val158met polymorphism, was a predictor of placebo effects and tested our hypothesis in a subset of 104 patients from a previously reported randomized controlled trial in irritable bowel syndrome (IBS. The three treatment arms from this study were: no-treatment ("waitlist", placebo treatment alone ("limited" and, placebo treatment "augmented" with a supportive patient-health care provider interaction. The primary outcome measure was change from baseline in IBS-Symptom Severity Scale (IBS-SSS after three weeks of treatment. In a regression model, the number of methionine alleles in COMT val158met was linearly related to placebo response as measured by changes in IBS-SSS (p = .035. The strongest placebo response occurred in met/met homozygotes treated in the augmented placebo arm. A smaller met/met associated effect was observed with limited placebo treatment and there was no effect in the waitlist control. These data support our hypothesis that the COMT val158met polymorphism is a potential biomarker of placebo response.

  8. Microangiopathic complications related to different alleles of ...

    Egyptian Journal of Biochemistry and Molecular Biology. Journal Home ... Microangiopathic complications related to different alleles of manganese superoxide dismutase gene in diabetes mellitus type 1. TM EL Masry ... 23(2) 2005: 155-167 ...

  9. Metsämaisema ulkoilijoiden kokemana

    Vuohijoki, Jaana

    2010-01-01

    Työn aiheena oli tutkia, miten ulkoilijat kokevat metsämaiseman Tampereella. Tavoitteena oli selvittää ulkoilijoiden maisema-arvostuksia sekä suhtautumista metsänhoidon toimenpiteisiin. Tutkimus toteutettiin maastohaastatteluina Tampereella kolmella eri asuinalueella: Hallilassa, Leinolassa ja Tesomajärvellä. Otoskooksi muodostui kymmenen haastattelua aluetta kohti, mutta yhdeltä vastaajalta ei ehditty kysyä kaikkia kysymyksiä. Vastaajat olivat yleisesti ottaen tyytyväisiä alueiden metsän...

  10. Association of BDNF Val66Met Polymorphism and Brain BDNF levels with Major Depression and Suicide.

    Youssef, Mariam M; Underwood, Mark D; Huang, Yung-Yu; Hsiung, Shu-Chi; Liu, Yan; Simpson, Norman R; Bakalian, Mihran J; Rosoklija, Gorazd B; Dwork, Andrew J; Arango, Victoria; Mann, J John

    2018-02-08

    Brain-derived neurotrophic factor (BDNF) is implicated in the pathophysiology of major depressive disorder (MDD) and suicide. Both are partly caused by early life adversity (ELA) and ELA reduces BDNF protein levels. This study examines the association of BDNF Val66Met polymorphism and brain BDNF levels with depression and suicide. We hypothesized that both MDD and ELA would be associated with the Met allele and lower brain BDNF levels. Such an association would be consistent with low BDNF mediating the effect of ELA on adulthood suicide and MDD. BDNF Val66Met polymorphism was genotyped in postmortem brains of 37 suicide decedents and 53 non-suicides. Additionally, BDNF protein levels were determined by Western blot in dorsolateral prefrontal cortex (Brodmann area 9; BA9), anterior cingulate cortex (ACC, BA24), caudal brainstem and rostral brainstem. The relationships between these measures and MDD, death by suicide and reported ELA were examined. Subjects with the Met allele had an increased risk for depression. Depressed patients also have lower BDNF levels in ACC and caudal brainstem compared with non-depressed subjects. No effect of history of suicide death or ELA was observed with genotype, but lower BDNF levels in ACC were found in subjects who had been exposed to ELA and/or died by suicide compared to non-suicide decedents and no reported ELA. This study provides further evidence implicating low brain BDNF and the BDNF Met allele in major depression risk. Future studies should seek to determine how altered BDNF expression contributes to depression and suicide. © The Author(s) 2018. Published by Oxford University Press on behalf of CINP.

  11. Allele Workbench: transcriptome pipeline and interactive graphics for allele-specific expression.

    Carol A Soderlund

    Full Text Available Sequencing the transcriptome can answer various questions such as determining the transcripts expressed in a given species for a specific tissue or condition, evaluating differential expression, discovering variants, and evaluating allele-specific expression. Differential expression evaluates the expression differences between different strains, tissues, and conditions. Allele-specific expression evaluates expression differences between parental alleles. Both differential expression and allele-specific expression have been studied for heterosis (hybrid vigor, where the hybrid has improved performance over the parents for one or more traits. The Allele Workbench software was developed for a heterosis study that evaluated allele-specific expression for a mouse F1 hybrid using libraries from multiple tissues with biological replicates. This software has been made into a distributable package, which includes a pipeline, a Java interface to build the database, and a Java interface for query and display of the results. The required input is a reference genome, annotation file, and one or more RNA-Seq libraries with optional replicates. It evaluates allelic imbalance at the SNP and transcript level and flags transcripts with significant opposite directional allele-specific expression. The Java interface allows the user to view data from libraries, replicates, genes, transcripts, exons, and variants, including queries on allele imbalance for selected libraries. To determine the impact of allele-specific SNPs on protein folding, variants are annotated with their effect (e.g., missense, and the parental protein sequences may be exported for protein folding analysis. The Allele Workbench processing results in transcript files and read counts that can be used as input to the previously published Transcriptome Computational Workbench, which has a new algorithm for determining a trimmed set of gene ontology terms. The software with demo files is available

  12. Abnormal segregation of alleles in CEPH pedigree DNAs arising from allele loss in lymphoblastoid DNA.

    Royle, N J; Armour, J A; Crosier, M; Jeffreys, A J

    1993-01-01

    Somatic events that result in the reduction to hemi- or homozygosity at all loci affected by the event have been identified in lymphoblastoid DNA from mothers of two CEPH families. Using suitably informative probes, the allele deficiencies were detected by the abnormal transmission of alleles from grandparents to grandchildren, with the apparent absence of the alleles from the parent. Undetected somatic deficiencies in family DNAs could result in misscoring of recombination events and consequently introduce errors into linkage analysis.

  13. Influence of COMT val158met genotype on the depressed brain during emotional processing and working memory.

    Esther M Opmeer

    Full Text Available Major depressive disorder (MDD has been associated with abnormal prefrontal-limbic interactions and altered catecholaminergic neurotransmission. The val158met polymorphism on the catechol-O-methyltransferase (COMT gene has been shown to influence prefrontal cortex (PFC activation during both emotional processing and working memory (WM. Although COMT-genotype is not directly associated with MDD, it may affect MDD pathology by altering PFC activation, an endophenotype associated with both COMT and MDD. 125 participants, including healthy controls (HC, n=28 and MDD patients were genotyped for the COMT val158met polymorphism and underwent functional magnetic resonance imaging (fMRI-neuroimaging during emotion processing (viewing of emotional facial expressions and a WM task (visuospatial planning. Within HC, we observed a positive correlation between the number of met-alleles and right inferior frontal gyrus activation during emotional processing, whereas within patients the number of met-alleles was not correlated with PFC activation. During WM a negative correlation between the number of met-alleles and middle frontal gyrus activation was present in the total sample. In addition, during emotional processing there was an effect of genotype in a cluster including the amygdala and hippocampus. These results demonstrate that COMT genotype is associated with relevant endophenotypes for MDD. In addition, presence of MDD only interacts with genotype during emotional processing and not working memory.

  14. Is neurofeedback effectief bij kinderen met ADHD?

    de Hen, M.H.; Geurts, H.M.

    2008-01-01

    Kan neurofeedback verantwoord ingezet worden bij de behandeling van kinderen met ADHD? Omdeze vraag te beantwoorden worden zeven recente onderzoeken naar de effectiviteit van neurofeedback bij kinderen met ADHD geanalyseerd. Ondanks dat de resultaten in eerste instantie lijken te suggereren dat

  15. COMT Val(108/158)Met polymorphism effects on emotional brain function and negativity bias.

    Williams, Leanne M; Gatt, Justine M; Grieve, Stuart M; Dobson-Stone, Carol; Paul, Robert H; Gordon, Evian; Schofield, Peter R

    2010-11-15

    Biases toward processing negative versus positive information vary as a function of level of awareness, and are modulated by monoamines. Excessive biases are associated with individual differences in mood and emotional stability, and emotional disorder. Here, we examined the impact of the catechol-O-methyltransferase (COMT) Val(108/158)Met polymorphism, involved in dopamine and norepinephrine catabolism, on both emotional brain function and self-reported negativity bias. COMT genotyping and self-reported level of negativity bias were completed for 46 healthy participants taking part in the Brain Resource International Database. Functional MRI was undertaken during perception of facial expressions of fear and happiness presented under unmasked (consciously identified) and masked (to prevent conscious detection) conditions. Structural MR images were also acquired. A greater number of COMT Met alleles predicted increased activation in brainstem, amygdala, basal ganglia and medial prefrontal regions for conscious fear, but decreased activation for conscious happiness. This pattern was also apparent for brainstem activation for the masked condition. Effects were most apparent for females. These differences could not be explained by gray matter variations. The Met-related profile of activation, particularly prefrontally, predicted greater negativity bias associated with risk for emotional disorder. The findings suggest that the COMT Met allele modulates neural substrates of negative versus positive emotion processing. This effect may contribute to negativity biases, which confer susceptibility for emotional disorders. Copyright 2010 Elsevier Inc. All rights reserved.

  16. Word je met Donkey Konga een betere muzikant? : Muziek leren spelen met de spelcomputer

    Tom Langhorst

    2010-01-01

    Kan de spelcomputer behulpzaam zijn bij de ontwikkeling van het muzikale gevoel? Met die vraag in het achterhoofd bekijkt Tom Langhorst hier kritisch het Nintendo-spel Donkey Konga, waarin de speler mee kan drummen met bekende popsongs.

  17. The Pleiotropic MET Receptor Network: Circuit Development and the Neural-Medical Interface of Autism.

    Eagleson, Kathie L; Xie, Zhihui; Levitt, Pat

    2017-03-01

    People with autism spectrum disorder and other neurodevelopmental disorders (NDDs) are behaviorally and medically heterogeneous. The combination of polygenicity and gene pleiotropy-the influence of one gene on distinct phenotypes-raises questions of how specific genes and their protein products interact to contribute to NDDs. A preponderance of evidence supports developmental and pathophysiological roles for the MET receptor tyrosine kinase, a multifunctional receptor that mediates distinct biological responses depending upon cell context. MET influences neuron architecture and synapse maturation in the forebrain and regulates homeostasis in gastrointestinal and immune systems, both commonly disrupted in NDDs. Peak expression of synapse-enriched MET is conserved across rodent and primate forebrain, yet regional differences in primate neocortex are pronounced, with enrichment in circuits that participate in social information processing. A functional risk allele in the MET promoter, enriched in subgroups of children with autism spectrum disorder, reduces transcription and disrupts socially relevant neural circuits structurally and functionally. In mice, circuit-specific deletion of Met causes distinct atypical behaviors. MET activation increases dendritic complexity and nascent synapse number, but synapse maturation requires reductions in MET. MET mediates its specific biological effects through different intracellular signaling pathways and has a complex protein interactome that is enriched in autism spectrum disorder and other NDD candidates. The interactome is coregulated in developing human neocortex. We suggest that a gene as pleiotropic and highly regulated as MET, together with its interactome, is biologically relevant in normal and pathophysiological contexts, affecting central and peripheral phenotypes that contribute to NDD risk and clinical symptoms. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  18. Association of ghrelin Leu72Met polymorphism with type 2 diabetes mellitus in Chinese population.

    Liu, Jing; Liu, Jia; Tian, Li-min; Liu, Ju-xiang; Bing, Ya-jun; Zhang, Ji-ping; Wang, Yun-Fang; Zhang, Lu-yan

    2012-08-10

    Ghrelin, a novel endogenous ligand for the growth hormone secretagogue receptor, is considered to implicate the development of the type 2 diabetes mellitus (T2DM). The Leu72Met (+408C>A) polymorphism of the preproghrelin, has been linked to obesity, insulin resistance and diabetes. To investigate the distribution of ghrelin gene Leu72Met polymorphism and its association with the type 2 diabetes mellitus in Chinese population. We conducted a case-control study on 877 patients with T2DM and 864 controls, which were genotyped by the polymerase chain reaction (PCR) technique, denaturing high performance liquid chromatography (DHPLC) and DNA sequence analysis. Laboratory analyses were carried out in the hospital laboratory. No significant difference in the Leu72Met genotype distributions and allele frequency was observed between type 2 diabetes mellitus and controls (both P>0.05). The polymorphism was not associated with T2DM. However, among the T2DM group, the patients carrying Leu72Leu genotype had significantly increased levels of FPG and serum creatinine compared with variant genotypes (Leu72Met and Met72Met) (Ppolymorphism of the preproghrelin gene was not associated with T2DM in Chinese population. However, it may have some roles in the etiology of insulin resistance. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. BDNFval66met affects neural activation pattern during fear conditioning and 24 h delayed fear recall.

    Lonsdorf, Tina B; Golkar, Armita; Lindström, Kara M; Haaker, Jan; Öhman, Arne; Schalling, Martin; Ingvar, Martin

    2015-05-01

    Brain-derived neurotrophic factor (BDNF), the most abundant neutrophin in the mammalian central nervous system, is critically involved in synaptic plasticity. In both rodents and humans, BDNF has been implicated in hippocampus- and amygdala-dependent learning and memory and has more recently been linked to fear extinction processes. Fifty-nine healthy participants, genotyped for the functional BDNFval66met polymorphism, underwent a fear conditioning and 24h-delayed extinction protocol while skin conductance and blood oxygenation level dependent (BOLD) responses (functional magnetic resonance imaging) were acquired. We present the first report of neural activation pattern during fear acquisition 'and' extinction for the BDNFval66met polymorphism using a differential conditioned stimulus (CS)+ > CS- comparison. During conditioning, we observed heightened allele dose-dependent responses in the amygdala and reduced responses in the subgenual anterior cingulate cortex in BDNFval66met met-carriers. During early extinction, 24h later, we again observed heightened responses in several regions ascribed to the fear network in met-carriers as opposed to val-carriers (insula, amygdala, hippocampus), which likely reflects fear memory recall. No differences were observed during late extinction, which likely reflects learned extinction. Our data thus support previous associations of the BDNFval66met polymorphism with neural activation in the fear and extinction network, but speak against a specific association with fear extinction processes. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  20. Estimated allele substitution effects underlying genomic evaluation models depend on the scaling of allele counts

    Bouwman, Aniek C.; Hayes, Ben J.; Calus, Mario P.L.

    2017-01-01

    Background: Genomic evaluation is used to predict direct genomic values (DGV) for selection candidates in breeding programs, but also to estimate allele substitution effects (ASE) of single nucleotide polymorphisms (SNPs). Scaling of allele counts influences the estimated ASE, because scaling of

  1. Modulating effect of COMT Val(158)Met polymorphism on interference resolution during a working memory task.

    Jaspar, Mathieu; Dideberg, Vinciane; Bours, Vincent; Maquet, Pierre; Collette, Fabienne

    2015-04-01

    Genetic variability related to the catechol-O-methyltransferase (COMT) gene has received increasing attention in the last 15years, in particular as a potential modulator of the neural substrates underlying inhibitory processes and updating in working memory (WM). In an event-related functional magnetic resonance imaging (fMRI) study, we administered a modified version of the Sternberg probe recency task (Sternberg, 1966) to 43 young healthy volunteers, varying the level of interference across successive items. The task was divided into two parts (high vs. low interference) to induce either proactive or reactive control processes. The participants were separated into three groups according to their COMT Val(158)Met genotype [Val/Val (VV); Val/Met (VM); Met/Met (MM)]. The general aim of the study was to determine whether COMT polymorphism has a modulating effect on the neural substrates of interference resolution during WM processing. Results indicate that interfering trials were associated with greater involvement of frontal cortices (bilateral medial frontal gyrus, left precentral and superior frontal gyri, right inferior frontal gyrus) in VV homozygous subjects (by comparison to Met allele carriers) only in the proactive condition of the task. In addition, analysis of peristimulus haemodynamic responses (PSTH) revealed that the genotype-related difference observed in the left SFG was specifically driven by a larger increase in activity from the storage to the recognition phase of the interfering trials in VV homozygous subjects. These results confirm the impact of COMT genotype on inhibitory processes during a WM task, with an advantage for Met allele carriers. Interestingly, this impact on frontal areas is present only when the level of interference is high, and especially during the transition from storage to recognition in the left superior frontal gyrus. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Met1-linked Ubiquitination in Immune Signalling

    Fiil, Berthe Katrine; Gyrd-Hansen, Mads

    2014-01-01

    Methionine 1-linked ubiquitin chains (Met1-Ub), or linear ubiquitin, has emerged as a central post-translational modification in innate immune signalling. Molecular machinery that assembles, senses and, more recently, disassembles Met1-Ub has been identified, and technical advances have enabled...... identification of physiological substrates for Met1-Ub in response to activation of innate immune receptors. These discoveries have significantly advanced our understanding of how non-degradative ubiquitin modifications control pro-inflammatory responses mediated by nuclear factor κB and mitogen...

  3. Mars MetNet Mission Payload Overview

    Harri, A.-M.; Haukka, H.; Alexashkin, S.; Guerrero, H.; Schmidt, W.; Genzer, M.; Vazquez, L.

    2012-09-01

    A new kind of planetary exploration mission for Mars is being developed in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission [1] is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide crucial scientific data about the Martian atmospheric phenomena.

  4. Allelic genealogies in sporophytic self-incompatibility systems in plants

    Schierup, Mikkel Heide; Vekemans, Xavier; Christiansen, Freddy Bugge

    1998-01-01

    , alleles act codominantly in both pollen and style, in the SSIdom model, alleles form a dominance hierarchy, and in SSIdomcod, alleles are codominant in the style and show a dominance hierarchy in the pollen. Coalescence times of alleles rarely differ more than threefold from those under gametophytic self...

  5. Association of BDNF Val66Met polymorphism with HPA and SAM axis reactivity to psychological and physical stress

    Tsuru J

    2014-11-01

    Full Text Available Jusen Tsuru,1 Yoshihiro Tanaka,1 Yoshinobu Ishitobi,1 Yoshihiro Maruyama,1 Ayako Inoue,1 Aimi Kawano,1 Rie Ikeda,1 Tomoko Ando,1 Harumi Oshita,2 Saeko Aizawa,1 Koji Masuda,1 Haruka Higuma,1 Masayuki Kanehisa,1 Taiga Ninomiya,1 Jotaro Akiyoshi1 1Department of Neuropsychiatry, 2Department of Applied Linguistics, Faculty of Medicine, Oita University, Oita, Japan Background: Decreased expression of brain-derived neurotrophic factor (BDNF is implicated in enhanced stress responses. The BDNF Val66Met polymorphism is associated with psychological changes; for example, carriers of the Met allele exhibit increased harm avoidance as well as a higher prevalence of depression and anxiety disorder.Methods: To analyze the effects of BDNF Val66Met on stress responses, we tested 226 university students (88 women and 138 men using a social stress procedure (Trier Social Stress Test [TSST] and an electrical stimulation stress test. Stress indices were derived from repeated measurements of salivary α-amylase, salivary cortisol, heart rate, and psychological testing during the stress tests. All subjects were genotyped for the Val66Met polymorphism (G196A.Results: A significant three-way interaction (time [3 levels] × BDNF [Val/Val, Val/Met, Met/Met]; P<0.05 was demonstrated that revealed different salivary cortisol responses in the TSST but not in electrical stimulation. Met/Met women had stronger cortisol responses than Val/Met and Val/Val individuals in the TSST. Met/Met men exhibited stronger salivary cortisol responses than Val/Met and Val/Val individuals in the TSST.Conclusion: These results indicate that a common, functionally significant polymorphism in BDNF had different effects on hypothalamic–pituitary–adrenocortical axis reactivity but not on sympathetic adrenomedullary reactivity in TSST and electrical stimulation tests. Keywords: stress, brain-derived neurotrophic factor, cortisol, saliva

  6. BDNF Val66Met polymorphism, life stress and depression: A meta-analysis of gene-environment interaction.

    Zhao, Mingzhe; Chen, Lu; Yang, Jiarun; Han, Dong; Fang, Deyu; Qiu, Xiaohui; Yang, Xiuxian; Qiao, Zhengxue; Ma, Jingsong; Wang, Lin; Jiang, Shixiang; Song, Xuejia; Zhou, Jiawei; Zhang, Jian; Chen, Mingqi; Qi, Dong; Yang, Yanjie; Pan, Hui

    2018-02-01

    Depression is thought to be multifactorial in etiology, including genetic and environmental components. While a number of gene-environment interaction studies have been carried out, meta-analyses are scarce. The present meta-analysis aimed to quantify evidence on the interaction between brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and stress in depression. Included were 31 peer-reviewed with a pooled total of 21060 participants published before October 2016 and literature searches were conducted using PubMed, Wolters Kluwer, Web of Science, EBSCO, Elsevier Science Direct and Baidu Scholar databases. The results indicated that the Met allele of BDNF Val66Met polymorphism significantly moderated the relationship between stress and depression (Z=2.666, p = 0.003). The results of subgroup analysis concluded that stressful life events and childhood adversity separately interacted with the Met allele of BDNF Val66Met polymorphism in depression (Z = 2.552, p = 0.005; Z = 1.775, p = 0.03). The results could be affected by errors or bias in primary studies which had small sample sizes with relatively lower statistic power. We could not estimate how strong the interaction effect between gene and environment was. We found evidence that supported the hypothesis that BDNF Val66Met polymorphism moderated the relationship between stress and depression, despite the fact that many included individual studies did not show this effect. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Gesloten kringloop met omgekeerde osmose of membraandestilatie

    Stijger, H.; Os, van E.A.

    2011-01-01

    TNO heeft samen met Wageningen UR Glastuinbouw een inventarisatie uitgevoerd naar geschikte zuiveringstechnieken om de waterstroom op tuinbouwbedrijven gesloten te krijgen. Uit de haalbaarheidstudie komen twee veelbelovende technieken naar voren die op vrij korte termijn inzetbaar zijn: omgekeerde

  8. Mars MetNet Mission Status

    Harri, A.-M.; Aleksashkin, S.; Arruego, I.; Schmidt, W.; Genzer, M.; Vazquez, L.; Haukka, H.; Palin, M.; Nikkanen, T.

    2015-10-01

    New kind of planetary exploration mission for Mars is under development in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semihard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested.

  9. Mars MetNet Precursor Mission Status

    Harri, A.-M.; Aleksashkin, S.; Guerrero, H.; Schmidt, W.; Genzer, M.; Vazquez, L.; Haukka, H.

    2013-09-01

    We are developing a new kind of planetary exploration mission for Mars in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested.

  10. Bio-composiet : Thermoplastische kunsstof met natuurvezels

    Beurden, van K.M.M. (Karin); Goselink, E.A. (Erik)

    2013-01-01

    Een biocomposiet wordt samengesteld uit een vezel en een hars. In dit document worden twee verwerkingsvormen van biocomposieten behandeld: - Vezel/poeder versterkt kunststof (granulaat); - Kunststof plaatmateriaal versterkt met een weefsel (laminaat), ook wel Sizopreg® genoemd. Door een

  11. Intern transport beter te plannen met computer

    Annevelink, E.

    1999-01-01

    Verbetering van intern transport in de potplantenteelt. Door getoetste vuistregels te combineren met toegepaste wiskunde is automatische planning van het intern transport binnen handbereik. Dit leidt tot minder transportbewegingen en tijdsbesparing bij het plannen

  12. Fosfaatwerking ogranische meststoffen vergelijkbaar met kunstmest

    Ehlert, P.A.I.; Pasterkamp, H.P.

    2000-01-01

    Gegevens in bijgaande tabel: Indicatieve fosfaatgehalten en de relatieve verdeling over mineraalfosfaat en organisch gebonden fosfaat in meststoffen met per mestsoort gegevens over het totaal fosfaatgehalte, het percentage mineraal fosfaat en het percentage organisch fosfaat

  13. Technisch lego met een Duplo-interface

    Pimentel, A.; Schipper, D.

    2008-01-01

    Daedalus is een ontwerpflow op systeemniveau waarmee techneuten snel kunnen experimenteren met verschillende multiprocessorarchitecturen tijdens de vroege stadia van het ontwerptraject. Het is het resultaat van tien jaar onderzoek en ontwikkeling binnen de Progress-projecten Artemis en Artemisia.

  14. Extraboard performance : TriMet case study.

    2012-02-01

    This paper examines extraboard operations and management at TriMet, the transit provider for the Portland Oregon metropolitan area. The : extraboard consists of a pool of operators who fill open work resulting from absences and other causes. The pape...

  15. Fifty years of genetic load

    Wallace, B.

    1991-01-01

    This book discusses the radiation effects on Drosophila. It was originally thought that irradiating Drosophila would decrease the average fitness of the population, thereby leading to information about the detrimental effects of mutations. Surprisingly, the fitness of the irradiated population turned out to be higher than that of the control population. The original motivation for the experiment was as a test of genetic load theory. The average fitness of a population is depressed by deleterious alleles held in the population by the balance between mutation and natural selection. The depression is called the genetic load of the population. The load dose not depend on the magnitude of the deleterious effect of alleles, but only on the mutation rate

  16. MMPM - Mars MetNet Precursor Mission

    Harri, A.-M.; Schmidt, W.; Pichkhadze, K.; Linkin, V.; Vazquez, L.; Uspensky, M.; Polkko, J.; Genzer, M.; Lipatov, A.; Guerrero, H.; Alexashkin, S.; Haukka, H.; Savijarvi, H.; Kauhanen, J.

    2008-09-01

    We are developing a new kind of planetary exploration mission for Mars - MetNet in situ observation network based on a new semi-hard landing vehicle called the Met-Net Lander (MNL). The eventual scope of the MetNet Mission is to deploy some 20 MNLs on the Martian surface using inflatable descent system structures, which will be supported by observations from the orbit around Mars. Currently we are working on the MetNet Mars Precursor Mission (MMPM) to deploy one MetNet Lander to Mars in the 2009/2011 launch window as a technology and science demonstration mission. The MNL will have a versatile science payload focused on the atmospheric science of Mars. Detailed characterization of the Martian atmospheric circulation patterns, boundary layer phenomena, and climatology cycles, require simultaneous in-situ measurements by a network of observation posts on the Martian surface. The scientific payload of the MetNet Mission encompasses separate instrument packages for the atmospheric entry and descent phase and for the surface operation phase. The MetNet mission concept and key probe technologies have been developed and the critical subsystems have been qualified to meet the Martian environmental and functional conditions. Prototyping of the payload instrumentation with final dimensions was carried out in 2003-2006.This huge development effort has been fulfilled in collaboration between the Finnish Meteorological Institute (FMI), the Russian Lavoschkin Association (LA) and the Russian Space Research Institute (IKI) since August 2001. Currently the INTA (Instituto Nacional de Técnica Aeroespacial) from Spain is also participating in the MetNet payload development. To understand the behavior and dynamics of the Martian atmosphere, a wealth of simultaneous in situ observations are needed on varying types of Martian orography, terrain and altitude spanning all latitudes and longitudes. This will be performed by the Mars MetNet Mission. In addition to the science aspects the

  17. Interaction between 5-HTTLPR and BDNF Val66Met polymorphisms on HPA axis reactivity in preschoolers.

    Dougherty, Lea R; Klein, Daniel N; Congdon, Eliza; Canli, Turhan; Hayden, Elizabeth P

    2010-02-01

    This study examined whether the interaction between the serotonin transporter promoter region (5-HTTLPR) and brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms was associated with hypothalamic-pituitary-adrenal (HPA) axis reactivity to stress. A community sample of 144 preschool-aged children was genotyped and exposed to stress-inducing laboratory tasks. Salivary cortisol was obtained at four time points during a standardized laboratory assessment before and after stressors involving separation from a parent and frustrating tasks. Children homozygous for the short-5-HTTLPR allele and carrying the Met-BDNF allele evidenced a significantly lower initial level of cortisol, followed by a positive increase in cortisol in response to the laboratory stressors. In contrast, children who were homozygous for the short-5-HTTLPR and the Val-BDNF alleles evidenced a greater decline in cortisol in response to the laboratory stressors. Findings indicated that the BDNF gene moderated the association between 5-HTTLPR and children's biological stress responses, suggesting that epistatic effects play a role in individual differences in stress regulation, and possibly genetic vulnerability to stress-related disorders. Copyright 2009 Elsevier B.V. All rights reserved.

  18. Mars MetNet Mission Status

    Harri, Ari-Matti; Aleksashkin, Sergei; Arruego, Ignacio; Schmidt, Walter; Genzer, Maria; Vazquez, Luis; Haukka, Harri

    2015-04-01

    New kind of planetary exploration mission for Mars is under development in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested. 1. MetNet Lander The MetNet landing vehicles are using an inflatable entry and descent system instead of rigid heat shields and parachutes as earlier semi-hard landing devices have used. This way the ratio of the payload mass to the overall mass is optimized. The landing impact will burrow the payload container into the Martian soil providing a more favorable thermal environment for the electronics and a suitable orientation of the telescopic boom with external sensors and the radio link antenna. It is planned to deploy several tens of MNLs on the Martian surface operating at least partly at the same time to allow meteorological network science. 2. Scientific Payload The payload of the two MNL precursor models includes the following instruments: Atmospheric instruments: 1. MetBaro Pressure device 2. MetHumi Humidity device 3. MetTemp Temperature sensors Optical devices: 1. PanCam Panoramic 2. MetSIS Solar irradiance sensor with OWLS optical wireless system for data transfer 3. DS Dust sensor The descent processes dynamic properties are monitored by a special 3-axis accelerometer combined with a 3-axis gyrometer. The data will be sent via auxiliary beacon antenna throughout the

  19. RHD alleles in the Tunisian population

    Ouchari, Mouna; Jemni-Yaacoub, Saloua; Chakroun, Taher; Abdelkefi, Saida; Houissa, Batoul; Hmida, Slama

    2013-01-01

    Background: A comprehensive survey of RHD alleles in Tunisia population was lacking. The aim of this study was to use a multiplex RHD typing assay for simultaneous detection of partial D especially with RHD/RHCE deoxyribonucleic acid (DNA) sequence exchange mechanism and some weak D alleles. Materials and Methods: Six RHD specific primer sets were designed to amplify RHD exons 3, 4, 5, 6, 7 and 9. DNA from 2000 blood donors (1777 D+ and 223 D-) from several regions was selected for RHD genotyping using a PCR multiplex assay. Further molecular investigations were done to characterize the RHD variants that were identified by the PCR multiplex assay. Results: In the 1777 D+ samples, only 10 individuals showed the absence of amplification of exons 4 and 5 that were subsequently identified by PCR-SSP as weak D type 4 variants. No hybrid allele was detected. In the 223 D-, RHD amplification of some exons was observed only in 5 samples: 4 individuals expressed only RHD exon 9, and one subject lacking exons 4 and 5. These samples were then screened by PCR-SSPs on d(C) ces and weak D type 4, respectively. Conclusion: The weak D type 4 appears to be the most common D variant allele. We have not found any partial D variant. Findings also indicated that RHD gene deletion is the most prevalent cause of the D- phenotype in the Tunisian population. PMID:24014941

  20. Diversity of Lactase Persistence Alleles in Ethiopia

    Jones, BL; Raga, TO; Liebert, Anke

    2013-01-01

    The persistent expression of lactase into adulthood in humans is a recent genetic adaptation that allows the consumption of milk from other mammals after weaning. In Europe, a single allele (−13910∗T, rs4988235) in an upstream region that acts as an enhancer to the expression of the lactase gene ...

  1. Lack of association between urotensin-II (UTS2 gene polymorphisms (Thr21Met and Ser89Asn and migraine

    Betül Ozan

    2017-08-01

    Full Text Available Migraine is a common neurovascular brain disorder with heterogeneous clinical presentation, including recurrent headache attacks. The pathophysiology of migraine is complex, and a number of genomic regions have been associated with the development of migraine. In this study, we analyzed the allele and genotype frequencies of the urotensin-II gene (UTS2 polymorphisms, Thr21Met and Ser89Asn, among Turkish patients with migraine. A total of 146 patients with migraine (14 with aura [MA group] and 132 without aura [MO group] were genotyped for Thr21Met and Ser89Asn polymorphisms and compared with 154 age- and sex-matched healthy controls. The UTS2 gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP. No significant differences were observed in allele and genotype frequencies for Thr21Met and Ser89Asn polymorphisms between the patients with migraine and control group. Similarly, we did not observe significant differences in allele and genotype frequencies between MA and MO and control group. Moreover, the haplotype analysis showed no association between UTS2 gene haplotypes (MN, MS, TN, and TS and migraine. In summary, Thr21Met and Ser89Asn polymorphisms of the UTS2 gene are not risk factors for migraine in our sample of Turkish migraine patients.

  2. COMT Val158Met polymorphism influences the susceptibility to framing in decision-making: OFC-amygdala functional connectivity as a mediator.

    Gao, Xiaoxue; Gong, Pingyuan; Liu, Jinting; Hu, Jie; Li, Yue; Yu, Hongbo; Gong, Xiaoliang; Xiang, Yang; Jiang, Changjun; Zhou, Xiaolin

    2016-05-01

    Individuals tend to avoid risk in a gain frame, in which options are presented in a positive way, but seek risk in a loss frame, in which the same options are presented negatively. Previous studies suggest that emotional responses play a critical role in this "framing effect." Given that the Met allele of COMT Val158Met polymorphism (rs4680) is associated with the negativity bias during emotional processing, this study investigated whether this polymorphism is associated with individual susceptibility to framing and which brain areas mediate this gene-behavior association. Participants were genotyped, scanned in resting state, and completed a monetary gambling task with options (sure vs risky) presented as potential gains or losses. The Met allele carriers showed a greater framing effect than the Val/Val homozygotes as the former gambled more than the latter in the loss frame. Moreover, the gene-behavior association was mediated by resting-state functional connectivity (RSFC) between orbitofrontal cortex (OFC) and bilateral amygdala. Met allele carriers showed decreased RSFC, thereby demonstrating higher susceptibility to framing than Val allele carriers. These findings demonstrate the involvement of COMT Val158Met polymorphism in the framing effect in decision-making and suggest RSFC between OFC and amygdala as a neural mediator underlying this gene-behavior association. Hum Brain Mapp 37:1880-1892, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. Estimating the probability of allelic drop-out of STR alleles in forensic genetics

    Tvedebrink, Torben; Eriksen, Poul Svante; Mogensen, Helle Smidt

    2009-01-01

    In crime cases with available DNA evidence, the amount of DNA is often sparse due to the setting of the crime. In such cases, allelic drop-out of one or more true alleles in STR typing is possible. We present a statistical model for estimating the per locus and overall probability of allelic drop......-out using the results of all STR loci in the case sample as reference. The methodology of logistic regression is appropriate for this analysis, and we demonstrate how to incorporate this in a forensic genetic framework....

  4. The BDNF Val66Met polymorphism affects HPA-axis reactivity to acute stress.

    Alexander, Nina; Osinsky, Roman; Schmitz, Anja; Mueller, Eva; Kuepper, Yvonne; Hennig, Juergen

    2010-07-01

    Growing evidence suggests that individual differences in HPA-axis reactivity to psychosocial stress are partly due to heritable influences. However, knowledge about the role of specific genetic variants remains very limited to date. Since brain-derived neurotrophic factor (BDNF) not only exhibits neurotrophic actions but is also involved in the regulation of hypothalamic neuropeptides, we investigated the role of a common functional polymorphism within the BDNF gene (BDNF Val66Met) in the context of endocrine and cardiovascular stress reactivity. Healthy male adults (N=100) were genotyped and exposed to a standardized laboratory stress task (Public Speaking). Saliva cortisol and self-reported mood levels were obtained at 6 time points prior to the stressor and during an extended recovery period. Furthermore, heart rate reactivity as an indicator of sympathetic activation was monitored continuously during the experimental procedure. We report a small, but significant effect of the BDNF Val66Met polymorphism on stress reactivity. More precisely, carriers of the met-allele showed a significantly attenuated HPA-axis and cardiovascular reactivity to the psychosocial stressor compared to subjects with the val/val genotype. Furthermore, the diminished physiological response in met-allele carriers was also attended by significantly lower self-reported ratings of perceived stress and nervousness. Our findings of a diminished endocrine and cardiovascular stress response in healthy male adults is consistent with a previously published study and adds further evidence for a crucial role of the BDNF Val66Met polymorphism in the modulation of stress reactivity. Copyright 2010. Published by Elsevier Ltd.

  5. Suicide attempt, clinical correlates, and BDNF Val66Met polymorphism in chronic patients with schizophrenia.

    Xia, Haisen; Zhang, Guangya; Du, Xiangdong; Zhang, Yingyang; Yin, Guangzhong; Dai, Jing; He, Man-Xi; Soares, Jair C; Li, Xiaosi; Zhang, Xiang Yang

    2018-02-01

    Recent evidence suggests the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of suicidal behavior. Because schizophrenia patients usually have high suicide rates and numerous studies have suggested that BDNF may contribute to the psychopathology of schizophrenia, we hypothesized that the functional polymorphism of BDNF (Val66Met) was associated with suicide attempts in patients with schizophrenia in a Chinese Han population. This polymorphism was genotyped in 825 chronic schizophrenia patients with (n = 123) and without (n = 702) suicide attempts and 445 healthy controls without a history of suicide attempts using a case-control design. The schizophrenia symptoms were assessed by the Positive and Negative Syndrome Scale. There were no significant differences in BDNF Val66Met genotype and allele distributions between the patients and healthy controls. However, we found the Val allele (p = .023) and the Val/Val genotypes (p = .058) to be associated with a history of suicide attempts. Moreover, some clinical characteristics, including age and cigarettes smoked each day, interacted with the BDNF gene variant and appeared to play an important role in suicide attempts among schizophrenia patients. The BDNF Val66Met polymorphism itself and its interaction with some clinical variables may influence suicide attempts among schizophrenia patients. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  6. Preproghrelin Leu72Met polymorphism in patients with type 2 diabetes mellitus.

    Ukkola, O; Kesäniemi, Y A

    2003-10-01

    The association between the Leu72Met polymorphism of the preproghrelin gene and diabetic complications was examined in patients with type 2 diabetes mellitus. A total of 258 patients with type 2 diabetes mellitus and 522 control subjects were screened. Genotypes were determined by polymerase chain reaction technique. The diagnosis of coronary heart disease was based on clinical and ECG criteria. Laboratory analyses were carried out in the hospital laboratory. No differences in the genotype distributions and allele frequencies of the preproghrelin Leu72Met polymorphism were found between type 2 diabetes mellitus patients and controls. The polymorphism was not associated with macro- or micro-angiopathy or hypertension. However, Leu72Met polymorphism was associated with serum creatinine (P = 0.006) and lipoprotein(a) [Lp(a)] levels (P = 0.006) with Leu72Leu subjects showing the highest values. This association was observed only amongst diabetic group. The Leu72Met polymorphism of the preproghrelin gene was not related to cardiovascular disease in type 2 diabetes mellitus patients. Leu72Met polymorphism was, however, associated with serum creatinine and Lp(a) levels in diabetic patients. The mechanism might be associated with a possible change in ghrelin product and its somatotropic effect.

  7. Genetic Correlates of Maladaptive Beliefs: COMT VAL(158)MET and Irrational Cognitions Linked Depending on Distress.

    Podina, Ioana; Popp, Radu; Pop, Ioan; David, Daniel

    2015-11-01

    Maladaptive/irrational beliefs are significant cognitive vulnerability mechanisms in psychopathology. They are more likely to be associated with a genetic vulnerability marker under conditions of emotional distress when irrational beliefs are more salient. Therefore, in the current study we investigated the COMT Val(158)Met gene variation in relation to irrational beliefs, assuming this relationship depended on the level of emotional distress. Two hundred and sixty-seven genotyped volunteers were assessed for core/general maladaptive beliefs, as well as trait emotional distress. We focused on context-independent measures of irrational beliefs and emotional distress in the absence of a stressor. As expected, the relationship between COMT Val(158)Met and irrational beliefs depended on the level of emotional distress (f(2)=.314). The COMT Val(158)Met-irrationality association was significant only when individuals fell in the average to above average range of emotional distress. Furthermore, within this range the Met allele seemed to relate to higher irrational beliefs. These results were significant for overall irrational beliefs and its subtypes, but not for rational beliefs, the functional counterpart of irrationality. In light of the study's limitations, the results should be considered as preliminary. If replicable, these findings have potential implications for therapygenetics, changing the view that COMT Val(158)Met might be of greater relevance when treatment modality does not rely on cognitive variables. Copyright © 2015. Published by Elsevier Ltd.

  8. MetBaro - Pressure Device for Mars MetNet Lander

    Haukka, Harri; Polkko, Jouni; Harri, Ari-Matti; Schmidt, Walter; Leinonen, Jussi; Genzer, Maria; Mäkinen, Teemu

    2010-05-01

    MetNet Mars Mission focused for Martian atmospheric science is based on a new semihard landing vehicle called the MetNet Lander (MNL). The MNL will have a versatile science payload focused on the atmospheric science of Mars. The scientific payload of the MetNet Mission encompasses separate instrument packages for the atmospheric entry and descent phase and for the surface operation phase. MetBaro is the pressure sensor of MetNet Lander designed to work on Martian surface. It is based on Barocap® technology developed by Vaisala, Inc. MetBaro is a capacitive type of sensing device where capasitor plates are moved by ambient pressure. MetBaro device consists of two pressure transducers including a total of 4 Barocap® sensor heads of high-stability and high-resolution types. The long-term stability of MetBaro is in order of 20…50 µBar and resolution a few µBar. MetBaro is small, lightweighed and has low power consumption. It weighs about 50g without wires and controlling FPGA, and consumes 15 mW of power. A similar device has successfully flown in Phoenix mission, where it performed months of measurements on Martian ground. Another device is also part of the Mars Science Laboratory REMS instrument (to be launched in 2011).

  9. MetHumi - Humidity Device for Mars MetNet Lander

    Genzer, Maria; Polkko, Jouni; Harri, Ari-Matti; Schmidt, Walter; Leinonen, Jussi; Mäkinen, Teemu; Haukka, Harri

    2010-05-01

    MetNet Mars Mission focused for Martian atmospheric science is based on a new semihard landing vehicle called the MetNet Lander (MNL). The MNL will have a versatile science payload focused on the atmospheric science of Mars. The scientific payload of the MetNet Mission encompasses separate instrument packages for the atmospheric entry and descent phase and for the surface operation phase. MetHumi is the humidity sensor of MetNet Lander designed to work on Martian surface. It is based on Humicap® technology developed by Vaisala, Inc. MetHumi is a capacitive type of sensing device where an active polymer film changes capacitance as function of relative humidity. One MetHumi device package consists of one humidity transducer including three Humicap® sensor heads, an accurate temperature sensor head (Thermocap® by Vaisala, Inc.) and constant reference channels. MetHumi is very small, lightweighed and has low power consumption. It weighs only about 15 g without wires, and consumes 15 mW of power. MetHumi can make meaningful relative humidity measurements in range of 0 - 100%RH down to -70°C ambient temperature, but it survives even -135°C ambient temperature.

  10. Quantitative threefold allele-specific PCR (QuanTAS-PCR) for highly sensitive JAK2 V617F mutant allele detection

    Zapparoli, Giada V; Jorissen, Robert N; Hewitt, Chelsee A; McBean, Michelle; Westerman, David A; Dobrovic, Alexander

    2013-01-01

    The JAK2 V617F mutation is the most frequent somatic change in myeloproliferative neoplasms, making it an important tumour-specific marker for diagnostic purposes and for the detection of minimal residual disease. Sensitive quantitative assays are required for both applications, particularly for the monitoring of minimal residual disease, which requires not only high sensitivity but also very high specificity. We developed a highly sensitive probe-free quantitative mutant-allele detection method, Quantitative Threefold Allele-Specific PCR (QuanTAS-PCR), that is performed in a closed-tube system, thus eliminating the manipulation of PCR products. QuantTAS-PCR uses a threefold approach to ensure allele-specific amplification of the mutant sequence: (i) a mutant allele-specific primer, (ii) a 3′dideoxy blocker to suppress false-positive amplification from the wild-type template and (iii) a PCR specificity enhancer, also to suppress false-positive amplification from the wild-type template. Mutant alleles were quantified relative to exon 9 of JAK2. We showed that the addition of the 3′dideoxy blocker suppressed but did not eliminate false-positive amplification from the wild-type template. However, the addition of the PCR specificity enhancer near eliminated false-positive amplification from the wild-type allele. Further discrimination between true and false positives was enabled by using the quantification cycle (Cq) value of a single mutant template as a cut-off point, thus enabling robust distinction between true and false positives. As 10,000 JAK2 templates were used per replicate, the assay had a sensitivity of 1/10 -4 per replicate. Greater sensitivity could be reached by increasing the number of replicates analysed. Variation in replicates when low mutant-allele templates were present necessitated the use of a statistics-based approach to estimate the load of mutant JAK2 copies. QuanTAS-PCR showed comparable quantitative results when validated against a

  11. C-MET overexpression and amplification in gliomas.

    Kwak, Yoonjin; Kim, Seong-Ik; Park, Chul-Kee; Paek, Sun Ha; Lee, Soon-Tae; Park, Sung-Hye

    2015-01-01

    We investigated c-Met overexpression and MET gene amplification in gliomas to determine their incidence and prognostic significance. c-Met immunohistochemistry and MET gene fluorescence in situ hybridization were carried out on tissue microarrays from 250 patients with gliomas (137 grade IV GBMs and 113 grade II and III diffuse gliomas). Clinicopathological features of these cases were reviewed. c-Met overexpression and MET gene amplification were detected in 13.1% and 5.1% of the GBMs, respectively. All the MET-amplified cases showed c-Met overexpression, but MET amplification was not always concordant with c-Met overexpression. None of grade II and III gliomas demonstrated c-Met overexpression or MET gene amplification. Mean survival of the GBM patients with MET amplification was not significantly different from patients without MET amplification (P=0.155). However, GBM patients with c-Met overexpression survived longer than patients without c-Met overexpression (P=0.035). Although MET amplification was not related to poor GBM prognosis, it is partially associated with the aggressiveness of gliomas, as MET amplification was found only in grade IV, not in grade II and III gliomas. We suggest that MET inhibitor therapy may be beneficial in about 5% GBMs, which was the incidence of MET gene amplification found in the patients included in this study.

  12. Allele-Selective Transcriptome Recruitment to Polysomes Primed for Translation: Protein-Coding and Noncoding RNAs, and RNA Isoforms.

    Roshan Mascarenhas

    Full Text Available mRNA translation into proteins is highly regulated, but the role of mRNA isoforms, noncoding RNAs (ncRNAs, and genetic variants remains poorly understood. mRNA levels on polysomes have been shown to correlate well with expressed protein levels, pointing to polysomal loading as a critical factor. To study regulation and genetic factors of protein translation we measured levels and allelic ratios of mRNAs and ncRNAs (including microRNAs in lymphoblast cell lines (LCL and in polysomal fractions. We first used targeted assays to measure polysomal loading of mRNA alleles, confirming reported genetic effects on translation of OPRM1 and NAT1, and detecting no effect of rs1045642 (3435C>T in ABCB1 (MDR1 on polysomal loading while supporting previous results showing increased mRNA turnover of the 3435T allele. Use of high-throughput sequencing of complete transcript profiles (RNA-Seq in three LCLs revealed significant differences in polysomal loading of individual RNA classes and isoforms. Correlated polysomal distribution between protein-coding and non-coding RNAs suggests interactions between them. Allele-selective polysome recruitment revealed strong genetic influence for multiple RNAs, attributable either to differential expression of RNA isoforms or to differential loading onto polysomes, the latter defining a direct genetic effect on translation. Genes identified by different allelic RNA ratios between cytosol and polysomes were enriched with published expression quantitative trait loci (eQTLs affecting RNA functions, and associations with clinical phenotypes. Polysomal RNA-Seq combined with allelic ratio analysis provides a powerful approach to study polysomal RNA recruitment and regulatory variants affecting protein translation.

  13. Samen in Zee met Zelfregulatie: Een Design-Based Aanpak met Vmbo Leraren

    Jossberger, Helen; Brand-Gruwel, Saskia; Boshuizen, Els; Van de Wiel, Margje

    2010-01-01

    Jossberger, H., Brand-Gruwel, S., Boshuizen, H. P. A., & Van der Wiel, M. (2010, June). Samen in Zee met Zelfregulatie: Een Design-Based Aanpak met Vmbo Leraren. Poster presented at the 37th Onderwijs Research Dagen (ORD), Enschede, Nederland.

  14. MetBaro - Pressure Instrument for Mars MetNet Lander

    Polkko, J.; Haukka, H.; Harri, A.-M.; Schmidt, W.; Leinonen, J.; Mäkinen, T.

    2009-04-01

    THE METNET MISSION FOCUSED ON THE Martian atmospheric science is based on a new semihard landing vehicle called the MetNet Lander (MNL). The MNL will have a versatile science payload focused on the atmospheric science of Mars. The scientific payload of the MetNet Mission encompasses separate instrument packages for the atmospheric entry and descent phase and for the surface operation phase. MetBaro is the pressure instrument of MetNet Lander designed to work on Martian surface. It is based on Barocap® technology developed by Vaisala, Inc. MetBaro is a capacitic type of sensing device where capasitor plates are moved by ambient pressure. MetBaro device consists of two pressure transducers including a total of 6 Barocap® sensor heads of high-stability and high-resolution types. The long-term stability of MetBaro is in order of 20…50 µBar and resolution a few µBar. MetBaro is small, lightweighed and has low power consumption. It weighs about 50g without wires and controlling FPGA, and consumes 15 mW of power. A similar device has successfully flown in Phoenix mission, where it performed months of measurements on Martian ground. Another device is also part of the Mars Science Laboratory REMS instrument (to be launched in 2011).

  15. Inhaken met sociale media in 60 minuten

    Thijs Waardenburg; Komala Mazerant

    2018-01-01

    Met creatieve content die slim inhaakt op actuele gebeurtenissen kun je elke dag nieuwe mensen bereiken. Goedkoper dan adverteren op sociale media, en sympathieker bovendien.Thijs Waardenburg en Komala Mazerant leggen uit hoe je kansrijke inhakers bedenkt en communiceert om je bereik op sociale

  16. Varroabestrijding met bijenbroed als mijtenval (2)

    Calis, J.; Beetsma, J.; Boot, W.J.; Eijnde, van den J.; Ruijter, de A.

    1994-01-01

    Bij deze bestrijdingsmethode worden belegde darreraten uit een moergoede veger overgehangen naar het moerloze en later broedloze hoofdvolk. Hier worden de mijten die zich op de bijen bevinden gevangen. Nadat de laatste darreraat uit een hoofdvolk is verwijderd, wordt het bijenvolk met Perizine

  17. Beeldverwerking met de Micron Automatic Processor

    Goyens, Frank

    2017-01-01

    Deze thesis is een onderzoek naar toepassingen binnen beeldverwerking op de Micron Automata Processor hardware. De hardware wordt vergeleken met populaire hedendaagse hardware. Ook bevat dit onderzoek nuttige informatie en strategieën voor het ontwikkelen van nieuwe toepassingen. Bevindingen in dit onderzoek omvatten proof of concept algoritmes en een praktische toepassing.

  18. Groen proceswater: zuivering brouwerijprocesafvalwater met microalgen

    Dijk, van W.; Weide, van der R.Y.; Kroon, A.

    2016-01-01

    In 2012 is het project Groen Proceswater gestart. Hierin worden de mogelijkheden van zuivering van brouwerijprocesafvalwater met behulp van microalgen onderzocht. Dit is gedaan in een samenwerkingsverband van Heineken Nederland BV, Algae Food & Fuel en WUR-ACRRES. De resultaten behaald in 2012

  19. Evangelisch Commando, onze omgamg met de buitenkerkelijke ...

    Test

    Of J. en E. dus interkerklik is, bly 'n vraag! Die gedeelte oor die „Oorzaken van buitenkerklijkheid is prikkelend en interessant. Die vraag is net of dit nie nog dieper gesoek moet word, nl. in die herontwaking van die Heidendom wat sig sins die Renaissance hardnekkig deur sit met die outonomie van die mens in die sentrum.

  20. Risicoanalyse voor buisleidingen met brandbare vloeistoffen

    van Vliet AAC; Laheij GMH; Wolting AG; CEV

    2006-01-01

    De minimale veiligheidsafstanden tussen buisleidingen met brandbare vloeistoffen en bebouwingen kunnen gelijk blijven of iets verkleind worden. Dit is de conclusie na een herberekening van de afstanden uit een circulaire uit 1991. In Nederland ligt zo'n 1850 kilometer aan ondergrondse buisleiding

  1. A brief report on mets system

    Fernandes, W.A.

    Mets system is basically a gas monitoring system, used for the detection of underwater gas. The system consists of a sensor, datalogger and energy module. The sensor works on the diffusion techniques. The system can be deployed to a water depth...

  2. Determination of allele frequencies in nine short tandem repeat loci ...

    SERVER

    2008-04-17

    Apr 17, 2008 ... the normal cellular process of replication of DNA molecules. ... probability of a certain genetic variant (alleles) occuring in ... have preservatives that hinder spoilage and are easily packaged .... Allele distribution at Nine STR.

  3. A new electrophoresis technique to separate microsatellite alleles ...

    A new electrophoresis technique to separate microsatellite alleles* ... African Journal of Biotechnology ... with the CEQTM 8000 Genetic Analysis System and ABI 3130xl DNA Sequencer easily separated products and determined allelic size, ...

  4. Allele specific expression and methylation in the bumblebee, Bombus terrestris

    Zoë Lonsdale

    2017-09-01

    Full Text Available The social hymenoptera are emerging as models for epigenetics. DNA methylation, the addition of a methyl group, is a common epigenetic marker. In mammals and flowering plants methylation affects allele specific expression. There is contradictory evidence for the role of methylation on allele specific expression in social insects. The aim of this paper is to investigate allele specific expression and monoallelic methylation in the bumblebee, Bombus terrestris. We found nineteen genes that were both monoallelically methylated and monoallelically expressed in a single bee. Fourteen of these genes express the hypermethylated allele, while the other five express the hypomethylated allele. We also searched for allele specific expression in twenty-nine published RNA-seq libraries. We found 555 loci with allele-specific expression. We discuss our results with reference to the functional role of methylation in gene expression in insects and in the as yet unquantified role of genetic cis effects in insect allele specific methylation and expression.

  5. Comparative frequency and allelic distribution of ABO and Rh (D ...

    Gourab Dewan

    2015-02-18

    Feb 18, 2015 ... desh and having borders with India and Myanmar (Fig. 1). It is a hilly area with ..... calculated allelic frequencies for ABO/Rh systems previously. Therefore, allelic .... in backward caste population of Uttar Pradesh, India. Not Sci.

  6. Association mapping and favourable QTL alleles for fibre quality ...

    Cheng-Guang Dong

    A total of 201 markers were polymorphic and generated 394 allele loci, and 403 ... identified as containing favourable allele loci related to fibre quality traits. The identified .... environment. Field management followed respective local practices.

  7. Genotype-phenotype correlation and functional studies in patients with cystic fibrosis bearing CFTR complex alleles.

    Terlizzi, Vito; Castaldo, Giuseppe; Salvatore, Donatello; Lucarelli, Marco; Raia, Valeria; Angioni, Adriano; Carnovale, Vincenzo; Cirilli, Natalia; Casciaro, Rosaria; Colombo, Carla; Di Lullo, Antonella Miriam; Elce, Ausilia; Iacotucci, Paola; Comegna, Marika; Scorza, Manuela; Lucidi, Vincenzina; Perfetti, Anna; Cimino, Roberta; Quattrucci, Serena; Seia, Manuela; Sofia, Valentina Maria; Zarrilli, Federica; Amato, Felice

    2017-04-01

    The effect of complex alleles in cystic fibrosis (CF) is poorly defined for the lack of functional studies. To describe the genotype-phenotype correlation and the results of either in vitro and ex vivo studies performed on nasal epithelial cells (NEC) in a cohort of patients with CF carrying cystic fibrosis transmembrane conductance regulator ( CFTR ) complex alleles. We studied 70 homozygous, compound heterozygous or heterozygous for CFTR mutations: p.[Arg74Trp;Val201Met;Asp1270Asn], n=8; p.[Ile148Thr;Ile1023_Val1024del], n=5; p.[Arg117Leu;Leu997Phe], n=6; c.[1210-34TG[12];1210-12T[5];2930C>T], n=3; p.[Arg74Trp;Asp1270Asn], n=4; p.Asp1270Asn, n=2; p.Ile148Thr, n=6; p.Leu997Phe, n=36. In 39 patients, we analysed the CFTR gating activity on NEC in comparison with patients with CF (n=8) and carriers (n=4). Finally, we analysed in vitro the p.[Arg74Trp;Val201Met;Asp1270Asn] complex allele. The p.[Ile148Thr;Ile1023_Val1024del] caused severe CF in five compound heterozygous with a class I-II mutation. Their CFTR activity on NEC was comparable with patients with two class I-II mutations (mean 7.3% vs 6.9%). The p.[Arg74Trp;Asp1270Asn] and the p.Asp1270Asn have scarce functional effects, while p.[Arg74Trp;Val201Met;Asp1270Asn] caused mild CF in four of five subjects carrying a class I-II mutation in trans , or CFTR-related disorders (CFTR-RD) in three having in trans a class IV-V mutation. The p.[Arg74Trp;Val201Met;Asp1270Asn] causes significantly (pT] and a class I-II mutation had mild CF or CFTR-RD (gating activity: 18.5-19.0%). The effect of complex alleles partially depends on the mutation in trans . Although larger studies are necessary, the CFTR activity on NEC is a rapid contributory tool to classify patients with CFTR dysfunction. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  8. Allele and genotype frequencies of -β lactoglobulin gene in Iranian ...

    STORAGESEVER

    2009-08-04

    Aug 4, 2009 ... Blood samples were supplied from 80 Najdi cattle and 80 buffalo from different cities of Khouzestan province. ... The allele B of β-Lactoglobulin occurred at a higher frequency than the allele A in both. Najdi cattle and buffalo. .... that of the B allele in both groups of animals studied. Expected heterozygosity ...

  9. Directional Positive Selection on an Allele of Arbitrary Dominance

    Teshima, Kosuke M.; Przeworski, Molly

    2006-01-01

    Most models of positive directional selection assume codominance of the beneficial allele. We examine the importance of this assumption by implementing a coalescent model of positive directional selection with arbitrary dominance. We find that, for a given mean fixation time, a beneficial allele has a much weaker effect on diversity at linked neutral sites when the allele is recessive.

  10. Association of BDNF Val66Met polymorphism with HPA and SAM axis reactivity to psychological and physical stress.

    Tsuru, Jusen; Tanaka, Yoshihiro; Ishitobi, Yoshinobu; Maruyama, Yoshihiro; Inoue, Ayako; Kawano, Aimi; Ikeda, Rie; Ando, Tomoko; Oshita, Harumi; Aizawa, Saeko; Masuda, Koji; Higuma, Haruka; Kanehisa, Masayuki; Ninomiya, Taiga; Akiyoshi, Jotaro

    2014-01-01

    Decreased expression of brain-derived neurotrophic factor (BDNF) is implicated in enhanced stress responses. The BDNF Val66Met polymorphism is associated with psychological changes; for example, carriers of the Met allele exhibit increased harm avoidance as well as a higher prevalence of depression and anxiety disorder. To analyze the effects of BDNF Val66Met on stress responses, we tested 226 university students (88 women and 138 men) using a social stress procedure (Trier Social Stress Test [TSST]) and an electrical stimulation stress test. Stress indices were derived from repeated measurements of salivary α-amylase, salivary cortisol, heart rate, and psychological testing during the stress tests. All subjects were genotyped for the Val66Met polymorphism (G196A). A significant three-way interaction (time [3 levels] × BDNF [Val/Val, Val/Met, Met/Met]; PBDNF had different effects on hypothalamic-pituitary-adrenocortical axis reactivity but not on sympathetic adrenomedullary reactivity in TSST and electrical stimulation tests.

  11. Association between COMT Polymorphism Val158Met and Opioid Consumption in Patients with Postoperative Pain: A Meta-Analysis

    Bo Hu

    2018-01-01

    Full Text Available Background/Aims: Several factors influencing postoperative pain and the effect of opioid analgesics have been investigated on an individual level. The aim of this study was to clarify the impact of catecholamine-O-methyltransferase (COMT gene Val158Met on opioid consumption in postoperative patients. Methods: A systematic review and meta-analysis of the literature up to September 30, 2017, were performed by using PubMed, Cochrane Library, ISI Web of Science, and Chinese National Knowledge Infrastructure (CNKI database. The meta-analysis examined all studies involving the association between genetic polymorphisms of COMT Val158Met and opioid consumption during the acute postoperative period. Results: Of the 153 identified studies, 23 studies were retrieved for systematic review and 10 studies were retrieved for meta-analysis. However, it was impossible to conduct meta-analysis on the association between COMT Val158Met polymorphism and postoperative pain because of heterogeneity of the data. Overall, meta-analysis showed that COMT Val/Met carriers consumed less opioid for analgesia within the first 24 hours after surgery (SMD = 0.14, 95% CI = [0.03, 0.25], P = 0.01 but not within 48 hours (SMD = 0.14, 95% CI = [0.08, 0.36], P = 0.21. There was no significant difference in opioid consumption between Val/ Val and Met/Met patients. Conclusion: Patients with Val/Met but not Met/Met allele variant consumed less opioid, though larger and better-designed studies are required to obtain an exclusive conclusion about the correlation between postoperative pain and COMT Val158Met polymorphism.

  12. Efeito do teor metálico em catalisadores Co/Al2O3 aplicados à reação de reforma a vapor de etanol Effect of metal load in Co/Al2o3 catalysts for ethanol steam reforming

    Rudye K. S. Santos

    2005-08-01

    Full Text Available The development of cobalt catalysts to produce hydrogen from ethanol is the goal of this investigation. Co/Al2O3 catalysts were prepared by impregnation and characterized by atomic absorption, nitrogen adsorption, X-ray diffraction, Raman spectroscopy, temperature programmed reduction and carbon analysis. The catalysts contained Co3O4 oxide and Co3+ and Co2+ species interacting with alumina. The cobalt load affects the crystal size and the crystalline structure and higher Co loads influence the reaction mechanism, changing the selectivity of the catalysts, decreasing the amount of CO produced and avoiding the formation of products catalyzed by the support. The ethanol conversion was 50-70% with 10-<1% of CO in the hydrogen.

  13. De Doop met de Heilige Geest

    S. C.W. Duvenage.

    1965-03-01

    Full Text Available Ds. Molenaar begin sy boek, waarvan hy self die publikasienie beleef het nie, deur te wys op 'n groot tekort, ’n manko,nie alleen in die Gereformeerde vroomheid of lewe nie maarook in die Gereformeerde teologie. Hy beskou dit as hoogsmerkwaardig dat die Gereformeerde teologie in die verledeso goed as niks raakgesien het van die groot betekenis vandie sogenaamde doop met die Heilige Gees nie. Daarby meenhy dat die Gereformeerde predikante verleë sit met die Pinkterfees.Talle probleme meen hy vir die Gereformeerde teoloograak te sien, veral ten aansien van die moontlikhede van dieGees teenoor die so tasbare „onmoontIikhede” in ons lewe. Dieprobleme is syns insiens nie onoplosbaar nie, as mens maardie moontlikhede van die Gees nie beperk tot die verlede nie.

  14. MET and Small-Cell Lung Cancer

    Francesco Gelsomino

    2014-10-01

    Full Text Available Small-cell lung cancer (SCLC is one of the most aggressive lung tumors. The majority of patients with SCLC are diagnosed at an advanced stage. This tumor type is highly sensitive to chemo-radiation treatment, with very high response rates, but invariably relapses. At this time, treatment options are still limited and the prognosis of these patients is poor. A better knowledge of the molecular biology of SCLC allowed us to identify potential druggable targets. Among these, the MET/HGF axis seems to be one of the most aberrant signaling pathways involved in SCLC invasiveness and progression. In this review, we describe briefly all recent literature on the different molecular profiling in SCLC; in particular, we discuss the specific alterations involving c-MET gene and their implications as a potential target in SCLC.

  15. Catechol-O-methyltransferase Val(158)Met association with parahippocampal physiology during memory encoding in schizophrenia.

    Di Giorgio, A; Caforio, G; Blasi, G; Taurisano, P; Fazio, L; Romano, R; Ursini, G; Gelao, B; Bianco, L Lo; Papazacharias, A; Sinibaldi, L; Popolizio, T; Bellomo, A; Bertolino, A

    2011-08-01

    Catechol-O-methyltransferase (COMT) Val158Met has been associated with activity of the mesial temporal lobe during episodic memory and it may weakly increase risk for schizophrenia. However, how this variant affects parahippocampal and hippocampal physiology when dopamine transmission is perturbed is unclear. The aim of the present study was to compare the effects of the COMT Val158Met genotype on parahippocampal and hippocampal physiology during encoding of recognition memory in patients with schizophrenia and in healthy subjects. Using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI), we studied 28 patients with schizophrenia and 33 healthy subjects matched for a series of sociodemographic and genetic variables while they performed a recognition memory task. We found that healthy subjects had greater parahippocampal and hippocampal activity during memory encoding compared to patients with schizophrenia. We also found different activity of the parahippocampal region between healthy subjects and patients with schizophrenia as a function of the COMT genotype, in that the predicted COMT Met allele dose effect had an opposite direction in controls and patients. Our results demonstrate a COMT Val158Met genotype by diagnosis interaction in parahippocampal activity during memory encoding and may suggest that modulation of dopamine signaling interacts with other disease-related processes in determining the phenotype of parahippocampal physiology in schizophrenia. © Cambridge University Press 2010

  16. BDNF val66met polymorphism affects aging of multiple types of memory.

    Kennedy, Kristen M; Reese, Elizabeth D; Horn, Marci M; Sizemore, April N; Unni, Asha K; Meerbrey, Michael E; Kalich, Allan G; Rodrigue, Karen M

    2015-07-01

    The BDNF val66met polymorphism (rs6265) influences activity-dependent secretion of brain-derived neurotrophic factor in the synapse, which is crucial for learning and memory. Individuals homozygous or heterozygous for the met allele have lower BDNF secretion than val homozygotes and may be at risk for reduced declarative memory performance, but it remains unclear which types of declarative memory may be affected and how aging of memory across the lifespan is impacted by the BDNF val66met polymorphism. This cross-sectional study investigated the effects of BDNF polymorphism on multiple indices of memory (item, associative, prospective, subjective complaints) in a lifespan sample of 116 healthy adults aged 20-93 years. Advancing age showed a negative effect on item, associative and prospective memory, but not on subjective memory complaints. For item and prospective memory, there were significant age×BDNF group interactions, indicating the adverse effect of age on memory performance across the lifespan was much stronger in the BDNF met carriers than for the val homozygotes. BDNF met carriers also endorsed significantly greater subjective memory complaints, regardless of age, and showed a trend (pmemory performance compared to val homozygotes. These results suggest that genetic predisposition to the availability of brain-derived neurotrophic factor, by way of the BDNF val66met polymorphism, exerts an influence on multiple indices of episodic memory - in some cases in all individuals regardless of age (subjective memory and perhaps associative memory), in others as an exacerbation of age-related differences in memory across the lifespan (item and prospective memory). This article is part of a Special Issue entitled Memory & Aging. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. BDNF val66met modulates the association between childhood trauma, cognitive and brain abnormalities in psychoses.

    Aas, Monica; Haukvik, Unn K; Djurovic, Srdjan; Bergmann, Ørjan; Athanasiu, Lavinia; Tesli, Martin S; Hellvin, Tone; Steen, Nils Eiel; Agartz, Ingrid; Lorentzen, Steinar; Sundet, Kjetil; Andreassen, Ole A; Melle, Ingrid

    2013-10-01

    Brain derived neurotrophic factor (BDNF) is important for brain development and plasticity, and here we tested if the functional BDNF val66met variant modulates the association between high levels of childhood abuse, cognitive function, and brain abnormalities in psychoses. 249 patients with a broad DSM-IV schizophrenia spectrum disorder or bipolar disorder were consecutively recruited to the TOP research study (mean±age: 30.7±10.9; gender: 49% males). History of childhood trauma was obtained using the Childhood Trauma Questionnaire. Cognitive function was assessed through a standardized neuropsychological test battery. BDNF val66met was genotyped using standardized procedures. A sub-sample of n=106 Caucasians with a broad DSM-IV schizophrenia spectrum disorder or bipolar disorder (mean±age: 32.67±10.85; 49% males) had data on sMRI. Carriers of the Methionine (met) allele exposed to high level of childhood abuse demonstrated significantly poorer cognitive functioning compared to homozygotic Valine (val/val) carriers. Taking in consideration multiple testing, using a more conservative p value, this was still shown for physical abuse and emotional abuse, as well as a trend level for sexual abuse. Further, met carriers exposed to high level of childhood sexual abuse showed reduced right hippocampal volume (r(2)=0.43; p=0.008), and larger right and left lateral ventricles (r(2)=0.37; p=0.002, and r(2)=0.27; p=0.009, respectively). Our findings were independent of age, gender, diagnosis and intracranial volume. Our data demonstrate that in patients with psychoses, met carriers of the BDNF val66met with high level of childhood abuse have more cognitive and brain abnormalities than all other groups. © 2013.

  18. Metáfora y estructura conceptual

    Emilia Castaño

    2012-01-01

    Full Text Available La lingüística cognitiva siempre ha argumentado que la metáfora no pertenece exclusivamente al lenguaje, sino que es una competencia que se basa en la habilidad humana de concebir un dominio de experiencia en términos de otro. Entendida así, la metáfora no puede ser otra cosa que un fenómeno conceptual. No obstante, pocos adeptos de la lingüística cognitiva han concentrados sus esfuerzos en catalogar manifestaciones metafóricas en ámbitos no lingüísticos. En este trabajo, sugerimos que es factible encontrar pruebas de que la metáfora es un proceso conceptual y, como tal, se manifiesta en esferas que no son estrictamente lingüísticas. Para ello, aportamos un seguido de evidencias muy diversas, como por ejemplo su papel en el razonamiento lógico-matemático de los niños en la fase preoperacional del desarrollo cognitivo, la programación de interfaces para aplicaciones informáticas y los resultados de tres estudios empíricos realizados recientemente en el campo  de la psicología cognitiva que analizan los efectos whorfianos en la conceptualización del tiempo y los efectos del espacio en la memoria emocional.

  19. Plasminogen alleles influence susceptibility to invasive aspergillosis.

    Aimee K Zaas

    2008-06-01

    Full Text Available Invasive aspergillosis (IA is a common and life-threatening infection in immunocompromised individuals. A number of environmental and epidemiologic risk factors for developing IA have been identified. However, genetic factors that affect risk for developing IA have not been clearly identified. We report that host genetic differences influence outcome following establishment of pulmonary aspergillosis in an exogenously immune suppressed mouse model. Computational haplotype-based genetic analysis indicated that genetic variation within the biologically plausible positional candidate gene plasminogen (Plg; Gene ID 18855 correlated with murine outcome. There was a single nonsynonymous coding change (Gly110Ser where the minor allele was found in all of the susceptible strains, but not in the resistant strains. A nonsynonymous single nucleotide polymorphism (Asp472Asn was also identified in the human homolog (PLG; Gene ID 5340. An association study within a cohort of 236 allogeneic hematopoietic stem cell transplant (HSCT recipients revealed that alleles at this SNP significantly affected the risk of developing IA after HSCT. Furthermore, we demonstrated that plasminogen directly binds to Aspergillus fumigatus. We propose that genetic variation within the plasminogen pathway influences the pathogenesis of this invasive fungal infection.

  20. DQB1*06:02 allele-specific expression varies by allelic dosage, not narcolepsy status

    Weiner Lachmi, Karin; Lin, Ling; Kornum, Birgitte Rahbek

    2012-01-01

    The association of narcolepsy-cataplexy, a sleep disorder caused by the loss of hypocretin/orexin neurons in the hypothalamus, with DQA1*01:02-DQB1*06:02 is one of the tightest known single-allele human leukocyte antigen (HLA) associations. In this study, we explored genome-wide expression...

  1. COMT ValMet moderation of cannabis-induced psychosis: a momentary assessment study of 'switching on' hallucinations in the flow of daily life.

    Henquet, C; Rosa, A; Delespaul, P; Papiol, S; Fananás, L; van Os, J; Myin-Germeys, I

    2009-02-01

    A functional polymorphism in the catechol-o-methyltransferase gene (COMT Val(158)Met) may moderate the psychosis-inducing effects of cannabis. In order to extend this finding to dynamic effects in the flow of daily life, a momentary assessment study of psychotic symptoms in response to cannabis use was conducted. The experience sampling technique was used to collect data on cannabis use and occurrence of symptoms in daily life in patients with a psychotic disorder (n = 31) and healthy controls (n = 25). Carriers of the COMT Val(158)Met Val allele, but not subjects with the Met/Met genotype, showed an increase in hallucinations after cannabis exposure, conditional on prior evidence of psychometric psychosis liability. The findings confirm that in people with psychometric evidence of psychosis liability, COMT Val(158)Met genotype moderates the association between cannabis and psychotic phenomena in the flow of daily life.

  2. The frequency of allelic lethals and complementation maps in natural populations of drosophila melanogaster from Mexico

    Salceda Victor M.

    2004-01-01

    Full Text Available Departing from a previous study on the genetic loads affecting the second chromosome of Drosophila melanogaster in four natural populations, 171 lethal chromosomes were recovered and maintained as a balanced stocks in the condition Cy L / 1 (l=lethal; of those lethais 24 correspond to population A, 50 to populations B and C and 47 to population D. later on an intra-population allelism test for the four populations was performed for each one. A total of 3807 inter lethal crosses were done yielding a total of i 10 allelic combinations, from them the respective percentage of allelism for each population was calculated and they are as follow: 3.98 % for population A, 1.80 % for population B, 3.67 % for population C and 2.96 % for population D. the observed values for the frequency of allelism in these populations are not significantly different from those reported by other authors in similar studies in natural and/or experimental populations. Beside these values the frequency for singles, doubles, triplets and even quadruplets present in each population were determined, they shown the presence of various complementation maps due to the clustering of few different lethals: also a large complementation map formed by a large cluster involving the presence of 26 different lethals found in population D all of them combined constituting a single unit was found.

  3. Differential impact of Met receptor gene interaction with early-life stress on neuronal morphology and behavior in mice.

    Heun-Johnson, Hanke; Levitt, Pat

    2018-02-01

    Early adversity in childhood increases the risk of anxiety, mood, and post-traumatic stress disorders in adulthood, and specific gene-by-environment interactions may increase risk further. A common functional variant in the promoter region of the gene encoding the human MET receptor tyrosine kinase (rs1858830 ' C' allele) reduces expression of MET and is associated with altered cortical circuit function and structural connectivity. Mice with reduced Met expression exhibit changes in anxiety-like and conditioned fear behavior, precocious synaptic maturation in the hippocampus, and reduced neuronal arbor complexity and synaptogenesis. These phenotypes also can be produced independently by early adversity in wild-type mice. The present study addresses the outcome of combining early-life stress and genetic influences that alter timing of maturation on enduring functional and structural phenotypes. Using a model of reduced Met expression ( Met +/- ) and early-life stress from postnatal day 2-9, social, anxiety-like, and contextual fear behaviors in later life were measured. Mice that experienced early-life stress exhibited impairments in social interaction, whereas alterations in anxiety-like behavior and fear learning were driven by Met haploinsufficiency, independent of rearing condition. Early-life stress or reduced Met expression decreased arbor complexity of ventral hippocampal CA1 pyramidal neurons projecting to basolateral amygdala. Paradoxically, arbor complexity in Met +/- mice was increased following early-life stress, and thus not different from arbors in wild-type mice raised in control conditions. The changes in dendritic morphology are consistent with the hypothesis that the physiological state of maturation of CA1 neurons in Met +/- mice influences their responsiveness to early-life stress. The dissociation of behavioral and structural changes suggests that there may be phenotype-specific sensitivities to early-life stress.

  4. Lipid ratio as a suitable tool to identify individuals with MetS risk: A case- control study.

    Abbasian, Maryam; Delvarianzadeh, Mehri; Ebrahimi, Hossein; Khosravi, Farideh

    2017-11-01

    This study aimed to compare the serum lipids ratio in staff with and without metabolic syndrome (MetS) who were working in Shahroud University of Medical Sciences. This case-control study was conducted in 2015 on 499 personnel aged 30-60 years old. ATP III criteria were used to diagnose patients with MetS. The data were analyzed by using logistic regression and ROC curve. Mean lipid ratio was higher in individuals having the MetS in both sexes compared with those without. In addition, the mean levels of lipid ratios significantly increased with increasing number of MetS components in both sexes. Also it could be concluded that TG/HDL-C ratio is the best marker for the diagnosis of MetS in men and women. Moreover, the cut-off point for the TG/HDL-C was 2.86 in women and 4.03 in men. It was found that for any unit of increases in the TG/HDL-C, the risk of developing the MetS will increase by 2.12 times. TG/HDL-C ratio is found to be the best clinical marker for the diagnosis of MetS compare with other lipid ratios, therefore it is recommended to be used as a feasible tool to identify individuals with MetS risk. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  5. Metáfora y conceptos abstractos

    Danesi, Marcel

    2006-01-01

    La gran cantidad de datos recolectados sobre la metáfora sugiere enfáticamente que muchos de los conceptos abstractos, si no la mayoría, son codificables y reconocibles primordialmente como «ideas metaforizadas», es decir como conceptos que se derivan cognitivamente mediante el razonamiento metafórico y un proceso de asociación metafórica que en este artículo se denominará estratificación [layering] (Gibbs, 1994; Goatley, 1997). La literatura más actualizada sobre lo que se ha denominado Teor...

  6. XRCC3 Thr241Met Polymorphism is not Associated with Lung Cancer Risk in a Romanian Population.

    Catana, Andreea; Pop, Monica; Marginean, Dragos Horea; Blaga, Ioana Cristina; Porojan, Mihai Dumitru; Popp, Radu Anghel; Pop, Ioan Victor

    2016-01-01

    Deoxyribonucleic Acid (DNA) repair mechanisms play a critical role in protecting the cellular genome against carcinogens. X-ray cross-complementing gene 3 (XRCC3) is involved in DNA repair and therefore certain genetic polymorphisms that occur in DNA repair genes may affect the ability to repair DNA defects and may represent a risk factor in carcinogenesis. The purpose of our study was to investigate the association between XRCC3 gene substitution of Threonine with Methionine in codon 241 of XRCC3 gene (Thr241Met) polymorphism and the risk of lung cancer, in a Romanian population. We recruited 93 healthy controls and 85 patients with lung cancer, all smokers. Thr241Met, XRCC3 gene genotyping was determined by multiplex Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Statistical analysis (OR, recessive model), did not revealed an increased risk for lung cancer, for the variant 241Met allele and Thr241Met genotypes (p=0.138, OR=0.634, CI=0.348-1.157; p=0.023, OR=0.257, CI=0.085-6.824). Also, there were no positive statistical associations between Thr241Met polymorphism of XRCC3 gene, gender, tobacco and various histopathological tumor type of lung cancer. In conclusion, the results of the study suggest that the XRCC3 gene Thr241Met polymorphism is not associated with an increased risk for the development of lung cancer in this Romanian group.

  7. BDNF val66met Polymorphism Impairs Hippocampal Long-Term Depression by Down-Regulation of 5-HT3 Receptors

    Rui Hao

    2017-10-01

    Full Text Available Brain-derived neurotrophic factor (BDNF is a key regulator of neuronal plasticity and cognitive functions. BDNF val66met polymorphism, a human single-nucleotide polymorphism (SNP in the pro-domain of BDNF gene, is associated with deficits in activity-dependent BDNF secretion and hippocampus-dependent memory. However, the underlying mechanism remains unclear. Here we show that in the BDNFMet/Met mouse line mimicking the human SNP, BDNF expression in the hippocampus was decreased. There was a reduction in the total number of cells in hippocampal CA1 region, while hippocampal expression of mRNAs for NR2a, 2b, GluR1, 2 and GABAARβ3 subunits were up-regulated. Although basal glutamatergic neurotransmission was unaltered, hippocampal long-term depression (LTD induced by low-frequency stimulation was impaired, which was partially rescued by exogenous application of BDNF. Interestingly, 5-HT3a receptors were down-regulated in the hippocampus of BDNFMet/Met mice, whereas 5-HT2c receptors were up-regulated. Moreover, impaired LTD in BDNFMet/Met mice was reversed by 5-HT3aR agonist. Thus, these observations indicate that BDNF val66met polymorphism changes hippocampal synaptic plasticity via down-regulation of 5-HT3a receptors, which may underlie cognition dysfunction of Met allele carriers.

  8. Nitric oxide synthase gene G298 allele

    Nagib El-Kilany, Galal E.; Nayel, Ehab; Hazzaa, Sahar

    2004-01-01

    Background: Nitric oxide (NO) has an important effect on blood pressure, arterial wall, and the basal release of endothelial NO in hypertension (HPN) may be reduced. Until now, there is no solid data revealing the potential role of the polymorphism of the nitric oxide synthase gene (NOS) in patients with HPN and microvascular angina. Aim: The aim of the present study is to investigate the gene of endothelial nitric oxide synthase (eNOS), as the polymorphism of this gene may be a putative candidate for HPN and initiate the process of atherosclerosis. Methods: Sixty participants were recruited for this study; 50 were hypertensive patients complaining of chest pain [30 of them have electrocardiogram (EKG) changes of ischemia], 20 had isolated HPN, and 10 healthy volunteers served as control. All patients underwent stress myocardial perfusion imaging (MPI) and coronary angiography. Genotyping of eNOS for all patients and controls was performed. The linkages between HPN, microvascular angina and eNOS gene polymorphism were investigated. Results: MPI and coronary angiography revealed that 15 patients had chest pain with true ischemia and reversible myocardial perfusion defects (multiple and mild) but normal epicardial coronary arteries (microvascular angina), while 15 patients had significant coronary artery disease (CAD), and 20 hypertensive patients showed normal perfusion scan and coronary angiography. The prevalence of the NOS G 298 allele was higher in the hypertensive group with microvascular angina (documented by MPI) than it was among the control participants (P<.005). The eNOS allele was significantly higher in the hypertensive group than in the control participants, but there was no significant difference in homozygote mutants among hypertensive participants, x-syndrome and patients with CAD. Conclusion: eNOS gene polymorphism is proved to be an important etiology in microvascular angina (x-syndrome) among hypertensive patients. In addition, the eNOS mutant

  9. Dissection of combinatorial control by the Met4 transcriptional complex.

    Lee, Traci A; Jorgensen, Paul; Bognar, Andrew L; Peyraud, Caroline; Thomas, Dominique; Tyers, Mike

    2010-02-01

    Met4 is the transcriptional activator of the sulfur metabolic network in Saccharomyces cerevisiae. Lacking DNA-binding ability, Met4 must interact with proteins called Met4 cofactors to target promoters for transcription. Two types of DNA-binding cofactors (Cbf1 and Met31/Met32) recruit Met4 to promoters and one cofactor (Met28) stabilizes the DNA-bound Met4 complexes. To dissect this combinatorial system, we systematically deleted each category of cofactor(s) and analyzed Met4-activated transcription on a genome-wide scale. We defined a core regulon for Met4, consisting of 45 target genes. Deletion of both Met31 and Met32 eliminated activation of the core regulon, whereas loss of Met28 or Cbf1 interfered with only a subset of targets that map to distinct sectors of the sulfur metabolic network. These transcriptional dependencies roughly correlated with the presence of Cbf1 promoter motifs. Quantitative analysis of in vivo promoter binding properties indicated varying levels of cooperativity and interdependency exists between members of this combinatorial system. Cbf1 was the only cofactor to remain fully bound to target promoters under all conditions, whereas other factors exhibited different degrees of regulated binding in a promoter-specific fashion. Taken together, Met4 cofactors use a variety of mechanisms to allow differential transcription of target genes in response to various cues.

  10. Allele Frequency - JSNP | LSDB Archive [Life Science Database Archive metadata

    Full Text Available nd 39 SNPs are assayed in three (POP_*) and two (RIKEN_japanese_*) panels, respectively. Derived from Flat f... assay (JBIC-allele and RIKEN_japanese_*), TaqMan assay (RIKEN-allele) or direct sequencing / allelic discri...unteers under informed consent RIKEN_japanese_normal_weight - 711 unrelated japanese normal weight volunteer...s ( body mass index RIKEN_japanese_obese - 796 unrelated japanese obese patients

  11. Autosomal dominant polycystic kidney disease in a family with mosaicism and hypomorphic allele.

    Reiterová, Jana; Štekrová, Jitka; Merta, Miroslav; Kotlas, Jaroslav; Elišáková, Veronika; Lněnička, Petr; Korabečná, Marie; Kohoutová, Milada; Tesař, Vladimír

    2013-03-15

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of inherited kidney disease that results in renal failure. ADPKD is a systemic disorder with cysts and connective tissue abnormalities involving many organs. ADPKD caused by mutations in PKD1 gene is significantly more severe than the cases caused by PKD2 gene mutations. The large intra-familial variability of ADPKD highlights a role for genetic background. Here we report a case of ADPKD family initially appearing unlinked to the PKD1 or PKD2 loci and the influence of mosaicism and hypomorphic allele on the variability of the clinical course of the disease. A grandmother with the PKD1 gene mutation in mosaicism (p.Val1105ArgfsX4) and with mild clinical course of ADPKD (end stage renal failure at the age of 77) seemed to have ADPKD because of PKD2 gene mutation. On the other hand, her grandson had a severe clinical course (end stage renal disease at the age of 45) in spite of the early treatment of mild hypertension. There was found by mutational analysis of PKD genes that the severe clinical course was caused by PKD1 gene frameshifting mutation inherited from his father and mildly affected grandmother in combination with inherited hypomorphic PKD1 allele with described missense mutation (p.Thr2250Met) from his clinically healthy mother. The sister with two cysts and with PKD1 hypomorphic allele became the kidney donor to her severely affected brother. We present the first case of ADPKD with the influence of mosaicism and hypomorphic allele of the PKD1 gene on clinical course of ADPKD in one family. Moreover, this report illustrates the role of molecular genetic testing in assessing young related kidney donors for patients with ADPKD.

  12. Molecular characterization of both alleles in an unusual Tay-Sachs disease BI variant

    Coulter-Mackie, M.B. (Univ. of Western Ontario, London (Canada) Child Health Research Institute, Children' s Hospital of Western Ontario, London (Canada) Child Parent Resource Institute, London, Ontario (Canada))

    1994-06-01

    In a recent report, the authors described an exon 6 mutation in a Tay-Sachs B1 variant patient, first reported by Gordon et al. (1988), who displayed a typical B1 variant biochemical phenotype - i.e., (a) significant levels of hexosaminidase A (Hex A) activity in an assay with a neutral synthetic substrate, 4-methylumbelliferyl-[beta]-N-acetylglucosamide, and (b) <2% of control Hex A in a test on the sulfated substrate, 4-methylumbelliferyl-[beta]-N-acetylglucosamide-6-sulfate. The patient was found to carry a double mutation (G[sub 574][yields]C [val[sub 192][yields]leu] and G[sub 598][yields]A [val[sub 200][yields]met]) inherited from her mother. Only the 574 mutation produced a deleterious effect on Hex A activity in transfected COS0-1 cells, producing a B1 variant biochemical phenotype. The paternal allele apparently caused decreased abundance of mRNA, since no candidate paternal mutations were found in cloned reverse transcription-PCR (RT-PCR) products in the reported study. The biochemical phenotype of the original patient and the properties of the cDNA carrying the G[sub 574] [yields] C mutation in transient expression studies were compatible with a B1 variant mutation. The possibility remained that there might be some contribution from the paternal allele to the patient's phenotype. However, the paternal allele produces relatively low yields of a largely mis-spliced mRNA whose product would not be functional. Therefore, the G[sub 574] [yields] C (val[yields]leu) mutation in the maternal allele is clearly confirmed as a B1 variant mutation with all the ramifications for the substrate binding site and/or catalytic center that this implies.

  13. Database for the ampC alleles in Acinetobacter baumannii.

    Nabil Karah

    Full Text Available Acinetobacter baumannii is a troublesome opportunistic pathogen with a high capacity for clonal dissemination. We announce the establishment of a database for the ampC locus in A. baumannii, in which novel ampC alleles are differentiated based on the occurrence of ≥ 1 nucleotide change, regardless of whether it is silent or missense. The database is openly accessible at the pubmlst platform for A. baumannii (http://pubmlst.org/abaumannii/. Forty-eight distinctive alleles of the ampC locus have so far been identified and deposited in the database. Isolates from clonal complex 1 (CC1, according to the Pasteur multilocus sequence typing scheme, had a variety of the ampC locus alleles, including alleles 1, 3, 4, 5, 6, 7, 8, 13, 14, 17, and 18. On the other hand, isolates from CC2 had the ampC alleles 2, 3, 19, 20, 21, 22, 23, 24, 26, 27, 28, and 46. Allele 3 was characteristic for sequence types ST3 or ST32. The ampC alleles 10, 16, and 25 were characteristic for CC10, ST16, and CC25, respectively. Our study points out that novel gene databases, in which alleles are numbered based on differences in their nucleotide identities, should replace traditional records that use amino acid substitutions to define new alleles.

  14. Saving energy with paint. Coating with ceramic globules; Energie besparen met verf. Coating met keramische bolletjes

    Willemse, R. [Coateq Coatings, Haarlem (Netherlands)

    2011-07-01

    The special paint coating of ThermoShield saves energy. The coating consists for 50% of hollow, vacuum ceramic globules. The waterborne damp-open coating with capillary function resists rain water and removes redundant water in case of draught and it reflects sunlight. [Dutch] Met de speciale verfcoating ThermoShield kan energie worden bespaard. De coating bestaat voor 50% uit holle, vacuum getrokken keramische bolletjes. De watergedragen damp-open coating met capillaire werking stoot bij regen water af en voert bij droogte overtollig vocht af en reflecteert zonlicht.

  15. MET Standards for Electro-Technical Officers

    Janusz Mindykowski

    2014-12-01

    Full Text Available The paper deals with one of the most important changes in the STCW 1978 as amended in 2010 Convention, from the point of view of the watchkeeping officers responsible for control, maintenance, diagnostic and repair of electrical and electronic installations on board of ships. Some reasons, why the MET Standards for Electro-Technical had to be developed and implemented are shortly analyzed and described. A legislative way towards and a short description of the minimum standards competence for ETO are presented. Next, new tools supporting ETO’s standards implementation are appointed. Finally, the future works as well as the concluding remarks concerning discussed issue are formulated and commented on.

  16. Tidal analysis of Met rocket wind data

    Bedinger, J. F.; Constantinides, E.

    1976-01-01

    A method of analyzing Met Rocket wind data is described. Modern tidal theory and specialized analytical techniques were used to resolve specific tidal modes and prevailing components in observed wind data. A representation of the wind which is continuous in both space and time was formulated. Such a representation allows direct comparison with theory, allows the derivation of other quantities such as temperature and pressure which in turn may be compared with observed values, and allows the formation of a wind model which extends over a broader range of space and time. Significant diurnal tidal modes with wavelengths of 10 and 7 km were present in the data and were resolved by the analytical technique.

  17. Metástasis hipofisaria Hypophyseal metastasis

    Miguel Ángel Yanes Quesada

    2009-04-01

    Full Text Available mayoría son lesiones silentes descubiertas accidentalmente en las autopsia. La aparición de metástasis sintomáticas es, en cambio, excepcional. DESARROLLO: se describen aquí los hallazgos clínicos y radiológicos de una paciente femenina de 69 años, con un carcinoma indiferenciado del pulmón, diagnosticado hace 2 años y medio, que comenzó con cefalea y trastornos visuales sin hipopituitarismo ni diabetes insípida. Se le realizó resonancia magnética nuclear y se le diagnosticó una lesión hipofisaria, que fue operada por vía tranesfenoidal, y se informó por anatomía patológica una metástasis del carcinoma del pulmón. CONCLUSIONES: la paciente se encuentra en estos momentos recibiendo quimioterapia, radioterapia y anticuerpo monoclonal con evolución favorable.INTRODUCTION: metastatic tumors of hypophyseal gland are infrequent. Most are silent lesions discovered accidentally in necropsy. Appearance of symptomatic metastasis is however, exceptional. DEVELOPMENT: we describe here clinical and radiological findings in a female patient aged 69, presenting with a non-differential carcinoma of lung, diagnosed two years a half ago, starting with headache and visual disorders without hypopituitarism and insipidus diabetes. We made a nuclear magnetic resonance and diagnosis was a hypophyseal lesion operated on by trans-esphenoidal route, and Pathological Anatomy Service reports a metastasis of lung carcinoma. CONCLUSIONS: patient receives chemotherapy, radiotherapy, and monoclonal antibody with a favorable evolution.

  18. The COMTval158met polymorphism is associated with symptom relief during exposure-based cognitive-behavioral treatment in panic disorder

    Bergström Jan

    2010-11-01

    Full Text Available Abstract Background Cognitive behavioral therapy (CBT represents a learning process leading to symptom relief and resulting in long-term changes in behavior. CBT for panic disorder is based on exposure and exposure-based processes can be studied in the laboratory as extinction of experimentally acquired fear responses. We have recently demonstrated that the ability to extinguish learned fear responses is associated with a functional genetic polymorphism (COMTval158met in the COMT gene and this study was aimed at transferring the experimental results on the COMTval158met polymorphism on extinction into a clinical setting. Methods We tested a possible effect of the COMTval158met polymorphism on the efficacy of CBT, in particular exposure-based treatment modules, in a sample of 69 panic disorder patients. Results We present evidence that panic patients with the COMTval158met met/met genotype may profit less from (exposure-based CBT treatment methods as compared to patients carrying at least one val-allele. No association was found with the 5-HTTLPR/rs25531 genotypes which is presented as additional material. Conclusions We were thus able to transfer findings on the effect of the COMTval158met polymorphism from an experimental extinction study obtained using healthy subjects to a clinical setting. Furthermore patients carrying a COMT val-allele tend to report more anxiety and more depression symptoms as compared to those with the met/met genotype. Limitations of the study as well as possible clinical implications are discussed. Trial registration Clinical Trial Registry name: Internet-Versus Group-Administered Cognitive Behavior Therapy for Panic Disorder (IP2. Registration Identification number: NCT00845260, http://www.clinicaltrials.gov/ct2/show/NCT00845260

  19. Molecular screening of the ghrelin gene in Italian obese children: the Leu72Met variant is associated with an earlier onset of obesity.

    Miraglia del Giudice, E; Santoro, N; Cirillo, G; Raimondo, P; Grandone, A; D'Aniello, A; Di Nardo, M; Perrone, L

    2004-03-01

    To test whether ghrelin variants could play a role in modulating some aspects of the obese phenotype during childhood. We screened the ghrelin gene in 300 Italian obese children and adolescents (mean age 10.5+/-3.2 y; range 4-19 y) and 200 controls by using the single-strand conformation polymorphism and the restriction fragment length polymoprhism analysis. No mutations were detected with the exception of two previously described polymorphisms, Arg51Gln and Leu72Met. For both variations, allelic frequencies were similar between patients and controls. Interestingly, we showed that the Leu72Met polymorphism was associated with differences in the age at obesity onset. Patients with the Met72 allele became obese earlier than homozygous patients for the wild Leu72 allele. The logrank test comparing the plots of the complement of Kaplan-Meier estimates between the two groups of patients was statistically significant (Pghrelin variations cause the obesity due to single-gene mutations. The Leu72Met polymorphism of the ghrelin gene seems to play a role in anticipating the onset of obesity among children suggesting, therefore, that ghrelin may be involved in the pathophysiology of human adiposity.

  20. The effect of the COMT val(158)met polymorphism on neural correlates of semantic verbal fluency.

    Krug, Axel; Markov, Valentin; Sheldrick, Abigail; Krach, Sören; Jansen, Andreas; Zerres, Klaus; Eggermann, Thomas; Stöcker, Tony; Shah, N Jon; Kircher, Tilo

    2009-12-01

    Variation in the val(158)met polymorphism of the COMT gene has been found to be associated with cognitive performance. In functional neuroimaging studies, this dysfunction has been linked to signal changes in prefrontal areas. Given the complex modulation and functional heterogeneity of frontal lobe systems, further specification of COMT gene-related phenotypes differing in prefrontally mediated cognitive performance are of major interest. Eighty healthy individuals (54 men, 26 women; mean age 23.3 years) performed an overt semantic verbal fluency task while brain activation was measured with functional magnetic resonance imaging (fMRI). COMT val(158)met genotype was determined and correlated with brain activation measured with fMRI during the task. Although there were no differences in performance, brain activation in the left inferior frontal gyrus [Brodmann area 10] was positively correlated with the number of val alleles in the COMT gene. COMT val(158)met status modulates brain activation during the language production on a semantic level in an area related to executive functions.

  1. AllelicImbalance: An R/ bioconductor package for detecting, managing, and visualizing allele expression imbalance data from RNA sequencing

    Gådin, Jesper R.; van't Hooft, Ferdinand M.; Eriksson, Per

    2015-01-01

    the possible biases. Results: We present AllelicImblance, a software program that is designed to detect, manage, and visualize allelic imbalances comprehensively. The purpose of this software is to allow users to pose genetic questions in any RNA sequencing experiment quickly, enhancing the general utility...... of RNA sequencing. The visualization features can reveal notable, non-trivial allelic imbalance behavior over specific regions, such as exons. Conclusions: The software provides a complete framework to perform allelic imbalance analyses of aligned RNA sequencing data, from detection to visualization...

  2. Multimer Formation Explains Allelic Suppression of PRDM9 Recombination Hotspots.

    Baker, Christopher L; Petkova, Pavlina; Walker, Michael; Flachs, Petr; Mihola, Ondrej; Trachtulec, Zdenek; Petkov, Petko M; Paigen, Kenneth

    2015-09-01

    Genetic recombination during meiosis functions to increase genetic diversity, promotes elimination of deleterious alleles, and helps assure proper segregation of chromatids. Mammalian recombination events are concentrated at specialized sites, termed hotspots, whose locations are determined by PRDM9, a zinc finger DNA-binding histone methyltransferase. Prdm9 is highly polymorphic with most alleles activating their own set of hotspots. In populations exhibiting high frequencies of heterozygosity, questions remain about the influences different alleles have in heterozygous individuals where the two variant forms of PRDM9 typically do not activate equivalent populations of hotspots. We now find that, in addition to activating its own hotspots, the presence of one Prdm9 allele can modify the activity of hotspots activated by the other allele. PRDM9 function is also dosage sensitive; Prdm9+/- heterozygous null mice have reduced numbers and less active hotspots and increased numbers of aberrant germ cells. In mice carrying two Prdm9 alleles, there is allelic competition; the stronger Prdm9 allele can partially or entirely suppress chromatin modification and recombination at hotspots of the weaker allele. In cell cultures, PRDM9 protein variants form functional heteromeric complexes which can bind hotspots sequences. When a heteromeric complex binds at a hotspot of one PRDM9 variant, the other PRDM9 variant, which would otherwise not bind, can still methylate hotspot nucleosomes. We propose that in heterozygous individuals the underlying molecular mechanism of allelic suppression results from formation of PRDM9 heteromers, where the DNA binding activity of one protein variant dominantly directs recombination initiation towards its own hotspots, effectively titrating down recombination by the other protein variant. In natural populations with many heterozygous individuals, allelic competition will influence the recombination landscape.

  3. Resultaten boomkorsurvey 2013: BTS met onderzoeksvaartuigen Isis en Tridens (interview met Ingeborg de Boois)

    Boois, de I.J.

    2013-01-01

    Van begin augustus tot half september heeft IMARES de boomkorsurvey (BTS) uitgevoerd met de onderzoeksschepen Isis en Tridens. Op 29 maart 2014 wordt een bijeenkomst georganiseerd voor geinteresseerden, waar de resultaten van zowel de BTS als de bedrijfssurvey gepresenteerd worden. De BTS wordt

  4. Pastoors naar de PFA: nieuwe impuls voor samenwerking met de wetenschap (interview met Martin Pastoors)

    Pastoors, M.A.

    2014-01-01

    De Pelagic Freezer-trawler Association (PFA) heeft visserijonderzoeler Martin Pastoors aangenomen als 'Chief Science Officer'. De afgelopen tien jaar is de PFA zich steeds meer bezig gaan houden met wetenschappelijk onderzoek. Bijvoorbeeld door het ontwikkelen van nieuwe manieren om data te

  5. Milde voedselverwerkingstechnologie II : milde conservering met hoge druk : nieuwe ontwikkelingen

    Matser, A.M.; Ven, van der C.; Berg, van den R.

    2004-01-01

    Met behulp van hogedruktechnologie kunnen producten langer houdbaar worden gemaakt. Deze bekende techniek kent de laatste tijd nieuwe ontwikkelingen en toepassingen . Naast pasteuriseren door een hogedrukbehandeling bij kamertemperatuur is het nu ook mogelijk om te steriliseren met hoge druk. Ook

  6. MetNet Network Mission for Martian Atmospheric Investigations

    Harri, A.-M.; Alexashkin, S.; Arrugeo, I.; Schmidt, W.; Vazquez, L.; Genzer, M.; Haukka, H.

    2014-07-01

    A new kind of planetary exploration mission for Mars called MetNet is being developed for martian atmospheric investigations. The eventual scope of the MetNet Mission is to deploy tens of small landers on the martian surface.

  7. Dimensionering van de Uniqfill chemischer wasser met lamellen

    Starmans, D.A.J.

    2006-01-01

    In dit rapport wordt een eerste aanzet gegeven tot de modellering van een kruisstroom chemische wasser met lamellen. Met behulp van bestaande metingen is de stofoverdrachtscoëfficiënt afgeschat, waarna scenario's voor nieuwe wassers doorgerekend konden worden.

  8. Klimaatverandering en de stadsboom (interview met Jitze Kopinga)

    Bennink, P.; Kopinga, J.

    2010-01-01

    Bomen in de stad staan vaak op warme plaatsen met een gebrekkige waterhuishouding. Volgens het KNMI zal Nederland in de toekomst steeds vaker met hitte en droogte te maken hebben. Wat betekent dat voor onze stadsbomen?

  9. Load forecasting

    Mak, H.

    1995-01-01

    Slides used in a presentation at The Power of Change Conference in Vancouver, BC in April 1995 about the changing needs for load forecasting were presented. Technological innovations and population increase were said to be the prime driving forces behind the changing needs in load forecasting. Structural changes, market place changes, electricity supply planning changes, and changes in planning objectives were other factors discussed. It was concluded that load forecasting was a form of information gathering, that provided important market intelligence

  10. MET amplification, expression, and exon 14 mutations in colorectal adenocarcinoma.

    Zhang, Meng; Li, Guichao; Sun, Xiangjie; Ni, Shujuan; Tan, Cong; Xu, Midie; Huang, Dan; Ren, Fei; Li, Dawei; Wei, Ping; Du, Xiang

    2018-04-08

    MET amplification, expression, and splice mutations at exon 14 result in dysregulation of the MET signaling pathway. The aim of this study was to identify the relationship between MET amplification, protein or mRNA expression, and mutations in colorectal cancer (CRC). MET immunohistochemistry (IHC) was used for MET protein expression analysis and fluorescence in situ hybridization (FISH) was used for MET amplification detection. Both analyses were performed in tissue microarrays (TMA) containing 294 of colorectal adenocarcinoma tissue samples and 131 samples of adjacent normal epithelial tissue. MET mRNA expression was examined by real-time quantitative polymerase chain reaction (qRT-PCR) in 72 fresh colorectal adenocarcinoma tissue samples and adjacent normal colon tissue. PCR sequencing was performed to screen for MET exon 14 splice mutations in 59 fresh CRC tissue samples. Our results showed that MET protein expression was higher in colorectal tumor tissue than in adjacent normal intestinal epithelium. Positive MET protein expression was associated with significantly poorer overall survival (OS) and disease-free survival (DFS). Multivariate analysis revealed that positive MET protein expression was an independent risk factor for DFS, but not for OS. MET mRNA expression was upregulated in tumor tissues compared with the adjacent normal tissues. The incidence of MET amplification was 4.4%. None of the patients was positive for MET mutation. Collectively, MET was overexpressed in colorectal adenocarcinoma, and its positive protein expression predicted a poorer outcome in CRC patients. Furthermore, according to our results, MET amplification and 14 exon mutation are extremely rare events in colorectal adenocarcinoma. Copyright © 2018. Published by Elsevier Inc.

  11. Effect of MET on formation and vigor of wheat roots

    Wang Bingkui; Jin Ziyu; Zhao Miaozhen; Zhao Yanshen

    1993-01-01

    Effect of MET on the formation and vigor of roots of wheat seedlings were studied. The results showed that 50 ∼ 200 ppm MET inhibited vertical elongation of roots, increased root, shoot ratio and enhanced the formation and vigor of roots. But MET had no effect on the dry weight of roots. The activity of peroxidase was decreased and the proportion of assimilates in roots was increased by MET treatment compared with the control

  12. Estimating and testing the effect of allelic recombination on the ...

    Jane

    2011-01-21

    Jan 21, 2011 ... The significance of the correlation coefficient as well as the fitted regression model was obtained using. Analysis of Variance method. Key words: Allele, genotype, regression, correlation, F-ratio, analysis of variance. INTRODUCTION .... while if the allelic replacement is being made on an Aa individual the ...

  13. Low Penetrance Alleles in Colorectal Cancer: the arachidonic acid pathway

    C.L.E. Siezen

    2006-01-01

    textabstractIn summary, we can conclude that we have successfully identified low penetrance alleles in the PPAR., PLA2G2A and ALOX15 genes, conferring differential colorectal adenoma risk, and two such alleles in the PTGS2 gene, one of which is also involved in colorectal cancer risk. These

  14. Comparison of bovine lymphocyte antigen DRB3.2 allele ...

    STORAGESEVER

    2008-08-04

    Aug 4, 2008 ... The bovine lymphocyte antigen (BoLA-DRB3) gene encodes cell ... alleles were more resistant to clinical mastitis. ... DRB3.2 allele pattern in two Iranian Holstein cow .... observed and the number of immune parameters with.

  15. Evolutionary dynamics of sporophytic self-incompatibility alleles in plants

    Schierup, Mikkel Heide; Vekemans, Xavier; Christiansen, Freddy Bugge

    1997-01-01

    codominantly in both pollen and style (SSIcod), in the second, alleles form a dominance hierarchy in pollen and style (SSIdom). In the third model, alleles interact codominantly in the style and form a dominance hierarchy in the pollen (SSIdomcod). The SSIcod model behaves similarly to the model...

  16. Human minisatellite alleles detectable only after PCR amplification.

    Armour, J A; Crosier, M; Jeffreys, A J

    1992-01-01

    We present evidence that a proportion of alleles at two human minisatellite loci is undetected by standard Southern blot hybridization. In each case the missing allele(s) can be identified after PCR amplification and correspond to tandem arrays too short to detect by hybridization. At one locus, there is only one undetected allele (population frequency 0.3), which contains just three repeat units. At the second locus, there are at least five undetected alleles (total population frequency 0.9) containing 60-120 repeats; they are not detected because these tandem repeats give very poor signals when used as a probe in standard Southern blot hybridization, and also cross-hybridize with other sequences in the genome. Under these circumstances only signals from the longest tandemly repeated alleles are detectable above the nonspecific background. The structures of these loci have been compared in human and primate DNA, and at one locus the short human allele containing three repeat units is shown to be an intermediate state in the expansion of a monomeric precursor allele in primates to high copy number in the longer human arrays. We discuss the implications of such loci for studies of human populations, minisatellite isolation by cloning, and the evolution of highly variable tandem arrays.

  17. Comparative frequency and allelic distribution of ABO and Rh (D ...

    Background: Allelic distribution of major blood groups (ABO and rhesus) has not been defined in Bangladeshi population. Determinants of blood group frequency in this region have not been studied properly. Aim: To determine ABO and rhesus blood group frequency and allelic distribution in a multiethnic area of ...

  18. Apolipoprotein E4 allele does not influence serum triglyceride ...

    This study investigated how the APOε4 allele affects the serum triglyceride response after a fatmeal in apparently healthy black South African young adults. Sixty students were successfully screened for APOE genotype using Restriction Fragment Length Polymorphism (RFLP) and were divided into four groups; the ε2 allele ...

  19. Innoveren met serious games : Wat is serious gaming?

    Werkhoven, P.J.

    2008-01-01

    Het begrip serious gaming is inmiddels gekaapt door vele aanbieders van wat vroeger simulatie en virtual reality technologie genoemd werd. Met die technologie kunnen we mensen laten rondlopen in virtuele gebouwen en landschappen, al dan niet met grote projectieschermen of met brillen op. Maar dat is

  20. Groen proceswater: zuivering brouwerijprocesafvalwater met microalgen : Resultaten onderzoek 2013

    Dijk, van W.; Diem, van A.; Doornbusch, P.; Grobben-Gaastra, S.A.; Kleinhout, G.; Kroon, A.; Weide, van der R.Y.

    2014-01-01

    Afgelopen jaar is de pilot met het kweken van algen met afvalwater van de brouwerijlocatie Zoeterwoude geslaagd. Dit is gedaan in een samenwerkingsverband van Heineken Nederland BV, Algae Food & Fuel en WUR-Acrres. Dit is de eerste inline pilot in de wereld waarbij met LED verlichting op 1000 L

  1. Erlotinib e metástases cerebrais

    Fernando Barata

    2008-10-01

    Full Text Available Resumo: Relatamos dois casos de carcinoma pulmonar de não pequenas células (CPNPC com metástases cerebrais que após quimioterapia sistémica receberam em segunda e terceira linha erlotinib 150 mg/dia, oral, com resposta completa das lesões secundárias cerebrais e franca resposta parcial das lesões torácicas.A metastização cerebral, bastante prevalente no contexto do CPNPC, está associada a escassas opções terapêuticas eficazes e, consequentemente, a uma sobre-vida mediana de 4 a 6 meses.Estes casos alertam para o erlotinib como uma excelente opção terapêutica para estes doentes. Os autores propõem um ensaio clínico com este fármaco neste grupo de doentes, procurando determinar da resposta objectiva.Rev Port Pneumol 2008; XIV (Supl 3: S35-S42 Abstract: We report two cases of brain metastases in context of non small cell lung cancer (NSCLC. After having progressed to chemotherapy they received erlotinib 150 mg/m2 orally daily, with complete response of brain metastasis and partial response of thoracic lesions.Brain metastases are both prevalent and a major cause of mortality in NSCLC, with few systemic treatment options. Median survival after whole brain radiotherapy is 4-6 months and the role of systemic therapy for brain metastases is limited with the most drugs use to stage IV disease ineffective in this setting.This case demonstrates that brain metastases may be sensitive to erlotinib and give to us growing body of evidence that EGFR-associated tyrosine kinase inhibition is a feasible strategy in the management of NSCLC patients with brain metastasesWe propose further study into the continued use of this drug in the situation where there is a differential response.Rev Port Pneumol 2008; XIV (Supl 3: S35-S42 Palavras-chave: Erlotinib, metástase cerebral, cancro do pulmão, Key-words: Erlotinib, brain metastasis, lung cancer

  2. The BDNF val-66-met Polymorphism Affects Neuronal Morphology and Synaptic Transmission in Cultured Hippocampal Neurons from Rett Syndrome Mice

    Xin Xu

    2017-07-01

    Full Text Available Brain-derived neurotrophic factor (Bdnf has been implicated in several neurological disorders including Rett syndrome (RTT, an X-linked neurodevelopmental disorder caused by loss-of-function mutations in the transcriptional modulator methyl-CpG-binding protein 2 (MECP2. The human BDNF gene has a single nucleotide polymorphism (SNP—a methionine (met substitution for valine (val at codon 66—that affects BDNF’s trafficking and activity-dependent release and results in cognitive dysfunction. Humans that are carriers of the met-BDNF allele have subclinical memory deficits and reduced hippocampal volume and activation. It is still unclear whether this BDNF SNP affects the clinical outcome of RTT individuals. To evaluate whether this BDNF SNP contributes to RTT pathophysiology, we examined the consequences of expression of either val-BDNF or met-BDNF on dendrite and dendritic spine morphology, and synaptic function in cultured hippocampal neurons from wildtype (WT and Mecp2 knockout (KO mice. Our findings revealed that met-BDNF does not increase dendritic growth and branching, dendritic spine density and individual spine volume, and the number of excitatory synapses in WT neurons, as val-BDNF does. Furthermore, met-BDNF reduces dendritic complexity, dendritic spine volume and quantal excitatory synaptic transmission in Mecp2 KO neurons. These results suggest that the val-BDNF variant contributes to RTT pathophysiology, and that BDNF-based therapies should take into consideration the BDNF genotype of the RTT individuals.

  3. Phase I Trial of Anti-MET Monoclonal Antibody in MET-Overexpressed Refractory Cancer.

    Lee, Jeeyun; Kim, Seung Tae; Park, Sungju; Lee, Sujin; Park, Se Hoon; Park, Joon Oh; Lim, Ho Yeong; Ahn, Hongmo; Bok, Haesook; Kim, Kyoung-Mee; Ahn, Myung Ju; Kang, Won Ki; Park, Young Suk

    2018-06-01

    Samsung Advance Institute of Technology-301 (SAIT301) is a human immunoglobulin G2 antibody that can specifically target mesenchymal epithelial transition factor (c-MET). This novel antibody has higher priority over hepatocyte growth factors when binding to the Sema domain of c-MET and accelerates the internalization and degradation of c-MET, proving its powerful antitumor activities in intra- as well as extracellular areas. SAIT301 was administered intravenously once every 3 weeks in c-MET overexpressed solid tumor patients, focusing on metastatic colorectal cancer (CRC) according to common clinical phase I criteria. Dose escalation was performed according to a modified Fibonacci design, following the conventional 3+3 design. The purpose of this phase I study was to assess the safety profile, to establish the recommended dose for clinical phase II studies and to assess potential anticancer activity of the compound. Sixteen patients with a median age of 56 (range, 39-69) years were enrolled in the study. The most common adverse events were decreased appetite (50.0%), hypophosphatemia, fatigue and dizziness (25.0%, respectively), and diarrhea, blood alkaline phosphatase increased and dyspnea (18.8%, respectively). For tumor response, no patients achieved complete response. One (9.1%) CRC patient had a partial response in the 1.23 mg/kg group, 4 (36.4%) patients achieved stable disease (2 in the 0.41 mg/kg group, 2 in the 1.23 mg/kg group, 0 in the 3.69 mg/kg group, and 1 in the 8.61 mg/kg group). Because of the increase in dose-limiting toxicities (DLTs) at 8.61 mg/kg, the 3.69 mg/kg dose was considered the maximum tolerated dose and selected for further assessment in phase II. We successfully completed a phase I trial with MET antibody in a MET-overexpressed patient population focusing on CRC, and found that the DLTs were alkaline phosphatase elevation or hypophosphatemia. The recommended dose of SAIT301 for phase II is the dose of 3.69 mg/kg. Copyright © 2018

  4. Assigning breed origin to alleles in crossbred animals.

    Vandenplas, Jérémie; Calus, Mario P L; Sevillano, Claudia A; Windig, Jack J; Bastiaansen, John W M

    2016-08-22

    For some species, animal production systems are based on the use of crossbreeding to take advantage of the increased performance of crossbred compared to purebred animals. Effects of single nucleotide polymorphisms (SNPs) may differ between purebred and crossbred animals for several reasons: (1) differences in linkage disequilibrium between SNP alleles and a quantitative trait locus; (2) differences in genetic backgrounds (e.g., dominance and epistatic interactions); and (3) differences in environmental conditions, which result in genotype-by-environment interactions. Thus, SNP effects may be breed-specific, which has led to the development of genomic evaluations for crossbred performance that take such effects into account. However, to estimate breed-specific effects, it is necessary to know breed origin of alleles in crossbred animals. Therefore, our aim was to develop an approach for assigning breed origin to alleles of crossbred animals (termed BOA) without information on pedigree and to study its accuracy by considering various factors, including distance between breeds. The BOA approach consists of: (1) phasing genotypes of purebred and crossbred animals; (2) assigning breed origin to phased haplotypes; and (3) assigning breed origin to alleles of crossbred animals based on a library of assigned haplotypes, the breed composition of crossbred animals, and their SNP genotypes. The accuracy of allele assignments was determined for simulated datasets that include crosses between closely-related, distantly-related and unrelated breeds. Across these scenarios, the percentage of alleles of a crossbred animal that were correctly assigned to their breed origin was greater than 90 %, and increased with increasing distance between breeds, while the percentage of incorrectly assigned alleles was always less than 2 %. For the remaining alleles, i.e. 0 to 10 % of all alleles of a crossbred animal, breed origin could not be assigned. The BOA approach accurately assigns

  5. 3D RoboMET Characterization

    Madison, Jonathan D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Susan, Donald F. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Kilgo, Alice C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-10-01

    The goal of this project is to generate 3D microstructural data by destructive and non-destructive means and provide accompanying characterization and quantitative analysis of such data. This work is a continuing part of a larger effort to relate material performance variability to microstructural variability. That larger effort is called “Predicting Performance Margins” or PPM. In conjunction with that overarching initiative, the RoboMET.3D™ is a specific asset of Center 1800 and is an automated serialsectioning system for destructive analysis of microstructure, which is called upon to provide direct customer support to 1800 and non-1800 customers. To that end, data collection, 3d reconstruction and analysis of typical and atypical microstructures have been pursued for the purposes of qualitative and quantitative characterization with a goal toward linking microstructural defects and/or microstructural features with mechanical response. Material systems examined in FY15 include precipitation hardened 17-4 steel, laser-welds of 304L stainless steel, thermal spray coatings of 304L and geological samples of sandstone.

  6. Coriocarcinoma con metástasis pulmonar

    Vicia Sánchez Abalos

    2014-05-01

    Full Text Available Se presenta el caso clínico de una fémina de 44 años de edad, con 32 semanas de embarazo, la cual fuera ingresada en la Unidad de Cuidados Intensivos del Hospital General Docente "Dr. Juan Bruno Zayas Alfonso" de Santiago de Cuba, por presentar insuficiencia respiratoria aguda como consecuencia de una sepsis. La paciente fue tratada con cefalosporina de tercera generación y ventilación mecánica no invasiva, pero se mantuvieron las características gasométricas de hipoxemia y una mala reacción terapéutica, por lo que se requirió instrumentación de las vías respiratorias y soporte hemodinámico, sin lograr regresión del cuadro clínico, lo cual condujo a un paro cardiorrespiratorio y, con ello, a la muerte. La necropsia mostró un coriocarcinoma del endometrio con metástasis pulmonar

  7. A risk allele for nicotine dependence in CHRNA5 is a protective allele for cocaine dependence.

    Grucza, Richard A; Wang, Jen C; Stitzel, Jerry A; Hinrichs, Anthony L; Saccone, Scott F; Saccone, Nancy L; Bucholz, Kathleen K; Cloninger, C Robert; Neuman, Rosalind J; Budde, John P; Fox, Louis; Bertelsen, Sarah; Kramer, John; Hesselbrock, Victor; Tischfield, Jay; Nurnberger, John I; Almasy, Laura; Porjesz, Bernice; Kuperman, Samuel; Schuckit, Marc A; Edenberg, Howard J; Rice, John P; Goate, Alison M; Bierut, Laura J

    2008-12-01

    A nonsynonymous coding polymorphism, rs16969968, of the CHRNA5 gene that encodes the alpha-5 subunit of the nicotinic acetylcholine receptor (nAChR) has been found to be associated with nicotine dependence. The goal of this study was to examine the association of this variant with cocaine dependence. Genetic association analysis was performed in two independent samples of unrelated case and control subjects: 1) 504 European Americans participating in the Family Study on Cocaine Dependence (FSCD) and 2) 814 European Americans participating in the Collaborative Study on the Genetics of Alcoholism (COGA). In the FSCD, there was a significant association between the CHRNA5 variant and cocaine dependence (odds ratio = .67 per allele, p = .0045, assuming an additive genetic model), but in the reverse direction compared with that previously observed for nicotine dependence. In multivariate analyses that controlled for the effects of nicotine dependence, both the protective effect for cocaine dependence and the previously documented risk effect for nicotine dependence were statistically significant. The protective effect for cocaine dependence was replicated in the COGA sample. In COGA, effect sizes for habitual smoking, a proxy phenotype for nicotine dependence, were consistent with those observed in FSCD. The minor (A) allele of rs16969968, relative to the major G allele, appears to be both a risk factor for nicotine dependence and a protective factor for cocaine dependence. The biological plausibility of such a bidirectional association stems from the involvement of nAChRs with both excitatory and inhibitory modulation of dopamine-mediated reward pathways.

  8. The interaction of BDNF Val66Met, PTSD, and child abuse on psychophysiological reactivity and HPA axis function in a sample of Gulf War Veterans.

    Young, Dmitri A; Neylan, Thomas C; O'Donovan, Aoife; Metzler, Thomas; Richards, Anne; Ross, Jessica A; Inslicht, Sabra S

    2018-08-01

    While the BDNF Val66Met polymorphism has been linked to various psychological disorders, limited focus has been on its relationship to posttraumatic stress disorder (PTSD) and early traumas such as child abuse. Therefore, we assessed whether Val66Met was associated with fear potentiated psychophysiological response and HPA axis dysfunction and whether PTSD status or child abuse history moderated these outcomes in a sample of Veterans. 226 and 173 participants engaged in a fear potentiated acoustic startle paradigm and a dexamethasone suppression test (DST) respectively. Fear conditions included no, ambiguous, and high threat conditions. Psychophysiological response measures included electromyogram (EMG), skin conductance response (SCR), and heart rate. The Clinician Administered PTSD Scale (CAPS) and the Trauma History Questionnaire (THQ) were used to assess PTSD status and child abuse history respectively. Met allele carriers exhibited greater SCR magnitudes in the no and ambiguous threat conditions (p < 0.01 and p < 0.05 respectively). Met carriers with PTSD exhibited greater physiological response magnitudes in the ambiguous (SCR, p < 0.001) and high threat conditions (SCR and heart rate, both p ≤ 0.005). Met carrier survivors of child abuse exhibited blunted heart rate magnitudes in the high threat condition (p < 0.01). Met allele carries with PTSD also exhibited greater percent cortisol suppression (p < 0.005). Limitations included small sample size and the cross-sectional nature of the data. The Val66met may impact PTSD susceptibility differentially via enhanced threat sensitivity and HPA axis dysregulation. Child abuse may moderate Val66Met's impact on threat reactivity. Future research should explore how neuronal mechanisms might mediate this risk. Published by Elsevier B.V.

  9. BDNF Val66Met in preclinical Alzheimer's disease is associated with short-term changes in episodic memory and hippocampal volume but not serum mBDNF.

    Lim, Yen Ying; Rainey-Smith, Stephanie; Lim, Yoon; Laws, Simon M; Gupta, Veer; Porter, Tenielle; Bourgeat, Pierrick; Ames, David; Fowler, Christopher; Salvado, Olivier; Villemagne, Victor L; Rowe, Christopher C; Masters, Colin L; Zhou, Xin Fu; Martins, Ralph N; Maruff, Paul

    2017-11-01

    The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism Met allele exacerbates amyloid (Aβ) related decline in episodic memory (EM) and hippocampal volume (HV) over 36-54 months in preclinical Alzheimer's disease (AD). However, the extent to which Aβ+ and BDNF Val66Met is related to circulating markers of BDNF (e.g. serum) is unknown. We aimed to determine the effect of Aβ and the BDNF Val66Met polymorphism on levels of serum mBDNF, EM, and HV at baseline and over 18-months. Non-demented older adults (n = 446) underwent Aβ neuroimaging and BDNF Val66Met genotyping. EM and HV were assessed at baseline and 18 months later. Fasted blood samples were obtained from each participant at baseline and at 18-month follow-up. Aβ PET neuroimaging was used to classify participants as Aβ- or Aβ+. At baseline, Aβ+ adults showed worse EM impairment and lower serum mBDNF levels relative to Aβ- adults. BDNF Val66Met polymorphism did not affect serum mBDNF, EM, or HV at baseline. When considered over 18-months, compared to Aβ- Val homozygotes, Aβ+ Val homozygotes showed significant decline in EM and HV but not serum mBDNF. Similarly, compared to Aβ+ Val homozygotes, Aβ+ Met carriers showed significant decline in EM and HV over 18-months but showed no change in serum mBDNF. While allelic variation in BDNF Val66Met may influence Aβ+ related neurodegeneration and memory loss over the short term, this is not related to serum mBDNF. Longer follow-up intervals may be required to further determine any relationships between serum mBDNF, EM, and HV in preclinical AD.

  10. The COMT Val158 allele is associated with impaired delayed-match-to-sample performance in ADHD

    Matthews Natasha

    2012-05-01

    Full Text Available Abstract Background This study explored the association between three measures of working memory ability and genetic variation in a range of catecholamine genes in a sample of children with ADHD. Methods One hundred and eighteen children with ADHD performed three working memory measures taken from the CANTAB battery (Spatial Span, Delayed-match-to-sample, and Spatial Working Memory. Associations between performance on working memory measures and allelic variation in catecholamine genes (including those for the noradrenaline transporter [NET1], the dopamine D4 and D2 receptor genes [DRD4; DRD2], the gene encoding dopamine beta hydroxylase [DBH] and catechol-O-methyl transferase [COMT] were investigated using regression models that controlled for age, IQ, gender and medication status on the day of test. Results Significant associations were found between performance on the delayed-match-to-sample task and COMT genotype. More specifically, val/val homozygotes produced significantly more errors than did children who carried a least one met allele. There were no further associations between allelic variants and performance across the other working memory tasks. Conclusions The working memory measures employed in the present study differed in the degree to which accurate task performance depended upon either the dynamic updating and/or manipulation of items in working memory, as in the spatial span and spatial working memory tasks, or upon the stable maintenance of representations, as in the delay-match–to-sample task. The results are interpreted as evidence of a relationship between tonic dopamine levels associated with the met COMT allele and the maintenance of stable working memory representations required to perform the delayed-match-to-sample-task.

  11. Beam loading

    Boussard, Daniel

    1987-01-01

    We begin by giving a description of the radio-frequency generator-cavity-beam coupled system in terms of basic quantities. Taking beam loading and cavity detuning into account, expressions for the cavity impedance as seen by the generator and as seen by the beam are derived. Subsequently methods of beam-loading compensation by cavity detuning, radio-frequency feedback and feedforward are described. Examples of digital radio-frequency phase and amplitude control for the special case of superco...

  12. Mannose-binding lectin variant alleles and HLA-DR4 alleles are associated with giant cell arteritis

    Jacobsen, Soren; Baslund, Bo; Madsen, Hans O.

    2002-01-01

    /GCA, MBL variant alleles were associated with signs of increased inflammatory activity and clinical signs of arteritic manifestations. This was not found for HLA-DR4 alleles. These findings indicate that HLA-DR4 and MBL are contributing to the pathophysiology of GCA at different levels in the disease...... alleles in controls, patients with PMR only, and patients with GCA was 37, 32, and 53% (p = 0.01), respectively. HLA-DRB1*04 was found in 47% of patients with PMR only and in 54% of patients with GCA, which differed significantly from the 35% found in controls (p = 0.01). HLA-DR4 alleles were...... not associated with any clinical phenotypes of PMR/GCA, whereas MBL variant alleles were associated with cranial arteritis, high erythrocyte sedimentation rate, and low B-hemoglobin. CONCLUSION: We found MBL variant alleles and HLA-DR4 alleles to be weak susceptibility markers for GCA. In patients with PMR...

  13. The derived allele of ASPM is associated with lexical tone perception.

    Patrick C M Wong

    Full Text Available The ASPM and MCPH1 genes have been implicated in the adaptive evolution of the human brain [Mekel-Bobrov N. et al., 2005. Ongoing adaptive evolution of ASPM, a brain size determinant in homo sapiens. Science 309; Evans P.D. et al., 2005. Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans. Science 309]. Curiously, experimental attempts have failed to connect the implicated SNPs in these genes with higher-level brain functions. These results stand in contrast with a population-level study linking the population frequency of their alleles with the tendency to use lexical tones in a language [Dediu D., Ladd D.R., 2007. Linguistic tone is related to the population frequency of the adaptive haplogroups of two brain size genes, ASPM and microcephalin. Proc. Natl. Acad. Sci. U.S.A. 104]. In the present study, we found a significant correlation between the load of the derived alleles of ASPM and tone perception in a group of European Americans who did not speak a tone language. Moreover, preliminary results showed a significant correlation between ASPM load and hemodynamic responses to lexical tones in the auditory cortex, and such correlation remained after phonemic awareness, auditory working memory, and non-verbal IQ were controlled. As in previous studies, no significant correlation between ASPM and cognitive measures were found. MCPH1 did not correlate with any measures. These results suggest that the association between the recently derived allele of ASPM is likely to be specific and is tied to higher level brain functions in the temporal cortex related to human communication.

  14. Research progress in c-Met and hepatocellular carcinoma

    WANG Changqing

    2015-06-01

    Full Text Available c-Met plays a pivotal role in the development and progression of hepatocellular carcinoma (HCC, which can lead to proliferation, survival, cytoskeleton reorganization, separation and diffusion, and angiogenesis of tumor cells. Moreover, c-Met is an important prognostic factor for HCC. In HCC, c-Met acts as an activator of a series of signaling pathways, including PI3K/AKT/mTOR, ERK/MAPK, and Rac-Pak. In recent years, it has been reported that small-molecule kinase inhibitors can abolish phosphorylation at the intracellular carboxyl terminal of c-Met, and then inhibit the recruitment of signal convertors and downstream signaling pathways, which finally achieve anti-tumor activities. Based on the carcinogenic activity of c-Met in HCC, this paper points out that selective inhibitors of c-Met hold promise for targeted therapies for HCC.

  15. allelic variation of hmw glutenin subunits of ethiopian bread wheat

    journal

    High molecular weight glutenins are often effective in identifying wheat (Triticum ... There were highly significant differences between genotypes and banding ... was without deliberate selection pressure towards high Glu-1 scoring alleles ...

  16. Association mapping and favorable QTL alleles for fiber quality traits ...

    A total of 201 markers were polymorphic and generated 394 ... identified favorable QTL alleles and typical accessions for fiber quality are excellent genetic resources for future cotton .... Field management followed respective local practices.

  17. Apolipoprotein e4 allele and cognitive decline in elderly men

    Feskens, E.J.M.; Havekes, L.M.; Kalmijn, S.; Knijff, P. de; Launer, L.J.; Kromhout, D.

    1994-01-01

    Objectives - To determine whether polymorphism of apolipoprotein E - notably, the e4 allele - predicts cognitive deterioration in the general population. Design - Population based cohort investigated in 1990 and in 1993. Setting - Zutphen, the Netherlands. Subjects - Representative cohort of 538

  18. Association between allelic variants of the human glucocorticoid receptor gene and autoimmune diseases: A systematic review and meta-analysis.

    Herrera, Cristian; Marcos, Miguel; Carbonell, Cristina; Mirón-Canelo, José Antonio; Espinosa, Gerard; Cervera, Ricard; Chamorro, Antonio-Javier

    2018-05-01

    The human glucocorticoid receptor gene (NR3C1) is considered to play a role in the differences and sensitivities of the glucocorticoid response in individuals with autoimmune diseases. The objective of this study was to examine by means of a systematic review previous findings regarding allelic variants of NR3C1 in relation to the risk of developing systemic autoimmune diseases. Studies that analysed the genotype distribution of NR3C1 allelic variants among patients with systemic autoimmune diseases were retrieved. A meta-analysis was conducted with a random effects model. Odds ratios (ORs) and their confidence intervals (CIs) were calculated. In addition, sub-analysis by ethnicity, sensitivity analysis and tests for heterogeneity of the results were performed. Eleven studies met the inclusion criteria for meta-analysis. We found no evidence that the analysed NR3C1 polymorphisms, rs6198, rs56149945, and rs6189/rs6190, modulate the risk of developing a systemic autoimmune disease. Nonetheless, a protective role for the minor allele of rs41423247 was found among Caucasians (OR=0.78; 95% CI: 0.65, 0.92; P=0.004). A subgroup analysis according to underlying diseases revealed no significant association either for Behçet's disease or rheumatoid arthritis, while correlations between NR3C1 polymorphisms and disease activity or response to glucocorticoids could not be evaluated due to insufficient data. There is no clear evidence that the analysed NR3C1 allelic variants confer a risk for developing systemic autoimmune diseases although the minor G allele of rs41423247 may be protective among Caucasians. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Design and Implementation of Image Research for the Columbia Mets

    1992-01-01

    the other hand, developed an unusual camaraderie through identifying with their underdog Mets." (7) Teams are finding good public relations programs do...supports the club. Question 24 was designed to measure brand loyalty by respondents to Mets sponsors versus non-Mets sponsors. Finally, question 27...be done to attract crowds. Especially with a brand new stadium. The Carolinas, in my opinion, are big minor league baseball states. Let’s get people

  20. Effective implementation of novel MET pharmacodynamic assays in translational studies.

    Srivastava, Apurva K; Navas, Tony; Herrick, William G; Hollingshead, Melinda G; Bottaro, Donald P; Doroshow, James H; Parchment, Ralph E

    2017-01-01

    MET tyrosine kinase (TK) dysregulation is significantly implicated in many types of cancer. Despite over 20 years of drug development to target MET in cancers, a pure anti-MET therapeutic has not yet received market approval. The failure of two recently concluded phase III trials point to a major weakness in biomarker strategies to identify patients who will benefit most from MET therapies. The capability to interrogate oncogenic mutations in MET via circulating tumor DNA (ctDNA) provides an important advancement in identification and stratification of patients for MET therapy. However, a wide range in type and frequency of these mutations suggest there is a need to carefully link these mutations to MET dysregulation, at least in proof-of-concept studies. In this review, we elaborate how we can utilize recently developed and validated pharmacodynamic biomarkers of MET not only to show target engagement, but more importantly to quantitatively measure MET dysregulation in tumor tissues. The MET assay endpoints provide evidence of both canonical and non-canonical MET signaling, can be used as "effect markers" to define biologically effective doses (BEDs) for molecularly targeted drugs, confirm mechanism-of-action in testing combination of drugs, and establish whether a diagnostic test is reporting MET dysregulation. We have established standard operating procedures for tumor biopsy collections to control pre-analytical variables that have produced valid results in proof-of-concept studies. The reagents and procedures are made available to the research community for potential implementation on multiple platforms such as ELISA, quantitative immunofluorescence assay (qIFA), and immuno-MRM assays.

  1. DRD4 dopamine receptor allelic diversity in various primate species

    Adamson, M.; Higley, D. [NIAAA, Rockville, MD (United States); O`Brien, S. [NCI, Frederick, MD (United States)] [and others

    1994-09-01

    The DRD4 dopamine receptor is uniquely characterized by a 48 bp repeating segment within the coding region, located in exon III. Different DRD4 alleles are produced by the presence of additional 48 bp repeats, each of which adds 16 amino acids to the length of the 3rd intracytoplasmic loop of the receptor. The DRD4 receptor is therefore an intriguing candidate gene for behaviors which are influenced by dopamine function. In several human populations, DRD4 alleles with 2-8 and 10 repeats have previously been identified, and the 4 and 7 repeat alleles are the most abundant. We have determined DRD4 genotypes in the following nonhuman primate species: chimpanzee N=2, pygmy chimpanzee N=2, gorilla N=4, siamang N=2, Gelada baboon N=1, gibbon N=1, orangutan (Bornean and Sumatran) N=62, spider monkey N=4, owl monkey N=1, Colobus monkey N=1, Patas monkey N=1, ruffed lemur N=1, rhesus macaque N=8, and vervet monkey N=28. The degree of DRD4 polymorphism and which DRD4 alleles were present both showed considerable variation across primate species. In contrast to the human, rhesus macaque monkeys were monomorphic. The 4 and 7 repeat allels, highly abundant in the human, may not be present in certain other primates. For example, the four spider monkeys we studied showed the 7, 8 and 9 repeat length alleles and the only gibbon we analyzed was homozygous for the 9 repeat allele (thus far not observed in the human). Genotyping of other primate species and sequencing of the individual DRD4 repeat alleles in different species may help us determine the ancestral DRD4 repeat length and identify connections between DRD4 genotype and phenotype.

  2. Allele frequency distribution for 21 autosomal STR loci in Nepal.

    Kraaijenbrink, T; van Driem, G L; Opgenort, J R M L; Tuladhar, N M; de Knijff, P

    2007-05-24

    The allele frequency distributions of 21 autosomal loci contained in the AmpFlSTR Identifiler, the Powerplex 16 and the FFFL multiplex PCR kits, was studied in 953 unrelated individuals from Nepal. Several new alleles (i.e. not yet reported in the NIST Short Tandem Repeat DNA Internet DataBase [http://www.cstl.nist.gov/biotech/strbase/]) have been detected in the process.

  3. Targeting MET Amplification as a New Oncogenic Driver

    Kawakami, Hisato [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Okamoto, Isamu, E-mail: okamotoi@kokyu.med.kyushu-u.ac.jp [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Center for Clinical and Translational Research, Kyushu University Hospital, 3-1-1 Maidashi, Higashiku, Fukuoka 812-8582 (Japan); Okamoto, Wataru [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Division of Transrlational Research, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577 (Japan); Tanizaki, Junko [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, HIM223, 450 Brookline Avenue, Boston, MA 02215 (United States); Nakagawa, Kazuhiko [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Nishio, Kazuto [Department of Genome Biology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan)

    2014-07-22

    Certain genetically defined cancers are dependent on a single overactive oncogene for their proliferation and survival, a phenomenon known as “oncogene addiction”. A new generation of drugs that selectively target such “driver oncogenes” manifests a clinical efficacy greater than that of conventional chemotherapy in appropriate genetically defined patients. MET is a proto-oncogene that encodes a receptor tyrosine kinase, and aberrant activation of MET signaling occurs in a subset of advanced cancers as result of various genetic alterations including gene amplification, polysomy, and gene mutation. Our preclinical studies have shown that inhibition of MET signaling either with the small-molecule MET inhibitor crizotinib or by RNA interference targeted to MET mRNA resulted in marked antitumor effects in cancer cell lines with MET amplification both in vitro and in vivo. Furthermore, patients with non-small cell lung cancer or gastric cancer positive for MET amplification have shown a pronounced clinical response to crizotinib. Accumulating preclinical and clinical evidence thus suggests that MET amplification is an “oncogenic driver” and therefore a valid target for treatment. However, the prevalence of MET amplification has not been fully determined, possibly in part because of the difficulty in evaluating gene amplification. In this review, we provide a rationale for targeting this genetic alteration in cancer therapy.

  4. Targeting MET Amplification as a New Oncogenic Driver

    Kawakami, Hisato; Okamoto, Isamu; Okamoto, Wataru; Tanizaki, Junko; Nakagawa, Kazuhiko; Nishio, Kazuto

    2014-01-01

    Certain genetically defined cancers are dependent on a single overactive oncogene for their proliferation and survival, a phenomenon known as “oncogene addiction”. A new generation of drugs that selectively target such “driver oncogenes” manifests a clinical efficacy greater than that of conventional chemotherapy in appropriate genetically defined patients. MET is a proto-oncogene that encodes a receptor tyrosine kinase, and aberrant activation of MET signaling occurs in a subset of advanced cancers as result of various genetic alterations including gene amplification, polysomy, and gene mutation. Our preclinical studies have shown that inhibition of MET signaling either with the small-molecule MET inhibitor crizotinib or by RNA interference targeted to MET mRNA resulted in marked antitumor effects in cancer cell lines with MET amplification both in vitro and in vivo. Furthermore, patients with non-small cell lung cancer or gastric cancer positive for MET amplification have shown a pronounced clinical response to crizotinib. Accumulating preclinical and clinical evidence thus suggests that MET amplification is an “oncogenic driver” and therefore a valid target for treatment. However, the prevalence of MET amplification has not been fully determined, possibly in part because of the difficulty in evaluating gene amplification. In this review, we provide a rationale for targeting this genetic alteration in cancer therapy

  5. Preproghrelin Leu72Met polymorphism in obese Korean children.

    Jo, Dae-Sun; Kim, Se-Lim; Kim, Sun-Young; Hwang, Pyoung Han; Lee, Kee-Hyoung; Lee, Dae-Yeol

    2005-11-01

    Ghrelin is a novel gut-brain peptide that has somatotropic, orexigenic, and adipogenic effects. We examined the preproghrelin Leu72Met polymorphism in 222 obese Korean children to determine whether it is associated with obesity. The frequencies of the Leu72Met polymorphism were 29.3% in obese, 32.3% in overweight, and 32.5% in lean Korean children. No significant difference was found between Met72 carrier and non-carrier obese children with respect to BMI, total body fat, serum triglycerides, total cholesterol, or LDL-cholesterol levels. Our data suggest that the preproghrelin Leu72Met polymorphism is not associated with obesity in children.

  6. Mars MetNet Mission Pressure and Humidity Devices

    Haukka, H.; Harri, A.-M.; Schmidt, W.; Genzer, M.; Polkko, J.; Kemppinen, O.; Leinonen, J.

    2012-09-01

    A new kind of planetary exploration mission for Mars is being developed in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission [1] is based on a new semi-hard landing vehicle called MetNet Lander (MNL). MetBaro and MetHumi are part of the scientific payload of the MNL. Main scientific goal of both devices is to measure the meteorological phenomena (pressure and humidity) of the Martian atmosphere and complement the previous Mars mission atmospheric measurements (Viking and Phoenix) for better understanding of the Martian atmospheric conditions.

  7. ALEA: a toolbox for allele-specific epigenomics analysis.

    Younesy, Hamid; Möller, Torsten; Heravi-Moussavi, Alireza; Cheng, Jeffrey B; Costello, Joseph F; Lorincz, Matthew C; Karimi, Mohammad M; Jones, Steven J M

    2014-04-15

    The assessment of expression and epigenomic status using sequencing based methods provides an unprecedented opportunity to identify and correlate allelic differences with epigenomic status. We present ALEA, a computational toolbox for allele-specific epigenomics analysis, which incorporates allelic variation data within existing resources, allowing for the identification of significant associations between epigenetic modifications and specific allelic variants in human and mouse cells. ALEA provides a customizable pipeline of command line tools for allele-specific analysis of next-generation sequencing data (ChIP-seq, RNA-seq, etc.) that takes the raw sequencing data and produces separate allelic tracks ready to be viewed on genome browsers. The pipeline has been validated using human and hybrid mouse ChIP-seq and RNA-seq data. The package, test data and usage instructions are available online at http://www.bcgsc.ca/platform/bioinfo/software/alea CONTACT: : mkarimi1@interchange.ubc.ca or sjones@bcgsc.ca Supplementary information: Supplementary data are available at Bioinformatics online. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Allele-specific MMP-3 transcription under in vivo conditions

    Chaoyong, Zhu [Atherosclerosis Research Unit, King Gustav V Research Institute, Department of Medicine, Karolinska Institute, Stockholm (Sweden); Odeberg, Jacob [Atherosclerosis Research Unit, King Gustav V Research Institute, Department of Medicine, Karolinska Institute, Stockholm (Sweden); Department of Biotechnology, AlbaNova University Center, Royal Institute of Technology, Stockholm (Sweden); Hamsten, Anders [Atherosclerosis Research Unit, King Gustav V Research Institute, Department of Medicine, Karolinska Institute, Stockholm (Sweden); Eriksson, Per [Atherosclerosis Research Unit, King Gustav V Research Institute, Department of Medicine, Karolinska Institute, Stockholm (Sweden)

    2006-09-29

    A common matrix metalloproteinases-3 (MMP-3) -1612 5A/6A promoter polymorphism is associated with risk for cardiovascular disease, rheumatoid arthritis, and other diseases. Here we used the haplotype chromatin immunoprecipitation method to study allele-specific MMP-3 expression under in vivo conditions in heterozygous THP-1 cells. Pyrosequencing was used to analyse the ratio of 5A-allele to 6A-allele after chromatin immunoprecipitation using an antibody against phosphorylated active RNA polymerase II. There was no allele-specific difference in transcriptional activity during basal conditions, i.e., in unstimulated monocytic THP-1 cells. However, after stimulation of MMP-3 expression by monocyte differentiation or incubation with IL-1{beta}, the haplotype containing the 5A-allele was associated with higher transcriptional activity compared with the 6A-containing haplotype. Electromobility shift assay demonstrated increased binding of nuclear proteins to the 5A-allele after monocyte differentiation. In conclusion, the common MMP-3 5A/6A promoter polymorphism appears to be functional only during specific environmental conditions involving inflammation.

  9. SSR allelic variation in almond (Prunus dulcis Mill.).

    Xie, Hua; Sui, Yi; Chang, Feng-Qi; Xu, Yong; Ma, Rong-Cai

    2006-01-01

    Sixteen SSR markers including eight EST-SSR and eight genomic SSRs were used for genetic diversity analysis of 23 Chinese and 15 international almond cultivars. EST- and genomic SSR markers previously reported in species of Prunus, mainly peach, proved to be useful for almond genetic analysis. DNA sequences of 117 alleles of six of the 16 SSR loci were analysed to reveal sequence variation among the 38 almond accessions. For the four SSR loci with AG/CT repeats, no insertions or deletions were observed in the flanking regions of the 98 alleles sequenced. Allelic size variation of these loci resulted exclusively from differences in the structures of repeat motifs, which involved interruptions or occurrences of new motif repeats in addition to varying number of AG/CT repeats. Some alleles had a high number of uninterrupted repeat motifs, indicating that SSR mutational patterns differ among alleles at a given SSR locus within the almond species. Allelic homoplasy was observed in the SSR loci because of base substitutions, interruptions or compound repeat motifs. Substitutions in the repeat regions were found at two SSR loci, suggesting that point mutations operate on SSRs and hinder the further SSR expansion by introducing repeat interruptions to stabilize SSR loci. Furthermore, it was shown that some potential point mutations in the flanking regions are linked with new SSR repeat motif variation in almond and peach.

  10. Origin of allelic diversity in antirrhinum S locus RNases.

    Xue, Y; Carpenter, R; Dickinson, H G; Coen, E S

    1996-01-01

    In many plant species, self-incompatibility (SI) is genetically controlled by a single multiallelic S locus. Previous analysis of S alleles in the Solanaceae, in which S locus ribonucleases (S RNases) are responsible for stylar expression of SI, has demonstrated that allelic diversity predated speciation within this family. To understand how allelic diversity has evolved, we investigated the molecular basis of gametophytic SI in Antirrhinum, a member of the Scrophulariaceae, which is closely related to the Solanaceae. We have characterized three Antirrhinum cDNAs encoding polypeptides homologous to S RNases and shown that they are encoded by genes at the S locus. RNA in situ hybridization revealed that the Antirrhinum S RNase are primarily expressed in the stylar transmitting tissue. This expression is consistent with their proposed role in arresting the growth of self-pollen tubes. S alleles from the Scrophulariaceae form a separate group from those of the Solanaceae, indicating that new S alleles have been generated since these families separated (approximately 40 million years). We propose that the recruitment of an ancestral RNase gene into SI occurred during an early stage of angiosperm evolution and that, since that time, new alleles subsequently have arisen at a low rate. PMID:8672882

  11. Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and post-stroke dementia: a hospital-based study from northern Iran.

    Rezaei, Sajjad; Asgari Mobarake, Karim; Saberi, Alia; Keshavarz, Parvaneh; Leili, Ehsan Kazemnejad

    2016-06-01

    Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with functional and cognitive outcomes of stroke and plays a key role in preventing neuronal death. This study aimed to answer the following question: does BDNF Val66Met polymorphism prognosticate survival status and risk of post-stroke dementia (PSD)? In a retrospective cohort study, 206 patients with ischemic stroke (IS) entered the study. They were consecutively being admitted to the neurology clinic in Poursina Hospital (northern Iran) from 2012 to 2014. The diagnosis of PSD was based on DSM-5 criteria. The current and the premorbid cognitive statuses of the patients were respectively assessed through the third edition of Addenbrooke's Cognitive Examination and the Informant Questionnaire on Cognitive Decline in the Elderly. BDNF Val66Met gene polymorphism was determined by PCR-RFLP. On average, 48 patients (23.3 %) developed PSD 6 months after IS. Log-rank test showed that the survival rate of at least one Val-allele carriers was significantly lower than that of Met/Met homozygotes (P = 0.0005), and the former developed PSD sooner than the latter (375, 492 days, respectively). Cox model showed that heterozygous carriers of Val/Met were at greater risk of PSD over time (HR 2.280, 95 % CI 1.566-4.106, P = 0.006). However, the risk ratio of patients with PSD among different BDNF genotypes decreased after adjusting demographic, clinical, and vascular risk factors, and was no longer statistically significant (AHR 2.434, 95 % CI 0.597-9.926, P = 0.215). Val-allele carriers or Val/Met genotypes were more quickly diagnosed as having dementia after IS. However, this genetic vulnerability became more destructive when it was added to demographic, clinical, and vascular risk factors.

  12. The brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism affects memory performance in older adults.

    Azeredo, Lucas A de; De Nardi, Tatiana; Levandowski, Mateus L; Tractenberg, Saulo G; Kommers-Molina, Julia; Wieck, Andrea; Irigaray, Tatiana Q; Silva, Irênio G da; Grassi-Oliveira, Rodrigo

    2017-01-01

    Memory impairment is an important contributor to the reduction in quality of life experienced by older adults, and genetic risk factors seem to contribute to variance in age-related cognitive decline. Brain-derived neurotrophic factor (BDNF) is an important nerve growth factor linked with development and neural plasticity. The Val66Met polymorphism in the BDNF gene has been associated with impaired episodic memory in adults, but whether this functional variant plays a role in cognitive aging remains unclear. The purpose of this study was to investigate the effects of the BDNF Val66Met polymorphism on memory performance in a sample of elderly adults. Eighty-seven subjects aged > 55 years were recruited using a community-based convenience sampling strategy in Porto Alegre, Brazil. The logical memory subset of the Wechsler Memory Scale-Revised was used to assess immediate verbal recall (IVR), delayed verbal recall (DVR), and memory retention rate. BDNF Met allele carriers had lower DVR scores (p = 0.004) and a decline in memory retention (p = 0.017) when compared to Val/Val homozygotes. However, we found no significant differences in IVR between the two groups (p = 0.088). These results support the hypothesis of the BDNF Val66Met polymorphism as a risk factor associated with cognitive impairment, corroborating previous findings in young and older adults.

  13. The brain-derived neurotrophic factor (BDNF gene Val66Met polymorphism affects memory performance in older adults

    Lucas A. de Azeredo

    Full Text Available Objective: Memory impairment is an important contributor to the reduction in quality of life experienced by older adults, and genetic risk factors seem to contribute to variance in age-related cognitive decline. Brain-derived neurotrophic factor (BDNF is an important nerve growth factor linked with development and neural plasticity. The Val66Met polymorphism in the BDNF gene has been associated with impaired episodic memory in adults, but whether this functional variant plays a role in cognitive aging remains unclear. The purpose of this study was to investigate the effects of the BDNF Val66Met polymorphism on memory performance in a sample of elderly adults. Methods: Eighty-seven subjects aged > 55 years were recruited using a community-based convenience sampling strategy in Porto Alegre, Brazil. The logical memory subset of the Wechsler Memory Scale-Revised was used to assess immediate verbal recall (IVR, delayed verbal recall (DVR, and memory retention rate. Results: BDNF Met allele carriers had lower DVR scores (p = 0.004 and a decline in memory retention (p = 0.017 when compared to Val/Val homozygotes. However, we found no significant differences in IVR between the two groups (p = 0.088. Conclusion: These results support the hypothesis of the BDNF Val66Met polymorphism as a risk factor associated with cognitive impairment, corroborating previous findings in young and older adults.

  14. Insulin-Independent GABAA Receptor-Mediated Response in the Barrel Cortex of Mice with Impaired Met Activity.

    Lo, Fu-Sun; Erzurumlu, Reha S; Powell, Elizabeth M

    2016-03-30

    Autism spectrum disorder (ASD) is a neurodevelopmental disorder caused by genetic variants, susceptibility alleles, and environmental perturbations. The autism associated geneMETtyrosine kinase has been implicated in many behavioral domains and endophenotypes of autism, including abnormal neural signaling in human sensory cortex. We investigated somatosensory thalamocortical synaptic communication in mice deficient in Met activity in cortical excitatory neurons to gain insights into aberrant somatosensation characteristic of ASD. The ratio of excitation to inhibition is dramatically increased due to decreased postsynaptic GABAAreceptor-mediated inhibition in the trigeminal thalamocortical pathway of mice lacking active Met in the cerebral cortex. Furthermore, in contrast to wild-type mice, insulin failed to increase GABAAreceptor-mediated response in the barrel cortex of mice with compromised Met signaling. Thus, lacking insulin effects may be a risk factor in ASD pathogenesis. A proposed common cause of neurodevelopmental disorders is an imbalance in excitatory neural transmission, provided by the glutamatergic neurons, and the inhibitory signals from the GABAergic interneurons. Many genes associated with autism spectrum disorders impair synaptic transmission in the expected cell type. Previously, inactivation of the autism-associated Met tyrosine kinase receptor in GABAergic interneurons led to decreased inhibition. In thus report, decreased Met signaling in glutamatergic neurons had no effect on excitation, but decimated inhibition. Further experiments indicate that loss of Met activity downregulates GABAAreceptors on glutamatergic neurons in an insulin independent manner. These data provide a new mechanism for the loss of inhibition and subsequent abnormal excitation/inhibition balance and potential molecular candidates for treatment or prevention. Copyright © 2016 the authors 0270-6474/16/363691-07$15.00/0.

  15. Procedures for identifying S-allele genotypes of Brassica.

    Wallace, D H

    1979-11-01

    Procedures are described for efficient selection of: (1) homozygous and heterozygous S-allele genotypes; (2) homozygous inbreds with the strong self- and sib-incompatibility required for effective seed production of single-cross F1 hybrids; (3) heterozygous genotypes with the high self- and sib-incompatibility required for effective seed production of 3- and 4-way hybrids.From reciprocal crosses between two first generation inbred (I1) plants there are three potential results: both crosses are incompatible; one is incompatible and the other compatible; and both are compatible. Incompatibility of both crosses is useful information only when combined with data from other reciprocal crosses. Each compatible cross, depending on whether its reciprocal is incompatible or compatible, dictates alternative reasoning and additional reciprocal crosses for efficiently and simultaneously identifying: (A) the S-allele genotype of all individual I1 plants, and (B) the expressions of dominance or codominance in pollen and stigma (sexual organs) of an S-allele heterozygous genotype. Reciprocal crosses provide the only efficient means of identifying S-allele genotypes and also the sexual-organ x S-allele-interaction types.Fluorescent microscope assay of pollen tube penetration into the style facilitates quantitation within 24-48 hours of incompatibility and compatibility of the reciprocal crosses. A procedure for quantitating the reciprocal difference is described that maximizes informational content of the data about interactions between S alleles in pollen and stigma of the S-allele-heterozygous genotype.Use of the non-inbred Io generation parent as a 'known' heterozygous S-allele genotype in crosses with its first generation selfed (I1) progeny usually reduces at least 7 fold the effort required for achieving objectives 1, 2, and 3, compared to the method of making reciprocal crosses only among I1 plants.Identifying the heterozygous and both homozygous S-allele genotypes during

  16. Beam loading

    Gamp, Alexander

    2013-01-01

    We begin by giving a description of the radio-frequency generator-cavity-beam coupled system in terms of basic quantities. Taking beam loading and cavity detuning into account, expressions for the cavity impedance as seen by the generator and as seen by the beam are derived. Subsequently methods of beam-loading compensation by cavity detuning, radio-frequency feedback and feedforward are described. Examples of digital radio-frequency phase and amplitude control for the special case of superconducting cavities are also given. Finally, a dedicated phase loop for damping synchrotron oscillations is discussed.

  17. Beam loading

    Gamp, Alexander

    2013-01-01

    We begin by giving a description of the radio-frequency generator-cavity-beam coupled system in terms of basic quantities. Taking beam loading and cavity detuning into account, expressions for the cavity impedance as seen by the generator and as seen by the beam are derived. Subsequently methods of beam-loading compensation by cavity detuning, radio-frequency feedback and feedforward are described. Examples of digital radio-frequency phase and amplitude control for the special case of superconducting cavities are also given. Finally, a dedicated phase loop for damping synchrotron oscillations is discussed. (author)

  18. MET Expression in Primary and Metastatic Clear Cell Renal Cell Carcinoma: Implications of Correlative Biomarker Assessment to MET Pathway Inhibitors

    Brian Shuch

    2015-01-01

    Full Text Available Aims. Inhibitors of the MET pathway hold promise in the treatment for metastatic kidney cancer. Assessment of predictive biomarkers may be necessary for appropriate patient selection. Understanding MET expression in metastases and the correlation to the primary site is important, as distant tissue is not always available. Methods and Results. MET immunofluorescence was performed using automated quantitative analysis and a tissue microarray containing matched nephrectomy and distant metastatic sites from 34 patients with clear cell renal cell carcinoma. Correlations between MET expressions in matched primary and metastatic sites and the extent of heterogeneity were calculated. The mean expression of MET was not significantly different between primary tumors when compared to metastases (P=0.1. MET expression weakly correlated between primary and matched metastatic sites (R=0.5 and a number of cases exhibited very high levels of discordance between these tumors. Heterogeneity within nephrectomy specimens compared to the paired metastatic tissues was not significantly different (P=0.39. Conclusions. We found that MET expression is not significantly different in primary tumors than metastatic sites and only weakly correlates between matched sites. Moderate concordance of MET expression and significant expression heterogeneity may be a barrier to the development of predictive biomarkers using MET targeting agents.

  19. Aptamers Binding to c-Met Inhibiting Tumor Cell Migration.

    Birgit Piater

    Full Text Available The human receptor tyrosine kinase c-Met plays an important role in the control of critical cellular processes. Since c-Met is frequently over expressed or deregulated in human malignancies, blocking its activation is of special interest for therapy. In normal conditions, the c-Met receptor is activated by its bivalent ligand hepatocyte growth factor (HGF. Also bivalent antibodies can activate the receptor by cross linking, limiting therapeutic applications. We report the generation of the RNA aptamer CLN64 containing 2'-fluoro pyrimidine modifications by systematic evolution of ligands by exponential enrichment (SELEX. CLN64 and a previously described single-stranded DNA (ssDNA aptamer CLN3 exhibited high specificities and affinities to recombinant and cellular expressed c-Met. Both aptamers effectively inhibited HGF-dependent c-Met activation, signaling and cell migration. We showed that these aptamers did not induce c-Met activation, revealing an advantage over bivalent therapeutic molecules. Both aptamers were shown to bind overlapping epitopes but only CLN3 competed with HGF binding to cMet. In addition to their therapeutic and diagnostic potential, CLN3 and CLN64 aptamers exhibit valuable tools to further understand the structural and functional basis for c-Met activation or inhibition by synthetic ligands and their interplay with HGF binding.

  20. Alternative Fuels Data Center: Workplace Charging Success: MetLife

    future." Several others noted that their decision to purchase or lease a PEV was based on MetLife's : MetLife " By making PEV charging stations more readily available to employees, we can encourage more promote alternative transportation. By making PEV charging stations more readily available to employees

  1. Invloed krachtvoerniveau op vleesproduktiekenmerken van Piemontese met zwartbont kruislingstieren

    Hanekamp, W.J.A.

    1989-01-01

    Met 3 ronden van elk 36 Piemontese X zwartbonte kruislingstieren is het effect van extra krachtvoer vergeleken met de normaal gangbare gift naast onbeperkt snijmaoskuil. De stieren waren gehuisvest in een natuurlijk geventileerde stal (space-boarding)en op een volledige roostervloer.

  2. Interview met Leon Deben: van tegenstellingen leer je het meeste

    van Diepen, A.; Huisman, C.

    2008-01-01

    Wat in de jaren zeventig begonnen is als Sociologie van bouwen en wonen is uitgegroeid tot Stadssociologie. Leon Deben heeft het medeopgebouwd. Hij nam onlangs afscheid van de universiteit met een rede over de openbare ruimte. "Het centrale bestuur van de stad is druk met de waan van de dag en dan

  3. Mindfulness voor volwassenen met een licht verstandelijke beperking

    Punt, M.; Helmond, P.E.; Meirmans, M.; Otten, R.; Speckens, A.E.M.

    2016-01-01

    Mensen met een licht verstandelijke beperking (LVB) hebben veelal te maken met een opeenstapeling van verschillende biologische, psychologische en sociale factoren, waardoor zij vijf tot zes keer meer kans hebben op het ontwikkelen van psychopathologie dan normaal begaafden (Allen, 2008; Buckles,

  4. 'Epistemology models ontology'− In gesprek met John Polkinghorne

    Test

    7 Jun 2011 ... maar met die aard daarvan. Polkinghorne wil met sy boek One World (1996) presies sê wat die titel suggereer. Hiervoor kry hy die oplossing by sy mentor en latere kollega, Paul Dirac. Vir meer as 30 jaar het Dirac dieselfde leerstoel in Fisika aan Cambridge beklee as Isaac Newton (Polkinghorne 2005:34).

  5. Efficacy of c-Met inhibitor for advanced prostate cancer

    Tu, William H; Zhu, Chunfang; Clark, Curtis; Christensen, James G; Sun, Zijie

    2010-01-01

    Aberrant expression of HGF/SF and its receptor, c-Met, often correlates with advanced prostate cancer. Our previous study showed that expression of c-Met in prostate cancer cells was increased after attenuation of androgen receptor (AR) signalling. This suggested that current androgen ablation therapy for prostate cancer activates c-Met expression and may contribute to development of more aggressive, castration resistant prostate cancer (CRPC). Therefore, we directly assessed the efficacy of c-Met inhibition during androgen ablation on the growth and progression of prostate cancer. We tested two c-Met small molecule inhibitors, PHA-665752 and PF-2341066, for anti-proliferative activity by MTS assay and cell proliferation assay on human prostate cancer cell lines with different levels of androgen sensitivity. We also used renal subcapsular and castrated orthotopic xenograft mouse models to assess the effect of the inhibitors on prostate tumor formation and progression. We demonstrated a dose-dependent inhibitory effect of PHA-665752 and PF-2341066 on the proliferation of human prostate cancer cells and the phosphorylation of c-Met. The effect on cell proliferation was stronger in androgen insensitive cells. The c-Met inhibitor, PF-2341066, significantly reduced growth of prostate tumor cells in the renal subcapsular mouse model and the castrated orthotopic mouse model. The effect on cell proliferation was greater following castration. The c-Met inhibitors demonstrated anti-proliferative efficacy when combined with androgen ablation therapy for advanced prostate cancer

  6. Load sensor

    Van den Ende, D.; Almeida, P.M.R.; Dingemans, T.J.; Van der Zwaag, S.

    2007-01-01

    The invention relates to a load sensor comprising a polymer matrix and a piezo-ceramic material such as PZT, em not bedded in the polymer matrix, which together form a compos not ite, wherein the polymer matrix is a liquid crystalline resin, and wherein the piezo-ceramic material is a PZT powder

  7. Carbohydrate Loading.

    Csernus, Marilyn

    Carbohydrate loading is a frequently used technique to improve performance by altering an athlete's diet. The objective is to increase glycogen stored in muscles for use in prolonged strenuous exercise. For two to three days, the athlete consumes a diet that is low in carbohydrates and high in fat and protein while continuing to exercise and…

  8. Absence of the HLA-G*0113N allele in Amerindian populations from the Brazilian Amazon region.

    Mendes-Junior, Celso T; Castelli, Erick C; Moreau, Philippe; Simões, Aguinaldo L; Donadi, Eduardo A

    2010-04-01

    The HLA-G gene is predominantly expressed at the maternal-fetal interface and has been associated with maternal-fetal tolerance. The HLA-G*0113N is a null allele defined by the insertion of a premature stop codon at exon 2, observed in a single Ghanaian individual. Likewise the G*0105N allele, the occurrence of the HLA-G*0113N in a population from an area with high pathogen load suggests that the reduced HLA-G expression in G*0113N heterozygous placentas could improve the intrauterine defense against infections. The presence of the G*0113N allele here was investigated in 150 Amerindians from five isolated tribes that inhabit the Central Amazon and in 295 admixed individuals from the State of São Paulo, Southeastern Brazil, previously genotyped for HLA-G. No copy of the G*0113N null allele was found in both population samples by exon 2 sequence-based analysis, reinforcing its restricted occurrence in Africa.

  9. Detecting imbalanced expression of SNP alleles by minisequencing on microarrays

    Dahlgren Andreas

    2004-10-01

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

  10. Drop-out probabilities of IrisPlex SNP alleles

    Andersen, Jeppe Dyrberg; Tvedebrink, Torben; Mogensen, Helle Smidt

    2013-01-01

    In certain crime cases, information about a perpetrator's phenotype, including eye colour, may be a valuable tool if no DNA profile of any suspect or individual in the DNA database matches the DNA profile found at the crime scene. Often, the available DNA material is sparse and allelic drop-out...... of true alleles is possible. As part of the validation of the IrisPlex assay in our ISO17025 accredited, forensic genetic laboratory, we estimated the probability of drop-out of specific SNP alleles using 29 and 30 PCR cycles and 25, 50 and 100 Single Base Extension (SBE) cycles. We observed no drop-out...... when the amount of DNA was greater than 125 pg for 29 cycles of PCR and greater than 62 pg for 30 cycles of PCR. With the use of a logistic regression model, we estimated the allele specific probability of drop-out in heterozygote systems based on the signal strength of the observed allele...

  11. Common breast cancer risk alleles and risk assessment

    Näslund-Koch, C; Nordestgaard, B G; Bojesen, S E

    2017-01-01

    general population were followed in Danish health registries for up to 21 years after blood sampling. After genotyping 72 breast cancer risk loci, each with 0-2 alleles, the sum for each individual was calculated. We used the simple allele sum instead of the conventional polygenic risk score......, as it is likely more sensitive in detecting associations with risks of other endpoints than breast cancer. RESULTS: Breast cancer incidence in the 19,010 women was increased across allele sum quintiles (log-rank trend test; p=1*10(-12)), but not incidence of other cancers (p=0.41). Age- and study-adjusted hazard...... ratio for the 5(th) vs. 1(st) allele sum quintile was 1.82(95% confidence interval;1.53-2.18). Corresponding hazard ratios per allele were 1.04(1.03-1.05) and 1.05(1.02-1.08) for breast cancer incidence and mortality, similar across risk factors. In 50-year old women, the starting age for screening...

  12. A strategy to discover genes that carry multi-allelic or mono-allelic risk for common diseases: A cohort allelic sums test (CAST)

    Morgenthaler, Stephan; Thilly, William G.

    2007-01-01

    A method is described to discover if a gene carries one or more allelic mutations that confer risk for any specified common disease. The method does not depend upon genetic linkage of risk-conferring mutations to high frequency genetic markers such as single nucleotide polymorphisms. Instead, the sums of allelic mutation frequencies in case and control cohorts are determined and a statistical test is applied to discover if the difference in these sums is greater than would be expected by chance. A statistical model is presented that defines the ability of such tests to detect significant gene-disease relationships as a function of case and control cohort sizes and key confounding variables: zygosity and genicity, environmental risk factors, errors in diagnosis, limits to mutant detection, linkage of neutral and risk-conferring mutations, ethnic diversity in the general population and the expectation that among all exonic mutants in the human genome greater than 90% will be neutral with regard to any effect on disease risk. Means to test the null hypothesis for, and determine the statistical power of, each test are provided. For this 'cohort allelic sums test' or 'CAST', the statistical model and test are provided as an Excel (TM) program, CASTAT (C) at http://epidemiology.mit.edu. Based on genetics, technology and statistics, a strategy of enumerating the mutant alleles carried in the exons and splice sites of the estimated ∼25,000 human genes in case cohort samples of 10,000 persons for each of 100 common diseases is proposed and evaluated: A wide range of possible conditions of multi-allelic or mono-allelic and monogenic, multigenic or polygenic (including epistatic) risk are found to be detectable using the statistical criteria of 1 or 10 ''false positive'' gene associations per 25,000 gene-disease pair-wise trials and a statistical power of >0.8. Using estimates of the distribution of both neutral and gene-inactivating nondeleterious mutations in humans and

  13. The COMT Val158 Met polymorphism as an associated risk factor for Alzheimer disease and mild cognitive impairment in APOE 4 carriers

    Borda Sandra

    2009-09-01

    Full Text Available Abstract Background The aim of this study is to examine the influence of the catechol-O-methyltranferase (COMT gene (polymorphism Val158 Met as a risk factor for Alzheimer's disease (AD and mild cognitive impairment of amnesic type (MCI, and its synergistic effect with the apolipoprotein E gene (APOE. A total of 223 MCI patients, 345 AD and 253 healthy controls were analyzed. Clinical criteria and neuropsychological tests were used to establish diagnostic groups. The DNA Bank of the University of the Basque Country (UPV-EHU (Spain determined COMT Val158 Met and APOE genotypes using real time polymerase chain reaction (rtPCR and polymerase chain reaction (PCR, and restriction fragment length polymorphism (RFLPs, respectively. Multinomial logistic regression models were used to determine the risk of AD and MCI. Results Neither COMT alleles nor genotypes were independent risk factors for AD or MCI. The high activity genotypes (GG and AG showed a synergistic effect with APOE ε4 allele, increasing the risk of AD (OR = 5.96, 95%CI 2.74-12.94, p In MCI patients such as synergistic effect was only found between AG and APOE ε4 allele (OR = 3.21 95%CI 1.56-6.63, p = 0.02 and was greater in men (OR = 5.88 95%CI 1.69-20.42, p Conclusion COMT (Val158 Met polymorphism is not an independent risk factor for AD or MCI, but shows a synergistic effect with APOE ε4 allele that proves greater in women with AD.

  14. Implication of HLA-DMA Alleles in Corsican IDDM

    P. Cucchi-Mouillot

    1998-01-01

    Full Text Available The HLA-DM molecule catalyses the CLIP/antigen peptide exchange in the classical class II peptide-binding groove. As such, DM is an antigen presentation regulator and may be linked to autoimmune diseases. Using PCR derived methods, a relationship was revealed between DM gene polymorphism and IDDM, in a Corsican population. The DMA*0101 allele was observed to confer a significant predisposition to this autoimmune disease while the DMA*0102 allele protected significantly. Experiments examining polymorphism of the HLA-DRB1 gene established that these relationships are not a consequence of linkage disequilibrium with HLA-DRB1 alleles implicated in this pathology. The study of the DMA gene could therefore be an additional tool for early IDDM diagnosis in the Corsican population.

  15. Load sensor

    Van den Ende, D.; Almeida, P.M.R.; Dingemans, T.J.; Van der Zwaag, S.

    2007-01-01

    The invention relates to a load sensor comprising a polymer matrix and a piezo-ceramic material such as PZT, em not bedded in the polymer matrix, which together form a compos not ite, wherein the polymer matrix is a liquid crystalline resin, and wherein the piezo-ceramic material is a PZT powder forming 30-60% by volume of the composite, and wherein the PZT powder forms 40-50% by volume of the composite.

  16. Population differentiation in allele frequencies of obesity-associated SNPs.

    Mao, Linyong; Fang, Yayin; Campbell, Michael; Southerland, William M

    2017-11-10

    Obesity is emerging as a global health problem, with more than one-third of the world's adult population being overweight or obese. In this study, we investigated worldwide population differentiation in allele frequencies of obesity-associated SNPs (single nucleotide polymorphisms). We collected a total of 225 obesity-associated SNPs from a public database. Their population-level allele frequencies were derived based on the genotype data from 1000 Genomes Project (phase 3). We used hypergeometric model to assess whether the effect allele at a given SNP is significantly enriched or depleted in each of the 26 populations surveyed in the 1000 Genomes Project with respect to the overall pooled population. Our results indicate that 195 out of 225 SNPs (86.7%) possess effect alleles significantly enriched or depleted in at least one of the 26 populations. Populations within the same continental group exhibit similar allele enrichment/depletion patterns whereas inter-continental populations show distinct patterns. Among the 225 SNPs, 15 SNPs cluster in the first intron region of the FTO gene, which is a major gene associated with body-mass index (BMI) and fat mass. African populations exhibit much smaller blocks of LD (linkage disequilibrium) among these15 SNPs while European and Asian populations have larger blocks. To estimate the cumulative effect of all variants associated with obesity, we developed the personal composite genetic risk score for obesity. Our results indicate that the East Asian populations have the lowest averages of the composite risk scores, whereas three European populations have the highest averages. In addition, the population-level average of composite genetic risk scores is significantly correlated (R 2 = 0.35, P = 0.0060) with obesity prevalence. We have detected substantial population differentiation in allele frequencies of obesity-associated SNPs. The results will help elucidate the genetic basis which may contribute to population

  17. A common mutation associated with the Duarte galactosemia allele

    Elsas, L.J.; Dembure, P.P.; Langley, S.; Paulk, E.M.; Hjelm, L.N.; Fridovich-Keil, J. (Emory Univ. School of Medicine, Atlanta, GA (United States))

    1994-06-01

    The human cDNA and gene for galactose-1-phosphate uridyl transferase (GALT) have been cloned and sequenced. A prevalant mutation (Q188R) is known to cause classic galactosemia (G/G). G/G galactosemia has an incidence of 1/38,886 in 1,396,766 Georgia live-born infants, but a more common variant of galactosemia, Duarte, has an unknown incidence. The proposed Duarte biochemical phenotypes of GALT are as follows: D/N, D/D, and D/G, which have [approximately]75%, 50%, and 25% of normal GALT activity, respectively. In addition, the D allele has isoforms of its enzyme that have more acidic pI than normal. Here the authors systematically determine (a) the prevalence of an A-to-G transition at base pair 2744 of exon 10 in the GALT gene, a transition that produces a codon change converting asparagine to aspartic acid at position 314 (N314D), and (b) the association of this mutation with the Duarte biochemical phenotype. The 2744G nucleotide change adds an AvaII (SinI) cut site, which was identified in PCR-amplified DNA. In 111 biochemically unphenotyped controls with no history of galactosemia, 13 N314D alleles were identified (prevalence 5.9%). In a prospective study, 40 D alleles were biochemically phenotyped, and 40 N314D alleles were found. By contrast, in 36 individuals known not to have the Duarte biochemical phenotype, no N314D alleles were found. The authors conclude that the N314D mutation is a common allele that probably causes the Duarte GALT biochemical phenotype and occurs in a predominantly Caucasian, nongalactosemic population, with a prevalence of 5.9%. 36 refs., 3 figs., 2 tabs.

  18. Distribution of a pseudodeficiency allele among Tay-Sachs carriers

    Tomczak, J.; Grebner, E.E. (Thomas Jefferson Univ., Philadelphia, PA (United States)); Boogen, C. (Univ. of Essen Medical School (Germany))

    1993-08-01

    Recently Triggs-Raine et al. (1992) identified a new mutation in the gene coding for the [alpha]-subunit of [beta]-hexosaminidase A (hex A), the enzyme whose deficiency causes Tay-Sachs disease. This mutation, a C[sub 739]-to-T transition in exon 7, results in an altered enzyme that is active (albeit at reduced levels) in cells but that has essentially no activity in serum. This so-called pseudodeficient allele was first detected in compound heterozygotes who also carried a Tay-Sachs disease allele and therefore had no detectable hex A in their serum but who were in good health. Carriers of this apparently benign mutation are generally indistinguishable from carriers of a lethal mutation by means of routine enzyme-based screening tests, because the product of the pseudodeficient allele is not detectable in serum and has decreased activity in cells. This suggests that some individuals who have been classified as Tay-Sachs carriers are actually carriers of the pseudodeficient allele and are not at risk to have a child affected with Tay-Sachs disease. The pseudodeficient allele may also be responsible for some inconclusive diagnoses, where leukocyte values fall below the normal range but are still above the carrier range. The fact that there are now two mutant alleles (the psuedodeficient and the adult) that are indistinguishable from the lethal infantile mutations by means of enzyme assay yet that are phenotypically very different and that together may account for as much as 12% of enzyme-defined carriers on the basis of the data here suggests that DNA analysis should be part of a comprehensive screening program. It will be particularly useful to identify the mutations in couples at risk, before they undergo prenatal diagnosis. DNA analysis will also resolve some inconclusive diagnoses.

  19. Reduced Height (Rht Alleles Affect Wheat Grain Quality.

    Richard Casebow

    Full Text Available The effects of dwarfing alleles (reduced height, Rht in near isogenic lines on wheat grain quality are characterised in field experiments and related to effects on crop height, grain yield and GA-sensitivity. Alleles included those that conferred GA-insensitivity (Rht-B1b, Rht-B1c, Rht-D1b, Rht-D1c as well as those that retained GA-sensitivity (rht(tall, Rht8, Rht8 + Ppd-D1a, Rht12. Full characterisation was facilitated by including factors with which the effects of Rht alleles are known to interact for grain yield (i.e. system, [conventional or organic]; tillage intensity [plough-based, minimum or zero]; nitrogen fertilizer level [0-450 kg N/ha]; and genetic backgrounds varying in height [cvs Maris Huntsman, Maris Widgeon, and Mercia]. Allele effects on mean grain weight and grain specific weight were positively associated with final crop height: dwarfing reduced these quality criteria irrespective of crop management or GA-sensitivity. In all but two experiments the effects of dwarfing alleles on grain nitrogen and sulphur concentrations were closely and negatively related to effects on grain yield, e.g. a quadratic relationship between grain yield and crop height manipulated by the GA-insensitive alleles was mirrored by quadratic relationships for nitrogen and sulphur concentrations: the highest yields and most dilute concentrations occurred around 80cm. In one of the two exceptional experiments the GA-insensitive Rht-B1b and Rht-B1c significantly (P<0.05 reduced grain nitrogen concentration in the absence of an effect on yield, and in the remaining experiment the GA-sensitive Rht8 significantly reduced both grain yield and grain nitrogen concentration simultaneously. When Rht alleles diluted grain nitrogen concentration, N:S ratios and SDS-sedimentation volumes were often improved. Hagberg falling number (HFN was negatively related to crop height but benefits from dwarfing were only seen for GA-insensitive alleles. For HFN, therefore, there

  20. Reduced Height (Rht) Alleles Affect Wheat Grain Quality.

    Casebow, Richard; Hadley, Caroline; Uppal, Rajneet; Addisu, Molla; Loddo, Stefano; Kowalski, Ania; Griffiths, Simon; Gooding, Mike

    2016-01-01

    The effects of dwarfing alleles (reduced height, Rht) in near isogenic lines on wheat grain quality are characterised in field experiments and related to effects on crop height, grain yield and GA-sensitivity. Alleles included those that conferred GA-insensitivity (Rht-B1b, Rht-B1c, Rht-D1b, Rht-D1c) as well as those that retained GA-sensitivity (rht(tall), Rht8, Rht8 + Ppd-D1a, Rht12). Full characterisation was facilitated by including factors with which the effects of Rht alleles are known to interact for grain yield (i.e. system, [conventional or organic]; tillage intensity [plough-based, minimum or zero]; nitrogen fertilizer level [0-450 kg N/ha]; and genetic backgrounds varying in height [cvs Maris Huntsman, Maris Widgeon, and Mercia]. Allele effects on mean grain weight and grain specific weight were positively associated with final crop height: dwarfing reduced these quality criteria irrespective of crop management or GA-sensitivity. In all but two experiments the effects of dwarfing alleles on grain nitrogen and sulphur concentrations were closely and negatively related to effects on grain yield, e.g. a quadratic relationship between grain yield and crop height manipulated by the GA-insensitive alleles was mirrored by quadratic relationships for nitrogen and sulphur concentrations: the highest yields and most dilute concentrations occurred around 80cm. In one of the two exceptional experiments the GA-insensitive Rht-B1b and Rht-B1c significantly (Pgrain nitrogen concentration in the absence of an effect on yield, and in the remaining experiment the GA-sensitive Rht8 significantly reduced both grain yield and grain nitrogen concentration simultaneously. When Rht alleles diluted grain nitrogen concentration, N:S ratios and SDS-sedimentation volumes were often improved. Hagberg falling number (HFN) was negatively related to crop height but benefits from dwarfing were only seen for GA-insensitive alleles. For HFN, therefore, there was the strongest evidence for

  1. A common allele on chromosome 9 associated with coronary heartdisease

    McPherson, Ruth; Pertsemlidis, Alexander; Kavaslar, Nihan; Stewart, Alexandre; Roberts, Robert; Cox, David R.; Hinds, David; Pennachio, Len; Tybjaerg-Hansen, Anne; Folsom, Aaron R.; Boerwinkle,Eric; Hobbs, Helen H.; Cohen, Jonathan C.

    2007-03-01

    Coronary heart disease (CHD) is a major cause of death in Western countries. Here we used genome-wide association scanning to identify a 58 kb interval on chromosome 9 that was consistently associated with CHD in six independent samples. The interval contains no annotated genes and is not associated with established CHD risk factors such as plasma lipoproteins, hypertension or diabetes. Homozygotes for the risk allele comprise 20-25% of Caucasians and have a {approx}30-40% increased risk of CHD. These data indicate that the susceptibility allele acts through a novel mechanism to increase CHD risk in a large fraction of the population.

  2. COMT Val158Met genotype is associated with reward learning: A replication study and meta-analysis

    Corral-Frías, Nadia S.; Pizzagalli, Diego A.; Carré, Justin; Michalski, Lindsay J; Nikolova, Yuliya S.; Perlis, Roy H.; Fagerness, Jesen; Lee, Mary R.; Conley, Emily Drabant; Lancaster, Thomas M.; Haddad, Stephen; Wolf, Aaron; Smoller, Jordan W.; Hariri, Ahmad R.; Bogdan, Ryan

    2016-01-01

    Identifying mechanisms through which individual differences in reward learning emerge offers an opportunity to understand both a fundamental form of adaptive responding as well as etiological pathways through which aberrant reward learning may contribute to maladaptive behaviors and psychopathology. One candidate mechanism through which individual differences in reward learning may emerge is variability in dopaminergic reinforcement signaling. A common functional polymorphism within the catechol-O-methyl transferase gene (COMT; rs4680, Val158Met) has been linked to reward learning where homozygosity for the Met allele (associated with heightened prefrontal dopamine function and decreased dopamine synthesis in the midbrain) has been associated with relatively increased reward learning. Here, we used a probabilistic reward learning task to asses response bias, a behavioral form of reward learning, across 3 separate samples that were combined for analyses (age: 21.80 ± 3.95; n=392; 268 female; European-American, n=208). We replicate prior reports that COMT rs4680 Met allele homozygosity is associated with increased reward learning in European-American participants (β=0.20, t= 2.75, p< 0.01; ΔR2= 0.04). Moreover, a meta-analysis of 4 studies, including the current one, confirmed the association between COMT rs4680 genotype and reward learning (95% CI −0.11 to −0.03; z=3.2; p<0.01). These results suggest that variability in dopamine signaling associated with COMT rs4680 influences individual differences in reward which may potentially contribute to psychopathology characterized by reward dysfunction. PMID:27138112

  3. Associations of Leu72Met Polymorphism of Preproghrelin with Ratios of Plasma Lipids Are Diversified by a High-Carbohydrate Diet in Healthy Chinese Adolescents.

    Su, Mi; Qiu, Li; Wang, Qian; Jiang, Zhen; Liu, Xiao Juan; Lin, Jia; Fang, Ding Zhi

    2015-01-01

    The association of preproghrelin Leu72Met polymorphism with plasma lipids profile was inconsistently reported and needs more studies to be confirmed. Our study was to investigate the changes of plasma lipids ratios after a high-carbohydrate (high-CHO) diet in healthy Chinese adolescents with different genotypes of this polymorphism. Fifty-three healthy university students were given a washout diet of 54.1% carbohydrate for 7 days, followed by a high-CHO diet of 70.1% carbohydrate for 6 days. The anthropometric and biological parameters were analyzed at baseline and before and after the high-CHO diet. When compared with those before the high-CHO diet, body mass index (BMI) decreased in the male and female Met72 allele carriers. Decreased low-/high-density lipoprotein cholesterol (LDL-C/HDL-C) was observed in all participants except the female subjects with the Leu72Leu genotype. TG/HDL-C and log (TG/HDL-C) were increased only in the female subjects with the Leu72Leu genotype. These results suggest that the Met72 allele of preproghrelin Leu72Met polymorphism may be associated with decreased BMI induced by the high-CHO diet in male and female adolescents, while the Leu72 allele with increased TG/HDL-C and log (TG/HDL-C) in the female adolescents only. Furthermore, the decreasing effect of the high-CHO diet on LDL/HDL-C may be eliminated in the female Leu72Leu homozygotes. © 2015 S. Karger AG, Basel.

  4. The BDNF Val66Met polymorphism has opposite effects on memory circuits of multiple sclerosis patients and controls.

    Francesco Fera

    Full Text Available Episodic memory deficits are frequent symptoms in Multiple Sclerosis and have been associated with dysfunctions of the hippocampus, a key region for learning. However, it is unclear whether genetic factors that influence neural plasticity modulate episodic memory in MS. We thus studied how the Brain Derived Neurotrophic Factor Val(66Met genotype, a common polymorphism influencing the hippocampal function in healthy controls, impacted on brain networks underlying episodic memory in patients with Multiple Sclerosis. Functional magnetic resonance imaging was used to assess how the Brain Derived Neurotrophic Factor Val(66Met polymorphism modulated brain regional activity and functional connectivity in 26 cognitively unimpaired Multiple Sclerosis patients and 25 age- and education-matched healthy controls while performing an episodic memory task that included encoding and retrieving visual scenes. We found a highly significant group by genotype interaction in the left posterior hippocampus, bilateral parahippocampus, and left posterior cingulate cortex. In particular, Multiple Sclerosis patients homozygous for the Val(66 allele, relative to Met(66 carriers, showed greater brain responses during both encoding and retrieval while the opposite was true for healthy controls. Furthermore, a robust group by genotype by task interaction was detected for the functional connectivity between the left posterior hippocampus and the ipsilateral posterior cingulate cortex. Here, greater hippocampus-posterior cingulate cortex connectivity was observed in Multiple Sclerosis Met(66 carriers relative to Val(66 homozygous during retrieval (but not encoding while, again, the reverse was true for healthy controls. The Val(66Met polymorphism has opposite effects on hippocampal circuitry underlying episodic memory in Multiple Sclerosis patients and healthy controls. Enhancing the knowledge of how genetic factors influence cognitive functions may improve the clinical

  5. Role of Met Axis in Head and Neck Cancer

    Xu, Yiru, E-mail: xuyiru@umich.edu; Fisher, Gary J., E-mail: xuyiru@umich.edu [Department of Dermatology, University of Michigan, Ann Arbor, MI 48109 (United States)

    2013-11-26

    Head and neck cancer is the sixth most common type of cancer worldwide. Despite advances in aggressive multidisciplinary treatments, the 5-year survival rate for this dreadful disease is only 50%, mostly due to high rate of recurrence and early involvement of regional lymph nodes and subsequent metastasis. Understanding the molecular mechanisms responsible for invasion and metastasis is one of the most pressing goals in the field of head and neck cancer. Met, also known as hepatocyte growth factor receptor (HGFR), is a member of the receptor protein tyrosine kinase (RPTK) family. There is compelling evidence that Met axis is dysregulated and plays important roles in tumorigenesis, progression, metastasis, angiogenesis, and drug resistance in head and neck cancer. We describe in this review current understanding of Met axis in head and neck cancer biology and development of therapeutic inhibitors targeting Met axis.

  6. Met flora meer fauna de stad in trekken

    Hoffman, M.H.A.

    2010-01-01

    Meer flora en fauna in de stedelijke omgeving begint met de aanplant van gevarieerd groen. Plant Publicity Holland geeft in een overzicht aan welke bomen, heesters en vaste planten daarvoor geschikt zijn.

  7. Mars MetNet Mission - Martian Atmospheric Observational Post Network

    Harri, A.-M.; Haukka, H.; Aleksashkin, S.; Arruego, I.; Schmidt, W.; Genzer, M.; Vazquez, L.; Siikonen, T.; Palin, M.

    2017-09-01

    A new kind of planetary exploration mission for Mars is under development in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested.

  8. Leven met de varroamijt in de 21ste eeuw

    Blacquiere, T.; Cornelissen, B.; Smeekens, C.C.; Steen, van der J.J.M.

    2002-01-01

    Overzicht van voorhanden bestrijdingsmethoden tegen Varroa destructor op de korte termijn en vooruitzichten voor de bestrijding op langere termijn. In de nabije toekomst gaat het om bestrijding met diergeneesmiddelen van natuurlijke oorsprong (mierenzuur, oxaalzuur, thymol) in het kader van een

  9. Mars MetNet Mission - Martian Atmospheric Observational Post Network

    Hari, Ari-Matti; Haukka, Harri; Aleksashkin, Sergey; Arruego, Ignacio; Schmidt, Walter; Genzer, Maria; Vazquez, Luis; Siikonen, Timo; Palin, Matti

    2017-04-01

    A new kind of planetary exploration mission for Mars is under development in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested. 1. MetNet Lander The MetNet landing vehicles are using an inflatable entry and descent system instead of rigid heat shields and parachutes as earlier semi-hard landing devices have used. This way the ratio of the payload mass to the overall mass is optimized. The landing impact will burrow the payload container into the Martian soil providing a more favorable thermal environment for the electronics and a suitable orientation of the telescopic boom with external sensors and the radio link antenna. It is planned to deploy several tens of MNLs on the Martian surface operating at least partly at the same time to allow meteorological network science. 2. Strawman Scientific Payload The strawman payload of the two MNL precursor models includes the following instruments: Atmospheric instruments: - MetBaro Pressure device - MetHumi Humidity device - MetTemp Temperature sensors Optical devices: - PanCam Panoramic - MetSIS Solar irradiance sensor with OWLS optical wireless system for data transfer - DS Dust sensor Composition and Structure Devices: Tri-axial magnetometer MOURA Tri-axial System Accelerometer The descent processes dynamic properties are monitored by a special 3-axis

  10. Novel HLA Class I Alleles Associated with Indian Leprosy Patients

    U. Shankarkumar

    2003-01-01

    A*0101, Cw*04011, and Cw*0602 leprosy patients was observed when compared to the controls. Further haplotype A*1102-B*4006-Cw*1502 was significantly increased among the lepromatous leprosy patients when compared to the controls. It seems that HLA class I alleles play vital roles in disease association/pathogenesis with leprosy among Indians.

  11. Molecular monitoring of resistant dhfr and dhps allelic haplotypes in ...

    Objective: The present study assesses the frequency of resistant dhfr and dhps alleles in Morogoro-Mvomero district in south eastern Tanzania and contrast their rate of change during 17 years of SP second line use against five years of SP first line use. Methodology: Cross sectional surveys of asymptomatic infections were ...

  12. Multifragment alleles in DNA fingerprints of the parrot, Amazona ventralis

    Brock, M.K.; White, B.N.

    1991-01-01

    Human DNA probes that identify variable numbers of tandem repeat loci are being used to generate DNA fingerprints in many animal and plant species. In most species the majority of the sc rable autoradiographic bands of the DNA fingerprint represent alleles from numerous unlinked loci. This study was initiated to use DNA fingerprints to determine the amount of band-sharing among captive Hispaniolan parrots (Amazona ventralis) with known genetic relationships. This would form the data base to examine DNA fingerprints of the closely related and endangered Puerto Rican parrot (A. vittata) and to estimate the degree of inbreeding in the relic population. We found by segregation analysis of the bands scored in the DNA fingerprints of the Hispaniolan parrots that there may be as few as two to five loci identified by the human 33.15 probe. Furthermore, at one locus we identified seven alleles, one of which is represented by as many as 19 cosegregating bands. It is unknown how common multiband alleles might be in natural populations, and their existence will cause problems in the assessment of relatedness by band-sharing analysis. We believe, therefore, that a pedigree analysis should be included in all DNA fingerprinting studies, where possible, in order to estimate the number of loci identified by a minisatellite DNA probe and to examine the nature of their alleles.

  13. Allele frequency distribution for 21 autosomal STR loci in Bhutan.

    Kraaijenbrink, Thirsa; van Driem, George L; Tshering of Gaselô, Karma; de Knijff, Peter

    2007-07-20

    We studied the allele frequency distribution of 21 autosomal STR loci contained in the AmpFlSTR Identifiler (Applied Biosystems), the Powerplex 16 (Promega) and the FFFL (Promega) multiplex PCR kits among 936 individuals from the Royal Kingdom of Bhutan. As such these are the first published autosomal DNA results from this country.

  14. Allelic prevalence of intron 3 insertion/deletion genetic ...

    Leila Fallahzadeh-Abarghooei

    2015-03-18

    Mar 18, 2015 ... Tabriz (East Azerbaijan province; belong to Azaris), and Yasuj (Kohgiluyeh va Boyer-Ahmad pro- vince; belong to Lurs), respectively. Genotypic analysis of the Ins/Del XRCC4 polymorphism was detected by the PCR method. Results: The prevalence of the Del allele in Shiraz, Abarku, Tabriz, and Yasuj was ...

  15. Allele frequency analysis of Chinese chestnut ( Castanea mollissima ...

    The aim of this study was to establish a method for allele frequency detection in bulk samples. The abundance of polymerase chain reaction (PCR) products in bulk leaf samples was detected using fluorescent labeled Simple sequence repeat (SSR) primers and an Applied biosystems (AB) automatic DNA analyzer.

  16. Association of LEI0258 microsatellite alleles with antibody response ...

    SERVER

    2008-03-18

    Mar 18, 2008 ... (MHC) B region on chicken Micro-chromosome 16 has been demonstrated by many workers to be ... promising DNA markers in characterizing MHC B genes. Identifying marker alleles (bands) ..... SAS/STAT Users' Guide,. Release 6.12 Edition, SAS Institute Inc, Cary, North Carolina. USA. Taylor RL (2004).

  17. Distribution of HIV-1 resistance-conferring polymorphic alleles SDF ...

    Polymorphic allelic variants of chemokine receptors CCR2 and CCR5, as well as of stromal-derived factor-1 SDF-1, the ligand for the chemokine receptor CXCR4, are known to have protective effects against HIV-1 infection and to be involved with delay in disease progression. We have studied the DNA polymorphisms at ...

  18. HLA-A alleles differentially associate with severity to Plasmodium ...

    Human Leukocyte Antigen (HLA), particularly HLA-B and class II alleles have been differentially associated with disease outcomes in different populations following infection with the malaria Plasmodium falciparum. However, the effect of HLA-A on malaria infection and/or disease is not fully understood. Recently, HLA-A ...

  19. Clonal Ordering of 17p and 5q Allelic Losses in Barrett Dysplasia and Adenocarcinoma

    Blount, Patricia L.; Meltzer, Stephen J.; Yin, Jing; Huang, Ying; Krasna, Mark J.; Reid, Brian J.

    1993-04-01

    Both 17p and 5q allelic losses appear to be involved in the pathogenesis or progression of many human solid tumors. In colon carcinogenesis, there is strong evidence that the targets of the 17p and 5q allelic losses are TP53, the gene encoding p53, and APC, respectively. It is widely accepted that 5q allelic losses precede 17p allelic losses in the progression to colonic carcinoma. The data, however, supporting this proposed order are largely based on the prevalence of 17p and 5q allelic losses in adenomas and unrelated adenocarcinomas from different patients. We investigated the order in which 17p and 5q allelic losses developed during neoplastic progression in Barrett esophagus by evaluating multiple aneuploid cell populations from the same patient. Using DNA content flow cytometric cell sorting and polymerase chain reaction, 38 aneuploid cell populations from 14 patients with Barrett esophagus who had high grade dysplasia, cancer or both were evaluated for 17p and 5q allelic losses. 17p allelic losses preceded 5q allelic losses in 7 patients, both 17p and 5q allelic losses were present in all aneuploid populations of 4 patients, and only 17p (without 5q) allelic losses were present in the aneuploid populations of 3 patients. In no patient did we find that a 5q allelic loss preceded a 17p allelic loss. Our data suggest that 17p allelic losses typically occur before 5q allelic losses during neoplastic progression in Barrett esophagus.

  20. No association of the Arg51Gln and Leu72Met polymorphisms of the ghrelin gene and polycystic ovary syndrome.

    Wang, Kehua; Wang, Leiguang; Zhao, Yueran; Shi, Yuhua; Wang, Laicheng; Chen, Zi-Jiang

    2009-02-01

    Ghrelin plays a role in regulating glucose metabolism and energy balance. Polymorphisms in preproghrelin and ghrelin gene could be responsible for obesity, insulin resistance and low ghrelin levels observed in some individuals. The objective of this study was to evaluate the influence of two single-nucleotide polymorphisms (SNPs) of ghrelin gene on the clinical, the hormonal and metabolic features in women with polycystic ovary syndrome (PCOS) in a Chinese population. A large sample of Chinese PCOS (n = 271) women and a control group (n = 296) of healthy women matched for age were studied. Hormone and metabolic profiles were measured and blood samples were collected for genotype and allelic frequency analysis. Non-synonymous SNPs in the coding region (exon 2) of the preproghrelin gene (Arg51Gln (346 G>A) and Leu72Met (408 C>A) were studied using PCR and restriction fragment length polymorphism analysis. The polymorphism Arg51Gln was not found in the cohorts studied. The distribution of Leu72Met was similar in PCOS group and in healthy controls. There was no significant difference in age, BMI, waist-hip-ratio and levels of FSH, LH, estradiol, testosterone and prolactin between PCOS patients with different genotypes, and the level of plasma glucose and insulin was also similar. No association was found between Leu72Met and Arg51Gln polymorphisms in the ghrelin gene and PCOS in Chinese population.

  1. Effect of BDNF val(66)met polymorphism on declarative memory and its neural substrate: a meta-analysis.

    Kambeitz, Joseph P; Bhattacharyya, Sagnik; Kambeitz-Ilankovic, Lana M; Valli, Isabel; Collier, David A; McGuire, Philip

    2012-10-01

    Brain derived neurotrophic factor (BDNF) is a critical component of the molecular mechanism of memory formation. Variation in the BDNF gene, particularly the rs6265 (val(66)met) single nucleotide polymorphism (SNP), has been linked to variability in human memory performance and to both the structure and physiological response of the hippocampus, which plays a central role in memory processing. However, these effects have not been consistently reported, which may reflect the modest size of the samples studied to date. Employing a meta-analytic approach, we examined the effect of the BDNF val(66)met polymorphism on human memory (5922 subjects) and hippocampal structure (2985 subjects) and physiology (362 subjects). Our results suggest that variations in the rs6265 SNP of the BDNF gene have a significant effect on memory performance, and on both the structure and physiology of the hippocampus, with carriers of the met allele being adversely affected. These results underscore the role of BDNF in moderating variability between individuals in human memory performance and in mediating some of the neurocognitive impairments underlying neuropsychiatric disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. The impact of the CACNA1C risk allele on limbic structures and facial emotions recognition in bipolar disorder subjects and healthy controls.

    Soeiro-de-Souza, Márcio Gerhardt; Otaduy, Maria Concepción Garcia; Dias, Carolina Zadres; Bio, Danielle S; Machado-Vieira, Rodrigo; Moreno, Ricardo Alberto

    2012-12-01

    Impairments in facial emotion recognition (FER) have been reported in bipolar disorder (BD) during all mood states. FER has been the focus of functional magnetic resonance imaging studies evaluating differential activation of limbic regions. Recently, the α1-C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene has been described as a risk gene for BD and its Met allele found to increase CACNA1C mRNA expression. In healthy controls, the CACNA1C risk (Met) allele has been reported to increase limbic system activation during emotional stimuli and also to impact on cognitive function. The aim of this study was to investigate the impact of CACNA1C genotype on FER scores and limbic system morphology in subjects with BD and healthy controls. Thirty-nine euthymic BD I subjects and 40 healthy controls were submitted to a FER recognition test battery and genotyped for CACNA1C. Subjects were also examined with a 3D 3-Tesla structural imaging protocol. The CACNA1C risk allele for BD was associated to FER impairment in BD, while in controls nothing was observed. The CACNA1C genotype did not impact on amygdala or hippocampus volume neither in BD nor controls. Sample size. The present findings suggest that a polymorphism in calcium channels interferes FER phenotype exclusively in BD and doesn't interfere on limbic structures morphology. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. QuASAR: quantitative allele-specific analysis of reads.

    Harvey, Chris T; Moyerbrailean, Gregory A; Davis, Gordon O; Wen, Xiaoquan; Luca, Francesca; Pique-Regi, Roger

    2015-04-15

    Expression quantitative trait loci (eQTL) studies have discovered thousands of genetic variants that regulate gene expression, enabling a better understanding of the functional role of non-coding sequences. However, eQTL studies are costly, requiring large sample sizes and genome-wide genotyping of each sample. In contrast, analysis of allele-specific expression (ASE) is becoming a popular approach to detect the effect of genetic variation on gene expression, even within a single individual. This is typically achieved by counting the number of RNA-seq reads matching each allele at heterozygous sites and testing the null hypothesis of a 1:1 allelic ratio. In principle, when genotype information is not readily available, it could be inferred from the RNA-seq reads directly. However, there are currently no existing methods that jointly infer genotypes and conduct ASE inference, while considering uncertainty in the genotype calls. We present QuASAR, quantitative allele-specific analysis of reads, a novel statistical learning method for jointly detecting heterozygous genotypes and inferring ASE. The proposed ASE inference step takes into consideration the uncertainty in the genotype calls, while including parameters that model base-call errors in sequencing and allelic over-dispersion. We validated our method with experimental data for which high-quality genotypes are available. Results for an additional dataset with multiple replicates at different sequencing depths demonstrate that QuASAR is a powerful tool for ASE analysis when genotypes are not available. http://github.com/piquelab/QuASAR. fluca@wayne.edu or rpique@wayne.edu Supplementary Material is available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Segregation of male-sterility alleles across a species boundary.

    Weller, S G; Sakai, A K; Culley, T M; Duong, L; Danielson, R E

    2014-02-01

    Hybrid zones may serve as bridges permitting gene flow between species, including alleles influencing the evolution of breeding systems. Using greenhouse crosses, we assessed the likelihood that a hybrid zone could serve as a conduit for transfer of nuclear male-sterility alleles between a gynodioecious species and a hermaphroditic species with very rare females in some populations. Segregation patterns in progeny of crosses between rare females of hermaphroditic Schiedea menziesii and hermaphroditic plants of gynodioecious Schiedea salicaria heterozygous at the male-sterility locus, and between female S. salicaria and hermaphroditic plants from the hybrid zone, were used to determine whether male-sterility was controlled at the same locus in the parental species and the hybrid zone. Segregations of females and hermaphrodites in approximately equal ratios from many of the crosses indicate that the same nuclear male-sterility allele occurs in the parent species and the hybrid zone. These rare male-sterility alleles in S. menziesii may result from gene flow from S. salicaria through the hybrid zone, presumably facilitated by wind pollination in S. salicaria. Alternatively, rare male-sterility alleles might result from a reversal from gynodioecy to hermaphroditism in S. menziesii, or possibly de novo evolution of male sterility. Phylogenetic analysis indicates that some species of Schiedea have probably evolved separate sexes independently, but not in the lineage containing S. salicaria and S. menziesii. High levels of selfing and expression of strong inbreeding depression in S. menziesii, which together should favour females in populations, argue against a reversal from gynodioecy to hermaphroditism in S. menziesii. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  5. COMT (Val158Met and BDNF (Val66Met Genes Polymorphism in Schizophrenia: A Case-Control Report

    ramin saravani

    2017-10-01

    Full Text Available Objective: The effects of human brain-derived neurotropic factor (BDNF Val66Met (G>A and the human Catechol-O-methylTransferase (COMT Val158Met (G>A polymorphisms on Schizophrenia (SCZ risk were evaluated.Methods: This case control study included 92 SCZ patients and 92 healthy controls (HCs. Genotyping of both variants were conducted using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR.Results: The findings showed that BDNF Val66Met (G>A variant increased the risk of SCZ (OR=2.008 95%CI=1.008-4.00, P=0.047, GA vs. GG, OR=3.876 95%CI=1.001-14.925, P=0.049. AA vs. GG, OR=2.272. 95%CI=1.204-4.347, P=0.011, GA+AA vs. GG, OR=2.22 95%CI=1.29-3.82. P=0.005, A vs. G. COMT Val158Met (G>A polymorphism was not associated with the risk/protective of SCZ.Conclusion: The results proposed that BDNF Val66Met (G>A polymorphism may increase the risk of SCZ development and did not support an association between COMT Val158Met (G>A variant and risk/protective of SCZ. Further studies and different ethnicities are recommended to confirm the findings.

  6. A comparison of metabolic syndrome (MetS) risk factors in Filipino women and Filipino American women: a pilot study.

    Ancheta, Irma B; Battie, Cynthia A; Tuason, Teresa; Ancheta, Christine V

    2012-01-01

    Cardiovascular disease (CVD) is a significant cause of morbidity and mortality in women of Filipino ethnicity. The objective of our work was to determine if metabolic syndrome (MetS), a modifiable CVD risk factor, differs in women as a function of country of residency and to determine if, CVD prevention strategies need to differ for these groups of Filipino women. Data were collected in community-based health screenings for this cross-sectional study. PARTICIPANTS were recruited at places of worship in southeast United States (n=60) and Central Visayas, Philippines (n=56). Prevalence of MetS and its component factors as defined by the International Diabetes Federation criteria. The prevalence of MetS in Filipino women (FW) and Filipino American women (FAW) groups was similar (52% vs 55%, P=.08) although the prevalence of elevated waist circumference was greater for FAW (78% vs 59%, P=.03). Conversely, the percentage of FW women with risk-associated high-density lipoprotein (HDL) levels was higher than the FAW group (84% vs 42%, PFilipino women regardless of the country of residency although the FAW tended to have higher rates of central obesity while the FW tended to have higher rates of risk-associated HDL levels. Further research should examine the cause of these differences in order to develop better cardiovascular screening and intervention strategies.

  7. Deleterious alleles in the human genome are on average younger than neutral alleles of the same frequency

    Kiezun, Adam; Pulit, Sara L.; Francioli, Laurent C.; van Dijk, Freerk; Swertz, Morris; Boomsma, Dorret I.; van Duijn, Cornelia M.; Slagboom, P. Eline; van Ommen, G. J. B.; Wijmenga, Cisca; de Bakker, Paul I. W.; Sunyaev, Shamil R.

    Large-scale population sequencing studies provide a complete picture of human genetic variation within the studied populations. A key challenge is to identify, among the myriad alleles, those variants that have an effect on molecular function, phenotypes, and reproductive fitness. Most non-neutral

  8. COMT Val158Met polymorphism moderates the association between PTSD symptom severity and hippocampal volume.

    Hayes, Jasmeet P; Logue, Mark W; Reagan, Andrew; Salat, David; Wolf, Erika J; Sadeh, Naomi; Spielberg, Jeffrey M; Sperbeck, Emily; Hayes, Scott M; McGlinchey, Regina E; Milberg, William P; Verfaellie, Mieke; Stone, Annjanette; Schichman, Steven A; Miller, Mark W

    2017-03-01

    Memory-based alterations are among the hallmark symptoms of posttraumatic stress disorder (PTSD) and may be associated with the integrity of the hippocampus. However, neuroimaging studies of hippocampal volume in individuals with PTSD have yielded inconsistent results, raising the possibility that various moderators, such as genetic factors, may influence this association. We examined whether the catechol-O-methyltransferase (COMT) Val158Met polymorphism, which has previously been shown to be associated with hippocampal volume in healthy individuals, moderates the association between PTSD and hippocampal volume. Recent war veterans underwent structural MRI on a 3 T scanner. We extracted volumes of the right and left hippocampus using FreeSurfer and adjusted them for individual differences in intracranial volume. We assessed PTSD severity using the Clinician-Administered PTSD Scale. Hierarchical linear regression was used to model the genotype (Val158Met polymorphism) × PTSD severity interaction and its association with hippocampal volume. We included 146 white, non-Hispanic recent war veterans (90% male, 53% with diagnosed PTSD) in our analyses. A significant genotype × PTSD symptom severity interaction emerged such that individuals with greater current PTSD symptom severity who were homozygous for the Val allele showed significant reductions in left hippocampal volume. The direction of proposed effects is unknown, thus precluding definitive assessment of whether differences in hippocampal volume reflect a consequence of PTSD, a pre-existing characteristic, or both. Our findings suggest that the COMT polymorphism moderates the association between PTSD and hippocampal volume. These results highlight the role that the dopaminergic system has in brain structure and suggest a possible mechanism for memory disturbance in individuals with PTSD.

  9. Requirements to be met by the operation manual

    1981-03-01

    The rule applies to the contents and the lay-out of the operating manual for stationary nuclear power plants. The draft contains: 1. General requirement to be met by the contents of the operating manual. The operating manual to be arranged in 4 parts (part 1: internal rules and regulations; part 2: operation overall plant; part 3: incidents; part 4: operation systems). Safety specifications to be included in the manual, the exemption being the system of technical documentation. 2. General requirements to be met by the lay-out of the operating manual. Comprehensibility; legibility; structure and subdivisions; arrangement of the instructions and design of the manuals cover. 3. Requirements to be met by part 1. Defining the various internal rules and regulations (personnel management); rules and regulations concerning inspections and shift work; maintenance and repair; radiation protection; guard duty and admission; alarm; fire protection; first aid. 4. Requirements to be met by part 2. Provisions and operational limitations; limit values important from the point of view of safety; normal operation; anomalous operation; in-service inspections. 6. Requirements to be met by part 3. 7. Annex: Rules, regulations and stipulations mentioned in the rule draft. (orig.)

  10. Hydrogen storage capacity of titanium met-cars

    Akman, N; Durgun, E; Yildirim, T; Ciraci, S

    2006-01-01

    The adsorption of hydrogen molecules on the titanium metallocarbohedryne (met-car) cluster has been investigated by using the first-principles plane wave method. We have found that, while a single Ti atom at the corner can bind up to three hydrogen molecules, a single Ti atom on the surface of the cluster can bind only one hydrogen molecule. Accordingly, a Ti 8 C 12 met-car can bind up to 16 H 2 molecules and hence can be considered as a high-capacity hydrogen storage medium. Strong interaction between two met-car clusters leading to the dimer formation can affect H 2 storage capacity slightly. Increasing the storage capacity by directly inserting H 2 into the met-car or by functionalizing it with an Na atom have been explored. It is found that the insertion of neither an H 2 molecule nor an Na atom could further promote the H 2 storage capacity of a Ti 8 C 12 cluster. We have also tested the stability of the H 2 -adsorbed Ti 8 C 12 met-car with ab initio molecular dynamics calculations which have been carried out at room temperature

  11. MetReS, an Efficient Database for Genomic Applications.

    Vilaplana, Jordi; Alves, Rui; Solsona, Francesc; Mateo, Jordi; Teixidó, Ivan; Pifarré, Marc

    2018-02-01

    MetReS (Metabolic Reconstruction Server) is a genomic database that is shared between two software applications that address important biological problems. Biblio-MetReS is a data-mining tool that enables the reconstruction of molecular networks based on automated text-mining analysis of published scientific literature. Homol-MetReS allows functional (re)annotation of proteomes, to properly identify both the individual proteins involved in the processes of interest and their function. The main goal of this work was to identify the areas where the performance of the MetReS database performance could be improved and to test whether this improvement would scale to larger datasets and more complex types of analysis. The study was started with a relational database, MySQL, which is the current database server used by the applications. We also tested the performance of an alternative data-handling framework, Apache Hadoop. Hadoop is currently used for large-scale data processing. We found that this data handling framework is likely to greatly improve the efficiency of the MetReS applications as the dataset and the processing needs increase by several orders of magnitude, as expected to happen in the near future.

  12. No association of the neuropeptide Y (Leu7Pro) and ghrelin gene (Arg51Gln, Leu72Met, Gln90Leu) single nucleotide polymorphisms with eating disorders.

    Kindler, Jochen; Bailer, Ursula; de Zwaan, Martina; Fuchs, Karoline; Leisch, Friedrich; Grün, Bettina; Strnad, Alexandra; Stojanovic, Mirjana; Windisch, Julia; Lennkh-Wolfsberg, Claudia; El-Giamal, Nadja; Sieghart, Werner; Kasper, Siegfried; Aschauer, Harald

    2011-06-01

    Genetic factors likely contribute to the biological vulnerability of eating disorders. Case-control association study on one neuropeptide Y gene (Leu7Pro) polymorphism and three ghrelin gene (Arg51Gln, Leu72Met and Gln90Leu) polymorphisms. 114 eating disorder patients (46 with anorexia nervosa, 30 with bulimia nervosa, 38 with binge eating disorder) and 164 healthy controls were genotyped. No differences were detected between patients and controls for any of the four polymorphisms in allele frequency and genotype distribution (P > 0.05). Allele frequencies and genotypes had no significant influence on body mass index (P > 0.05) in eating disorder patients. Positive findings of former case-control studies of associations between ghrelin gene polymorphisms and eating disorders could not be replicated. Neuropeptide Y gene polymorphisms have not been investigated in eating disorders before.

  13. Rocket experiment METS - Microwave Energy Transmission in Space

    Kaya, N.; Matsumoto, H.; Akiba, R.

    A Microwave Energy Transmission in Space (METS) rocket experiment is being planned by the Solar Power Satellite Working Group at the Institute of Space and Astronautical Science in Japan for the forthcoming International Space Year, 1992. The METS experiment is an advanced version of the previous MINIX rocket experiment (Matsumoto et al., 1990). This paper describes a conceptual design of the METS rocket experiment. It aims at verifying a newly developed microwave energy transmission system for space use and to study nonlinear effects of the microwave energy beam in the space plasma environment. A high power microwave of 936 W will be transmitted by the new phased-array antenna from a mother rocket to a separated target (daughter rocket) through the ionospheric plasma. The active phased-array system has a capability of focusing the microwave energy around any spatial point by controlling the digital phase shifters individually.

  14. Rocket experiment METS Microwave Energy Transmission in Space

    Kaya, N.; Matsumoto, H.; Akiba, R.

    A METS (Microwave Energy Transmission in Space) rocket experiment is being planned by the SPS (Solar Power Satellite) Working Group at the Institute of Space and Astronautical Science (ISAS) in Japan for the forthcoming International Space Year (ISY), 1992. The METS experiment is an advanced version of our MINIX rocket experiment. This paper describes the conceptual design for the METS rocket experiment. Aims are to verify the feasibility of a newly developed microwave energy transmission system designed for use in space and to study nonlinear effects of the microwave energy beam on space plasma. A high power microwave (936 W) will be transmitted by a new phase-array antenna from a mother rocket to a separate target (daughter rocket) through the Earth's ionospheric plasma. The active phased-array system has the capability of being able to focus the microwave energy at any spatial point by individually controlling the digital phase shifters.

  15. El acertijo de la metáfora visual

    De la Rosa Alzate, Adriana; Universidad Autónoma de Occidente

    2016-01-01

    En este artículo se presentan los resultados de la investigación sobre el proceso de interpretación de la metáfora visual, en niños entre tres y cuatro años de edad. El propósito de la investigación fue dar cuenta del proceso de interpretación de la metáfora visual y del razonamiento involucrado. La metáfora visual se entiende como un fenómeno en el que los objetos representados presentan transformaciones que traen como consecuencia la emergencia de nuevas categorías e incluso la ambigüedad, ...

  16. Met Ed gets reprieve: banks lend tax money

    Utroska, D.

    1981-01-01

    A consortium of banks agreed to loan Metropolitan Edison $23 million to pay its April 15 state taxes and temporarily relieve a cash-flow problem that is leading to default after the Pennsylvania Public Utility Commission expedited a rate request. The continued solvency of Met Ed is a matter of speculation because the present credit formula is based on liquid assets which the PUC did not address. While the action taken by the bankers gives Met Ed a reprieve, it does not provide a long-term solution. The Revolving Credit Agreement will expire on October 1. Met Ed is still faced with the problem of relicensing Three Mile Island-1 unit and the cost of underwriting the cleanup of the No. 2 unit

  17. Association of the Leu72Met polymorphism of the ghrelin gene with the risk of Type 2 diabetes in subjects with impaired glucose tolerance in the Finnish Diabetes Prevention Study.

    Mager, U; Lindi, V; Lindström, J; Eriksson, J G; Valle, T T; Hämäläinen, H; Ilanne-Parikka, P; Keinänen-Kiukaanniemi, S; Tuomilehto, J; Laakso, M; Pulkkinen, L; Uusitupa, M

    2006-06-01

    Ghrelin is a gut-brain regulatory peptide stimulating appetite and controlling energy balance. In previous studies, the Leu72Met polymorphism of the ghrelin gene has been associated with obesity and impaired insulin secretion. We investigated whether the Leu72Met polymorphism is associated with the incidence of Type 2 diabetes in subjects with impaired glucose tolerance (IGT) participating in the Finnish Diabetes Prevention Study (DPS). DPS was a longitudinal intervention study carried out in five participating centres in Finland. A total of 522 subjects with IGT were randomized into either an intervention or a control group and DNA was available from 507 subjects. The Leu72Met polymorphism was screened by the restriction fragment length polymorphism method. There were no differences in clinical and anthropometric characteristics among the genotypes at baseline. IGT subjects with the Met72 allele were at higher risk of developing Type 2 diabetes than subjects with the Leu72Leu genotype (P = 0.046). Our data also demonstrated that IGT subjects with the common Leu72Leu genotype developed Type 2 diabetes less frequently under intervention circumstances than subjects with the Met72 allele (OR = 0.28, 95% CI 0.10-0.79; P = 0.016). Subjects with the Leu72Leu genotype had a lower risk for the development of Type 2 diabetes. This was observed particularly in the study subjects who underwent an intensive diet and exercise intervention. Defective first-phase insulin secretion related to the Met72 allele might be one factor contributing to the conversion to Type 2 diabetes.

  18. Load testing circuit

    2009-01-01

    A load testing circuit a circuit tests the load impedance of a load connected to an amplifier. The load impedance includes a first terminal and a second terminal, the load testing circuit comprising a signal generator providing a test signal of a defined bandwidth to the first terminal of the load...

  19. Remembering the early days of the Met Lab

    Katz, J.J.

    1990-01-01

    The Met Lab was set up by the war-time Manhattan District, US Corp of Engineers to (i) find a system using normal uranium in which a chain reaction would occur; (ii) to show that if such a chain reaction did occur, it would be possible to separate plutonium chemically from the uranium matrix and the fission products formed in the chain reactions; and (iii) to prepare plans for the large-scale production of plutonium. Chemistry Section C-1 of the Met Lab was assigned the responsibility for developing separation methods for plutonium production on the industrial scale. This report describes some aspects of daily life in Section C-1

  20. Sustainable energy with thermochemical storage; Duurzame energie met thermochemische opslag

    Bakker, M. [ECN Efficiency and Infrastructure, Petten (Netherlands)

    2010-03-15

    The Energy research Centre of the Netherlands ECN) foresees an important role for heat in sustainable construction of buildings. Using salt hydrates the surplus of heat can be stored in the summer which then can be used in the winter. By means of thermochemical storage natural gas for heating tap water or houses is no longer necessary. [Dutch] Energieonderzoek Centrum Nederland (ECN) ziet voor warmteopslag een belangrijke rol weggelegd in het duurzaam bouwen. Met behulp van zouthydraten kan de overtollige warmte in de zomer opgeslagen worden om deze in de winter weer vrij te maken. Met deze thermochemische opslag is in de nabije toekomst aardgas overbodig voor de verwarming van kraanwater of woonhuis.

  1. Physiological Signaling and Structure of the HGF Receptor MET

    Gianluca Baldanzi

    2014-12-01

    Full Text Available The “hepatocyte growth factor” also known as “scatter factor”, is a multifunctional cytokine with the peculiar ability of simultaneously triggering epithelial cell proliferation, movement and survival. The combination of those proprieties results in the induction of an epithelial to mesenchymal transition in target cells, fundamental for embryogenesis but also exploited by tumor cells during metastatization. The hepatocyte growth factor receptor, MET, is a proto-oncogene and a prototypical transmembrane tyrosine kinase receptor. Inhere we discuss the MET molecular structure and the hepatocyte growth factor driven physiological signaling which coordinates epithelial proliferation, motility and morphogenesis.

  2. Multimer Formation Explains Allelic Suppression of PRDM9 Recombination Hotspots

    Baker, C.L.; Petkova, P.; Walker, M.; Flachs, Petr; Mihola, Ondřej; Trachtulec, Zdeněk; Petkov, P.M.; Paigen, K.

    2015-01-01

    Roč. 11, č. 9 (2015), e1005512-e1005512 ISSN 1553-7390 R&D Projects: GA ČR GAP305/10/1931; GA ČR(CZ) GA14-20728S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378050 Keywords : recombination * PRDM9 * allelic competition Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.528, year: 2014

  3. [Phenotypic effects of puroindoline gene alleles of bread wheat].

    Chebotar, S V; Kurakina, K O; Khokhlov, O M; Chebotar, H O; Syvolap, Iu M

    2012-01-01

    85 winter bread wheat varieties and lines that have been developed mostly in Ukraine were analyzed with NIR for parameters of hardness and protein content. The hardness data were compared with the data of puroindoline gene alleles analysis done earlier and the published data. Significant variation of parameters of hardness was revealed when there was low polymorphism of puroindoline genes indicating the presence of additional genes that influence the hardness parameters.

  4. Allele-Specific DNA Methylation Detection by Pyrosequencing®

    Kristensen, Lasse Sommer; Johansen, Jens Vilstrup; Grønbæk, Kirsten

    2015-01-01

    DNA methylation is an epigenetic modification that plays important roles in healthy as well as diseased cells, by influencing the transcription of genes. In spite the fact that human somatic cells are diploid, most of the currently available methods for the study of DNA methylation do not provide......-effective protocol for allele-specific DNA methylation detection based on Pyrosequencing(®) of methylation-specific PCR (MSP) products including a single nucleotide polymorphism (SNP) within the amplicon....

  5. TRPV6 alleles do not influence prostate cancer progression

    Kessler, Thorsten; Wissenbach, Ulrich; Grobholz, Rainer; Flockerzi, Veit

    2009-01-01

    Abstract Background The transient receptor potential, subfamily V, member 6 (TRPV6) is a Ca2+ selective cation channel. Several studies have shown that TRPV6 transcripts are expressed in locally advanced prostatic adenocarcinoma, metastatic and androgen-insensitive prostatic lesions but are undetectable in healthy prostate tissue and benign prostatic hyperplasia. Two allelic variants of the human trpv6 gene have been identified which are transcribed into two independent mRNAs, TRPV6a and TRPV...

  6. Mutant power: using mutant allele collections for yeast functional genomics.

    Norman, Kaitlyn L; Kumar, Anuj

    2016-03-01

    The budding yeast has long served as a model eukaryote for the functional genomic analysis of highly conserved signaling pathways, cellular processes and mechanisms underlying human disease. The collection of reagents available for genomics in yeast is extensive, encompassing a growing diversity of mutant collections beyond gene deletion sets in the standard wild-type S288C genetic background. We review here three main types of mutant allele collections: transposon mutagen collections, essential gene collections and overexpression libraries. Each collection provides unique and identifiable alleles that can be utilized in genome-wide, high-throughput studies. These genomic reagents are particularly informative in identifying synthetic phenotypes and functions associated with essential genes, including those modeled most effectively in complex genetic backgrounds. Several examples of genomic studies in filamentous/pseudohyphal backgrounds are provided here to illustrate this point. Additionally, the limitations of each approach are examined. Collectively, these mutant allele collections in Saccharomyces cerevisiae and the related pathogenic yeast Candida albicans promise insights toward an advanced understanding of eukaryotic molecular and cellular biology. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  7. The protease inhibitor PI*S allele and COPD

    Hersh, C P; Ly, N P; Berkey, C S

    2005-01-01

    In many countries, the protease inhibitor (SERPINA1) PI*S allele is more common than PI*Z, the allele responsible for most cases of chronic obstructive pulmonary disease (COPD) due to severe alpha 1-antitrypsin deficiency. However, the risk of COPD due to the PI*S allele is not clear. The current...... authors located studies that addressed the risk of COPD or measured lung function in individuals with the PI SZ, PI MS and PI SS genotypes. A separate meta-analysis for each genotype was performed. Aggregating data from six studies, the odds ratio (OR) for COPD in PI SZ compound heterozygotes compared...... with PI MM (normal) individuals was significantly increased at 3.26 (95% confidence intervals (CI): 1.24-8.57). In 17 cross-sectional and case-control studies, the OR for COPD in PI MS heterozygotes was 1.19 (95%CI: 1.02-1.38). However, PI MS genotype was not associated with COPD risk after correcting...

  8. The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with increased body mass index and insulin resistance measures in bipolar disorder and schizophrenia.

    Bonaccorso, Stefania; Sodhi, Monsheel; Li, Jiang; Bobo, William V; Chen, Yuejin; Tumuklu, Mevhibe; Theleritis, Christos; Jayathilake, Karuna; Meltzer, Herbert Y

    2015-08-01

    We tested the hypothesis that a common functional variant in brain-derived neurotrophic factor (BDNF), Val66Met, which has been shown to be associated with increased body mass index (BMI) in schizophrenia (SCZ) and schizoaffective disorder (SAD), is also associated with antipsychotic-induced weight gain in bipolar disorder (BPD). Association of Val66Met with other metabolic measures, including high- and low-density cholesterol, triglycerides, total cholesterol, fasting blood glucose, and hemoglobin A1c, was also tested. This was a 12-month, prospective, randomized trial of two atypical antipsychotic drugs (APDs) with moderate (risperidone) or high (olanzapine) risk to cause weight gain. Subjects were diagnosed as having BPD (n = 90) and SCZ or SAD (n = 76). BMI was significantly greater in all diagnoses for Met66 allele carriers at six months (p = 0.01). Met66 carriers with BPD showed a greater increase in the triglycerides/high-density (HDL) cholesterol ratio (p = 0.01), a key marker for metabolic syndrome related to insulin resistance, and log-triglycerides (p = 0.04), after three or six months of treatment. Met66 carriers had the greatest increase in log-triglycerides (p = 0.03) and triglycerides/HDL cholesterol ratio after three months of treatment with risperidone (p = 0.003), and the highest BMI at six months (p = 0.01). The positive association of BNDF Val66Met with high BMI values replicates previous findings in patients with SCZ and indicates the BDNF Val66Met genotype as a potential risk factor for obesity and insulin resistance measures in patients with BPD receiving antipsychotics as well. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. TRPV6 alleles do not influence prostate cancer progression

    Kessler, Thorsten; Wissenbach, Ulrich; Grobholz, Rainer; Flockerzi, Veit

    2009-01-01

    The transient receptor potential, subfamily V, member 6 (TRPV6) is a Ca 2+ selective cation channel. Several studies have shown that TRPV6 transcripts are expressed in locally advanced prostatic adenocarcinoma, metastatic and androgen-insensitive prostatic lesions but are undetectable in healthy prostate tissue and benign prostatic hyperplasia. Two allelic variants of the human trpv6 gene have been identified which are transcribed into two independent mRNAs, TRPV6a and TRPV6b. We now asked, whether the trpv6a allele is correlated with the onset of prostate cancer, with the Gleason score and the tumour stage. Genomic DNA of prostate cancer patients and control individuals was isolated from resections of prostatic adenocarcinomas and salivary fluid respectively. Genotyping of SNPs of the TRPV6 gene was performed by restriction length polymorphism or by sequencing analysis. RNA used for RT-PCR was isolated from prostate tissue. Data sets were analyzed by Chi-Square test. We first characterized in detail the five polymorphisms present in the protein coding exons of the trpv6 gene and show that these polymorphisms are coupled and are underlying the TRPV6a and the TRPV6b variants. Next we analysed the frequencies of the two TRPV6 alleles using genomic DNA from saliva samples of 169 healthy individuals. The homozygous TRPV6b genotype predominated with 86%, whereas no homozygous TRPV6a carriers could be identified. The International HapMap Project identified a similar frequency for an Utah based population whereas in an African population the a-genotype prevailed. The incidence of prostate cancer is several times higher in African populations than in non-African and we then investigated the TRPV6a/b frequencies in 141 samples of prostatic adenocarcinoma. The TRPV6b allele was found in 87% of the samples without correlation with Gleason score and tumour stage. Our results show that the frequencies of trpv6 alleles in healthy control individuals and prostate cancer patients

  10. TRPV6 alleles do not influence prostate cancer progression.

    Kessler, Thorsten; Wissenbach, Ulrich; Grobholz, Rainer; Flockerzi, Veit

    2009-10-26

    The transient receptor potential, subfamily V, member 6 (TRPV6) is a Ca(2+) selective cation channel. Several studies have shown that TRPV6 transcripts are expressed in locally advanced prostatic adenocarcinoma, metastatic and androgen-insensitive prostatic lesions but are undetectable in healthy prostate tissue and benign prostatic hyperplasia. Two allelic variants of the human trpv6 gene have been identified which are transcribed into two independent mRNAs, TRPV6a and TRPV6b. We now asked, whether the trpv6a allele is correlated with the onset of prostate cancer, with the Gleason score and the tumour stage. Genomic DNA of prostate cancer patients and control individuals was isolated from resections of prostatic adenocarcinomas and salivary fluid respectively. Genotyping of SNPs of the TRPV6 gene was performed by restriction length polymorphism or by sequencing analysis. RNA used for RT-PCR was isolated from prostate tissue. Data sets were analyzed by Chi-Square test. We first characterized in detail the five polymorphisms present in the protein coding exons of the trpv6 gene and show that these polymorphisms are coupled and are underlying the TRPV6a and the TRPV6b variants. Next we analysed the frequencies of the two TRPV6 alleles using genomic DNA from saliva samples of 169 healthy individuals. The homozygous TRPV6b genotype predominated with 86%, whereas no homozygous TRPV6a carriers could be identified. The International HapMap Project identified a similar frequency for an Utah based population whereas in an African population the a-genotype prevailed. The incidence of prostate cancer is several times higher in African populations than in non-African and we then investigated the TRPV6a/b frequencies in 141 samples of prostatic adenocarcinoma. The TRPV6b allele was found in 87% of the samples without correlation with Gleason score and tumour stage. Our results show that the frequencies of trpv6 alleles in healthy control individuals and prostate cancer patients

  11. TRPV6 alleles do not influence prostate cancer progression

    Flockerzi Veit

    2009-10-01

    Full Text Available Abstract Background The transient receptor potential, subfamily V, member 6 (TRPV6 is a Ca2+ selective cation channel. Several studies have shown that TRPV6 transcripts are expressed in locally advanced prostatic adenocarcinoma, metastatic and androgen-insensitive prostatic lesions but are undetectable in healthy prostate tissue and benign prostatic hyperplasia. Two allelic variants of the human trpv6 gene have been identified which are transcribed into two independent mRNAs, TRPV6a and TRPV6b. We now asked, whether the trpv6a allele is correlated with the onset of prostate cancer, with the Gleason score and the tumour stage. Methods Genomic DNA of prostate cancer patients and control individuals was isolated from resections of prostatic adenocarcinomas and salivary fluid respectively. Genotyping of SNPs of the TRPV6 gene was performed by restriction length polymorphism or by sequencing analysis. RNA used for RT-PCR was isolated from prostate tissue. Data sets were analyzed by Chi-Square test. Results We first characterized in detail the five polymorphisms present in the protein coding exons of the trpv6 gene and show that these polymorphisms are coupled and are underlying the TRPV6a and the TRPV6b variants. Next we analysed the frequencies of the two TRPV6 alleles using genomic DNA from saliva samples of 169 healthy individuals. The homozygous TRPV6b genotype predominated with 86%, whereas no homozygous TRPV6a carriers could be identified. The International HapMap Project identified a similar frequency for an Utah based population whereas in an African population the a-genotype prevailed. The incidence of prostate cancer is several times higher in African populations than in non-African and we then investigated the TRPV6a/b frequencies in 141 samples of prostatic adenocarcinoma. The TRPV6b allele was found in 87% of the samples without correlation with Gleason score and tumour stage. Conclusion Our results show that the frequencies of trpv6

  12. Loads and loads and loads: The influence of prospective load, retrospective load, and ongoing task load in prospective memory

    Beat eMeier

    2015-06-01

    Full Text Available In prospective memory tasks different kinds of load can occur. Adding a prospective memory task can impose a load on ongoing task performance. Adding ongoing task load can affect prospective memory performance. The existence of multiple target events increases prospective load and adding complexity to the to-be-remembered action increases retrospective load. In two experiments, we systematically examined the effects of these different types of load on prospective memory performance. Results showed an effect of prospective load on costs in the ongoing task for categorical targets (Experiment 2, but not for specific targets (Experiment 1. Retrospective load and ongoing task load both affected remembering the retrospective component of the prospective memory task. We suggest that prospective load can enhance costs in the ongoing task due to additional monitoring requirements. Retrospective load and ongoing task load seem to impact the division of resources between the ongoing task and retrieval of the retrospective component, which may affect disengagement from the ongoing task. In general, the results demonstrate that the different types of load affect prospective memory differentially.

  13. Zuivering brouwerijprocesafvalwater met behulp van microalgen: Resultaten onderzoek 2012

    Dijk, van W.; Schipperus, R.; Grobben, S.A.; Weide, van der R.Y.

    2013-01-01

    In een samenwerkingsverband van Heineken Nederland BV, Algae Food & Fuel en WUR (Acrres) is in 2012 een onderzoeksproject gestart om de mogelijkheden van zuivering van procesafvalwater van de brouwerijen met behulp van algen te onderzoeken. In het kader van dit project is in 2012 een

  14. Christus' offer bij Paulus vergeleken met de offeropvattingen van Philo

    Stelma, Juurd Hari

    1938-01-01

    Een vergelijking der offeropvattingen van Paulus en Philo brengt ons in aanraking met twee principieel verschillende voorstellingen aangaande het offer. Het offer van Christus is voor Paulus de gave Gods, waardoor de macht van de zonde en dood vernietigd en de schuld verzoend is. Door de

  15. Constant Cremer, voetballer in Tilburg met Afrikaanse wortels

    Drs. Thijs Kemmeren

    2012-01-01

    Constant Cremer is de eerste zwarte voetballer in Nederland. Hij is geboren in Belgisch Congo. Hij speelde bij Willem II in het seizoen 1904 -1905 en werd met Willem II Brabvants kampioen. Constant werd, als een donkere mulat een held in Tilburg. Hij kwam uiteindelijk terecht in Nederland Indie en

  16. Workshop ALOUD 'Onderzoek voor, door en met de OU'

    Gijselaers, Jérôme; De Groot, Renate

    2015-01-01

    Vraagt u zich wel eens af wat de doorsnee kenmerken zijn van de OU-student? Hoeveel studenten daadwerkelijk starten met de studeren? Wie van deze groep succesvol zijn? En welke verschillen er zitten tussen de faculteiten? En wilt u meedenken over wat voor details we van studenten willen weten voor

  17. Beoordeling gezondheidsrisico's door sporten op kunstgrasvelden met rubbergranulaat

    Oomen AG; de Groot GM; CPV; M&V

    2016-01-01

    Uit nieuw onderzoek van het RIVM blijkt dat het risico voor de gezondheid van sporten op kunstgrasvelden die zijn ingestrooid met rubbergranulaat, praktisch verwaarloosbaar is. Dat betekent dat het verantwoord is om op deze velden te sporten. Aanleiding voor het onderzoek is de maatschappelijke

  18. Van Weel: "Werken met minimumbuis de gebruikelijke, maar foute weg"

    Staalduinen, van J.; Weel, van P.A.

    2008-01-01

    Door het aanzuigen en in de kas brengen van relatief droge, voorverwarmde buitenlucht is de RV in de kas te verlagen en beter te beheersen. Omdat ook de verticale temperatuurverschillen afnemen, is het mogelijk om intensiever te schermen. Met Aircobreezeventilatoren, die via kieren of gaten lucht

  19. Ervaringen met ICT-onderzoek in het HBO.

    van Leeuwen, H.; Teeuw, W.J.; Tangelder, R.; Griffioen, P.; Krose, B.; Schouten, B.

    2011-01-01

    In dit artikel wordt het belang aangegeven van onderzoeksvaardigheden in het HBO. Met de komst van de lectoraten en de nieuwe positionering van het HBO is het belangrijk om een antwoord te vinden hoe het onderzoek binnen het HBO vormgegeven moet worden. Hierbij wordt gekeken naar de bruikbaarheid

  20. Imidacloprid of niet? (interview met Sjef van der Steen)

    Kleis, R.; Steen, van der J.J.M.

    2014-01-01

    Is bijensterfte het werk van neonicotinoïden? Ja, zeggen en denken velen. Volgens hen zijn de neo’s rechtstreeks verantwoordelijk voor de hoge sterfte onder bijen. Nee, toont Wagenings onderzoek aan. Intussen lijkt het met de sterfte voorzichtig de goede kant op te gaan.

  1. Vers bloed voor spinazie (interview met C. Kik)

    Nijland, R.; Kik, C.

    2011-01-01

    Chris Kik van het Centrum voor Genetische Bronnen Nederland (CGN) keerde afgelopen weekend terug van een eenmansexpeditie door Azerbeidzjan, Georgië en Armenië. Resultaat van de reis: een koffer volgepropt met 53 witte linnen zakjes zaad van wilde en lokaal geteelde spinazie. Dat materiaal gaat

  2. Slim in het verkeer met open data : adviesrapport

    Boelens, Danny; Plasmeyer, Luuk; van Heesewijk, Nick; Smeenge, Tetiana; Hoekzema, Niek; McCreesh, Séamus

    2013-01-01

    Rapport in opdracht van de gemeente Groningen. Aanleiding voor het schrijven van dit rapport is dat de gemeente Groningen graag wil weten hoe ze met het gebruik van open data het (openbaar) vervoer voor studenten in en naar de stad Groningen kunnen verbeteren. Het onderzoek richtte zich daarom op

  3. Een bepalingsmethode voor thallium in regenwater met behulp van voltammetrie

    Struijs; J.; Wolfs; P.M.; Esseveld; F.G.van

    1985-01-01

    In dit rapport wordt een bepalingmethode beschreven voor thallium in het nanogram/liter-gebied, waarbij gebruik wordt gemaakt van differentiele pulse-anodic stripping voltammetry (DPASV) aan de dunne kwikfilm. Met deze techniek blijkt het mogelijk om de concentratie van dit element rechtstreeks

  4. Subtiel verleiden met nudging : Verhogen van enquêterespons

    V. Versluis; dr. A.F. de Wild

    2015-01-01

    De nonrespons op enquêtes onder studenten is vaak hoog, waardoor verkregen informatie niet altijd betrouwbaar en valide is. Met nudges, subtiele interventies die gebaseerd zijn op inzichten uit de psychologie en sociologie, kan de respons op enquêtes aanzienlijk worden verhoogd. Bij de uitrol van

  5. Aan de slag met honors : praktijklessen uit Europa

    Wolfensberger, Marca; Hogenstijn, Maarten

    2015-01-01

    In de brochure ‘Aan de slag met honors’ worden onderzoeksresultaten van het onderzoeksproject Honors in Europe hertaald naar tips voor succesvol en inspirerend honorsonderwijs. De brochure is grotendeels gebaseerd op het boek Talent Development in European Higher Education – Honors programs in the

  6. San Diego Met High School: Personalization as a Foundation

    Principal Leadership, 2010

    2010-01-01

    The mission of San Diego Met High School is to prepare students for college and the workforce through active learning, academic rigor, and community involvement in a small school setting. Because personalization is a key component of the school culture, advisories of 20-25 students work with the same teachers for all four years. Advisers, parents,…

  7. Randvoorwaarden ontwerp happy games voor ouderen met dementie

    Dr. A.L. Cordia

    2014-01-01

    Deze publicatie is in twee fasen tot stand gekomen tijdens het In Touch onderzoek. De eerste fase had als doel de randvoorwaarden te bepalen voor het ontwerpen van drie nieuwe iPad spellen voor ouderen met dementie en betrof een beperkt literatuuronderzoek op gerelateerde onderwerpen, daar

  8. Stalboekje varkens : natuurlijk gezond met kruiden en andere natuurproducten

    Groot, M.J.; Kleijer-Ligtenberg, G.; Asseldonk, van T.

    2014-01-01

    Het streven om het gebruik van antibiotica terug te dringen vraagt om een ander management. Goede voeding, huisvesting en hygiëne zijn hierbij belangrijk. In dit boekje worden handvaten gegeven om met natuurlijke middelen de gezondheid van de dieren te bevorderen en zo ziektes te voorkomen. Tevens

  9. Met hard werken alleen is niets mis : werkdruk en stress

    Klein Hesselink, J.; Man, M. de; Heeten, W. den

    1996-01-01

    Als men continu onder flinke druk werkt en die druk ook als last wordt ervaren, ontstaan klachten. Omgaan met werkdruk en werkstress is te leren. De cursus 'Anders werken' biedt die mogelijkheid. Dit artikel geeft na enige statische gevens over stress een nadere definiëring van het begrip

  10. Kenmerken en recidivecijfers van ex-terbeschikkinggestelden met een zedendelict

    Schönberger, H.J.M.; Kogel, C.H. de; Bregman, I.M.

    2012-01-01

    Dit rapport beschrijft de omvang, achtergrondkenmerken en recidivegegevens van tbs-gestelden met een zedendelict als indexdelict. Het indexdelict is het delict waarvoor de tbs-maatregel is opgelegd. Twee populaties zedendelinquenten komen aan de orde. De eerste populatie, de 'uitstroompopulatie',

  11. Praktijkervaringen met de Venlow energy kas 2010-2012

    Kempkes, F.L.K.; Janse, J.

    2013-01-01

    NL De energiebesparing bij het nieuwe telen werd tot nu toe altijd bereikt door meer schermen te gebruiken. Een alternatief is toepassing van isolatieglas dat door de komst van coatings zoals Anti Refl ectie een vergelijkbare transmissie heeft als standaard enkel glas. Met een aangepast

  12. MET-RODOS: A comprehensive atmospheric dispersion module

    Mikkelsen, T.; Thykier-Nielsen, S.; Astrup, P.

    1997-01-01

    A comprehensive meteorological dispersion module called MET-RODOS is being developed to serve the real-time RODOS(1-3) decision support system with an integrated prediction capability for airborne radioactive spread, deposition and gamma radiation exposure on all scales. Deposition, ground level ...

  13. Vakansiehuis met swembad. Herman Koch. Vertaal deur Daniel ...

    - tig minuten (“my verkoopspunt”), maar. “[p]asiënte verwar tyd met aandag”. Marc luistert niet echt, want een huisarts. “hoef mense nie gesond te maak nie” (12). En als ze zich niet laten afschepen, doet hij maar een rectaal touché, want “hulle.

  14. Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with early-onset bipolar disorder.

    Nassan, Malik; Croarkin, Paul E; Luby, Joan L; Veldic, Marin; Joshi, Paramjit T; McElroy, Susan L; Post, Robert M; Walkup, John T; Cercy, Kelly; Geske, Jennifer R; Wagner, Karen D; Cuellar-Barboza, Alfredo B; Casuto, Leah; Lavebratt, Catharina; Schalling, Martin; Jensen, Peter S; Biernacka, Joanna M; Frye, Mark A

    2015-09-01

    Brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) functional polymorphism has been implicated in early-onset bipolar disorder. However, results of studies are inconsistent. We aimed to further explore this association. DNA samples from the Treatment of Early Age Mania (TEAM) and Mayo Clinic Bipolar Disorder Biobank were investigated for association of rs6265 with early-onset bipolar disorder. Bipolar cases were classified as early onset if the first manic or depressive episode occurred at age ≤19 years (versus adult-onset cases at age >19 years). After quality control, 69 TEAM early-onset bipolar disorder cases, 725 Mayo Clinic bipolar disorder cases (including 189 early-onset cases), and 764 controls were included in the analysis of association, assessed with logistic regression assuming log-additive allele effects. Comparison of TEAM cases with controls suggested association of early-onset bipolar disorder with the rs6265 minor allele [odds ratio (OR) = 1.55, p = 0.04]. Although comparison of early-onset adult bipolar disorder cases from the Mayo Clinic versus controls was not statistically significant, the OR estimate indicated the same direction of effect (OR = 1.21, p = 0.19). When the early-onset TEAM and Mayo Clinic early-onset adult groups were combined and compared with the control group, the association of the minor allele rs6265 was statistically significant (OR = 1.30, p = 0.04). These preliminary analyses of a relatively small sample with early-onset bipolar disorder are suggestive that functional variation in BDNF is implicated in bipolar disorder risk and may have a more significant role in early-onset expression of the disorder. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Identification of common bean alleles resistant to anthracnose using RAPD

    Ana L.M. Castanheira

    1999-12-01

    Full Text Available RAPD markers were identified close to common bean alleles responsible for resistance to the fungus Colletotrichum lindemuthianum and may be useful in selecting plants resistant to this pathogen. DNA from F2 plants of the crosses Carioca 300V x P45, Carioca 300V x Ouro and P24 x Ouro was amplified by RAPD. Line P45 has the Co.4 allele for resistance, and the Ouro cultivar has the Co.5 allele. The primer OPC08 amplified a DNA fragment of about 1059 bp linked to the Co.4 allele. The recombination frequency was 0.133 (SE = 0.039; 95% CI = 0.056-0.211. Using the primer OPF10 a DNA fragment of about 912 bp was amplified and found to be associated with the Co.5 allele. The recombination frequency was 0.115 (SE = 0.038; 95% CI = 0.041-0.189. A second marker (1122 pb amplified by the OPR03 primer was identified in the population P24 x Ouro. The recombination frequency for this marker was 0.363 (SE = 0.081; 95% CI = 0.205-0.522. Both these markers flanked the Co.5 allele. The markers identified in this study may be useful in identifying lines with the Co.4 and Co.5 alleles.Marcadores RAPD foram identificados próximos de alelos do feijão responsáveis pela resistência ao Colletotrichum lindemuthianum, visando auxiliar na seleção de plantas resistentes ao patógeno. Empregou-se o método dos bulks segregantes de DNA extraídos de plantas F2 dos seguintes cruzamentos: Carioca 300V x P45, Carioca 300V x Ouro e P24 x Ouro. A linhagem P45 é portadora do alelo Co.4 de resistência e o cultivar Ouro é portador do alelo Co.5, os quais foram marcados. Procedeu-se à reação RAPD dos bulks e foi identificado o iniciador OPC08 que amplificou um fragmento de DNA com cerca de 1059 pb, ligado ao alelo Co.4. A freqüência de recombinação foi de 0,133 (erro padrão 0,039 e o intervalo de confiança foi 0,056 e 0,211, com 95% de probabilidade. Em relação ao alelo Co.5 foi identificado um fragmento de DNA amplificado pelo iniciador OPF10 com cerca de 912 pb, na

  16. Allelic inhibition of displacement activity: a simplified one tube allele-specific PCR for evaluation of ITPA polymorphisms.

    Galmozzi, E; Facchetti, F; Degasperi, E; Aghemo, A; Lampertico, P

    2013-02-01

    Recently, genome-wide association studies (GWAS) in patients with chronic hepatitis C virus (HCV) infection have identified two functional single nucleotide polymorphisms (SNPs) in the inosine triphosphatase (ITPA) gene, that are associated strongly and independently with hemolytic anemia in patients exposed to pegylated-interferon (Peg-IFN) plus ribavirin (RBV) combined therapy. Here has been developed a simplified allele discrimination polymerase chain reaction (PCR) assay named allelic inhibition of displacement activity (AIDA) for evaluation of ITPA polymorphisms. AIDA system relies on three unlabeled primers only, two outer common primers and one inner primer with allele-specific 3' terminus mismatch. DNA samples from 192 patients with chronic HCV infection were used to validate the AIDA system and results were compared with the gold standard TaqMan(®) SNP genotyping assay. Concordant data were obtained for all samples, granting for high specificity of the method. In conclusion, AIDA is a practical one-tube method to reproducibly and to assess accurately rs7270101 and rs1127354 ITPA SNPs. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. HLA Dr beta 1 alleles in Pakistani patients with rheumatoid arthritis

    Naqi, N.; Ahmed, T.A.; Bashir, M.M.

    2011-01-01

    Objective: To determine frequencies of HLA DR beta 1 alleles in rheumatoid arthritis in Pakistani patients. Study Design: Cross sectional / analytical study. Place and Duration of Study: Department of Immunology, Armed Forces Institute of Pathology, Rawalpindi in collaboration with Rheumatology departments of Military Hospital, Rawalpindi and Fauji Foundation Hospital, Rawalpindi, from January 2009 to January 2010. Methodology: HLA DR beta 1 genotyping of one hundred Pakistani patients, diagnosed as having RA as per American College of Rheumatology revised criteria 1987, was done. HLA DR beta 1 genotyping was carried out at allele group level (DR beta 1*01-DR beta 1*16) by sequence specific primers in RA patients. Comparison of HLA DR beta 1 allele frequencies between patients and control groups was made using Pearson's chi-square test to find possible association of HLA DR?1 alleles with RA in Pakistani rheumatoid patients. Results: HLA DR beta 1*04 was expressed with significantly increased frequency in patients with rheumatoid arthritis (p <0.05). HLA DR?1*11 was expressed statistically significantly more in control group as compared to rheumatoid patients indicating a possible protective effect. There was no statistically significant difference observed in frequencies of HLA DR beta 1 allele *01, DR beta 1 allele *03, DR beta 1 allele *07, DR beta 1 allele *08, DR beta 1 allele *09, DR beta 1 allele *10, DR beta 1 allele *12, DR beta 1 allele *13, DR beta 1 allele *14, DR?1 allele *15 and DR beta 1 allele *16 between patients and control groups. Conclusion: The identification of susceptible HLA DR beta 1 alleles in Pakistani RA patients may help physicians to make early decisions regarding initiation of early intensive therapy with disease modifying anti rheumatic medicines and biological agents decreasing disability in RA patients. (author)

  18. MetAssimulo:Simulation of Realistic NMR Metabolic Profiles

    De Iorio Maria

    2010-10-01

    Full Text Available Abstract Background Probing the complex fusion of genetic and environmental interactions, metabolic profiling (or metabolomics/metabonomics, the study of small molecules involved in metabolic reactions, is a rapidly expanding 'omics' field. A major technique for capturing metabolite data is 1H-NMR spectroscopy and this yields highly complex profiles that require sophisticated statistical analysis methods. However, experimental data is difficult to control and expensive to obtain. Thus data simulation is a productive route to aid algorithm development. Results MetAssimulo is a MATLAB-based package that has been developed to simulate 1H-NMR spectra of complex mixtures such as metabolic profiles. Drawing data from a metabolite standard spectral database in conjunction with concentration information input by the user or constructed automatically from the Human Metabolome Database, MetAssimulo is able to create realistic metabolic profiles containing large numbers of metabolites with a range of user-defined properties. Current features include the simulation of two groups ('case' and 'control' specified by means and standard deviations of concentrations for each metabolite. The software enables addition of spectral noise with a realistic autocorrelation structure at user controllable levels. A crucial feature of the algorithm is its ability to simulate both intra- and inter-metabolite correlations, the analysis of which is fundamental to many techniques in the field. Further, MetAssimulo is able to simulate shifts in NMR peak positions that result from matrix effects such as pH differences which are often observed in metabolic NMR spectra and pose serious challenges for statistical algorithms. Conclusions No other software is currently able to simulate NMR metabolic profiles with such complexity and flexibility. This paper describes the algorithm behind MetAssimulo and demonstrates how it can be used to simulate realistic NMR metabolic profiles with

  19. A high-throughput method for genotyping S-RNase alleles in apple

    Larsen, Bjarne; Ørgaard, Marian; Toldam-Andersen, Torben Bo

    2016-01-01

    We present a new efficient screening tool for detection of S-alleles in apple. The protocol using general and multiplexed primers for PCR reaction and fragment detection on an automatized capillary DNA sequencer exposed a higher number of alleles than any previous studies. Analysis of alleles...

  20. Expression and loss of alleles in cultured mouse embryonic fibroblasts and stem cells carrying allelic fluorescent protein genes

    Stringer Saundra L

    2006-10-01

    Full Text Available Abstract Background Loss of heterozygosity (LOH contributes to many cancers, but the rate at which these events occur in normal cells of the body is not clear. LOH would be detectable in diverse cell types in the body if this event were to confer an obvious cellular phenotype. Mice that carry two different fluorescent protein genes as alleles of a locus would seem to be a useful tool for addressing this issue because LOH would change a cell's phenotype from dichromatic to monochromatic. In addition, LOH caused by mitotic crossing over might be discernable in tissues because this event produces a pair of neighboring monochromatic cells that are different colors. Results As a step in assessing the utility of this approach, we derived primary embryonic fibroblast populations and embryonic stem cell lines from mice that carried two different fluorescent protein genes as alleles at the chromosome 6 locus, ROSA26. Fluorescence activated cell sorting (FACS showed that the vast majority of cells in each line expressed the two marker proteins at similar levels, and that populations exhibited expression noise similar to that seen in bacteria and yeast. Cells with a monochromatic phenotype were present at frequencies on the order of 10-4 and appeared to be produced at a rate of approximately 10-5 variant cells per mitosis. 45 of 45 stably monochromatic ES cell clones exhibited loss of the expected allele at the ROSA26 locus. More than half of these clones retained heterozygosity at a locus between ROSA26 and the centromere. Other clones exhibited LOH near the centromere, but were disomic for chromosome 6. Conclusion Allelic fluorescent markers allowed LOH at the ROSA26 locus to be detected by FACS. LOH at this locus was usually not accompanied by LOH near the centromere, suggesting that mitotic recombination was the major cause of ROSA26 LOH. Dichromatic mouse embryonic cells provide a novel system for studying genetic/karyotypic stability and factors

  1. APOE-ε4 Allele Altered the Rest-Stimulus Interactions in Healthy Middle-Aged Adults.

    Feng-Xian Yan

    Full Text Available The apolipoprotein E-ε4 allele is a well-known genetic risk factor for late-onset Alzheimer's disease, which also impacts the cognitive functions and brain network connectivity in healthy middle-aged adults without dementia. Previous studies mainly focused on the effects of apolipoprotein E-ε4 allele on single index using task or resting-state fMRI. However, how these evoked and spontaneous BOLD indices interact with each other remains largely unknown. Therefore, we evaluated the 'rest-stimulus interaction' between working-memory activation and resting-state connectivity in middle-aged apolipoprotein E-ε4 carriers (n=9 and non-carriers (n=8. Four n-back task scans (n = 0, 1, 2, 3 and one resting-state scan were acquired at a 3T clinical MRI scanner. The working-memory beta maps of low-, moderate-, and high-memory loads and resting-state connectivity maps of default mode, executive control, and hippocampal networks were derived and compared between groups. Apolipoprotein E-ε4 carriers presented declined working-memory activation in the high-memory load across whole brain regions and reduced hippocampal connectivity compared with non-carriers. In addition, disrupted rest-stimulus interactions were found in the right anterior insula and bilateral parahippocampal regions for middle-aged adults with apolipoprotein E-ε4 allele. The rest-stimulus interaction improved the detectability of network integrity changes in apolipoprotein E-ε4 carriers, demonstrating the disrupted intrinsic connectivity within the executive-functional regions and the modulated memory-encoding capability within hippocampus-related regions.

  2. 75 FR 1007 - MetLife, Inc. and MetLife Capital Trust V; Notice of Application

    2010-01-07

    ... the definition of investment company by section 3(b) of the Act or by the rules or regulations under... Act for an exclusion from the definition of an investment company. To the extent MetLife or another... definition of a ``parent company'' in rule 3a-5(b)(2)(i) solely because it is an ``insurance company'' or...

  3. BDNF Val 66 Met and 5-HTTLPR genotype moderate the impact of early psychosocial adversity on plasma brain-derived neurotrophic factor and depressive symptoms: a prospective study.

    Buchmann, Arlette F; Hellweg, Rainer; Rietschel, Marcella; Treutlein, Jens; Witt, Stephanie H; Zimmermann, Ulrich S; Schmidt, Martin H; Esser, Günter; Banaschewski, Tobias; Laucht, Manfred; Deuschle, Michael

    2013-08-01

    Recent studies have emphasized an important role for neurotrophins, such as brain-derived neurotrophic factor (BDNF), in regulating the plasticity of neural circuits involved in the pathophysiology of stress-related diseases. The aim of the present study was to examine the interplay of the BDNF Val⁶⁶Met and the serotonin transporter promoter (5-HTTLPR) polymorphisms in moderating the impact of early-life adversity on BDNF plasma concentration and depressive symptoms. Participants were taken from an epidemiological cohort study following the long-term outcome of early risk factors from birth into young adulthood. In 259 individuals (119 males, 140 females), genotyped for the BDNF Val⁶⁶Met and the 5-HTTLPR polymorphisms, plasma BDNF was assessed at the age of 19 years. In addition, participants completed the Beck Depression Inventory (BDI). Early adversity was determined according to a family adversity index assessed at 3 months of age. Results indicated that individuals homozygous for both the BDNF Val and the 5-HTTLPR L allele showed significantly reduced BDNF levels following exposure to high adversity. In contrast, BDNF levels appeared to be unaffected by early psychosocial adversity in carriers of the BDNF Met or the 5-HTTLPR S allele. While the former group appeared to be most susceptible to depressive symptoms, the impact of early adversity was less pronounced in the latter group. This is the first preliminary evidence indicating that early-life adverse experiences may have lasting sequelae for plasma BDNF levels in humans, highlighting that the susceptibility to this effect is moderated by BDNF Val⁶⁶Met and 5-HTTLPR genotype. Copyright © 2013. Published by Elsevier B.V.

  4. Genetic sensitivity to the caregiving context: The influence of 5httlpr and BDNF val66met on indiscriminate social behavior

    Drury, Stacy S; Gleason, Mary Margaret; Theall, Katherine; Smyke, Anna T; Nelson, Charles A; Fox, Nathan A; Zeanah, Charles H

    2014-01-01

    Evidence that gene x environment interactions can reflect differential sensitivity to the environmental context, rather than risk or resilience, is increasing. To test this model, we examined the genetic contribution to indiscriminate social behavior, in the setting of a randomized controlled trial of foster care compared to institutional rearing. Children enrolled in the Bucharest Early Intervention Project (BEIP) were assessed comprehensively before the age of 30 months and subsequently randomized to either care as usual (CAUG) or high quality foster care (FCG). Indiscriminate social behavior was assessed at four time points, baseline, 30 months, 42 months and 54 months of age, using caregiver report with the Disturbances of Attachment Interview (DAI). General linear mixed-effects models were used to examine the effect of the interaction between group status and functional polymorphisms in Brain Derived Neurotrophic Factor (BDNF) and the Serotonin Transporter (5htt) on levels of indiscriminate behavior over time. Differential susceptibility, relative to levels of indiscriminate behavior, was demonstrated in children with either the s/s 5httlpr genotype or met 66 BDNF allele carriers. Specifically children with either the s/s 5httlpr genotype or met66 carriers in BDNF demonstrated the lowest levels of indiscriminate behavior in the FCG and the highest levels in the CAUG. Children with either the long allele of the 5httlpr or val/val genotype of BDNF demonstrated little difference in levels of indiscriminate behaviors over time and no group x genotype interaction. Children with both plasticity genotypes had the most signs of indiscriminate behavior at 54 months if they were randomized to the CAUG in the institution, while those with both plasticity genotypes randomized to the FCG intervention had the fewest signs at 54 months. Strikingly children with no plasticity alleles demonstrated no intervention effect on levels of indiscriminate behavior at 54 months. These

  5. Improvements to a Markerless Allelic Exchange System for Bacillus anthracis.

    Roger D Plaut

    Full Text Available A system was previously developed for conducting I-SceI-mediated allelic exchange in Bacillus anthracis. In this system, recombinational loss of a chromosomally-integrated allelic exchange vector is stimulated by creation of a double-stranded break within the vector by the homing endonuclease I-SceI. Although this system is reasonably efficient and represents an improvement in the tools available for allelic exchange in B. anthracis, researchers are nonetheless required to "pick and patch" colonies in order to identify candidate "exchangeants." In the present study, a number of improvements have been made to this system: 1 an improved I-SceI-producing plasmid includes oriT so that both plasmids can now be introduced by conjugation, thus avoiding the need for preparing electro-competent cells of each integration intermediate; 2 antibiotic markers have been changed to allow the use of the system in select agent strains; and 3 both plasmids have been marked with fluorescent proteins, allowing the visualization of plasmid segregation on a plate and obviating the need for "picking and patching." These modifications have made the process easier, faster, and more efficient, allowing for parallel construction of larger numbers of mutant strains. Using this improved system, the genes encoding the tripartite anthrax toxin were deleted singly and in combination from plasmid pXO1 of Sterne strain 34F2. In the course of this study, we determined that DNA transfer to B. anthracis could be accomplished by conjugation directly from a methylation-competent E. coli strain.

  6. HLA-DR alleles among Pakistani patients of coeliac disease

    Saleem, N.; Ahmed, T.A.; Bashir, M.; Ali, S.; Iqbal, M.

    2013-01-01

    Objectives: To investigate whether certain DR alleles might also contribute to the genetic susceptibility among Coeliac disease patients in Pakistan. Methods: The case-control study was conducted at the Military Hospital, Rawalpindi, from October 2011 to January 2012, and analysed 25 children diagnosed to have coeliac disease as per the criteria set by the European Society of Paediatric Gastroenterology and Nutrition, which included histopathological alterations in duodenal biopsies, clinical response to gluten withdrawal, and presence of anti-endomyseal antibodies. Patients were compared with a group of 150 healthy subjects. Dioxyribonucleic acid was extracted from peripheral blood collected in ethylenediaminetetraacetic acid.K3. Human leukocyte antigen DRB1 typing was carried out on allele level (DRB1*01 - DRB1*16) using sequence specific primers. Human leukocyte antigen type was determined by agarose gel electrophoresis and results were recorded. Phenotype frequency of various alleles among the patient group and the control group was calculated by direct counting, and significance of their association was determined by Fisher Exact Test. Results: A total of 11 (44%) female paediatric coeliac patients in age range 1-9 (mean 7.2+-4.8 years) and 14 (56%) male paediatric patients in the age range 6-14 (mean 8.6+-5.1 years) were genotyped for HLA-DRB1 loci. A statistically significant positive association of the disease with HLA-DRB1*03 (n=23; 92% versus n=31; 21% in controls, p <0.01) was observed. Conclusion: HLA-DRB1*03 is associated with increased risk of developing coeliac disease. (author)

  7. Exploring new alleles for frost tolerance in winter rye.

    Erath, Wiltrud; Bauer, Eva; Fowler, D Brian; Gordillo, Andres; Korzun, Viktor; Ponomareva, Mira; Schmidt, Malthe; Schmiedchen, Brigitta; Wilde, Peer; Schön, Chris-Carolin

    2017-10-01

    Rye genetic resources provide a valuable source of new alleles for the improvement of frost tolerance in rye breeding programs. Frost tolerance is a must-have trait for winter cereal production in northern and continental cropping areas. Genetic resources should harbor promising alleles for the improvement of frost tolerance of winter rye elite lines. For frost tolerance breeding, the identification of quantitative trait loci (QTL) and the choice of optimum genome-based selection methods are essential. We identified genomic regions involved in frost tolerance of winter rye by QTL mapping in a biparental population derived from a highly frost tolerant selection from the Canadian cultivar Puma and the European elite line Lo157. Lines per se and their testcrosses were phenotyped in a controlled freeze test and in multi-location field trials in Russia and Canada. Three QTL on chromosomes 4R, 5R, and 7R were consistently detected across environments. The QTL on 5R is congruent with the genomic region harboring the Frost resistance locus 2 (Fr-2) in Triticeae. The Puma allele at the Fr-R2 locus was found to significantly increase frost tolerance. A comparison of predictive ability obtained from the QTL-based model with different whole-genome prediction models revealed that besides a few large, also small QTL effects contribute to the genomic variance of frost tolerance in rye. Genomic prediction models assigning a high weight to the Fr-R2 locus allow increasing the selection intensity for frost tolerance by genome-based pre-selection of promising candidates.

  8. The Rh allele frequencies in Gaza city in Palestine

    Skaik Younis

    2011-01-01

    Full Text Available Background: The Rh blood group system is the second most clinically significant blood group system. It includes 49 antigens, but only five (D, C, E, c and e are the most routinely identified due to their unique relation to hemolytic disease of the newborn (HDN and transfusion reactions. Frequency of the Rh alleles showed variation, with regard to race and ethnic. Objectives: The purpose of the study was to document the Rh alleles′ frequencies amongst males (M and females (F in Gaza city in Palestine. Materials and Methods: Two hundred and thirty-two blood samples (110 M and 122 F were tested against monoclonal IgM anti-C,anti-c, anti-E, anti-e and a blend of monoclonal/polyclonal IgM/IgG anti-D. The expected Rh phenotypes were calculated using gene counting method. Results: The most frequent Rh antigen in the total sample was e, while the least frequent was E.The order of the combined Rh allele frequencies in both M and F was CDe > cDe > cde > CdE > cDE > Cde > CDE. A significant difference was reported between M and F regarding the phenotypic frequencies (P < 0.05. However, no significance (P > 0.05 was reported with reference to the observed and expected Rh phenotypic frequencies in either M or F students. Conclusion: It was concluded that the Rh antigens, alleles and phenotypes in Gaza city have unique frequencies, which may be of importance to the Blood Transfusion Center in Gaza city and anthropology.

  9. Allele-sharing models: LOD scores and accurate linkage tests.

    Kong, A; Cox, N J

    1997-11-01

    Starting with a test statistic for linkage analysis based on allele sharing, we propose an associated one-parameter model. Under general missing-data patterns, this model allows exact calculation of likelihood ratios and LOD scores and has been implemented by a simple modification of existing software. Most important, accurate linkage tests can be performed. Using an example, we show that some previously suggested approaches to handling less than perfectly informative data can be unacceptably conservative. Situations in which this model may not perform well are discussed, and an alternative model that requires additional computations is suggested.

  10. Allelic drop-out probabilities estimated by logistic regression

    Tvedebrink, Torben; Eriksen, Poul Svante; Asplund, Maria

    2012-01-01

    We discuss the model for estimating drop-out probabilities presented by Tvedebrink et al. [7] and the concerns, that have been raised. The criticism of the model has demonstrated that the model is not perfect. However, the model is very useful for advanced forensic genetic work, where allelic drop-out...... is occurring. With this discussion, we hope to improve the drop-out model, so that it can be used for practical forensic genetics and stimulate further discussions. We discuss how to estimate drop-out probabilities when using a varying number of PCR cycles and other experimental conditions....

  11. Remote Sensing of Volcanic ASH at the Met Office

    Marenco F.

    2016-01-01

    Full Text Available The eruption of Eyjafjallajökull in 2010 has triggered the rapid development of volcanic ash remote sensing activities at the Met Office. Volcanic ash qualitative and quantitative mapping have been achieved using lidar on board the Facility for Airborne Atmospheric Measurements (FAAM research aircraft, and using improved satellite retrieval algorithms. After the eruption, a new aircraft facility, the Met Office Civil Contingencies Aircraft (MOCCA, has been set up to enable a rapid response, and a network of ground-based remote sensing sites with lidars and sunphotometers is currently being developed. Thanks to these efforts, the United Kingdom (UK will be much better equipped to deal with such a crisis, should it happen in the future.

  12. Operational Use of OGC Web Services at the Met Office

    Wright, Bruce

    2010-05-01

    The Met Office has adopted the Service-Orientated Architecture paradigm to deliver services to a range of customers through Rich Internet Applications (RIAs). The approach uses standard Open Geospatial Consortium (OGC) web services to provide information to web-based applications through a range of generic data services. "Invent", the Met Office beta site, is used to showcase Met Office future plans for presenting web-based weather forecasts, product and information to the public. This currently hosts a freely accessible Weather Map Viewer, written in JavaScript, which accesses a Web Map Service (WMS), to deliver innovative web-based visualizations of weather and its potential impacts to the public. The intention is to engage the public in the development of new web-based services that more accurately meet their needs. As the service is intended for public use within the UK, it has been designed to support a user base of 5 million, the analysed level of UK web traffic reaching the Met Office's public weather information site. The required scalability has been realised through the use of multi-tier tile caching: - WMS requests are made for 256x256 tiles for fixed areas and zoom levels; - a Tile Cache, developed in house, efficiently serves tiles on demand, managing WMS request for the new tiles; - Edge Servers, externally hosted by Akamai, provide a highly scalable (UK-centric) service for pre-cached tiles, passing new requests to the Tile Cache; - the Invent Weather Map Viewer uses the Google Maps API to request tiles from Edge Servers. (We would expect to make use of the Web Map Tiling Service, when it becomes an OGC standard.) The Met Office delivers specialist commercial products to market sectors such as transport, utilities and defence, which exploit a Web Feature Service (WFS) for data relating forecasts and observations to specific geographic features, and a Web Coverage Service (WCS) for sub-selections of gridded data. These are locally rendered as maps or

  13. Estimation of METs by Accelerometers while Walking and Running

    Kurihara, Yosuke; Watanabe, Kajiro; Yoneyama, Mitsuru

    It is quite important for Japan to maintain or promote the health condition of elderly citizens. Given the circumstances, the Ministry of Health, Labour and Welfare has established the standards for the activities and exercises for promoting the health, and quantitatively determined the exercise intensity on 107 items of activities. This exercise intensity, however, requires recording the type and the duration of the activity to be calculated. In this paper, the exercise intensities are surmised using 3D accelerometer while the subjects are walking and running. As the result, the exercise intensities were surmised to be within the root mean square error of 1.2[METs] for walking and 3.2[METs] for running respectively.

  14. Testing ATLAS Z+MET excess with LHC run 2

    Lu, Xiaochuan; Terada, Takahiro

    2016-05-01

    The ATLAS collaboration reported a 3σ excess in the search of events containing on-Z dilepton, jets, and large missing momentum (MET) in the 8 TeV LHC run. Motivated by this excess, many models of new physics have been proposed. Recently, the ATLAS and CMS collaborations reported new results for similar Z+MET channels in the 13 TeV run. In this paper, we comprehensively discuss the consistency between the proposed models and the LHC results of Run 1 and Run 2. We find that in models with heavy gluino production, there is generically some tension between the 8 TeV and 13 TeV results. On the other hand, models with light squark production provide relatively better fitting to both results.

  15. Cetuximab-Induced MET Activation Acts as a Novel Resistance Mechanism in Colon Cancer Cells

    Na Song

    2014-04-01

    Full Text Available Aberrant MET expression and hepatocyte growth factor (HGF signaling are implicated in promoting resistance to targeted agents; however, the induced MET activation by epidermal growth factor receptor (EGFR inhibitors mediating resistance to targeted therapy remains elusive. In this study, we identified that cetuximab-induced MET activation contributed to cetuximab resistance in Caco-2 colon cancer cells. MET inhibition or knockdown sensitized Caco-2 cells to cetuximab-mediated growth inhibition. Additionally, SRC activation promoted cetuximab resistance by interacting with MET. Pretreatment with SRC inhibitors abolished cetuximab-mediated MET activation and rendered Caco-2 cells sensitive to cetuximab. Notably, cetuximab induced MET/SRC/EGFR complex formation. MET inhibitor or SRC inhibitor suppressed phosphorylation of MET and SRC in the complex, and MET inhibitor singly led to disruption of complex formation. These results implicate alternative targeting of MET or SRC as rational strategies for reversing cetuximab resistance in colon cancer.

  16. MetWAMer: eukaryotic translation initiation site prediction

    Brendel Volker

    2008-09-01

    Full Text Available Abstract Background Translation initiation site (TIS identification is an important aspect of the gene annotation process, requisite for the accurate delineation of protein sequences from transcript data. We have developed the MetWAMer package for TIS prediction in eukaryotic open reading frames of non-viral origin. MetWAMer can be used as a stand-alone, third-party tool for post-processing gene structure annotations generated by external computational programs and/or pipelines, or directly integrated into gene structure prediction software implementations. Results MetWAMer currently implements five distinct methods for TIS prediction, the most accurate of which is a routine that combines weighted, signal-based translation initiation site scores and the contrast in coding potential of sequences flanking TISs using a perceptron. Also, our program implements clustering capabilities through use of the k-medoids algorithm, thereby enabling cluster-specific TIS parameter utilization. In practice, our static weight array matrix-based indexing method for parameter set lookup can be used with good results in data sets exhibiting moderate levels of 5'-complete coverage. Conclusion We demonstrate that improvements in statistically-based models for TIS prediction can be achieved by taking the class of each potential start-methionine into account pending certain testing conditions, and that our perceptron-based model is suitable for the TIS identification task. MetWAMer represents a well-documented, extensible, and freely available software system that can be readily re-trained for differing target applications and/or extended with existing and novel TIS prediction methods, to support further research efforts in this area.

  17. Brain-derived neurotrophic factor gene val66met polymorphism and executive functioning in patients with bipolar disorder Polimorfismo do gene do fator neurotrófico derivado do cérebro val66met e função executiva em pacientes com transtorno bipolar

    Juliana Fernandes Tramontina

    2009-06-01

    Full Text Available OBJECTIVE: In the present study, we investigate the association between the val66met polymorphism of the brain-derived neurotrophic factor (BNDF and the performance on the Wisconsin Card Sorting Test in a sample of Caucasian Brazilian patients with bipolar disorder. METHOD: Sixty-four patients with bipolar disorder were assessed and their performance on the Wisconsin Card Sorting Test was compared with the allele frequency and genotype of the val66met polymorphism of the brain-derived neurotrophic factor. RESULTS: The percentage of non-perseverative errors was significantly higher among patients with the val/val genotype. There was no association between (BNDF genotype frequency and other Wisconsin Card Sorting Test domains. CONCLUSION: Our results did not replicate previous descriptions of an association between a worse cognitive performance and the presence of the met allele of the val66met brain-derived neurotrophic factor gene polymorphism.OBJETIVO: O presente estudo tem por objetivo investigar a associação entre o polimorfismo val66met do gene do fator neurotrófico derivado do cérebro (BDNF e o desempenho cognitivo no Teste Wisconsin de Classificação de Cartas em uma amostra de pacientes bipolares brasileiros caucasianos. MÉTODO: Sessenta e quatro pacientes com transtorno bipolar foram avaliados em relação a sua cognição por meio do Teste Wisconsin de Classificação de Cartas que foi comparada com a freqüência alélica e genotípica do polimorfismo val66met do gene do fator neurotrófico derivado do cérebro. RESULTADOS: O percentual de erros não-perseverativos foi significativamente maior nos indivíduos com genótipo val/val. Não foi encontrada diferença significativa entre a freqüência genotípica do polimorfismo do BDNF e os outros domínios do Teste Wisconsin de Classificação de Cartas. CONCLUSÃO: O estudo do polimorfismo val66met em relação ao desempenho executivo em pacientes bipolares caucasianos de uma

  18. Distribution load estimation (DLE)

    Seppaelae, A; Lehtonen, M [VTT Energy, Espoo (Finland)

    1998-08-01

    The load research has produced customer class load models to convert the customers` annual energy consumption to hourly load values. The reliability of load models applied from a nation-wide sample is limited in any specific network because many local circumstances are different from utility to utility and time to time. Therefore there is a need to find improvements to the load models or, in general, improvements to the load estimates. In Distribution Load Estimation (DLE) the measurements from the network are utilized to improve the customer class load models. The results of DLE will be new load models that better correspond to the loading of the distribution network but are still close to the original load models obtained by load research. The principal data flow of DLE is presented

  19. El sexo de las metáforas

    Pérez Sedeño, Eulalia

    2011-02-01

    Full Text Available The hypothesis that states metaphors are structurally determinant in our social relations, routines, and experience has been accepted broadly in the last decades. Moreover, metaphors are to be found in many different levels of scientific practices, and have a diverse set of functions in science. Therefore, they impregnate all scientific enterprise. In this work we examine selected gender metaphors used in biology. We show metaphors are effective precisely because its effectiveness depends on shared social conventions, kinship relations and, authority that, by convention, is given to those that use them.

    La tesis de que las metáforas estructuran gran parte de nuestras relaciones sociales y nuestra experiencia cotidiana ha sido ampliamente aceptada en las últimas décadas. En la ciencia, además, aparecen en muchos niveles y desempeñan diversas funciones, impregnando todo el quehacer científico. En este trabajo se examinan algunas metáforas de género usadas en biología. Se muestra que las metáforas eficaces lo son porque su efectividad depende de las convenciones sociales compartidas, los parecidos de familia ya vigentes y de la autoridad que, por convención, se otorga a quienes las usan.

  20. The EGFR/ErbB3 Pathway Acts as a Compensatory Survival Mechanism upon c-Met Inhibition in Human c-Met+ Hepatocellular Carcinoma.

    Steven N Steinway

    Full Text Available c-Met, a high-affinity receptor for Hepatocyte Growth Factor (HGF, plays a critical role in tumor growth, invasion, and metastasis. Hepatocellular carcinoma (HCC patients with activated HGF/c-Met signaling have a significantly worse prognosis. Targeted therapies using c-Met tyrosine kinase inhibitors are currently in clinical trials for HCC, although receptor tyrosine kinase inhibition in other cancers has demonstrated early success. Unfortunately, therapeutic effect is frequently not durable due to acquired resistance.We utilized the human MHCC97-H c-Met positive (c-Met+ HCC cell line to explore the compensatory survival mechanisms that are acquired after c-Met inhibition. MHCC97-H cells with stable c-Met knockdown (MHCC97-H c-Met KD cells were generated using a c-Met shRNA vector with puromycin selection and stably transfected scrambled shRNA as a control. Gene expression profiling was conducted, and protein expression was analyzed to characterize MHCC97-H cells after blockade of the c-Met oncogene. A high-throughput siRNA screen was performed to find putative compensatory survival proteins, which could drive HCC growth in the absence of c-Met. Findings from this screen were validated through subsequent analyses.We have previously demonstrated that treatment of MHCC97-H cells with a c-Met inhibitor, PHA665752, results in stasis of tumor growth in vivo. MHCC97-H c-Met KD cells demonstrate slower growth kinetics, similar to c-Met inhibitor treated tumors. Using gene expression profiling and siRNA screening against 873 kinases and phosphatases, we identified ErbB3 and TGF-α as compensatory survival factors that are upregulated after c-Met inhibition. Suppressing these factors in c-Met KD MHCC97-H cells suppresses tumor growth in vitro. In addition, we found that the PI3K/Akt signaling pathway serves as a negative feedback signal responsible for the ErbB3 upregulation after c-Met inhibition. Furthermore, in vitro studies demonstrate that

  1. Effects of the APOE ε2 Allele on Mortality and Cognitive Function in the Oldest Old

    Lindahl-Jacobsen, Rune; Tan, Qihua; Mengel-From, Jonas

    2013-01-01

    Some studies indicate that the APOE ε2 allele may have a protective effect on mortality and mental health among the elderly adults. We investigated the effect of the APOE ε2 allele on cognitive function and mortality in 1651 members of the virtually extinct Danish 1905 birth cohort. We found...... no protective effect of the APOE ε2 allele on mortality compared with the APOE ε3 allele. The point estimates indicated an increased protection against cognitive decline over time for persons with the APOE ε2 allele. Cognitive score did not significantly modify the mortality risk of the various APOE genotypes....... We did not find a protective effect of the APOE ε2 allele on mortality among the oldest old, but in agreement with our previous findings, we found a 22% increased mortality risk for APOE ε4 carriers. The APOE ε2 allele may be protective on cognitive decline among the oldest old....

  2. A matching-allele model explains host resistance to parasites.

    Luijckx, Pepijn; Fienberg, Harris; Duneau, David; Ebert, Dieter

    2013-06-17

    The maintenance of genetic variation and sex despite its costs has long puzzled biologists. A popular idea, the Red Queen Theory, is that under rapid antagonistic coevolution between hosts and their parasites, the formation of new rare host genotypes through sex can be advantageous as it creates host genotypes to which the prevailing parasite is not adapted. For host-parasite coevolution to lead to an ongoing advantage for rare genotypes, parasites should infect specific host genotypes and hosts should resist specific parasite genotypes. The most prominent genetics capturing such specificity are matching-allele models (MAMs), which have the key feature that resistance for two parasite genotypes can reverse by switching one allele at one host locus. Despite the lack of empirical support, MAMs have played a central role in the theoretical development of antagonistic coevolution, local adaptation, speciation, and sexual selection. Using genetic crosses, we show that resistance of the crustacean Daphnia magna against the parasitic bacterium Pasteuria ramosa follows a MAM. Simulation results show that the observed genetics can explain the maintenance of genetic variation and contribute to the maintenance of sex in the facultatively sexual host as predicted by the Red Queen Theory. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. An allele of the crm gene blocks cyanobacterial circadian rhythms.

    Boyd, Joseph S; Bordowitz, Juliana R; Bree, Anna C; Golden, Susan S

    2013-08-20

    The SasA-RpaA two-component system constitutes a key output pathway of the cyanobacterial Kai circadian oscillator. To date, rhythm of phycobilisome associated (rpaA) is the only gene other than kaiA, kaiB, and kaiC, which encode the oscillator itself, whose mutation causes completely arrhythmic gene expression. Here we report a unique transposon insertion allele in a small ORF located immediately upstream of rpaA in Synechococcus elongatus PCC 7942 termed crm (for circadian rhythmicity modulator), which results in arrhythmic promoter activity but does not affect steady-state levels of RpaA. The crm ORF complements the defect when expressed in trans, but only if it can be translated, suggesting that crm encodes a small protein. The crm1 insertion allele phenotypes are distinct from those of an rpaA null; crm1 mutants are able to grow in a light:dark cycle and have no detectable oscillations of KaiC phosphorylation, whereas low-amplitude KaiC phosphorylation rhythms persist in the absence of RpaA. Levels of phosphorylated RpaA in vivo measured over time are significantly altered compared with WT in the crm1 mutant as well as in the absence of KaiC. Taken together, these results are consistent with the hypothesis that the Crm polypeptide modulates a circadian-specific activity of RpaA.

  4. Characterization of a Weak Allele of Zebrafish cloche Mutant

    Ma, Ning; Huang, Zhibin; Chen, Xiaohui; He, Fei; Wang, Kun; Liu, Wei; Zhao, Linfeng; Xu, Xiangmin; Liao, Wangjun; Ruan, Hua; Luo, Shenqiu; Zhang, Wenqing

    2011-01-01

    Hematopoiesis is a complicated and dynamic process about which the molecular mechanisms remain poorly understood. Danio rerio (zebrafish) is an excellent vertebrate system for studying hematopoiesis and developmental mechanisms. In the previous study, we isolated and identified a cloche 172 (clo 172) mutant, a novel allele compared to the original cloche (clo) mutant, through using complementation test and initial mapping. Here, according to whole mount in-situ hybridization, we report that the endothelial cells in clo 172 mutant embryos, although initially developed, failed to form the functional vascular system eventually. In addition, further characterization indicates that the clo 172 mutant exhibited weaker defects instead of completely lost in primitive erythroid cells and definitive hematopoietic cells compared with the clo s5 mutant. In contrast, primitive myeloid cells were totally lost in clo 172 mutant. Furthermore, these reappeared definitive myeloid cells were demonstrated to initiate from the remaining hematopoietic stem cells (HSCs) in clo 172 mutant, confirmed by the dramatic decrease of lyc in clo 172 runx1w84x double mutant. Collectively, the clo 172 mutant is a weak allele compared to the clo s5 mutant, therefore providing a model for studying the early development of hematopoietic and vascular system, as well as an opportunity to further understand the function of the cloche gene. PMID:22132109

  5. Characterization of ROP18 alleles in human toxoplasmosis.

    Sánchez, Víctor; de-la-Torre, Alejandra; Gómez-Marín, Jorge Enrique

    2014-04-01

    The role of the virulent gene ROP18 polymorphisms is not known in human toxoplasmosis. A total of 320 clinical samples were analyzed. In samples positive for ROP18 gene, we determined by an allele specific PCR, if patients got the upstream insertion positive ROP18 sequence Toxoplasma strain (mouse avirulent strain) or the upstream insertion negative ROP18 sequence Toxoplasma strain (mouse virulent strain). We designed an ELISA assay for antibodies against ROP18 derived peptides from the three major clonal lineages of Toxoplasma. 20 clinical samples were of quality for ROP18 allele analysis. In patients with ocular toxoplasmosis, a higher inflammatory reaction on eye was associated to a PCR negative result for the upstream region of ROP18. 23.3%, 33% and 16.6% of serums from individuals with ocular toxoplasmosis were positive for type I, type II and type III ROP18 derived peptides, respectively but this assay was affected by cross reaction. The absence of Toxoplasma ROP18 promoter insertion sequence in ocular toxoplasmosis was correlated with severe ocular inflammatory response. Determination of antibodies against ROP18 protein was not useful for serotyping in human toxoplasmosis. © 2013.

  6. Distribution load estimation - DLE

    Seppaelae, A. [VTT Energy, Espoo (Finland)

    1996-12-31

    The load research project has produced statistical information in the form of load models to convert the figures of annual energy consumption to hourly load values. The reliability of load models is limited to a certain network because many local circumstances are different from utility to utility and time to time. Therefore there is a need to make improvements in the load models. Distribution load estimation (DLE) is the method developed here to improve load estimates from the load models. The method is also quite cheap to apply as it utilises information that is already available in SCADA systems

  7. Distribution load estimation - DLE

    Seppaelae, A [VTT Energy, Espoo (Finland)

    1997-12-31

    The load research project has produced statistical information in the form of load models to convert the figures of annual energy consumption to hourly load values. The reliability of load models is limited to a certain network because many local circumstances are different from utility to utility and time to time. Therefore there is a need to make improvements in the load models. Distribution load estimation (DLE) is the method developed here to improve load estimates from the load models. The method is also quite cheap to apply as it utilises information that is already available in SCADA systems

  8. Seasonal Changes in Brain Serotonin Transporter Binding in Short Serotonin Transporter Linked Polymorphic Region-Allele Carriers but Not in Long-Allele Homozygotes

    Kalbitzer, Jan; Erritzoe, David; Holst, Klaus K

    2010-01-01

    of the short 5-HTTLPR allele but not in homozygote carriers of the long allele. Conclusions: Our findings are in line with S-carriers having an increased response in neural circuits involved in emotional processing to stressful environmental stimuli but here demonstrated as a endophenotype with dynamic changes...

  9. Low frequency of the scrapile resistance-associated allele and presence of lysine-171 allele of the prion protein gene in Italian Biellese ovine breed

    Acutis, P.L.; Sbaiz, L.; Verburg, F.J.; Riina, M.V.; Ru, G.; Moda, G.; Caramelli, M.; Bossers, A.

    2004-01-01

    Frequencies of polymorphisms at codons 136, 154 and 171 of the prion protein (PrP) gene were studied in 1207 pure-bred and cross-bred Italian Biellese rams, a small ovine breed of about 65 000 head in Italy. Aside from the five most common alleles (VRQ, ARQ, ARR, AHQ and ARH), the rare ARK allele

  10. On the genetics of loss aversion: An interaction effect of BDNF Val66Met and DRD2/ANKK1 Taq1a.

    Voigt, Gesine; Montag, Christian; Markett, Sebastian; Reuter, Martin

    2015-12-01

    Loss aversion is the tendency to overweight losses compared with gains in decision situations. Several studies have investigated the neurobiological background of this phenomenon and it was found that activation in the mesolimbic-mesocortical dopamine system during a gambling decision correlates with loss aversion. In a behavioral experiment with N = 143 subjects, the present study investigates the influence of 2 functional single-nucleotide polymorphisms on the BDNF gene (BDNF Val66Met polymorphism) and ANKK1 gene (DRD2 Taq1a/ANKK1 polymorphism), that are known to affect the dopamine system, on loss aversion. Additionally, associations of alexithymia, a personality construct describing the disability to consciously experience emotions in the self, with loss aversion and with the mentioned polymorphisms were assessed using the TAS-20 questionnaire, to replicate associations that have been reported before. Results revealed a significant interaction effect of the 2 polymorphisms on loss aversion. Carriers of the genetic constellation 66Met+/A1+ had the lowest loss aversion scores, compared with all other allelic groups. According to the literature this allelic configuration is characterized by a relatively low D2/3 receptor binding in the striatum and an impaired activity-dependent secretion of BDNF. This is the first study showing that loss aversion is related to naturally occurring differences in dopamine function. (c) 2015 APA, all rights reserved).

  11. Deelname aan de samenleving van mensen met een beperking: participatiemonitor 2007.

    Hoogen, P. van den; Cardol, M.; Speet, M.; Spreeuwenberg, P.; Rijken, M.

    2008-01-01

    Hoe doen mensen met een beperking mee in de maatschappij? Mensen met een lichamelijke beperking wonen en werken meestal net als iedereen, en ook zij zijn niet altijd tevreden met hun werk. Mensen met een verstandelijke beperking wonen en werken vaak in een speciale omgeving. Het overheidsbeleid

  12. Brain-derived neurotrophic factor (Val66Met and serotonin transporter (5-HTTLPR polymorphisms modulate plasticity in inhibitory control performance over time but independent of inhibitory control training

    Sören Enge

    2016-07-01

    Full Text Available Several studies reported training-induced improvements in executive function tasks and also observed transfer to untrained tasks. However, the results are mixed and there is large interindividual variability within and across studies. Given that training-related performance changes would require modification, growth or differentiation at the cellular and synaptic level in the brain, research on critical moderators of brain plasticity potentially explaining such changes is needed. In the present study, a pre-post-follow-up design (N=122 and a three-weeks training of two response inhibition tasks (Go/NoGo and Stop-Signal was employed and genetic variation (Val66Met in the brain-derived neurotrophic factor (BDNF promoting differentiation and activity-dependent synaptic plasticity was examined. Because Serotonin (5-HT signaling and the interplay of BDNF and 5-HT are known to critically mediate brain plasticity, genetic variation in the 5-HT transporter (5-HTTLPR was also addressed. The overall results show that the kind of training (i.e., adaptive vs. non-adaptive did not evoke genotype-dependent differences. However, in the Go/NoGo task, better inhibition performance (lower commission errors were observed for BDNF Val/Val genotype carriers compared to Met-allele ones supporting similar findings from other cognitive tasks. Additionally, a gene-gene interaction suggests a more impulsive response pattern (faster responses accompanied by higher commission error rates in homozygous l-allele carriers relative to those with the s-allele of 5-HTTLPR. This, however, is true only in the presence of the Met-allele of BDNF, while the Val/Val genotype seems to compensate for such non-adaptive responding. Intriguingly, similar results were obtained for the Stop-Signal task. Here, differences emerged at post-testing, while no differences were observed at T1. In sum, although no genotype-dependent differences between the relevant training groups emerged suggesting

  13. MET gene exon 14 deletion created using the CRISPR/Cas9 system enhances cellular growth and sensitivity to a MET inhibitor.

    Togashi, Yosuke; Mizuuchi, Hiroshi; Tomida, Shuta; Terashima, Masato; Hayashi, Hidetoshi; Nishio, Kazuto; Mitsudomi, Tetsuya

    2015-12-01

    MET splice site mutations resulting in an exon 14 deletion have been reported to be present in about 3% of all lung adenocarcinomas. Patients with lung adenocarcinoma and a MET splice site mutation who have responded to MET inhibitors have been reported. The CRISPR/Cas9 system is a recently developed genome-engineering tool that can easily and rapidly cause small insertions or deletions. We created an in vitro model for MET exon 14 deletion using the CRISPR/Cas9 system and the HEK293 cell line. The phenotype, which included MET inhibitor sensitivity, was then investigated in vitro. Additionally, MET splice site mutations were analyzed in several cancers included in The Cancer Genome Atlas (TCGA) dataset. An HEK293 cell line with a MET exon 14 deletion was easily and rapidly created; this cell line had a higher MET protein expression level, enhanced MET phosphorylation, and prolonged MET activation. In addition, a direct comparison of phenotypes using this system demonstrated enhanced cellular growth, colony formation, and MET inhibitor sensitivity. In the TCGA dataset, lung adenocarcinomas had the highest incidence of MET exon 14 deletions, while other cancers rarely carried such mutations. Approximately 10% of the lung adenocarcinoma samples without any of driver gene alterations carried the MET exon 14 deletion. These findings suggested that this system may be useful for experiments requiring the creation of specific mutations, and the present experimental findings encourage the development of MET-targeted therapy against lung cancer carrying the MET exon 14 deletion. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Deelname aan de samenleving van mensen met een beperking: participatiemonitor 2007.

    Hoogen, P. van den; Cardol, M.; Speet, M.; Spreeuwenberg, P.; Rijken, M.

    2008-01-01

    Hoe doen mensen met een beperking mee in de maatschappij? Mensen met een lichamelijke beperking wonen en werken meestal net als iedereen, en ook zij zijn niet altijd tevreden met hun werk. Mensen met een verstandelijke beperking wonen en werken vaak in een speciale omgeving. Het overheidsbeleid is erop gericht dat iedereen – dus ook mensen met een beperking – zoveel mogelijk ‘gewoon mee kan doen’ in de maatschappij. Bijvoorbeeld werken bij een gewone werkgever, schoolgaan op een gewone school...

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

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

    2009-09-01

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

  16. Erasure and reestablishment of random allelic expression imbalance after epigenetic reprogramming.

    Jeffries, Aaron Richard; Uwanogho, Dafe Aghogho; Cocks, Graham; Perfect, Leo William; Dempster, Emma; Mill, Jonathan; Price, Jack

    2016-10-01

    Clonal level random allelic expression imbalance and random monoallelic expression provides cellular heterogeneity within tissues by modulating allelic dosage. Although such expression patterns have been observed in multiple cell types, little is known about when in development these stochastic allelic choices are made. We examine allelic expression patterns in human neural progenitor cells before and after epigenetic reprogramming to induced pluripotency, observing that loci previously characterized by random allelic expression imbalance (0.63% of expressed genes) are generally reset to a biallelic state in induced pluripotent stem cells (iPSCs). We subsequently neuralized the iPSCs and profiled isolated clonal neural stem cells, observing that significant random allelic expression imbalance is reestablished at 0.65% of expressed genes, including novel loci not found to show allelic expression imbalance in the original parental neural progenitor cells. Allelic expression imbalance was associated with altered DNA methylation across promoter regulatory regions, with clones characterized by skewed allelic expression being hypermethylated compared to their biallelic sister clones. Our results suggest that random allelic expression imbalance is established during lineage commitment and is associated with increased DNA methylation at the gene promoter. © 2016 Jeffries et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  17. Intrinsic MYH7 expression regulation contributes to tissue level allelic imbalance in hypertrophic cardiomyopathy.

    Montag, Judith; Syring, Mandy; Rose, Julia; Weber, Anna-Lena; Ernstberger, Pia; Mayer, Anne-Kathrin; Becker, Edgar; Keyser, Britta; Dos Remedios, Cristobal; Perrot, Andreas; van der Velden, Jolanda; Francino, Antonio; Navarro-Lopez, Francesco; Ho, Carolyn Yung; Brenner, Bernhard; Kraft, Theresia

    2017-08-01

    HCM, the most common inherited cardiac disease, is mainly caused by mutations in sarcomeric genes. More than a third of the patients are heterozygous for mutations in the MYH7 gene encoding for the β-myosin heavy chain. In HCM-patients, expression of the mutant and the wildtype allele can be unequal, thus leading to fractions of mutant and wildtype mRNA and protein which deviate from 1:1. This so-called allelic imbalance was detected in whole tissue samples but also in individual cells. There is evidence that the severity of HCM not only depends on the functional effect of the mutation itself, but also on the fraction of mutant protein in the myocardial tissue. Allelic imbalance has been shown to occur in a broad range of genes. Therefore, we aimed to examine whether the MYH7-alleles are intrinsically expressed imbalanced or whether the allelic imbalance is solely associated with the disease. We compared the expression of MYH7-alleles in non-HCM donors and in HCM-patients with different MYH7-missense mutations. In the HCM-patients, we identified imbalanced as well as equal expression of both alleles. Also at the protein level, allelic imbalance was determined. Most interestingly, we also discovered allelic imbalance and balance in non-HCM donors. Our findings therefore strongly indicate that apart from mutation-specific mechanisms, also non-HCM associated allelic-mRNA expression regulation may account for the allelic imbalance of the MYH7 gene in HCM-patients. Since the relative amount of mutant mRNA and protein or the extent of allelic imbalance has been associated with the severity of HCM, individual analysis of the MYH7-allelic expression may provide valuable information for the prognosis of each patient.

  18. Advanced CerMet ceramic composites for medical applications.

    Dittmer, Robert; Schaefer, Christian M; Fischer, Jean-Francois; Hausch, Ulrich; Troetzschel, Jens; Specht, Heiko

    2017-11-01

    Implantable active devices such as pacemakers are facing rigorous requirements. Because they reside within the body for years, materials applied in this surrounding must exhibit biocompatibility and extraordinary reliability. They also have to provide a number of functional properties. In this work we present a method that enables the realization of a highly complex profile of properties by means of a dual composite approach. Using multilayer technology, an electrical conductor is embedded into a ceramic matrix, thus, creating conductive paths that are insulated from each other. In addition to this macroscopically hybrid architecture, this approach features a second composite aspect: the conductor is not composed of a single metallic phase, but is a ceramic-metal mixture. Owing to its interpenetrating microstructure, this CerMet allows for a strong and hermetic integration of the conductor into the ceramic matrix otherwise impossible due to mismatch in thermal expansion. In fact, the CerMet ceramic composite exhibits a higher strength than the pure ceramic as revealed by a three-point bending test study. At the same time, the CerMet offers high and virtually metal-like conductor properties, enabling a down-scaling of the conductive paths to 150µm diameter and smaller. Furthermore, the described composite is biocompatible, non-magnetic, and chemically inert, which is vital for the application in active, implantable, medical devices. Beside the general fabrication route, we present the microstructural, functional, and mechanical properties of this newly developed class of dual composites. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Sandscape - engaging people in Met Office science through sand sculpture

    Liggins, Felicity; Dowell, Ellen; Wardley, Jamie; Jamieson, Claire

    2017-04-01

    In 2015, the Met Office's award-winning outreach programme, designed to inspire the next generation of scientists and engineers, delivered one of its most ambitious and creative activities to date. It explored how scientists and artists can come together to create an engaging experience for young people and families. This activity was called Sandscape. Sandscape is an interactive sand sculpture workshop exploring how weather and climate affect our health. Budding sand sculptors are shown how to fashion elaborate structures from sand and water - creating a landscape with bridges, skyscrapers, forests and factories. As they work, participants are encouraged by the scientists delivering the activity to reflect on what makes a healthy city, considering how the natural and built environments influence air quality and circulation and how this impacts our health. Topics discussed include urban heat islands, air pollution and dispersion modelling, pollen forecasting and predicting the wind-borne spread of animal diseases. Each hour long workshop culminates in a dramatic demonstration that uses dry ice to represent clean air circulating from mountains, along rivers and into cities. Here we present an overview of Sandscape, identify the strengths and challenges of such a collaborative, innovative and playful approach to public engagement and share the results of our evaluation. Sandscape was originally supported by the Met Office and the Wellcome Trust, and produced by Einstein's Garden in collaboration with the Met Office, scientists from the University of Exeter and sand sculptors from Sand in Your Eye. It was first presented in Einstein's Garden at Green Man festival 2015, an independent music and arts festival held annually in Wales, and has since been invited to run at the 2015 Bournemouth Arts By the Sea Festival and Teignmouth's TRAIL Sculpture Festival in the summer of 2016.

  20. Met receptor inhibitor SU11274 localizes in the endoplasmic reticulum.

    Wiest, Edwin J; Smith, Heather Jensen; Hollingsworth, Michael A

    2018-07-02

    We discovered that SU11274, a class I c-Met inhibitor, fluoresces when excited by 488 nm laser light and showed rapid specific accumulation in distinct subcellular compartments. Given that SU11274 reduces cancer cell viability, we exploited these newly identified spectral properties to determine SU11274 intracellular distribution and accumulation in human pancreatic cancer cells. The aim of the studies reported here was to identify organelle(s) to which SU11274 is trafficked. We conclude that SU11274 rapidly and predominantly accumulates in the endoplasmic reticulum. Copyright © 2018. Published by Elsevier Inc.

  1. A Comparative Study of virtual and operational met mast data

    Orhan, Dr Ö Emre; Ahmet, Gökhan

    2014-01-01

    Performance of wind assessment studies depend on the adequacy and duration of the wind data. For a reasonable wind assessment, at least one full year wind data is needed so that, all the variations throughout the year are represented. On the other hand, it is always a question of time and cost how to get the wind data. On-site measurements are the most common way of obtaining wind data but it is the most expensive and time consuming as well. Apart from onsite data, there are also reanalysis long term data sources like MERRA, NCAR, etc. Time and spatial resolution of these long term data are lower compared to on-site measurements but in cases where on-site measurements are not available, they are also utilized. On top of on-site and reanalysis wind data, weather forecasting models like WRF, MM5 are available. Although, these models mainly are used for forecasting services, flexibility of the models makes them suitable for preliminary resource assessment purposes. In this study, comparisons of annual energy production estimations are computed using virtual and on-site met mast data separately for a specific time range. The widely used weather research and forecasting model (WRF) is used to provide virtual met mast data. Once WRF simulations are completed, interpolation routines are employed in order to extract data for a specific location. The on-site met mast is located inside a wind farm project area which is under development. Project site is located in the south of Turkey. There are four different met masts, three of them recording wind data presently. On-site measurements together with WRF results are used to obtain energy yields for the project area. The performance of both methodologies is compared. It has been observed that WRF can as well serve as a preliminary model in cases where no other data source is available but the model has to be implemented with great care depending on the project site conditions

  2. Cementitious Stabilization of Mixed Wastes with High Salt Loadings

    Spence, R.D.; Burgess, M.W.; Fedorov, V.V.; Downing, D.J.

    1999-01-01

    Salt loadings approaching 50 wt % were tolerated in cementitious waste forms that still met leach and strength criteria, addressing a Technology Deficiency of low salt loadings previously identified by the Mixed Waste Focus Area. A statistical design quantified the effect of different stabilizing ingredients and salt loading on performance at lower loadings, allowing selection of the more effective ingredients for studying the higher salt loadings. In general, the final waste form needed to consist of 25 wt % of the dry stabilizing ingredients to meet the criteria used and 25 wt % water to form a workable paste, leaving 50 wt % for waste solids. The salt loading depends on the salt content of the waste solids but could be as high as 50 wt % if all the waste solids are salt

  3. Alkaline transition of pseudoazurin Met16X mutant proteins: protein stability influenced by the substitution of Met16 in the second sphere coordination.

    Abdelhamid, Rehab F; Obara, Yuji; Kohzuma, Takamitsu

    2008-01-01

    Several blue copper proteins are known to change the active site structure at alkaline pH (alkaline transition). Spectroscopic studies of Met16Phe, Met16Tyr, Met16Trp, and Met16Val pseudoazurin variants were performed to investigate the second sphere role through alkaline transition. The visible electronic absorption and resonance Raman spectra of Met16Phe, Met16Tyr, and Met16Trp variants showed the increasing of axial component at pH approximately 11 like wild-type PAz. The visible electronic absorption and far-UV CD spectra of Met16Val demonstrated that the destabilization of the protein structure was triggered at pH>11. Resonance Raman (RR) spectra of PAz showed that the intensity-weighted averaged Cu-S(Cys) stretching frequency was shifted to higher frequency region at pH approximately 11. The higher frequency shift of Cu-S(Cys) bond is implied the stronger Cu-S(Cys) bond at alkaline transition pH approximately 11. The visible electronic absorption and far-UV CD spectra of Met16X PAz revealed that the Met16Val variant is denatured at pH>11, but Met16Phe, Met16Tyr, and Met16Trp mutant proteins are not denatured even at pH>11. These observations suggest that Met16 is important to maintain the protein structure through the possible weak interaction between methionine -SCH3 part and coordinated histidine imidazole moiety. The introduction of pi-pi interaction in the second coordination sphere may be contributed to the enhancement of protein structure stability.

  4. A first-in-human phase I study of SAR125844, a selective MET tyrosine kinase inhibitor, in patients with advanced solid tumours with MET amplification.

    Angevin, Eric; Spitaleri, Gianluca; Rodon, Jordi; Dotti, Katia; Isambert, Nicolas; Salvagni, Stefania; Moreno, Victor; Assadourian, Sylvie; Gomez, Corinne; Harnois, Marzia; Hollebecque, Antoine; Azaro, Analia; Hervieu, Alice; Rihawi, Karim; De Marinis, Filippo

    2017-12-01

    Dysregulated MET signalling is implicated in oncogenesis. The safety and preliminary efficacy of a highly selective MET kinase inhibitor (SAR125844) was investigated in patients with advanced solid tumours and MET dysregulation. This was a phase I dose-escalation (3 + 3 design [50-740 mg/m 2 ]) and dose-expansion study. In the dose escalation, patients had high total MET (t-MET) expression by immunohistochemistry (IHC) or MET amplification by fluorescence in situ hybridisation. In the dose expansion, patients had MET amplification (including a subset of patients with non-small cell lung cancer [NSCLC]) or phosphorylated-MET (p-MET) expression (IHC). Objectives were determination of maximum tolerated dose (MTD) of once-weekly intravenous SAR125844 based on dose-limiting toxicities; safety and pharmacokinetic profile; preliminary efficacy of SAR125844 MTD in the expansion cohort. In total, 72 patients were enrolled: dose escalation, N = 33; dose expansion, N = 39; 570 mg/m 2 was established as the MTD. Most frequent treatment-emergent adverse events (AEs) were asthenia/fatigue (58.3%), nausea (31.9%), and abdominal pain, constipation, and dyspnea (27.8% for each); 58.3% of patients reported grade 3 AEs (19.4% were treatment related). Of the 29 evaluable patients with MET amplification treated at 570 mg/m 2 , five achieved a partial response, including four of 22 with NSCLC; 17 patients had stable disease. No response was observed in patients with high p-MET solid tumours. There was no correlation between tumour response and t-MET status or MET gene copy number. The MTD of once-weekly SAR125844 was 570 mg/m 2 ; SAR125844 was well tolerated, with significant antitumour activity in patients with MET-amplified NSCLC. NCT01391533. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  5. The Microcephalin Ancestral Allele in a Neanderthal Individual

    Lari, Martina; Rizzi, Ermanno; Milani, Lucio; Corti, Giorgio; Balsamo, Carlotta; Vai, Stefania; Catalano, Giulio; Pilli, Elena; Longo, Laura; Condemi, Silvana; Giunti, Paolo; Hänni, Catherine; De Bellis, Gianluca; Orlando, Ludovic; Barbujani, Guido; Caramelli, David

    2010-01-01

    Background The high frequency (around 0.70 worlwide) and the relatively young age (between 14,000 and 62,000 years) of a derived group of haplotypes, haplogroup D, at the microcephalin (MCPH1) locus led to the proposal that haplogroup D originated in a human lineage that separated from modern humans >1 million years ago, evolved under strong positive selection, and passed into the human gene pool by an episode of admixture circa 37,000 years ago. The geographic distribution of haplogroup D, with marked differences between Africa and Eurasia, suggested that the archaic human form admixing with anatomically modern humans might have been Neanderthal. Methodology/Principal Findings Here we report the first PCR amplification and high- throughput sequencing of nuclear DNA at the microcephalin (MCPH1) locus from Neanderthal individual from Mezzena Rockshelter (Monti Lessini, Italy). We show that a well-preserved Neanderthal fossil dated at approximately 50,000 years B.P., was homozygous for the ancestral, non-D, allele. The high yield of Neanderthal mtDNA sequences of the studied specimen, the pattern of nucleotide misincorporation among sequences consistent with post-mortem DNA damage and an accurate control of the MCPH1 alleles in all personnel that manipulated the sample, make it extremely unlikely that this result might reflect modern DNA contamination. Conclusions/Significance The MCPH1 genotype of the Monti Lessini (MLS) Neanderthal does not prove that there was no interbreeding between anatomically archaic and modern humans in Europe, but certainly shows that speculations on a possible Neanderthal origin of what is now the most common MCPH1 haplogroup are not supported by empirical evidence from ancient DNA. PMID:20498832

  6. Introgressive hybridization: brown bears as vectors for polar bear alleles.

    Hailer, Frank

    2015-03-01

    The dynamics and consequences of introgression can inform about numerous evolutionary processes. Biologists have therefore long been interested in hybridization. One challenge, however, lies in the identification of nonadmixed genotypes that can serve as a baseline for accurate quantification of admixture. In this issue of Molecular Ecology, Cahill et al. (2015) analyse a genomic data set of 28 polar bears, eight brown bears and one American black bear. Polar bear alleles are found to be introgressed into brown bears not only near a previously identified admixture zone on the Alaskan Admiralty, Baranof and Chichagof (ABC) Islands, but also far into the North American mainland. Elegantly contrasting admixture levels at autosomal and X chromosomal markers, Cahill and colleagues infer that male-biased dispersal has spread these introgressed alleles away from the Late Pleistocene contact zone. Compared to a previous study on the ABC Island population in which an Alaskan brown bear served as a putatively admixture-free reference, Cahill et al. (2015) utilize a newly sequenced Swedish brown bear as admixture baseline. This approach reveals that brown bears have been impacted by introgression from polar bears to a larger extent (up to 8.8% of their genome), than previously known, including the bear that had previously served as admixture baseline. No evidence for introgression of brown bear into polar bear is found, which the authors argue could be a consequence of selection. Besides adding new exciting pieces to the puzzle of polar/brown bear evolutionary history, the study by Cahill and colleagues highlights that wildlife genomics is moving from analysing single genomes towards a landscape genomics approach. © 2015 John Wiley & Sons Ltd.

  7. The microcephalin ancestral allele in a Neanderthal individual.

    Martina Lari

    Full Text Available BACKGROUND: The high frequency (around 0.70 worldwide and the relatively young age (between 14,000 and 62,000 years of a derived group of haplotypes, haplogroup D, at the microcephalin (MCPH1 locus led to the proposal that haplogroup D originated in a human lineage that separated from modern humans >1 million years ago, evolved under strong positive selection, and passed into the human gene pool by an episode of admixture circa 37,000 years ago. The geographic distribution of haplogroup D, with marked differences between Africa and Eurasia, suggested that the archaic human form admixing with anatomically modern humans might have been Neanderthal. METHODOLOGY/PRINCIPAL FINDINGS: Here we report the first PCR amplification and high-throughput sequencing of nuclear DNA at the microcephalin (MCPH1 locus from Neanderthal individual from Mezzena Rockshelter (Monti Lessini, Italy. We show that a well-preserved Neanderthal fossil dated at approximately 50,000 years B.P., was homozygous for the ancestral, non-D, allele. The high yield of Neanderthal mtDNA sequences of the studied specimen, the pattern of nucleotide misincorporation among sequences consistent with post-mortem DNA damage and an accurate control of the MCPH1 alleles in all personnel that manipulated the sample, make it extremely unlikely that this result might reflect modern DNA contamination. CONCLUSIONS/SIGNIFICANCE: The MCPH1 genotype of the Monti Lessini (MLS Neanderthal does not prove that there was no interbreeding between anatomically archaic and modern humans in Europe, but certainly shows that speculations on a possible Neanderthal origin of what is now the most common MCPH1 haplogroup are not supported by empirical evidence from ancient DNA.

  8. The association of 5-HTR2A-1438A/G, COMTVal158Met, MAOA-LPR, DATVNTR and 5-HTTVNTR gene polymorphisms and antisocial personality disorder in male heroin-dependent Chinese subjects.

    Yang, Mei; Kavi, Vasish; Wang, Wenfu; Wu, Zhimei; Hao, Wei

    2012-03-30

    To explore the association between the 5-HTR2A-1438A/G, COMTVal158Met, MAOA-LPR, DATVNTR and 5-HTTVNTR polymorphisms with comorbidity of antisocial personality disorder in male heroin-dependent patients. In case control study, we compared the polymorphic distributions of 5-HTR2A-1438A/G, COMTVal158Met, MAOA-LPR, DATVNTR and 5-HTTVNTR in 588 male heroin-dependent patients (including 311 patients with antisocial personality disorder and 277 patients without antisocial personality disorder) and 194 normal males by genotypes, alleles, and interaction between genes. Between male heroin-dependent patients with antisocial personality disorder and normal males, and between male heroin-dependent patients with and without antisocial personality disorder, the distributions of 5-HTTVNTR polymorphic genotypes and alleles were in statistical significance. Individuals carrying 10R allele were in higher risk of the comorbidity of antisocial personality disorder and heroin dependence. By MDR analyses, the interaction between 5-HTTVNTR and DATVNTR was close to statistical significance in predicting the risk of antisocial personality disorder in male heroin dependent patients. In male heroin dependent patients, individuals carrying 5-HTTVNTR 10R allele or/and DATVNTR 9R allele were in higher risks of co-occurring antisocial personality disorder, while individuals with 5-HTTVNTR 12R/12R and DATVNTR 10R/10R genotypes together were in lower risks of antisocial personality disorder. 5-HTTVNTR, and the interaction between 5-HTTVNTR and DATVNTR may be associated with the comorbidity of antisocial personality disorder in male heroin-dependent patients. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Verification of space weather forecasts at the UK Met Office

    Bingham, S.; Sharpe, M.; Jackson, D.; Murray, S.

    2017-12-01

    The UK Met Office Space Weather Operations Centre (MOSWOC) has produced space weather guidance twice a day since its official opening in 2014. Guidance includes 4-day probabilistic forecasts of X-ray flares, geomagnetic storms, high-energy electron events and high-energy proton events. Evaluation of such forecasts is important to forecasters, stakeholders, model developers and users to understand the performance of these forecasts and also strengths and weaknesses to enable further development. Met Office terrestrial near real-time verification systems have been adapted to provide verification of X-ray flare and geomagnetic storm forecasts. Verification is updated daily to produce Relative Operating Characteristic (ROC) curves and Reliability diagrams, and rolling Ranked Probability Skill Scores (RPSSs) thus providing understanding of forecast performance and skill. Results suggest that the MOSWOC issued X-ray flare forecasts are usually not statistically significantly better than a benchmark climatological forecast (where the climatology is based on observations from the previous few months). By contrast, the issued geomagnetic storm activity forecast typically performs better against this climatological benchmark.

  10. The performance of FLake in the Met Office Unified Model

    Gabriel Gerard Rooney

    2013-12-01

    Full Text Available We present results from the coupling of FLake to the Met Office Unified Model (MetUM. The coupling and initialisation are first described, and the results of testing the coupled model in local and global model configurations are presented. These show that FLake has a small statistical impact on screen temperature, but has the potential to modify the weather in the vicinity of areas of significant inland water. Examination of FLake lake ice has revealed that the behaviour of lakes in the coupled model is unrealistic in some areas of significant sub-grid orography. Tests of various modifications to ameliorate this behaviour are presented. The results indicate which of the possible model changes best improve the annual cycle of lake ice. As FLake has been developed and tuned entirely outside the Unified Model system, these results can be interpreted as a useful objective measure of the performance of the Unified Model in terms of its near-surface characteristics.

  11. La metáfora como proceso cognitivo

    Luz Amparo Fajardo Uribe

    2006-01-01

    Full Text Available La metáfora es un mecanismo que hace posible conceptualizar y reconceptualizar el mundo a partir de la traslación de rasgos de un dominio de origen a un dominio de llegada. En esa medida, la metáfora no necesita inventar nuevos términos para referirse a la realidad, sino que a partir de los ya existentes brinda una visión diferente de ésta en tanto que ha sido enriquecida con la afectividad y la emotividad del sujeto cognoscente. Por esa razón, la comprensión y producción metafórica requiere más de la competencia comunicativa que de la competencia lingüística, dado que el sentido que éste adopta depende del contexto comunicativo y no de la constitución léxica, morfológica sintáctica del enunciado.

  12. Carnitine palmitoyltransferase 1B 531K allele carriers sustain a higher respiratory quotient after aerobic exercise, but β3-adrenoceptor 64R allele does not affect lipolysis: a human model.

    Eduardo Gómez-Gómez

    Full Text Available Carnitine palmitoyltransferase IB (CPT1B and adrenoceptor beta-3 (ADRB3 are critical regulators of fat metabolism. CPT1B transports free acyl groups into mitochondria for oxidation, and ADRB3 triggers lipolysis in adipocytes, and their respective polymorphisms E531K and W64R have been identified as indicators of obesity in population studies. It is therefore important to understand the effects of these mutations on ADRB3 and CPT1B function in adipose and skeletal muscle tissue, respectively. This study aimed to analyze the rate of lipolysis of plasma indicators (glycerol, free fatty acids, and beta hydroxybutyrate and fat oxidation (through the non-protein respiratory quotient. These parameters were measured in 37 participants during 30 min of aerobic exercise at approximately 62% of maximal oxygen uptake, followed by 30 min of recovery. During recovery, mean respiratory quotient values were higher in K allele carriers than in non-carriers, indicating low post-exercise fatty acid oxidation rates. No significant differences in lipolysis or lipid oxidation were observed between R and W allele carriers of ADRB3 at any time during the aerobic load. The substitution of glutamic acid at position 531 by lysine in the CPT1B protein decreases the mitochondrial beta-oxidation pathway, which increases the non-protein respiratory quotient value during recovery from exercise. This may contribute to weight gain or reduced weight-loss following exercise.

  13. Enhancement of allele discrimination by introduction of nucleotide mismatches into siRNA in allele-specific gene silencing by RNAi.

    Yusuke Ohnishi

    Full Text Available Allele-specific gene silencing by RNA interference (RNAi is therapeutically useful for specifically inhibiting the expression of disease-associated alleles without suppressing the expression of corresponding wild-type alleles. To realize such allele-specific RNAi (ASP-RNAi, the design and assessment of small interfering RNA (siRNA duplexes conferring ASP-RNAi is vital; however, it is also difficult. In a previous study, we developed an assay system to assess ASP-RNAi with mutant and wild-type reporter alleles encoding the Photinus and Renilla luciferase genes. In line with experiments using the system, we realized that it is necessary and important to enhance allele discrimination between mutant and corresponding wild-type alleles. Here, we describe the improvement of ASP-RNAi against mutant alleles carrying single nucleotide variations by introducing base substitutions into siRNA sequences, where original variations are present in the central position. Artificially mismatched siRNAs or short-hairpin RNAs (shRNAs against mutant alleles of the human Prion Protein (PRNP gene, which appear to be associated with susceptibility to prion diseases, were examined using this assessment system. The data indicates that introduction of a one-base mismatch into the siRNAs and shRNAs was able to enhance discrimination between the mutant and wild-type alleles. Interestingly, the introduced mismatches that conferred marked improvement in ASP-RNAi, appeared to be largely present in the guide siRNA elements, corresponding to the 'seed region' of microRNAs. Due to the essential role of the 'seed region' of microRNAs in their association with target RNAs, it is conceivable that disruption of the base-pairing interactions in the corresponding seed region, as well as the central position (involved in cleavage of target RNAs, of guide siRNA elements could influence allele discrimination. In addition, we also suggest that nucleotide mismatches at the 3'-ends of sense

  14. Association of apolipoprotein E allele {epsilon}4 with late-onset sporadic Alzheimer`s disease

    Lucotte, G.; David, F.; Berriche, S. [Regional Center of Neurogenetics, Reims (France)] [and others

    1994-09-15

    Apolipoprotein E, type {epsilon}4 allele (ApoE {epsilon}4), is associated with late-onset sporadic Alzheimer`s disease (AD) in French patients. The association is highly significant (0.45 AD versus 0.12 controls for {epsilon}4 allele frequencies). These data support the involvement of ApoE {epsilon}4 allele as a very important risk factor for the clinical expression of AD. 22 refs., 1 fig., 3 tabs.

  15. The Role of the Val66Met Polymorphism of the Brain Derived Neurotrophic Factor Gene in Coping Strategies Relevant to Depressive Symptoms.

    Warren Caldwell

    Full Text Available Disturbances of brain derived neurotrophic factor (BDNF signalling have been implicated in the evolution of depression, which likely arises, in part, as a result of diminished synaptic plasticity. Predictably, given stressor involvement in depression, BDNF is affected by recent stressors as well as stressors such as neglect experienced in early life. The effects of early life maltreatment in altering BDNF signalling may be particularly apparent among those individuals with specific BDNF polymorphisms. We examined whether polymorphisms of the Val66Met genotype might be influential in moderating how early-life events play out with respect to later coping styles, cognitive flexibility and depressive features. Among male and female undergraduate students (N = 124, childhood neglect was highly related to subsequent depressive symptoms. This outcome was moderated by the BDNF polymorphism in the sense that depressive symptoms appeared higher in Met carriers who reported low levels of neglect than in those with the Val/Val allele. However, under conditions of high neglect depressive symptoms only increased in the Val/Val individuals. In effect, the Met polymorphism was associated with depressive features, but did not interact with early life neglect in predicting later depressive features. It was further observed that among the Val/Val individuals, the relationship between neglect and depression was mediated by emotion-focused styles and diminished perceived control, whereas this mediation was not apparent in Met carriers. In contrast to the more typical view regarding this polymorphism, the data are consistent with the perspective that in the presence of synaptic plasticity presumably associated with the Val/Val genotype, neglect allows for the emergence of specific appraisal and coping styles, which are tied to depression. In the case of the reduced degree of neuroplasticity expected in the Met carriers, early life adverse experiences are not tied

  16. The divergent impact of catechol-O-methyltransferase (COMT) Val158Met genetic polymorphisms on executive function in adolescents with discrete patterns of childhood adversity.

    Zhang, Huihui; Li, Jie; Yang, Bei; Ji, Tao; Long, Zhouting; Xing, Qiquan; Shao, Di; Bai, Huayu; Sun, Jiwei; Cao, Fenglin

    2018-02-01

    Catechol-O-methyltransferase (COMT) Val 158 Met functional polymorphisms play a crucial role in the development of executive function (EF), but their effect may be moderated by environmental factors such as childhood adversity. The present study aimed at testing the divergent impact of the COMT Val 158 Met genotype on EF in non-clinical adolescents with discrete patterns of childhood adversity. A total of 341 participants completed the Childhood Trauma Questionnaire, the self-reported version of the Behavior Rating Inventory of Executive Function, and self-administered questionnaires on familial function. The participants' COMT Val 158 Met genotype was determined. Associations among the variables were explored using latent class analysis and general linear models. We found that Val/Val homozygotes showed significantly worse performance on behavioral shift, relative to Met allele carriers (F=5.921, p=0.015, Partial η 2 =0.018). Moreover, three typical patterns of childhood adversity, namely, low childhood adversity (23.5%), childhood neglect (59.8%), and high childhood adversity (16.7%), were found. Both childhood neglect and high childhood adversity had a negative impact on each aspect of EF and on global EF performance. Importantly, these results provided evidence for significant interaction effects, as adolescents with the Val/Val genotype showed inferior behavioral shift performance than Met carriers (F=6.647, p=0.010, Partial η 2 =0.020) in the presence of high childhood adversity. Furthermore, there were no differences between the genotypes for childhood neglect and low childhood adversity. Overall, this is the first study to show that an interaction between the COMT genotype and childhood adversity affects EF in non-clinical adolescents. These results suggest that the COMT genotype may operate as a susceptibility gene vulnerable to an adverse environment. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Higher Levels of c-Met Expression and Phosphorylation Identify Cell Lines With Increased Sensitivity to AMG-458, a Novel Selective c-Met Inhibitor With Radiosensitizing Effects

    Li Bo; Torossian, Artour; Sun, Yunguang; Du, Ruihong; Dicker, Adam P.; Lu Bo

    2012-01-01

    Purpose: c-Met is overexpressed in some non-small cell lung cancer (NSCLC) cell lines and tissues. Cell lines with higher levels of c-Met expression and phosphorylation depend on this receptor for survival. We studied the effects of AMG-458 on 2 NSCLC cell lines. Methods and Materials: 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl) -2H-tetrazolium assays assessed the sensitivities of the cells to AMG-458. Clonogenic survival assays illustrated the radiosensitizing effects of AMG-458. Western blot for cleaved caspase 3 measured apoptosis. Immunoblotting for c-Met, phospho-Met (p-Met), Akt/p-Akt, and Erk/p-Erk was performed to observe downstream signaling. Results: AMG-458 enhanced radiosensitivity in H441 but not in A549. H441 showed constitutive phosphorylation of c-Met. A549 expressed low levels of c-Met, which were phosphorylated only in the presence of exogenous hepatocyte growth factor. The combination of radiation therapy and AMG-458 treatment was found to synergistically increase apoptosis in the H441 cell line but not in A549. Radiation therapy, AMG-458, and combination treatment were found to reduce p-Akt and p-Erk levels in H441 but not in A549. H441 became less sensitive to AMG-458 after small interfering RNA knockdown of c-Met; there was no change in A549. After overexpression of c-Met, A549 became more sensitive, while H441 became less sensitive to AMG-458. Conclusions: AMG-458 was more effective in cells that expressed higher levels of c-Met/p-Met, suggesting that higher levels of c-Met and p-Met in NSCLC tissue may classify a subset of tumors that are more sensitive to molecular therapies against this receptor.

  18. Loads and loads and loads: the influence of prospective load, retrospective load, and ongoing task load in prospective memory

    Meier, Beat; Zimmermann, Thomas D.

    2015-01-01

    In prospective memory tasks different kinds of load can occur. Adding a prospective memory task can impose a load on ongoing task performance. Adding ongoing task load (OTL) can affect prospective memory performance. The existence of multiple target events increases prospective load (PL) and adding complexity to the to-be-remembered action increases retrospective load (RL). In two experiments, we systematically examined the effects of these different types of load on prospective memory performance. Results showed an effect of PL on costs in the ongoing task for categorical targets (Experiment 2), but not for specific targets (Experiment 1). RL and OTL both affected remembering the retrospective component of the prospective memory task. We suggest that PL can enhance costs in the ongoing task due to additional monitoring requirements. RL and OTL seem to impact the division of resources between the ongoing task and retrieval of the retrospective component, which may affect disengagement from the ongoing task. In general, the results demonstrate that the different types of load affect prospective memory differentially. PMID:26082709

  19. Loads and loads and loads: the influence of prospective load, retrospective load, and ongoing task load in prospective memory.

    Meier, Beat; Zimmermann, Thomas D

    2015-01-01

    In prospective memory tasks different kinds of load can occur. Adding a prospective memory task can impose a load on ongoing task performance. Adding ongoing task load (OTL) can affect prospective memory performance. The existence of multiple target events increases prospective load (PL) and adding complexity to the to-be-remembered action increases retrospective load (RL). In two experiments, we systematically examined the effects of these different types of load on prospective memory performance. Results showed an effect of PL on costs in the ongoing task for categorical targets (Experiment 2), but not for specific targets (Experiment 1). RL and OTL both affected remembering the retrospective component of the prospective memory task. We suggest that PL can enhance costs in the ongoing task due to additional monitoring requirements. RL and OTL seem to impact the division of resources between the ongoing task and retrieval of the retrospective component, which may affect disengagement from the ongoing task. In general, the results demonstrate that the different types of load affect prospective memory differentially.

  20. Allele specific expression in worker reproduction genes in the bumblebee Bombus terrestris

    Harindra E. Amarasinghe

    2015-07-01

    Full Text Available Methylation has previously been associated with allele specific expression in ants. Recently, we found methylation is important in worker reproduction in the bumblebee Bombus terrestris. Here we searched for allele specific expression in twelve genes associated with worker reproduction in bees. We found allele specific expression in Ecdysone 20 monooxygenase and IMP-L2-like. Although we were unable to confirm a genetic or epigenetic cause for this allele specific expression, the expression patterns of the two genes match those predicted for imprinted genes.

  1. Association between the CCR5 32-bp deletion allele and late onset of schizophrenia

    Rasmussen, Henrik Berg; Timm, Sally; Wang, August G

    2006-01-01

    OBJECTIVE: The 32-bp deletion allele in chemokine receptor CCR5 has been associated with several immune-mediated diseases and might be implicated in schizophrenia as well. METHOD: The authors genotyped DNA samples from 268 schizophrenia patients and 323 healthy subjects. Age at first admission...... of the deletion allele in the latter subgroup of patients. CONCLUSIONS: These findings suggest that the CCR5 32-bp deletion allele is a susceptibility factor for schizophrenia with late onset. Alternatively, the CCR5 32-bp deletion allele may act as a modifier by delaying the onset of schizophrenia without...

  2. Allele frequency changes due to hitch-hiking in genomic selection programs

    Liu, Huiming; Sørensen, Anders Christian; Meuwissen, Theo H E

    2014-01-01

    of inbreeding due to changes in allele frequencies and hitch-hiking. This study aimed at understanding the impact of using long-term genomic selection on changes in allele frequencies, genetic variation and the level of inbreeding. Methods Selection was performed in simulated scenarios with a population of 400......-BLUP, Genomic BLUP and Bayesian Lasso. Changes in allele frequencies at QTL, markers and linked neutral loci were investigated for the different selection criteria and different scenarios, along with the loss of favourable alleles and the rate of inbreeding measured by pedigree and runs of homozygosity. Results...

  3. Peripheral subnuclear positioning suppresses Tcrb recombination and segregates Tcrb alleles from RAG2.

    Chan, Elizabeth A W; Teng, Grace; Corbett, Elizabeth; Choudhury, Kingshuk Roy; Bassing, Craig H; Schatz, David G; Krangel, Michael S

    2013-11-26

    Allelic exclusion requires that the two alleles at antigen-receptor loci attempt to recombine variable (V), diversity (D), and joining (J) gene segments [V(D)J recombination] asynchronously in nuclei of developing lymphocytes. It previously was shown that T-cell receptor β (Tcrb) alleles frequently and stochastically associate with the nuclear lamina and pericentromeric heterochromatin in CD4(-)CD8(-) thymocytes. Moreover, rearranged alleles were underrepresented at these locations. Here we used 3D immunofluorescence in situ hybridization to identify recently rearranged Tcrb alleles based on the accumulation of the DNA-repair protein 53BP1. We found that Tcrb alleles recombine asynchronously in double-negative thymocytes and that V(D)J recombination is suppressed on peripheral as compared with central Tcrb alleles. Moreover, the recombination events that did take place at the nuclear periphery preferentially occurred on Tcrb alleles that were partially dissociated from the nuclear lamina. To understand better the mechanism by which V(D)J recombination is suppressed at the nuclear periphery, we evaluated the subnuclear distribution of recombination-activating gene 2 (RAG2) protein. We found that RAG2 abundance was reduced at the nuclear periphery. Moreover, RAG2 was distributed differently from RNA polymerase II and histone H3K4 trimethylation. Our data suggest that the nuclear periphery suppresses V(D)J recombination, at least in part, by segregating Tcrb alleles from RAG proteins.

  4. The new Met Office strategy for seasonal forecasts

    Hewson, T. D.

    2012-04-01

    In October 2011 the Met Office began issuing a new-format UK seasonal forecast, called "The 3-month Outlook". Government interest in a UK-relevant product had been heightened by infrastructure issues arising during the severe cold of previous winters. At the same time there was evidence that the Met Office's "GLOSEA4" long range forecasting system exhibited some hindcast skill for the UK, that was comparable to its hindcast skill for the larger (and therefore less useful) 'northern Europe' region. Also, the NAO- and AO- signals prevailing in the previous two winters had been highlighted by the GLOSEA4 model well in advance. This presentation will initially give a brief overview of GLOSEA4, describing key features such as evolving sea-ice, a well-resolved stratosphere, and the perturbation strategy. Skill measures will be shown, along with forecasts for the last 3 winters. The new structure 3-month outlook will then be described and presented. Previously, our seasonal forecasts had been based on a tercile approach. The new format outlook aims to substantially improve upon this by illustrating graphically, and with text, the full range of possible outcomes, and by placing those outcomes in the context of climatology. In one key component the forecast pdfs (probability density functions) are displayed alongside climatological pdfs. To generate the forecast pdf we take the bias-corrected GLOSEA4 output (42 members), and then incorporate, via expert team, all other relevant information. Firstly model forecasts from other centres are examined. Then external 'forcing factors', such as solar, and the state of the land-ocean-ice system, are referenced, assessing how well the models represent their influence, and bringing in statistical relationships where appropriate. The expert team thereby decides upon any changes to the GLOSEA4 data, employing an interactive tool to shift, expand or contract the forecast pdfs accordingly. The full modification process will be illustrated

  5. Brain-derived neurotrophic factor Val66Met polymorphism and cognitive function in persons with cardiovascular disease.

    Szabo, Ashley J; Alosco, Michael L; Miller, Lindsay A; McGeary, John E; Poppas, Athena; Cohen, Ronald A; Gunstad, John

    2013-12-01

    Cognitive impairment is common among persons with cardiovascular disease (CVD), and several potential aetiological mechanisms have been described, including contributions of genetic markers such as variations in the brain-derived neurotrophic (BDNF) gene. This current study examined the associations of BDNF genotype with cognitive function among individuals with CVD. This study included 110 participants with CVD who completed a comprehensive neuropsychological battery that assessed global cognitive function, attention/executive function, memory, language, and visuospatial abilities. All participants also underwent blood draw to provide a DNA sample that was used to determine BDNF genotype. Carriers of either one or two copies of the methionine allele of BDNF were categorized into one group (n = 33); non-carriers were categorized into a second group (n = 77). After adjustment for demographic and medical characteristics, hierarchical regression analyses revealed persons with one or more methionine alleles displayed better performance than valine/valine individuals for attention/executive function (β = 0.22, P = 0.047) and memory (β = 0.25, P = 0.03), as well as a trend for language (β = 0.19, P = 0.08) and visuospatial abilities (β = 0.21, P = 0.06). BDNF Val66Met had little impact on cognitive functioning in a sample of older adults with CVD, and significant findings contradicted that predicted by past work. Future work is much needed to clarify the mechanisms of these findings, particularly studies examining both circulating BDNF levels and genetic variation in the BDNF gene and cognitive function over time. © 2013 The Authors. Psychogeriatrics © 2013 Japanese Psychogeriatric Society.

  6. PHA665752, a small-molecule inhibitor of c-Met, inhibits hepatocyte growth factor-stimulated migration and proliferation of c-Met-positive neuroblastoma cells

    Crosswell, Hal E; Dasgupta, Anindya; Alvarado, Carlos S; Watt, Tanya; Christensen, James G; De, Pradip; Durden, Donald L; Findley, Harry W

    2009-01-01

    c-Met is a tyrosine kinase receptor for hepatocyte growth factor/scatter factor (HGF/SF), and both c-Met and its ligand are expressed in a variety of tissues. C-Met/HGF/SF signaling is essential for normal embryogenesis, organogenesis, and tissue regeneration. Abnormal c-Met/HGF/SF signaling has been demonstrated in different tumors and linked to aggressive and metastatic tumor phenotypes. In vitro and in vivo studies have demonstrated inhibition of c-Met/HGF/SF signaling by the small-molecule inhibitor PHA665752. This study investigated c-Met and HGF expression in two neuroblastoma (NBL) cell lines and tumor tissue from patients with NBL, as well as the effects of PHA665752 on growth and motility of NBL cell lines. The effect of the tumor suppressor protein PTEN on migration and proliferation of tumor cells treated with PHA665752 was also evaluated. Expression of c-Met and HGF in NBL cell lines SH-EP and SH-SY5Y and primary tumor tissue was assessed by immunohistochemistry and quantitative RT-PCR. The effect of PHA665752 on c-Met/HGF signaling involved in NBL cell proliferation and migration was evaluated in c-Met-positive cells and c-Met-transfected cells. The transwell chemotaxis assay and the MTT assay were used to measure migration and proliferation/cell-survival of tumor cells, respectively. The PPAR-γ agonist rosiglitazone was used to assess the effect of PTEN on PHA665752-induced inhibition of NBL cell proliferation/cell-survival and migration High c-Met expression was detected in SH-EP cells and primary tumors from patients with advanced-stage disease. C-Met/HGF signaling induced both migration and proliferation of SH-EP cells. Migration and proliferation/cell-survival were inhibited by PHA665752 in a dose-dependent manner. We also found that induced overexpression of PTEN following treatment with rosiglitazone significantly enhanced the inhibitory effect of PHA665752 on NBL-cell migration and proliferation. c-Met is highly expressed in most tumors from

  7. HLA –DRB1*, DQB1* Alleles In Hydatid Patients By Molecular Typing

    mehdi Mosayebi

    2007-10-01

    Full Text Available Mosayebi M1, Dalimi Asl A2, Moazeni M3, Mosayebi Gh4 1. Ph.D Student, Department of Parasitology, Faculty of medicine, Tarbiat Modarres University 2. Professor, Department of Parasitology, Faculty of medicine, Tarbiat Modarres University 3. Professor, Department of Immunology, Faculty of medicine, Tarbiat Modarres University 4. Assistant professor, Department of Immunology, Faculty of medicine, Arak Medical Sciences University Abstract Background: Hydatidosis is a important disease that results from infection with larvae of the dog tape worm , Echinococcus granulosus in human and farm animals .Resistance or susceptibility to infectious diseases , for example , cystic and alveolar echinococcosis is restricted by individual host factors and immunologic responses,in many surveys has been shown.The target of this study that is the first survey dealing with the correlation between HLA-DRB1*& DQB1* alleles and cystic echinococcosis in Iranian patient,is investigation HLA-DRB1*and DQB1* allelic polymorphism in Iranian patient with hydatidosis . Materials and methods: The study was carried out on 56 patients with confirmed cystic echinococcosis and 30 apparently healthy individuals living on Arak area by HLA-DRB1*& DQB1* typing with PCR-SSP method.The first step was founding patients and blood sampling .DNA was prepared from whole blood and we used PCR-SSP with 31 primer mixes for per sample . PCR reaction mixtures were loaded in agarose gels and after electrophoresis , geles were examine under UV illumination and gel document . Analyse of results carried out with specific software and frequency& interpretation tables and homogeneity test for calculation of P-value in χ2 test with fisher΄s exact test . significant samples with logistic regression analysed and Odds-ratio calculate . Results: A statistically significant positive association was found between HLA-DQB1*02 and the occurrence of cystic echinococcosis(P<0.05,(Odds-ratio=2.87 Conclusion: The

  8. Metallography at the Met Lab -- The first fifty years

    Lee, R.H.

    1995-01-01

    The Met Lab at the University of Chicago was established to build the world's first nuclear reactor. The object was to see if a pile (CP-1) could be built to create a sustained chain reaction, i.e., controlled nuclear fission. New materials of the very best quality were needed and people of many skills worked together to achieve the goal as quickly as possible. This is the story of a select group of people who were scientific and engineering pioneers in this new field. Research continued at new sites on more advanced reactors and cooling systems. Many problems were encountered in the fabrication of reactor components, and metallography was a crucial method of analyzing the reactions and quality of consolidation. 1996 will be the 50th anniversary of the beginning of the National Laboratories, so it is appropriate to commemorate and recall some pioneering achievements

  9. Pyramiding genes and alleles for improving energy cane biomass yield

    Ming, Ray [University of Illinois at Urbana-Champaign; Nagai, Chifumi [Hawaii Agriculture Research Center; Yu, Qingyi [Texas A & M AgriLife Research

    2018-03-23

    could potentially regulate biomass yield. Differentially expressed genes, PIF3 and EIL5, involved in gibberellin and ethylene pathway could play an important role in biomass accumulation. Differential gene expression analysis was also carried out on the LU population. High-biomass yield was mainly determined by assimilation of carbon in source tissues. The high-level expression of fermentative genes in the low-biomass group was likely induced by their low-energy status. The haploid (tetraploid) genome of S. spontanium AP85-441 was sequenced with chromosome level assembly and allele defined annotation. This reference genome along with the upcoming S. officinarum genome will allow us to identify genes and alleles contributed to biomass yield.

  10. The MeteoMet2 project—highlights and results

    Merlone, A.; Sanna, F.; Beges, G.; Bell, S.; Beltramino, G.; Bojkovski, J.; Brunet, M.; del Campo, D.; Castrillo, A.; Chiodo, N.; Colli, M.; Coppa, G.; Cuccaro, R.; Dobre, M.; Drnovsek, J.; Ebert, V.; Fernicola, V.; Garcia-Benadí, A.; Garcia-Izquierdo, C.; Gardiner, T.; Georgin, E.; Gonzalez, A.; Groselj, D.; Heinonen, M.; Hernandez, S.; Högström, R.; Hudoklin, D.; Kalemci, M.; Kowal, A.; Lanza, L.; Miao, P.; Musacchio, C.; Nielsen, J.; Nogueras-Cervera, M.; Oguz Aytekin, S.; Pavlasek, P.; de Podesta, M.; Rasmussen, M. K.; del-Río-Fernández, J.; Rosso, L.; Sairanen, H.; Salminen, J.; Sestan, D.; Šindelářová, L.; Smorgon, D.; Sparasci, F.; Strnad, R.; Underwood, R.; Uytun, A.; Voldan, M.

    2018-02-01

    Launched in 2011 within the European Metrology Research Programme (EMRP) of EURAMET, the joint research project ‘MeteoMet’—Metrology for Meteorology—is the largest EMRP consortium; national metrology institutes, universities, meteorological and climate agencies, research institutes, collaborators and manufacturers are working together, developing new metrological techniques, as well as improving existing ones, for use in meteorological observations and climate records. The project focuses on humidity in the upper and surface atmosphere, air temperature, surface and deep-sea temperatures, soil moisture, salinity, permafrost temperature, precipitation, and the snow albedo effect on air temperature. All tasks are performed using a rigorous metrological approach and include the design and study of new sensors, new calibration facilities, the investigation of sensor characteristics, improved techniques for measurements of essential climate variables with uncertainty evaluation, traceability, laboratory proficiency and the inclusion of field influencing parameters, long-lasting measurements, and campaigns in remote and extreme areas. The vision for MeteoMet is to take a step further towards establishing full data comparability, coherency, consistency, and long-term continuity, through a comprehensive evaluation of the measurement uncertainties for the quantities involved in the global climate observing systems and the derived observations. The improvement in quality of essential climate variables records, through the inclusion of measurement uncertainty budgets, will also highlight possible strategies for the reduction of the uncertainty. This contribution presents selected highlights of the MeteoMet project and reviews the main ongoing activities, tasks and deliverables, with a view to its possible future evolution and extended impact.

  11. c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target.

    Ozawa, Yohei; Nakamura, Yasuhiro; Fujishima, Fumiyoshi; Felizola, Saulo J A; Takeda, Kenichiro; Okamoto, Hiroshi; Ito, Ken; Ishida, Hirotaka; Konno, Takuro; Kamei, Takashi; Miyata, Go; Ohuchi, Noriaki; Sasano, Hironobu

    2015-06-03

    c-Met is widely known as a poor prognostic factor in various human malignancies. Previous studies have suggested the involvement of c-Met and/or its ligand, hepatocyte growth factor (HGF), in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients. The expression of c-Met and HGF was immunohistochemically assessed in 104 surgically obtained tissue specimens. The correlation between c-Met/HGF expression and patients' clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with HGF and/or c-Met inhibitor in ESCC cell lines. Elevated expression of c-Met was significantly correlated with tumor depth and pathological stage. Patients with high c-Met expression had significantly worse survival. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor under HGF stimulation significantly inhibited the invasive capacity of an ESCC cell line with elevated c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor. The results of our study identified c-Met expression as an independent prognostic factor in ESCC patients and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with elevated c-Met expression.

  12. c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target

    Ozawa, Yohei; Nakamura, Yasuhiro; Fujishima, Fumiyoshi; Felizola, Saulo JA; Takeda, Kenichiro; Okamoto, Hiroshi; Ito, Ken; Ishida, Hirotaka; Konno, Takuro; Kamei, Takashi; Miyata, Go; Ohuchi, Noriaki; Sasano, Hironobu

    2015-01-01

    c-Met is widely known as a poor prognostic factor in various human malignancies. Previous studies have suggested the involvement of c-Met and/or its ligand, hepatocyte growth factor (HGF), in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients. The expression of c-Met and HGF was immunohistochemically assessed in 104 surgically obtained tissue specimens. The correlation between c-Met/HGF expression and patients’ clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with HGF and/or c-Met inhibitor in ESCC cell lines. Elevated expression of c-Met was significantly correlated with tumor depth and pathological stage. Patients with high c-Met expression had significantly worse survival. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor under HGF stimulation significantly inhibited the invasive capacity of an ESCC cell line with elevated c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor. The results of our study identified c-Met expression as an independent prognostic factor in ESCC patients and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with elevated c-Met expression. The online version of this article (doi:10.1186/s12885-015-1450-3) contains supplementary material, which is available to authorized users

  13. Investigating the relationship between FMR1 allele length and cognitive ability in children: a subtle effect of the normal allele range on the normal ability range?

    Loat, C S; Craig, G; Plomin, R; Craig, I W

    2006-09-01

    The FMR1 gene contains a trinucleotide repeat tract which can expand from a normal size of around 30 repeats to over 200 repeats, causing mental retardation (Fragile X Syndrome). Evidence suggests that premutation males (55-200 repeats) are susceptible to a late-onset tremor/ataxia syndrome and females to premature ovarian failure, and that intermediate alleles ( approximately 41-55 repeats) and premutations may be in excess in samples with special educational needs. We explored the relationship between FMR1 allele length and cognitive ability in 621 low ability and control children assessed at 4 and 7 years, as well as 122 students with high IQ. The low and high ability and control samples showed no between-group differences in incidence of longer alleles. In males there was a significant negative correlation between allele length and non-verbal ability at 4 years (p = 0.048), academic achievement in maths (p = 0.003) and English (p = 0.011) at 7 years, and IQ in the high ability group (p = 0.018). There was a significant negative correlation between allele length and a standardised score for IQ and general cognitive ability at age 7 in the entire male sample (p = 0.002). This suggests that, within the normal spectrum of allele length, increased repeat numbers may have a limiting influence on cognitive performance.

  14. Type 2 diabetes risk alleles demonstrate extreme directional differentiation among human populations, compared to other diseases.

    Rong Chen

    Full Text Available Many disease-susceptible SNPs exhibit significant disparity in ancestral and derived allele frequencies across worldwide populations. While previous studies have examined population differentiation of alleles at specific SNPs, global ethnic patterns of ensembles of disease risk alleles across human diseases are unexamined. To examine these patterns, we manually curated ethnic disease association data from 5,065 papers on human genetic studies representing 1,495 diseases, recording the precise risk alleles and their measured population frequencies and estimated effect sizes. We systematically compared the population frequencies of cross-ethnic risk alleles for each disease across 1,397 individuals from 11 HapMap populations, 1,064 individuals from 53 HGDP populations, and 49 individuals with whole-genome sequences from 10 populations. Type 2 diabetes (T2D demonstrated extreme directional differentiation of risk allele frequencies across human populations, compared with null distributions of European-frequency matched control genomic alleles and risk alleles for other diseases. Most T2D risk alleles share a consistent pattern of decreasing frequencies along human migration into East Asia. Furthermore, we show that these patterns contribute to disparities in predicted genetic risk across 1,397 HapMap individuals, T2D genetic risk being consistently higher for individuals in the African populations and lower in the Asian populations, irrespective of the ethnicity considered in the initial discovery of risk alleles. We observed a similar pattern in the distribution of T2D Genetic Risk Scores, which are associated with an increased risk of developing diabetes in the Diabetes Prevention Program cohort, for the same individuals. This disparity may be attributable to the promotion of energy storage and usage appropriate to environments and inconsistent energy intake. Our results indicate that the differential frequencies of T2D risk alleles may

  15. Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project.

    Cross, Deanna S; Ivacic, Lynn C; Stefanski, Elisha L; McCarty, Catherine A

    2010-06-17

    There is a lack of knowledge regarding the frequency of disease associated polymorphisms in populations and population attributable risk for many populations remains unknown. Factors that could affect the association of the allele with disease, either positively or negatively, such as race, ethnicity, and gender, may not be possible to determine without population based allele frequencies.Here we used a panel of 51 polymorphisms previously associated with at least one disease and determined the allele frequencies within the entire Personalized Medicine Research Project population based cohort. We compared these allele frequencies to those in dbSNP and other data sources stratified by race. Differences in allele frequencies between self reported race, region of origin, and sex were determined. There were 19544 individuals who self reported a single racial category, 19027 or (97.4%) self reported white Caucasian, and 11205 (57.3%) individuals were female. Of the 11,208 (57%) individuals with an identifiable region of origin 8337 or (74.4%) were German.41 polymorphisms were significantly different between self reported race at the 0.05 level. Stratification of our Caucasian population by self reported region of origin revealed 19 polymorphisms that were significantly different (p = 0.05) between individuals of different origins. Further stratification of the population by gender revealed few significant differences in allele frequencies between the genders. This represents one of the largest population based allele frequency studies to date. Stratification by self reported race and region of origin revealed wide differences in allele frequencies not only by race but also by region of origin within a single racial group. We report allele frequencies for our Asian/Hmong and American Indian populations; these two minority groups are not typically selected for population allele frequency detection. Population wide allele frequencies are important for the design and

  16. A new variation in the promoter region, the -604 C>T, and the Leu72Met polymorphism of the ghrelin gene are associated with protection to insulin resistance.

    Zavarella, S; Petrone, A; Zampetti, S; Gueorguiev, M; Spoletini, M; Mein, C A; Leto, G; Korbonits, M; Buzzetti, R

    2008-04-01

    Previous studies suggested that polymorphisms in the coding region of the preproghrelin were involved in the etiology of obesity and might modulate glucose-induced insulin secretion. We evaluated the association of a new variation, -604C>T, in the promoter region of the ghrelin gene, of Leu72Met (247C>A) and of Gln90Leu (265A>T), all haplotype-tagging single nucleotide polymorphisms (SNPs), with measures of insulin sensitivity in 1420 adult individuals. The three SNPs were genotyped using ABI PRISM 7900 HT Sequence Detection System. We used multiple linear regression analysis for quantitative traits and THESIAS software for haplotype analysis. We observed a protective effect exerted by Met72 variant of Leu72Met SNP on insulin resistance parameters; a significant decreasing trend from Leu/Leu to Leu/Met and to Met/Met homozygous subjects in triglycerides, fasting insulin levels and HOMA-IR index (P=0.02, 0.01 and 0.003, respectively), and, consistently, an increase in ghrelin levels (P=0.003) was found. A significant decrease from CC to TC and to TT genotypes in insulin levels and HOMA-IR index was also detected (P=0.00l for both), but only in subjects homozygous for Leu72, where the protective effect of Met72 was not present. The haplotype analysis results supported the data obtained by the evaluation of each single SNP, showing the highest value of insulin levels and HOMA-IR index in the -604(c)247(c) haplotype intermediate value in -604(T)247(C) and lowest value in -604(C)247(A). Our observations suggest a protective role of the Met72 variant and of -604 T allele in modulating insulin resistance. These SNPs or an unknown functional variant in linkage disequilibrium could increase ghrelin levels and probably insulin sensitivity.

  17. Wind Loads on Structures

    Dyrbye, Claes; Hansen, Svend Ole

    Wind loads have to be taken into account when designing civil engineering structures. The wind load on structures can be systematised by means of the wind load chain: wind climate (global), terrain (wind at low height), aerodynamic response (wind load to pressure), mechanical response (wind...... pressure to structural response) and design criteria. Starting with an introduction of the wind load chain, the book moves on to meteorological considerations, atmospheric boundary layer, static wind load, dynamic wind load and scaling laws used in wind-tunnel tests. The dynamic wind load covers vibrations...... induced by wind turbulence, vortex shedding, flutter and galloping. The book gives a comprehensive treatment of wind effects on structures and it will be useful for consulting engineers designing wind-sensitive structures. It will also be valuable for students of civil engineering as textbook...

  18. Carbohydrate-Loading Diet

    ... Grape juice (12 ounces) 55 225 Lunch Milk, chocolate, reduced fat (12 ounces) 45 285 4 slices ... usual during carbohydrate loading to get the same benefits as a man does. Despite carbohydrate loading, you ...

  19. Autonomous Propellant Loading Project

    National Aeronautics and Space Administration — The AES Autonomous Propellant Loading (APL) project consists of three activities. The first is to develop software that will automatically control loading of...

  20. Fuel pellet loading apparatus

    1980-01-01

    Apparatus is described for loading a predetermined amount of nuclear fuel pellets into nuclear fuel elements and particularly for the automatic loading of fuel pellets from within a sealed compartment. (author)

  1. Limit loads in nozzles

    Zouain, N.

    1983-01-01

    The static method for the evaluation of the limit loads of a perfectly elasto-plastic structure is presented. Using the static theorem of Limit Analysis and the Finite Element Method, a lower bound for the colapso load can be obtained through a linear programming problem. This formulation if then applied to symmetrically loaded shells of revolution and some numerical results of limit loads in nozzles are also presented. (Author) [pt

  2. Leukemogenic Ptpn11 allele causes defective erythropoiesis in mice.

    Tatiana Usenko

    Full Text Available Src homology 2 (SH2 domain-containing phosphatase 2 (SHP2, encoded by PTPN11, regulates signaling networks and cell fate in many tissues. Expression of oncogenic PTPN11 in the hematopoietic compartment causes myeloproliferative neoplasm (MPN in humans and mice. However, the stage-specific effect(s of mutant Ptpn11 on erythroid development have remained unknown. We found that expression of an activated, leukemogenic Ptpn11 allele, Ptpn11D61Y, specifically in the erythroid lineage causes dyserythropoiesis in mice. Ptpn11D61Y progenitors produce excess cKIT+ CD71+ Ter119- cells and aberrant numbers of cKITl° CD71+ erythroblasts. Mutant erythroblasts show elevated activation of ERK, AKT and STAT3 in response to EPO stimulation, and MEK inhibitor treatment blocks Ptpn11D61Y-evoked erythroid hyperproliferation in vitro. Thus, the expression of oncogenic Ptpn11 causes dyserythropoiesis in a cell-autonomous manner in vivo.

  3. Hypomorphic temperature-sensitive alleles of NSDHL cause CK syndrome.

    McLarren, Keith W; Severson, Tesa M; du Souich, Christèle; Stockton, David W; Kratz, Lisa E; Cunningham, David; Hendson, Glenda; Morin, Ryan D; Wu, Diane; Paul, Jessica E; An, Jianghong; Nelson, Tanya N; Chou, Athena; DeBarber, Andrea E; Merkens, Louise S; Michaud, Jacques L; Waters, Paula J; Yin, Jingyi; McGillivray, Barbara; Demos, Michelle; Rouleau, Guy A; Grzeschik, Karl-Heinz; Smith, Raffaella; Tarpey, Patrick S; Shears, Debbie; Schwartz, Charles E; Gecz, Jozef; Stratton, Michael R; Arbour, Laura; Hurlburt, Jane; Van Allen, Margot I; Herman, Gail E; Zhao, Yongjun; Moore, Richard; Kelley, Richard I; Jones, Steven J M; Steiner, Robert D; Raymond, F Lucy; Marra, Marco A; Boerkoel, Cornelius F

    2010-12-10

    CK syndrome (CKS) is an X-linked recessive intellectual disability syndrome characterized by dysmorphism, cortical brain malformations, and an asthenic build. Through an X chromosome single-nucleotide variant scan in the first reported family, we identified linkage to a 5 Mb region on Xq28. Sequencing of this region detected a segregating 3 bp deletion (c.696_698del [p.Lys232del]) in exon 7 of NAD(P) dependent steroid dehydrogenase-like (NSDHL), a gene that encodes an enzyme in the cholesterol biosynthesis pathway. We also found that males with intellectual disability in another reported family with an NSDHL mutation (c.1098 dup [p.Arg367SerfsX33]) have CKS. These two mutations, which alter protein folding, show temperature-sensitive protein stability and complementation in Erg26-deficient yeast. As described for the allelic disorder CHILD syndrome, cells and cerebrospinal fluid from CKS patients have increased methyl sterol levels. We hypothesize that methyl sterol accumulation, not only cholesterol deficiency, causes CKS, given that cerebrospinal fluid cholesterol, plasma cholesterol, and plasma 24S-hydroxycholesterol levels are normal in males with CKS. In summary, CKS expands the spectrum of cholesterol-related disorders and insight into the role of cholesterol in human development. Copyright © 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  4. Distribution of coat-color-associated alleles in the domestic horse population and Przewalski's horse.

    Reissmann, Monika; Musa, Lutfi; Zakizadeh, Sonia; Ludwig, Arne

    2016-11-01

    Considering the hidden mode of inheritance of some coat-color-associated alleles, we investigated the presence/absence of coat-color-associated alleles in 1093 domestic horses of 55 breeds and 20 specimens of Przewalski's horse. For coat-color genotyping, allele specific PCR, pyrosequencing and Li-Cor analyses were conducted on 12 coat-color-associated alleles of five genes. Our data provide deep insight into the distribution of coat-color-associated alleles within breeds. We found that the alleles for the basic colorations (bay, black, and chestnut) are widely distributed and occur in nearly all breeds. Alleles leading to dilutions or patterns are rare in domestic breeds and were not found in Przewalski's horse. Higher frequencies of these alleles are only found in breeds that are selected for their expressed phenotypes (e.g., Kinsky horse, Lewitzer, Tinker). Nevertheless, our study produced strong evidence that molecular testing of the coat color is necessary for well-defined phenotyping to avoid unexpected colorations of offspring that can result in legal action.

  5. An Updated Collection of Sequence Barcoded Temperature-Sensitive Alleles of Yeast Essential Genes.

    Kofoed, Megan; Milbury, Karissa L; Chiang, Jennifer H; Sinha, Sunita; Ben-Aroya, Shay; Giaever, Guri; Nislow, Corey; Hieter, Philip; Stirling, Peter C

    2015-07-14

    Systematic analyses of essential gene function using mutant collections in Saccharomyces cerevisiae have been conducted using collections of heterozygous diploids, promoter shut-off alleles, through alleles with destabilized mRNA, destabilized protein, or bearing mutations that lead to a temperature-sensitive (ts) phenotype. We previously described a method for construction of barcoded ts alleles in a systematic fashion. Here we report the completion of this collection of alleles covering 600 essential yeast genes. This resource covers a larger gene repertoire than previous collections and provides a complementary set of strains suitable for single gene and genomic analyses. We use deep sequencing to characterize the amino acid changes leading to the ts phenotype in half of the alleles. We also use high-throughput approaches to describe the relative ts behavior of the alleles. Finally, we demonstrate the experimental usefulness of the collection in a high-content, functional genomic screen for ts alleles that increase spontaneous P-body formation. By increasing the number of alleles and improving the annotation, this ts collection will serve as a community resource for probing new aspects of biology for essential yeast genes. Copyright © 2015 Kofoed et al.

  6. Mannose-binding lectin variant alleles and the risk of arterial thrombosis in systemic lupus erythematosus

    Øhlenschlaeger, Tommy; Garred, Peter; Madsen, Hans O

    2004-01-01

    Cardiovascular disease is an important complication in patients with systemic lupus erythematosus (SLE). Variant alleles of the mannose-binding lectin gene are associated with SLE as well as with severe atherosclerosis. We determined whether mannose-binding lectin variant alleles were associated...

  7. Correlation in chicken between the marker LEI0258 alleles and Major Histocompatibility Complex sequences

    Chazara, Olympe; Juul-Madsen, Helle Risdahl; Chang, Chi-Seng

    Background The LEI0258 marker is located within the B region of the chicken Major Histocompatibility Complex (MHC), and is surprisingly well associated with serology. Therefore, the correlation between the LEI0258 alleles and the MHC class I and the class II alleles at the level of sequences is w...

  8. Genotype calling in tetraploid species from bi-allelic marker data using mixture models

    Voorrips, R.E.; Gort, G.; Vosman, B.

    2011-01-01

    Background: Automated genotype calling in tetraploid species was until recently not possible, which hampered genetic analysis. Modern genotyping assays often produce two signals, one for each allele of a bi-allelic marker. While ample software is available to obtain genotypes (homozygous for either

  9. A new mutation for Huntington disease following maternal transmission of an intermediate allele

    Semaka, Alicia; Kay, Chris; Belfroid, René D. M.; Bijlsma, Emilia K.; Losekoot, Monique; van Langen, Irene M.; van Maarle, Merel C.; Oosterloo, Mayke; Hayden, Michael R.; van Belzen, Martine J.

    2015-01-01

    New mutations for Huntington disease (HD) originate from CAG repeat expansion of intermediate alleles (27-35 CAG). Expansions of such alleles into the pathological range (≥ 36 CAG) have been exclusively observed in paternal transmission. We report the occurrence of a new mutation that defies the

  10. Radiation Chemical Studies of Gly-Met-Gly in Aqueous Solution

    Barata-Vallejo, Sebastian; Ferreri, Carla; Zhang, Tao; Permentier, Hjalmar; Bischoff, Rainer; Bobrowski, Krzysztof; Chatgilialoglu, Chryssostomos

    2016-01-01

    Important biological consequences are related to the reaction of HO(•) radicals with methionine (Met). Several fundamental aspects remain to be defined when Met is an amino acid residue incorporated in the interior of peptides and proteins. The present study focuses on Gly-Met-Gly, the simplest

  11. Muziektherapie voor kinderen en jongeren met ASS : En overzicht van de relevante literatuur

    Pater, Mathieu; van Yperen, Tom

    Muziektherapie wordt met grote regelmaat toegepast bij kinderen en jongeren met een autismespectrumstoornis (ASS). De vraag is of dit effect heeft. Dit artikel geeft een overzicht van de recente literatuur op dit vlak. Over de periode 1990 tot en met 2016 zijn 33 studies gevonden naar de inzet en

  12. Met .naturalis in zee: Nederlands koraalrifonderzoek in de Indo-Pacific

    Hoeksema, B.W.

    2003-01-01

    In een serie arikelen onder de naam 'Met Naturalis in zee', zal Onderwatersport in samenwerking met het Leidse museum Naturalis met enige regelmaat aandacht besteden aan Nederlands biologisch koraalrifonderzoek in de Indische en de Stille Oceaan. Bert Hoeksema schreef de introductie van de serie.

  13. The HGF Receptor c-Met Is Overexpressed in Esophageal Adenocarcinoma

    Luis J. Herrera

    2005-01-01

    Full Text Available The hepatocyte growth factor (HGF receptor, Met, has established oncogenic properties; however, its expression and function in esophageal adenocarcinoma (EA remain poorly understood. We aimed to determine the expression and potential alterations in Met expression in EA. Met expression was investigated in surgical specimens of EA, Barrett's esophagus (BE, and normal esophagus (NE using immunohistochemistry (IHC and quantitative reverse transcriptase polymerase chain reaction. Met expression, phosphorylation, and the effect of COX-2 inhibition on expression were examined in EA cell lines. IHC demonstrated intense Met immunoreactivity in all (100% EA and dysplastic BE specimens. In contrast, minimal immunostaining was observed in BE without dysplasia or NE specimens. Met mRNA and protein levels were increased in three EA cell lines, and Met protein was phosphorylated in the absence of serum. Sequence analysis found the kinase domain of c-met to be wild type in all three EA cell lines. HGF mRNA expression was identified in two EA cell lines. In COX-2-overexpressing cells, COX-2 inhibition decreased Met expression. Met is consistently overexpressed in EA surgical specimens and in three EA cell lines. Met dysregulation occurs early in Barrett's dysplasia to adenocarcinoma sequence. Future study of Met inhibition as a potential biologic therapy for EA is warranted.

  14. Mogelijkheden om vroeg tijdig bladrandproblemen te signaleren met MIPS bij Hortensia

    Noort, van F.R.; Jalink, H.

    2010-01-01

    Met geavanceerde camera technieken zijn beelden vast te leggen van fotosynthese activiteit en het is ook mogelijk gebleken om bladgedeelten met stress vast te leggen, zonder dat deze stress met het blote oog al te zien is. Dit opent perspectieven om monitorringonderzoek te doen naar het ontstaan van

  15. Spatial electric load forecasting

    Willis, H Lee

    2002-01-01

    Spatial Electric Load Forecasting Consumer Demand for Power and ReliabilityCoincidence and Load BehaviorLoad Curve and End-Use ModelingWeather and Electric LoadWeather Design Criteria and Forecast NormalizationSpatial Load Growth BehaviorSpatial Forecast Accuracy and Error MeasuresTrending MethodsSimulation Method: Basic ConceptsA Detailed Look at the Simulation MethodBasics of Computerized SimulationAnalytical Building Blocks for Spatial SimulationAdvanced Elements of Computerized SimulationHybrid Trending-Simulation MethodsAdvanced

  16. Cognitive Load and Cooperation

    Døssing, Felix Sebastian; Piovesan, Marco; Wengström, Erik Roland

    2017-01-01

    We study the effect of intuitive and reflective processes on cooperation using cognitive load. Compared with time constraint, which has been used in the previous literature, cognitive load is a more direct way to block reflective processes, and thus a more suitable way to study the link between...... intuition and cooperation. Using a repeated public goods game, we study the effect of different levels of cognitive load on contributions. We show that a higher cognitive load increases the initial level of cooperation. In particular, subjects are significantly less likely to fully free ride under high...... cognitive load....

  17. Association between the CCR5 32-bp deletion allele and late onset of schizophrenia

    Rasmussen, H.B.; Timm, S.; Wang, A.G.

    2006-01-01

    OBJECTIVE: The 32-bp deletion allele in chemokine receptor CCR5 has been associated with several immune-mediated diseases and might be implicated in schizophrenia as well. METHOD: The authors genotyped DNA samples from 268 schizophrenia patients and 323 healthy subjects. Age at first admission...... to a psychiatric hospital department served as a measure of disease onset. RESULTS: Patients and comparison subjects differed marginally in their genotype distribution, with a slightly higher frequency of the deletion allele seen in the patients. The authors found the deletion allele to be associated with higher......-onset schizophrenia) and healthy subjects differed significantly. This was reflected in an increased frequency of the deletion allele in the patient subgroup. Patients with ages at first admission below and above 40 years significantly differed in distribution of genotypes and alleles, with an overrepresentation...

  18. Angiotensin-converting enzyme (ACE) alleles in the Quechua, a high altitude South American native population.

    Rupert, J L; Devine, D V; Monsalve, M V; Hochachka, P W

    1999-01-01

    Recently it was reported that an allelic variant of the gene encoding angiotensin-converting enzyme (ACE) was significantly over-represented in a cohort of elite British mountaineers. It was proposed that this may be evidence for a specific genetic factor influencing the human capacity for physical performance. The implication that this allele could enhance performance at high altitude prompted us to determine its frequency in Quechua speaking natives living at altitudes greater than 3000m on the Andean Altiplano in South America. We found that the frequency of the putative performance allele in the Quechuas, although significantly higher than in Caucasians, was not different from lowland Native American populations. This observation suggests that, although the higher frequency of the 'performance allele' may have facilitated the migration of the ancestral Quechua to the highlands, the ACE insertion allele has not been subsequently selected for in this high altitude population.

  19. Allele-specific characterization of alanine: glyoxylate aminotransferase variants associated with primary hyperoxaluria.

    Melissa D Lage

    Full Text Available Primary Hyperoxaluria Type 1 (PH1 is a rare autosomal recessive kidney stone disease caused by deficiency of the peroxisomal enzyme alanine: glyoxylate aminotransferase (AGT, which is involved in glyoxylate detoxification. Over 75 different missense mutations in AGT have been found associated with PH1. While some of the mutations have been found to affect enzyme activity, stability, and/or localization, approximately half of these mutations are completely uncharacterized. In this study, we sought to systematically characterize AGT missense mutations associated with PH1. To facilitate analysis, we used two high-throughput yeast-based assays: one that assesses AGT specific activity, and one that assesses protein stability. Approximately 30% of PH1-associated missense mutations are found in conjunction with a minor allele polymorphic variant, which can interact to elicit complex effects on protein stability and trafficking. To better understand this allele interaction, we functionally characterized each of 34 mutants on both the major (wild-type and minor allele backgrounds, identifying mutations that synergize with the minor allele. We classify these mutants into four distinct categories depending on activity/stability results in the different alleles. Twelve mutants were found to display reduced activity in combination with the minor allele, compared with the major allele background. When mapped on the AGT dimer structure, these mutants reveal localized regions of the protein that appear particularly sensitive to interactions with the minor allele variant. While the majority of the deleterious effects on activity in the minor allele can be attributed to synergistic interaction affecting protein stability, we identify one mutation, E274D, that appears to specifically affect activity when in combination with the minor allele.

  20. Peak load arrangements : Assessment of Nordel guidelines

    2009-07-01

    taken after consultation with parties in other Nordic countries, and involving also regulators and TSOs. In NordREG's view there are basically three principles that should be guiding any decision to introduce peak load arrangements in the Nordic countries: i), the peak load arrangements should be introduced only in situations when security of supply cannot be met without these arrangements. Since the decision to introduce peak load arrangements might be of a political/legal nature, the length of such arrangement cannot be fixed. However, there should be a regular evaluation by the competent authority of any need or prolonged need for peak load arrangements and its effects of price formation in the Nordic market. ii), when peak load arrangements are introduced they should be designed to minimize the adverse effects on price formation in the Nordic market. Furthermore, if there are to be peak load arrangements, there might be a need for how to distinguish these peak load reserves from other reserves at the disposal of the TSOs. However, this issue needs further discussions and development. iii), Nordic consultation should be carried out where the views of all relevant authorities and stake holders in the market affected are invited. It is recommended that the governments consult with their Nordic counter parties before submitting legal proposals on peak load arrangements affecting Nordic price formation. These consultations should also be with regulators and TSOs who are involved in the design of the actual peak load arrangements. (Author)

  1. AKT-ions with a TWIST between EMT and MET.

    Tang, Huifang; Massi, Daniela; Hemmings, Brian A; Mandalà, Mario; Hu, Zhengqiang; Wicki, Andreas; Xue, Gongda

    2016-09-20

    The transcription factor Twist is an important regulator of cranial suture during embryogenesis. Closure of the neural tube is achieved via Twist-triggered cellular transition from an epithelial to mesenchymal phenotype, a process known as epithelial-mesenchymal transition (EMT), characterized by a remarkable increase in cell motility. In the absence of Twist activity, EMT and associated phenotypic changes in cell morphology and motility can also be induced, albeit moderately, by other transcription factor families, including Snail and Zeb. Aberrant EMT triggered by Twist in human mammary tumour cells was first reported to drive metastasis to the lung in a metastatic breast cancer model. Subsequent analysis of many types of carcinoma demonstrated overexpression of these unique EMT transcription factors, which statistically correlated with worse outcome, indicating their potential as biomarkers in the clinic. However, the mechanisms underlying their activation remain unclear. Interestingly, increasing evidence indicates they are selectively activated by distinct intracellular kinases, thereby acting as downstream effectors facilitating transduction of cytoplasmic signals into nucleus and reprogramming EMT and mesenchymal-epithelial transition (MET) transcription to control cell plasticity. Understanding these relationships and emerging data indicating differential phosphorylation of Twist leads to complex and even paradoxical functionalities, will be vital to unlocking their potential in clinical settings.

  2. Mecanismo cognitivos en la memoria; la Metáfora

    Francisco José Ruiz de Mendoza Ibañez

    2010-12-01

    Full Text Available La Lingüística Cognitiva (LC es una disciplina que, pese a su juventud, ha experimentado un desarrollo vertiginoso en los últimos treinta años1. Uno de los mayores logros de la LC (que la distingue de enfoques anteriores sobre el lenguaje como el estructuralismo y el generativismo chomskyano radica en no considerar el lenguaje como un sistema autosuficiente, sino más bien como una facultad cognitiva que interactúa con otras capacidades como son la percepción, la atención, la memoria, la emoción y el razonamiento. Por tanto, en LC los significados son parte de nuestro mundo conceptual. En la versión más temprana de la TMC Lakoff y Johnson defienden que tanto el lenguaje como el pensamiento están ligados y se estructuran de acuerdo con la experiencia corpórea (embodied experience. Así, la experiencia perceptual y espacial es la base para la categorización del mundo de manera que estas categorías (que pertenecen a dominios concretos se hacen corresponder con dominios más abstractos como los de la emoción, el tiempo o la estructura. Por tanto, la metáfora queda definida como un conjunto de correspondencias (conceptual mapping entre un dominio fuente (más concreto y un dominio meta (más abstracto.

  3. The Val66Met brain-derived neurotrophic factor gene variant interacts with early pain exposure to predict cortisol dysregulation in 7-year-old children born very preterm: Implications for cognition.

    Chau, C M Y; Cepeda, I L; Devlin, A M; Weinberg, J; Grunau, R E

    2017-02-07

    Early stress in the form of repetitive neonatal pain, in infants born very preterm, is associated with long-term dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and with poorer cognitive performance. Brain-derived neurotrophic factor (BDNF) which is important in synaptic plasticity and cognitive functions is reduced by stress. Therefore the BDNF Val66Met variant, which affects secretion of BDNF, may interact with early exposure to pain-related stress in children born very preterm, to differentially affect HPA regulation that in turn may be associated with altered cognitive performance. The aims of this study were to investigate whether in children born very preterm, the BDNF Val66Met variant modulates the association between neonatal pain-related stress and cortisol levels at age 7years, and if cortisol levels were related to cognitive function. Furthermore, we examined whether these relationships were sex-specific. Using a longitudinal cohort design, N=90 children born very preterm (24-32weeks gestation) were followed from birth to age 7years. Cortisol was assayed from hair as an index of cumulative stress and from saliva to measure reactivity to a cognitive challenge. BDNF Val66Met variant was genotyped at 7years using real-time polymerase chain reaction (PCR). Using generalized linear modeling, in boys with the Met allele, greater neonatal pain-related stress (adjusted for clinical risk factors) predicted lower hair cortisol (p=0.006) and higher reactivity salivary cortisol (p=0.002). In both boys and girls with the Met allele, higher salivary cortisol reactivity was correlated with lower IQ (r=-0.60; p=0.001) and poorer visual-motor integration (r=-0.48; p=0.008). Our findings show associations between lower BDNF availability (presence of the Met allele) and vulnerability to neonatal pain/stress in boys, but not girls. This exploratory study suggests new directions for research into possible mechanisms underlying how neonatal pain/stress is

  4. Optimisation of load control

    Koponen, P.

    1998-01-01

    Electricity cannot be stored in large quantities. That is why the electricity supply and consumption are always almost equal in large power supply systems. If this balance were disturbed beyond stability, the system or a part of it would collapse until a new stable equilibrium is reached. The balance between supply and consumption is mainly maintained by controlling the power production, but also the electricity consumption or, in other words, the load is controlled. Controlling the load of the power supply system is important, if easily controllable power production capacity is limited. Temporary shortage of capacity causes high peaks in the energy price in the electricity market. Load control either reduces the electricity consumption during peak consumption and peak price or moves electricity consumption to some other time. The project Optimisation of Load Control is a part of the EDISON research program for distribution automation. The following areas were studied: Optimization of space heating and ventilation, when electricity price is time variable, load control model in power purchase optimization, optimization of direct load control sequences, interaction between load control optimization and power purchase optimization, literature on load control, optimization methods and field tests and response models of direct load control and the effects of the electricity market deregulation on load control. An overview of the main results is given in this chapter

  5. Optimisation of load control

    Koponen, P [VTT Energy, Espoo (Finland)

    1998-08-01

    Electricity cannot be stored in large quantities. That is why the electricity supply and consumption are always almost equal in large power supply systems. If this balance were disturbed beyond stability, the system or a part of it would collapse until a new stable equilibrium is reached. The balance between supply and consumption is mainly maintained by controlling the power production, but also the electricity consumption or, in other words, the load is controlled. Controlling the load of the power supply system is important, if easily controllable power production capacity is limited. Temporary shortage of capacity causes high peaks in the energy price in the electricity market. Load control either reduces the electricity consumption during peak consumption and peak price or moves electricity consumption to some other time. The project Optimisation of Load Control is a part of the EDISON research program for distribution automation. The following areas were studied: Optimization of space heating and ventilation, when electricity price is time variable, load control model in power purchase optimization, optimization of direct load control sequences, interaction between load control optimization and power purchase optimization, literature on load control, optimization methods and field tests and response models of direct load control and the effects of the electricity market deregulation on load control. An overview of the main results is given in this chapter

  6. c-MET receptor tyrosine kinase as a molecular target in advanced hepatocellular carcinoma.

    Granito, Alessandro; Guidetti, Elena; Gramantieri, Laura

    2015-01-01

    c-MET is the membrane receptor for hepatocyte growth factor (HGF), also known as scatter factor or tumor cytotoxic factor, a mitogenic growth factor for hepatocytes. HGF is mainly produced by cells of mesenchymal origin and it mainly acts on neighboring epidermal and endothelial cells, regulating epithelial growth and morphogenesis. HGF/MET signaling has been identified among the drivers of tumorigenesis in human cancers. As such, c-MET is a recognized druggable target, and against it, targeted agents are currently under clinical investigation. c-MET overexpression is a common event in a wide range of human malignancies, including gastric, lung, breast, ovary, colon, kidney, thyroid, and liver carcinomas. Despite c-MET overexpression being reported by a large majority of studies, no evidence for a c-MET oncogenic addiction exists in hepatocellular carcinoma (HCC). In particular, c-MET amplification is a rare event, accounting for 4%-5% of cases while no mutation has been identified in c-MET oncogene in HCC. Thus, the selection of patient subgroups more likely to benefit from c-MET inhibition is challenging. Notwithstanding, c-MET overexpression was reported to be associated with increased metastatic potential and poor prognosis in patients with HCC, providing a rationale for its therapeutic inhibition. Here we summarize the role of activated HGF/MET signaling in HCC, its prognostic relevance, and the implications for therapeutic approaches in HCC.

  7. Prognostic impact of tumor MET expression among patients with stage IV gastric cancer

    Erichsen, Rune; Kelsh, Michael A; Oliner, Kelly S

    2016-01-01

    PURPOSE: We aimed to investigate the prevalence and prognostic impact of tumor mesenchymal epithelial transition factor (MET) expression in stage IV gastric cancers in a real-world clinical setting because existing evidence is sparse. METHODS: The study included archived cancer specimens from 103...... stage IV gastric cancer patients (2003-2010). We analyzed MET-protein expression by immunohistochemistry (MET-positive if ≥25% of tumor cells showed MET expression). We calculated overall survival using the Kaplan-Meier method and hazard ratios comparing mortality among MET-positive and MET.......6 months), corresponding to an adjusted hazard ratio of 2.2 (95% confidence interval, 1.3-3.7). CONCLUSIONS: Tumor MET expression is prevalent and has substantial prognostic impact in stage IV gastric cancer patients....

  8. A protective effect of the BDNF Met/Met genotype in obesity in healthy Caucasian subjects but not in patients with coronary heart disease.

    Sustar, A; Nikolac Perkovic, M; Nedic Erjavec, G; Svob Strac, D; Pivac, N

    2016-08-01

    Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor with an important role in the regulation of body weight, body mass index (BMI) and obesity. Increased BMI that leads to obesity is a substantial risk factor for coronary heart disease (CHD). The functional BDNF Val66Met polymorphism (rs6265) has been associated with CHD, obesity and BMI. The aim of the study was to determine the association between BDNF rs6265 polymorphism and CHD and/or BMI in patients with CHD and healthy control subjects. The study included 704 Caucasian subjects: 206 subjects with CHD and 498 healthy control subjects. The BDNF rs6265 genotype frequency was similar in male and female subjects, and there were no differences in the frequency of the BDNF rs6265 genotypes in 206 patients with CHD and in 498 healthy subjects. When study participants were subdivided according to the BMI categories into normal weight, overweight and obese subjects, significantly different BDNF rs6265 genotype frequency was found within healthy subjects, but not within patients with CHD. Healthy subjects, but not patients with CHD, subdivided into carriers of the Met/Met, Met/Val and Val/Val genotype, had different BMI scores. The BDNF rs6265 genotype frequency was similar in male and female subjects, and there were no differences in the frequency of the BDNF rs6265 genotypes in 206 patients with CHD and in 498 healthy subjects. When study participants were subdivided according to the BMI categories into normal weight, overweight and obese subjects, significantly different BDNF rs6265 genotype frequency was found within healthy subjects, but not within patients with CHD. Healthy subjects, but not patients with CHD, subdivided into carriers of the Met/Met, Met/Val and Val/Val genotype, had different BMI scores. BDNF rs6265 polymorphism was not associated with a diagnosis of CHD or with BMI categories among patients with CHD. In contrast, healthy Caucasians, carriers of the BDNF Met/Met genotype, had more

  9. A Costa Rican family affected with Charcot-Marie-Tooth disease due to the myelin protein zero (MPZ p.Thr124Met mutation shares the Belgian haplotype

    Alejandro Leal

    2014-12-01

    Full Text Available The p.Thr124Met mutation in the myelin protein zero (MPZ causes the Charcot-Marie-Tooth disease type 2J, a peripheral neuropathy with additional symptoms as pupillary alterations and deafness. It was observed in several families around the world originating e. g. from Germany, Belgium, Japan, Italy and North America. Here we report Central American patients originating from a family in Costa Rica carrying this mutation. Clinical, electrophysiological and molecular analysis of patients and controls were performed, including gene and linked markers´ sequencing. Carriers share almost the entire haplotype with two non related Belgian CMT patients. As a result of the haplotype analysis, based on ten markers (seven SNPs, two microsatellites and an intronic polyA stretch, the founder effect hypothesis for this allele migration is suggestive. Rev. Biol. Trop. 62 (4: 1285-1293. Epub 2014 December 01.

  10. Allele Age Under Non-Classical Assumptions is Clarified by an Exact Computational Markov Chain Approach.

    De Sanctis, Bianca; Krukov, Ivan; de Koning, A P Jason

    2017-09-19

    Determination of the age of an allele based on its population frequency is a well-studied problem in population genetics, for which a variety of approximations have been proposed. We present a new result that, surprisingly, allows the expectation and variance of allele age to be computed exactly (within machine precision) for any finite absorbing Markov chain model in a matter of seconds. This approach makes none of the classical assumptions (e.g., weak selection, reversibility, infinite sites), exploits modern sparse linear algebra techniques, integrates over all sample paths, and is rapidly computable for Wright-Fisher populations up to N e  = 100,000. With this approach, we study the joint effect of recurrent mutation, dominance, and selection, and demonstrate new examples of "selective strolls" where the classical symmetry of allele age with respect to selection is violated by weakly selected alleles that are older than neutral alleles at the same frequency. We also show evidence for a strong age imbalance, where rare deleterious alleles are expected to be substantially older than advantageous alleles observed at the same frequency when population-scaled mutation rates are large. These results highlight the under-appreciated utility of computational methods for the direct analysis of Markov chain models in population genetics.

  11. S-allele diversity in Sorbus aucuparia and Crataegus monogyna (Rosaceae: Maloideae).

    Raspé, O; Kohn, J R

    2002-06-01

    RT-PCR was used to obtain the first estimates from natural populations of allelic diversity at the RNase-based gametophytic self-incompatibility locus in the Rosaceae. A total of 20 alleles were retrieved from 20 Sorbus aucuparia individuals, whereas 17 alleles were found in 13 Crataegus monogyna samples. Estimates of population-level allele numbers fall within the range observed in the Solanaceae, the only other family with RNase-based incompatibility for which estimates are available. The nucleotide diversity of S-allele sequences was found to be much lower in the two Rosaceae species as compared with the Solanaceae. This was not due to a lower sequence divergence among most closely related alleles. Rather, it is the depth of the entire genealogy that differs markedly in the two families, with Rosaceae S-alleles exhibiting more recent apparent coalescence. We also investigated patterns of selection at the molecular level by comparing nucleotide diversity at synonymous and nonsynonymous sites. Stabilizing selection was inferred for the 5' region of the molecule, while evidence of diversifying selection was present elsewhere.

  12. Sensory Gating and Alpha-7 Nicotinic Receptor Gene Allelic Variants in Schizoaffective Disorder, Bipolar Type

    Martin, Laura F.; Leonard, Sherry; Hall, Mei-Hua; Tregellas, Jason R.; Freedman, Robert; Olincy, Ann

    2011-01-01

    Objectives Single nucleotide allelic variants in the promoter region of the chromosome 15 alpha-7 acetylcholine nicotinic receptor gene (CHRNA7) are associated with both schizophrenia and the P50 auditory evoked potential sensory gating deficit. The purpose of this study was to determine if CHRNA7 promoter allelic variants are also associated with abnormal P50 ratios in persons with schizoaffective disorder, bipolar type. Methods P50 auditory evoked potentials were recorded in a paired stimulus paradigm in 17 subjects with schizoaffective disorder, bipolar type. The P50 test to conditioning ratio was used as the measure of sensory gating. Mutation screening of the CHRNA7 promoter region was performed on the subjects’ DNA samples. Comparisons to previously obtained data from persons with schizophrenia and controls were made. Results Subjects with schizophrenia, regardless of allele status, had an abnormal mean P50 ratio. Subjects with schizoaffective disorder, bipolar type and a variant allele had an abnormal mean P50 ratio, whereas those schizoaffective subjects with the common alleles had a normal mean P50 ratio. Normal control subjects had a normal mean ratio, but controls with variant alleles had higher P50 ratios. Conclusions In persons with bipolar type schizoaffective disorder, CHRNA7 promoter region allelic variants are linked to the capacity to inhibit the P50 auditory evoked potential and thus are associated with a type of illness genetically and biologically more similar to schizophrenia. PMID:17192894

  13. Preferential Allele Expression Analysis Identifies Shared Germline and Somatic Driver Genes in Advanced Ovarian Cancer

    Halabi, Najeeb M.; Martinez, Alejandra; Al-Farsi, Halema; Mery, Eliane; Puydenus, Laurence; Pujol, Pascal; Khalak, Hanif G.; McLurcan, Cameron; Ferron, Gwenael; Querleu, Denis; Al-Azwani, Iman; Al-Dous, Eman; Mohamoud, Yasmin A.; Malek, Joel A.; Rafii, Arash

    2016-01-01

    Identifying genes where a variant allele is preferentially expressed in tumors could lead to a better understanding of cancer biology and optimization of targeted therapy. However, tumor sample heterogeneity complicates standard approaches for detecting preferential allele expression. We therefore developed a novel approach combining genome and transcriptome sequencing data from the same sample that corrects for sample heterogeneity and identifies significant preferentially expressed alleles. We applied this analysis to epithelial ovarian cancer samples consisting of matched primary ovary and peritoneum and lymph node metastasis. We find that preferentially expressed variant alleles include germline and somatic variants, are shared at a relatively high frequency between patients, and are in gene networks known to be involved in cancer processes. Analysis at a patient level identifies patient-specific preferentially expressed alleles in genes that are targets for known drugs. Analysis at a site level identifies patterns of site specific preferential allele expression with similar pathways being impacted in the primary and metastasis sites. We conclude that genes with preferentially expressed variant alleles can act as cancer drivers and that targeting those genes could lead to new therapeutic strategies. PMID:26735499

  14. Genetic dissection of the Drosophila melanogaster female head transcriptome reveals widespread allelic heterogeneity.

    King, Elizabeth G; Sanderson, Brian J; McNeil, Casey L; Long, Anthony D; Macdonald, Stuart J

    2014-05-01

    Modern genetic mapping is plagued by the "missing heritability" problem, which refers to the discordance between the estimated heritabilities of quantitative traits and the variance accounted for by mapped causative variants. One major potential explanation for the missing heritability is allelic heterogeneity, in which there are multiple causative variants at each causative gene with only a fraction having been identified. The majority of genome-wide association studies (GWAS) implicitly assume that a single SNP can explain all the variance for a causative locus. However, if allelic heterogeneity is prevalent, a substantial amount of genetic variance will remain unexplained. In this paper, we take a haplotype-based mapping approach and quantify the number of alleles segregating at each locus using a large set of 7922 eQTL contributing to regulatory variation in the Drosophila melanogaster female head. Not only does this study provide a comprehensive eQTL map for a major community genetic resource, the Drosophila Synthetic Population Resource, but it also provides a direct test of the allelic heterogeneity hypothesis. We find that 95% of cis-eQTLs and 78% of trans-eQTLs are due to multiple alleles, demonstrating that allelic heterogeneity is widespread in Drosophila eQTL. Allelic heterogeneity likely contributes significantly to the missing heritability problem common in GWAS studies.

  15. Genetic dissection of the Drosophila melanogaster female head transcriptome reveals widespread allelic heterogeneity.

    Elizabeth G King

    2014-05-01

    Full Text Available Modern genetic mapping is plagued by the "missing heritability" problem, which refers to the discordance between the estimated heritabilities of quantitative traits and the variance accounted for by mapped causative variants. One major potential explanation for the missing heritability is allelic heterogeneity, in which there are multiple causative variants at each causative gene with only a fraction having been identified. The majority of genome-wide association studies (GWAS implicitly assume that a single SNP can explain all the variance for a causative locus. However, if allelic heterogeneity is prevalent, a substantial amount of genetic variance will remain unexplained. In this paper, we take a haplotype-based mapping approach and quantify the number of alleles segregating at each locus using a large set of 7922 eQTL contributing to regulatory variation in the Drosophila melanogaster female head. Not only does this study provide a comprehensive eQTL map for a major community genetic resource, the Drosophila Synthetic Population Resource, but it also provides a direct test of the allelic heterogeneity hypothesis. We find that 95% of cis-eQTLs and 78% of trans-eQTLs are due to multiple alleles, demonstrating that allelic heterogeneity is widespread in Drosophila eQTL. Allelic heterogeneity likely contributes significantly to the missing heritability problem common in GWAS studies.

  16. Heat pumps combined with cold storage; Warmtepompen gecombineerd met koudeopslag

    Van Ingen, M.A. [Techniplan Adviseurs, Rotterdam (Netherlands)

    1999-09-01

    The architects of the new Nike head office building in Hilversum, Netherlands, opted for a heat pump combined with a cold storage system. The most efficient design was found to be a single central location for the production of heat and cold, with distribution lines to each of the five buildings. The cold storage system provides direct cooling and indirect heating: the heat pump raises the low-temperature heat from the cold storage to a usable temperature (augmented by district heating when necessary). In addition, the heat pump generates cold as a by-product in winter, which can be stored in the sources system and utilised during the following summer. The heat pump can also be used for cooling, for peak load supply and for any short-term storage requirement in emergencies

  17. Type 2 Diabetes Risk Allele Loci in the Qatari Population.

    Sarah L O'Beirne

    Full Text Available The prevalence of type 2 diabetes (T2D is increasing in the Middle East. However, the genetic risk factors for T2D in the Middle Eastern populations are not known, as the majority of studies of genetic risk for T2D are in Europeans and Asians.All subjects were ≥3 generation Qataris. Cases with T2D (n = 1,124 and controls (n = 590 were randomly recruited and assigned to the 3 known Qatari genetic subpopulations [Bedouin (Q1, Persian/South Asian (Q2 and African (Q3]. Subjects underwent genotyping for 37 single nucleotide polymorphisms (SNPs in 29 genes known to be associated with T2D in Europeans and/or Asian populations, and an additional 27 tag SNPs related to these susceptibility loci. Pre-study power analysis suggested that with the known incidence of T2D in adult Qataris (22%, the study population size would be sufficient to detect significant differences if the SNPs were risk factors among Qataris, assuming that the odds ratio (OR for T2D SNPs in Qatari's is greater than or equal to the SNP with highest known OR in other populations.Haplotype analysis demonstrated that Qatari haplotypes in the region of known T2D risk alleles in Q1 and Q2 genetic subpopulations were similar to European haplotypes. After Benjamini-Hochberg adjustment for multiple testing, only two SNPs (rs7903146 and rs4506565, both associated with transcription factor 7-like 2 (TCF7L2, achieved statistical significance in the whole study population. When T2D subjects and control subjects were assigned to the known 3 Qatari subpopulations, and analyzed individually and with the Q1 and Q2 genetic subpopulations combined, one of these SNPs (rs4506565 was also significant in the admixed group. No other SNPs associated with T2D in all Qataris or individual genetic subpopulations.With the caveats of the power analysis, the European/Asian T2D SNPs do not contribute significantly to the high prevalence of T2D in the Qatari population, suggesting that the genetic risks for T2D are

  18. Racial Differences in Prediction of Time to Prostate Cancer Diagnosis in a Prospective Screening Cohort of High-Risk Men: Effect of TMPRSS2 Met160Val

    Giri, Veda N.; Ruth, Karen; Hughes, Lucinda; Uzzo, Robert G.; Chen, David Y.T.; Boorjian, Stephen A.; Viterbo, Rosalia; Rebbeck, Timothy R.

    2011-01-01

    Introduction The TMPRSS2-ERG gene fusion occurs in >50% of prostate tumors and has been associated with poor outcomes. The T-allele (Valine) of the Met160Val (rs12329760) in TMPRSS2 has been associated with this fusion. We evaluated this polymorphism with respect to self-identified race or ethnicity (SIRE), time to prostate cancer (PCA) diagnosis, and screening parameters in the Prostate Cancer Risk Assessment Program, a prospective screening program for high-risk men. Patients and Methods 631 men ages 35-69 years were studied. “High-risk” was defined as ≥ one first degree or two second degree relatives with PCA, any African American (AA) man regardless of familial PCA, and men with BRCA1/2 mutations. Men with elevated PSA or other indications for PCA underwent biopsy. Men were followed from time of study entry to PCA diagnosis. Cox models were used to evaluate time to PCA diagnosis by genotype. Results Genotype distribution differed significantly by SIRE (CT/TT vs. CC, p<0.0001). Among 183 Caucasian men with at least one follow-up visit, PCA was more than doubled in men carrying CT/TT vs CC genotypes (HR= 2.55, 95% CI=1.14-5.70) after controlling for age and PSA. No association was seen among AA men by TMPRSS2 genotype. Conclusions The T-allele of the Met160Val variant in TMPRSS2, which has been associated with the TMPRSS2-ERG fusion, may be informative of time to PCA diagnosis for a subset of high-risk Caucasian men who are undergoing regular PCA screening. This variant along with other genetic markers warrant further study for personalizing PCA screening. PMID:20735386

  19. Concentrated loads on concrete

    Lorenzen, Karen Grøndahl; Nielsen, Mogens Peter

    1997-01-01

    This report deals with concentrated loads on concrete.A new upper bound solution in the axisymmetrical case of a point load in the center of the end face of a cylinder is developed.Based on previous work dealing with failure mechanisms and upper bound solutions, new approximate formulas are devel......This report deals with concentrated loads on concrete.A new upper bound solution in the axisymmetrical case of a point load in the center of the end face of a cylinder is developed.Based on previous work dealing with failure mechanisms and upper bound solutions, new approximate formulas...

  20. Critical Axial Load

    Walt Wells

    2008-01-01

    Full Text Available Our objective in this paper is to solve a second order differential equation for a long, simply supported column member subjected to a lateral axial load using Heun's numerical method. We will use the solution to find the critical load at which the column member will fail due to buckling. We will calculate this load using Euler's derived analytical approach for an exact solution, as well as Euler's Numerical Method. We will then compare the three calculated values to see how much they deviate from one another. During the critical load calculation, it will be necessary to calculate the moment of inertia for the column member.

  1. Load regulating expansion fixture

    Wagner, L.M.; Strum, M.J.

    1998-01-01

    A free standing self contained device for bonding ultra thin metallic films, such as 0.001 inch beryllium foils is disclosed. The device will regulate to a predetermined load for solid state bonding when heated to a bonding temperature. The device includes a load regulating feature, whereby the expansion stresses generated for bonding are regulated and self adjusting. The load regulator comprises a pair of friction isolators with a plurality of annealed copper members located there between. The device, with the load regulator, will adjust to and maintain a stress level needed to successfully and economically complete a leak tight bond without damaging thin foils or other delicate components. 1 fig

  2. Laterally loaded masonry

    Raun Gottfredsen, F.

    In this thesis results from experiments on mortar joints and masonry as well as methods of calculation of strength and deformation of laterally loaded masonry are presented. The strength and deformation capacity of mortar joints have been determined from experiments involving a constant compressive...... stress and increasing shear. The results show a transition to pure friction as the cohesion is gradually destroyed. An interface model of a mortar joint that can take into account this aspect has been developed. Laterally loaded masonry panels have also been tested and it is found to be characteristic...... that laterally loaded masonry exhibits a non-linear load-displacement behaviour with some ductility....

  3. Electrical load modeling

    Valgas, Helio Moreira; Pinto, Roberto del Giudice R.; Franca, Carlos [Companhia Energetica de Minas Gerais (CEMIG), Belo Horizonte, MG (Brazil); Lambert-Torres, Germano; Silva, Alexandre P. Alves da; Pires, Robson Celso; Costa, Junior, Roberto Affonso [Escola Federal de Engenharia de Itajuba, MG (Brazil)

    1994-12-31

    Accurate dynamic load models allow more precise calculations of power system controls and stability limits, which are critical mainly in the operation planning of power systems. This paper describes the development of a computer program (software) for static and dynamic load model studies using the measurement approach for the CEMIG system. Two dynamic load model structures are developed and tested. A procedure for applying a set of measured data from an on-line transient recording system to develop load models is described. (author) 6 refs., 17 figs.

  4. Systematic Functional Interrogation of Rare Cancer Variants Identifies Oncogenic Alleles | Office of Cancer Genomics

    Cancer genome characterization efforts now provide an initial view of the somatic alterations in primary tumors. However, most point mutations occur at low frequency, and the function of these alleles remains undefined. We have developed a scalable systematic approach to interrogate the function of cancer-associated gene variants. We subjected 474 mutant alleles curated from 5,338 tumors to pooled in vivo tumor formation assays and gene expression profiling. We identified 12 transforming alleles, including two in genes (PIK3CB, POT1) that have not been shown to be tumorigenic.

  5. [Analysis of allele dropout at TH01 locus in paternity testing].

    Lai, Li; Shen, Xiao-li; Xue, Shi-jie; Hu, Jie

    2013-10-01

    To analyze allele dropout at TH01 locus in paternity testing in order to determine the accurate genotype. To use a two STR loci genotyping system to verify an abnormal genotype for the TH01 locus with PCR using specific primers, cloning and DNA sequencing. A rare allele at TH01 locus named 5.2, which was undetectable with PowerPlex 21 system, was detected with an Identifiler system. Genetic variations may result in rare alleles and loci loss. To avoid misjudgment, laboratories should have a variety of methods for detecting loci loss.

  6. Suspension Array for Multiplex Detection of Eight Fungicide-Resistance Related Alleles in Botrytis cinerea

    Zhang, Xin; Xie, Fei; Lv, Baobei; Zhao, Pengxiang; Ma, Xuemei

    2016-01-01

    A simple and high-throughput assay to detect fungicide resistance is required for large-scale monitoring of the emergence of resistant strains of Botrytis cinerea. Using suspension array technology performed on a Bio-Plex 200 System, we developed a single-tube allele-specific primer extension (ASPE) assay that can simultaneously detect eight alleles in one reaction. These eight alleles include E198 and 198A of the β-Tubulin gene (BenA), H272 and 272Y of the Succinate dehydrogenase iron–sulfur...

  7. Overdispersion in allelic counts and θ-correction in forensic genetics

    Tvedebrink, Torben

    2010-01-01

    We present a statistical model for incorporating the extra variability in allelic counts due to subpopulation structures. In forensic genetics, this effect is modelled by the identical-by-descent parameter θ, which measures the relationship between pairs of alleles within a population relative...... with computation of the profile log-likelihood, confidence intervals and hypothesis testing. In order to compare our method with existing methods, we reanalysed FBI data from Budowle and Moretti (1999) with allele counts in six US subpopulations. Furthermore, we investigate properties of our methodology from...

  8. Fine Mapping Seronegative and Seropositive Rheumatoid Arthritis to Shared and Distinct HLA Alleles by Adjusting for the Effects of Heterogeneity

    Han, Buhm; Diogo, Dorothee; Eyre, Steve; Kallberg, Henrik; Zhernakova, Alexandra; Bowes, John; Padyukov, Leonid; Okada, Yukinori; Gonzalez-Gay, Miguel A.; Rantapaa-Dahlqvist, Solbritt; Martin, Javier; Huizinga, Tom W. J.; Plenge, Robert M.; Worthington, Jane; Gregersen, Peter K.; Klareskog, Lars; de Bakker, Paul I. W.; Raychaudhuri, Soumya

    2014-01-01

    Despite progress in defining human leukocyte antigen (HLA) alleles for anti-citrullinated-protein-autoantibody-positive (ACPA(+)) rheumatoid arthritis (RA), identifying HLA alleles for ACPA-negative (ACPA(-)) RA has been challenging because of clinical heterogeneity within clinical cohorts. We

  9. The role of maternal stress during pregnancy, maternal discipline, and child COMT Val158Met genotype in the development of compliance.

    Kok, Rianne; Bakermans-Kranenburg, Marian J; van Ijzendoorn, Marinus H; Velders, Fleur P; Linting, Mariëlle; Jaddoe, Vincent W V; Hofman, Albert; Verhulst, Frank C; Tiemeier, Henning

    2013-07-01

    Maternal discipline is an important predictor of child committed compliance. Maternal stress can affect both parenting and child development. In a large population-based cohort study (N = 613) we examined whether maternal discipline mediated the association between maternal stress during pregnancy and child compliance, and whether COMT or DRD4 polymorphisms moderated the association between maternal discipline and child compliance. Family-related and general stress were measured through maternal self-report and genetic material was collected through cord blood sampling at birth. Mother-child dyads were observed at 36 months in disciplinary tasks in which the child was not allowed to touch attractive toys. Maternal discipline and child compliance were observed in two different tasks and independently coded. The association between family stress during pregnancy and child committed compliance was mediated by maternal positive discipline. Children with more COMT Met alleles seemed more susceptible to maternal positive discipline than children with more COMT Val alleles. Copyright © 2012 Wiley Periodicals, Inc.

  10. In vivo detection of c-Met expression in a rat C6 glioma model.

    Towner, R A; Smith, N; Doblas, S; Tesiram, Y; Garteiser, P; Saunders, D; Cranford, R; Silasi-Mansat, R; Herlea, O; Ivanciu, L; Wu, D; Lupu, F

    2008-01-01

    The tyrosine kinase receptor, c-Met, and its substrate, the hepatocyte growth factor (HGF), are implicated in the malignant progression of glioblastomas. In vivo detection of c-Met expression may be helpful in the diagnosis of malignant tumours. The C6 rat glioma model is a widely used intracranial brain tumour model used to study gliomas experimentally. We used a magnetic resonance imaging (MRI) molecular targeting agent to specifically tag the cell surface receptor, c-Met, with an anti-c-Met antibody (Ab) linked to biotinylated Gd (gadolinium)-DTPA (diethylene triamine penta acetic acid)-albumin in rat gliomas to detect overexpression of this antigen in vivo. The anti-c-Met probe (anti-c-Met-Gd-DTPA-albumin) was administered intravenously, and as determined by an increase in MRI signal intensity and a corresponding decrease in regional T(1) relaxation values, this probe was found to detect increased expression of c-Met protein levels in C6 gliomas. In addition, specificity for the binding of the anti-c-Met contrast agent was determined by using fluorescence microscopic imaging of the biotinylated portion of the targeting agent within neoplastic and 'normal'brain tissues following in vivo administration of the anti-c-Met probe. Controls with no Ab or with a normal rat IgG attached to the contrast agent component indicated no non-specific binding to glioma tissue. This is the first successful visualization of in vivo overexpression of c-Met in gliomas.

  11. The potential roles of hepatocyte growth factor (HGF-MET pathway inhibitors in cancer treatment

    Parikh RA

    2014-06-01

    Full Text Available Rahul A Parikh,1 Peng Wang,2 Jan H Beumer,3 Edward Chu,1 Leonard J Appleman11Division of Hematology-Oncology, University of Pittsburgh School of Medicine, Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA; 2Division of Medical Oncology, University of Kentucky College of Medicine, Markey Cancer Center, Lexington, KY, USA; 3University of Pittsburgh School of Pharmacy, Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USAAbstract: MET is located on chromosome 7q31 and is a proto-oncogene that encodes for hepatocyte growth factor (HGF receptor, a member of the receptor tyrosine kinase (RTK family. HGF, also known as scatter factor (SF, is the only known ligand for MET. MET is a master regulator of cell growth and division (mitogenesis, mobility (motogenesis, and differentiation (morphogenesis; it plays an important role in normal development and tissue regeneration. The HGF-MET axis is frequently dysregulated in cancer by MET gene amplification, translocation, and mutation, or by MET or HGF protein overexpression. MET dysregulation is associated with an increased propensity for metastatic disease and poor overall prognosis across multiple tumor types. Targeting the dysregulated HGF-MET pathway is an area of active research; a number of monoclonal antibodies to HGF and MET, as well as small molecule inhibitors of MET, are under development. This review summarizes the key biological features of the HGF-MET axis, its dysregulation in cancer, and the therapeutic agents targeting the HGF-MET axis, which are in development.Keywords: MET inhibitor, HGF inhibitor, cancer

  12. Population estimators or progeny tests: what is the best method to assess null allele frequencies at SSR loci?

    Oddou-Muratorio, S.; Vendramin, G.G.; Buiteveld, J.; Fady, B.

    2009-01-01

    Nuclear SSRs are notorious for having relatively high frequencies of null alleles, i.e. alleles that fail to amplify and are thus recessive and undetected in heterozygotes. In this paper, we compare two kinds of approaches for estimating null allele frequencies at seven nuclear microsatellite

  13. The Met receptor tyrosine kinase prevents zebrafish primary motoneurons from expressing an incorrect neurotransmitter

    Eisen Judith S

    2008-07-01

    Full Text Available Abstract Background Expression of correct neurotransmitters is crucial for normal nervous system function. How neurotransmitter expression is regulated is not well-understood; however, previous studies provide evidence that both environmental signals and intrinsic differentiation programs are involved. One environmental signal known to regulate neurotransmitter expression in vertebrate motoneurons is Hepatocyte growth factor, which acts through the Met receptor tyrosine kinase and also affects other aspects of motoneuron differentiation, including axonal extension. Here we test the role of Met in development of motoneurons in embryonic zebrafish. Results We found that met is expressed in all early developing, individually identified primary motoneurons and in at least some later developing secondary motoneurons. We used morpholino antisense oligonucleotides to knock down Met function and found that Met has distinct roles in primary and secondary motoneurons. Most secondary motoneurons were absent from met morpholino-injected embryos, suggesting that Met is required for their formation. We used chemical inhibitors to test several downstream pathways activated by Met and found that secondary motoneuron development may depend on the p38 and/or Akt pathways. In contrast, primary motoneurons were present in met morpholino-injected embryos. However, a significant fraction of them had truncated axons. Surprisingly, some CaPs in met morpholino antisense oligonucleotide (MO-injected embryos developed a hybrid morphology in which they had both a peripheral axon innervating muscle and an interneuron-like axon within the spinal cord. In addition, in met MO-injected embryos primary motoneurons co-expressed mRNA encoding Choline acetyltransferase, the synthetic enzyme for their normal neurotransmitter, acetylcholine, and mRNA encoding Glutamate decarboxylase 1, the synthetic enzyme for GABA, a neurotransmitter never normally found in these motoneurons, but

  14. Load Balancing in Hypergraphs

    Delgosha, Payam; Anantharam, Venkat

    2018-03-01

    Consider a simple locally finite hypergraph on a countable vertex set, where each edge represents one unit of load which should be distributed among the vertices defining the edge. An allocation of load is called balanced if load cannot be moved from a vertex to another that is carrying less load. We analyze the properties of balanced allocations of load. We extend the concept of balancedness from finite hypergraphs to their local weak limits in the sense of Benjamini and Schramm (Electron J Probab 6(23):13, 2001) and Aldous and Steele (in: Probability on discrete structures. Springer, Berlin, pp 1-72, 2004). To do this, we define a notion of unimodularity for hypergraphs which could be considered an extension of unimodularity in graphs. We give a variational formula for the balanced load distribution and, in particular, we characterize it in the special case of unimodular hypergraph Galton-Watson processes. Moreover, we prove the convergence of the maximum load under some conditions. Our work is an extension to hypergraphs of Anantharam and Salez (Ann Appl Probab 26(1):305-327, 2016), which considered load balancing in graphs, and is aimed at more comprehensively resolving conjectures of Hajek (IEEE Trans Inf Theory 36(6):1398-1414, 1990).

  15. Structural load combinations

    Hwang, H.; Reich, M.; Ellingwood, B.; Shinozuka, M.

    1985-01-01

    This paper presents the latest results of the program entitled, ''Probability Based Load Combinations For Design of Category I Structures''. In FY 85, a probability-based reliability analysis method has been developed to evaluate safety of shear wall structures. The shear walls are analyzed using stick models with beam elements and may be subjected to dead load, live load and in-plane eqrthquake. Both shear and flexure limit states are defined analytically. The limit state probabilities can be evaluated on the basis of these limit states. Utilizing the reliability analysis method mentioned above, load combinations for the design of shear wall structures have been established. The proposed design criteria are in the load and resistance factor design (LRFD) format. In this study, the resistance factors for shear and flexure and load factors for dead and live loads are preassigned, while the load factor for SSE is determined for a specified target limit state probability of 1.0 x 10 -6 or 1.0 x 10 -5 during a lifetime of 40 years. 23 refs., 9 tabs

  16. Load Induced Blindness

    Macdonald, James S. P.; Lavie, Nilli

    2008-01-01

    Although the perceptual load theory of attention has stimulated a great deal of research, evidence for the role of perceptual load in determining perception has typically relied on indirect measures that infer perception from distractor effects on reaction times or neural activity (see N. Lavie, 2005, for a review). Here we varied the level of…

  17. Structural load combinations

    Hwang, H.; Reich, M.; Ellingwood, B.; Shinozuka, M.

    1986-01-01

    This paper presents the latest results of the program entitled, ''Probability Based Load Combinations For Design of Category I Structures''. In FY 85, a probability-based reliability analysis method has been developed to evaluate safety of shear wall structures. The shear walls are analyzed using stick models with beam elements and may be subjected to dead load, live load and in-plane earthquake. Both shear and flexure limit states are defined analytically. The limit state probabilities can be evaluated on the basis of these limit states. Utilizing the reliability analysis method mentioned above, load combinations for the design of shear wall structures have been established. The proposed design criteria are in the load and resistance factor design (LRFD) format. In this study, the resistance factors for shear and flexure and load factors for dead and live loads are preassigned, while the load factor for SSE is determined for a specified target limit state probability of 1.0 x 10 -6 or 1.0 x 10 -5 during a lifetime of 40 years

  18. Load event: Aircraft crash

    Fritsch, H.

    1985-01-01

    The bibliography includes 48 quotations, up to the year 1983, on the following issues: Experiments and computational methods. Design load for the dimensioning of reinforced concrete buildings and components with respect to the dynamic load in the event of an aircraft crash. (orig./HP) [de

  19. Identification of Ppd-B1 alleles in common wheat cultivars by CAPS marker.

    Okoń, S; Kowalczyk, K; Miazga, D

    2012-05-01

    Photoperiod response is a major determinant of the duration of growth stages in common wheat. In common wheat, many genes play a role in determining flowering time, but the Ppd genes located on the homoeologous group 2 play a major role. Of these Ppd-B1 is located on the short arm of 2B. In 107 common wheat cultivars grown in Poland and neighboring countries, the identification of Ppd-B1 alleles using in-del analysis by using a CAPS markers was investigated. 87 cultivars were shown to carry dominant Ppd-B1 alleles. This shows that Ppd-B1 alleles is have been widely used in common wheat breeding programme in these countries. Recessive ppd-B1 alleles were found only in 20 cultivars (12 Polish, 5 former Soviet Union, 2 German, 1 Swedish).

  20. The power and statistical behaviour of allele-sharing statistics when ...

    Unknown

    3Human Genetics Division, School of Medicine, University of Southampton, Southampton SO16 6YD, UK. Abstract ... that the statistic S-#alleles gives good performance for recessive ... (H50) of the families are linked to the single marker. The.

  1. Allele-Specific Alternative mRNA processing (ASARP) | Informatics Technology for Cancer Research (ITCR)

    A software pipeline for prediction of allele-specific alternative RNA processing events using single RNA-seq data. The current version focuses on prediction of alternative splicing and alternative polyadenylation modulated by genetic variants.

  2. Fitness differences due to allelic variation at Esterase-4 locus in ...

    KAVITA KRISHNAMOORTI

    2017-08-31

    Aug 31, 2017 ... Keywords. esterases; null allele; reproductive fitness; natural selection; Drosophila ananassae. .... cific substrate (1-naphthylacetate AR) and stain (fast blue. RR). On the ... transferred to fresh food vials and eggs were counted.

  3. Fitness differences due to allelic variation at Esterase-4 Locus in ...

    Navya

    2017-01-04

    Jan 4, 2017 ... specific substrate (1-Naphthylacetate AR) and stain (Fast blue RR). On the basis of ... After 24 hr. each pair was transferred to fresh food vials .... derived from the natural populations harbour allelic variation that affects lifespan.

  4. Comparative population analysis of metallothionein promoter alleles suggests stress-induced microevolution in the field.

    Janssens, T.K.S.; Del Rio Lopez, R.; Mariën, A.G.H.; Timmermans, M.J.T.N.; Montagne-Wajer, K; van Straalen, N.M.; Roelofs, D.

    2008-01-01

    We investigate a model system for microevolution of transcriptional regulation: metallothionein expression in springtails. A previous survey of the metallothionein promoter in Orchesella cincta (Collembola) revealed nine alleles with differential basal activities and responses to cadmium and

  5. Comparative population analysis of metallothionein promoter alleles suggests stress-induced microevolution in the field

    Janssens, Thierry K S; Lopéz, Ricardo del Rio; Mariën, Janine; Timmermans, Martijn J T N; Montagne-Wajer, K; van Straalen, Nico M; Roelofs, Dick

    2008-01-01

    We investigate a model system for microevolution of transcriptional regulation: metallothionein expression in springtails. A previous survey of the metallothionein promoter in Orchesella cincta (Collembola) revealed nine alleles with differential basal activities and responses to cadmium and

  6. Allelic Dropout in the ENG Gene, Affecting the Results of Genetic Testing in Hereditary Hemorrhagic Telangiectasia

    Tørring, Pernille M; Kjeldsen, A.D.; Ousager, L.B.

    2012-01-01

    Background: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant vascular disorder with three disease-causing genes identified to date: ENG, ACVRL1, and SMAD4. We report an HHT patient with allelic dropout that on routine sequence analysis for a known mutation in the family (c.817......-3T>G in ENG) initially seemed to be homozygous for the mutation. Aim: To explore the possibility of allelic dropout causing a false result in this patient. Methods: Mutation analysis of additional family members was performed and haplotype analysis carried out. New primers were designed to reveal...... the presence of a possible sequence variant, which could explain the presumed allelic dropout. Results: Allelic dropout caused by a six-nucleotide duplication close to the standard reverse primer was the assumed cause of a false homozygous diagnosis. Conclusion: Sequence variants outside of the primer regions...

  7. The number of self-incompatibility alleles in a finite, subdivided population

    Schierup, M H

    1998-01-01

    The actual and effective number of gametophytic self-incompatibility alleles maintained at mutation-drift-selection equilibrium in a finite population subdivided as in the island model is investigated by stochastic simulations. The existing theory founded by Wright predicts that for a given...... population size the number of alleles maintained increases monotonically with decreasing migration as is the case for neutral alleles. The simulation results here show that this is not true. At migration rates above Nm = 0.01-0.1, the actual and effective number of alleles is lower than for an undivided...... of individuals in the population but it underestimates the neutral effective size of the subdivided population. Udgivelsesdato: 1998-Jun...

  8. Haptoglobin genotyping of Vietnamese: global distribution of HP del, complete deletion allele of the HP gene.

    Soejima, Mikiko; Agusa, Tetsuro; Iwata, Hisato; Fujihara, Junko; Kunito, Takashi; Takeshita, Haruo; Lan, Vi Thi Mai; Minh, Tu Binh; Takahashi, Shin; Trang, Pham Thi Kim; Viet, Pham Hung; Tanabe, Shinsuke; Koda, Yoshiro

    2015-01-01

    The haptoglobin (HP) gene deletion allele (HP(del)) is responsible for anhaptoglobinemia and a genetic risk factor for anaphylaxis reaction after transfusion due to production of the anti-HP antibody. The distribution of this allele has been explored by several groups including ours. Here, we studied the frequency of HP(del) in addition to the distribution of common HP genotypes in 293 Vietnamese. The HP(del) was encountered with the frequency of 0.020. The present result suggested that this deletion allele is restricted to East and Southeast Asians. Thus, this allele seems to be a potential ancestry informative marker for these populations. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Using multi-locus allelic sequence data to estimate genetic divergence among four Lilium (Liliaceae) cultivars

    Shahin, A.; Smulders, M.J.M.; Tuyl, van J.M.; Arens, P.F.P.; Bakker, F.T.

    2014-01-01

    Next Generation Sequencing (NGS) may enable estimating relationships among genotypes using allelic variation of multiple nuclear genes simultaneously. We explored the potential and caveats of this strategy in four genetically distant Lilium cultivars to estimate their genetic divergence from

  10. Allele mining across DREB1A and DREB1B in diverse rice ...

    Low temperature stress is one of the major limiting factors affecting rice productivity in higher altitudes. DREB1A and ..... to isolate useful alleles from related genotypes. A total of ... work also suggests that DREB induction and cold response.

  11. Samen leven met ME/CVS : Een onderzoek naar de rol van partnersteun en ziekterepresentaties bij coping met en adaptatie aan ME/CVS.

    Marleen Hofman, [No Value

    2013-01-01

    Achtergrond: Het chronisch vermoeidheidssyndroom (CVS) is een chronische ziekte die wordt gekenmerkt door ernstige vermoeidheid die vaak gepaard gaat met reumatische, infectieuze en neuropsychiatrische klachten. Het is een ernstig invaliderende aandoening waar tot nog toe geen genezende behandeling

  12. Diversity Outbred Mice at 21: Maintaining Allelic Variation in the Face of Selection

    Elissa J. Chesler

    2016-12-01

    Full Text Available Multi-parent populations (MPPs capture and maintain the genetic diversity from multiple inbred founder strains to provide a resource for high-resolution genetic mapping through the accumulation of recombination events over many generations. Breeding designs that maintain a large effective population size with randomized assignment of breeders at each generation can minimize the impact of selection, inbreeding, and genetic drift on allele frequencies. Small deviations from expected allele frequencies will have little effect on the power and precision of genetic analysis, but a major distortion could result in reduced power and loss of important functional alleles. We detected strong transmission ratio distortion in the Diversity Outbred (DO mouse population on chromosome 2, caused by meiotic drive favoring transmission of the WSB/EiJ allele at the R2d2 locus. The distorted region harbors thousands of polymorphisms derived from the seven non-WSB founder strains and many of these would be lost if the sweep was allowed to continue. To ensure the utility of the DO population to study genetic variation on chromosome 2, we performed an artificial selection against WSB/EiJ alleles at the R2d2 locus. Here, we report that we have purged the WSB/EiJ allele from the drive locus while preserving WSB/EiJ alleles in the flanking regions. We observed minimal disruption to allele frequencies across the rest of the autosomal genome. However, there was a shift in haplotype frequencies of the mitochondrial genome and an increase in the rate of an unusual sex chromosome aneuploidy. The DO population has been restored to genome-wide utility for genetic analysis, but our experience underscores that vigilant monitoring of similar genetic resource populations is needed to ensure their long-term utility.

  13. Analysis of FBN1 allele expression by dermal fibroblasts from Marfan syndrome patients

    Putman, E.A.; Cao, S.N.; Milewicz, D.M. [Univ. of Texas Medical School, Houston, TX (United States)

    1994-09-01

    Screening for mutations in the FBN1 cDNA from Marfan patient cell strains has detected mutations in only 10-15% of patients. In an attempt to explain this poor detection rate, we examined FBN1 allele expression and fibrillin synthesis by 26 cell strains from Marfan patients. DNA from the patients and 10 controls was assessed for the presence of a polymorphic Rsa I restriction site in the 3{prime} untranslated region of the FBN1 gene. Twelve of 26 patient and 5 of 10 control DNAs were heterozygous. Fibroblast RNA from the heterozygous cell strains was reverse-transcribed and subsequently PCR amplified using a [{sup 32}P]-labelled primer, digested with Rsa I and analyzed. Although 3 samples showed no transcript from one allele by ethidium bromide staining, a Betagen scanner detected low levels (10-15%) of that allele. In addition, there was unequal expression of the two alleles in three other patients; for example, only 30% expression from one allele. The remaining patients and the controls had equal expression of each allele. Fibrillin protein synthesis by fibroblasts from these heterozygous patients was also examined. After a 30 minute pulse with [{sup 35}S]-cysteine, cell lysates were collected and proteins analyzed by SDS-PAGE. The amount of fibrillin produced relative to a reference protein was determined using a Betagen scanner. Fibrillin protein synthesis was reduced in 2 of the 3 patients with very low RNA production from one of the FBN1 alleles. All other Marfan and control cell strains showed normal amounts of fibrillin synthesized. The low expression levels from one allele may contribute to, but not fully account for, the low detection rate of FBN1 mutations. Interestingly, protein synthesis levels were not affected in 4 of 6 cell strains demonstrating low levels of RNA expression.

  14. Semiparametric Allelic Tests for Mapping Multiple Phenotypes: Binomial Regression and Mahalanobis Distance.

    Majumdar, Arunabha; Witte, John S; Ghosh, Saurabh

    2015-12-01

    Binary phenotypes commonly arise due to multiple underlying quantitative precursors and genetic variants may impact multiple traits in a pleiotropic manner. Hence, simultaneously analyzing such correlated traits may be more powerful than analyzing individual traits. Various genotype-level methods, e.g., MultiPhen (O'Reilly et al. []), have been developed to identify genetic factors underlying a multivariate phenotype. For univariate phenotypes, the usefulness and applicability of allele-level tests have been investigated. The test of allele frequency difference among cases and controls is commonly used for mapping case-control association. However, allelic methods for multivariate association mapping have not been studied much. In this article, we explore two allelic tests of multivariate association: one using a Binomial regression model based on inverted regression of genotype on phenotype (Binomial regression-based Association of Multivariate Phenotypes [BAMP]), and the other employing the Mahalanobis distance between two sample means of the multivariate phenotype vector for two alleles at a single-nucleotide polymorphism (Distance-based Association of Multivariate Phenotypes [DAMP]). These methods can incorporate both discrete and continuous phenotypes. Some theoretical properties for BAMP are studied. Using simulations, the power of the methods for detecting multivariate association is compared with the genotype-level test MultiPhen's. The allelic tests yield marginally higher power than MultiPhen for multivariate phenotypes. For one/two binary traits under recessive mode of inheritance, allelic tests are found to be substantially more powerful. All three tests are applied to two different real data and the results offer some support for the simulation study. We propose a hybrid approach for testing multivariate association that implements MultiPhen when Hardy-Weinberg Equilibrium (HWE) is violated and BAMP otherwise, because the allelic approaches assume HWE

  15. No evidence for allelic association between bipolar disorder and monoamine oxidase A gene polymorphisms

    Craddock, N.; Daniels, J.; Roberts, E. [Univ. of Wales, College of Medicine, Cardiff (United Kingdom)] [and others

    1995-08-14

    We have tested the hypothesis that DNA markers in the MAOA gene show allelic association with bipolar affective disorder. Eighty-four unrelated Caucasian patients with DSM III-R bipolar disorder and 84 Caucasian controls were typed for three markers in MAOA: a dinucleotide repeat in intron 2, a VNTR in intron 1, and an Fnu4HI RFLP in exon 8. No evidence for allelic association was observed between any of the markers and bipolar disorder. 9 refs., 1 tab.

  16. QuASAR-MPRA: accurate allele-specific analysis for massively parallel reporter assays.

    Kalita, Cynthia A; Moyerbrailean, Gregory A; Brown, Christopher; Wen, Xiaoquan; Luca, Francesca; Pique-Regi, Roger

    2018-03-01

    The majority of the human genome is composed of non-coding regions containing regulatory elements such as enhancers, which are crucial for controlling gene expression. Many variants associated with complex traits are in these regions, and may disrupt gene regulatory sequences. Consequently, it is important to not only identify true enhancers but also to test if a variant within an enhancer affects gene regulation. Recently, allele-specific analysis in high-throughput reporter assays, such as massively parallel reporter assays (MPRAs), have been used to functionally validate non-coding variants. However, we are still missing high-quality and robust data analysis tools for these datasets. We have further developed our method for allele-specific analysis QuASAR (quantitative allele-specific analysis of reads) to analyze allele-specific signals in barcoded read counts data from MPRA. Using this approach, we can take into account the uncertainty on the original plasmid proportions, over-dispersion, and sequencing errors. The provided allelic skew estimate and its standard error also simplifies meta-analysis of replicate experiments. Additionally, we show that a beta-binomial distribution better models the variability present in the allelic imbalance of these synthetic reporters and results in a test that is statistically well calibrated under the null. Applying this approach to the MPRA data, we found 602 SNPs with significant (false discovery rate 10%) allele-specific regulatory function in LCLs. We also show that we can combine MPRA with QuASAR estimates to validate existing experimental and computational annotations of regulatory variants. Our study shows that with appropriate data analysis tools, we can improve the power to detect allelic effects in high-throughput reporter assays. http://github.com/piquelab/QuASAR/tree/master/mpra. fluca@wayne.edu or rpique@wayne.edu. Supplementary data are available online at Bioinformatics. © The Author (2017). Published by

  17. SNP calling, genotype calling, and sample allele frequency estimation from new-generation sequencing data

    Nielsen, Rasmus; Korneliussen, Thorfinn Sand; Albrechtsen, Anders

    2012-01-01

    We present a statistical framework for estimation and application of sample allele frequency spectra from New-Generation Sequencing (NGS) data. In this method, we first estimate the allele frequency spectrum using maximum likelihood. In contrast to previous methods, the likelihood function is cal...... be extended to various other cases including cases with deviations from Hardy-Weinberg equilibrium. We evaluate the statistical properties of the methods using simulations and by application to a real data set....

  18. The link between some alleles on human leukocyte antigen system and autism in children.

    Mostafa, Gehan A; Shehab, Abeer A; Al-Ayadhi, Laila Y

    2013-02-15

    The reason behind the initiation of autoimmunity to brain in some patients with autism is not well understood. There is an association between some autoimmune disorders and specific alleles of human leukocyte antigen (HLA) system. Thus, we examined the frequency of some HLA-DRB1 alleles in 100 autistic children and 100 healthy matched-children by differential hybridization with sequence-specific oligonucleotide probes. The risk of association between acquisition or absence of these alleles and autism and also a history of autoimmune diseases in autistic relatives was studied. Autistic children had significantly higher frequency of HLA-DRB1*11 allele than controls (P<0.001). In contrast, autistic children had significantly lower frequency of HLA-DRB1*03 allele than controls (P<0.001). Acquisition of HLA-DRB1*011 and absence of HLA-DRB1*3 had significant risk for association with autism (odds ratio: 3.21 and 0.17, respectively; 95% CI: 1.65-6.31 and 0.06-0.45, respectively). HLA-DRB1*11 had a significant risk for association with a family history of autoimmunity in autistic children (odds ratio: 5.67; 95% CI: 2.07-16.3). In conclusions, the link of some HLA alleles to autism and to family history of autoimmunity indicates the possible contributing role of these alleles to autoimmunity in some autistic children. Despite a relatively small sample size, we are the first to report a probable protective association of HLA-DRB1*03 allele with autism. It warrants a replication study of a larger sample to validate the HLA-DRB1 genetic association with autism. This is important to determine whether therapeutic modulations of the immune function are legitimate avenues for novel therapy in selected cases of autism. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Anti-c-MET Nanobody - a new potential drug in multiple myeloma treatment.

    Slørdahl, Tobias Schmidt; Denayer, Tinneke; Moen, Siv Helen; Standal, Therese; Børset, Magne; Ververken, Cedric; Rø, Torstein Baade

    2013-11-01

    c-MET is the tyrosine kinase receptor of the hepatocyte growth factor (HGF). HGF-c-MET signaling is involved in many human malignancies, including multiple myeloma (MM). Recently, multiple agents have been developed directed to interfere at different levels in HGF-c-MET signaling pathway. Nanobodies are therapeutic proteins based on the smallest functional fragments of heavy-chain-only antibodies. In this study, we wanted to determine the anticancer effect of a novel anti-c-MET Nanobody in MM. We examined the effects of an anti-c-MET Nanobody on thymidine incorporation, migration, adhesion of MM cells, and osteoblastogenesis in vitro. Furthermore, we investigated the effects of the Nanobody on HGF-dependent c-MET signaling by Western blotting. We show that the anti-c-MET Nanobody effectively inhibited thymidine incorporation of ANBL-6 MM cells via inhibition of an HGF autocrine growth loop and thymidine incorporation in INA-6 MM cells induced by exogenous HGF. HGF-induced migration and adhesion of INA-6 were completely and specifically blocked by the Nanobody. Furthermore, the Nanobody abolished the inhibiting effect of HGF on bone morphogenetic protein-2-induced alkaline phosphatase activity and the mineralization of human mesenchymal stem cells. Finally, we show that the Nanobody reduced phosphorylation of tyrosine residues in c-MET, MAPK, and Akt. We also compared the Nanobody with anti-c-MET monoclonal antibodies and revealed the similar or better effect. The anti-c-MET Nanobody inhibited MM cell migration, thymidine incorporation, and adhesion, and blocked the HGF-mediated inhibition of osteoblastogenesis. The anti-c-MET Nanobody might represent a novel therapeutic agent in the treatment of MM and other cancers driven by HGF-c-MET signaling. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Cooperative interaction of MUC1 with the HGF/c-Met pathway during hepatocarcinogenesis.

    Bozkaya, Giray; Korhan, Peyda; Cokaklı, Murat; Erdal, Esra; Sağol, Ozgül; Karademir, Sedat; Korch, Christopher; Atabey, Neşe

    2012-09-11

    Hepatocyte growth factor (HGF) induced c-Met activation is known as the main stimulus for hepatocyte proliferation and is essential for liver development and regeneration. Activation of HGF/c-Met signaling has been correlated with aggressive phenotype and poor prognosis in hepatocellular carcinoma (HCC). MUC1 is a transmembrane mucin, whose over-expression is reported in most cancers. Many of the oncogenic effects of MUC1 are believed to occur through the interaction of MUC1 with signaling molecules. To clarify the role of MUC1 in HGF/c-Met signaling, we determined whether MUC1 and c-Met interact cooperatively and what their role(s) is in hepatocarcinogenesis. MUC1 and c-Met over-expression levels were determined in highly motile and invasive, mesenchymal-like HCC cell lines, and in serial sections of cirrhotic and HCC tissues, and these levels were compared to those in normal liver tissues. Co-expression of both c-Met and MUC1 was found to be associated with the differentiation status of HCC. We further demonstrated an interaction between c-Met and MUC1 in HCC cells. HGF-induced c-Met phosphorylation decreased this interaction, and down-regulated MUC1 expression. Inhibition of c-Met activation restored HGF-mediated MUC1 down-regulation, and decreased the migratory and invasive abilities of HCC cells via inhibition of β-catenin activation and c-Myc expression. In contrast, siRNA silencing of MUC1 increased HGF-induced c-Met activation and HGF-induced cell motility and invasion. These findings indicate that the crosstalk between MUC1 and c-Met in HCC could provide an advantage for invasion to HCC cells through the β-catenin/c-Myc pathway. Thus, MUC1 and c-Met could serve as potential therapeutic targets in HCC.

  1. c-MET receptor tyrosine kinase as a molecular target in advanced hepatocellular carcinoma

    Granito A

    2015-04-01

    Full Text Available Alessandro Granito,1 Elena Guidetti,1 Laura Gramantieri2,3 1Dipartimento di Scienze Mediche e Chirurgiche Università di Bologna, Bologna, Italy; 2Dipartimento dell'Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 3Centro di Ricerca Biomedica Applicata (CRBA, Azienda Ospedaliero-Universitaria Policlinico S Orsola-Malpighi e Università di Bologna, Bologna, Italy Abstract: c-MET is the membrane receptor for hepatocyte growth factor (HGF, also known as scatter factor or tumor cytotoxic factor, a mitogenic growth factor for hepatocytes. HGF is mainly produced by cells of mesenchymal origin and it mainly acts on neighboring epidermal and endothelial cells, regulating epithelial growth and morphogenesis. HGF/MET signaling has been identified among the drivers of tumorigenesis in human cancers. As such, c-MET is a recognized druggable target, and against it, targeted agents are currently under clinical investigation. c-MET overexpression is a common event in a wide range of human malignancies, including gastric, lung, breast, ovary, colon, kidney, thyroid, and liver carcinomas. Despite c-MET overexpression being reported by a large majority of studies, no evidence for a c-MET oncogenic addiction exists in hepatocellular carcinoma (HCC. In particular, c-MET amplification is a rare event, accounting for 4%–5% of cases while no mutation has been identified in c-MET oncogene in HCC. Thus, the selection of patient subgroups more likely to benefit from c-MET inhibition is challenging. Notwithstanding, c-MET overexpression was reported to be associated with increased metastatic potential and poor prognosis in patients with HCC, providing a rationale for its therapeutic inhibition. Here we summarize the role of activated HGF/MET signaling in HCC, its prognostic relevance, and the implications for therapeutic approaches in HCC. Keywords: hepatocellular carcinoma, c-MET, clinical trials

  2. De betekenis van Paulus' oproep tot de groet met de heilige kus

    Voogd, Joanna Bernarda

    Dit boek is een studie naar de betekenis van de Paulijnse oproep tot de groet met de heilige kus. In vier passages in het Nieuwe Testament is deze oproep vindbaar: “Groet alle broeders (en zusters) met de heilige kus” (1 Tes 5:26) of “groet elkaar met de heilige kus” (1 Kor 16:20; 2 Kor 13:12 en

  3. User-Defined Meteorological (MET) Profiles from Climatological and Extreme Condition Data

    2018-04-01

    ARL-TN-0876 ● MAR 2018 US Army Research Laboratory User-Defined Meteorological (MET) Profiles from Climatological and Extreme...needed. Do not return it to the originator. ARL-TN-0876 ● MAR 2018 US Army Research Laboratory User-Defined Meteorological (MET...User-Defined Meteorological (MET) Profiles from Climatological and Extreme Condition Data 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM

  4. Cooperative interaction of MUC1 with the HGF/c-Met pathway during hepatocarcinogenesis

    Bozkaya Giray

    2012-09-01

    Full Text Available Abstract Background Hepatocyte growth factor (HGF induced c-Met activation is known as the main stimulus for hepatocyte proliferation and is essential for liver development and regeneration. Activation of HGF/c-Met signaling has been correlated with aggressive phenotype and poor prognosis in hepatocellular carcinoma (HCC. MUC1 is a transmembrane mucin, whose over-expression is reported in most cancers. Many of the oncogenic effects of MUC1 are believed to occur through the interaction of MUC1 with signaling molecules. To clarify the role of MUC1 in HGF/c-Met signaling, we determined whether MUC1 and c-Met interact cooperatively and what their role(s is in hepatocarcinogenesis. Results MUC1 and c-Met over-expression levels were determined in highly motile and invasive, mesenchymal-like HCC cell lines, and in serial sections of cirrhotic and HCC tissues, and these levels were compared to those in normal liver tissues. Co-expression of both c-Met and MUC1 was found to be associated with the differentiation status of HCC. We further demonstrated an interaction between c-Met and MUC1 in HCC cells. HGF-induced c-Met phosphorylation decreased this interaction, and down-regulated MUC1 expression. Inhibition of c-Met activation restored HGF-mediated MUC1 down-regulation, and decreased the migratory and invasive abilities of HCC cells via inhibition of β-catenin activation and c-Myc expression. In contrast, siRNA silencing of MUC1 increased HGF-induced c-Met activation and HGF-induced cell motility and invasion. Conclusions These findings indicate that the crosstalk between MUC1 and c-Met in HCC could provide an advantage for invasion to HCC cells through the β-catenin/c-Myc pathway. Thus, MUC1 and c-Met could serve as potential therapeutic targets in HCC.

  5. Self-incompatibility of Prunus tenella and evidence that reproductively isolated species of Prunus have different SFB alleles coupled with an identical S-RNase allele.

    Surbanovski, Nada; Tobutt, Kenneth R; Konstantinović, Miroslav; Maksimović, Vesna; Sargent, Daniel J; Stevanović, Vladimir; Bosković, Radovan I

    2007-05-01

    Many species of Prunus display an S-RNase-based gametophytic self-incompatibility (SI), controlled by a single highly polymorphic multigene complex termed the S-locus. This comprises tightly linked stylar- and pollen-expressed genes that determine the specificity of the SI response. We investigated SI of Prunus tenella, a wild species found in small, isolated populations on the Balkan peninsula, initially by pollination experiments and identifying stylar-expressed RNase alleles. Nine P. tenella S-RNase alleles (S(1)-S(9)) were cloned; their sequence analysis showed a very high ratio of non-synonymous to synonymous nucleotide substitutions (K(a)/K(s)) and revealed that S-RNase alleles of P. tenella, unlike those of Prunus dulcis, show positive selection in all regions except the conserved regions and that between C2 and RHV. Remarkably, S(8)-RNase, was found to be identical to S(1)-RNase from Prunus avium, a species that does not interbreed with P. tenella and, except for just one amino acid, to S(11) of P. dulcis. However, the corresponding introns and S-RNase-SFB intergenic regions showed considerable differences. Moreover, protein sequences of the pollen-expressed SFB alleles were not identical, harbouring 12 amino-acid replacements between those of P. tenella SFB(8) and P. avium SFB(1). Implications of this finding for hypotheses about the evolution of new S-specificities are discussed.

  6. Prevalence of Huntington's disease gene CAG trinucleotide repeat alleles in patients with bipolar disorder.

    Ramos, Eliana Marisa; Gillis, Tammy; Mysore, Jayalakshmi S; Lee, Jong-Min; Alonso, Isabel; Gusella, James F; Smoller, Jordan W; Sklar, Pamela; MacDonald, Marcy E; Perlis, Roy H

    2015-06-01

    Huntington's disease is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms that are caused by huntingtin gene (HTT) CAG trinucleotide repeat alleles of 36 or more units. A greater than expected prevalence of incompletely penetrant HTT CAG repeat alleles observed among individuals diagnosed with major depressive disorder raises the possibility that another mood disorder, bipolar disorder, could likewise be associated with Huntington's disease. We assessed the distribution of HTT CAG repeat alleles in a cohort of individuals with bipolar disorder. HTT CAG allele sizes from 2,229 Caucasian individuals diagnosed with DSM-IV bipolar disorder were compared to allele sizes in 1,828 control individuals from multiple cohorts. We found that HTT CAG repeat alleles > 35 units were observed in only one of 4,458 chromosomes from individuals with bipolar disorder, compared to three of 3,656 chromosomes from control subjects. These findings do not support an association between bipolar disorder and Huntington's disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Mutation intolerant genes and targets of FMRP are enriched for nonsynonymous alleles in schizophrenia.

    Leonenko, Ganna; Richards, Alexander L; Walters, James T; Pocklington, Andrew; Chambert, Kimberly; Al Eissa, Mariam M; Sharp, Sally I; O'Brien, Niamh L; Curtis, David; Bass, Nicholas J; McQuillin, Andrew; Hultman, Christina; Moran, Jennifer L; McCarroll, Steven A; Sklar, Pamela; Neale, Benjamin M; Holmans, Peter A; Owen, Michael J; Sullivan, Patrick F; O'Donovan, Michael C

    2017-10-01

    Risk of schizophrenia is conferred by alleles occurring across the full spectrum of frequencies from common SNPs of weak effect through to ultra rare alleles, some of which may be moderately to highly penetrant. Previous studies have suggested that some of the risk of schizophrenia is attributable to uncommon alleles represented on Illumina exome arrays. Here, we present the largest study of exomic variation in schizophrenia to date, using samples from the United Kingdom and Sweden (10,011 schizophrenia cases and 13,791 controls). Single variants, genes, and gene sets were analyzed for association with schizophrenia. No single variant or gene reached genome-wide significance. Among candidate gene sets, we found significant enrichment for rare alleles (minor allele frequency [MAF] schizophrenia by excluding a role for uncommon exomic variants (0.01 ≤ MAF ≥ 0.001) that confer a relatively large effect (odds ratio [OR] > 4). We also show risk alleles within this frequency range exist, but confer smaller effects and should be identified by larger studies. © 2017 Wiley Periodicals, Inc.

  8. Allelic variation of bile salt hydrolase genes in Lactobacillus salivarius does not determine bile resistance levels.

    Fang, Fang

    2009-09-01

    Commensal lactobacilli frequently produce bile salt hydrolase (Bsh) enzymes whose roles in intestinal survival are unclear. Twenty-six Lactobacillus salivarius strains from different sources all harbored a bsh1 allele on their respective megaplasmids. This allele was related to the plasmid-borne bsh1 gene of the probiotic strain UCC118. A second locus (bsh2) was found in the chromosomes of two strains that had higher bile resistance levels. Four Bsh1-encoding allele groups were identified, defined by truncations or deletions involving a conserved residue. In vitro analyses showed that this allelic variation was correlated with widely varying bile deconjugation phenotypes. Despite very low activity of the UCC118 Bsh1 enzyme, a mutant lacking this protein had significantly lower bile resistance, both in vitro and during intestinal transit in mice. However, the overall bile resistance phenotype of this and other strains was independent of the bsh1 allele type. Analysis of the L. salivarius transcriptome upon exposure to bile and cholate identified a multiplicity of stress response proteins and putative efflux proteins that appear to broadly compensate for, or mask, the effects of allelic variation of bsh genes. Bsh enzymes with different bile-degrading kinetics, though apparently not the primary determinants of bile resistance in L. salivarius, may have additional biological importance because of varying effects upon bile as a signaling molecule in the host.

  9. Human leukocyte antigen class II susceptibility conferring alleles among non-insulin dependent diabetes mellitus patients

    Tipu, H.N.; Ahmed, T.A.; Bashir, M.M.

    2010-01-01

    To determine the frequency of Human Leukocyte Antigen (HLA) class II susceptibility conferring alleles among type 2 Diabetes mellitus patients, in comparison with healthy controls. Cross-sectional comparative study. Patients with non-insulin dependent Diabetes mellitus meeting World Health Organization criteria were studied. These were compared with age and gender matched healthy control subjects. For each subject (patients as well as controls), DNA was extracted from ethylene diamine tetra-acetate sample and HLA class II DRB1 typing was carried out at allele group level (DRB1*01-DRB1*16) by sequence specific primers. Human leukocyte antigen DRB1 type was determined by agarose gel electrophoresis and results were recorded. Frequencies were determined as number of an allele divided by total number of alleles per group; p-value was computed using Pearson's chi-square test. Among the 100 patients, there were 63 males and 37 females with 68 controls. A total of 13 different HLA DRB1 alleles were detected, with DRB1*15 being the commonest in both the groups. The allele DRB1*13 had statistically significant higher frequency in patient group as compared to controls (p 0.005). HLA DRB1*13 was found with a significantly increased frequency in non-insulin dependent Diabetes mellitus. (author)

  10. Null alleles and sequence variations at primer binding sites of STR loci within multiplex typing systems.

    Yao, Yining; Yang, Qinrui; Shao, Chengchen; Liu, Baonian; Zhou, Yuxiang; Xu, Hongmei; Zhou, Yueqin; Tang, Qiqun; Xie, Jianhui

    2018-01-01

    Rare variants are widely observed in human genome and sequence variations at primer binding sites might impair the process of PCR amplification resulting in dropouts of alleles, named as null alleles. In this study, 5 cases from routine paternity testing using PowerPlex ® 21 System for STR genotyping were considered to harbor null alleles at TH01, FGA, D5S818, D8S1179, and D16S539, respectively. The dropout of alleles was confirmed by using alternative commercial kits AGCU Expressmarker 22 PCR amplification kit and AmpFℓSTR ® . Identifiler ® Plus Kit, and sequencing results revealed a single base variation at the primer binding site of each STR locus. Results from the collection of previous reports show that null alleles at D5S818 were frequently observed in population detected by two PowerPlex ® typing systems and null alleles at D19S433 were mostly observed in Japanese population detected by two AmpFℓSTR™ typing systems. Furthermore, the most popular mutation type appeared the transition from C to T with G to A, which might have a potential relationship with DNA methylation. Altogether, these results can provide helpful information in forensic practice to the elimination of genotyping discrepancy and the development of primer sets. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Interlaboratory comparison of fig (Ficus carica L. microsatellite genotyping data and determination of reference alleles

    Matjaž HLADNIK

    2018-04-01

    Full Text Available Microsatellites have been identified as the marker of choice in plant genotyping projects. However, due to length discrepancies obtained between different laboratories for the same allele, interlaboratory comparison of fingerprinting results is often a difficult task. The objectives of this study were to compare genotyping results of two laboratories, to evaluate genetic parameters of microsatellite markers and to determine reference allele sizes for fig cultivars from the Istrian peninsula.Genotyping results of ninety fig (Ficus carica L. accessions were comparable between the laboratories despite differences observed when comparing electropherograms of different capillary electrophoresis systems. Differences in lengths of the same alleles were detected due to different PCR methods and laboratory equipment, but the distances between alleles of the same locus were preserved. However, locus FSYC01 exhibited one allele dropout which led to misidentification of 28 heterozygotes as homozygote individuals suggesting this locus as unreliable. Allele dropout was assigned to the tail PCR technology or to a touchdown PCR protocol.Genotypes of twenty-four reference cultivars from the Istrian peninsula were confirmed by both laboratories. These results will contribute to the usage of markers with greater reliability, discrimination power and consequently, to more reliable standardization with other fig genotyping projects.

  12. MET overexpression, gene amplification and relevant clinicopathological features in gastric adenocarcinoma.

    Zhang, Jing; Guo, Lei; Liu, Xiuyun; Li, Wenbin; Ying, Jianming

    2017-02-07

    This study was conducted to investigate the expression of MET in Chinese gastric adenocarcinoma cohort, the correlation between MET overexpression and clinical pathological features, HER2 expression and MET gene amplification. A total of 816 gastric adenocarcinoma patients were included and MET and HER2 immunohistochemical (IHC) staining were performed. IHC and dual-color silver in situ hybridization analysis were performed in the tissue microarrays, constructed from the 240 patients who were randomly selected. MET overexpression (IHC 3+) was observed in 6.0% (49/816) of the cohort. MET overexpression rate was higher in patients with poor prognostic factors, such as clinical stages III/IV (p =0.012) and pathologic stages T3/T4 (p =0.027). The HER2 overexpression (IHC 3+) rate was 8.8% (72/816) and MET overexpression rate was higher in HER2 positive patients (9.7%, 7/72). A high concordance rate (94.6%) between MET overexpression and gene amplification was demonstrated. Therefore, MET overexpression could serve as a prognostic biomarker and a potential therapeutic target for gastric cancer.

  13. Design and synthesis of 3,3'-biscoumarin-based c-Met inhibitors.

    Xu, Jimin; Ai, Jing; Liu, Sheng; Peng, Xia; Yu, Linqian; Geng, Meiyu; Nan, Fajun

    2014-06-14

    A library of biscoumarin-based c-Met inhibitors was synthesized, based on optimization of 3,3'-biscoumarin hit 3, which was identified as a non-ATP competitive inhibitor of c-Met from a diverse library of coumarin derivatives. Among these compounds, 38 and 40 not only showed potent enzyme activities with IC50 values of 107 nM and 30 nM, respectively, but also inhibited c-Met phosphorylation in BaF3/TPR-Met and EBC-1 cells.

  14. Characterization of HGF/Met Signaling in Cell Lines Derived From Urothelial Carcinoma of the Bladder

    Lee, Young H. [Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Apolo, Andrea B. [Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Agarwal, Piyush K.; Bottaro, Donald P., E-mail: dbottaro@helix.nih.gov [Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2014-11-25

    There is mounting evidence of oncogenic hepatocyte growth factor (HGF)/Met signaling in urothelial carcinoma (UC) of the bladder. The effects of three kinase inhibitors, cabozantinib, crizotinib and EMD1214063, on HGF-driven signaling and cell growth, invasion and tumorigenicity were analyzed in cultured UC cell lines. SW780 xenograft growth in SCID and human HGF knock-in SCID (hHGF/SCID) mice treated with cabozantinib or vehicle, as well as tumor levels of Met and pMet, were also determined. Met content was robust in most UC-derived cell lines. Basal pMet content and effector activation state in quiescent cells were low, but significantly enhanced by added HGF, as were cell invasion, proliferation and anchorage independent growth. These HGF-driven effects were reversed by Met inhibitor treatment. Tumor xenograft growth was significantly higher in hHGF/SCID mice vs. SCID mice and significantly inhibited by cabozantinib, as was tumor phospho-Met content. These studies indicate the prevalence and functionality of the HGF/Met signaling pathway in UC cells, suggest that paracrine HGF may contribute to UC tumor growth and progression, and that support further preclinical investigation of Met inhibitors for the treatment of UC is warranted.

  15. Single-molecule photobleaching reveals increased MET receptor dimerization upon ligand binding in intact cells

    Dietz, Marina S; Haße, Daniel; Ferraris, Davide M; Göhler, Antonia; Niemann, Hartmut H; Heilemann, Mike

    2013-01-01

    The human receptor tyrosine kinase MET and its ligand hepatocyte growth factor/scatter factor are essential during embryonic development and play an important role during cancer metastasis and tissue regeneration. In addition, it was found that MET is also relevant for infectious diseases and is the target of different bacteria, amongst them Listeria monocytogenes that induces bacterial uptake through the surface protein internalin B. Binding of ligand to the MET receptor is proposed to lead to receptor dimerization. However, it is also discussed whether preformed MET dimers exist on the cell membrane. To address these issues we used single-molecule fluorescence microscopy techniques. Our photobleaching experiments show that MET exists in dimers on the membrane of cells in the absence of ligand and that the proportion of MET dimers increases significantly upon ligand binding. Our results indicate that partially preformed MET dimers may play a role in ligand binding or MET signaling. The addition of the bacterial ligand internalin B leads to an increase of MET dimers which is in agreement with the model of ligand-induced dimerization of receptor tyrosine kinases.

  16. Recent advances in the discovery of small molecule c-Met Kinase inhibitors.

    Parikh, Palak K; Ghate, Manjunath D

    2018-01-01

    c-Met is a prototype member of a subfamily of heterodimeric receptor tyrosine kinases (RTKs) and is the receptor for hepatocyte growth factor (HGF). Binding of HGF to its receptor c-Met, initiates a wide range of cellular signalling, including those involved in proliferation, motility, migration and invasion. Importantly, dysregulated HGF/c-Met signalling is a driving factor for numerous malignancies and promotes tumour growth, invasion, dissemination and/or angiogenesis. Dysregulated HGF/c-Met signalling has also been associated with poor clinical outcomes and resistance acquisition to some approved targeted therapies. Thus, c-Met kinase has emerged as a promising target for cancer drug development. Different therapeutic approaches targeting the HGF/c-Met signalling pathway are under development for targeted cancer therapy, among which small molecule inhibitors of c-Met kinase constitute the largest effort within the pharmaceutical industry. The review is an effort to summarize recent advancements in medicinal chemistry development of small molecule c-Met kinase inhibitors as potential anti-cancer agents which would certainly help future researchers to bring further developments in the discovery of small molecule c-Met kinase inhibitors. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  17. Preproghrelin Leu72Met polymorphism in Chinese subjects with coronary artery disease and controls.

    Tang, Na-Ping; Wang, Lian-Sheng; Yang, Li; Gu, Hai-Juan; Zhu, Huai-Jun; Zhou, Bo; Sun, Qing-Min; Cong, Ri-Hong; Wang, Bin

    2008-01-01

    Ghrelin, a novel endogenous ligand for the growth hormone secretagogue receptor, is considered to exert a protective effect against atherosclerosis. The Leu72Met (+408C>A) polymorphic variant of the preproghrelin, the gene for the ghrelin precursor, has been linked to obesity, diabetes and metabolic syndrome. However, it is unclear whether this polymorphism is associated with coronary artery disease (CAD). We conducted a case-control study with 317 CAD patients and 323 controls to investigate the potential association of the Leu72Met polymorphism with the occurrence of CAD and CAD-related phenotypes in Chinese population. No significant difference in the Leu72Met genotype frequency was observed between CAD patients and controls (P=NS). The Leu72Met polymorphism was not associated with hypertension, diabetes, dyslipidemia, the number of diseased vessels, plasma total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol or fasting glucose levels in CAD patients. However, among CAD patients, those with variant genotypes (Leu72Met and Met72Met) had lower BMI (24.4+/-0.3 kg/m(2)) than Leu72Leu carriers (25.4+/-0.2 kg/m(2), adjusted P=0.033). Our data indicate that the preproghrelin Leu72Met polymorphism is not associated with CAD in Chinese population. However, the Leu72Met variant is associated with BMI among CAD patients.

  18. Preproghrelin Leu72Met polymorphism is not associated with type 2 diabetes mellitus.

    Kim, Sun-Young; Jo, Dae-Sun; Hwang, Pyoung Han; Park, Ji Hyun; Park, Sung Kwang; Yi, Ho Keun; Lee, Dae-Yeol

    2006-03-01

    Ghrelin is a novel gut-brain peptide, which exerts somatotropic, orexigenic, and adipogenic effects. Genetic variants of ghrelin have been associated with both obesity and insulin metabolism. In this study, we determined a role of preproghrelin Leu72Met polymorphism on type 2 diabetes mellitus and its relationship to variables studied. Genotypes were assessed by polymerase chain reaction. Frequencies of the Leu72Met polymorphism were found to be 35.4% in the type 2 diabetic patients and 32.5% in the normal controls. The Leu72Met polymorphism was not associated with hypertension, macroangiopathy, retinopathy, serum cholesterol, triglyceride, blood urea nitrogen, HbA(1c), lipoprotein (a), fasting insulin, or 24-hour urinary protein levels in the type 2 diabetic group. However, the Leu72Met polymorphism was clearly associated with serum creatinine levels in the diabetic group, as the Met72 carriers exhibited lower serum creatinine levels than the Met72 noncarriers. Our data indicate that the preproghrelin Leu72Met polymorphism is not associated with type 2 diabetes mellitus. However, the Leu72Met polymorphism is associated with serum creatinine levels. These data suggest that Met72 carrier status may be a predictable marker for diabetic nephropathy or renal impairment in type 2 diabetes mellitus.

  19. Ran GTPase promotes cancer progression via Met receptor-mediated downstream signaling

    Yuen, Hiu-Fung; Chan, Ka-Kui; Platt-Higgins, Angela; Dakir, El-Habib; Matchett, Kyle B.; Haggag, Yusuf Ahmed; Jithesh, Puthen V.; Habib, Tanwir; Faheem, Ahmed; Dean, Fennell A.; Morgan, Richard; Rudland, Philip S.; El-Tanani, Mohamed

    2016-01-01

    It has been shown previously that cancer cells with an activated oncogenic pathway, including Met activation, require Ran for growth and survival. Here, we show that knockdown of Ran leads to a reduction of Met receptor expression in several breast and lung cancer cell lines. This, in turn suppressed HGF expression and the Met-mediated activation of the Akt pathway, as well as cell adhesion, migration, and invasion. In a cell line model where Met amplification has previously been shown to contribute to gefitinib resistance, Ran knockdown sensitized cells to gefitinib-mediated inhibition of Akt and ERK1/2 phosphorylation and consequently reduced cell proliferation. We further demonstrate that Met reduction-mediated by knockdown of Ran, occurs at the post-transcriptional level, probably via a matrix metalloproteinase. Moreover, the level of immunoreactive Ran and Met are positively associated in human breast cancer specimens, suggesting that a high level of Ran may be a pre-requisite for Met overexpression. Interestingly, a high level of immunoreactive Ran dictates the prognostic significance of Met, indicating that the co-overexpression of Met and Ran may be associated with cancer progression and could be used in combination as a prognostic indicator. PMID:27716616

  20. Role of Methoprene-tolerant (Met in adult morphogenesis and in adult ecdysis of Blattella germanica.

    Jesus Lozano

    Full Text Available Juvenile Hormone (JH represses metamorphosis of young instars in insects. One of the main players in hormonal signalling is Methoprene-tolerant (Met, which plays the role of JH receptor. Using the Polyneopteran insect Blattella germanica as the model and RNAi for transcript depletion, we have confirmed that Met transduces the antimetamorphic signal of JH in young nymphs and plays a role in the last nymphal instar moult in this species. Previously, the function of Met as the JH receptor had been demonstrated in the Eumetabola clade, with experiments in Holometabola (in the beetle Tribolium castaneum and in their sister group Paraneoptera (in the bug Pyrrhocoris apterus. Our result shows that the function of Met as JH receptor is also conserved in the more basal Polyneoptera. The function of Met as JH transducer might thus predate the evolutionary innovation of metamorphosis. Moreover, expression of Met was also found in last nymphal instar of B. germanica, when JH is absent. Depletion of Met in this stage provoked deficiencies in wing growth and ecdysis problems in the imaginal moult. Down-regulation of the ecdysone-inducible gene E75A and Insulin-Like-Peptide 1 in these Met-depleted specimens suggest that Met is involved in the ecdysone and insulin signalling pathways in last nymphal instar, when JH is virtually absent.