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Sample records for underlying genetic defects

  1. Homozygosity mapping and targeted sanger sequencing reveal genetic defects underlying inherited retinal disease in families from pakistan.

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    Maleeha Maria

    Full Text Available Homozygosity mapping has facilitated the identification of the genetic causes underlying inherited diseases, particularly in consanguineous families with multiple affected individuals. This knowledge has also resulted in a mutation dataset that can be used in a cost and time effective manner to screen frequent population-specific genetic variations associated with diseases such as inherited retinal disease (IRD.We genetically screened 13 families from a cohort of 81 Pakistani IRD families diagnosed with Leber congenital amaurosis (LCA, retinitis pigmentosa (RP, congenital stationary night blindness (CSNB, or cone dystrophy (CD. We employed genome-wide single nucleotide polymorphism (SNP array analysis to identify homozygous regions shared by affected individuals and performed Sanger sequencing of IRD-associated genes located in the sizeable homozygous regions. In addition, based on population specific mutation data we performed targeted Sanger sequencing (TSS of frequent variants in AIPL1, CEP290, CRB1, GUCY2D, LCA5, RPGRIP1 and TULP1, in probands from 28 LCA families.Homozygosity mapping and Sanger sequencing of IRD-associated genes revealed the underlying mutations in 10 families. TSS revealed causative variants in three families. In these 13 families four novel mutations were identified in CNGA1, CNGB1, GUCY2D, and RPGRIP1.Homozygosity mapping and TSS revealed the underlying genetic cause in 13 IRD families, which is useful for genetic counseling as well as therapeutic interventions that are likely to become available in the near future.

  2. Homozygosity mapping and targeted sanger sequencing reveal genetic defects underlying inherited retinal disease in families from pakistan

    NARCIS (Netherlands)

    Maria, M.; Ajmal, M.; Azam, M.; Waheed, N.K.; Siddiqui, S.N.; Mustafa, B.; Ayub, H.; Ali, L.; Ahmad, S.; Micheal, S.; Hussain, A.; Shah, S.T.; Ali, S.H.; Ahmed, W.; Khan, Y.M.; Hollander, A.I. den; Haer-Wigman, L.; Collin, R.W.J.; Khan, M.I.; Qamar, R.; Cremers, F.P.M.

    2015-01-01

    BACKGROUND: Homozygosity mapping has facilitated the identification of the genetic causes underlying inherited diseases, particularly in consanguineous families with multiple affected individuals. This knowledge has also resulted in a mutation dataset that can be used in a cost and time effective

  3. Genetic Counseling for Congenital Heart Defects

    Science.gov (United States)

    ... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Genetic Counseling for Congenital Heart Defects Updated:Jan 19,2018 ... person with congenital heart disease considers having children. Genetic counseling can help answer these questions and address your ...

  4. Identification of genetic defects underlying FVII deficiency in 10 patients belonging to eight unrelated families of the North provinces from Tunisia

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    Elmahmoudi Hejer

    2012-08-01

    Full Text Available Abstract Inherited factor VII (FVII deficiency is a rare disorder characterized by a bleeding phenotype varying from mild to severe. To date, more than 200 mutations have been described along the F7 gene encoding for FVII. The aim of this study was the identification of genetic defects underlying FVII deficiency in 10 patients belonging to eight unrelated families of the North provinces from Tunisia. Mutation detection was performed by sequencing the whole F7 gene coding region, exon-intron boundaries and about 400 bp of the promoter region. We identified 5 mutations in five unrelated families; the novel p.F328Y mutation and the reported mutations: p.R304Q, p.M298I, IVS1aG > A and p.G-39G. For the remaining 5 patients we didn’t identified any mutations using PCR/Sequencing protocol. In conclusion, this study represents the first comprehensive molecular series of FVII deficiency affected patients in Tunisia from the North. We will try in the future to continue the molecular study for Tunisian patients from Center and South provinces in order to have a complete idea about the FVII deficiency mutational profile in our country. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1288044089753085

  5. Genetic epidemiology of neural tube defects.

    Science.gov (United States)

    Lupo, Philip J; Agopian, A J; Castillo, Heidi; Castillo, Jonathan; Clayton, Gerald H; Dosa, Nienke P; Hopson, Betsy; Joseph, David B; Rocque, Brandon G; Walker, William O; Wiener, John S; Mitchell, Laura E

    2017-12-11

    It has been estimated that 60-70% of neural tube defects (NTDs) have a genetic component, but few causative genes have been identified. The lack of information on genes associated with non-syndromic NTDs in humans is especially notable as the "genomic revolution" has led to new tools (e.g., genome-wide genotyping arrays, next-generation sequencing) that are helping to elucidate the full spectrum of genetic variation (from common to rare) contributing to complex traits, including structural birth defects. However, the application of modern genomic approaches to the study of NTDs has lagged behind that of some other common structural birth defects. This may be due to the difficulty of assembling large study cohorts for anencephaly or spina bifida. The purpose of this review is to outline the evolution of genetic studies of NTDs, from studies of familial aggregation to candidate gene and genome-wide association studies, through whole-exome and whole-genome sequencing. Strategies for addressing gaps in NTD genetic research are also explored.

  6. Basement Membrane Defects in Genetic Kidney Diseases

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    Christine Chew

    2018-01-01

    Full Text Available The glomerular basement membrane (GBM is a specialized structure with a significant role in maintaining the glomerular filtration barrier. This GBM is formed from the fusion of two basement membranes during development and its function in the filtration barrier is achieved by key extracellular matrix components including type IV collagen, laminins, nidogens, and heparan sulfate proteoglycans. The characteristics of specific matrix isoforms such as laminin-521 (α5β2γ1 and the α3α4α5 chain of type IV collagen are essential for the formation of a mature GBM and the restricted tissue distribution of these isoforms makes the GBM a unique structure. Detailed investigation of the GBM has been driven by the identification of inherited abnormalities in matrix proteins and the need to understand pathogenic mechanisms causing severe glomerular disease. A well-described hereditary GBM disease is Alport syndrome, associated with a progressive glomerular disease, hearing loss, and lens defects due to mutations in the genes COL4A3, COL4A4, or COL4A5. Other proteins associated with inherited diseases of the GBM include laminin β2 in Pierson syndrome and LMX1B in nail patella syndrome. The knowledge of these genetic mutations associated with GBM defects has enhanced our understanding of cell–matrix signaling pathways affected in glomerular disease. This review will address current knowledge of GBM-associated abnormalities and related signaling pathways, as well as discussing the advances toward disease-targeted therapies for patients with glomerular disease.

  7. Genetic, chromosomal, and syndromic causes of neural tube defects

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    Seidahmed, Mohammed Z.; Abdelbasit, Omer B.; Shaheed, Meeralebbae M.; Alhussein, Khalid A.; Miqdad, Abeer M.; Samadi, Abdulmohsen S.; Khalil, Mohammed I.; Al-Mardawi, Elham; Salih, Mustafa A.

    2014-01-01

    Objective: To ascertain the incidence, and describe the various forms of neural tube defects (NTDs) due to genetic, chromosomal, and syndromic causes. Methods: We carried out a retrospective analysis of data retrieved from the medical records of newborn infants admitted to the Neonatal Intensive Care Unit with NTDs and their mothers spanning 14 years (1996-2009) at the Security Forces Hospital, Riyadh, Saudi Arabia. The cases were ascertained by a perinatologist, neonatologist, geneticist, radiologist, and neurologist. The literature was reviewed via a MEDLINE search. Only liveborn babies were included. Permission from the Educational Committee at the Security Forces Hospital was obtained prior to the collection of data. Results: Out of 103 infants with NTDs admitted during this period, 20 (19.4%) were found to have an underlying genetic syndromic, chromosomal and/or other anomalies. There were 5 cases of Meckel-Gruber syndrome, 2 Joubert syndrome, one Waardenburg syndrome, one Walker-Warburg syndrome, 2 chromosomal disorders, 2 caudal regression, one amniotic band disruption sequence, one associated with omphalocele, one with diaphragmatic hernia, and 4 with multiple congenital anomalies. Conclusions: There is a high rate of underlying genetic syndromic and/or chromosomal causes of NTDs in the Saudi Arabian population due to the high consanguinity rate. Identification of such association can lead to more accurate provisions of genetic counseling to the family including preimplantation genetic diagnosis or early termination of pregnancies associated with lethal conditions. PMID:25551112

  8. Genetics Home Reference: abdominal wall defect

    Science.gov (United States)

    ... wall defects managed in a tertiary center in Japan. J Obstet Gynaecol Res. 2009 Feb;35(1): ... Reviewed : August 2016 Published : March 6, 2018 The resources on this site should not be used as a ... Department of Health & Human Services National Institutes of Health National Library of ...

  9. Genetic Engineering and the Amelioration of Genetic Defect

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    Lederberg, Joshua

    1970-01-01

    Discusses the claims for a brave new world of genetic manipulation" and concludes that if we could agree upon applying genetic (or any other effective) remedies to global problems we probably would need no rescourse to them. Suggests that effective methods of preventing genetic disease are prevention of mutations and detection and…

  10. The behaviour of defective fuel under power cycling conditions

    International Nuclear Information System (INIS)

    Anand, A.K.; Anantharaman, K.; Basu, S.

    1980-01-01

    This paper describes the irradiation carried out with a defective fuel pin and the changes in the activity released to the coolant under power cycling conditions. This also describes the future experiments, which are being planned. (author)

  11. A missense mutation underlies defective SOCS4 function in a family with autoimmunity

    NARCIS (Netherlands)

    Arts, P.; Plantinga, T.S.; Berg, J.M. van den; Gilissen, C.; Veltman, J.A.; Trotsenburg, A.S. van; Veerdonk, F.L. van de; Kuijpers, T.W.; Hoischen, A.; Netea, M.G.

    2015-01-01

    OBJECTIVE: The aim of this study was to determine the genetic and immunological defects underlying familial manifestations of an autoimmune disorder. METHODS: Whole-exome sequencing was performed on the index patient with various manifestations of autoimmunity, including hypothyroidism, vitiligo and

  12. Defective renal calcium reabsorption in genetic hypercalciuric rats.

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    Tsuruoka, S; Bushinsky, D A; Schwartz, G J

    1997-05-01

    Idiopathic hypercalciuria is a frequent cause of calcium (Ca) containing kidney stones. We have previously shown that there is increased intestinal Ca absorption in selectively inbred genetic hypercalciuric stone forming (GHS) rats; however, excess Ca excretion persists when the rats are fed a low Ca diet indicating a defect in renal Ca reabsorption and/or increased bone resorption. To determine if GHS rats have a defect in renal Ca reabsorption we performed 14C-inulin clearance studies on parathyroidectomized female GHS and control (Ctl) rats. After three baseline collections, chlorothiazide (CTZ) or furosemide (FUR) was infused and three more collections were obtained. Both GFR and filtered load of Ca did not differ among the groups; however, fractional and absolute excretion (UcaV) of Ca was three times higher in GHS rats. The increased Ca excretion was not diminished by a low Ca diet. Urine flow rate nearly tripled in all rats after either FUR or CTZ. After CTZ, UcaV was decreased to a greater extent in GHS compared to Ctl rats. After FUR, UcaV was increased to a greater extent in Ctl rats compared to GHS rats. These data indicate that GHS rats have a defect in renal Ca reabsorption, in addition to increased intestinal Ca absorption. The effect of CTZ was greater, and that of FUR was smaller, in GHS compared with Ctl rats, suggesting that the defect in renal Ca handling might be at the level of the thick ascending limb.

  13. Genetic analysis of metabolic defects in the spontaneously hypertensive rat

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Zídek, Václav; Musilová, Alena; Šimáková, Miroslava; Kostka, Vlastimil; Mlejnek, Petr; Křen, Vladimír; Křenová, D.; Bílá, V.; Míková, B.; Jáchymová, M.; Horký, K.; Kazdová, L.; St.Lezin, E.; Kurtz, W. T.

    2002-01-01

    Roč. 13, č. 5 (2002), s. 253-258 ISSN 0938-8990 R&D Projects: GA MŠk LN00A079; GA ČR GV204/98/K015; GA ČR GA305/00/1646; GA MŠk NB5299 Grant - others:NIH(US) RO1 HL56028; NIH(US) PO1 HL35018; HHMI(US) 55000331 Institutional research plan: CEZ:AV0Z5011922 Keywords : metabolic defects * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.233, year: 2002

  14. Under-reporting of major birth defects in Northwest Russia: a registry-based study

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    Kovalenko, Anton A.; Brenn, Tormod; Odland, Jon Øyvind; Nieboer, Evert; Krettek, Alexandra; Anda, Erik Eik

    2017-01-01

    ABSTRACT The objective was to assess the prevalence of selected major birth defects, based on data from two medical registries in Murmansk County, and compare the observed rates with those available for Norway and Arkhangelsk County, Northwest Russia. It included all newborns (≥22 completed weeks of gestation) registered in the Murmansk County Birth Registry (MCBR) and born between 1 January 2006 and 31 December 2009 (n=35,417). The infants were followed-up post-partum for 2 years through direct linkage to the Murmansk Regional Congenital Defects Registry (MRCDR). Birth defects identified and confirmed in both registries constituted the “cases” and corresponded to one or more of the 21 birth defect types reportable to health authorities in Moscow. The overall prevalence of major birth defects recorded in the MRCDR was 50/10,000 before linkage and 77/10,000 after linkage with the MCBR. Routine under-reporting to the MRCDR of 40% cases was evident. This study demonstrates that birth registry data improved case ascertainment and official prevalence assessments and reduced the potential of under-reporting by physicians. The direct linkage of the two registries revealed that hypospadias cases were the most prevalent among the major birth defects in Murmansk County. A bbreviations: ICD-10, International Classification of Diseases, 10th revision; MCBR, Murmansk County Birth Registry; MRCDR, Murmansk Regional Congenital Defects Registry; MGC, Murmansk Genetics Center PMID:28853333

  15. A case of extensive Aplasia Cutis Congenita with underlying skull defect and central nervous system malformation: discussion of large skin defects, complications, treatment and outcome.

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    Burkhead, A; Poindexter, G; Morrell, D S

    2009-08-01

    Aplasia Cutis Congenita (ACC) is a rare condition characterized by the absence of a portion of skin at birth. Skin defects are usually small (0.5 to 3 cm) and located on the scalp. Although there can be other physical or genetic abnormalities, ACC is most often a benign isolated condition. Rarely is an underlying bony defect present, and this association increases the rate of complications. We report a case of a newborn male with ACC of the entire crown and vertex scalp, non-ossified parietal skull and dysplastic corpus callosum. The patient's skull and skin defects were treated non-surgically, and he recovered well.

  16. An Automated Defect Prediction Framework using Genetic Algorithms: A Validation of Empirical Studies

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    Juan Murillo-Morera

    2016-05-01

    Full Text Available Today, it is common for software projects to collect measurement data through development processes. With these data, defect prediction software can try to estimate the defect proneness of a software module, with the objective of assisting and guiding software practitioners. With timely and accurate defect predictions, practitioners can focus their limited testing resources on higher risk areas. This paper reports the results of three empirical studies that uses an automated genetic defect prediction framework. This framework generates and compares different learning schemes (preprocessing + attribute selection + learning algorithms and selects the best one using a genetic algorithm, with the objective to estimate the defect proneness of a software module. The first empirical study is a performance comparison of our framework with the most important framework of the literature. The second empirical study is a performance and runtime comparison between our framework and an exhaustive framework. The third empirical study is a sensitivity analysis. The last empirical study, is our main contribution in this paper. Performance of the software development defect prediction models (using AUC, Area Under the Curve was validated using NASA-MDP and PROMISE data sets. Seventeen data sets from NASA-MDP (13 and PROMISE (4 projects were analyzed running a NxM-fold cross-validation. A genetic algorithm was used to select the components of the learning schemes automatically, and to assess and report the results. Our results reported similar performance between frameworks. Our framework reported better runtime than exhaustive framework. Finally, we reported the best configuration according to sensitivity analysis.

  17. Displacement defect formation in complex oxide crystals under irradiation

    NARCIS (Netherlands)

    Ubizskii, SB; Matkovskii, AO; Mironova-Ulmane, N; Skvortsova, [No Value; Suchocki, A; Zhydachevskii, YA; Potera, P

    The work is devoted to an analysis of formation processes of the radiation displacement defects (RDDs) and colour centres (CCs) in complex oxide crystals under irradiation. The calculation results on: the displacement process simulation as well as an analysis of the RDD and CC accumulation kinetics

  18. Genetic defects of hydrogen peroxide generation in the thyroid gland.

    Science.gov (United States)

    Weber, G; Rabbiosi, S; Zamproni, I; Fugazzola, L

    2013-04-01

    Hydrogen peroxide (H2O2) is a key element in thyroid hormone biosynthesis. It is the substrate used by thyroid peroxidase for oxidation and incorporation of iodine into thyroglobulin, a process known as organification. The main enzymes composing the H2O2-generating system are the dual oxidase 2 (DUOX2) and the recently described DUOX maturation factor 2 (DUOXA2). Defects in these reactions lead to reduced thyroid hormone synthesis and hypothyroidism, with consequent increased TSH secretion and goiter. Since the first report in 2002 of DUOX2 mutations causing congenital hypothryoidism (CH), to date 25 different mutations have been described. Affected patients show a positive perchlorate discharge test and high phenotypic variability, ranging from transient to permanent forms of CH. Up to now, only two cases of CH due to DUOXA2 defects have been published. They also suggest the existence of a great genotype-phenotype variability. The phenotypic expression is probably influenced by genetic background and environmental factors. DUOX and DUOXA constitute a redundant system in which DUOX1/DUOXA1 can at least partially replace the function of DUOX2/DUOXA2. Furthermore, increased nutritional iodide could ensure a better use of H2O2 provided by DUOX1.

  19. Effect of Concomitant Birth Defects and Genetic Anomalies on Infant Mortality in Tetralogy of Fallot.

    Science.gov (United States)

    Jernigan, Eric G; Strassle, Paula D; Stebbins, Rebecca C; Meyer, Robert E; Nelson, Jennifer S

    2017-08-15

    A substantial proportion of infants born with tetralogy of Fallot (TOF) die in infancy. A better understanding of the heterogeneity associated with TOF, including extracardiac malformations and chromosomal anomalies is vital to stratifying risk and optimizing outcomes during infancy. Using the North Carolina Birth Defects Monitoring Program, infants diagnosed with TOF and born between 2003 and 2012 were included. Kaplan-Meier survival curves were used to estimate cumulative 1-year mortality, stratified by the presence of concomitant birth defects (BDs) and chromosomal anomalies. Multivariable logistic regression was used to estimate the direct effect of each concomitant BD, after adjusting for all others. A total of 496 infants with TOF were included, and 15% (n = 76) died. The number of concomitant BD systems was significantly associated with the risk of death at 1-year, p < 0.0001. Specifically, the risk of mortality was 8% among infants with TOF with or without additional cardiac defects, 16% among infants with TOF and 1 extracardiac BD system, 19% among infants with 2 extracardiac BD systems, and 39% among infants with ≥ 3 extracardiac BD systems. After adjustment, concomitant eye and gastrointestinal defects were significantly associated increased with 1-year mortality, odds ratio 2.83 (95% confidence interval, 1.08-7.32) and odds ratio 4.43 (95% confidence interval, 1.57, 12.45), respectively. Infants with trisomy 13 or trisomy 18 were also significantly more likely to die, p < 0.0001. Both concomitant BDs and genetic anomalies increase the risk of mortality among infants with TOF. Future studies are needed to identify the underlying genetic and socioeconomic risk factors for high-risk TOF infants. Birth Defects Research 109:1154-1165, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  20. DNA mismatch repair enzymes: genetic defects and autoimmunity.

    Science.gov (United States)

    Muro, Yoshinao; Sugiura, Kazumitsu; Mimori, Tsuneyo; Akiyama, Masashi

    2015-03-10

    DNA mismatch repair (MMR) is one of the several DNA repair pathways conserved from bacteria to humans. The primary function of MMR is to eliminate the mismatch of base-base insertions and deletions that appear as a consequence of DNA polymerase errors at DNA synthesis. The genes encoding the DNA MMR enzymes (MMREs) are highly conserved throughout evolution. In humans, there are two sets of MMREs, corresponding to homologues of the bacterial MutLS systems. The human MutS enzymes consist of MSH2, MSH3 and MSH6, and the human MutL enzymes include MLH1, MLH3, PMS1 and PMS2. Since the beginning of this century, a few reports on autoantibodies to some MMREs have been reported in autoimmune inflammatory myopathy, cancer and hematological disorders. This review charts the functional structures of MMREs, their genetic defects and associated disorders, and autoimmunity to MMREs, including our recent data that was the first to analyze autoantibodies against all seven kinds of MMREs in systemic autoimmune diseases, including idiopathic inflammatory myopathies. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. The effects of defects on copper melting under hydrostatic and shock loading

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Shengnian [Los Alamos National Laboratory; An, Qi [Los Alamos National Laboratory; Germann, Timothy C [Los Alamos National Laboratory; Han, Li - Bo [USTC

    2009-07-24

    With molecular dynamics (MD) simulations, we investigate the effects of defects on Cu melting under hydrostatic and shock wave loading. We explore preexistent defects including vacancies, stacking faults and grain boundaries, as well as shock-induced defects. Depending on defect characteristics (energy and concentration), defects may have negligible or considerable effects on melting at MD scales However, it is expected that defects have more pronounced effects at heating rates lower than the MD rates.

  2. Unsupervised defect segmentation of patterned materials under NIR illumination

    International Nuclear Information System (INIS)

    Millan, Maria S; Escofet, Jaume; Rallo, Miquel

    2011-01-01

    An unsupervised detection method for automatic flaw segmentation in patterned materials (textile, non-woven, paper) that has no need of any defect-free references or a training stage is presented in this paper. Printed materials having a pattern of colored squares, bands, etc. superimposed to the background texture can be advantageously analyzed using NIR illumination and a camera with enough sensitivity to this region of the spectrum. The contrast reduction of the pattern in the NIR image facilitates material inspection and defect segmentation. Underdetection and misdetection errors can be reduced in comparison with the inspection performed under visible illumination. For woven fabrics, with periodic structure, the algorithm is based on the structural feature extraction of the weave repeat from the Fourier transform of the sample image. These features are used to define a set of multiresolution bandpass filters adapted to the fabric structure that operate in the Fourier domain. Inverse Fourier transformation, binarization and merging of the information obtained at different scales lead to the output image that contains flaws segmented from the fabric background. For non-woven and random textured materials, the algorithm combines the multiresolution Gabor analysis of the sample image with a statistical analysis of the wavelet coefficients corresponding to each detail. The information of all the channels is merged in a single binary output image where the defect appears segmented from the background. The method is applicable to random, non-periodic, and periodic textures. Since all the information to inspect a sample is obtained from the sample itself, the method is proof against heterogeneities between different samples of the material, in-plane positioning errors, scale variations and lack of homogeneous illumination. Experimental results are presented for a variety of materials and defects.

  3. Genetic defects in downregulation of IgE production and a new genetic classification of atopy

    Directory of Open Access Journals (Sweden)

    Naomi Kondo

    2004-01-01

    Full Text Available Atopic disorders, such as asthma, eczema and rhinitis, develop due to the interactions between genetic and environmental factors. Atopy is characterized by enhanced IgE responses to environmental antigens. The production of IgE is upregulated by Th2 cytokines, in particular interleukin (IL-4, and downregulated by Th1 cytokines, in particular interferon (IFN-γ. In the present review, we present the genetic factors responsible for IgE production and genetic defects in the downregulation (brake of IgE production, especially in terms of IL-12 and IL-18 signaling, mutations of the IL-12 receptor β2 chain gene and mutations of the IL-18 receptor α chain gene in atopy. Moreover, we newly present a genetic classification of atopy. There are four categories of genes that control the expression of allergic disorders, which include: (i antigen recognition; (ii IgE production (downregulation=brake; and upregulation; (iii the production and release of mediators; and (iv events on target organs. In the near future, this genetic classification will facilitate the development of tailor-made treatment.

  4. Graded Geometric Structures Underlying F-Theory Related Defect Theories

    Science.gov (United States)

    Oikonomou, V. K.

    2013-08-01

    In the context of F-theory, we study the related eight-dimensional super-Yang-Mills theory and reveal the underlying supersymmetric quantum mechanics algebra that the fermionic fields localized on the corresponding defect theory are related to. Particularly, the localized fermionic fields constitute a graded vector space, and in turn this graded space enriches the geometric structures that can be built on the initial eight-dimensional space. We construct the implied composite fiber bundles, which include the graded affine vector space and demonstrate that the composite sections of this fiber bundle are in one-to-one correspondence to the sections of the square root of the canonical bundle corresponding to the submanifold on which the zero modes are localized.

  5. Genetic defects in a His-Purkinje system transcription factor, IRX3, cause lethal cardiac arrhythmias.

    Science.gov (United States)

    Koizumi, Akiko; Sasano, Tetsuo; Kimura, Wataru; Miyamoto, Yoshihiro; Aiba, Takeshi; Ishikawa, Taisuke; Nogami, Akihiko; Fukamizu, Seiji; Sakurada, Harumizu; Takahashi, Yoshihide; Nakamura, Hiroaki; Ishikura, Tomoyuki; Koseki, Haruhiko; Arimura, Takuro; Kimura, Akinori; Hirao, Kenzo; Isobe, Mitsuaki; Shimizu, Wataru; Miura, Naoyuki; Furukawa, Tetsushi

    2016-05-07

    Ventricular fibrillation (VF), the main cause of sudden cardiac death (SCD), occurs most frequently in the acute phase of myocardial infarction: a certain fraction of VF, however, develops in an apparently healthy heart, referred as idiopathic VF. The contribution of perturbation in the fast conduction system in the ventricle, the His-Purkinje system, for idiopathic VF has been implicated, but the underlying mechanism remains unknown. Irx3/IRX3 encodes a transcription factor specifically expressed in the His-Purkinje system in the heart. Genetic deletion of Irx3 provides a mouse model of ventricular fast conduction disturbance without anatomical or contraction abnormalities. The aim of this study was to examine the link between perturbed His-Purkinje system and idiopathic VF in Irx3-null mice, and to search for IRX3 genetic defects in idiopathic VF patients in human. Telemetry electrocardiogram recording showed that Irx3-deleted mice developed frequent ventricular tachyarrhythmias mostly at night. Ventricular tachyarrhythmias were enhanced by exercise and sympathetic nerve activation. In human, the sequence analysis of IRX3 exons in 130 probands of idiopathic VF without SCN5A mutations revealed two novel IRX3 mutations, 1262G>C (R421P) and 1453C>A (P485T). Ventricular fibrillation associated with physical activities in both probands with IRX3 mutations. In HL-1 cells and neonatal mouse ventricular myocytes, IRX3 transfection up-regulated SCN5A and connexin-40 mRNA, which was attenuated by IRX3 mutations. IRX3 genetic defects and resultant functional perturbation in the His-Purkinje system are novel genetic risk factors of idiopathic VF, and would improve risk stratification and preventive therapy for SCD in otherwise healthy hearts. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  6. Beginning and growth of defects under coatings during fatigue tests

    International Nuclear Information System (INIS)

    Flavenot, J.F.; Dumousseau, P.; Bernard, J.L.; Slama, G.; Doule, A.

    1983-01-01

    To estimate the defects of some tubes of PWR, tensile fatigue test have been repeated on materials having real defects at the interface of a 16 MND 5 steel and of its stainless steel coating. To simulate the real working conditions, these tests have been carried out at 300 0 C. The results obtained, allow to follow the complete defect evolution. The evolution of the shape and the growth of the defect in the 16 MND 5 steel and in the stainless steel are described. Prediction models concerning the beginning and the growth of such defects agree with the results obtained [fr

  7. Birth defects and genetic disorders among Arab Americans--Michigan, 1992-2003.

    Science.gov (United States)

    Yanni, Emad A; Copeland, Glenn; Olney, Richard S

    2010-06-01

    Birth defects and genetic disorders are leading causes of infant morbidity and mortality in many countries. Population-based data on birth defects among Arab-American children have not been documented previously. Michigan has the second largest Arab-American community in the United States after California. Using data from the Michigan Birth Defects Registry (MBDR), which includes information on parents' country of birth and ancestry, birth prevalences were estimated in offspring of Michigan women of Arab ancestry for 21 major categories of birth defects and 12 congenital endocrine, metabolic, and hereditary disorders. Compared with other non-Hispanic white children in Michigan, Arab-American children had similar or lower birth prevalences of the selected types of structural birth defects, with higher rates of certain hereditary blood disorders and three categories of metabolic disorders. These estimates are important for planning preconception and antenatal health care, genetic counseling, and clinical care for Arab Americans.

  8. Overview of Epidemiology, Genetics, Birth Defects, and Chromosome Abnormalities Associated With CDH

    OpenAIRE

    Pober, Barbara R.

    2007-01-01

    Congenital diaphragmatic hernia (CDH) is a common and well-studied birth defect. The etiology of most cases remains unknown but increasing evidence points to genetic causation. The data supporting genetic etiologies which are detailed below include the association of CDH with recurring chromosome abnormalities, the existence of CDH-multiplex families, and the co-occurrence of CDH with additional congenital malformations.

  9. Contribution of Implanted, Genetically Modified Muscle Progenitor Cells Expressing BMP-2 to New Bone Formation in a Rat Osseous Defect.

    Science.gov (United States)

    De La Vega, Rodolfo E; De Padilla, Consuelo Lopez; Trujillo, Miguel; Quirk, Nicholas; Porter, Ryan M; Evans, Christopher H; Ferreira, Elisabeth

    2018-01-03

    Because muscle contains osteoprogenitor cells and has a propensity to form bone, we have explored its utility in healing large osseous defects. Healing is achieved by the insertion of muscle fragments transduced with adenovirus encoding BMP-2 (Ad.BMP-2). However, it is not known whether the genetically modified muscle contributes osteoprogenitor cells to healing defects or merely serves as a local source of BMP-2. This question is part of the larger debate on the fate of progenitor cells introduced into sites of tissue damage to promote regeneration. To address this issue, we harvested fragments of muscle from rats constitutively expressing GFP, transduced them with Ad.BMP-2, and implanted them into femoral defects in wild-type rats under various conditions. GFP + cells persisted within defects for the entire 8 weeks of the experiments. In the absence of bone formation, these cells presented as fibroblasts. When bone was formed, GFP + cells were present as osteoblasts and osteocytes and also among the lining cells of new blood vessels. The genetically modified muscle thus contributed progenitor cells as well as BMP-2 to the healing defect, a property of great significance in light of the extensive damage to soft tissue and consequent loss of endogenous progenitors in problematic fractures. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  10. Thermal buckling behavior of defective CNTs under pre-load: A molecular dynamics study.

    Science.gov (United States)

    Mehralian, Fahimeh; Tadi Beni, Yaghoub; Kiani, Yaser

    2017-05-01

    Current study is concentrated on the extraordinary properties of defective carbon nanotubes (CNTs). The role of vacancy defects in thermal buckling response of precompressed CNTs is explored via molecular dynamics (MD) simulations. Defective CNTs are initially compressed at a certain ratio of their critical buckling strain and then undergo a uniform temperature rise. Comprehensive study is implemented on both armchair and zigzag CNTs with different vacancy defects including monovacancy, symmetric bivacancy and asymmetric bivacancy. The results reveal that defects have a pronounced impact on the buckling behavior of CNTs; interestingly, defective CNTs under compressive pre-load show higher resistance to thermal buckling than pristine ones. In the following, the buckling response of defective CNTs is shown to be dependent on the vacancy defects, location of defects and chirality. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Highly selective defect-mediated photochemical CO2 conversion over fluorite ceria under ambient conditions.

    Science.gov (United States)

    Jiang, Dong; Wang, Wenzhong; Gao, Erping; Sun, Songmei; Zhang, Ling

    2014-02-25

    A highly selective defect-mediated photochemical CO2 conversion to CO over defective CeO2 nanorods under ambient conditions (CO2 400 ppm) is presented. The local strain and surface oxygen vacancies embedded in the defect-rich CeO2 are suggested to play a decisive role in mediating the photochemical CO2 conversion.

  12. Detection of Defective Sensors in Phased Array Using Compressed Sensing and Hybrid Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Shafqat Ullah Khan

    2016-01-01

    Full Text Available A compressed sensing based array diagnosis technique has been presented. This technique starts from collecting the measurements of the far-field pattern. The system linking the difference between the field measured using the healthy reference array and the field radiated by the array under test is solved using a genetic algorithm (GA, parallel coordinate descent (PCD algorithm, and then a hybridized GA with PCD algorithm. These algorithms are applied for fully and partially defective antenna arrays. The simulation results indicate that the proposed hybrid algorithm outperforms in terms of localization of element failure with a small number of measurements. In the proposed algorithm, the slow and early convergence of GA has been avoided by combining it with PCD algorithm. It has been shown that the hybrid GA-PCD algorithm provides an accurate diagnosis of fully and partially defective sensors as compared to GA or PCD alone. Different simulations have been provided to validate the performance of the designed algorithms in diversified scenarios.

  13. Safety assessment of pipes with multiple local wall thinning defects under pressure and bending moment

    International Nuclear Information System (INIS)

    Peng Jian; Zhou Changyu; Xue Jilin; Dai Qiao; He Xiaohua

    2011-01-01

    The safety assessment of pipes with local wall thinning defects is highly important in engineering. Most attention has been paid on the safety assessment of pipe with single local wall thinning defect, while the studies about multiple local wall thinning defects are not nearly enough. However, the interaction of multiple local wall thinning defects in some conditions is great, and may have a great impact on the safety assessment. In the present standard API 579/ASME FFS, the safety assessment of pipes with multiple local wall thinning defects is given, while as well as the influence of load condition, the influences of arrangement and relative depth of defects are ignored, which may influence the safety assessment considerably. In this paper, the influence of the interaction between multiple local wall thinning defects on the remaining strength of pipes at different arrangements and depths of defects under different load conditions (pressure, tension-bending moment and compression-bending moment) are studied. A quantified index is defined to describe the interaction between defects quantitatively. For different arrangements and relative depths of defects, based on a limit value 0.05 of the quantified index of the interaction between defects, a relatively systematic safety assessment of pipes with multiple local wall thinning defects under different load conditions has been proposed.

  14. Centrosome Defects, Genetic Instability and Breast Cancer Progression

    Science.gov (United States)

    2006-08-01

    et al. (1996). "Genetic divergence in the clonal evolution of breast cancer." Cancer Res 56(7): 1493-7. Gromley, A., C. Yeaman, et al. (2005...Kennedy, B. K., Barbie , D. A., Classon, M., Dyson, N. & Harlow, E. Nuclear organization of DNA replication in primary mammalian cells. Genes Dev 14

  15. Targeting a genetic defect: cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Nico Derichs

    2013-03-01

    Full Text Available Cystic fibrosis (CF is caused by genetic mutations that affect the cystic fibrosis transmembrane conductance regulator (CFTR protein. These mutations can impact the synthesis and transfer of the CFTR protein to the apical membrane of epithelial cells, as well as influencing the gating or conductance of chloride and bicarbonate ions through the channel. CFTR dysfunction results in ionic imbalance of epithelial secretions in several organ systems, such as the pancreas, gastrointestinal tract, liver and the respiratory system. Since discovery of the CFTR gene in 1989, research has focussed on targeting the underlying genetic defect to identify a disease-modifying treatment for CF. Investigated management strategies have included gene therapy and the development of small molecules that target CFTR mutations, known as CFTR modulators. CFTR modulators are typically identified by high-throughput screening assays, followed by preclinical validation using cell culture systems. Recently, one such modulator, the CFTR potentiator ivacaftor, was approved as an oral therapy for CF patients with the G551D-CFTR mutation. The clinical development of ivacaftor not only represents a breakthrough in CF care but also serves as a noteworthy example of personalised medicine.

  16. Overview of Epidemiology, Genetics, Birth Defects, and Chromosome Abnormalities Associated With CDH

    Science.gov (United States)

    Pober, Barbara R.

    2010-01-01

    Congenital diaphragmatic hernia (CDH) is a common and well-studied birth defect. The etiology of most cases remains unknown but increasing evidence points to genetic causation. The data supporting genetic etiologies which are detailed below include the association of CDH with recurring chromosome abnormalities, the existence of CDH-multiplex families, and the co-occurrence of CDH with additional congenital malformations. PMID:17436298

  17. Overview of epidemiology, genetics, birth defects, and chromosome abnormalities associated with CDH.

    Science.gov (United States)

    Pober, Barbara R

    2007-05-15

    Congenital diaphragmatic hernia (CDH) is a common and well-studied birth defect. The etiology of most cases remains unknown but increasing evidence points to genetic causation. The data supporting genetic etiologies which are detailed below include the association of CDH with recurring chromosome abnormalities, the existence of CDH-multiplex families, and the co-occurrence of CDH with additional congenital malformations. (c) 2007 Wiley-Liss, Inc.

  18. Controlling the Usability Evaluation Process under Varying Defect Visibility

    NARCIS (Netherlands)

    Schmettow, Martin; Blackwell, Alan F.

    2009-01-01

    In cases where usability is a mission critical system quality it is becoming essential to know whether an evaluation study has identified the majority of existing defects. Previous work has shown that procedures for estimating the progress of evaluation studies have to account for variation in

  19. Impact of Genetic Defects on Coronary Atherosclerosis among Turkish Cypriots.

    Science.gov (United States)

    Conkbayir, Cenk; Fahrioglu Yamaci, Rezan; Gencer, Pinar; Barin, Burc; Yucel, Genco; Yildiz, Cenk Eray; Ugurlucan, Murat; Basak, A Nazli

    2017-10-30

    The distribution of gene variants in the Turkish Cypriot population with coronary artery disease has not been investigated. In this study, we sought to research different genetic variants in the susceptibility to coronary artery disease and to identify possible associations between various clinical parameters and the genes involved in blood coagulation as well as glucose and lipid metabolism among the Turkish Cypriots and compared the results with the respective Turkish patients from Turkey. Methods: A total of 187 individuals with coronary artery disease, namely 87 Turkish Cypriot individuals from Northern Cyprus, and 100 Turkish patients from Turkey, were investigated. The presence of CAD was documented with coronary angiography. The genetic susceptibility to coronary artery disease in the cohorts was studied using the variants FV Leiden (G1691A), Factor V R2 mutation (FVR2)(H1299R), PTH (G20210A), FXIII (V34L), β-Fibrinogen (-455 G>A), PAI-1 (4G/5G), HPA1 (a/b), MTHFR [C677T] and [A1298C], ACE (I/D), Apo B (R3500Q), and Apo E, in addition to the well-known risk factors associated with coronary artery disease. Age, male sex, diabetes mellitus, hyperlipidemia, triglycerides, HDL, and triglyceride/HDL ratio were significantly associated with (P cholesterol (P = .08) was marginally associated with coronary artery disease in the Turkish Cypriot population. The mutations in the MTHFR [C677T] gene variant were marginally higher in the Turkish Cypriot cohort when compared with the Turkish patients from Turkey (P = .06). No significant direct association of any of the gene variants with coronary artery disease in the Turkish Cypriot cohort could be defined. Several of the genetic variants were associated indirectly with the risk factors for coronary artery disease in Turkish Cypriots. MTHFR [A1298C] was found to be marginally associated with low HDL cholesterol (P = .08). MTHFR [C677] wild-type allele was significantly associated with a decreased rate of high LDL

  20. Epidemiologic and Genetic Aspects of Spina Bifida and Other Neural Tube Defects

    Science.gov (United States)

    Au, Kit Sing; Ashley-Koch, Allison; Northrup, Hope

    2010-01-01

    The worldwide incidence of neural tube defects (NTDs) ranges from 1.0 to 10.0 per 1,000 births with almost equal frequencies between two major categories: anencephaly and spina bifida (SB). Epidemiological studies have provided valuable insight for (a) researchers to identify nongenetic and genetic factors contributing to etiology, (b) public…

  1. Identification of genetic defects in primary immunodeficiencies by whole exome sequencing

    DEFF Research Database (Denmark)

    Christiansen, Mette; Jensen, Jens Magnus Bernth; Veirum, Jens Erik

    2014-01-01

    to hypogammaglobulinaemia, and increased risk of both infections as well as cancer. We employed whole exome sequencing (WES) to identify mutations associated with primary immunodeficiency in severely affected children. We present WES data on 2 patients with severe immunodeficiency. WES was performed using TruSeq exome kit...... microorganisms. These defects may result in life-threatening bacterial and fungal infections and excessive inflammatory reactions leading to granulomatous lesions. II) Mutations in DNA double strand break repair genes which impacts V(D)J recombination, class switching and lymphocyte maturation leading...... combined genetic variations contributing to an overall functional defect. This explains the fact that monogenic defects are rare among clinically immune compromised patients, and that patients present with a high degree of clinical variability due to private compound immune defects....

  2. Aggregation of Frenkel defects under irradiation: a mesoscopic approach

    International Nuclear Information System (INIS)

    Soppe, W.; Kotomin, E.

    1993-08-01

    The radiation-induced aggregation of Frenkel defects in solids is studied in terms of a mesoscopic approach. The asymmetry in elastic interactions between mobile interstitials (I-I) and between interstitials and vacancies (I-V) plays a decisive role in the aggregation of similar defects. The conditions for defect aggregation are studied in detail for NaCl crystals. The critical dose rate for aggregation has been calculated as a function of the temperature as well as the aggregation rate as a function of temperature and dose rate. Furthermore, the role of deep traps (like impurities and di-vacancies), reducing the mobility of interstitials, and the role of dislocations serving as sinks for interstitials, are studied. The aggregation appears to reach a maximum at a distinct temperature which is in agreement both with experiment and the Jain-Lidiard theory. The model also predicts a shift of this maximum towards lower temperatures if the dose rate is decreased. The consequences of the model for the disposal of nuclear waste in rock salt formations, are briefly discussed. (orig.)

  3. Evolution of surface defects in platinum alloy wire under drawing

    Science.gov (United States)

    Loginov, Yu. N.; Pervukhin, A. E.; Babailov, N. A.

    2017-12-01

    The shape and chemical composition of particles polluting the surface of ultrafine wire made of the platinum Pt92.5Pd4Rh3.5 alloy has been revealed by electron microscopy and microspectral analysis. The phenomenon of the appearance of pores in the particles, which are elongated in the direction of drawing, has been discovered. The problem of calculating the stress-strain state is stated by the finite element method. After solving the problem, it is demonstrated that the appearance of additional defects is related to the proportion of stresses in the scheme of metal forming by drawing.

  4. Auto-oscillations of temperature and defect density in impure crystals under irradiation

    International Nuclear Information System (INIS)

    Selishchev, P.A.; Sugakov, V.I.

    1990-01-01

    Appearance of auto-oscillations in temperature and defect density of impurity crystals under irradiation is studied. It is shown that at certain critical parameters stationary distribution of temperature and defect density of the sample irradiated becomes unstable as regards the formation of temporal dissipative structures: auto-oscillations of temperature and defect density. Critical parameters are determined (the rate of defect formation, temperature of crystal environment, etc.) and the frequency of appearing auto-oscillations, its dependence on irradiation conditions and crystal properties are found

  5. USE OF GENETICALLY MODIFIED MUSCLE AND FAT GRAFTS TO REPAIR DEFECTS IN BONE AND CARTILAGE

    Science.gov (United States)

    Evans, C.H.; Liu, F.-J.; Glatt, V.; Hoyland, J.A.; Kirker-Head, C.; Walsh, A.; Betz, O.; Wells, J.W.; Betz, V.; Porter, R.M.; Saad, F.A.; Gerstenfeld, L.C.; Einhorn, T.A.; Harris, M.B.; Vrahas, M.S.

    2015-01-01

    We report a novel technology for the rapid healing of large osseous and chondral defects, based upon the genetic modification of autologous skeletal muscle and fat grafts. These tissues were selected because they not only possess mesenchymal progenitor cells and scaffolding properties, but also can be biopsied, genetically modified and returned to the patient in a single operative session. First generation adenovirus vector carrying cDNA encoding human bone morphogenetic protein-2 (Ad.BMP-2) was used for gene transfer to biopsies of muscle and fat. To assess bone healing, the genetically modified (“gene activated”) tissues were implanted into 5mm-long critical size, mid-diaphyseal, stabilized defects in the femora of Fischer rats. Unlike control defects, those receiving gene-activated muscle underwent rapid healing, with evidence of radiologic bridging as early as 10 days after implantation and restoration of full mechanical strength by 8 weeks. Histologic analysis suggests that the grafts rapidly differentiated into cartilage, followed by efficient endochondral ossification. Fluorescence in situ hybridization detection of Y-chromosomes following the transfer of male donor muscle into female rats demonstrated that at least some of the osteoblasts of the healed bone were derived from donor muscle. Gene activated fat also healed critical sized defects, but less quickly than muscle and with more variability. Anti-adenovirus antibodies were not detected. Pilot studies in a rabbit osteochondral defect model demonstrated the promise of this technology for healing cartilage defects. Further development of these methods should provide ways to heal bone and cartilage more expeditiously, and at lower cost, than is presently possible. PMID:20073015

  6. Defect production in Ar irradiated graphene membranes under different initial applied strains

    Energy Technology Data Exchange (ETDEWEB)

    Martinez-Asencio, J., E-mail: jesusmartinez@ua.es [Dept. Física Aplicada, Facultad de Ciencias, Fase II, Universidad de Alicante, Alicante E-036090 (Spain); Ruestes, C.J.; Bringa, E. [CONICET and Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo, Mendoza 5500 (Argentina); Caturla, M.J. [Dept. Física Aplicada, Facultad de Ciencias, Fase II, Universidad de Alicante, Alicante E-036090 (Spain)

    2017-02-15

    Highlights: • Defects in graphene membranes are formed due to 140 eV Ar ions irradiation using MD. • Different initial strains are applied, which influence the type and number of defects. • Mono-vacancies, di-vacancies and tri-vacancies production behaves linearly with dose. • The total number of defects under compression is slightly higher than under tension. - Abstract: Irradiation with low energy Ar ions of graphene membranes gives rise to changes in the mechanical properties of this material. These changes have been associated to the production of defects, mostly isolated vacancies. However, the initial state of the graphene membrane can also affect its mechanical response. Using molecular dynamics simulations we have studied defect production in graphene membranes irradiated with 140 eV Ar ions up to a dose of 0.075 × 10{sup 14} ions/cm{sup 2} and different initial strains, from −0.25% (compressive strain) to 0.25% (tensile strain). For all strains, the number of defects increases linearly with dose with a defect production of about 80% (80 defects every 100 ions). Defects are mostly single vacancies and di-vacancies, although some higher order clusters are also observed. Two different types of di-vacancies have been identified, the most common one being two vacancies at first nearest neighbours distance. Differences in the total number of defects with the applied strain are observed which is related to the production of a higher number of di-vacancies under compressive strain compared to tensile strain. We attribute this effect to the larger out-of-plane deformations of compressed samples that could favor the production of defects in closer proximity to others.

  7. Maternal obesity and tobacco use modify the impact of genetic variants on the occurrence of conotruncal heart defects.

    Directory of Open Access Journals (Sweden)

    Xinyu Tang

    Full Text Available Conotruncal heart defects (CTDs are among the most severe birth defects worldwide. Studies of CTDs indicate both lifestyle behaviors and genetic variation contribute to the risk of CTDs. Based on a hybrid design using data from 616 case-parental and 1645 control-parental triads recruited for the National Birth Defects Prevention Study between 1997 and 2008, we investigated whether the occurrence of CTDs is associated with interactions between 921 maternal and/or fetal single nucleotide polymorphisms (SNPs and maternal obesity and tobacco use. The maternal genotypes of the variants in the glutamate-cysteine ligase, catalytic subunit (GCLC gene and the fetal genotypes of the variants in the glutathione S-transferase alpha 3 (GSTA3 gene were associated with an elevated risk of CTDs among obese mothers. The risk of delivering infants with CTDs among obese mothers carrying AC genotype for a variant in the GCLC gene (rs6458939 was 2.00 times the risk among those carrying CC genotype (95% confidence interval: 1.41, 2.38. The maternal genotypes of several variants in the glutathione-S-transferase (GST family of genes and the fetal genotypes of the variants in the GCLC gene interacted with tobacco exposures to increase the risk of CTDs. Our study suggests that the genetic basis underlying susceptibility of the developing heart to the adverse effects of maternal obesity and tobacco use involve both maternal and embryonic genetic variants. These results may provide insights into the underlying pathophysiology of CTDs, and ultimately lead to novel prevention strategies.

  8. Genetic defects and the role of helper T-cells in the pathogenesis of common variable immunodeficiency

    Directory of Open Access Journals (Sweden)

    Reza Yazdani

    2014-01-01

    Full Text Available Common variable immunodeficfiiency (CVID is a primary immunodeficiency syndrome representing a heterogeneous set of disorders resulting mostly in antibody deficiency and recurrent infections. However, inflammatory and autoimmune disorders and some kinds of malignancies are frequently reported as a part of the syndrome. Although it is one of the most widespread primary immunodeficiency, only recently some genetic defects in CVID have been identified. Mutations have been detected in inducible T-cell costimulator (ICOS, transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI, B-cell activating factor-receptor (BAFF-R, B-cell receptor complex (CD19, CD21 and CD81 and CD20. On the other hand, recent studies have shown a decrease in T-helper-17 cells frequency and their characteristic cytokines in CVID patients and this emphasis on the vital role of the T-cells in immunopathogenesis of the CVID. Furthermore, in the context of autoimmune diseases accompanying CVID, interleukin 9 has recently attracted a plenty of considerations. However, the list of defects is expanding as exact immunologic pathways and genetic disorders in CVID are not yet defined. In this review, we have a special focus on the immunopathogenesis of CVID, recent advances in understanding the underlying etiology and genetics for patients.

  9. The Genetic and Environmental Factors Underlying Hypospadias

    Science.gov (United States)

    Pask, Andrew; Heloury, Yves; Sinclair, Andrew H.

    2016-01-01

    Hypospadias results from a failure of urethral closure in the male phallus and affects 1 in 200–300 boys. It is thought to be due to a combination of genetic and environmental factors. The development of the penis progresses in 2 stages: an initial hormone-independent phase and a secondary hormone-dependent phase. Here, we review the molecular pathways that contribute to each of these stages, drawing on studies from both human and mouse models. Hypospadias can occur when normal development of the phallus is disrupted, and we provide evidence that mutations in genes underlying this developmental process are causative. Finally, we discuss the environmental factors that may contribute to hypospadias and their potential immediate and transgen erational epigenetic impacts. PMID:26613581

  10. Mechanical properties and fracture behaviour of defective phosphorene nanotubes under uniaxial tension

    Science.gov (United States)

    Liu, Ping; Pei, Qing-Xiang; Huang, Wei; Zhang, Yong-Wei

    2017-12-01

    The easy formation of vacancy defects and the asymmetry in the two sublayers of phosphorene nanotubes (PNTs) may result in brand new mechanical properties and failure behaviour. Herein, we investigate the mechanical properties and fracture behaviour of defective PNTs under uniaxial tension using molecular dynamics simulations. Our simulation results show that atomic vacancies cause local stress concentration and thus significantly reduce the fracture strength and fracture strain of PNTs. More specifically, a 1% defect concentration is able to reduce the fracture strength and fracture strain by as much as 50% and 66%, respectively. Interestingly, the reduction in the mechanical properties is found to depend on the defect location: a defect located in the outer sublayer has a stronger effect than one located in the inner layer, especially for PNTs with a small diameter. Temperature is also found to strongly influence the mechanical properties of both defect-free and defective PNTs. When the temperature is increased from 0 K to 400 K, the fracture strength and fracture strain of defective PNTs with a defect concentration of 1% are reduced further by 71% and 61%, respectively. These findings are of great importance for the structural design of PNTs as building blocks in nanodevices.

  11. Consideration of critical axial properties of pristine and defected carbon nanotubes under compression.

    Science.gov (United States)

    Ranjbartoreh, A R; Su, D; Wang, G

    2012-06-01

    Carbon nanotubes are hexagonally configured carbon atoms in cylindrical structures. Exceptionally high mechanical strength, electrical conductivity, surface area, thermal stability and optical transparency of carbon nanotubes outperformed other known materials in numerous advanced applications. However, their mechanical behaviors under practical loading conditions remain to be demonstrated. This study investigates the critical axial properties of pristine and defected single- and multi-walled carbon nanotubes under axial compression. Molecular dynamics simulation method has been employed to consider the destructive effects of Stone-Wales and atom vacancy defects on mechanical properties of armchair and zigzag carbon nanotubes under compressive loading condition. Armchair carbon nanotube shows higher axial stability than zigzag type. Increase in wall number leads to less susceptibility of multi-walled carbon nanotubes to defects and higher stability of them under axial compression. Atom vacancy defect reveals higher destructive effect than Stone-Wales defect on mechanical properties of carbon nanotubes. Critical axial strain of single-walled carbon nanotube declines by 67% and 26% due to atom vacancy and Stone-Wales defects.

  12. Family-based studies to identify genetic variants that cause congenital heart defects.

    Science.gov (United States)

    Arrington, Cammon B; Bleyl, Steven B; Brunelli, Luca; Bowles, Neil E

    2013-07-01

    Congenital heart defects (CHDs) are the most common congenital abnormalities. Analysis of large multigenerational families has led to the identification of a number of genes for CHDs. However, identifiable variations in these genes are the cause of a small proportion of cases of CHDs, suggesting significant genetic heterogeneity. In addition, large families with CHDs are rare, making the identification of additional genes difficult. Next-generation sequencing technologies will provide an opportunity to identify more genes in the future. However, the significant genetic variation between individuals will present a challenge to distinguish between 'pathogenic' and 'benign' variants. We have demonstrated that the analysis of multiple individuals in small families using combinations of algorithms can reduce the number of candidate variants to a small, manageable number. Thus, the analysis of small nuclear families or even distantly related 'sporadic' cases may begin to uncover the 'dark matter' of CHD genetics.

  13. Polymers under ionizing radiation: the study of energy transfers to radiation induced defects

    International Nuclear Information System (INIS)

    Ventura, A.

    2013-01-01

    Radiation-induced defects created in polymers submitted to ionizing radiations, under inert atmosphere, present the same trend as a function of the dose. When the absorbed dose increases, their concentrations increase then level off. This behavior can be assigned to energy transfers from the polymer to the previously created macromolecular defects; the latter acting as energy sinks. During this thesis, we aimed to specify the influence of a given defect, namely the trans-vinylene, in the behavior of polyethylene under ionizing radiations. For this purpose, we proposed a new methodology based on the specific insertion, at various concentrations, of trans-vinylene groups in the polyethylene backbone through chemical synthesis. This enables to get rid of the variety of created defects on one hand and on the simultaneity of their creation on the other hand. Modified polyethylenes, containing solely trans-vinylene as odd groups, were irradiated under inert atmosphere, using either low LET beams (gamma, beta) or high LET beams (swift heavy ions). During irradiations, both macromolecular defects and H 2 emission were quantified. According to experimental results, among all defects, the influence of the trans-vinylene on the behavior of polyethylene is predominant. (author) [fr

  14. Ab initio study of native defects in SnO under strain

    KAUST Repository

    Bianchi Granato, Danilo

    2014-04-01

    Tin monoxide (SnO) has promising properties to be applied as a p-type semiconductor in transparent electronics. To this end, it is necessary to understand the behaviour of defects in order to control them. We use density functional theory to study native defects of SnO under tensile and compressive strain. We show that Sn vacancies are less stable under tension and more stable under compression, irrespectively of the charge state. In contrast, O vacancies behave differently for different charge states. It turns out that the most stable defect under compression is the +1 charged O vacancy in an Sn-rich environment and the charge neutral O interstitial in an O-rich environment. Therefore, compression can be used to transform SnO from a p-type into either an n-type or an undoped semiconductor. Copyright © EPLA, 2014.

  15. Aplasia cutis congenita of the scalp with large underlying skull defect: a case report

    International Nuclear Information System (INIS)

    Leboucq, N.; Montoya y Martinez, P.; Montoya-Vigo, F.; Castan, P.

    1994-01-01

    Localised agenesis of the scalp is the most frequent patern in aplasia cutis congenita (ACC), a congenital absence of the skin and occasionally of deeper layers. Several clinical groups are characterised by the location and pattern of skin defects, associated malformations and the mode of inheritance. Death occurs in 20 % of cases, secondary to the associated anomalies, to infections or to haemorrhage from ulceration of the sagittal sinus when there is also a defect of the underlying skull. In this latter case, we close the defect by two rotational scalp flaps (Orticochea technique) at birth. A three-dimensional CT study is useful for showing the extent of the skull defect and the deformity of the craniofacial complex and the changes in the bone after treatment. (orig.)

  16. Structural evolution of defective graphene under heat treatment and gamma irradiation

    Science.gov (United States)

    Zhang, Yifei; Shi, Jie; Chen, Cheng; Li, Nan; Xu, Zhiwei; Liu, Liangsen; Zhao, Lihuan; Li, Jing; Jing, Miaolei

    2018-03-01

    We have studied the structural change of defective graphene built by annealing in different temperature under the condition of gamma irradiation. Firstly, we found the heat treatment not only reduced but also striped the graphene. This behavior made defects become more firstly and then become less with the increase of temperature. And then gamma irradiation removed some oxygen-containing groups, by a simultaneous changed over carbon in the graphitic lattice from sp3 to sp2. Also, the gamma irradiation decreased the interlayer spacing between graphene lowest to 3.391 Å and made a crosslink which resulting in the size of the ordered gaining. A variation was detected by Raman spectroscopy that the amorphous carbon was declined after gamma irradiation. Furtherly we found the degree of this decline raised first and then diminished with the increase in the number of defects. The change in repair capacity of gamma irradiation presented a strategy for repairing the defects of graphene.

  17. Cancers and genetic defects resulting from the use of various energy sources

    International Nuclear Information System (INIS)

    Myers, D.K.

    1978-06-01

    A review of recent literature on carcinogenic effects of chemical products derived from the combustion of organic fuels suggests that the numbers of fatal cancers and genetic defects induced by utilization of fossil fuels may be much greater than the numbers induced by utilization of nuclear power to produce the same amount of energy. Despite the uncertainties involved in these estimates, the maximum risk of fatal cancers due to carcinogenic by-products associated with the production of electricity by any of these methods appears to be remarkably low compared with the risk of other fatal hazards in Canada and the U.S.A. (author)

  18. Relationships of RNA polymerase II genetic interactors to transcription start site usage defects and growth in Saccharomyces cerevisiae.

    Science.gov (United States)

    Jin, Huiyan; Kaplan, Craig D

    2014-11-06

    Transcription initiation by RNA Polymerase II (Pol II) is an essential step in gene expression and regulation in all organisms. Initiation requires a great number of factors, and defects in this process can be apparent in the form of altered transcription start site (TSS) selection in Saccharomyces cerevisiae (Baker's yeast). It has been shown previously that TSS selection in S. cerevisiae is altered in Pol II catalytic mutants defective in a conserved active site feature known as the trigger loop. Pol II trigger loop mutants show growth phenotypes in vivo that correlate with biochemical defects in vitro and exhibit wide-ranging genetic interactions. We assessed how Pol II mutant growth phenotypes and TSS selection in vivo are modified by Pol II genetic interactors to estimate the relationship between altered TSS selection in vivo and organismal fitness of Pol II mutants. We examined whether the magnitude of TSS selection defects could be correlated with Pol II mutant-transcription factor double mutant phenotypes. We observed broad genetic interactions among Pol II trigger loop mutants and General Transcription Factor (GTF) alleles, with reduced-activity Pol II mutants especially sensitive to defects in TFIIB. However, Pol II mutant growth defects could be uncoupled from TSS selection defects in some Pol II allele-GTF allele double mutants, whereas a number of other Pol II genetic interactors did not influence ADH1 start site selection alone or in combination with Pol II mutants. Initiation defects are likely only partially responsible for Pol II allele growth phenotypes, with some Pol II genetic interactors able to exacerbate Pol II mutant growth defects while leaving initiation at a model TSS selection promoter unaffected. Copyright © 2015 Jin and Kaplan.

  19. Classification of Atrial Septal Defect and Ventricular Septal Defect with Documented Hemodynamic Parameters via Cardiac Catheterization by Genetic Algorithms and Multi-Layered Artificial Neural Network

    Directory of Open Access Journals (Sweden)

    Mustafa Yıldız

    2012-08-01

    Full Text Available Introduction: We aimed to develop a classification method to discriminate ventricular septal defect and atrial septal defect by using severalhemodynamic parameters.Patients and Methods: Forty three patients (30 atrial septal defect, 13 ventricular septal defect; 26 female, 17 male with documentedhemodynamic parameters via cardiac catheterization are included to study. Such parameters as blood pressure values of different areas,gender, age and Qp/Qs ratios are used for classification. Parameters, we used in classification are determined by divergence analysismethod. Those parameters are; i pulmonary artery diastolic pressure, ii Qp/Qs ratio, iii right atrium pressure, iv age, v pulmonary arterysystolic pressure, vi left ventricular sistolic pressure, vii aorta mean pressure, viii left ventricular diastolic pressure, ix aorta diastolicpressure, x aorta systolic pressure. Those parameters detected from our study population, are uploaded to multi-layered artificial neuralnetwork and the network was trained by genetic algorithm.Results: Trained cluster consists of 14 factors (7 atrial septal defect and 7 ventricular septal defect. Overall success ratio is 79.2%, andwith a proper instruction of artificial neural network this ratio increases up to 89%.Conclusion: Parameters, belonging to artificial neural network, which are needed to be detected by the investigator in classical methods,can easily be detected with the help of genetic algorithms. During the instruction of artificial neural network by genetic algorithms, boththe topology of network and factors of network can be determined. During the test stage, elements, not included in instruction cluster, areassumed as in test cluster, and as a result of this study, we observed that multi-layered artificial neural network can be instructed properly,and neural network is a successful method for aimed classification.

  20. Generator scheduling under competitive environment using genetic ...

    African Journals Online (AJOL)

    In this paper, genetic algorithm (GA) is used to solve the GENCOs profit based unit commitment problem (PBUCP) in a dayahead competitive electricity markets considering power and reserve generations simultaneously, whereas enhanced lambda iteration (ELI) method is used to solve the economic dispatch (ED) ...

  1. Intraspecific Genetic dynamics under Climate Change

    DEFF Research Database (Denmark)

    Florez Rodriguez, Alexander

    Climate change has a deep influence on the maintenance and generation of global biodiversity. Past contractions, expansions and shifts in species’ ranges drove to changes in species genetic diversity. Noteworthy, the interaction among: climate change, range, population size and extinction is ofte...

  2. Molecular marker studies in riverine buffaloes, for characterization and diagnosis of genetic defects

    International Nuclear Information System (INIS)

    Yadav, B.R.

    2005-01-01

    The buffalo is probably the last livestock species to have been domesticated, with many genetic, physiological and behavioural traits not yet well understood. Molecular markers have been used for characterizing animals and breeds, diagnosing diseases and identifying anatomical and physiological anomalies. RFLP studies showed low heterozygosity, but genomic and oligonucleotide probes showed species-specific bands useful for identification of carcass or other unknown samples. Use of RAPD revealed band frequencies, band sharing frequencies, genetic distances, and genetic and identity indexes in different breeds. Bovine microsatellite primers indicate that 70.9% of bovine loci were conserved in buffalo. Allele numbers, sizes, frequencies, heterozygosity and polymorphism information content showed breed-specific patterns. Different marker types - genomic and oligonucleotide probes, RAPD and microsatellites - are useful in parent identification. Individual specific DNA fingerprinting techniques were applied with twin-born animal (XX/XY) chimerism, sex identification, anatomically defective and XO individuals. Molecular markers are a potential tool for geneticists and breeders to evaluate existing germplasm and to manipulate it to develop character-specific strains and to provide the basis for effective genetic conservation. (author)

  3. The radiation defect accumulation in scintillative crystals of caesium halides under intense electron beam irradiation

    CERN Document Server

    Galiy, P V

    1999-01-01

    The characteristics of defect accumulation and radiolysis at CsI crystals under mean energies of electron irradiation at wide dose rates and ranges of doses have been investigated by such methods: thermostimulated exoelectron emission (TSEE), Auger electron spectroscopy (AES) and optical absorption spectroscopy (OAS). The limit dose rates and absorbed doses of electron irradiation that lead to defects accumulation at room temperature in crystals volume and also surface stoichiometry violation have been evaluated. The doses of electron irradiation that lead to CsI radiolysis, with caesium coagulation in metallic phase have been determined. Some quasi periodic connection of such process with irradiation dose was observed.

  4. Genetic and environmental effects on a meat spotting defect in seasoned dry-cured ham

    Directory of Open Access Journals (Sweden)

    Giulio Pagnacco

    2011-01-01

    Full Text Available Purpose of this investigation was to determine the nature of a visible spotting defect on the slice of dry-cured ham and assess environmental and genetic causes of this frequent problem. A group of 233 pigs from commercial cross-breeding lines, progeny of ten boars and forty seven sows, was raised in a single herd to obtain the “Italian Heavy Pig”, typically slaughtered at 160 ± 10 kg live weight and older than 9 months of age. A quality evaluation of their right dry-cured hams, seasoned according to the Parma P.D.O. protocol, was undertaken. Each ham was cross-sectioned to obtain a slice of Semimembranosus, Semitendinosus and Biceps Femoris muscles. The focused phenotype was the presence/absence of brownish spots in these muscles, which represent a remarkable meat defect with strong impact on the final sale price. Environmental and management factors were considered in order to evaluate variability related to the phenotype. Animals were raised on two different flooring types (concrete and slatted floor and a Vitamin C diet was also supplemented in the last 45 days before slaughtering to half of the animals. While the pre-planned environmental effects did not show any significant contribution to the total variability of the phenotype, the genetic analysis showed a near to zero value for heritability with a consistent 0.32 repeatability. The proportion of the total phenotypic variance was explained by an important dominance genetic component (0.26 indicating that the technological seasoning process may play a secondary role on the expression of this phenotype.

  5. Corrosion Behavior of X80 Steel with Coupled Coating Defects under Alternating Current Interference in Alkaline Environment.

    Science.gov (United States)

    Li, Zhong; Li, Caiyu; Qian, Hongchang; Li, Jun; Huang, Liang; Du, Cuiwei

    2017-06-28

    The corrosion behavior of X80 steel in the presence of coupled coating defects was simulated and studied under the interference of alternating current (AC) in an alkaline environment. The results from electrochemical measurements showed that the electrode potential of the coating defect with the smaller exposed area was lower than that with the larger area, which indicated that the steel with the smaller coating defect was more prone to corrosion. The result of weight loss tests also showed that the smaller coating defect had induced a higher corrosion rate. However, the corrosion rate of X80 steel at the larger coating defect decreased gradually with the increase of the larger defect area at a constant smaller defect area. The corrosion morphology images showed that the coating defects with smaller areas suffered from more severe pitting corrosion.

  6. Recurrent candidiasis and early-onset gastric cancer in a patient with a genetically defined partial MYD88 defect.

    Science.gov (United States)

    Vogelaar, Ingrid P; Ligtenberg, Marjolijn J L; van der Post, Rachel S; de Voer, Richarda M; Kets, C Marleen; Jansen, Trees J G; Jacobs, Liesbeth; Schreibelt, Gerty; de Vries, I Jolanda M; Netea, Mihai G; Hoogerbrugge, Nicoline

    2016-04-01

    Gastric cancer is caused by both genetic and environmental factors. A woman who suffered from recurrent candidiasis throughout her life developed diffuse-type gastric cancer at the age of 23 years. Using whole-exome sequencing we identified a germline homozygous missense variant in MYD88. Immunological assays on peripheral blood mononuclear cells revealed an impaired immune response upon stimulation with Candida albicans, characterized by a defective production of the cytokine interleukin-17. Our data suggest that a genetic defect in MYD88 results in an impaired immune response and may increase gastric cancer risk.

  7. Genetic abnormalities leading to qualitative defects of sperm morphology or function.

    Science.gov (United States)

    Ray, P F; Toure, A; Metzler-Guillemain, C; Mitchell, M J; Arnoult, C; Coutton, C

    2017-02-01

    Infertility, defined by the inability of conceiving a child after 1 year is estimated to concern approximately 50 million couples worldwide. As the male gamete is readily accessible and can be studied by a simple spermogram it is easier to subcategorize male than female infertility. Subjects with a specific sperm phenotype are more likely to have a common origin thus facilitating the search for causal factors. Male infertility is believed to be often multifactorial and caused by both genetic and extrinsic factors, but severe cases of male infertility are likely to have a predominant genetic etiology. Patients presenting with a monomorphic teratozoospermia such as globozoospermia or macrospermia with more than 85% of the spermatozoa presenting this specific abnormality have been analyzed permitting to identify several key genes for spermatogenesis such as AURKC and DPY19L2. The study of patients with other specific sperm anomalies such as severe alteration of sperm motility, in particular multiple morphological anomalies of the sperm flagella (MMAF) or sperm unability to fertilize the oocyte (oocyte activation failure syndrome) has also enable the identification of new infertility genes. Here we review the recent works describing the identification and characterization of gene defects having a direct qualitative effect on sperm morphology or function. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Genetic defects in fatty acid beta-oxidation and acyl-CoA dehydrogenases. Molecular pathogenesis and genotype-phenotype relationships

    DEFF Research Database (Denmark)

    Gregersen, Niels; Bross, Peter; Andresen, Brage S

    2004-01-01

    Mitochondrial fatty acid oxidation deficiencies are due to genetic defects in enzymes of fatty acid beta-oxidation and transport proteins. Genetic defects have been identified in most of the genes where nearly all types of sequence variations (mutation types) have been associated with disease. In...

  9. Electron-Ion Dynamics in Semiconductors with Defects under Ion Irradiation

    Science.gov (United States)

    Lee, Cheng-Wei; Schleife, André

    Long-term stability is challenging for semiconductor devices under ion radiation such as solar panels in outer space. Exposure to ion radiation induces formation of defects that ultimately reduce solar cell efficiency. It is well-known in the literature that high-energy ion radiation transfers energy to the materials mostly via electronic excitation which is traditionally hard to model. Previously, we demonstrated that Ehrenfest molecular dynamics based on time-dependent density functional theory correctly describes electronic stopping of semiconductors. To better understand the effect of excited electrons on evolution of defects during ion irradiation, we further investigate the time-evolution of occupation number and found that it is correlated to long-term ion dynamics after passage of proton. Furthermore, we found that the presence of excited electrons significantly reduces the atomic diffusion barrier, indicating this effect is essential for the analysis of defect formation and ion dynamics under ion radiation conditions. An award of computer time was provided by the Innovative and Novel Computational Impact on Theory and Experiment (INCITE) program.

  10. Radiation induced deep level defects in bipolar junction transistors under various bias conditions

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Chaoming; Yang, Jianqun [School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001 (China); Li, Xingji, E-mail: lxj0218@hit.edu.cn [School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001 (China); Ma, Guoliang [School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001 (China); Xiao, Liyi [Department of Astronautics, Harbin Institute of Technology, Harbin 150001 (China); Bollmann, Joachim [Institute of Electronics and Sensor Materials, TU Bergakademie Freiberg, 71691 (Germany)

    2015-12-15

    Bipolar junction transistor (BJT) is sensitive to ionization and displacement radiation effects in space. In this paper, 35 MeV Si ions were used as irradiation source to research the radiation damage on NPN and PNP bipolar transistors. The changing of electrical parameters of transistors was in situ measured with increasing irradiation fluence of 35 MeV Si ions. Using deep level transient spectroscopy (DLTS), defects in the bipolar junction transistors under various bias conditions are measured after irradiation. Based on the in situ electrical measurement and DLTS spectra, it is clearly that the bias conditions can affect the concentration of deep level defects, and the radiation damage induced by heavy ions.

  11. Radiation induced deep level defects in bipolar junction transistors under various bias conditions

    Science.gov (United States)

    Liu, Chaoming; Yang, Jianqun; Li, Xingji; Ma, Guoliang; Xiao, Liyi; Bollmann, Joachim

    2015-12-01

    Bipolar junction transistor (BJT) is sensitive to ionization and displacement radiation effects in space. In this paper, 35 MeV Si ions were used as irradiation source to research the radiation damage on NPN and PNP bipolar transistors. The changing of electrical parameters of transistors was in situ measured with increasing irradiation fluence of 35 MeV Si ions. Using deep level transient spectroscopy (DLTS), defects in the bipolar junction transistors under various bias conditions are measured after irradiation. Based on the in situ electrical measurement and DLTS spectra, it is clearly that the bias conditions can affect the concentration of deep level defects, and the radiation damage induced by heavy ions.

  12. Genetic Enhancement of Limb Defects in a Mouse Model of Cornelia de Lange Syndrome

    Science.gov (United States)

    LOPEZ-BURKS, MARTHA E.; SANTOS, ROSAYSELA; KAWAUCHI, SHIMAKO; CALOF, ANNE L.; LANDER, ARTHUR D.

    2016-01-01

    Cornelia de Lange Syndrome (CdLS) is characterized by a wide variety of structural and functional abnormalities in almost every organ system of the body. CdLS is now known to be caused by mutations that disrupt the function of the cohesin complex or its regulators, and studies of animal models and cell lines tell us that the effect of these mutations is to produce subtle yet pervasive dysregulation of gene expression. With many hundreds of mostly small gene expression changes occurring in every cell type and tissue, identifying the etiology of any particular birth defect is very challenging. Here we focus on limb abnormalities, which are commonly seen in CdLS. In the limb buds of the Nipbl-haploinsufficient mouse (Nipbl+/− mouse), a model for the most common form of CdLS, modest gene expression changes are observed in several candidate pathways whose disruption is known to cause limb abnormalities, yet the limbs of Nipbl+/− mice develop relatively normally. We hypothesized that further impairment of candidate pathways might produce limb defects similar to those seen in CdLS, and performed genetic experiments to test this. Focusing on Sonic hedgehog (Shh), Bone morphogenetic protein (Bmp), and Hox gene pathways, we show that decreasing Bmp or Hox function (but not Shh function) enhances polydactyly in Nipbl+/− mice, and in some cases produces novel skeletal phenotypes. However, frank limb reductions, as are seen in a subset of individuals with CdLS, do not occur, suggesting that additional signaling and/or gene regulatory pathways are involved in producing such dramatic changes. PMID:27120109

  13. Reproduction, Smell, and Neurodevelopmental Disorders: Genetic Defects in Different Hypogonadotropic Hypogonadal Syndromes

    Science.gov (United States)

    Valdes-Socin, Hernan; Rubio Almanza, Matilde; Tomé Fernández-Ladreda, Mariana; Debray, François Guillaume; Bours, Vincent; Beckers, Albert

    2014-01-01

    The neuroendocrine control of reproduction in mammals is governed by a neural hypothalamic network of nearly 1500 gonadotropin-releasing hormone (GnRH) secreting neurons that modulate the activity of the reproductive axis across life. Congenital hypogonadotropic hypogonadism (HH) is a clinical syndrome that is characterized by partial or complete pubertal failure. HH may result from inadequate hypothalamic GnRH axis activation, or a failure of pituitary gonadotropin secretion/effects. In man, several genes that participate in olfactory and GnRH neuronal migration are thought to interact during the embryonic life. A growing number of mutations in different genes are responsible for congenital HH. Based on the presence or absence of olfaction dysfunction, HH is divided in two syndromes: HH with olfactory alterations [Kallmann syndrome (KS)] and idiopathic hypogonadotropic hypogonadism (IHH) with normal smell (normosmic IHH). KS is a heterogeneous disorder affecting 1 in 5000 males, with a three to fivefold of males over females. KS is associated with mutations in KAL1, FGFR1/FGF8, FGF17, IL17RD, PROK2/PROKR2, NELF, CHD7, HS6ST1, FLRT3, SPRY4, DUSP6, SEMA3A, NELF, and WDR11 genes that are related to defects in neuronal migration. These reproductive and olfactory deficits include a variable non-reproductive phenotype, including sensorineural deafness, coloboma, bimanual synkinesis, craniofacial abnormalities, and/or renal agenesis. Interestingly, defects in PROKR2, FGFR1, FGF8, CHD7, DUSP6, and WDR11 genes are also associated with normosmic IHH, whereas mutations in KISS1/KISSR, TAC3/TACR3, GNRH1/GNRHR, LEP/LEPR, HESX1, FSHB, and LHB are only present in patients with normosmic IHH. In this paper, we summarize the reproductive, neurodevelopmental, and genetic aspects of HH in human pathology. PMID:25071724

  14. Rate theory modeling of defect evolution under cascade damage conditions: the influence of vacancy-type cascade remnants and application to the defect production characterization by microstructural analysis

    International Nuclear Information System (INIS)

    Katoh, Yutai; Muroga, Takeo; Kohyama, Akira; Stoller, R.E.; Namba, Chusei; Motojima, Osamu.

    1995-11-01

    Recent computational and experimental studies have confirmed that high energy cascades produce clustered defects of both vacancy- and interstitial-types as well as isolated point defects. However, the production probability, configuration, stability and other characteristics of the cascade clusters are not well understood in spite of the fact that clustered defect production would substantially affect the irradiation-induced microstructures and the consequent property changes in a certain range of temperatures and displacement rates. In this work, a model of point defect and cluster evolution in irradiated materials under cascade damage conditions was developed by combining the conventional reaction rate theory and the results from the latest molecular dynamics simulation studies. This paper provides a description of the model and a model-based fundamental investigation of the influence of configuration, production efficiency and the initial size distribution of cascade-produced vacancy clusters. In addition, using the model, issues on characterizing cascade-induced defect production by microstructural analysis will be discussed. In particular, the determination of cascade vacancy cluster configuration, surviving defect production efficiency and cascade-interaction volume is attempted by analyzing the temperature dependence of swelling rate and loop growth rate in austenitic steels and model alloys. (author)

  15. A common genetic factor underlies hypertension and other cardiovascular disorders

    Directory of Open Access Journals (Sweden)

    Spector Tim D

    2004-11-01

    Full Text Available Abstract Background Certain conditions characterised by blood vessel occlusion or vascular spasm have been found to cluster together in epidemiological studies. However the biological causes for these associations remain controversial. This study used a classical twin design to examine whether these conditions are linked through shared environmental exposures or by a common underlying genetic propensity to vasospasm. Methods We investigated the association between hypertension, migraine, Raynaud's phenomenon and coronary artery disease in twins from a national register. Phenotype status was determined using a questionnaire and the genetic and environmental association between phenotypes was estimated through variance components analysis. Results Responses were obtained from 2,204 individuals comprising 525 monozygotic and 577 dizygotic pairs. There was a significant genetic contribution to all four traits with heritabilities ranging from 0.34 to 0.64. Multivariate model-fitting demonstrated that a single common genetic factor underlies the four conditions. Conclusions We have confirmed an association between hypertension, migraine, Raynaud's phenomenon and coronary artery disease, and shown that a single genetic factor underlies them. The demonstration of a shared genetic factor explains the association between them and adds weight to the theory of an inherited predisposition to vasospasm.

  16. Evaluation of common genetic variants in 82 candidate genes as risk factors for neural tube defects

    LENUS (Irish Health Repository)

    Pangilinan, Faith

    2012-08-02

    AbstractBackgroundNeural tube defects (NTDs) are common birth defects (~1 in 1000 pregnancies in the US and Europe) that have complex origins, including environmental and genetic factors. A low level of maternal folate is one well-established risk factor, with maternal periconceptional folic acid supplementation reducing the occurrence of NTD pregnancies by 50-70%. Gene variants in the folate metabolic pathway (e.g., MTHFR rs1801133 (677 C > T) and MTHFD1 rs2236225 (R653Q)) have been found to increase NTD risk. We hypothesized that variants in additional folate\\/B12 pathway genes contribute to NTD risk.MethodsA tagSNP approach was used to screen common variation in 82 candidate genes selected from the folate\\/B12 pathway and NTD mouse models. We initially genotyped polymorphisms in 320 Irish triads (NTD cases and their parents), including 301 cases and 341 Irish controls to perform case–control and family based association tests. Significantly associated polymorphisms were genotyped in a secondary set of 250 families that included 229 cases and 658 controls. The combined results for 1441 SNPs were used in a joint analysis to test for case and maternal effects.ResultsNearly 70 SNPs in 30 genes were found to be associated with NTDs at the p < 0.01 level. The ten strongest association signals (p-value range: 0.0003–0.0023) were found in nine genes (MFTC, CDKN2A, ADA, PEMT, CUBN, GART, DNMT3A, MTHFD1 and T (Brachyury)) and included the known NTD risk factor MTHFD1 R653Q (rs2236225). The single strongest signal was observed in a new candidate, MFTC rs17803441 (OR = 1.61 [1.23-2.08], p = 0.0003 for the minor allele). Though nominally significant, these associations did not remain significant after correction for multiple hypothesis testing.ConclusionsTo our knowledge, with respect to sample size and scope of evaluation of candidate polymorphisms, this is the largest NTD genetic association study reported to date. The scale of the study and the

  17. Evaluation of common genetic variants in 82 candidate genes as risk factors for neural tube defects

    Directory of Open Access Journals (Sweden)

    Pangilinan Faith

    2012-08-01

    Full Text Available Abstract Background Neural tube defects (NTDs are common birth defects (~1 in 1000 pregnancies in the US and Europe that have complex origins, including environmental and genetic factors. A low level of maternal folate is one well-established risk factor, with maternal periconceptional folic acid supplementation reducing the occurrence of NTD pregnancies by 50-70%. Gene variants in the folate metabolic pathway (e.g., MTHFR rs1801133 (677 C > T and MTHFD1 rs2236225 (R653Q have been found to increase NTD risk. We hypothesized that variants in additional folate/B12 pathway genes contribute to NTD risk. Methods A tagSNP approach was used to screen common variation in 82 candidate genes selected from the folate/B12 pathway and NTD mouse models. We initially genotyped polymorphisms in 320 Irish triads (NTD cases and their parents, including 301 cases and 341 Irish controls to perform case–control and family based association tests. Significantly associated polymorphisms were genotyped in a secondary set of 250 families that included 229 cases and 658 controls. The combined results for 1441 SNPs were used in a joint analysis to test for case and maternal effects. Results Nearly 70 SNPs in 30 genes were found to be associated with NTDs at the p MFTC, CDKN2A, ADA, PEMT, CUBN, GART, DNMT3A, MTHFD1 and T (Brachyury and included the known NTD risk factor MTHFD1 R653Q (rs2236225. The single strongest signal was observed in a new candidate, MFTC rs17803441 (OR = 1.61 [1.23-2.08], p = 0.0003 for the minor allele. Though nominally significant, these associations did not remain significant after correction for multiple hypothesis testing. Conclusions To our knowledge, with respect to sample size and scope of evaluation of candidate polymorphisms, this is the largest NTD genetic association study reported to date. The scale of the study and the stringency of correction are likely to have contributed to real associations failing to survive

  18. Using bayesian models to assess the effects of under-reporting of cannabis use on the association with birth defects, national birth defects prevention study, 1997-2005

    NARCIS (Netherlands)

    Gelder, M.M.H.J. van; Donders, A.R.T.; Devine, O.; Roeleveld, N.; Reefhuis, J.; Prevention, S. National Birth

    2014-01-01

    BACKGROUND: Studies on associations between periconceptional cannabis exposure and birth defects have mainly relied on self-reported exposure. Therefore, the results may be biased due to under-reporting of the exposure. The aim of this study was to quantify the potential effects of this form of

  19. Clinical features and molecular genetic analysis of a boy with Prader-Willi syndrome caused by an imprinting defect

    DEFF Research Database (Denmark)

    Schulze, A; Hansen, Claus; Baekgaard, P

    1997-01-01

    Prader-Willi syndrome (PWS) is a neuroendocrine disorder caused by a non-functioning paternally derived gene(s) within the chromosome region 15q11-q13. Most cases result from microscopically visible deletions of paternal origin, or maternal uniparental disomy of chromosome 15. In both instances...... no recurrence has been reported. In rare cases, PWS is associated with lack of gene expression from the paternal allele due to an imprinting defect. We report the clinical features and the molecular genetic analysis of the first Danish child with PWS due to a defect of the putative imprinting centre (IC). When...

  20. Clinical features and molecular genetic analysis of a boy with Prader-Willi syndrome caused by an imprinting defect

    DEFF Research Database (Denmark)

    Schulze, A; Hansen, Claus; Baekgaard, P

    1997-01-01

    no recurrence has been reported. In rare cases, PWS is associated with lack of gene expression from the paternal allele due to an imprinting defect. We report the clinical features and the molecular genetic analysis of the first Danish child with PWS due to a defect of the putative imprinting centre (IC). When...... the imprinting mutation is inherited from a carrier father, the risk that future children will be affected is theoretically 50%. It is therefore important that these families are referred to a geneticist for counselling and further investigation. Prenatal diagnosis is currently only feasible when the mutation...

  1. Identification of genetic defects in primary immunodeficiencies by whole exome sequencing

    DEFF Research Database (Denmark)

    Christiansen, Mette; Jensen, Jens Magnus Bernth; Veirum, Jens Erik

    2014-01-01

    to hypogammaglobulinaemia, and increased risk of both infections as well as cancer. We employed whole exome sequencing (WES) to identify mutations associated with primary immunodeficiency in severely affected children. We present WES data on 2 patients with severe immunodeficiency. WES was performed using TruSeq exome kit...... and severe infections including sepsis. Second, we identified compound heterozygote stopgain mutations in RAD52 and a heterozygote mutation in LRRC8A in a 7 year-old girl with T-cell deficiency, reduced T-cell mediated B-cell activity, hypogammaglobulinaemia, prolonged splenomegali and benign adenopathy. RAD......52 has not previously been linked to immunodeficiency and we are currently investigating the functional consequences. Knowledge of the mechanisms underlying immunodeficiencies is a prerequisite for understanding disease pathogenesis. WES allows the demonstration of immune defects that may result from...

  2. New Design Method of UWB Microstrip Filters Using Adaptive Genetic Algorithms with Defected Ground Structures

    Directory of Open Access Journals (Sweden)

    Amir Reza Dastkhosh

    2010-01-01

    Full Text Available The effects of adaptive genetic algorithms (AGAs and defected ground structures (DGSs on performance optimization of tapered microstrip filter are investigated. The proposed structure achieves an ultra wide stopband with high attenuation within a small surface area, as well as 45% smaller size, in comparison with conventional filters. The parameters of the filter are optimized using in-home AGA code. In the proposed AGA algorithm, the crossover and mutation probabilities are adaptively changed according to the value of individual fitness. Then by utilizing the proposed DGS, a compact S-band lowpass filter with ultra-wide spurious free window is obtained. The proposed filter achieves an insertion loss of 0.8 dB from DC up to 4 GHz and 21 dB rejection in the stopband from 4.3 up to 60 GHz. The fabricated and measured results exhibit good agreement with the simulated results. They demonstrate that combining AGA and DGS yields best possible response for this group of filters.

  3. Linking a genetic defect in migraine to spreading depression in a computational model

    Directory of Open Access Journals (Sweden)

    Markus A. Dahlem

    2014-05-01

    Full Text Available Familial hemiplegic migraine (FHM is a rare subtype of migraine with aura. A mutation causing FHM type 3 (FHM3 has been identified in SCN1A encoding the Nav1.1 Na+ channel. This genetic defect affects the inactivation gate. While the Na+ tail currents following voltage steps are consistent with both hyperexcitability and hypoexcitability, in this computational study, we investigate functional consequences beyond these isolated events. Our extended Hodgkin–Huxley framework establishes a connection between genotype and cellular phenotype, i.e., the pathophysiological dynamics that spans over multiple time scales and is relevant to migraine with aura. In particular, we investigate the dynamical repertoire from normal spiking (milliseconds to spreading depression and anoxic depolarization (tens of seconds and show that FHM3 mutations render gray matter tissue more vulnerable to spreading depression despite opposing effects associated with action potential generation. We conclude that the classification in terms of hypoexcitability vs. hyperexcitability is too simple a scheme. Our mathematical analysis provides further basic insight into also previously discussed criticisms against this scheme based on psychophysical and clinical data.

  4. Genetics Home Reference: ankyloblepharon-ectodermal defects-cleft lip/palate syndrome

    Science.gov (United States)

    ... Home Health Conditions AEC syndrome Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome Printable PDF Open All Close All Enable ... the expand/collapse boxes. Description Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is a form of ectodermal dysplasia, ...

  5. Study of supersaturation of defects under neutron irradiation by Zener relaxation

    International Nuclear Information System (INIS)

    Gonzalez, Hector C.; Justus, Francisco J.W.

    2004-01-01

    Vacancy supersaturation in dynamic equilibrium under fast neutron irradiation could be determined by anelastic relaxation. This phenomenon is particularly noticeable in some substitutional binary alloys. Relaxation is due to the reordering of atoms pairs under a stress, being a local reordering at the atomic scale. Relaxation time (τ) is inversely proportional to the vacancy concentration (Cv) and decreases under irradiation because a dynamical equilibrium of vacancy concentration, higher than thermodynamic equilibrium, is established. Theoretical models allow estimating the magnitude of that supersaturation. Determinations of τ at different temperatures, with and without fast neutron irradiations, were made with an 'in situ' device placed in the high temperature loop in the RA1 CAC-CNEA reactor. An alloy Au-30% Ni was used, since it presents an appreciable Zener effect. The measurements were performed in a spring-shaped specimen in order to minimize temperature and flux gradients. An Arrhenius plot of τ was obtained, and it was observed that for temperatures lower than 220 C degrees a vacancy supersaturation exists. The lowest temperature of our experiments was 190 C degrees. A value of τ at this temperature was three times lower under irradiations. A plot of τ vs. fast neutron fluence (φ f t) at the irradiation temperature T= 203 C degrees was obtained. An increase of τ was observed. After an annealing at T = 280 C degrees, the value of τ recovers the value corresponding to the unirradiated case. This fact suggests that the loops produced by irradiation act as defect sinks. (author) [es

  6. Genetic and physiological controls of growth under water deficit.

    Science.gov (United States)

    Tardieu, François; Parent, Boris; Caldeira, Cecilio F; Welcker, Claude

    2014-04-01

    The sensitivity of expansive growth to water deficit has a large genetic variability, which is higher than that of photosynthesis. It is observed in several species, with some genotypes stopping growth in a relatively wet soil, whereas others continue growing until the lower limit of soil-available water. The responses of growth to soil water deficit and evaporative demand share an appreciable part of their genetic control through the colocation of quantitative trait loci as do the responses of the growth of different organs to water deficit. This result may be caused by common mechanisms of action discussed in this paper (particularly, plant hydraulic properties). We propose that expansive growth, putatively linked to hydraulic processes, determines the sink strength under water deficit, whereas photosynthesis determines source strength. These findings have large consequences for plant modeling under water deficit and for the design of breeding programs.

  7. Search for Genetic Variants Underlying Musical Aptitude and Related Traits

    OpenAIRE

    Ukkola-Vuoti, Liisa

    2013-01-01

    Music perception and practice represents complex cognitive functions of the brain. There is an abundance of data about the neurophysiological effects of music on the human brain, but heritability and especially molecular studies have been lacking. The development of genome technologies and bioinformatics has enabled the identification of genetic variants underlying complex human traits. These methods can be applied to normal human traits like music perception and performance. Prior to th...

  8. Identifying the genetic components underlying the pathophysiology of movement disorders

    Directory of Open Access Journals (Sweden)

    Ezquerra M

    2011-06-01

    Full Text Available Mario Ezquerra, Yaroslau Compta, Maria J MartiParkinson’s Disease and Movement Disorders Unit, Service of Neurology, Institute of Clinical Neurosciences, Hospital Clinic of Barcelona, IDIBAPS, CIBERNED, SpainAbstract: Movement disorders are a heterogeneous group of neurological conditions, few of which have been classically described as bona fide hereditary illnesses (Huntington’s chorea, for instance. Most are considered to be either sporadic or to feature varying degrees of familial aggregation (parkinsonism and dystonia. In the late twentieth century, Mendelian monogenic mutations were found for movement disorders with a clear and consistent family history. Although important, these findings apply only to very rare forms of movement disorders. Already in the twenty-first century, and taking advantage of the modern developments in genetics and molecular biology, growing attention is being paid to the complex genetics of movement disorders. The search for risk genetic variants (polymorphisms in large cohorts and the identification of different risk variants across different populations and ethnic groups are under way, with the most relevant findings to date corresponding to recent genome wide association studies in Parkinson’s disease. These new approaches focusing on risk variants may enable the design of screening tests for early or even preclinical disease, and the identification of likely therapeutic targets.Keywords: genetics, movement disorders, Parkinson’s disease, parkinsonism, dystonia

  9. Investigation on defects in Mg and Al alloys under dynamic loading by the small-angle scattering method

    International Nuclear Information System (INIS)

    Xia, Q.Z.; Chen, B.; Lebedev, V.T.; Lebedev, V.M.

    2006-01-01

    Defects inherent to metals and alloys, such as low-dimensional (dislocations), surface (borders of crystalline grains, interfaces, microcracks) and globular (precipitates, voids), are strongly influenced by mechanical treatment, especially dynamic. The dynamic treatment effects remain poorly investigated at the nanoscale level even in widely used materials, even those applications that need knowledge of structure transformation under loading. Our experiments were focused on the mechanisms of defects generation by dynamic loading as dependent on deformation rate. To investigate the nature of defects and their evolution in Al-base and Mg-base alloys under dynamic loading, we applied small-angle neutron scattering (SANS) in the range of momentum transfer q∼0.03-0.8 nm -1 corresponding to the spatial scale R∼2π/q∼10-200 nm of various defects. SANS studies before and after dynamic treatment with a moderate initial velocity of deformation (∼10-20 m/s) showed that the SANS pattern changed significantly for the Mg-base alloy but only slightly for the Al-base alloy. As we found in the Mg-base alloy, the number and form of defects after loading differ strongly from the initial ones due to a large number of new defects in the Mg-base sample

  10. Defect production in silica glasses under gamma-irradiation at the quenched nuclear reactor

    International Nuclear Information System (INIS)

    Mussaeva, M.A.; Kalanov, M.U.; Ibragimova, E.M.; Sandalov, V.N.; Muminov, M.L.

    2004-01-01

    Full text: Radiation defect production in oxides is highly interesting for atom and solar energy, and also for burying nuclear waste. Combine effect of neutron and gamma-radiation on materials was studied extensively and only neutrons are believed to displace atoms, although 60 Co-gamma quanta were proved to displace light anions (O, F) by inelastic mechanism. On the example of polished plates of pure fused quartz and barium-silica glasses containing nano-crystalline inclusions, and also nano-porous glass, the effect of gamma-radiation of the quenched reactor was studied in the energy range of 0.2-7 MeV. The time period was selected when practically constant current ∼10-20 nA is maintained in the ionizing chamber, corresponding to the average gamma-flux of 15-30 Gy/s. Optical absorption and photoluminescence spectra and also structure of the grasses were studied. It turned out, that the charged oxygen vacancies accumulation rate is higher in Barium glass than in the pure one, because for SiO 2 with small Z the photoelectric effect is weak, while the Compton scattering and photonuclear reactions prevail, and for Barium - just the opposite. The radiation-induced growth of the crystalline precipitates was noticed in the both glasses, which before had been attributed to the elastic atom displacements by fast neutrons. The density of Ba-glass increases with irradiation. The efficiency of defect production by the gamma-component even of the quenched reactor turned out much higher than that under irradiation with 60 Co gamma-source of ∼1.25 MeV to the equivalent dose at the current dose rate of ∼ 7 Gy/s (and before at 45 Gy/s). A 100-times increase of the surface proton conductivity was discovered in the porous glasses under gamma-irradiation due to water vapor radiolysis on the pore surface. The irradiated porous glass is recommended as an active electrode in the hydrogen fuel element. The work was done under the grant F2.1.2 from Center of Science and Technology

  11. Identification of Genetic Defects in 33 Probands with Stargardt Disease by WES-Based Bioinformatics Gene Panel Analysis.

    Directory of Open Access Journals (Sweden)

    Wei Xin

    Full Text Available Stargardt disease (STGD is the most common hereditary macular degeneration in juveniles, with loss of central vision occurring in the first or second decade of life. The aim of this study is to identify the genetic defects in 33 probands with Stargardt disease. Clinical data and genomic DNA were collected from 33 probands from unrelated families with STGD. Variants in coding genes were initially screened by whole exome sequencing. Candidate variants were selected from all known genes associated with hereditary retinal dystrophy and then confirmed by Sanger sequencing. Putative pathogenic variants were further validated in available family members and controls. Potential pathogenic mutations were identified in 19 of the 33 probands (57.6%. These mutations were all present in ABCA4, but not in the other four STGD-associated genes or in genes responsible for other retinal dystrophies. Of the 19 probands, ABCA4 mutations were homozygous in one proband and compound heterozygous in 18 probands, involving 28 variants (13 novel and 15 known. Analysis of normal controls and available family members in 12 of the 19 families further support the pathogenicity of these variants. Clinical manifestation of all probands met the diagnostic criteria of STGD. This study provides an overview of a genetic basis for STGD in Chinese patients. Mutations in ABCA4 are the most common cause of STGD in this cohort. Genetic defects in approximately 42.4% of STGD patients await identification in future studies.

  12. Phenomenology and Numerical Analysis of Relaxation Properties and Failure of Materials with Defects under Dynamic Loading

    National Research Council Canada - National Science Library

    Naimark, Oleg

    2002-01-01

    .... Statistical approach allowed the definition of nonlinearity of thermodynamic potential and the description of plastic instability and damage localization as the generation of collective modes in defects ensemble...

  13. Defects of diamond single crystal grown under high temperature and high pressure

    Energy Technology Data Exchange (ETDEWEB)

    Su, Qingcai, E-mail: suqc@sdu.edu.cn [Key Laboratory of Liquid Structure and Heredity of Materials (Ministry of Education), Shandong University, Jinan, P. R. China, 250061 (China); School of Materials Science and Engineering, Shandong University, Jinan, P. R. China, 250061 (China); Shandong Engineering Research Center for Superhard Materials, Zoucheng, P. R. China 273500 (China); Zhang, Jianhua [School of Mechanical Engineering, Shandong University, Jinan, P. R. China, 250061 (China); Li, Musen [Key Laboratory of Liquid Structure and Heredity of Materials (Ministry of Education), Shandong University, Jinan, P. R. China, 250061 (China); School of Materials Science and Engineering, Shandong University, Jinan, P. R. China, 250061 (China); Shandong Engineering Research Center for Superhard Materials, Zoucheng, P. R. China 273500 (China)

    2013-11-01

    The diamond single crystal, synthesized with Fe–Ni–C–B system of catalyst under high temperature and high pressure, had been observed by field emission scanning electron microscope and transmission electron microscope. The presence of a cellular structure suggested that the diamond grew from melted catalyst solution and there existed a zone of component supercooling zone in front of the solid–liquid interface. The main impurities in the diamond crystal was (FeNi){sub 23}C{sub 6}. The triangle screw pit revealed on the (111) plane was generated by the screw dislocation meeting the diamond (111) plane at the points of emergence of dislocations. A narrow twin plane was formed between the two (111) plane. - Highlights: • High pressure, high temperature synthesis of diamond single crystal. • Fe–Ni–C–B used as catalyst, graphite as carbon source. • The main impurity in the diamond crystal was (FeNi){sub 23}C{sub 6}. • Surface defects arose from screw dislocations and stacking faults.

  14. An ultrastructural and immunocytochemical study of a rare genetic sperm tail defect that causes infertility in humans.

    Science.gov (United States)

    Baccetti, Baccio; Bruni, Emanuele; Gambera, Laura; Moretti, Elena; Piomboni, Paola

    2004-08-01

    To characterize and describe the ontogenesis of a rare flagellar defect affecting the whole sperm population of a sterile man. Case report. Regional referral center for male infertility in Siena, Italy. A 28-year-old man with severe asthenozoospermia. Physical and hormonal assays, semen analysis, and testicular biopsy. Semen samples and testicular biopsies were analyzed by light and transmission electron microscopy; immunocytochemical study with anti-beta-tubulin and anti-AKAP 82 antibodies was performed to detect the presence and distribution of proteins. Ultrastructural analysis of ejaculated spermatozoa and testicular biopsy revealed absence of the fibrous sheath in the principal-piece region of the tail. Fibrous sheath-like structures were observed in cytoplasmic residues and residual bodies released by spermatids in the seminiferous epithelium. Other anomalies observed were supplementary axonemes and mitochondrial helix elongation. These features were confirmed by immunocytochemical staining. This rare sperm tail defect, characterized by absence of the fibrous sheath, presence of supplementary axonemes, and an abnormally elongated midpiece, originates in the seminiferous tubules during spermiogenesis, as detected in testicular biopsy sections. These defects occur in the whole sperm population, and therefore a genetic origin could be suggested.

  15. Complex genetics of glaucoma: defects in CYP1B1, and not MYOC ...

    Indian Academy of Sciences (India)

    with matched age and ethnicity. Analysis of the family mem- bers reveal that proband's younger sister, ... dence that PCG could be caused by MYOC mutations (Kaur et al. 2005). All these studies point to the fact that although ... primary congenital glaucoma (PCG); CYP1B1; MYOC; human genetics. Journal of Genetics, Vol.

  16. Nonhomologous recombination between defective poliovirus and coxsackievirus genomes suggests a new model of genetic plasticity for picornaviruses.

    Science.gov (United States)

    Holmblat, Barbara; Jégouic, Sophie; Muslin, Claire; Blondel, Bruno; Joffret, Marie-Line; Delpeyroux, Francis

    2014-08-05

    Most of the circulating vaccine-derived polioviruses (cVDPVs) implicated in poliomyelitis outbreaks in Madagascar have been shown to be recombinants between the type 2 poliovirus (PV) strain of the oral polio vaccine (Sabin 2) and another species C human enterovirus (HEV-C), such as type 17 coxsackie A virus (CA17) in particular. We studied intertypic genetic exchanges between PV and non-PV HEV-C by developing a recombination model, making it possible to rescue defective type 2 PV RNA genomes with a short deletion at the 3' end by the cotransfection of cells with defective or infectious CA17 RNAs. We isolated over 200 different PV/CA17 recombinants, using murine cells expressing the human PV receptor (PVR) and selecting viruses with PV capsids. We found some homologous (H) recombinants and, mostly, nonhomologous (NH) recombinants presenting duplications of parental sequences preferentially located in the regions encoding proteins 2A, 2B, and 3A. Short duplications appeared to be stable, whereas longer duplications were excised during passaging in cultured cells or after multiplication in PVR-transgenic mice, generating H recombinants with diverse sites of recombination. This suggests that NH recombination events may be a transient, intermediate step in the generation and selection of the fittest H recombinants. In addition to the classical copy-choice mechanism of recombination thought to generate mostly H recombinants, there may also be a modular mechanism of recombination, involving NH recombinant precursors, shaping the genomes of recombinant enteroviruses and other picornaviruses. Importance: The multiplication of circulating vaccine-derived polioviruses (cVDPVs) in poorly immunized human populations can render these viruses pathogenic, causing poliomyelitis outbreaks. Most cVDPVs are intertypic recombinants between a poliovirus (PV) strain and another human enterovirus, such as type 17 coxsackie A viruses (CA17). For further studies of the genetic exchanges

  17. Genetic polymorphisms of the TYMS gene are not associated with congenital cardiac septal defects in a Han Chinese population.

    Science.gov (United States)

    Zhao, Jian-Yuan; Sun, Jing-Wei; Gu, Zhuo-Ya; Wang, Jue; Wang, Er-Li; Yang, Xue-Yan; Qiao, Bin; Duan, Wen-Yuan; Huang, Guo-Ying; Wang, Hong-Yan

    2012-01-01

    Clinical research indicates that periconceptional administration of folic acid can reduce the occurrence of congenital cardiac septal defects (CCSDs). The vital roles of folate exhibits in three ways: the unique methyl donor for DNA expression regulation, the de novo biosynthesis of purine and pyrimidine for DNA construction, and the serum homocysteine removal. Thymidylate synthase (TYMS) is the solo catalysis enzyme for the de novo synthesis of dTMP, which is the essential precursor of DNA biosynthesis and repair process. To examine the role of TYMS in Congenital Cardiac Septal Defects (CCSDs) risk, we investigated whether genetic polymorphisms in the TYMS gene associated with the CCSDs in a Han Chinese population. Polymorphisms in the noncoding region of TYMS were identified via direct sequencing in 32 unrelated individuals composed of half CCSDs and half control subjects. Nine SNPs and two insertion/deletion polymorphisms were genotyped from two independent case-control studies involving a total of 529 CCSDs patients and 876 healthy control participants. The associations were examined by both single polymorphism and haplotype tests using logistic regression. We found that TYMS polymorphisms were not related to the altered CCSDs risk, and even to the changed risk of VSDs subgroup, when tested in both studied groups separately or in combination. In the haplotype analysis, there were no haplotypes significantly associated with risks for CCSDs either. Our results show no association between common genetic polymorphisms of the regulatory region of the TYMS gene and CCSDs in the Han Chinese population.

  18. Human syndromes with congenital patellar anomalies and the underlying gene defects.

    NARCIS (Netherlands)

    Bongers, E.M.H.F.; Kampen, A. van; Bokhoven, J.H.L.M. van; Knoers, N.V.A.M.

    2005-01-01

    Genetic disorders characterized by congenital patellar aplasia or hypoplasia belong to a clinically diverse and genetically heterogeneous group of lower limb malformations. Patella development involves different molecular and cellular mechanisms regulating dorso-ventral patterning, cartilage and

  19. Effect of vacancy defect on electrical properties of chiral single-walled carbon nanotube under external electrical field

    International Nuclear Information System (INIS)

    Luo Yu-Pin; Tien Li-Gan; Tsai Chuen-Horng; Lee Ming-Hsien; Li Feng-Yin

    2011-01-01

    Ab initio calculations demonstrated that the energy gap modulation of a chiral carbon nanotube with mono-vacancy defect can be achieved by applying a transverse electric field. The bandstructure of this defective carbon nanotube varying due to the external electric field is distinctly different from those of the perfect nanotube and defective zigzag nanotube. This variation in bandstructure strongly depends on not only the chirality of the nanotube and also the applied direction of the transverse electric field. A mechanism is proposed to explain the response of the local energy gap between the valence band maximum state and the local gap state under external electric field. Several potential applications of these phenomena are discussed. (condensed matter: electronic structure, electrical, magnetic, and optical properties)

  20. Preimplantation genetic diagnosis and rational choice under risk or uncertainty.

    Science.gov (United States)

    Zuradzki, Tomasz

    2014-11-01

    In this paper I present an argument in favour of a parental duty to use preimplantation genetic diagnosis (PGD). I argue that if embryos created in vitro were able to decide for themselves in a rational manner, they would sometimes choose PGD as a method of selection. Couples, therefore, should respect their hypothetical choices on a principle similar to that of patient autonomy. My thesis shows that no matter which moral doctrine couples subscribe to, they ought to conduct the PGD procedure in the situations when it is impossible to implant all of the created embryos and if there is a significant risk for giving birth to a child with a serious condition. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  1. Genetic Mutations, Birth Lengths, Weights and Head Circumferences of Children with IGF-I Receptor Defects. Comparison with other Congenital Defects in the GH/IGF-I axis.

    Science.gov (United States)

    Essakow, Jenna Lee; Lauterpacht, Aharon; Lilos, Pearl; Kauli, Rivka; Laron, Zvi

    2016-09-01

    In recent years more and more genetic defects along the GHRH-GH-IGF-I axis have been reported. Mutations of the IGF-I receptor (R) are a rare abnormality of whom only the heterozygote progenies survive. To summarize, from the literature, data on birth length, weight and head circumference of neonates with IGF-I-R mutations, and to correlate the data with that of other types of mutations in the GH/IGF-I axis. Sixty seven neonates from 24 published articles were included and forty seven different mutations of the IGF-I (R) located on chromosome 15 have been identified. Mean (±SD) birth length (BL), available for 26, (10 M, 16F) neonates with a gestational age of 34-41weeks, was 44.2±4cm; one was premature (30cm at 31 weeks). There was a significant correlation between birth length and gestational age (GA) r=0.71 (p>.001). Mean birth weight (BW) of 41 neonates (18M, 23F) was 2388±743gr. Two premature neonates weighed 650gr and 950gr respectively. The BW correlated significantly with gestational age, (males: r=0.68; p=0.007, females: r=0.49; p=0.024). The BMI of 25 neonates ranged from 6 to 13. In 22 records marked microcephaly was ascertained or stated. Nine of 16 mothers were short (133 -148cm), m±SD = 150.5±7.3cm. Copyright© of YS Medical Media ltd.

  2. Genetic Syndromes Associated with Congenital Cardiac Defects and Ophthalmologic Changes - Systematization for Diagnosis in the Clinical Practice

    Directory of Open Access Journals (Sweden)

    Priscila H. A. Oliveira

    Full Text Available Abstract Background: Numerous genetic syndromes associated with heart disease and ocular manifestations have been described. However, a compilation and a summarization of these syndromes for better consultation and comparison have not been performed yet. Objective: The objective of this work is to systematize available evidence in the literature on different syndromes that may cause congenital heart diseases associated with ocular changes, focusing on the types of anatomical and functional changes. Method: A systematic search was performed on Medline electronic databases (PubMed, Embase, Cochrane, Lilacs of articles published until January 2016. Eligibility criteria were case reports or review articles that evaluated the association of ophthalmic and cardiac abnormalities in genetic syndrome patients younger than 18 years. Results: The most frequent genetic syndromes were: Down Syndrome, Velo-cardio-facial / DiGeorge Syndrome, Charge Syndrome and Noonan Syndrome. The most associated cardiac malformations with ocular findings were interatrial communication (77.4%, interventricular communication (51.6%, patent ductus arteriosus (35.4%, pulmonary artery stenosis (25.8% and tetralogy of Fallot (22.5%. Conclusion: Due to their clinical variability, congenital cardiac malformations may progress asymptomatically to heart defects associated with high morbidity and mortality. For this reason, the identification of extra-cardiac characteristics that may somehow contribute to the diagnosis of the disease or reveal its severity is of great relevance.

  3. Analysis of displacement damage and defect production under cascade damage conditions

    DEFF Research Database (Denmark)

    Zinkle, S.J.; Singh, B.N.

    1993-01-01

    The production, annihilation, and accumulation of point defects in metals during displacive irradiation is dependent on a variety of physical conditions, including the nature and energy of the projectile particles and the irradiation temperature. This paper briefly reviews the evolution of the de......The production, annihilation, and accumulation of point defects in metals during displacive irradiation is dependent on a variety of physical conditions, including the nature and energy of the projectile particles and the irradiation temperature. This paper briefly reviews the evolution...

  4. Crack initiation and potential hot-spot formation around a cylindrical defect under dynamic compression

    Science.gov (United States)

    Ma, Xiao; Li, Xinguo; Zheng, Xianxu; Li, Kewu; Hu, Qiushi; Li, Jianling

    2017-11-01

    In recent decades, the hot-spot theory of condensed-phase explosives has been a compelling focus of scientific investigation attracting many researchers. The defect in the polymeric binder of the polymer-bonded explosive is called the intergranular defect. In this study, the real polymeric binder was substituted by poly(methyl methacrylate) (PMMA) as it is transparent and has similar thermodynamic properties to some binders. A set of modified split Hopkinson pressure bars equipped with a time-resolved shadowgraph was used to study the process of crack initiation and potential hot-spot formation around a cylindrical defect in PMMA. The new and significant phenomenon that the opening-mode crack emerged earlier than the shearing-mode crack from the cylindrical defect has been published for the first time in this paper. Furthermore, a two-dimensional numerical simulation was performed to show the evolution of both the stress field and the temperature field. The simulation results were in good agreement with the experiment. Finally, the law of potential hot-spot formation is discussed in detail.

  5. Deep level defects in dilute GaAsBi alloys grown under intense UV illumination

    Energy Technology Data Exchange (ETDEWEB)

    Mooney, P. M.; Tarun, Marianne; Beaton, D. A.; Mascarenhas, A.; Alberi, K.

    2016-07-21

    Dilute GaAs1-xBix alloys exhibiting narrow band edge photoluminescence (PL) were recently grown by molecular beam epitaxy (MBE) with the growth surface illuminated by intense UV radiation. To investigate whether the improved optical quality of these films results from a reduction in the concentration of deep level defects, p+/n and n+/p junction diodes were fabricated on both the illuminated and dark areas of several samples. Deep Level Transient Spectroscopy (DLTS) measurements show that the illuminated and dark areas of both the n- and p-type GaAs1-xBix epi-layers have similar concentrations of near mid-gap electron and hole traps, in the 1015 cm-3 range. Thus the improved PL spectra cannot be explained by a reduction in non-radiative recombination at deep level defects. We note that carrier freeze-out above 35 K is significantly reduced in the illuminated areas of the p-type GaAs1-xBix layers compared to the dark areas, allowing the first DLTS measurements of defect energy levels close to the valence band edge. These defect levels may account for differences in the PL spectra from the illuminated and dark areas of un-doped layers with a similar Bi fraction.

  6. Integrated Supply Chain Cooperative Inventory Model with Payment Period Being Dependent on Purchasing Price under Defective Rate Condition

    Directory of Open Access Journals (Sweden)

    Ming-Feng Yang

    2015-01-01

    Full Text Available In most commercial transactions, the buyer and vendor may usually agree to postpone payment deadline. During such delayed period, the buyer is entitled to keep the products without having to pay the sale price. However, the vendor usually hopes to receive full payment as soon as possible, especially when the transaction involves valuable items; yet, the buyer would offer a higher purchasing price in exchange of a longer postponement. Therefore, we assumed such permissible delayed period is dependent on the purchasing price. As for the manufacturing side, defective products are inevitable from time to time, and not all of those defective products can be repaired. Hence, we would like to add defective production and repair rate to our proposed model and discuss how these factors may affect profits. In addition, holding cost, ordering cost, and transportation cost will also be considered as we develop the integrated inventory model with price-dependent payment period under the possible condition of defective products. We would like to find the maximum of the joint expected total profit for our model and come up with a suitable inventory policy accordingly. In the end, we have also provided a numerical example to clearly illustrate possible solutions.

  7. Feasibility of percutaneous closure of atrial septal defects in adults under transthoracic echocardiography guidance using the Figulla atrial septal defect occluder device.

    Science.gov (United States)

    Ali, Mahmoud; Salah El-Din, Hesham; Bakhoum, Sameh; El-Sisi, Amal; Mahmood, Kareem; Farouk, Heba; Kandil, Hossam

    2018-01-01

    Closure of atrial septal defect (ASD) among adults under transthoracic echocardiography (TTE) guidance using devices other than the Amplatzer Septal Occluder has not been extensively tested. Assessment of the safety and efficiency of secundum ASD closure using the Occlutech Figulla ASD Occluder under TTE guidance in adult patients with hemodynamically significant secundum ASD. Twenty patients (mean age, 32.9 ± 9.7, 75% of them females) were enrolled in the study. All patients underwent TTE and transoesophageal echocardiography (TEE) to assess the characteristics of the ASD prior to percutaneous closure. Procedures were performed using the Figulla Occluder device under both fluoroscopic and TTE guidance. Follow-up clinical and TTE examinations were done at 1, 3, and 6 months following the procedure. TTE estimated mean ASD size was 21.7 ± 7.3 mm with adequate rims except for the aortic rim (deficient in one third of cases). Mean device size was 28.1 ± 8.6 mm with mean procedure and fluoroscopic times of 46.2 ± 16.4 and 15.7 ± 5.4 minutes respectively. ASD was successfully closed in all patients. Two patients showed a small residual shunt immediately after the device placement that disappeared by the end of the 2nd followup TTE examination. Transient complications were detected in 2 patients. All patients were asymptomatic during the follow-up period. Transcatheter closure of secundum ASD in adults under TTE guidance using the Occlutech Figulla ASD occluder device is safe and effective when performed in a tertiary center and by expert echocardiographers and interventional cardiologists.

  8. Trafficking defects and loss of ligand binding are the underlying causes of all reported DDR2 missense mutations found in SMED-SL patients.

    Science.gov (United States)

    Ali, Bassam R; Xu, Huifang; Akawi, Nadia A; John, Anne; Karuvantevida, Noushad S; Langer, Ruth; Al-Gazali, Lihadh; Leitinger, Birgit

    2010-06-01

    Spondylo-meta-epiphyseal dysplasia (SMED) with short limbs and abnormal calcifications (SMED-SL) is a rare, autosomal recessive human growth disorder, characterized by disproportionate short stature, short limbs, short broad fingers, abnormal metaphyses and epiphyses, platyspondyly and premature calcifications. Recently, three missense mutations and one splice-site mutation in the DDR2 gene were identified as causative genetic defects for SMED-SL, but the underlying cellular and biochemical mechanisms were not explored. Here we report a novel DDR2 missense mutation, c.337G>A (p.E113K), that causes SMED-SL in two siblings in the United Arab Emirates. Another DDR2 missense mutation, c.2254C>T (p.R752C), matching one of the previously reported SMED-SL mutations, was found in a second affected family. DDR2 is a plasma membrane receptor tyrosine kinase that functions as a collagen receptor. We expressed DDR2 constructs with the identified point mutations in human cell lines and evaluated their localization and functional properties. We found that all SMED-SL missense mutants were defective in collagen-induced receptor activation and that the three previously reported mutants (p.T713I, p.I726R and p.R752C) were retained in the endoplasmic reticulum. The novel mutant (p.E113K), in contrast, trafficked normally, like wild-type DDR2, but failed to bind collagen. This finding is in agreement with our recent structural data identifying Glu113 as an important amino acid in the DDR2 ligand-binding site. Our data thus demonstrate that SMED-SL can result from at least two different loss-of-function mechanisms: namely defects in DDR2 targeting to the plasma membrane or the loss of its ligand-binding activity.

  9. Tunneling recombination luminescence under excitation of PbWO4:Mo crystals in the defect-related absorption region

    International Nuclear Information System (INIS)

    Fabeni, P.; Krasnikov, A.; Kaerner, T.; Laguta, V.V.; Nikl, M.; Pazzi, G.P.; Zazubovich, S.

    2009-01-01

    Time-resolved emission and excitation spectra and luminescence decay kinetics were studied at 150-300 K for the green emission of PbWO 4 :Mo crystals. It was found that the slow (μs-ms) decay component observed under excitation in the defect-related absorption region (around 3.8-3.9 eV) arises from the G(II) emission which appears at the tunneling recombination of optically created electron and hole centers. The study of the emission decay kinetics at different temperatures and excitation intensities allowed concluding that both the monomolecular and the bimolecular tunneling recombination process can be stimulated in the mentioned energy range. The monomolecular process takes place in the isolated spatially correlated pairs of electron and hole centers produced without release of electrons into the conduction band. The bimolecular process takes place in the pairs of randomly distributed centers created at the trapping of free electrons from the conduction band. The formation of electron centers under irradiation in the defect-related absorption region was investigated by the electron spin resonance (ESR) and thermally stimulated luminescence (TSL) methods. The possibility of various photo-thermally stimulated defects creation processes, which take place with and without release of free electrons into the conduction band, was confirmed.

  10. A Reverse Genetics Approach for the Design of Methyltransferase-Defective Live Attenuated Avian Metapneumovirus Vaccines.

    Science.gov (United States)

    Zhang, Yu; Sun, Jing; Wei, Yongwei; Li, Jianrong

    2016-01-01

    Avian metapneumovirus (aMPV), also known as avian pneumovirus or turkey rhinotracheitis virus, is the causative agent of turkey rhinotracheitis and is associated with swollen head syndrome in chickens. aMPV belongs to the family Paramyxoviridae which includes many important human pathogens such as human respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and human parainfluenza virus type 3 (PIV3). The family also includes highly lethal emerging pathogens such as Nipah virus and Hendra virus, as well as agriculturally important viruses such as Newcastle disease virus (NDV). For many of these viruses, there is no effective vaccine. Here, we describe a reverse genetics approach to develop live attenuated aMPV vaccines by inhibiting the viral mRNA cap methyltransferase. The viral mRNA cap methyltransferase is an excellent target for the attenuation of paramyxoviruses because it plays essential roles in mRNA stability, efficient viral protein translation and innate immunity. We have described in detail the materials and methods used to generate recombinant aMPVs that lack viral mRNA cap methyltransferase activity. We have also provided methods to evaluate the genetic stability, pathogenesis, and immunogenicity of live aMPV vaccine candidates in turkeys.

  11. A Realistic Model Under Which the Genetic Code is Optimal

    NARCIS (Netherlands)

    Buhrman, Harry; van der Gulik, Peter T. S.; Klau, Gunnar W.; Schaffner, Christian; Speijer, Dave; Stougie, Leen

    2013-01-01

    The genetic code has a high level of error robustness. Using values of hydrophobicity scales as a proxy for amino acid character, and the mean square measure as a function quantifying error robustness, a value can be obtained for a genetic code which reflects the error robustness of that code. By

  12. Coeliac disease : investigation of the genetic factors underlying coeliac disease

    NARCIS (Netherlands)

    Belzen, M.J. (Martine Juliana) van

    2003-01-01

    Coeliac disease is a common food intolerance with a complex genetic aetiology. It is caused by ingestion of gluten peptides from wheat and related proteins from barley and rye in genetically susceptible individuals. The disease affects the small intestine and leads to abnormalities ranging from the

  13. Genetic Circuit Performance under Conditions Relevant for Industrial Bioreactors

    NARCIS (Netherlands)

    Moser, Felix; Broers, Nicolette J.; Hartmans, Sybe; Tamsir, Alvin; Kerkman, Richard; Roubos, Johannes A.; Bovenberg, Roel; Voigt, Christopher A.

    2012-01-01

    Synthetic genetic programs promise to enable novel applications in industrial processes. For such applications, the genetic circuits that compose programs will require fidelity in varying and complex environments. In this work, we report the performance of two synthetic circuits in Escherichia coli

  14. Worms under stress: unravelling genetic complex traits through perturbation

    NARCIS (Netherlands)

    Rodriguez Sanchez, M.

    2014-01-01

    The genetic architecture of an organism could be considered ‘the most amazing piece of engineering’ existing in nature. Looking from a certain distance, the genetic complexity of an organism could be described as an immense jigsaw puzzle. As in a real jigsaw, the connection between two pieces

  15. A Realistic Model under which the Genetic Code is Optimal

    NARCIS (Netherlands)

    Buhrman, H.; van der Gulik, P.T.S.; Klau, G.W.; Schaffner, C.; Speijer, D.; Stougie, L.

    2013-01-01

    The genetic code has a high level of error robustness. Using values of hydrophobicity scales as a proxy for amino acid character, and the mean square measure as a function quantifying error robustness, a value can be obtained for a genetic code which reflects the error robustness of that code. By

  16. Defected and Functionalized Germanene based Nanosensors under Sulfur Comprising Gas Exposure

    KAUST Repository

    Hussain, Tanveer

    2018-03-27

    Efficient sensing of sulfur containing toxic gases like H2S and SO2 is of outmost importance due to the adverse effects of these noxious gases. Absence of an efficient 2D based nanosensors capable of anchoring H2S and SO2 with feasible binding and an apparent variation in electronic properties upon the exposure of gas molecules has motivated us to explore the promise of germanene nano sheet (Ge-NS) for this purpose. In the present study, we have performed a comprehensive computational investigation by means of DFT based first principles calculations to envisage the structural, electronic and gas sensing properties of pristine, defected and metal substituted Ge-NS. Our initial screening has revealed that although interaction of SO2 on pristine Ge-NS is within the desirable range, however H2S binding is falling below the required values to guarantee an effective sensing. To improve the binding characteristics, we have considered the interactions between H2S and SO2 with defected and metal substituted Ge-NS. The systematic removals of Ge atoms from a reasonably large super cell lead to mono-vacancy, di-vacancies and tri-vacancies in Ge-NS. Similarly, different transition metals like As, Co, Cu, Fe, Ga, Ge Ni and Zn have been substituted into the monolayer to realize substituted Ge-NS. Our van der Waals corrected DFT calculations have concluded that the vacancy and substitution defects not only improve the binding characteristics but also enhance the sensing propensity of both H2S and SO2. The total and projected density of states show significant variations in electronic properties of pristine and defected Ge-NS before and after the exposure to the gases, which are essential in constituting a signal to be detected by the external circuit of the sensor. We strongly believe that out present work would not only advance the knowledge towards the application of Ge-NS based sensing, but also provide the motivation for the synthesis of an efficient nanosensors for H2S and SO

  17. Nonhomologous Recombination between Defective Poliovirus and Coxsackievirus Genomes Suggests a New Model of Genetic Plasticity for Picornaviruses

    Science.gov (United States)

    Holmblat, Barbara; Jégouic, Sophie; Muslin, Claire; Blondel, Bruno; Joffret, Marie-Line

    2014-01-01

    ABSTRACT Most of the circulating vaccine-derived polioviruses (cVDPVs) implicated in poliomyelitis outbreaks in Madagascar have been shown to be recombinants between the type 2 poliovirus (PV) strain of the oral polio vaccine (Sabin 2) and another species C human enterovirus (HEV-C), such as type 17 coxsackie A virus (CA17) in particular. We studied intertypic genetic exchanges between PV and non-PV HEV-C by developing a recombination model, making it possible to rescue defective type 2 PV RNA genomes with a short deletion at the 3′ end by the cotransfection of cells with defective or infectious CA17 RNAs. We isolated over 200 different PV/CA17 recombinants, using murine cells expressing the human PV receptor (PVR) and selecting viruses with PV capsids. We found some homologous (H) recombinants and, mostly, nonhomologous (NH) recombinants presenting duplications of parental sequences preferentially located in the regions encoding proteins 2A, 2B, and 3A. Short duplications appeared to be stable, whereas longer duplications were excised during passaging in cultured cells or after multiplication in PVR-transgenic mice, generating H recombinants with diverse sites of recombination. This suggests that NH recombination events may be a transient, intermediate step in the generation and selection of the fittest H recombinants. In addition to the classical copy-choice mechanism of recombination thought to generate mostly H recombinants, there may also be a modular mechanism of recombination, involving NH recombinant precursors, shaping the genomes of recombinant enteroviruses and other picornaviruses. PMID:25096874

  18. BMP2 genetically engineered MSCs and EPCs promote vascularized bone regeneration in rat critical-sized calvarial bone defects.

    Directory of Open Access Journals (Sweden)

    Xiaoning He

    Full Text Available Current clinical therapies for critical-sized bone defects (CSBDs remain far from ideal. Previous studies have demonstrated that engineering bone tissue using mesenchymal stem cells (MSCs is feasible. However, this approach is not effective for CSBDs due to inadequate vascularization. In our previous study, we have developed an injectable and porous nano calcium sulfate/alginate (nCS/A scaffold and demonstrated that nCS/A composition is biocompatible and has proper biodegradability for bone regeneration. Here, we hypothesized that the combination of an injectable and porous nCS/A with bone morphogenetic protein 2 (BMP2 gene-modified MSCs and endothelial progenitor cells (EPCs could significantly enhance vascularized bone regeneration. Our results demonstrated that delivery of MSCs and EPCs with the injectable nCS/A scaffold did not affect cell viability. Moreover, co-culture of BMP2 gene-modified MSCs and EPCs dramatically increased osteoblast differentiation of MSCs and endothelial differentiation of EPCs in vitro. We further tested the multifunctional bone reconstruction system consisting of an injectable and porous nCS/A scaffold (mimicking the nano-calcium matrix of bone and BMP2 genetically-engineered MSCs and EPCs in a rat critical-sized (8 mm caviarial bone defect model. Our in vivo results showed that, compared to the groups of nCS/A, nCS/A+MSCs, nCS/A+MSCs+EPCs and nCS/A+BMP2 gene-modified MSCs, the combination of BMP2 gene -modified MSCs and EPCs in nCS/A dramatically increased the new bone and vascular formation. These results demonstrated that EPCs increase new vascular growth, and that BMP2 gene modification for MSCs and EPCs dramatically promotes bone regeneration. This system could ultimately enable clinicians to better reconstruct the craniofacial bone and avoid donor site morbidity for CSBDs.

  19. Massively parallel sequencing and targeted exomes in familial kidney disease can diagnose underlying genetic disorders.

    Science.gov (United States)

    Mallett, Andrew J; McCarthy, Hugh J; Ho, Gladys; Holman, Katherine; Farnsworth, Elizabeth; Patel, Chirag; Fletcher, Jeffery T; Mallawaarachchi, Amali; Quinlan, Catherine; Bennetts, Bruce; Alexander, Stephen I

    2017-12-01

    Inherited kidney disease encompasses a broad range of disorders, with both multiple genes contributing to specific phenotypes and single gene defects having multiple clinical presentations. Advances in sequencing capacity may allow a genetic diagnosis for familial renal disease, by testing the increasing number of known causative genes. However, there has been limited translation of research findings of causative genes into clinical settings. Here, we report the results of a national accredited diagnostic genetic service for familial renal disease. An expert multidisciplinary team developed a targeted exomic sequencing approach with ten curated multigene panels (207 genes) and variant assessment individualized to the patient's phenotype. A genetic diagnosis (pathogenic genetic variant[s]) was identified in 58 of 135 families referred in two years. The genetic diagnosis rate was similar between families with a pediatric versus adult proband (46% vs 40%), although significant differences were found in certain panels such as atypical hemolytic uremic syndrome (88% vs 17%). High diagnostic rates were found for Alport syndrome (22 of 27) and tubular disorders (8 of 10), whereas the monogenic diagnostic rate for congenital anomalies of the kidney and urinary tract was one of 13. Quality reporting was aided by a strong clinical renal and genetic multidisciplinary committee review. Importantly, for a diagnostic service, few variants of uncertain significance were found with this targeted, phenotype-based approach. Thus, use of targeted massively parallel sequencing approaches in inherited kidney disease has a significant capacity to diagnose the underlying genetic disorder across most renal phenotypes. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  20. Coupled electronic and atomic effects on defect evolution in silicon carbide under ion irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yanwen [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Xue, Haizhou [Univ. of Tennessee, Knoxville, TN (United States); Zarkadoula, Eva [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Sachan, Ritesh [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Army Research Office, Triangle Park, NC (United States); Ostrouchov, Christopher [Univ. of Tennessee, Knoxville, TN (United States); Liu, Peng [Univ. of Tennessee, Knoxville, TN (United States); Shandong Univ., Jinan (China); Wang, Xue -lin [Shandong Univ., Jinan (China); Zhang, Shuo [Lanzhou Univ., Gansu Province (China); Wang, Tie Shan [Lanzhou Univ., Gansu Province (China); Weber, William J. [Univ. of Tennessee, Knoxville, TN (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2017-10-16

    Understanding energy dissipation processes in electronic/atomic subsystems and subsequent non-equilibrium defect evolution is a long-standing challenge in materials science. In the intermediate energy regime, energetic particles simultaneously deposit a significant amount of energy to both electronic and atomic subsystems of silicon carbide (SiC). Here we show that defect evolution in SiC closely depends on the electronic-to-nuclear energy loss ratio (Se/Sn), nuclear stopping powers (dE/dxnucl), electronic stopping powers (dE/dxele), and the temporal and spatial coupling of electronic and atomic subsystem for energy dissipation. The integrated experiments and simulations reveal that: (1) increasing Se/Sn slows damage accumulation; (2) the transient temperatures during the ionization-induced thermal spike increase with dE/dxele, which causes efficient damage annealing along the ion trajectory; and (3) for more condensed displacement damage within the thermal spike, damage production is suppressed due to the coupled electronic and atomic dynamics. Ionization effects are expected to be more significant in materials with covalent/ionic bonding involving predominantly well-localized electrons. Here, insights into the complex electronic and atomic correlations may pave the way to better control and predict SiC response to extreme energy deposition

  1. Corrosion and coating defects on buried pipelines under CP: Excavations data collection and analysis

    Energy Technology Data Exchange (ETDEWEB)

    Karcher, Sebastien; Campaignolle, Xavier; Masson, Bernard; Meyer, Michel [Gaz de France Research and Development Division, 361 avenue du President Wilson, BP33 93211 Saint Denis La Plaine (France)

    2004-07-01

    Onshore gas transmission pipelines are conjointly protected against external corrosion by an organic coating and by cathodic protection (CP). Owing to particular defects or coating aging in the long term in ground, the protective efficiency of this dual system may be impaired. Consequently, external corrosion may develop and, eventually, threaten the integrity of the line if not detected and mitigated in time. To ensure continued protection of its lines against external corrosion, Gaz de France carries out, routinely, several maintenance and monitoring activities on the CP system. In addition, above ground surveys allow a better assessment of possible coating faults. However, it is necessary to continuously improve the reliability of the corrosion prediction to optimize the maintenance of pipelines. When indications and measurements from any mean of inspection (in-line inspection or above ground surveys) lead to suspect the presence of any significant metal defect, an excavation of the concerned pipe section is performed. At each excavation location, many parameters are collected to document the existing conditions of coating and steel. If sufficiently extended and reliable, this information may help to understand the root causes for development of corrosion. Eventually, thorough analysis of field data resulting either from inspection or from maintenance operations could lead to corrosion prediction. Since the volume of these data is large, reliability and consistency of information is absolutely required. Gaz de France has implemented a systematic data collection procedure on excavation sites, together with data analysis through a range of treatment methods. Data on more than 1400 excavations, pertaining to a set of different selected pipelines, have been collected in a single database. The later contains data such as pipelines characteristics, local cathodic protection parameters at the time of excavation, coating defect description if any, characterization of

  2. simEye: computer-based simulation of visual perception under various eye defects using Zernike polynomials

    OpenAIRE

    Fink, Wolfgang; Micol, Daniel

    2006-01-01

    We describe a computer eye model that allows for aspheric surfaces and a three-dimensional computer-based ray-tracing technique to simulate optical properties of the human eye and visual perception under various eye defects. Eye surfaces, such as the cornea, eye lens, and retina, are modeled or approximated by a set of Zernike polynomials that are fitted to input data for the respective surfaces. A ray-tracing procedure propagates light rays using Snell’s law of refraction from an input objec...

  3. Defect generation in electronic devices under plasma exposure: Plasma-induced damage

    Science.gov (United States)

    Eriguchi, Koji

    2017-06-01

    The increasing demand for higher performance of ULSI circuits requires aggressive shrinkage of device feature sizes in accordance with Moore’s law. Plasma processing plays an important role in achieving fine patterns with anisotropic features in metal-oxide-semiconductor field-effect transistors (MOSFETs). This article comprehensively addresses the negative aspect of plasma processing — plasma-induced damage (PID). PID naturally not only modifies the surface morphology of materials but also degrades the performance and reliability of MOSFETs as a result of defect generation in the materials. Three key mechanisms of PID, i.e., physical, electrical, and photon-irradiation interactions, are overviewed in terms of modeling, characterization techniques, and experimental evidence reported so far. In addition, some of the emerging topics — control of parameter variability in ULSI circuits caused by PID and recovery of PID — are discussed as future perspectives.

  4. Summary of problems associated with primary damage and secondary defect aggregation under CTR irradiation conditions

    International Nuclear Information System (INIS)

    Hayns, M.R.

    1982-01-01

    Some of the important new quantities which need experimental verification and characterization to further our understanding of the irradiation damage processes in materials in CTR environments were highlighted. We have particularly emphasized the need to thoroughly understand the available simulation experiment conditions so that a proper correlation with the, as yet unobtainable, CTR conditions can be made. We have only focused upon the primary stages of the damage process and the nucleation of secondary defects. This should in no way be taken as implying that our understanding of the more basic quantities, such as diffusion in complex alloys, surface energies, stacking fault-energies, dislocation bias values, trap nature and binding energies, and phase stability (not segregation) is anywhere near adequate and further work is needed here as well as in the rather more exotic fields discussed in the body of the paper

  5. Cellular and Molecular Defects Underlying Invasive Fungal Infections—Revelations from Endemic Mycoses

    Directory of Open Access Journals (Sweden)

    Pamela P. Lee

    2017-06-01

    Full Text Available The global burden of fungal diseases has been increasing, as a result of the expanding number of susceptible individuals including people living with human immunodeficiency virus (HIV, hematopoietic stem cell or organ transplant recipients, patients with malignancies or immunological conditions receiving immunosuppressive treatment, premature neonates, and the elderly. Opportunistic fungal pathogens such as Aspergillus, Candida, Cryptococcus, Rhizopus, and Pneumocystis jiroveci are distributed worldwide and constitute the majority of invasive fungal infections (IFIs. Dimorphic fungi such as Histoplasma capsulatum, Coccidioides spp., Paracoccidioides spp., Blastomyces dermatiditis, Sporothrix schenckii, Talaromyces (Penicillium marneffei, and Emmonsia spp. are geographically restricted to their respective habitats and cause endemic mycoses. Disseminated histoplasmosis, coccidioidomycosis, and T. marneffei infection are recognized as acquired immunodeficiency syndrome (AIDS-defining conditions, while the rest also cause high rate of morbidities and mortalities in patients with HIV infection and other immunocompromised conditions. In the past decade, a growing number of monogenic immunodeficiency disorders causing increased susceptibility to fungal infections have been discovered. In particular, defects of the IL-12/IFN-γ pathway and T-helper 17-mediated response are associated with increased susceptibility to endemic mycoses. In this review, we put together the various forms of endemic mycoses on the map and take a journey around the world to examine how cellular and molecular defects of the immune system predispose to invasive endemic fungal infections, including primary immunodeficiencies, individuals with autoantibodies against interferon-γ, and those receiving biologic response modifiers. Though rare, these conditions provide importance insights to host defense mechanisms against endemic fungi, which can only be appreciated in unique

  6. Cellular and Molecular Defects Underlying Invasive Fungal Infections—Revelations from Endemic Mycoses

    Science.gov (United States)

    Lee, Pamela P.; Lau, Yu-Lung

    2017-01-01

    The global burden of fungal diseases has been increasing, as a result of the expanding number of susceptible individuals including people living with human immunodeficiency virus (HIV), hematopoietic stem cell or organ transplant recipients, patients with malignancies or immunological conditions receiving immunosuppressive treatment, premature neonates, and the elderly. Opportunistic fungal pathogens such as Aspergillus, Candida, Cryptococcus, Rhizopus, and Pneumocystis jiroveci are distributed worldwide and constitute the majority of invasive fungal infections (IFIs). Dimorphic fungi such as Histoplasma capsulatum, Coccidioides spp., Paracoccidioides spp., Blastomyces dermatiditis, Sporothrix schenckii, Talaromyces (Penicillium) marneffei, and Emmonsia spp. are geographically restricted to their respective habitats and cause endemic mycoses. Disseminated histoplasmosis, coccidioidomycosis, and T. marneffei infection are recognized as acquired immunodeficiency syndrome (AIDS)-defining conditions, while the rest also cause high rate of morbidities and mortalities in patients with HIV infection and other immunocompromised conditions. In the past decade, a growing number of monogenic immunodeficiency disorders causing increased susceptibility to fungal infections have been discovered. In particular, defects of the IL-12/IFN-γ pathway and T-helper 17-mediated response are associated with increased susceptibility to endemic mycoses. In this review, we put together the various forms of endemic mycoses on the map and take a journey around the world to examine how cellular and molecular defects of the immune system predispose to invasive endemic fungal infections, including primary immunodeficiencies, individuals with autoantibodies against interferon-γ, and those receiving biologic response modifiers. Though rare, these conditions provide importance insights to host defense mechanisms against endemic fungi, which can only be appreciated in unique climatic and

  7. Genetic studies on leaf rolling and some root traits under drought ...

    African Journals Online (AJOL)

    Genetic studies on leaf rolling and some root traits under drought conditions in rice (Oryza sativa L.) AA Allah. Abstract. Crossing was made between three resistant and two susceptible parents to determine the genetic characteristics under drought conditions during 2002 and 2003 rice growing seasons. The resistant ...

  8. Large-Scale Association Study Confirms Genetic Complexity Underlying Type 2 Diabetes

    OpenAIRE

    Barroso, Inês; Luan, Jian'an; Middelberg, Rita P. S; Harding, Anne-Helen; Franks, Paul W; Jakes, Rupert W; Clayton, David; Schafer, Alan J; O'Rahilly, Stephen; Wareham, Nicholas J

    2003-01-01

    Type 2 diabetes is an increasingly common, serious metabolic disorder with a substantial inherited component. It is characterised by defects in both insulin secretion and action. Progress in identification of specific genetic variants predisposing to the disease has been limited. To complement ongoing positional cloning efforts, we have undertaken a large-scale candidate gene association study. We examined 152 SNPs in 71 candidate genes for association with diabetes status and related phenoty...

  9. Isolation of cyanobacterial mutants exhibiting growth defects under microoxic conditions by transposon tagging mutagenesis of Synechocystis sp. PCC 6803.

    Science.gov (United States)

    Terauchi, Kazuki; Sobue, Riho; Furutani, Yuho; Aoki, Rina; Fujita, Yuichi

    2017-05-12

    Cyanobacteria are photosynthetic prokaryotes that perform oxygenic photosynthesis by extracting electrons from water, with the generation of oxygen as a byproduct. Cyanobacteria use oxygen not only for respiration to produce energy in the dark but also for biosynthesis of various metabolites, such as heme and chlorophyll. Oxygen levels dynamically fluctuate in the field environments, from hyperoxic at daytime to almost anaerobic at night. Thus, adaptation to anaerobiosis should be important for cyanobacteria to survive in low-oxygen and anaerobic environments. However, little is known about the molecular mechanisms of cyanobacterial anaerobiosis because cyanobacteria have been regarded as aerobic organisms. As a first step to elucidate cyanobacterial adaptation mechanisms to low-oxygen environments, we isolated five mutants, T-1-T-5, exhibiting growth defects under microoxic conditions. The mutants were obtained from a transposon-tagged mutant library of the cyanobacterium Synechocystis sp. PCC 6803, which was produced by in vitro transposon tagging of cyanobacterial genomic DNA. Southern blot analysis indicated that a kanamycin resistance gene was inserted in the genome as a single copy. We identified the chromosomal transposon-tagged locus in T-5. Two open reading frames (sll0577 and sll0578) were partially deleted by the insertion of the kanamycin resistance gene in T-5. A reverse transcription polymerase chain reaction suggested that these co-transcribed genes are constitutively expressed under both aerobic and microoxic conditions. Then, we isolated two mutants in which one of the two genes was individually disrupted. Only the mutants partially lacking an intact sll0578 gene showed growth defects under microoxic conditions, whereas it grew normally under aerobic conditions. sll0578 is annotated as purK encoding N 5 -carboxy-aminoimidazole ribonucleotide synthetase involved in purine metabolism. This result implies the unexpected physiological importance of Pur

  10. Genetic analysis of fertility restoration under CGMS system in rice ...

    Indian Academy of Sciences (India)

    Cytoplasmic genetic male sterility (CGMS) resulting from nuclear-cytoplasmic interaction has been commercially exploited for the production of F1 hybrid seed in rice. The. CGMS system involves three lines, namely a cytoplasmic male sterile (CMS) line, a maintainer line and a restorer line where restorer line (R line) ...

  11. Genetic analysis of fertility restoration under CGMS system in rice ...

    Indian Academy of Sciences (India)

    Abstract. We studied the genetics of fertility restoration by producing three-way test cross (TWTC) hybrids involved different combi- nations of restorers, maintainers and partial restorers of rice. Pollen and spikelet fertility of 16 TWTC hybrids were studied. Six TWTC involving restorer/restorer combinations as male parents ...

  12. Mitochondrial dysfunctions in cancer: genetic defects and oncogenic signaling impinging on TCA cycle activity.

    Science.gov (United States)

    Desideri, Enrico; Vegliante, Rolando; Ciriolo, Maria Rosa

    2015-01-28

    The tricarboxylic acid (TCA) cycle is a central route for oxidative metabolism. Besides being responsible for the production of NADH and FADH2, which fuel the mitochondrial electron transport chain to generate ATP, the TCA cycle is also a robust source of metabolic intermediates required for anabolic reactions. This is particularly important for highly proliferating cells, like tumour cells, which require a continuous supply of precursors for the synthesis of lipids, proteins and nucleic acids. A number of mutations among the TCA cycle enzymes have been discovered and their association with some tumour types has been established. In this review we summarise the current knowledge regarding alterations of the TCA cycle in tumours, with particular attention to the three germline mutations of the enzymes succinate dehydrogenase, fumarate hydratase and isocitrate dehydrogenase, which are involved in the pathogenesis of tumours, and to the aberrant regulation of TCA cycle components that are under the control of oncogenes and tumour suppressors. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Adaptive genetic potential of coniferous forest tree species under climate change: implications for sustainable forest management

    Science.gov (United States)

    Mihai, Georgeta; Birsan, Marius-Victor; Teodosiu, Maria; Dumitrescu, Alexandru; Daia, Mihai; Mirancea, Ionel; Ivanov, Paula; Alin, Alexandru

    2017-04-01

    Mountain ecosystems are extremely vulnerable to climate change. The real potential for adaptation depends upon the existence of a wide genetic diversity in trees populations, upon the adaptive genetic variation, respectively. Genetic diversity offers the guarantee that forest species can survive, adapt and evolve under the influence of changing environmental conditions. The aim of this study is to evaluate the genetic diversity and adaptive genetic potential of two local species - Norway spruce and European silver fir - in the context of regional climate change. Based on data from a long-term provenance experiments network and climate variables spanning over more than 50 years, we have investigated the impact of climatic factors on growth performance and adaptation of tree species. Our results indicate that climatic and geographic factors significantly affect forest site productivity. Mean annual temperature and annual precipitation amount were found to be statistically significant explanatory variables. Combining the additive genetic model with the analysis of nuclear markers we obtained different images of the genetic structure of tree populations. As genetic indicators we used: gene frequencies, genetic diversity, genetic differentiation, genetic variance, plasticity. Spatial genetic analyses have allowed identifying the genetic centers holding high genetic diversity which will be valuable sources of gene able to buffer the negative effects of future climate change. Correlations between the marginal populations and in the optimal vegetation, between the level of genetic diversity and ecosystem stability, will allow the assessment of future risks arising from current genetic structure. Therefore, the strategies for sustainable forest management have to rely on the adaptive genetic variation and local adaptation of the valuable genetic resources. This work was realized within the framework of the project GENCLIM (Evaluating the adaptive potential of the main

  14. Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III

    Science.gov (United States)

    Björkqvist, Jenny; de Maat, Steven; Lewandrowski, Urs; Di Gennaro, Antonio; Oschatz, Chris; Schönig, Kai; Nöthen, Markus M.; Drouet, Christian; Braley, Hal; Nolte, Marc W.; Sickmann, Albert; Panousis, Con; Maas, Coen; Renné, Thomas

    2015-01-01

    Hereditary angioedema type III (HAEIII) is a rare inherited swelling disorder that is associated with point mutations in the gene encoding the plasma protease factor XII (FXII). Here, we demonstrate that HAEIII-associated mutant FXII, derived either from HAEIII patients or recombinantly produced, is defective in mucin-type Thr309-linked glycosylation. Loss of glycosylation led to increased contact-mediated autoactivation of zymogen FXII, resulting in excessive activation of the bradykinin-forming kallikrein-kinin pathway. In contrast, both FXII-driven coagulation and the ability of C1-esterase inhibitor to bind and inhibit activated FXII were not affected by the mutation. Intravital laser-scanning microscopy revealed that, compared with control animals, both F12–/– mice reconstituted with recombinant mutant forms of FXII and humanized HAEIII mouse models with inducible liver-specific expression of Thr309Lys-mutated FXII exhibited increased contact-driven microvascular leakage. An FXII-neutralizing antibody abolished bradykinin generation in HAEIII patient plasma and blunted edema in HAEIII mice. Together, the results of this study characterize the mechanism of HAEIII and establish FXII inhibition as a potential therapeutic strategy to interfere with excessive vascular leakage in HAEIII and potentially alleviate edema due to other causes. PMID:26193639

  15. Defect formation and recrystallization in the silicon on sapphire films under Si{sup +} irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Shemukhin, A.A., E-mail: shemuhin@gmail.com [Skobeltsyn Institute of Nuclear Physics, Lomonosov Moscow State University, Moscow (Russian Federation); Nazarov, A.V.; Balakshin, Yu. V. [Skobeltsyn Institute of Nuclear Physics, Lomonosov Moscow State University, Moscow (Russian Federation); Chernysh, V.S. [Skobeltsyn Institute of Nuclear Physics, Lomonosov Moscow State University, Moscow (Russian Federation); Faculty of Physics, Lomonosov Moscow State University, Moscow (Russian Federation)

    2015-07-01

    Silicon-on-sapphire (SOS) is one of the most promising silicon-on-insulator (SOI) technologies. SOS structures are widely used in microelectronics, but to meet modern requirements the silicon layer should be 100 nm thick or less. The problem is in amount of damage in the interface layer, which decreases the quality of the produced devices. In order to improve the crystalline structure quality SOS samples with 300 nm silicon layers were implanted with Si{sup +} ions with energies in the range from 180 up to 230 keV with fluences in the range from 10{sup 14} up to 5 × 10{sup 15} cm{sup −2} at 0 °C. The crystalline structure of the samples was studied with RBS and the interface layer was studied with SIMS after subsequent annealing. It has been found out that to obtain silicon films with high lattice quality it is necessary to damage the sapphire lattice near the silicon–sapphire interface. Complete destruction of the strongly defected area and subsequent recrystallization depends on the energy of implanted ions and the substrate temperature. No significant mixing in the interface layer was observed with the SIMS.

  16. Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

    DEFF Research Database (Denmark)

    Lu, Yi; Cuellar-Partida, Gabriel; Painter, Jodie N

    2015-01-01

    Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address...... this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested...... that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We...

  17. Experimental evaluation of the common defects in the execution of reinforced concrete beams under flexural loading

    Directory of Open Access Journals (Sweden)

    T.M. Elrakib

    2012-04-01

    Full Text Available Design of any structural element should realize the appropriate load capacity to serve the purpose of construction beside the esthetical function. Therefore, the accompanied symptoms of distress during loading conditions like cracking, deflections, and strain distribution all over the section will definitely influence the performance of these elements and their durability in sequence. Flexural moment is the most dominant straining action in many of the reinforced concrete elements such as beams, slabs, and frames. Thus, in this investigation an experimental program was carried out on deficient concrete beams which were somewhat designated to simulate the possible defects in the field, like errors in the arrangement of main steel, splices in different places (even at the maximum moment zone. Faults of improper workmanship were represented using a beam of honey-combed concrete and other of insufficient cover. On the other hand, a control beam was parallely cast for the purpose of comparison. Measurements like strains of concrete and steel, deflections and propagation of cracks were all observed and detected to evaluate to how any of these practice faults influence the behavior of beams. It was found that well-arranged distribution of reinforcement improves the ductile behavior of failure and reduces the corresponding deflections. Meanwhile, eccentricity of main steel creates a sort of non-uniform stress distribution over the section and accelerates approaching failure stage. In addition, the honey-combed structure undergoes more symptoms of distress and approaches failure faster without intermediate stage. Despite the fewer grids of cracks noticed, the honey-combed beam exhibits higher deflection values.

  18. Length-scale and strain rate-dependent mechanism of defect formation and fracture in carbon nanotubes under tensile loading

    Science.gov (United States)

    Javvaji, Brahmanandam; Raha, S.; Mahapatra, D. Roy

    2017-02-01

    Electromagnetic and thermo-mechanical forces play a major role in nanotube-based materials and devices. Under high-energy electron transport or high current densities, carbon nanotubes fail via sequential fracture. The failure sequence is governed by certain length scale and flow of current. We report a unified phenomenological model derived from molecular dynamic simulation data, which successfully captures the important physics of the complex failure process. Length-scale and strain rate-dependent defect nucleation, growth, and fracture in single-walled carbon nanotubes with diameters in the range of 0.47 to 2.03 nm and length which is about 6.17 to 26.45 nm are simulated. Nanotubes with long length and small diameter show brittle fracture, while those with short length and large diameter show transition from ductile to brittle fracture. In short nanotubes with small diameters, we observe several structural transitions like Stone-Wales defect initiation, its propagation to larger void nucleation, formation of multiple chains of atoms, conversion to monatomic chain of atoms, and finally complete fracture of the carbon nanotube. Hybridization state of carbon-carbon bonds near the end cap evolves, leading to the formation of monatomic chain in short nanotubes with small diameter. Transition from ductile to brittle fracture is also observed when strain rate exceeds a critical value. A generalized analytical model of failure is established, which correlates the defect energy during the formation of atomic chain with aspect ratio of the nanotube and strain rate. Variation in the mechanical properties such as elastic modulus, tensile strength, and fracture strain with the size and strain rate shows important implications in mitigating force fields and ways to enhance the life of electronic devices and nanomaterial conversion via fracture in manufacturing.

  19. Length-scale and strain rate-dependent mechanism of defect formation and fracture in carbon nanotubes under tensile loading

    Energy Technology Data Exchange (ETDEWEB)

    Javvaji, Brahmanandam [Indian Institute of Science, Department of Aerospace Engineering (India); Raha, S. [Indian Institute of Science, Department of Computational and Data Sciences (India); Mahapatra, D. Roy, E-mail: droymahapatra@aero.iisc.ernet.in [Indian Institute of Science, Department of Aerospace Engineering (India)

    2017-02-15

    Electromagnetic and thermo-mechanical forces play a major role in nanotube-based materials and devices. Under high-energy electron transport or high current densities, carbon nanotubes fail via sequential fracture. The failure sequence is governed by certain length scale and flow of current. We report a unified phenomenological model derived from molecular dynamic simulation data, which successfully captures the important physics of the complex failure process. Length-scale and strain rate-dependent defect nucleation, growth, and fracture in single-walled carbon nanotubes with diameters in the range of 0.47 to 2.03 nm and length which is about 6.17 to 26.45 nm are simulated. Nanotubes with long length and small diameter show brittle fracture, while those with short length and large diameter show transition from ductile to brittle fracture. In short nanotubes with small diameters, we observe several structural transitions like Stone-Wales defect initiation, its propagation to larger void nucleation, formation of multiple chains of atoms, conversion to monatomic chain of atoms, and finally complete fracture of the carbon nanotube. Hybridization state of carbon-carbon bonds near the end cap evolves, leading to the formation of monatomic chain in short nanotubes with small diameter. Transition from ductile to brittle fracture is also observed when strain rate exceeds a critical value. A generalized analytical model of failure is established, which correlates the defect energy during the formation of atomic chain with aspect ratio of the nanotube and strain rate. Variation in the mechanical properties such as elastic modulus, tensile strength, and fracture strain with the size and strain rate shows important implications in mitigating force fields and ways to enhance the life of electronic devices and nanomaterial conversion via fracture in manufacturing.

  20. Structural and chemical disorder in semiconductors under pressure: Evidence in II-VI’s, role of photoactive defects, material predictions

    Science.gov (United States)

    Weinstein, Bernard A.; Lindberg, George P.; Gross, Nelson

    2017-05-01

    Hydrostatic pressure can sometimes generate structural and chemical disorder within crystals. We review pressure-Raman experiments on ZnSe, ZnTe, and CdSe showing evidence for these phenomena. In ZnSe and ZnTe Raman spectra recorded with low laser flux show only pre-transition structural disorder on approaching the lowest pressure transition, as is typical for first-order phase changes. Spectra recorded with higher laser flux (sub-band-gap) observe precipitation of anion nanocrystals. This behavior is absent in CdSe. A model is developed that considers the role of crystal defects. The defects promote plastic deformation assisted by photoexcitation of Jahn-Teller distortions. Nanocrystals can precipitate on dislocations in deformed regions under energetically favorable conditions. Model calculations based on theories for precipitation in metals account for the influence of pressure on the nanocrystal formation in ZnSe and ZnTe, and explain its absence in CdSe. Material maps are constructed to predict the tendencies for similar precipitation in III-V, II-VI, I-VII, and chalcopyrite crystals.

  1. Biology, Genetics, and Environment: Underlying Factors Influencing Alcohol Metabolism.

    Science.gov (United States)

    Wall, Tamara L; Luczak, Susan E; Hiller-Sturmhöfel, Susanne

    2016-01-01

    Gene variants encoding several of the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), are among the largest genetic associations with risk for alcohol dependence. Certain genetic variants (i.e., alleles)--particularly the ADH1B*2, ADH1B*3, ADH1C*1, and ALDH2*2 alleles--have been associated with lower rates of alcohol dependence. These alleles may lead to an accumulation of acetaldehyde during alcohol metabolism, which can result in heightened subjective and objective effects. The prevalence of these alleles differs among ethnic groups; ADH1B*2 is found frequently in northeast Asians and occasionally Caucasians, ADH1B*3 is found predominantly in people of African ancestry, ADH1C*1 varies substantially across populations, and ALDH2*2 is found almost exclusively in northeast Asians. Differences in the prevalence of these alleles may account at least in part for ethnic differences in alcohol consumption and alcohol use disorder (AUD). However, these alleles do not act in isolation to influence the risk of AUD. For example, the gene effects of ALDH2*2 and ADH1B*2 seem to interact. Moreover, other factors have been found to influence the extent to which these alleles affect a person's alcohol involvement, including developmental stage, individual characteristics (e.g., ethnicity, antisocial behavior, and behavioral undercontrol), and environmental factors (e.g., culture, religion, family environment, and childhood adversity).

  2. Legume genetic resources and transcriptome dynamics under abiotic stress conditions.

    Science.gov (United States)

    Abdelrahman, Mostafa; Jogaiah, Sudisha; Burritt, David J; Tran, Lam-Son Phan

    2018-01-04

    Grain legumes are an important source of nutrition and income for billions of consumers and farmers around the world. However, the low productivity of new legume varieties, due to the limited genetic diversity available for legume breeding programmes and poor policymaker support, combined with an increasingly unpredictable global climate is resulting in a large gap between current yields and the increasing demand for legumes as food. Hence, there is a need for novel approaches to develop new high-yielding legume cultivars that are able to cope with a range of environmental stressors. Next-generation technologies are providing the tools that could enable the more rapid and cost-effective genomic and transcriptomic studies for most major crops, allowing the identification of key functional and regulatory genes involved in abiotic stress resistance. In this review, we provide an overview of the recent achievements regarding abiotic stress resistance in a wide range of legume crops and highlight the transcriptomic and miRNA approaches that have been used. In addition, we critically evaluate the availability and importance of legume genetic resources with desirable abiotic stress resistance traits. © 2018 John Wiley & Sons Ltd.

  3. A simple genetic architecture underlies morphological variation in dogs.

    Directory of Open Access Journals (Sweden)

    Adam R Boyko

    2010-08-01

    Full Text Available Domestic dogs exhibit tremendous phenotypic diversity, including a greater variation in body size than any other terrestrial mammal. Here, we generate a high density map of canine genetic variation by genotyping 915 dogs from 80 domestic dog breeds, 83 wild canids, and 10 outbred African shelter dogs across 60,968 single-nucleotide polymorphisms (SNPs. Coupling this genomic resource with external measurements from breed standards and individuals as well as skeletal measurements from museum specimens, we identify 51 regions of the dog genome associated with phenotypic variation among breeds in 57 traits. The complex traits include average breed body size and external body dimensions and cranial, dental, and long bone shape and size with and without allometric scaling. In contrast to the results from association mapping of quantitative traits in humans and domesticated plants, we find that across dog breeds, a small number of quantitative trait loci (< or = 3 explain the majority of phenotypic variation for most of the traits we studied. In addition, many genomic regions show signatures of recent selection, with most of the highly differentiated regions being associated with breed-defining traits such as body size, coat characteristics, and ear floppiness. Our results demonstrate the efficacy of mapping multiple traits in the domestic dog using a database of genotyped individuals and highlight the important role human-directed selection has played in altering the genetic architecture of key traits in this important species.

  4. Genetics Home Reference: X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia

    Science.gov (United States)

    ... Conditions XMEN X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia Printable PDF Open All Close ... boxes. Description X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (typically known by the acronym ...

  5. Genetic dissection of seed vigour traits in maize (Zea mays L.) under ...

    Indian Academy of Sciences (India)

    [Shi Y., Li G., Tian Z., Wang Z., Wang X., Zhu Y., Chen Y., Guo S., Qi J., Zhang X. and Ku L. 2016 Genetic dissection of seed vigour traits in maize (Zea mays L.) under low-temperature conditions. J. Genet. 95, 1017–1022]. Introduction. Seed vigour, an important factor governing the seed qual- ity, reflects potential seed ...

  6. Modeling Metallic Precipitate Dissolution in Silicon Under Point Defect Injection: Final Subcontract Report, 20 January 2004--19 January 2005

    Energy Technology Data Exchange (ETDEWEB)

    Tan, T. Y.

    2005-05-01

    We have formulated the problem of gettering of metallic precipitates in Si for which there exists a volume misfit between the precipitate and the Si matrix material. The gettering process is modeled using an Al-Si liquid layer, and the volume misfit associated with dissolving the precipitates is assumed as accommodated by point defects, which may be dominated by vacancies (V), self-interstitials (I), or both contributing. Under the condition that V and I attained dynamical equilibrium, we found that for analytic purposes, the problem reduces to either the V or the I alone case, with the fast-diffusing case dominating. Our initial simulation results on gettering of FeSi2 (with a misfit of -0.15) showed that the process can be sped up by the injection of V.

  7. ACCURACY EVALUATION FOR THE NON-CONTACT DEFECT AREA MEASUREMENT AT THE COMPLEX-SHAPE SURFACES UNDER VIDEOENDOSCOPIC CONTROL

    Directory of Open Access Journals (Sweden)

    A. V. Gorevoy

    2014-07-01

    Full Text Available The problem of non-contact surface defect area measurement at complex-shape objects under videoendoscopic control is considered. Major factors contributing to the measurement uncertainty are analyzed for the first time. The proposed method of accuracy analysis is based on the evaluation of 3D coordinates of surface points from 2D projections under assumption of projective camera model and Mahalanobis distance minimization in the image plane. Expressions for area measurement error caused by sum-of-triangles approximation are obtained analytically for practically important cases of cylindrical and spherical surfaces. It is shown that the magnitude of this error component for a single triangle does not exceed 1% for the real values of parameters of the endoscopic imaging system. Expressions are derived for area measurement uncertainty evaluation on arbitrary shape surfaces, caused by measurement errors of 3D coordinates of individual points with and without a priori information about surface shape. Verification of the obtained expressions with real experiment data showed that area measurement error for a complex figure, given by a set of points, is mainly caused by ignoring the fact that these points belong to the surface. It is proved that the use of a priori information about investigated surface shape, which is often available from the design documentation, in many cases would radically improve the accuracy of surface defects area measurement. The presented results are valid for stereoscopic, shadow and phase methods of video endoscopic measurements and can be effectively used in development of new non-contact measuring endoscopic systems and modernization of existing ones.

  8. Structural defect accumulation in tungsten and tungsten-5wt.% tantalum under incremental proton damage

    Science.gov (United States)

    Ipatova, I.; Harrison, R. W.; Wady, P. T.; Shubeita, S. M.; Terentyev, D.; Donnelly, S. E.; Jimenez-Melero, E.

    2018-04-01

    We have performed proton irradiation of W and W-5wt.%Ta materials at 350 °C with a step-wise damage level increase up to 0.7 dpa and using two beam energies, namely 40 keV and 3 MeV, in order to probe the accumulation of radiation-induced lattice damage in these materials. Interstitial-type a/2 dislocation loops are formed under irradiation, and their size increases in W-5Ta up to a loop width of 21 ± 4 nm at 0.3 dpa, where loop saturation takes place. In contrast, the loop length in W increases progressively up to 183 ± 50 nm at 0.7 dpa, whereas the loop width remains relatively constant at 29 ± 7 nm at >0.3 dpa, giving rise to dislocation strings. The dislocation loops and tangles are observed in both materials examined after a 3 MeV proton irradiation at 350 °C. Ta doping delays the evolution of radiation-induced dislocation structures in W, and can consequently impact the hydrogen isotope retention under plasma exposure.

  9. IDENTIFYING DEFECT SIZE IN TWO DIMENSIONAL PLATES BASED ON BOUNDARY MEASUREMENTS USING REDUCED MODEL AND GENETIC ALGORITHM

    Directory of Open Access Journals (Sweden)

    BRAHIM BENAISSA

    2014-12-01

    Full Text Available ­In this study the proper orthogonal decomposition method is utilised as a model reduction technique in crack size estimation in a cracked plate under traction problem. The idea is to create a reduced model based on the results issued from finite element method, thus the crack size parameter is directly related to the boundary displacement obtained from the boundary nodes considered as sensor points. The inverse investigation is run using a genetic algorithm to minimization the error function expressed as the difference between data caused by the crack proposed by genetic algorithm in every individual and the one measured at the actual crack identity. The reduced model is validated by comparing the estimated structural response with the corresponding results from the finite element model. The effectiveness of the approach related to the used number of sensors is presented. Finally the stability of the method against uncertainty is tested by introducing different levels of white noise to the reference data.

  10. Performance of diverse wheat genetic stocks under moisture stress condition

    International Nuclear Information System (INIS)

    Seher, M.; Shabbir, G.; Rasheed, A.

    2015-01-01

    This study was conducted to evaluate divergent wheat germplasm for their performance under drought and control conditions. The germplasm consists of wheat land races of Pakistan, advanced D-genome synthetic derivatives and high yielding varieties of Pakistan. This wide array of germplasm was selected to identify sources, which can be opted later by the wheat breeders while breeding for drought tolerance. The evaluation parameters involved some important physiochemical testing and morphological characteristics in the field under drought and control conditions. Based on these parameters, 13 wheat genotypes were selected on the basis of their best performance regarding morphological and physiological parameters. These genotypes exhibited higher yield under drought stress conditions and increased percentage of proline, sugar, SOD and protein content under laboratory conditions as compared to the susceptible genotypes. Correlation studies revealed that grains per spike (GPS) and thousand grain weight (TGW) had direct relationship with spike length (SL), proline and sugar content under both control and drought conditions. Thus, these parameters can be used as selection criteria for the identification of tolerant genotypes. (author)

  11. Genetic variation of loci potentially under selection confounds species-genetic diversity correlations in a fragmented habitat.

    Science.gov (United States)

    Bertin, Angeline; Gouin, Nicolas; Baumel, Alex; Gianoli, Ernesto; Serratosa, Juan; Osorio, Rodomiro; Manel, Stephanie

    2017-01-01

    Positive species-genetic diversity correlations (SGDCs) are often thought to result from the parallel influence of neutral processes on genetic and species diversity. Yet, confounding effects of non-neutral mechanisms have not been explored. Here, we investigate the impact of non-neutral genetic diversity on SGDCs in high Andean wetlands. We compare correlations between plant species diversity and genetic diversity (GD) calculated with and without loci potentially under selection (outlier loci). The study system includes 2188 specimens from five species (three common aquatic macroinvertebrate and two dominant plant species) that were genotyped for 396 amplified fragment length polymorphism loci. We also appraise the importance of neutral processes on SGDCs by investigating the influence of habitat fragmentation features. Significant positive SGDCs were detected for all five species (mean SGDC = 0.52 ± 0.05). While only a few outlier loci were detected in each species, they resulted in significant decreases in GD and in SGDCs. This supports the hypothesis that neutral processes drive species-genetic diversity relationships in high Andean wetlands. Unexpectedly, the effects on genetic diversity GD of the habitat fragmentation characteristics in this study increased with the presence of outlier loci in two species. Overall, our results reveal pitfalls in using habitat features to infer processes driving SGDCs and show that a few loci potentially under selection are enough to cause a significant downward bias in SGDC. Investigating confounding effects of outlier loci thus represents a useful approach to evidence the contribution of neutral processes on species-genetic diversity relationships. © 2016 John Wiley & Sons Ltd.

  12. [Total hip arthroplasty in patients under 40 years of age and, if indicated, reconstruction of acetabular defects with bone impaction grafting].

    NARCIS (Netherlands)

    Kam, D.C.J. de; Gardeniers, J.W.M.; Veth, R.P.H.; Schreurs, B.W.

    2010-01-01

    OBJECTIVE: To determine the long-term results of primary cemented total hip arthroplasty in patients under the age of 40. In cases of acetabular defects, initial reconstruction with bone impaction grafting was performed. DESIGN: Cohort analysis. METHODS: Details of patients under the age of 40 who

  13. Genetic reconstitution of the human Adenovirus type 2 temperature-sensitive 1 mutant defective in endosomal escape

    Directory of Open Access Journals (Sweden)

    Gastaldelli Michele

    2009-10-01

    Full Text Available Abstract Human Adenoviruses infect the upper and lower respiratory tracts, the urinary and digestive tracts, lymphoid systems and heart, and give rise to epidemic conjunctivitis. More than 51 human serotypes have been identified to-date, and classified into 6 species A-F. The species C Adenoviruses Ad2 and Ad5 (Ad2/5 cause upper and lower respiratory disease, but how viral structure relates to the selection of particular infectious uptake pathways is not known. An adenovirus mutant, Ad2-ts1 had been isolated upon chemical mutagenesis in the past, and shown to have unprocessed capsid proteins. Ad2-ts1 fails to package the viral protease L3/p23, and Ad2-ts1 virions do not efficiently escape from endosomes. It had been suggested that the C22187T point mutation leading to the substitution of the conserved proline 137 to leucine (P137L in the L3/p23 protease was at least in part responsible for this phenotype. To clarify if the C22187T mutation is necessary and sufficient for the Ad2-ts1 phenotype, we sequenced the genes encoding the structural proteins of Ad2-ts1, and confirmed that the Ad2-ts1 DNA carries the point mutation C22187T. Introduction of C22187T to the wild-type Ad2 genome in a bacterial artificial chromosome (Ad2-BAC gave Ad2-BAC46 virions with the full Ad2-ts1 phenotype. Reversion of Ad2-BAC46 gave wild-type Ad2 particles indicating that P137L is necessary and sufficient for the Ad2-ts1 phenotype. The kinetics of Ad2-ts1 uptake into cells were comparable to Ad2 suggesting similar endocytic uptake mechanisms. Surprisingly, infectious Ad2 or Ad5 but not Ad2-ts1 uptake required CALM (clathrin assembly lymphoid myeloid protein, which controls clathrin-mediated endocytosis and membrane transport between endosomes and the trans-Golgi-network. The data show that no other mutations than P137L in the viral protease are necessary to give rise to particles that are defective in capsid processing and endosomal escape. This provides a basis for

  14. Structural and elastic properties of defect chalcopyrite HgGa{sub 2}S{sub 4} under high pressure

    Energy Technology Data Exchange (ETDEWEB)

    Gomis, O., E-mail: osgohi@fis.upv.es [Centro de Tecnologías Físicas: Acústica, Materiales y Astrofísica, MALTA Consolider Team, Universitat Politècnica de València, 46022 València (Spain); Santamaría-Pérez, D. [Departamento de Física Aplicada-ICMUV, MALTA Consolider Team, Universitat de València, Edificio de Investigación, C/Dr. Moliner 50, Burjassot, 46100 València (Spain); Departamento de Química Física I, Universidad Complutense de Madrid, MALTA Consolider Team, Avenida Complutense s/n, 28040 Madrid (Spain); Vilaplana, R.; Luna, R. [Centro de Tecnologías Físicas: Acústica, Materiales y Astrofísica, MALTA Consolider Team, Universitat Politècnica de València, 46022 València (Spain); Sans, J.A.; Manjón, F.J. [Instituto de Diseño para la Fabricación y Producción Automatizada, MALTA Consolider Team, Universitat Politècnica de València, 46022 València (Spain); Errandonea, D. [Departamento de Física Aplicada-ICMUV, MALTA Consolider Team, Universitat de València, Edificio de Investigación, C/Dr. Moliner 50, Burjassot, 46100 València (Spain); and others

    2014-01-15

    Highlights: • Single crystals of HgGa{sub 2}S{sub 4} with defect-chalcopyrite (DC) structure were synthesized. • High-pressure X-ray diffraction in DC-HgGa{sub 2}S{sub 4} was performed. • Equation of state of DC-HgGa{sub 2}S{sub 4} determined (bulk modulus of 48.4 GPa). • Calculated elastic constants of DC-HgGa{sub 2}S{sub 4} reported at different pressures. • DC-HgGa{sub 2}S{sub 4} becomes mechanically unstable above 13.8 GPa. -- Abstract: In this work, we focus on the study of the structural and elastic properties of mercury digallium sulfide (HgGa{sub 2}S{sub 4}) at high pressures. This compound belongs to the family of AB{sub 2}X{sub 4} ordered-vacancy compounds and exhibits a tetragonal defect chalcopyrite structure. X-ray diffraction measurements at room temperature have been performed under compression up to 15.1 GPa in a diamond anvil cell. Our measurements have been complemented and compared with ab initio total energy calculations. The axial compressibility and the equation of state of the low-pressure phase of HgGa{sub 2}S{sub 4} have been experimentally and theoretically determined and compared to other related ordered-vacancy compounds. The pressure dependence of the theoretical cation–anion and vacancy-anion distances and compressibilities in HgGa{sub 2}S{sub 4} are reported and discussed in comparison to other related ordered-vacancy compounds. Finally, the pressure dependence of the theoretical elastic constants and elastic moduli of HgGa{sub 2}S{sub 4} has been studied. Our calculations indicate that the low-pressure phase of HgGa{sub 2}S{sub 4} becomes mechanically unstable above 13.8 GPa.

  15. Production and stability of radiation-induced defects in MgAl2O4 under electronic excitation

    International Nuclear Information System (INIS)

    Yasuda, K.; Yamamoto, T.; Seki, S.; Shiiyama, K.; Matsumura, S.

    2008-01-01

    This paper investigates the formation process of radiation-induced defects in magnesium aluminate spinel and their stability using transmission electron microscopy, with emphasis on the effects of electronic excitation. Small interstitial-type dislocation loops disappeared under electron-induced electronic excitation. The elimination rate of the loops was found to be one order higher than for α-alumina. The disappearance of dislocation loops by a dissociation mechanism into isolated interstitials is discussed through analysis of the growth-and-shrink process of the loops. HARECXS analysis on cross section specimens irradiated with 350 MeV Au ions has shown the progress of cation disordering along ion tracks to be a function of electronic stopping power, (dE/dx) e . Cations were found to exchange their sites toward a random configuration. Such disordering appears from (dE/dx) e = 10 keV/nm, and increases in size with increasing (dE/dx) e to reach nearly 10 nm in diameter at 30 keV/nm, under an assumption of a fully disordered configuration

  16. A hybrid genetic-simulated annealing algorithm for the location-inventory-routing problem considering returns under e-supply chain environment.

    Science.gov (United States)

    Li, Yanhui; Guo, Hao; Wang, Lin; Fu, Jing

    2013-01-01

    Facility location, inventory control, and vehicle routes scheduling are critical and highly related problems in the design of logistics system for e-business. Meanwhile, the return ratio in Internet sales was significantly higher than in the traditional business. Many of returned merchandise have no quality defects, which can reenter sales channels just after a simple repackaging process. Focusing on the existing problem in e-commerce logistics system, we formulate a location-inventory-routing problem model with no quality defects returns. To solve this NP-hard problem, an effective hybrid genetic simulated annealing algorithm (HGSAA) is proposed. Results of numerical examples show that HGSAA outperforms GA on computing time, optimal solution, and computing stability. The proposed model is very useful to help managers make the right decisions under e-supply chain environment.

  17. A Hybrid Genetic-Simulated Annealing Algorithm for the Location-Inventory-Routing Problem Considering Returns under E-Supply Chain Environment

    Directory of Open Access Journals (Sweden)

    Yanhui Li

    2013-01-01

    Full Text Available Facility location, inventory control, and vehicle routes scheduling are critical and highly related problems in the design of logistics system for e-business. Meanwhile, the return ratio in Internet sales was significantly higher than in the traditional business. Many of returned merchandise have no quality defects, which can reenter sales channels just after a simple repackaging process. Focusing on the existing problem in e-commerce logistics system, we formulate a location-inventory-routing problem model with no quality defects returns. To solve this NP-hard problem, an effective hybrid genetic simulated annealing algorithm (HGSAA is proposed. Results of numerical examples show that HGSAA outperforms GA on computing time, optimal solution, and computing stability. The proposed model is very useful to help managers make the right decisions under e-supply chain environment.

  18. A Hybrid Genetic-Simulated Annealing Algorithm for the Location-Inventory-Routing Problem Considering Returns under E-Supply Chain Environment

    Science.gov (United States)

    Guo, Hao; Fu, Jing

    2013-01-01

    Facility location, inventory control, and vehicle routes scheduling are critical and highly related problems in the design of logistics system for e-business. Meanwhile, the return ratio in Internet sales was significantly higher than in the traditional business. Many of returned merchandise have no quality defects, which can reenter sales channels just after a simple repackaging process. Focusing on the existing problem in e-commerce logistics system, we formulate a location-inventory-routing problem model with no quality defects returns. To solve this NP-hard problem, an effective hybrid genetic simulated annealing algorithm (HGSAA) is proposed. Results of numerical examples show that HGSAA outperforms GA on computing time, optimal solution, and computing stability. The proposed model is very useful to help managers make the right decisions under e-supply chain environment. PMID:24489489

  19. Epileptic Encephalopathy in Childhood: A Stepwise Approach for Identification of Underlying Genetic Causes.

    Science.gov (United States)

    Patel, Jaina; Mercimek-Mahmutoglu, Saadet

    2016-10-01

    Epilepsy is one of the most common neurological disorders in childhood. Epilepsy associated with global developmental delay and cognitive dysfunction is defined as epileptic encephalopathy. Certain inherited metabolic disorders presenting with epileptic encephalopathy can be treated with disease specific diet, vitamin, amino acid or cofactor supplementations. In those disorders, disease specific therapy is successful to achieve good seizure control and improve long-term neurodevelopmental outcome. For this reason, intractable epilepsy with global developmental delay or history of developmental regression warrants detailed metabolic investigations for the possibility of an underlying treatable inherited metabolic disorder, which should be undertaken as first line investigations. An underlying genetic etiology in epileptic encephalopathy has been supported by recent studies such as array comparative genomic hybridization, targeted next generation sequencing panels, whole exome and whole genome sequencing. These studies report a diagnostic yield up to 70%, depending on the applied genetic testing as well as number of patients enrolled. In patients with epileptic encephalopathy, a stepwise approach for diagnostic work-up will help to diagnose treatable inherited metabolic disorders quickly. Application of detailed genetic investigations such as targeted next generation sequencing as second line and whole exome sequencing as third line testing will diagnose underlying genetic disease which will help for genetic counseling as well as guide for prenatal diagnosis. Knowledge of underlying genetic cause will provide novel insights into the pathogenesis of epileptic encephalopathy and pave the ground towards the development of targeted neuroprotective treatment strategies to improve the health outcome of children with epileptic encephalopathy.

  20. Evaluation of nonbiomedical and biomedical grade alginates for the transplantation of genetically modified articular chondrocytes to cartilage defects in a large animal model in vivo.

    Science.gov (United States)

    Heiligenstein, Susanne; Cucchiarini, Magali; Laschke, Matthias W; Bohle, Rainer M; Kohn, Dieter; Menger, Michael D; Madry, Henning

    2011-04-01

    Genetically modified chondrocytes embedded in alginate improve cartilage repair in experimental models, and alginates are clinically used for articular chondrocyte transplantation. In the present study, we tested the hypothesis that the alginate system allows for sustained transgene expression in cartilage defects in a preclinical large animal model in vivo. Primary cultures of ovine articular chondrocytes were transfected with the Photinus pyralis luc or the Escherichia coli lacZ genes in monolayer culture in vitro using eight different nonviral compounds. Optimally transfected chondrocytes were encapsulated in spheres composed of nonbiomedical or biomedical grade alginates for evaluation of luciferase expression, cell numbers and viabilities in vitro. Transfected chondrocytes encapsulated in spheres comprised of the different alginates were then implanted into osteochondral defects in the knee joints of sheep to examine the profiles of transgene expression in vivo. Ovine articular chondrocytes were efficiently transfected with FuGENE 6. Transgene expression was detectable after encapsulation in the alginates over 21 days in vitro. Transplantation of genetically modified chondrocytes to cartilage defects in vivo resulted in maximal transgene expression on day 1 after transfection, with a decrease by day 21, the longest time point evaluated. Remarkably, the reduction in luciferase activity was less pronounced when biomedical grade alginates were employed, compared to nonbiomedical grade alginates, suggesting that such alginates might be better suited to support elevated transgene expression after transplantation of genetically modified chondrocytes. This approach may be of value to study the effects of potential therapeutic genes upon cartilage repair in a clinically relevant setting. Copyright © 2011 John Wiley & Sons, Ltd.

  1. Engineered chromosome-based genetic mapping establishes a 3.7 Mb critical genomic region for Down syndrome-associated heart defects in mice.

    Science.gov (United States)

    Liu, Chunhong; Morishima, Masae; Jiang, Xiaoling; Yu, Tao; Meng, Kai; Ray, Debjit; Pao, Annie; Ye, Ping; Parmacek, Michael S; Yu, Y Eugene

    2014-06-01

    Trisomy 21 (Down syndrome, DS) is the most common human genetic anomaly associated with heart defects. Based on evolutionary conservation, DS-associated heart defects have been modeled in mice. By generating and analyzing mouse mutants carrying different genomic rearrangements in human chromosome 21 (Hsa21) syntenic regions, we found the triplication of the Tiam1-Kcnj6 region on mouse chromosome 16 (Mmu16) resulted in DS-related cardiovascular abnormalities. In this study, we developed two tandem duplications spanning the Tiam1-Kcnj6 genomic region on Mmu16 using recombinase-mediated genome engineering, Dp(16)3Yey and Dp(16)4Yey, spanning the 2.1 Mb Tiam1-Il10rb and 3.7 Mb Ifnar1-Kcnj6 regions, respectively. We found that Dp(16)4Yey/+, but not Dp(16)3Yey/+, led to heart defects, suggesting the triplication of the Ifnar1-Kcnj6 region is sufficient to cause DS-associated heart defects. Our transcriptional analysis of Dp(16)4Yey/+ embryos showed that the Hsa21 gene orthologs located within the duplicated interval were expressed at the elevated levels, reflecting the consequences of the gene dosage alterations. Therefore, we have identified a 3.7 Mb genomic region, the smallest critical genomic region, for DS-associated heart defects, and our results should set the stage for the final step to establish the identities of the causal gene(s), whose elevated expression(s) directly underlie this major DS phenotype.

  2. Development and application of a next-generation-sequencing (NGS approach to detect known and novel gene defects underlying retinal diseases

    Directory of Open Access Journals (Sweden)

    Audo Isabelle

    2012-01-01

    Full Text Available Abstract Background Inherited retinal disorders are clinically and genetically heterogeneous with more than 150 gene defects accounting for the diversity of disease phenotypes. So far, mutation detection was mainly performed by APEX technology and direct Sanger sequencing of known genes. However, these methods are time consuming, expensive and unable to provide a result if the patient carries a new gene mutation. In addition, multiplicity of phenotypes associated with the same gene defect may be overlooked. Methods To overcome these challenges, we designed an exon sequencing array to target 254 known and candidate genes using Agilent capture. Subsequently, 20 DNA samples from 17 different families, including four patients with known mutations were sequenced using Illumina Genome Analyzer IIx next-generation-sequencing (NGS platform. Different filtering approaches were applied to identify the genetic defect. The most likely disease causing variants were analyzed by Sanger sequencing. Co-segregation and sequencing analysis of control samples validated the pathogenicity of the observed variants. Results The phenotype of the patients included retinitis pigmentosa, congenital stationary night blindness, Best disease, early-onset cone dystrophy and Stargardt disease. In three of four control samples with known genotypes NGS detected the expected mutations. Three known and five novel mutations were identified in NR2E3, PRPF3, EYS, PRPF8, CRB1, TRPM1 and CACNA1F. One of the control samples with a known genotype belongs to a family with two clinical phenotypes (Best and CSNB, where a novel mutation was identified for CSNB. In six families the disease associated mutations were not found, indicating that novel gene defects remain to be identified. Conclusions In summary, this unbiased and time-efficient NGS approach allowed mutation detection in 75% of control cases and in 57% of test cases. Furthermore, it has the possibility of associating known gene

  3. Intraoperative device closure of perimembranous ventricular septal defects in the young children under transthoracic echocardiographic guidance; initial experience

    Directory of Open Access Journals (Sweden)

    Cao Hua

    2011-12-01

    Full Text Available Abstract Objectives This study aimed to assess the safety and feasibility of intraoperative device closure of perimembranous ventricular septal defects (VSD in young children guided by transthoracic echocardiography (TTE. Methods We enrolled 18 patients from our hospital to participate in the study from June 2011 to September 2011. A minimal inferior median incision was performed after full evaluation of the perimembranous VSD by real-time TTE, and a domestically made device was inserted to occlude the perimembranous VSD. The proper size of the device was determined by means of transthoracic echocardiographic analysis. Results Implantation was ultimately successful in 16 patients using TTE guidance. In these cases, the complete closure rate immediately following the operation and on subsequent follow-up was 100%. Symmetric devices were used in 14 patients, and asymmetric devices were used in two patients. Two patient were transformed to surgical treatment, one for significant residual shunting, and the other for unsuccessful wire penetration of the VSD. The follow-up periods were less than nine months, and only one patient had mild aortic regurgitation. There were no instances of residual shunt, noticeable aortic regurgitation, significant arrhythmia, thrombosis, or device failure. Conclusions Minimally invasive transthoracic device closure of perimembranous VSDs is safe and feasible, using a domestically made device under transthoracic echocardiographic guidance, without the need for cardiopulmonary bypass. This technique should be considered an acceptable alternative to surgery or device closure guided by transesophageal echocardiography in selected young children. However, a long-term evaluation of outcomes is necessary.

  4. Eye and vision defects in under-five-year-old children in Oman: A public health intervention study

    Directory of Open Access Journals (Sweden)

    Rajiv Khandekar

    2010-01-01

    Result : Among 1,520 examined children, three children had absent eyeball bilaterally and three had unilaterally absent eyeball. Strabismus and nystagmus were detected in 44 (2.9% and 18 (1.2% children respectively. ′Hiding Heidi′ test was normal in 530/537 (87% of children. Distant vision reading was ≥0.32 in 386/448 (86.2% eyes. Preferential looking test suggested that half of the children had defective vision (>2cpcm. Screening at ′1-2 year′ and ′3-4 years′ age group could significantly predict eye problems ( P≤0.001. Conclusion : Eye and vision screening of under-five kids helped in detection of eye problems in early stages. Instead of universal screening, high risk population or children of ′3 to 4′ years for vision and ′1 to 2′ years for ocular abnormalities is proposed The existing health services could not detect some children with eye problems and they were identified during such screening.

  5. Electron scattering in graphene by defects in underlying h-BN layer: First-principles transport calculations

    Science.gov (United States)

    Kaneko, Tomoaki; Ohno, Takahisa

    2018-03-01

    We investigate the electronic structure and the transport properties of graphene adsorbed onto h-BN with carbon impurities or atomic vacancies using density functional theory and the non-equilibrium Green's function method. We find that the transport properties are degraded due to carrier doping and scattering off of localized defect states in h-BN. When graphene is doped by introducing defects in h-BN, the transmission spectra become asymmetric owing to the reduction of the electronic density of states, which contributes significantly to the degradation of graphene transport properties as compared with the effect of defect levels.

  6. Genetic background has a major effect on the penetrance and severity of craniofacial defects in mice heterozygous for the gene encoding the nucleolar protein Treacle.

    Science.gov (United States)

    Dixon, Jill; Dixon, Michael James

    2004-04-01

    Treacher Collins syndrome (TCS) is a craniofacial disorder that results from mutations in TCOF1, which encodes the nucleolar protein Treacle. The severity of the clinical features exhibits wide variation and includes hypoplasia of the mandible and maxilla, abnormalities of the external ears and middle ear ossicles, and cleft palate. To determine the in vivo function of Treacle, we previously generated Tcof1 heterozygous mice on a mixed C57BL/6 and 129 background. These mice exhibited a lethal phenotype, which included abnormal development of the maxilla, absence of the eyes and nasal passages, and neural tube defects. Here, we show that placing the mutation onto different genetic backgrounds has a major effect on the penetrance and severity of the craniofacial and other defects. The offspring exhibit markedly variable strain-dependent phenotypes that range from extremely severe and lethal in a mixed CBA/Ca and 129 background, to apparently normal and viable in a mixed BALB/c and 129 background. In the former case, in addition to a profoundly severe craniofacial phenotype, CBA-derived heterozygous mice also exhibited delayed ossification of the long bones, rib fusions, and digit anomalies. The results of our studies indicate that factors in the different genetic backgrounds contribute extensively to the Tcof1 phenotype. Copyright 2004 Wiley-Liss, Inc.

  7. Genetic variation underlying psychosis-inducing effects of cannabis: critical review and future directions.

    Science.gov (United States)

    Decoster, Jeroen; van Os, Jim; Myin-Germeys, Inez; De Hert, Marc; van Winkel, Ruud

    2012-01-01

    Cannabis use is associated with an increased risk for psychotic disorder, yet most cannabis users do not develop psychosis, suggesting that other factors are also involved. This paper reviews the available evidence suggesting that differential sensitivity to the psychosis-inducing effects of cannabis may be related to underlying genetic liability. There is robust evidence that persons at psychometric risk for psychosis are most vulnerable to display psychotic symptoms subsequent to the use of cannabis. Multiple studies have also found that persons at familial risk for psychosis have an increased sensitivity to the effects of cannabis. Together, these findings support the concept of a biological interaction between cannabis use and one's underlying genetic vulnerability. At the molecular-genetic level, however, few (if any) interactions have been consistently replicated, although a reported interaction with variation in AKT1 is promising and deserves further follow-up. The apparent lack of consistent replication can be ascribed to problems of initial gene selection, statistical power, a bias towards positive results and insufficient attempts at true replication, leading to the conclusion that increased sample sizes, greater density of genetic markers and a stronger focus on true replication are necessary. The major challenge for molecular-genetic gene-environment interaction research will be to combine the agnostic detection of disorder-associated genetic variants from genome-wide studies with the hypothesis-based approach from epidemiological and neurobiological studies. Possible strategies for future cannabis interaction studies are discussed.

  8. Strategic production modeling for defective items with imperfect inspection process, rework, and sales return under two-level trade credit

    Directory of Open Access Journals (Sweden)

    Aditi Khanna

    2017-01-01

    Full Text Available Quality decisions are one of the major decisions in inventory management. It affects customer’s demand, loyalty and customer satisfaction and also inventory costs. Every manufacturing process is inherent to have some chance causes of variation which may lead to some defectives in the lot. So, in order to cater the customers with faultless products, an inspection process is inevitable, which may also be prone to errors. Thus for an operations manager, maintaining the quality of the lot and the screening process becomes a challenging task, when his objective is to determine the optimal order quantity for the inventory system. Besides these operational tasks, the goal is also to increase the customer base which eventually leads to higher profits. So, as a promotional tool, trade credit is being offered by both the retailer and supplier to their respective customers to encourage more frequent and higher volume purchases. Thus taking into account of these facts, a strategic production model is formulated here to study the combined effects of imperfect quality items, faulty inspection process, rework process, sales return under two level trade credit. The present study is a general framework for many articles and classical EPQ model. An analytical method is employed which jointly optimizes the retailer’s credit period and order quantity, so as to maximize the expected total profit per unit time. To study the behavior and application of the model, a numerical example has been cited and a comprehensive sensitivity analysis has been performed. The model can be widely applicable in manufacturing industries like textile, footwear, plastics, electronics, furniture etc.

  9. Cytoplasmic FMR1-Interacting Protein 2 Is a Major Genetic Factor Underlying Binge Eating.

    Science.gov (United States)

    Kirkpatrick, Stacey L; Goldberg, Lisa R; Yazdani, Neema; Babbs, R Keith; Wu, Jiayi; Reed, Eric R; Jenkins, David F; Bolgioni, Amanda F; Landaverde, Kelsey I; Luttik, Kimberly P; Mitchell, Karen S; Kumar, Vivek; Johnson, W Evan; Mulligan, Megan K; Cottone, Pietro; Bryant, Camron D

    2017-05-01

    Eating disorders are lethal and heritable; however, the underlying genetic factors are unknown. Binge eating is a highly heritable trait associated with eating disorders that is comorbid with mood and substance use disorders. Therefore, understanding its genetic basis will inform therapeutic development that could improve several comorbid neuropsychiatric conditions. We assessed binge eating in closely related C57BL/6 mouse substrains and in an F 2 cross to identify quantitative trait loci associated with binge eating. We used gene targeting to validate candidate genetic factors. Finally, we used transcriptome analysis of the striatum via messenger RNA sequencing to identify the premorbid transcriptome and the binge-induced transcriptome to inform molecular mechanisms mediating binge eating susceptibility and establishment. C57BL/6NJ but not C57BL/6J mice showed rapid and robust escalation in palatable food consumption. We mapped a single genome-wide significant quantitative trait locus on chromosome 11 (logarithm of the odds = 7.4) to a missense mutation in cytoplasmic FMR1-interacting protein 2 (Cyfip2). We validated Cyfip2 as a major genetic factor underlying binge eating in heterozygous knockout mice on a C57BL/6N background that showed reduced binge eating toward a wild-type C57BL/6J-like level. Transcriptome analysis of premorbid genetic risk identified the enrichment terms morphine addiction and retrograde endocannabinoid signaling, whereas binge eating resulted in the downregulation of a gene set enriched for decreased myelination, oligodendrocyte differentiation, and expression. We identified Cyfip2 as a major significant genetic factor underlying binge eating and provide a behavioral paradigm for future genome-wide association studies in populations with increased genetic complexity. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  10. Genetic Analysis of Serum-Derived Defective Hepatitis C Virus Genomes Revealed Novel ViralcisElements for Virus Replication and Assembly.

    Science.gov (United States)

    Li, Qingchao; Tong, Yimin; Xu, Yongfen; Niu, Junqi; Zhong, Jin

    2018-04-01

    Defective viral genomes (DVGs) of hepatitis C virus (HCV) exist, but their biological significances have not been thoroughly investigated. Here, we analyzed HCV DVGs circulating in patient sera that possess deletions in the structural protein-encoding region. About 30% of 41 HCV clinical isolates possess DVGs that originated from the full-length genome in the same patients. No correlation between DVGs, viremia, and alanine aminotransferase (ALT) levels was found. Sequencing analysis of DVGs revealed the existence of deletion hot spots, with upstream sites in E1 and downstream sites in E2 and NS2. Interestingly, the coding sequences for the core protein and the C-terminal protease domain of NS2 were always intact in DVGs despite the fact that both proteins are dispensable for HCV genome replication. Mechanistic studies showed that transmembrane segment 3 (TMS3) of NS2, located immediately upstream of its protease domain, was required for the cleavage of NS2-NS3 and the replication of DVGs. Moreover, we identified a highly conserved secondary structure (SL750) within the core domain 2-coding region that is critical for HCV genome packaging. In summary, our analysis of serum-derived HCV DVGs revealed novel viral cis elements that play important roles in virus replication and assembly. IMPORTANCE HCV DVGs have been identified in vivo and in vitro , but their biogenesis and physiological significances remain elusive. In addition, a conventional packaging signal has not yet been identified on the HCV RNA genome, and mechanisms underlying the specificity in the encapsidation of the HCV genome into infectious particles remain to be uncovered. Here, we identified new viral cis elements critical for the HCV life cycle by determining genetic constraints that define the boundary of serum-derived HCV DVGs. We found that transmembrane segment 3 of NS2, located immediately upstream of its protease domain, was required for the cleavage of NS2-NS3 and the replication of DVGs. We

  11. GENETIC VARIABILITY OF CULTURED PLANT TISSUES UNDER NORMAL CONDITIONS AND UNDER STRESS

    Directory of Open Access Journals (Sweden)

    Dolgikh Yu.I.

    2012-08-01

    Full Text Available The genetic variability induced by in vitro conditions known as somaclonal variation is of practical interest due to its potential uses in plant breeding but, on the other hand, if clonal propagation or transformation is main goal, it becomes an unwelcome phenomenon. Thus, it is important to know frequency, the genomic distribution, the mechanisms and factors influencing somaclonal variation. We studied variability of PCR-based DNA markers of cultured tissues and regenerated plants of maize and bread wheat. The original A188 line of maize and the somaclones obtained were tested using 38 RAPD and 10 ISSR primers. None of the A188 plants showed variation in the RAPD and ISSR spectra for any of the primers used. However, the PCR spectra obtained from the somaclones demonstrated some variations, i.e., 22 RAPD primers and 6 ISSR primers differentiated at least one somaclonal variant from the progenitor line. Six SCAR markers were developed based on several RAPD and ISSR fragments. The inheritance of these SCAR markers was verified in the selfing progeny of each somaclone in the R1–R4 generations and in the hybrids, with A188 as the parental line in the F1 and F2 generations. These markers were sequenced and bioinformatic searches were performed to understand the molecular events that may underlie the variability observed in the somaclones. All changes were found in noncoding sequences and were induced by different molecular events, such as the insertion of long terminal repeat transposon, precise miniature inverted repeat transposable element (MITE excision, microdeletion, recombination, and a change in the pool of mitochondrial DNA. In two groups of independently produced somaclones, the same features (morphological, molecular were variable, which confirms the theory of ‘hot spots’ occurring in the genome. The presence of the same molecular markers in the somaclones and in different non-somaclonal maize variants suggests that in some cases

  12. Cognitive mechanisms underlying disorganization of thought in a genetic syndrome (47,XXY)

    NARCIS (Netherlands)

    Van Rijn, Sophie; Aleman, Andre; De Sonneville, Leo; Swaab, Hanna

    Because of the risk for development of psychopathology such as psychotic symptoms, it has been suggested that studying men with the XXY karyotype may help in the search for underlying cognitive, neural and genetic mechanisms. The aim of this study was to identify cognitive mechanisms that may

  13. Genetic influence on blood pressure measured in the office, under laboratory stress and during real life

    NARCIS (Netherlands)

    Wang, Xiaoling; Ding, Xiuhua; Su, Shaoyong; Harshfield, Gregory; Treiber, Frank; Snieder, Harold

    To determine to what extent the genetic influences on blood pressure (BP) measured in the office, under psychologically stressful conditions in the laboratory and during real life are different from each other. Office BP, BP during a video game challenge and a social stressor interview, and 24-h

  14. A genetic analysis of relative growth rate and underlying components in Hordeum spontaneum

    NARCIS (Netherlands)

    Poorter, H.; Van Rijn, C.P.E.; Vanhala, T.K.; Verhoeven, K.J.F.; de Jong, Y.E.M.; Stams, A.J.M.; Lambers, H.

    2005-01-01

    Species from productive and unproductive habitats differ inherently in their relative growth rate (RGR) and a wide range of correlated quantitative traits. We investigated the genetic basis of this trait complex, and specifically assessed whether it is under the control of just one or a few genes

  15. Research of the Ion Current Density Influence on the Glass-Ceramics Surface Defects Forming under Ion-Beam Processing

    Directory of Open Access Journals (Sweden)

    V. G. Pozdnyakov

    2015-01-01

    Full Text Available Development of modern optics is primarily determined by manufacturing accuracy of the working surfaces of optical parts. Therefore, at the last stage of manufacturing optical parts the ion-beam treatment is applied. This method uses spraying the high-energy ions of heavy gases on the surface of a solid body. After an intense ion treatment there are microscopic defects, resembling chips, on the surface of polycrystalline glass. The aim of this work is to study distribution of the surface density of defects by sizes, depending on the density of ion current.Accelerator with an anode layer and a focused ion beam was used as an ion source. The accelerator worked on argon and created ion beam with Gaussian distribution of current density along the radius. The excess positive charge of the ion beam was compensated owing to ionization of residual gas. To eliminate the influence of slow ions with peripheral regions of the ion beam, the etching was performed through a circular aperture with a diameter of 40 mm.Surface treatment of the sample was carried out at the discharge voltage of 3800 V and current of 50 mA for 30 min. The maximum ion current density on the sample surface was 20.2 A/m2 and a power density was of 5.4·104 W/m2 .Distribution of defects by size was measured in three areas of the treated surface corresponding to different densities of ion current, namely: 20.2 A/m2 , 11.3A/m2 , and 3.4 A/m2 . Their number per area unit defines a density of defects.The results show that with increasing ion current density the density of defects on the surface of polycrystalline glass decreases. Thus a view of distribution function of defect density according to size is changed: density of small defects is reduced, and density of large ones increases. Also with increasing ion current density is observed an increase in the size of defects: a 6 times increase of the average size of defects results in 1.6 times increasing ion current density.These data will

  16. Genetic evidence for a role of Saccharomyces cerevisiae Mph1 in recombinational DNA repair under replicative stress.

    Science.gov (United States)

    Panico, Evandro Rocco; Ede, Christopher; Schildmann, Michael; Schürer, Kirsten Anke; Kramer, Wilfried

    2010-01-01

    In yeast as in human, DNA helicases play critical roles in assisting replication fork progression. The Saccharomyces cerevisiae MPH1 gene, homologue of human FANCM, has been involved in homologous recombination and DNA repair. We describe a synthetic growth defect of an mph1 deletion if combined with an srs2 deletion that can result-depending on the genetic background-in synthetic lethality. The lethality is suppressed by mutations in homologous recombination (rad51, rad52, rad55, rad57) and in the DNA damage checkpoint (rad9, rad24, rad17). Importantly, rad54 and mph1, epistatic for damage sensitivity, are subadditive for spontaneous mutator phenotype. Therefore, Mph1 could be placed at the Rad51-mediated strand invasion process, with a function distinct from Rad54. Moreover, siz1 mutation is viable with mph1 and additive for DNA damage sensitivity. mph1 srs2 double mutants, isolated in a background where they are viable, are synergistically sensitive to DNA damage. Moderate overexpression of SGS1 partially suppresses this sensitivity. Finally, we observe an epistatic relationship in terms of sensitivity to camptothecin of mms4 or mus81 to mph1. Overall, our results support a role of Mph1 in assisting replication progression. We propose two models for the resumption of DNA synthesis under replicative stress where Mph1 is placed at the sister chromatid interaction step.

  17. Recurrent candidiasis and early-onset gastric cancer in a patient with a genetically defined partial MYD88 defect

    NARCIS (Netherlands)

    Vogelaar, Ingrid P.; Ligtenberg, Marjolijn J L; van der Post, Rachel S.; de Voer, Richarda M.; Kets, C. Marleen; Jansen, Trees J G; Jacobs, Liesbeth; Schreibelt, Gerty; de Vries, I. Jolanda M; Netea, Mihai G.; Hoogerbrugge, Nicoline; Lubinski, Jan; Jakubowska, Anna; Teodorczyk, Urszula; Schackert, Hans K.; Aalfs, Cora M.; Gómez García, Encarna B.; Ranzani, Guglielmina N.; Molinaro, Valeria; van Hest, Liselotte P.; Hes, Frederik J.; Holinski-Feder, Elke; Genuardi, Maurizio; Ausems, Margreet G E M; Sijmons, Rolf H.; Wagner, Anja; van der Kolk, Lizet E.; Pinheiro, Hugo; Oliveira, Carla; Bjørnevoll, Inga; Høberg Vetti, Hildegunn; Van Krieken, J. Han J M

    2016-01-01

    Gastric cancer is caused by both genetic and environmental factors. A woman who suffered from recurrent candidiasis throughout her life developed diffuse-type gastric cancer at the age of 23 years. Using whole-exome sequencing we identified a germline homozygous missense variant in MYD88.

  18. Embedded defects

    International Nuclear Information System (INIS)

    Barriola, M.; Vachaspati, T.; Bucher, M.

    1994-01-01

    We give a prescription for embedding classical solutions and, in particular, topological defects in field theories which are invariant under symmetry groups that are not necessarily simple. After providing examples of embedded defects in field theories based on simple groups, we consider the electroweak model and show that it contains the Z string and a one-parameter family of strings called the W(α) string. It is argued that although the members of this family are gauge equivalent when considered in isolation, each member becomes physically distinct when multistring configurations are considered. We then turn to the issue of stability of embedded defects and demonstrate the instability of a large class of such solutions in the absence of bound states or condensates. The Z string is shown to be unstable for all values of the Higgs boson mass when θ W =π/4. W strings are also shown to be unstable for a large range of parameters. Embedded monopoles suffer from the Brandt-Neri-Coleman instability. Finally, we connect the electroweak string solutions to the sphaleron

  19. Genetic disorders of collagen.

    OpenAIRE

    Tsipouras, P; Ramirez, F

    1987-01-01

    Osteogenesis imperfecta, Ehlers-Danlos syndrome, and Marfan syndrome form a group of genetic disorders of connective tissue. These disorders exhibit remarkable clinical heterogeneity which reflects their underlying biochemical and molecular differences. Defects in collagen types I and III have been found in all three syndromes.

  20. AFLPs reveal different population genetic structure under contrasting environments in the marine snail Nucella lapillus L.

    Directory of Open Access Journals (Sweden)

    Belén Carro

    Full Text Available Dispersal has received growing attention in marine ecology, particularly since evidence obtained with up-to-date techniques challenged the traditional view. The dogwhelk Nucella lapillus L., a sedentary gastropod with direct development, is a good example: dispersal was traditionally assumed to be limited until studies with microsatellites disputed this idea. To shed some light on this controversy, the genetic structure of dogwhelk populations in northwest Spain was investigated with highly polymorphic AFLP markers giving special attention to the influence of hydrodynamic stress. In agreement with the expectations for a poor disperser, our results show a significant genetic structure at regional (<200 km and areal scales (<15 km. However, the spatial genetic structure varied with wave-exposure in the present case study: IBD was evident under sheltered conditions but absent from the exposed area where genetic differentiation was stronger. Our results provide evidence that differences in wave-exposure can exert a detectable influence on the genetic structure of coastal organisms, even in species without a planktonic larva.

  1. Genetic ablation of AQP2 in the mouse connecting tubules results in a mild urinary concentrating defect

    DEFF Research Database (Denmark)

    Kortenoeven, Marleen; Pedersen, Nis Borbye; Miller, Lance

    Body water balance is regulated in the kidney via the vasopressin (AVP) regulated water channel aquaporin-2 (AQP2) expressed in the connecting tubule (CNT) and the collecting duct (CD). Although crucial for the urinary concentrating mechanism, the relative role of AQP2 in the CNT and CD...... are not fully understood. To study the role of AQP2 in the CNT we generated a mouse model with a CNT-specific knock-out of AQP2. Confocal immunofluorescence microscopy of kidney sections demonstrated an absence of AQP2 immunolabeling in the CNT of the knock-out animals. 24 hour urine output was significantly...... in cortical kidney fractions with no compensatory changes in the AVP-regulated transporters NKCC2, AQP3 and AQP4. In conclusion, we have demonstrated that deletion of AQP2 from the CNT results in a mild urinary concentrating defect, without diminished maximal urinary concentrating ability. Our studies suggest...

  2. Genetic Adaptation to Growth Under Laboratory Conditions in Escherichia coli and Salmonella enterica

    Directory of Open Access Journals (Sweden)

    Anna Knöppel

    2018-04-01

    Full Text Available Experimental evolution under controlled laboratory conditions is becoming increasingly important to address various evolutionary questions, including, for example, the dynamics and mechanisms of genetic adaptation to different growth and stress conditions. In such experiments, mutations typically appear that increase the fitness under the conditions tested (medium adaptation, but that are not necessarily of interest for the specific research question. Here, we have identified mutations that appeared during serial passage of E. coli and S. enterica in four different and commonly used laboratory media and measured the relative competitive fitness and maximum growth rate of 111 genetically re-constituted strains, carrying different single and multiple mutations. Little overlap was found between the mutations that were selected in the two species and the different media, implying that adaptation occurs via different genetic pathways. Furthermore, we show that commonly occurring adaptive mutations can generate undesired genetic variation in a population and reduce the accuracy of competition experiments. However, by introducing media adaptation mutations with large effects into the parental strain that was used for the evolution experiment, the variation (standard deviation was decreased 10-fold, and it was possible to measure fitness differences between two competitors as small as |s| < 0.001.

  3. On holographic defect entropy

    Energy Technology Data Exchange (ETDEWEB)

    Estes, John [Blackett Laboratory, Imperial College,London SW7 2AZ (United Kingdom); Jensen, Kristan [Department of Physics and Astronomy, University of Victoria,Victoria, BC V8W 3P6 (Canada); C.N. Yang Institute for Theoretical Physics, SUNY Stony Brook,Stony Brook, NY 11794-3840 (United States); O’Bannon, Andy [Rudolf Peierls Centre for Theoretical Physics, University of Oxford,1 Keble Road, Oxford OX1 3NP (United Kingdom); Tsatis, Efstratios [8 Kotylaiou Street, Athens 11364 (Greece); Wrase, Timm [Stanford Institute for Theoretical Physics, Stanford University,Stanford, CA 94305 (United States)

    2014-05-19

    We study a number of (3+1)- and (2+1)-dimensional defect and boundary conformal field theories holographically dual to supergravity theories. In all cases the defects or boundaries are planar, and the defects are codimension-one. Using holography, we compute the entanglement entropy of a (hemi-)spherical region centered on the defect (boundary). We define defect and boundary entropies from the entanglement entropy by an appropriate background subtraction. For some (3+1)-dimensional theories we find evidence that the defect/boundary entropy changes monotonically under certain renormalization group flows triggered by operators localized at the defect or boundary. This provides evidence that the g-theorem of (1+1)-dimensional field theories generalizes to higher dimensions.

  4. On holographic defect entropy

    Science.gov (United States)

    Estes, John; Jensen, Kristan; O'Bannon, Andy; Tsatis, Efstratios; Wrase, Timm

    2014-05-01

    We study a number of (3 + 1)- and (2 + 1)-dimensional defect and boundary conformal field theories holographically dual to supergravity theories. In all cases the defects or boundaries are planar, and the defects are codimension-one. Using holography, we compute the entanglement entropy of a (hemi-)spherical region centered on the defect (boundary). We define defect and boundary entropies from the entanglement entropy by an appropriate background subtraction. For some (3 + 1)-dimensional theories we find evidence that the defect/boundary entropy changes monotonically under certain renormalization group flows triggered by operators localized at the defect or boundary. This provides evidence that the g-theorem of (1 + 1)-dimensional field theories generalizes to higher dimensions.

  5. Novel Genetic Variants of Sporadic Atrial Septal Defect (ASD) in a Chinese Population Identified by Whole-Exome Sequencing (WES).

    Science.gov (United States)

    Liu, Yong; Cao, Yu; Li, Yaxiong; Lei, Dongyun; Li, Lin; Hou, Zong Liu; Han, Shen; Meng, Mingyao; Shi, Jianlin; Zhang, Yayong; Wang, Yi; Niu, Zhaoyi; Xie, Yanhua; Xiao, Benshan; Wang, Yuanfei; Li, Xiao; Yang, Lirong; Wang, Wenju; Jiang, Lihong

    2018-03-05

    BACKGROUND Recently, mutations in several genes have been described to be associated with sporadic ASD, but some genetic variants remain to be identified. The aim of this study was to use whole-exome sequencing (WES) combined with bioinformatics analysis to identify novel genetic variants in cases of sporadic congenital ASD, followed by validation by Sanger sequencing. MATERIAL AND METHODS Five Han patients with secundum ASD were recruited, and their tissue samples were analyzed by WES, followed by verification by Sanger sequencing of tissue and blood samples. Further evaluation using blood samples included 452 additional patients with sporadic secundum ASD (212 male and 240 female patients) and 519 healthy subjects (252 male and 267 female subjects) for further verification by a multiplexed MassARRAY system. Bioinformatic analyses were performed to identify novel genetic variants associated with sporadic ASD. RESULTS From five patients with sporadic ASD, a total of 181,762 genomic variants in 33 exon loci, validated by Sanger sequencing, were selected and underwent MassARRAY analysis in 452 patients with ASD and 519 healthy subjects. Three loci with high mutation frequencies, the 138665410 FOXL2 gene variant, the 23862952 MYH6 gene variant, and the 71098693 HYDIN gene variant were found to be significantly associated with sporadic ASD (PASD (PASD, and supported the use of WES and bioinformatics analysis to identify disease-associated mutations.

  6. Birth Defects

    Science.gov (United States)

    A birth defect is a problem that happens while a baby is developing in the mother's body. Most birth defects happen during the first 3 months of ... in the United States is born with a birth defect. A birth defect may affect how the ...

  7. Identification of Sox8 as a modifier gene in a mouse model of Hirschsprung disease reveals underlying molecular defect.

    Science.gov (United States)

    Maka, Marzena; Stolt, C Claus; Wegner, Michael

    2005-01-01

    Mice carrying heterozygous mutations in the Sox10 gene display aganglionosis of the colon and represent a model for human Hirschsprung disease. Here, we show that the closely related Sox8 functions as a modifier gene for Sox10-dependent enteric nervous system defects as it increases both penetrance and severity of the defect in Sox10 heterozygous mice despite having no detectable influence on enteric nervous system development on its own. Sox8 exhibits an expression pattern very similar to Sox10 with occurrence in vagal and enteric neural crest cells and later confinement to enteric glia. Loss of Sox8 alleles in Sox10 heterozygous mice impaired colonization of the gut by enteric neural crest cells already at early times. Whereas proliferation, apoptosis, and neuronal differentiation were normal for enteric neural crest cells in the gut of mutant mice, apoptosis was dramatically increased in vagal neural crest cells outside the gut. The defects in enteric nervous system development of mice with Sox10 and Sox8 mutations are therefore likely caused by a reduction of the pool of undifferentiated vagal neural crest cells. Our study suggests that Sox8 and Sox10 are jointly required for the maintenance of these vagal neural crest stem cells.

  8. Renal thrombotic microangiopathy in patients with cblC defect : review of an under-recognized entity

    NARCIS (Netherlands)

    Beck, Bodo B; van Spronsen, FrancJan; Diepstra, Arjan; Berger, Rolf M F; Kömhoff, Martin

    Methylmalonic aciduria and homocystinuria, cobalamin C (cblC) type, is the most common genetic type of functional cobalamin (vitamin B-12) deficiency. This metabolic disease is characterized by marked heterogeneity of neurocognitive disease (microcephaly, seizures, developmental delay, ataxia,

  9. CoaSim: A Flexible Environment for Simulating Genetic Data under Coalescent Models

    DEFF Research Database (Denmark)

    Mailund; Schierup, Mikkel Heide; Pedersen, Christian Nørgaard Storm

    2005-01-01

    Background Coalescent simulations are playing a large role in interpreting large scale intra- polymorphism surveys and for planning and evaluating association studies. Coalescent of data sets under different models can be compared to the actual data to test different evolutionary factors and thus...... get insight into these. Results We have created the CoaSim application as a flexible environment for Monte various types of genetic data under equilibrium and non-equilibrium coalescent variety of applications. Interaction with the tool is through the Guile version scripting language. Scheme scripts...

  10. Sexually antagonistic selection on genetic variation underlying both male and female same-sex sexual behavior.

    Science.gov (United States)

    Berger, David; You, Tao; Minano, Maravillas R; Grieshop, Karl; Lind, Martin I; Arnqvist, Göran; Maklakov, Alexei A

    2016-05-13

    Intralocus sexual conflict, arising from selection for different alleles at the same locus in males and females, imposes a constraint on sex-specific adaptation. Intralocus sexual conflict can be alleviated by the evolution of sex-limited genetic architectures and phenotypic expression, but pleiotropic constraints may hinder this process. Here, we explored putative intralocus sexual conflict and genetic (co)variance in a poorly understood behavior with near male-limited expression. Same-sex sexual behaviors (SSBs) generally do not conform to classic evolutionary models of adaptation but are common in male animals and have been hypothesized to result from perception errors and selection for high male mating rates. However, perspectives incorporating sex-specific selection on genes shared by males and females to explain the expression and evolution of SSBs have largely been neglected. We performed two parallel sex-limited artificial selection experiments on SSB in male and female seed beetles, followed by sex-specific assays of locomotor activity and male sex recognition (two traits hypothesized to be functionally related to SSB) and adult reproductive success (allowing us to assess fitness consequences of genetic variance in SSB and its correlated components). Our experiments reveal both shared and sex-limited genetic variance for SSB. Strikingly, genetically correlated responses in locomotor activity and male sex-recognition were associated with sexually antagonistic fitness effects, but these effects differed qualitatively between male and female selection lines, implicating intralocus sexual conflict at both male- and female-specific genetic components underlying SSB. Our study provides experimental support for the hypothesis that widespread pleiotropy generates pervasive intralocus sexual conflict governing the expression of SSBs, suggesting that SSB in one sex can occur due to the expression of genes that carry benefits in the other sex.

  11. Novel genetic loci underlying human intracranial volume identified through genome-wide association

    Science.gov (United States)

    Adams, Hieab HH; Hibar, Derrek P; Chouraki, Vincent; Stein, Jason L; Nyquist, Paul A; Rentería, Miguel E; Trompet, Stella; Arias-Vasquez, Alejandro; Seshadri, Sudha; Desrivières, Sylvane; Beecham, Ashley H; Jahanshad, Neda; Wittfeld, Katharina; Van der Lee, Sven J; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S; Armstrong, Nicola J; Athanasiu, Lavinia; Axelsson, Tomas; Beiser, Alexa; Bernard, Manon; Bis, Joshua C; Blanken, Laura ME; Blanton, Susan H; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brickman, Adam M; Carmichael, Owen; Chakravarty, M Mallar; Chauhan, Ganesh; Chen, Qiang; Ching, Christopher RK; Cuellar-Partida, Gabriel; Den Braber, Anouk; Doan, Nhat Trung; Ehrlich, Stefan; Filippi, Irina; Ge, Tian; Giddaluru, Sudheer; Goldman, Aaron L; Gottesman, Rebecca F; Greven, Corina U; Grimm, Oliver; Griswold, Michael E; Guadalupe, Tulio; Hass, Johanna; Haukvik, Unn K; Hilal, Saima; Hofer, Edith; Hoehn, David; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Liao, Jiemin; Liewald, David CM; Lopez, Lorna M; Luciano, Michelle; Macare, Christine; Marquand, Andre; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; Mazoyer, Bernard; McKay, David R; McWhirter, Rebekah; Milaneschi, Yuri; Mirza-Schreiber, Nazanin; Muetzel, Ryan L; Maniega, Susana Muñoz; Nho, Kwangsik; Nugent, Allison C; Olde Loohuis, Loes M; Oosterlaan, Jaap; Papmeyer, Martina; Pappa, Irene; Pirpamer, Lukas; Pudas, Sara; Pütz, Benno; Rajan, Kumar B; Ramasamy, Adaikalavan; Richards, Jennifer S; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rommelse, Nanda; Rose, Emma J; Royle, Natalie A; Rundek, Tatjana; Sämann, Philipp G; Satizabal, Claudia L; Schmaal, Lianne; Schork, Andrew J; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V; Sprooten, Emma; Strike, Lachlan T; Teumer, Alexander; Thomson, Russell; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Meer, Dennis; Van Donkelaar, Marjolein MJ; Van Eijk, Kristel R; Van Erp, Theo GM; Van Rooij, Daan; Walton, Esther; Westlye, Lars T; Whelan, Christopher D; Windham, Beverly G; Winkler, Anderson M; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Xu, Bing; Yanek, Lisa R; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P; Agartz, Ingrid; Aggarwal, Neelum T; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A; Arepalli, Sampath; Assareh, Amelia A; Barral, Sandra; Bastin, Mark E; Becker, Diane M; Becker, James T; Bennett, David A; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I; Brodaty, Henry; Brouwer, Rachel M; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cahn, Wiepke; Calhoun, Vince D; Cannon, Dara M; Cavalleri, Gianpiero L; Chen, Christopher; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Dale, Anders M; Davies, Gareth E; De Geus, Eco JC; De Jager, Philip L; de Zubicaray, Greig I; Delanty, Norman; Depondt, Chantal; DeStefano, Anita L; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Espeseth, Thomas; Evans, Denis A; Fedko, Iryna O; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E; Fleischman, Debra A; Ford, Ian; Foroud, Tatiana M; Fox, Peter T; Francks, Clyde; Fukunaga, Masaki; Gibbs, J Raphael; Glahn, David C; Gollub, Randy L; Göring, Harald HH; Grabe, Hans J; Green, Robert C; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Hansell, Narelle K; Hardy, John; Hartman, Catharina A; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G; Heslenfeld, Dirk J; Ho, Beng-Choon; Hoekstra, Pieter J; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Hulshoff Pol, Hilleke E; Ikeda, Masashi; Ikram, M Kamran; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G; Jukema, J Wouter; Kahn, René S; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L; Longstreth, WT; Lopez, Oscar L; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S; McDonald, Colm; McIntosh, Andrew M; McMahon, Katie L; McMahon, Francis J; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W

    2016-01-01

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth. PMID:27694991

  12. Determination of the Genetic Architecture Underlying Short Wavelength Sensitivity in Lake Malawi Cichlids.

    Science.gov (United States)

    Nandamuri, Sri Pratima; Dalton, Brian E; Carleton, Karen L

    2017-06-01

    African cichlids are an exemplary system to study organismal diversity and rapid speciation. Species differ in external morphology including jaw shape and body coloration, but also differ in sensory systems including vision. All cichlids have 7 cone opsin genes with species differing broadly in which opsins are expressed. The differential opsin expression results in closely related species with substantial differences in spectral sensitivity of their photoreceptors. In this work, we take a first step in determining the genetic basis of opsin expression in cichlids. Using a second generation cross between 2 species with different opsin expression patterns, we make a conservative estimate that short wavelength opsin expression is regulated by a few loci. Genetic mapping in 96 F2 hybrids provides clear evidence of a cis-regulatory region for SWS1 opsin that explains 34% of the variation in expression between the 2 species. Additionally, in situ hybridization has shown that SWS1 and SWS2B opsins are coexpressed in individual single cones in the retinas of F2 progeny. Results from this work will contribute to a better understanding of the genetic architecture underlying opsin expression. This knowledge will help answer long-standing questions about the evolutionary processes fundamental to opsin expression variation and how this contributes to adaptive cichlid divergence. © The American Genetic Association 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Comparative proteomic analysis of genetically modified maize grown under different agroecosystems conditions in Brazil

    Science.gov (United States)

    2013-01-01

    Background Profiling technologies allow the simultaneous measurement and comparison of thousands of cell components without prior knowledge of their identity. In the present study, we used two-dimensional gel electrophoresis combined with mass spectrometry to evaluate protein expression of Brazilian genetically modified maize hybrid grown under different agroecosystems conditions. To this effect, leaf samples were subjected to comparative analysis using the near-isogenic non-GM hybrid as the comparator. Results In the first stage of the analysis, the main sources of variation in the dataset were identified by using Principal Components Analysis which correlated most of the variation to the different agroecosystems conditions. Comparative analysis within each field revealed a total of thirty two differentially expressed proteins between GM and non-GM samples that were identified and their molecular functions were mainly assigned to carbohydrate and energy metabolism, genetic information processing and stress response. Conclusions To the best of our knowledge this study represents the first evidence of protein identities with differentially expressed isoforms in Brazilian MON810 genetic background hybrid grown under field conditions. As global databases on outputs from “omics” analysis become available, these could provide a highly desirable benchmark for safety assessments. PMID:24304660

  14. Managing genetic tests, surveillance, and preventive medicine under a public health insurance system.

    Science.gov (United States)

    Filipova-Neumann, Lilia; Hoy, Michael

    2014-03-01

    There is a prospect in the medium to long term future of substantial advancements in the understanding of the relationship between disease and genetics. We consider the implications of increased information from genetic tests about predisposition to diseases from the perspective of managing health care provision under a public health insurance scheme. In particular, we consider how such information may potentially improve the targeting of medical surveillance (or prevention) activities to improve the chances of early detection of disease onset. We show that the moral hazard implications inherent in surveillance and prevention decisions that are chosen to be privately rather than socially optimal may be exacerbated by increased information about person-specific predisposition to disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Exploring the genetics underlying autoimmune diseases with network analysis and link prediction

    KAUST Repository

    Alanis Lobato, Gregorio

    2014-02-01

    Ever since the first Genome Wide Association Study (GWAS) was carried out we have seen an important number of discoveries of biological and clinical relevance. However, there are some scientists that consider that these research outcomes and their utility are far from what was expected from this experimental design. We instead believe that the thousands of genetic variants associated with complex disorders by means of GWASs are an extremely valuable source of information that needs to be mined in a different way. Based on this philosophy, we followed a holistic perspective to analyze GWAS data and explored the structural properties of the network representation of one of these datasets with the aim to advance our understanding of the genetic intricacies underlying autoimmune human diseases. The simplicity, computational efficiency and precision of the tools proposed in this paper represent a new means to address GWAS data and contribute to the better exploitation of these rich sources of information. © 2014 IEEE.

  16. Genome-wide association mapping in dogs enables identification of the homeobox gene, NKX2-8, as a genetic component of neural tube defects in humans.

    Directory of Open Access Journals (Sweden)

    Noa Safra

    Full Text Available Neural tube defects (NTDs is a general term for central nervous system malformations secondary to a failure of closure or development of the neural tube. The resulting pathologies may involve the brain, spinal cord and/or vertebral column, in addition to associated structures such as soft tissue or skin. The condition is reported among the more common birth defects in humans, leading to significant infant morbidity and mortality. The etiology remains poorly understood but genetic, nutritional, environmental factors, or a combination of these, are known to play a role in the development of NTDs. The variable conditions associated with NTDs occur naturally in dogs, and have been previously reported in the Weimaraner breed. Taking advantage of the strong linkage-disequilibrium within dog breeds we performed genome-wide association analysis and mapped a genomic region for spinal dysraphism, a presumed NTD, using 4 affected and 96 unaffected Weimaraners. The associated region on canine chromosome 8 (pgenome  =3.0 × 10(-5, after 100,000 permutations, encodes 18 genes, including NKX2-8, a homeobox gene which is expressed in the developing neural tube. Sequencing NKX2-8 in affected Weimaraners revealed a G to AA frameshift mutation within exon 2 of the gene, resulting in a premature stop codon that is predicted to produce a truncated protein. The exons of NKX2-8 were sequenced in human patients with spina bifida and rare variants (rs61755040 and rs10135525 were found to be significantly over-represented (p=0.036. This is the first documentation of a potential role for NKX2-8 in the etiology of NTDs, made possible by investigating the molecular basis of naturally occurring mutations in dogs.

  17. The joint regulation of genetic gain and inbreeding under mate selection.

    Science.gov (United States)

    Klieve, H M; Kinghorn, B P; Barwick, S A

    1994-01-12

    Stochastic simulation was used to evaluate a range of selection strategies with respect to both additive genetic response and inbreeding. Strategies involving selection on BLUP ebvs or individual phenotype, followed by random mating, were compared with mate selection strategies which used portfolio analysis to give joint consideration to genetic merit and inbreeding. An adapted Mean Of Total Absolute Deviations (MOTAD) method was used in a mate selection model to define optimal matings with regard to aggregate genetic merit and inbreeding for a base population h(2) of 0.2. Compared with random mating following selection on BLUP ebvs, inbreeding levels after 10 years of selection were able to be reduced under BLUP plus mate selection from ∼.23 to as little as .11. Additive genetic gain was either little compromised or increased. The results suggest that information linking expected levels of genetic merit and inbreeding can be used to find the preferred selection strategy. ZUSAMMENFASSUNG: Gemeinsame Kontrolle von Zuchtfortschritt und Inzucht bei Partnerselektion Es wurde stochastische Simulation zur Auswertung einer Reihe von Selektionsstrategien hinsichtlich Zuchtwertzuwachs und Inzucht verwendet. Strategien mit Selektion auf der Basis von BLUP ebvs oder individuellem Phänotyp mit nachfolgender Zufallspaarung wurden mit Partnerselektionsstrategien verglichen, die Portfolioanalyse zur gemeinsamen Beachtung von Zuchtwert und Inzucht verwendeten. Eine Methode adaptierter MITTELWERTE TOTALER ABSOLUTER ABWEICHUNGEN (MOTAD) Methode wurde beim Partnerselektionsmodell zur Definition optimaler Paarungen in Hinblick auf Gesamtzuchtwert und Inzucht bei einer Populationsheritabilität von 0,2 verwendet. Verglichen mit Zufallspaarung nach Selektion auf BLUP ebvs waren die Inzuchtgrade nach 10 Selektionsjahren von 0,23 auf 0,11 reduziert und additiver Zuchtfortschritt war dabei wenig beeinträchtigt oder nahm sogar zu. Die Ergebnisse weisen darauf hin, daß Information, die

  18. Genetic Parameter Estimates of Carcass Traits under National Scale Breeding Scheme for Beef Cattle

    Directory of Open Access Journals (Sweden)

    ChangHee Do

    2016-08-01

    productivity and carcass quality could be obtained under the national scale breeding scheme of Korea for Hanwoo and that continuous efforts to improve the breeding scheme should be made to increase genetic progress.

  19. Delimiting genetic units in Neotropical toads under incomplete lineage sorting and hybridization

    Directory of Open Access Journals (Sweden)

    Thomé Maria Tereza C

    2012-12-01

    Full Text Available Abstract Background Delimiting genetic units is useful to enhance taxonomic discovery and is often the first step toward understanding evolutionary mechanisms generating diversification. The six species within the Rhinella crucifer group of toads were defined under morphological criteria alone. Previous data suggest limited correspondence of these species to mitochondrial lineages, and morphological intergradation at transitions between forms suggests hybridization. Here we extensively sampled populations throughout the geographic distribution of the group and analyzed mitochondrial and nuclear sequence data to delimit genetic units using tree–based and allele frequency–based approaches. Results These approaches yielded complementary results, with allele frequency-based methods performing unexpectedly well given the limited number of loci examined. Both mitochondrial and nuclear markers supported a genetic structure of five units within the group, with three of the inferred units distributed within its main range, while two other units occur in separate isolates. The inferred units are mostly discordant with currently described forms: unequivocal association exists for only two of the six species in the group. Genetic evidence for hybridization exists for two pairs of units, with clear cyto–nuclear allele mixing observed in one case. Conclusions Our results confirmed that current taxonomy does not represent evolutionary units in the Rhinella crucifer group. Correspondence between genetically distinguishable units and the currently recognized species is only possible for Rhinella henseli and R. inopina. The recognition of other species relies on the reassessment of the geographic range of R. crucifer, the examination of the type series of R. ornata for hybrids, and on the use of additional markers to verify the genetic distinctiveness of R. abei. We state that R. pombali should not remain a valid species since its description appears to be

  20. Features of transformation of impurity-defect complexes in СdTe:Сl under the influence of microwave radiation

    Directory of Open Access Journals (Sweden)

    Budzulyak S. I.

    2014-08-01

    Full Text Available High-resistance cadmium telluride single crystals are promising material for production of ionizing radiation detectors. To increase crystal resistance, they are doped with chlorine. The detector quality depends on uniformity of chlorine impurity distribution over crystal. It is known that low-dose microwave irradiation can homogenize impurity distribution in a specimen. In the present work, we made an attempt to improve the detector material quality by using such post-technological treatment, as well as to study state variation for impurity-defect complexes. To this end, the effect of microwave irradiation on transformation of impurity-defect complexes in CdTe:Cl single crystals was investigated using low-temperature photoluminescence. It is shown that activation of ClTe donor centers by microwave irradiation for 10 s and presence of VCd acceptor centers in the specimens under investigation effectively facilitate formation of (VNd–ClTe defect centers at which excitons are bound. Detailed investigations of the band form for donor-acceptor pairs (DAPs in CdTe:Cl single crystals made it possible to determine the Huang—Rhys factor (that characterizes electron-phonon interaction in CdTe:Cl DAPs as a function of microwave treatment duration. It is shown for single crystals with NCl = 5·1017 cm–3 and 5·1019 cm–3 that the Huang—Rhys factor grows with microwave irradiation dose. This is related to both homogenization of donor and acceptor centers distribution and increase of donor—acceptor spacing. It is shown that microwave irradiation of CdTe:Cl single crystals results in concentration reduction for separate cadmium vacancies VCd because of formation of (VNd—ClTe defect centers at which excitons are bound.

  1. Histochemical examination of adipose derived stem cells combined with β-TCP for bone defects restoration under systemic administration of 1α,25(OH)2D3.

    Science.gov (United States)

    Feng, Wei; Lv, Shengyu; Cui, Jian; Han, Xiuchun; Du, Juan; Sun, Jing; Wang, Kefeng; Wang, Zhenming; Lu, Xiong; Guo, Jie; Oda, Kimimitsu; Amizuka, Norio; Xu, Xin; Li, Minqi

    2015-09-01

    The purpose of this study was to evaluate the effects of osteogenic differentiated adipose-derived stem cell (ADSC) loaded beta-tricalcium phosphate (β-TCP) in the restoration of bone defects under intraperitoneal administration of 1α,25-dihydroxyvitamin D3(1α,25(OH)2D3). ADSCs were isolated from the fat tissue of 8 week old Wister rats and co-cultured with β-TCP for 21 days under osteogenic induction. Then the ADSC-β-TCP complexes were implanted into bone defects in the femora of rats. 1α,25(OH)2D3 (VD) or normal saline (NS) was administrated intraperitoneally every other day after the surgery. Femora were harvested at day 7, day 14 and day 28 post-surgery. There were 4 groups for all specimens: β-TCP-NS group; β-TCP-ADSC-NS group; β-TCP-VD group and β-TCP-ADSC-VD group. Alkaline phosphatase (ALP) was up-regulated obviously in ADSC groups compared with non-ADSC groups at day 7, day 14 and day 28, although high expression of runt-related transcription factor 2 (RUNX2) was only seen at day 7. Furthermore, the number of TRAP-positive osteoclasts and the expression of cathepsin K (CK) were significantly decreased in VD groups compared with non-VD groups at day 7 and day 14. As a most significant finding, the β-TCP-ADSC-VD group showed the highest BV/TV ratio compared with the other three groups at day 28. Taken together, ADSC-loaded β-TCP under the administration of 1α,25(OH)2D3 made a promising therapy for bone defects restoration. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Genetic variability of garlic accessions as revealed by agro-morphological traits evaluated under different environments.

    Science.gov (United States)

    Hoogerheide, E S S; Azevedo Filho, J A; Vencovsky, R; Zucchi, M I; Zago, B W; Pinheiro, J B

    2017-05-31

    The cultivated garlic (Allium sativum L.) displays a wide phenotypic diversity, which is derived from natural mutations and phenotypic plasticity, due to dependence on soil type, moisture, latitude, altitude and cultural practices, leading to a large number of cultivars. This study aimed to evaluate the genetic variability shown by 63 garlic accessions belonging to Instituto Agronômico de Campinas and the Escola Superior de Agricultura "Luiz de Queiroz" germplasm collections. We evaluated ten quantitative characters in experimental trials conducted under two localities of the State of São Paulo: Monte Alegre do Sul and Piracicaba, during the agricultural year of 2007, in a randomized blocks design with five replications. The Mahalanobis distance was used to measure genetic dissimilarities. The UPGMA method and Tocher's method were used as clustering procedures. Results indicated significant variation among accessions (P < 0.01) for all evaluated characters, except for the percentage of secondary bulb growth in MAS, indicating the existence of genetic variation for bulb production, and germplasm evaluation considering different environments is more reliable for the characterization of the genotypic variability among garlic accessions, since it diminishes the environmental effects in the clustering of genotypes.

  3. Novel genetic loci underlying human intracranial volume identified through genome-wide association.

    Science.gov (United States)

    Adams, Hieab H H; Hibar, Derrek P; Chouraki, Vincent; Stein, Jason L; Nyquist, Paul A; Rentería, Miguel E; Trompet, Stella; Arias-Vasquez, Alejandro; Seshadri, Sudha; Desrivières, Sylvane; Beecham, Ashley H; Jahanshad, Neda; Wittfeld, Katharina; Van der Lee, Sven J; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S; Armstrong, Nicola J; Athanasiu, Lavinia; Axelsson, Tomas; Beiser, Alexa; Bernard, Manon; Bis, Joshua C; Blanken, Laura M E; Blanton, Susan H; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brickman, Adam M; Carmichael, Owen; Chakravarty, M Mallar; Chauhan, Ganesh; Chen, Qiang; Ching, Christopher R K; Cuellar-Partida, Gabriel; Braber, Anouk Den; Doan, Nhat Trung; Ehrlich, Stefan; Filippi, Irina; Ge, Tian; Giddaluru, Sudheer; Goldman, Aaron L; Gottesman, Rebecca F; Greven, Corina U; Grimm, Oliver; Griswold, Michael E; Guadalupe, Tulio; Hass, Johanna; Haukvik, Unn K; Hilal, Saima; Hofer, Edith; Hoehn, David; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Liao, Jiemin; Liewald, David C M; Lopez, Lorna M; Luciano, Michelle; Macare, Christine; Marquand, Andre; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; Mazoyer, Bernard; McKay, David R; McWhirter, Rebekah; Milaneschi, Yuri; Mirza-Schreiber, Nazanin; Muetzel, Ryan L; Maniega, Susana Muñoz; Nho, Kwangsik; Nugent, Allison C; Loohuis, Loes M Olde; Oosterlaan, Jaap; Papmeyer, Martina; Pappa, Irene; Pirpamer, Lukas; Pudas, Sara; Pütz, Benno; Rajan, Kumar B; Ramasamy, Adaikalavan; Richards, Jennifer S; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rommelse, Nanda; Rose, Emma J; Royle, Natalie A; Rundek, Tatjana; Sämann, Philipp G; Satizabal, Claudia L; Schmaal, Lianne; Schork, Andrew J; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V; Sprooten, Emma; Strike, Lachlan T; Teumer, Alexander; Thomson, Russell; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Meer, Dennis; Van Donkelaar, Marjolein M J; Van Eijk, Kristel R; Van Erp, Theo G M; Van Rooij, Daan; Walton, Esther; Westlye, Lars T; Whelan, Christopher D; Windham, Beverly G; Winkler, Anderson M; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Xu, Bing; Yanek, Lisa R; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P; Agartz, Ingrid; Aggarwal, Neelum T; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A; Arepalli, Sampath; Assareh, Amelia A; Barral, Sandra; Bastin, Mark E; Becker, Diane M; Becker, James T; Bennett, David A; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I; Brodaty, Henry; Brouwer, Rachel M; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cahn, Wiepke; Calhoun, Vince D; Cannon, Dara M; Cavalleri, Gianpiero L; Chen, Christopher; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Dale, Anders M; Davies, Gareth E; De Geus, Eco J C; De Jager, Philip L; de Zubicaray, Greig I; Delanty, Norman; Depondt, Chantal; DeStefano, Anita L; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Espeseth, Thomas; Evans, Denis A; Fedko, Iryna O; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E; Fleischman, Debra A; Ford, Ian; Foroud, Tatiana M; Fox, Peter T; Francks, Clyde; Fukunaga, Masaki; Gibbs, J Raphael; Glahn, David C; Gollub, Randy L; Göring, Harald H H; Grabe, Hans J; Green, Robert C; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Hansell, Narelle K; Hardy, John; Hartman, Catharina A; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G; Heslenfeld, Dirk J; Ho, Beng-Choon; Hoekstra, Pieter J; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Hulshoff Pol, Hilleke E; Ikeda, Masashi; Ikram, M Kamran; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G; Jukema, J Wouter; Kahn, René S; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L; Longstreth, W T; Lopez, Oscar L; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S; McDonald, Colm; McIntosh, Andrew M; McMahon, Katie L; McMahon, Francis J; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Mosley, Thomas H; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Nalls, Michael A; Nauck, Matthias; Nichols, Thomas E; Niessen, Wiro J; Nöthen, Markus M; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L; Ophoff, Roel A; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W J H; Pike, G Bruce; Potkin, Steven G; Psaty, Bruce M; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L; Romanczuk-Seiferth, Nina; Rotter, Jerome I; Ryten, Mina; Sacco, Ralph L; Sachdev, Perminder S; Saykin, Andrew J; Schmidt, Reinhold; Schofield, Peter R; Sigurdsson, Sigurdur; Simmons, Andy; Singleton, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soininen, Hilkka; Srikanth, Velandai; Steen, Vidar M; Stott, David J; Sussmann, Jessika E; Thalamuthu, Anbupalam; Tiemeier, Henning; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Tzourio, Christophe; Uitterlinden, Andre G; Hernández, Maria C Valdés; Van der Brug, Marcel; Van der Lugt, Aad; Van der Wee, Nic J A; Van Duijn, Cornelia M; Van Haren, Neeltje E M; Van T Ent, Dennis; Van Tol, Marie-Jose; Vardarajan, Badri N; Veltman, Dick J; Vernooij, Meike W; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M; Wassink, Thomas H; Weale, Michael E; Weinberger, Daniel R; Weiner, Michael W; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y; Wright, Clinton B; Zielke, H Ronald; Zonderman, Alan B; Deary, Ian J; DeCarli, Charles; Schmidt, Helena; Martin, Nicholas G; De Craen, Anton J M; Wright, Margaret J; Launer, Lenore J; Schumann, Gunter; Fornage, Myriam; Franke, Barbara; Debette, Stéphanie; Medland, Sarah E; Ikram, M Arfan; Thompson, Paul M

    2016-12-01

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρ genetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

  4. Genetic dyslexia risk variant is related to neural connectivity patterns underlying phonological awareness in children.

    Science.gov (United States)

    Skeide, Michael A; Kirsten, Holger; Kraft, Indra; Schaadt, Gesa; Müller, Bent; Neef, Nicole; Brauer, Jens; Wilcke, Arndt; Emmrich, Frank; Boltze, Johannes; Friederici, Angela D

    2015-09-01

    Phonological awareness is the best-validated predictor of reading and spelling skill and therefore highly relevant for developmental dyslexia. Prior imaging genetics studies link several dyslexia risk genes to either brain-functional or brain-structural factors of phonological deficits. However, coherent evidence for genetic associations with both functional and structural neural phenotypes underlying variation in phonological awareness has not yet been provided. Here we demonstrate that rs11100040, a reported modifier of SLC2A3, is related to the functional connectivity of left fronto-temporal phonological processing areas at resting state in a sample of 9- to 12-year-old children. Furthermore, we provide evidence that rs11100040 is related to the fractional anisotropy of the arcuate fasciculus, which forms the structural connection between these areas. This structural connectivity phenotype is associated with phonological awareness, which is in turn associated with the individual retrospective risk scores in an early dyslexia screening as well as to spelling. These results suggest a link between a dyslexia risk genotype and a functional as well as a structural neural phenotype, which is associated with a phonological awareness phenotype. The present study goes beyond previous work by integrating genetic, brain-functional and brain-structural aspects of phonological awareness within a single approach. These combined findings might be another step towards a multimodal biomarker for developmental dyslexia. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Sardinians genetic background explained by runs of homozygosity and genomic regions under positive selection.

    Science.gov (United States)

    Di Gaetano, Cornelia; Fiorito, Giovanni; Ortu, Maria Francesca; Rosa, Fabio; Guarrera, Simonetta; Pardini, Barbara; Cusi, Daniele; Frau, Francesca; Barlassina, Cristina; Troffa, Chiara; Argiolas, Giuseppe; Zaninello, Roberta; Fresu, Giovanni; Glorioso, Nicola; Piazza, Alberto; Matullo, Giuseppe

    2014-01-01

    The peculiar position of Sardinia in the Mediterranean sea has rendered its population an interesting biogeographical isolate. The aim of this study was to investigate the genetic population structure, as well as to estimate Runs of Homozygosity and regions under positive selection, using about 1.2 million single nucleotide polymorphisms genotyped in 1077 Sardinian individuals. Using four different methods--fixation index, inflation factor, principal component analysis and ancestry estimation--we were able to highlight, as expected for a genetic isolate, the high internal homogeneity of the island. Sardinians showed a higher percentage of genome covered by RoHs>0.5 Mb (F(RoH%0.5)) when compared to peninsular Italians, with the only exception of the area surrounding Alghero. We furthermore identified 9 genomic regions showing signs of positive selection and, we re-captured many previously inferred signals. Other regions harbor novel candidate genes for positive selection, like TMEM252, or regions containing long non coding RNA. With the present study we confirmed the high genetic homogeneity of Sardinia that may be explained by the shared ancestry combined with the action of evolutionary forces.

  6. The flowering repressor SVP underlies a novel Arabidopsis thaliana QTL interacting with the genetic background.

    Science.gov (United States)

    Méndez-Vigo, Belén; Martínez-Zapater, José M; Alonso-Blanco, Carlos

    2013-01-01

    The timing of flowering initiation is a fundamental trait for the adaptation of annual plants to different environments. Large amounts of intraspecific quantitative variation have been described for it among natural accessions of many species, but the molecular and evolutionary mechanisms underlying this genetic variation are mainly being determined in the model plant Arabidopsis thaliana. To find novel A. thaliana flowering QTL, we developed introgression lines from the Japanese accession Fuk, which was selected based on the substantial transgression observed in an F(2) population with the reference strain Ler. Analysis of an early flowering line carrying a single Fuk introgression identified Flowering Arabidopsis QTL1 (FAQ1). We fine-mapped FAQ1 in an 11 kb genomic region containing the MADS transcription factor gene SHORT VEGETATIVE PHASE (SVP). Complementation of the early flowering phenotype of FAQ1-Fuk with a SVP-Ler transgen demonstrated that FAQ1 is SVP. We further proved by directed mutagenesis and transgenesis that a single amino acid substitution in SVP causes the loss-of-function and early flowering of Fuk allele. Analysis of a worldwide collection of accessions detected FAQ1/SVP-Fuk allele only in Asia, with the highest frequency appearing in Japan, where we could also detect a potential ancestral genotype of FAQ1/SVP-Fuk. In addition, we evaluated allelic and epistatic interactions of SVP natural alleles by analysing more than one hundred transgenic lines carrying Ler or Fuk SVP alleles in five genetic backgrounds. Quantitative analyses of these lines showed that FAQ1/SVP effects vary from large to small depending on the genetic background. These results support that the flowering repressor SVP has been recently selected in A. thaliana as a target for early flowering, and evidence the relevance of genetic interactions for the intraspecific evolution of FAQ1/SVP and flowering time.

  7. The flowering repressor SVP underlies a novel Arabidopsis thaliana QTL interacting with the genetic background.

    Directory of Open Access Journals (Sweden)

    Belén Méndez-Vigo

    Full Text Available The timing of flowering initiation is a fundamental trait for the adaptation of annual plants to different environments. Large amounts of intraspecific quantitative variation have been described for it among natural accessions of many species, but the molecular and evolutionary mechanisms underlying this genetic variation are mainly being determined in the model plant Arabidopsis thaliana. To find novel A. thaliana flowering QTL, we developed introgression lines from the Japanese accession Fuk, which was selected based on the substantial transgression observed in an F(2 population with the reference strain Ler. Analysis of an early flowering line carrying a single Fuk introgression identified Flowering Arabidopsis QTL1 (FAQ1. We fine-mapped FAQ1 in an 11 kb genomic region containing the MADS transcription factor gene SHORT VEGETATIVE PHASE (SVP. Complementation of the early flowering phenotype of FAQ1-Fuk with a SVP-Ler transgen demonstrated that FAQ1 is SVP. We further proved by directed mutagenesis and transgenesis that a single amino acid substitution in SVP causes the loss-of-function and early flowering of Fuk allele. Analysis of a worldwide collection of accessions detected FAQ1/SVP-Fuk allele only in Asia, with the highest frequency appearing in Japan, where we could also detect a potential ancestral genotype of FAQ1/SVP-Fuk. In addition, we evaluated allelic and epistatic interactions of SVP natural alleles by analysing more than one hundred transgenic lines carrying Ler or Fuk SVP alleles in five genetic backgrounds. Quantitative analyses of these lines showed that FAQ1/SVP effects vary from large to small depending on the genetic background. These results support that the flowering repressor SVP has been recently selected in A. thaliana as a target for early flowering, and evidence the relevance of genetic interactions for the intraspecific evolution of FAQ1/SVP and flowering time.

  8. Unfolding an under-determined neutron spectrum using genetic algorithm based Monte Carlo

    International Nuclear Information System (INIS)

    Suman, V.; Sarkar, P.K.

    2011-01-01

    Spallation in addition to the other photon-neutron reactions in target materials and different components in accelerators may result in production of huge amount of energetic protons which further leads to the production of neutron and contributes to the main component of the total dose. For dosimetric purposes in accelerator facilities the detector measurements doesn't provide directly the actual neutron flux values but a cumulative picture. To obtain Neutron spectrum from the measured data, response functions of the measuring instrument together with the measurements are used into many unfolding techniques which are frequently used for unfolding the hidden spectral information. Here we discuss a genetic algorithm based unfolding technique which is in the process of development. Genetic Algorithm is a stochastic method based on natural selection, which mimics Darwinian theory of survival of the best. The above said method has been tested to unfold the neutron spectra obtained from a reaction carried out at an accelerator facility, with energetic carbon ions on thick silver target along with its respective neutron response of BC501A liquid scintillation detector. The problem dealt here is under-determined where the number of measurements is less than the required energy bin information. The results so obtained were compared with those obtained using the established unfolding code FERDOR, which unfolds data for completely determined problems. It is seen that the genetic algorithm based solution has a reasonable match with the results of FERDOR, when smoothening carried out by Monte Carlo is taken into consideration. This method appears to be a promising candidate for unfolding neutron spectrum in cases of under-determined and over-determined, where measurements are more. The method also has advantages of flexibility, computational simplicity and works well without need of any initial guess spectrum. (author)

  9. Sugarcane production under smallholder farming systems: Farmers preferred traits, constraints and genetic resources

    Directory of Open Access Journals (Sweden)

    Esayas Tena

    2016-05-01

    Full Text Available Smallholder sugarcane production sector is under researched and underdeveloped with limited industrial link and support. The objectives of this study were to assess the current state of sugarcane production, farmers’ perceived production constraints and preferred traits, and to collect germplasm grown by smallholder farmers in southern Ethiopia for strategic breeding and conservation. The study was conducted across 16 administrative zones, 28 districts and 56 peasant associations involving 560 smallholder sugarcane growers in southern Ethiopia using a participatory rural appraisal (PRA approach. Sugarcane genetic resources were collected through structured sampling. Findings from this study indicated that monocropping was identified as the predominant sugarcane farming system. Respondent farmers prioritized drought tolerance (21%, increased cane yield (20%, early maturity (18%, marketability (17%, and high biomass (14% as the top preferred traits of sugarcane. Ninety diverse sugarcane landraces were collected from homesteads of smallholder farmers. Findings from this study would serve as baseline information towards sugarcane research and development emphasising the constraints and preferences of smallholder sugarcane growers in Ethiopia or similar agro-ecologies. This is the first study to report farmers preferred traits and constraints, and genetic resources of sugarcane under smallholder farming systems in Ethiopia.

  10. ANTHOCYANIN PIGMENTATION IN TRITICUM AESTIVUM L.: GENETIC BASIS AND ROLE UNDER ABIOTIC STRESS CONDITIONS

    Directory of Open Access Journals (Sweden)

    Tereshchenko O.Yu.

    2012-08-01

    Full Text Available Anthocyanins are secondary metabolites of plants. They have a wide range of biological activity such as antioxidant, photoprotection, osmoregulation, heavy metal ions chelation, antimicrobial and antifungal activities, which help plants to survive under different stress conditions. Bread wheat (T. aestivum L. can have purple pigmentation provided by anthocyanin compounds in different organs, such as grain pericarp, coleoptile, culm, leaf blades, leaf sheaths, glumes and anthers. However, the genetic mechanisms underlying formation of these traits as well as contribution of the pigmentation to stress tolerance have not been widely studied in wheat. The aim of the current study was to investigate molecular-genetic mechanisms underlying anthocyanin pigmentation in different wheat organs and to estimate the role of the pigmentation under different abiotic stress conditions in wheat seedlings. In the current study, near-isogenic lines (NILs: cv. ‘Saratovskaya 29’ (‘S29’ and lines i:S29Pp1Pp2PF and i:S29Pp1Pp3P developed on the ‘S29’ background but having grain pericarp coloration (genes Pp and more intense coleoptile (Rc, culm (Pc, leaf blade (Plb, leaf sheath (Pls pigmentation in comparison with ‘S29’, were used. Comparative transcriptional analysis of the five structural genes Chs, Chi, F3h, Dfr, Ans, encoding enzymes participating in the anthocyanin biosynthesis, was performed in different organs of NILs. It was shown that the presence of the Rc, Pc, Plb, Pls and Pp alleles conferring strong anthocyanin pigmentation induced more intense transcription of the structural genes, suggesting the genes Rc, Pc, Plb, Pls and Pp to play a regulatory role in anthocyanin biosynthesis network. To evaluate the role of anthocyanins in stress response at the seedling stage, growth ability of the NILs and anthocyanin content in their coleoptiles were assessed after treatments with NaCl (100 and 200 mM, CdCl2 (25 and 50 μM and 15% PEG 6000

  11. New developments on the neurobiological and pharmaco-genetic mechanisms underlying internet and videogame addiction.

    Science.gov (United States)

    Weinstein, Aviv; Lejoyeux, Michel

    2015-03-01

    There is emerging evidence that the psychobiological mechanisms underlying behavioral addictions such as internet and videogame addiction resemble those of addiction for substances of abuse. Review of brain imaging, treatment and genetic studies on videogame and internet addiction. Literature search of published articles between 2009 and 2013 in Pubmed using "internet addiction" and "videogame addiction" as the search word. Twenty-nine studies have been selected and evaluated under the criteria of brain imaging, treatment, and genetics. Brain imaging studies of the resting state have shown that long-term internet game playing affected brain regions responsible for reward, impulse control and sensory-motor coordination. Brain activation studies have shown that videogame playing involved changes in reward and loss of control and that gaming pictures have activated regions similarly to those activated by cue-exposure to drugs. Structural studies have shown alterations in the volume of the ventral striatum possible as result of changes in reward. Furthermore, videogame playing was associated with dopamine release similar in magnitude to those of drugs of abuse and that there were faulty inhibitory control and reward mechanisms videogame addicted individuals. Finally, treatment studies using fMRI have shown reduction in craving for videogames and reduced associated brain activity. Videogame playing may be supported by similar neural mechanisms underlying drug abuse. Similar to drug and alcohol abuse, internet addiction results in sub-sensitivity of dopamine reward mechanisms. Given the fact that this research is in its early stage it is premature to conclude that internet addiction is equivalent to substance addictions. © American Academy of Addiction Psychiatry.

  12. A new plastic correction for the stress intensity factor of an under-clad defect in a PWR vessel subjected to a pressurised thermal shock

    International Nuclear Information System (INIS)

    Marie, S.; Nedelec, M.

    2007-01-01

    For the assessment of an under-clad defect in a vessel subjected to a cold pressurised thermal shock, plasticity is considered through the amplification β of the elastic stress intensity factor K I in the ferritic part of the vessel. An important effort has been made recently by CEA to improve the analytical tools in the frame of R and D activities funded by IRSN. The current solution in the French RSE-M code has been developed from fitted F.E. calculation results. A more physical solution is proposed in this paper. This takes into account two phenomena: the amplification of the elastic K I due to plasticity in the cladding and a plastic zone size correction in the ferritic part. The first correction has been established by representing the cladding plasticity by an imposed displacement on the crack faces at the interface between the cladding and the ferritic vessel. The corresponding elastic stress intensity factor is determined from the elastic plane strain asymptotic solution for the opening displacement. Plasticity in the ferritic steel is considered through a classical plastic zone size correction. The application of the solution to axisymmetric defects is first checked. The case of semi-elliptical defects is also investigated. For the correction determined at the interface between the cladding and the ferritic vessel, an amplification of the correction proposed for the deepest point is determined from a fitting of the 3D F.E. calculation results. It is also shown that the proposition of RSE-M, which consists in applying the same β correction at the deepest point and the interface point is not suitable. The applicability to a thermal shock, eventually combined with an internal pressure has been verified. For the deepest point, the proposed correction leads to similar results to the RSE-M method, but presents an extended domain of validity (no limits on the crack length are imposed)

  13. Genetic Parameters And Selection Response For Yield Traits In Bread Wheat Under Irrigated And Rainfed Environments

    Science.gov (United States)

    Khalil, Iftikhar Hussain; at-ur-Rahman, Hiday; Khan, Imran

    2008-01-01

    A set of 22 F5:7 experimental wheat lines along with four check cultivars (Dera-98, Fakhr-e-Sarhad, Ghaznavi-98 and Tatara) were evaluated as independent experiments under irrigated and rainfed environments using a randomized complete block design at NWFP Agricultural University, Peshawar during 2004-05. The two environments were statistically different for days to heading and spike length only. Highly significant genetic variability existed among the wheat lines (P<0.01) in the combined analysis across environments for all traits. Genotype×environment interactions were non-significant for all traits except 1000-grain weight indicating consistent performance of wheat genotypes across the two environments. Wheat lines and check cultivars were 2 to 5 days early in heading under rainfed environment compared to the irrigated. Plant height, spike length, 1000-grain weight, biological and grain yields were generally reduced under rainfed environment. Genetic variances were of greater magnitude than environmental variances for most of the traits in both environments. The heritability estimates were of higher magnitude (0.74 to 0.96) for days to heading, plant height, spike length, biological and grain yield, while medium (0.31 to 0.51) for 1000-grain weight. Selection differentials were negative for heading (-7.3 days in irrigated vs -9.4 days in rainfed) and plant height (-9.0 cm in irrigated vs -8.7 cm in rainfed) indicating possibility of selecting wheat genotypes with early heading and short plant stature. Positive selection differentials of 1.3 vs 1.6 cm for spike length, 3.8 vs 3.4 g for 1000-grain weight, 2488.2 vs 3139.7 kg ha-1 for biological yield and 691.6 vs 565.4 kg ha-1 for grain yield at 20% selection intensity were observed under irrigated and rainfed environments, respectively. Expected selection responses were 7.98 vs 8.91 days for heading, 8.20 vs 9.52 cm for plant height, 1.01 vs 1.61 cm for spike length, 2.12 vs 1.15 g for 1000-grain weight, 1655

  14. Defects at oxide surfaces

    CERN Document Server

    Thornton, Geoff

    2015-01-01

    This book presents the basics and characterization of defects at oxide surfaces. It provides a state-of-the-art review of the field, containing information to the various types of surface defects, describes analytical methods to study defects, their chemical activity and the catalytic reactivity of oxides. Numerical simulations of defective structures complete the picture developed. Defects on planar surfaces form the focus of much of the book, although the investigation of powder samples also form an important part. The experimental study of planar surfaces opens the possibility of applying the large armoury of techniques that have been developed over the last half-century to study surfaces in ultra-high vacuum. This enables the acquisition of atomic level data under well-controlled conditions, providing a stringent test of theoretical methods. The latter can then be more reliably applied to systems such as nanoparticles for which accurate methods of characterization of structure and electronic properties ha...

  15. Bone marrow stromal cell defects and 1 alpha,25-dihydroxyvitamin D3 deficiency underlying human myeloid leukemias.

    Science.gov (United States)

    Blazsek, I; Farabos, C; Quittet, P; Labat, M L; Bringuier, A F; Triana, B K; Machover, D; Reynes, M; Misset, J L

    1996-01-01

    Primary myelodysplasia (MDP) and acute and chronic myelogenous leukemias (AML, CML) are considered disorders of clonal stem cell division. Several constitutive gene defects that contribute to the development of abnormal cell behavior have been identified in the hematopoietic cells. The role of bone marrow stroma cells in leukemogenesis, however, has not been established. We studied the organization of the bone marrow (BM) microenvironment to see if it was impaired during the initiation and progression of these malignancies. The buffy coat, hematon, and plasma fractions were separated from BM aspirates taken from healthy donors and diseased subjects at distinct clinical stages. The structural integrity of the BM microenvironment was evaluated analyzing the morphogenetic unit, the hematon. The hematon is a multicellular complex that includes fibroblasts, adipocytes, endothelial cells, resident macrophages, hematopoietic cobblestone area-forming cells (CAFC), high-proliferative potential colony-forming cells (HPP-CFC), granulocyte-macrophage colony-forming unit (GM-CFU), burst-forming unit erythroid (BFU-E), and terminally differentiated cells in normal BM. Hematon complexes were present in most BM aspirates from healthy donors (46H+/55). But they were absent from most of the patients with MDP (21H+/62) and AML (5H+/24) in the first perceptible phase, and from those with CML throughout the disease (5H+/55). Hematon complexes were present in the BM aspirate in 22/36 AML patients at clinical remission after chemotherapy or differentiation therapy. The hematon fraction isolated from normal BM, contained 25 times more 25-hydroxyvitamin D3 and about 500-fold more 1alpha,25-dihydroxyvitamin D3 than the BM plasma. The concentration of 1alpha,25-dihydroxyvitamin D3 was low or undetectable in the BM plasma of some, but not all, patients with MDP (18/35) or AML (9/24). Thus, in the BM microenvironment, the metabolism of low-density lipids and lipophylic hormones are severely

  16. The pulley suture: A reliable option for closure of selected soft tissue defects under tension- three years experience of a tertiary care hospital.

    Science.gov (United States)

    Saeed, Sadaf; Ahmed, Syed Kamran; Chinoy, Muhammad Amin; Khan, Mansoor Ali

    2015-03-01

    To assess the outcome of closure of soft tissue defects through pulley suture in different clinical situations. The descriptive chart review was conducted at The Indus Hospital, Karachi, and comprised data from May 2008 to November 2011. A detailed questionnaire was developed to address variables of interest. All patients with less than three months of follow-up or inadequate information were excluded. The data was collected through Health Management Information System. Data was entered and analysed by SPSS 16. There were 259 patients with 289 wounds in the study. The mean age was 29.2±11.9 years. At follow-up of two weeks, there was wound dehiscence in 2.07%, infection in 0.69% and partial flap necrosis in 1.03% patients. At 12 weeks, hypertrophic scar was reported in 2.07% and stretched scar in 0.3% patients. Acute pain was not reported in the first week of surgery. Type of wound was found to have significant association with complications (p valuepulley suture can lead to primary closure of selected soft tissue defects under moderate tension. The technique, however, needs to be utilised by surgeons experienced in soft tissue reconstruction.

  17. Intrinsic and defect related luminescence in double oxide films of Al–Hf–O system under soft X-ray and VUV excitation

    International Nuclear Information System (INIS)

    Pustovarov, V.A.; Smirnova, T.P.; Lebedev, M.S.; Gritsenko, V.A.; Kirm, M.

    2016-01-01

    Low temperature time-resolved luminescence spectra in the region of 2.5–9.5 eV under soft X-ray excitation as well as time-resolved luminescence excitation spectra in the UV–VUV region (3.7–12 eV) of solid solutions Al x Hf y O 1−x−y thin films were investigated. The values of x and Al/Hf ratio were determined from X-ray photoelectron srectroscopy data. Hafnia films and films mixed with alumina were grown in a flow-type chemical vapor deposition reactor with argon as a carrier gas. In addition, pure alumina films were prepared by the atomic layer deposition method. A strong emission band with the peak position at 4.4 eV and with the decay time in the μs-range was revealed for pure hafnia films. The emission peak at 7.74 eV with short nanosecond decay kinetics was observed in the luminescence spectra for pure alumina films. These emission bands were ascribed to the radiative decay of self-trapped excitons (an intrinsic luminescence) in pure HfO 2 and Al 2 O 3 films, respectively. Along with intrinsic host emission, defect related luminescence bands with a larger Stokes shift were observed. In the emission spectra of the solid solution films (x=4; 17; 20 at%) the intrinsic emission bands are quenched and only the luminescence of defects (an anion vacancies) was observed. Based on transformation of the luminescence spectra and ns-luminescence decay kinetics, as well as changes in the time-resolved luminescence and luminescence excitation spectra, the relaxation processes in the films of solid solution are discussed. - Highlights: • Low temperature time−resolved PL spectra were studied in a broad range (1.5−9.5 eV). • We carried out a luminescent control of point defects (anion vacancies) and self−trapped excitons. • We observed photoluminescence of excitons bound on defects. • We observed changes of photoluminescence properties with varying ratio components.

  18. Genetic engineering of Trypanosoma (Dutonella vivax and in vitro differentiation under axenic conditions.

    Directory of Open Access Journals (Sweden)

    Simon D'Archivio

    2011-12-01

    Full Text Available Trypanosoma vivax is one of the most common parasites responsible for animal trypanosomosis, and although this disease is widespread in Africa and Latin America, very few studies have been conducted on the parasite's biology. This is in part due to the fact that no reproducible experimental methods had been developed to maintain the different evolutive forms of this trypanosome under laboratory conditions. Appropriate protocols were developed in the 1990s for the axenic maintenance of three major animal Trypanosoma species: T. b. brucei, T. congolense and T. vivax. These pioneer studies rapidly led to the successful genetic manipulation of T. b. brucei and T. congolense. Advances were made in the understanding of these parasites' biology and virulence, and new drug targets were identified. By contrast, challenging in vitro conditions have been developed for T. vivax in the past, and this per se has contributed to defer both its genetic manipulation and subsequent gene function studies. Here we report on the optimization of non-infective T. vivax epimastigote axenic cultures and on the process of parasite in vitro differentiation into metacyclic infective forms. We have also constructed the first T. vivax specific expression vector that drives constitutive expression of the luciferase reporter gene. This vector was then used to establish and optimize epimastigote transfection. We then developed highly reproducible conditions that can be used to obtain and select stably transfected mutants that continue metacyclogenesis and are infectious in immunocompetent rodents.

  19. A genetic-algorithm-aided stochastic optimization model for regional air quality management under uncertainty.

    Science.gov (United States)

    Qin, Xiaosheng; Huang, Guohe; Liu, Lei

    2010-01-01

    A genetic-algorithm-aided stochastic optimization (GASO) model was developed in this study for supporting regional air quality management under uncertainty. The model incorporated genetic algorithm (GA) and Monte Carlo simulation techniques into a general stochastic chance-constrained programming (CCP) framework and allowed uncertainties in simulation and optimization model parameters to be considered explicitly in the design of least-cost strategies. GA was used to seek the optimal solution of the management model by progressively evaluating the performances of individual solutions. Monte Carlo simulation was used to check the feasibility of each solution. A management problem in terms of regional air pollution control was studied to demonstrate the applicability of the proposed method. Results of the case study indicated the proposed model could effectively communicate uncertainties into the optimization process and generate solutions that contained a spectrum of potential air pollutant treatment options with risk and cost information. Decision alternatives could be obtained by analyzing tradeoffs between the overall pollutant treatment cost and the system-failure risk due to inherent uncertainties.

  20. Effects of trawl selectivity and genetic parameters on fish body length under long-term trawling

    Science.gov (United States)

    Yu, Yang; Sun, Peng; Cui, He; Sheng, Huaxiang; Zhao, Fenfang; Tang, Yanli; Chen, Zelin

    2015-10-01

    Long-term fishing pressure affects the biological characteristics of exploited fish stocks. The biological characteristics of hairtail ( Trichiurus lepturus) in the East China Sea are unable to recover because of long-term trawling. Fishing induces evolutionary effects on the fish's biological characteristics. Evidence of these changes includes small size at age, a shift to earlier age structure, and early maturation. Natural and artificial selection usually affect the fish's life history. Selection can induce different chances of reproduction, and individual fish can give a different genetic contribution to the next generation. In this study, analysis of time-dependent probability of significance and test of sensitivity were used to explore the effects of fish exploitation rate, mesh size, and heritability with long-term trawling. Results showed that fishing parameters were important drivers to exploited fish population. However, genetic traits altered by fishing were slow, and the changes in biological characteristics were weaker than those caused by fishing selection. Exploitation rate and mesh size exhibited similar evolutionary trend tendency under long-term fishing. The time-dependent probability of significance trend showed a gradual growth and tended to be stable. Therefore, the direction of fishing-induced evolution and successful management of fish species require considerable attention to contribute to sustainable fisheries in China.

  1. Genetic Algorithm for Multiuser Discrete Network Design Problem under Demand Uncertainty

    Directory of Open Access Journals (Sweden)

    Wu Juan

    2012-01-01

    Full Text Available Discrete network design is an important part of urban transportation planning. The purpose of this paper is to present a bilevel model for discrete network design. The upper-level model aims to minimize the total travel time under a stochastic demand to design a discrete network. In the lower-level model, demands are assigned to the network through a multiuser traffic equilibrium assignment. Generally, discrete network could affect path selections of demands, while the results of the multiuser traffic equilibrium assignment need to reconstruct a new discrete network. An iterative approach including an improved genetic algorithm and Frank-Wolfe algorithm is used to solve the bi-level model. The numerical results on Nguyen Dupuis network show that the model and the related algorithms were effective for discrete network design.

  2. Genetic architecture of factors underlying partial resistance to Alternaria leaf blight in carrot.

    Science.gov (United States)

    Le Clerc, Valérie; Pawelec, Anna; Birolleau-Touchard, Christelle; Suel, Anita; Briard, Mathilde

    2009-05-01

    In most production areas, Alternaria leaf blight (ALB) is recognized as the most common and destructive foliage disease in carrot. To assess the genetic architecture of carrot ALB resistance, two parental coupling maps were developed with similar number of dominant markers (around 70), sizes (around 650 cM), densities (around 9.5 cM), and marker composition. The F(2:3) progenies were evaluated in field and tunnel for two scoring dates. The continuous distribution of the disease severity value indicated that ALB resistance is under polygenic control. Three QTLs regions were found on three linkage groups. Two of them were tunnel or field specific and were detected only at the second screening date suggesting that the expression of these two QTLs regions involved in resistance to Alternaria dauci might depend on environment and delay after infection.

  3. Genetic variants in the folate pathway and the risk of neural tube defects: a meta-analysis of the published literature.

    Directory of Open Access Journals (Sweden)

    Ti Zhang

    Full Text Available BACKGROUND: Neural Tube Defects (NTDs are among the most prevalent and most severe congenital malformations worldwide. Polymorphisms in key genes involving the folate pathway have been reported to be associated with the risk of NTDs. However, the results from these published studies are conflicting. We surveyed the literature (1996-2011 and performed a comprehensive meta-analysis to provide empirical evidence on the association. METHODS AND FINDINGS: We investigated the effects of 5 genetic variants from 47 study populations, for a total of 85 case-control comparisons MTHFR C677T (42 studies; 4374 cases, 7232 controls, MTHFR A1298C (22 studies; 2602 cases, 4070 controls, MTR A2756G (9 studies; 843 cases, 1006 controls, MTRR A66G (8 studies; 703 cases, 1572 controls, and RFC-1 A80G (4 studies; 1107 cases, 1585 controls. We found a convincing evidence of dominant effects of MTHFR C677T (OR 1.23; 95%CI 1.07-1.42 and suggestive evidence of RFC-1 A80G (OR 1.55; 95%CI 1.24-1.92. However, we found no significant effects of MTHFR A1298C, MTR A2756G, MTRR A66G in risk of NTDs in dominant, recessive or in allelic models. CONCLUSIONS: Our meta-analysis strongly suggested a significant association of the variant MTHFR C677T and a suggestive association of RFC-1 A80G with increased risk of NTDs. However, other variants involved in folate pathway do not demonstrate any evidence for a significant marginal association on susceptibility to NTDs.

  4. Population genetics inference for longitudinally-sampled mutants under strong selection.

    Science.gov (United States)

    Lacerda, Miguel; Seoighe, Cathal

    2014-11-01

    Longitudinal allele frequency data are becoming increasingly prevalent. Such samples permit statistical inference of the population genetics parameters that influence the fate of mutant variants. To infer these parameters by maximum likelihood, the mutant frequency is often assumed to evolve according to the Wright-Fisher model. For computational reasons, this discrete model is commonly approximated by a diffusion process that requires the assumption that the forces of natural selection and mutation are weak. This assumption is not always appropriate. For example, mutations that impart drug resistance in pathogens may evolve under strong selective pressure. Here, we present an alternative approximation to the mutant-frequency distribution that does not make any assumptions about the magnitude of selection or mutation and is much more computationally efficient than the standard diffusion approximation. Simulation studies are used to compare the performance of our method to that of the Wright-Fisher and Gaussian diffusion approximations. For large populations, our method is found to provide a much better approximation to the mutant-frequency distribution when selection is strong, while all three methods perform comparably when selection is weak. Importantly, maximum-likelihood estimates of the selection coefficient are severely attenuated when selection is strong under the two diffusion models, but not when our method is used. This is further demonstrated with an application to mutant-frequency data from an experimental study of bacteriophage evolution. We therefore recommend our method for estimating the selection coefficient when the effective population size is too large to utilize the discrete Wright-Fisher model. Copyright © 2014 by the Genetics Society of America.

  5. Resistive switching phenomena of extended defects in Nb-doped SrTiO3 under influence of external gradients

    International Nuclear Information System (INIS)

    Rodenbuecher, Christian

    2014-01-01

    gradients on the physical and chemical properties of the surface layer it is demonstrated that a transformation between a Sr-rich and a Ti-rich surface layer can be induced easily illustrating the relevance of ionic movements and phase transformations for the resistive switching effect. On the nanoscale, the switching mechanism is investigated through the use of local conductivity atomic force microscopy with atomic resolution revealing the presence of conducting clusters with a size of 20-60 nm that can be switched independently between ON and OFF states. Since distinct inhomogeneities of the donor distribution are detected by various methods, it is assumed that the conducting clusters, which can be regarded as three-dimensional extended defects, are related to Nb segregation on the nanoscale, which already evolved during the crystal growth by the Verneuil method. In order to gain an insight into the processes taking place when switching the clusters, an emulation of switching is performed on the macroscale by applying extremal electrical gradients, resulting in an evolution of a phase transformation from strontium titanate to titanium oxide in the surface layer. At the end of the thesis, a potential phenomenological model for resistive switching of SrTiO 3 :Nb based on the experimental results as well as on ab initio and finite element simulations is presented.This is done after taking into account the formation of substoichiometric titanium oxide phases, which build up a switchable bridge between the conducting clusters, thereby illustrating that the resistive switching effect in oxides is a very complex phenomenon related to many different mechanisms that need to be considered.

  6. Efficacy of Rosuvastatin in Children With Homozygous Familial Hypercholesterolemia and Association With Underlying Genetic Mutations

    DEFF Research Database (Denmark)

    Stein, Evan A; Dann, Eldad J; Wiegman, Albert

    2017-01-01

    BACKGROUND: Homozygous familial hypercholesterolemia (HoFH), a rare genetic disorder, is characterized by extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) and accelerated atherosclerotic cardiovascular disease. Statin treatment starts at diagnosis, but no statin has been f...... and adults was related to underlying genetic mutations. (A Study to Evaluate the Efficacy and Safety of Rosuvastatin in Children and Adolescents With Homozygous Familial Hypercholesterolemia [HYDRA]; NCT02226198).......BACKGROUND: Homozygous familial hypercholesterolemia (HoFH), a rare genetic disorder, is characterized by extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) and accelerated atherosclerotic cardiovascular disease. Statin treatment starts at diagnosis, but no statin has been...... formally evaluated in, or approved for, HoFH children. OBJECTIVES: The authors sought to assess the LDL-C efficacy of rosuvastatin versus placebo in HoFH children, and the relationship with underlying genetic mutations. METHODS: This was a randomized, double-blind, 12-week, crossover study of rosuvastatin...

  7. Influence of ethnic traditional cultures on genetic diversity of rice landraces under on-farm conservation in southwest China.

    Science.gov (United States)

    Wang, Yanjie; Wang, Yanli; Sun, Xiaodong; Caiji, Zhuoma; Yang, Jingbiao; Cui, Di; Cao, Guilan; Ma, Xiaoding; Han, Bing; Xue, Dayuan; Han, Longzhi

    2016-10-27

    Crop genetic resources are important components of biodiversity. However, with the large-scale promotion of mono-cropping, genetic diversity has largely been lost. Ex-situ conservation approaches were widely used to protect traditional crop varieties worldwide. However, this method fails to maintain the dynamic evolutionary processes of crop genetic resources in their original habitats, leading to genetic diversity reduction and even loss of the capacity of resistance to new diseases and pests. Therefore, on-farm conservation has been considered a crucial complement to ex-situ conservation. This study aimed at clarifying the genetic diversity differences between ex-situ conservation and on-farm conservation and to exploring the influence of traditional cultures on genetic diversity of rice landraces under on-farm conservation. The conservation status of rice landrace varieties, including Indica and Japonica, non-glutinous rice (Oryza sativa) and glutinous rice (Oryza sativa var. glutinosa Matsum), was obtained through ethno-biology investigation method in 12 villages of ethnic groups from Guizhou, Yunnan and Guangxi provinces of China. The genetic diversity between 24 pairs of the same rice landraces from different times were compared using simple sequence repeat (SSR) molecular markers technology. The landrace paris studied were collected in 1980 and maintained ex-situ, while 2014 samples were collected on-farm in southwest of China. The results showed that many varieties of rice landraces have been preserved on-farm by local farmers for hundreds or thousands of years. The number of alleles (Na), effective number of alleles (Ne), Nei genetic diversity index (He) and Shannon information index (I) of rice landraces were significantly higher by 12.3-30.4 % under on-farm conservation than under ex-situ conservation. Compared with the ex-situ conservation approach, rice landraces under on-farm conservation programs had more alleles and higher genetic diversity. In

  8. Genetics

    Science.gov (United States)

    ... Likelihood of getting certain diseases Mental abilities Natural talents An abnormal trait (anomaly) that is passed down ... one of them has a genetic disorder. Information Human beings have cells with 46 chromosomes . These consist ...

  9. Transcriptomes Reveal Genetic Signatures Underlying Physiological Variations Imposed by Different Fermentation Conditions in Lactobacillus plantarum

    Science.gov (United States)

    Bongers, Roger S.; van Bokhorst-van de Veen, Hermien; Wiersma, Anne; Overmars, Lex; Marco, Maria L.; Kleerebezem, Michiel

    2012-01-01

    Lactic acid bacteria (LAB) are utilized widely for the fermentation of foods. In the current post-genomic era, tools have been developed that explore genetic diversity among LAB strains aiming to link these variations to differential phenotypes observed in the strains investigated. However, these genotype-phenotype matching approaches fail to assess the role of conserved genes in the determination of physiological characteristics of cultures by environmental conditions. This manuscript describes a complementary approach in which Lactobacillus plantarum WCFS1 was fermented under a variety of conditions that differ in temperature, pH, as well as NaCl, amino acid, and O2 levels. Samples derived from these fermentations were analyzed by full-genome transcriptomics, paralleled by the assessment of physiological characteristics, e.g., maximum growth rate, yield, and organic acid profiles. A data-storage and -mining suite designated FermDB was constructed and exploited to identify correlations between fermentation conditions and industrially relevant physiological characteristics of L. plantarum, as well as the associated transcriptome signatures. Finally, integration of the specific fermentation variables with the transcriptomes enabled the reconstruction of the gene-regulatory networks involved. The fermentation-genomics platform presented here is a valuable complementary approach to earlier described genotype-phenotype matching strategies which allows the identification of transcriptome signatures underlying physiological variations imposed by different fermentation conditions. PMID:22802930

  10. Concrete Mix Design for Service Life of RC Structures under Carbonation Using Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Seung-Jun Kwon

    2014-01-01

    Full Text Available Steel corrosion in reinforced concrete (RC structure is such a critical problem to structural safety that many researches have been performed for maintaining required performance during intended service life. This paper is for a numerical technique for obtaining optimum concrete mix proportions through genetic algorithm (GA for RC structures under carbonation which is considered as a serious deterioration in underground sites and big cities. For this study, mix proportions and CO2 diffusion coefficients are analyzed through the previous studies, and then the fitness function of CO2 diffusion coefficient is derived through regression analysis. The fitness function from 69 test results includes 5 variables of mix proportions such as w/c (water to cement ratio, cement content, sand content percentage, coarse aggregate content, and R.H. (relative humidity. Through GA technique, simulated mix proportions are obtained for 12 cases of verification and they show reasonable results with average relative error of 4.6%. Assuming intended service life and design parameters, intended CO2 diffusion coefficients and cement contents are determined and then related mix proportions are simulated. The proposed technique can provide initial concrete mix proportions which satisfy service life under carbonation.

  11. Plastic collapse of API 5L X65 pipe having dent defects under internal pressure and bending load

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Jong-hyun; Kim, Young-pyo; Kim, Cheol-man; Kim, Woo-sik [RandD Division, KOGAS, Ansan, (Korea, Republic of); Koo, Jae-mean; Seok, Chang-sung [Department of Mechanical Engineering, Sungkyunkwan University, Suwon, (Korea, Republic of)

    2010-07-01

    This paper studies the effect of the dent magnitude on the collapse of a dented pipe that is subjected to simultaneous internal pressure and in-plane bending. The evaluation was made with elastic-plastic finite element analyses. Dents of various depths were made on a pipe having a diameter of 762 mm and a wall thickness of 17.5 mm. The dented pipes were subjected to a closing or opening in-plane bending moment under various internal pressures. Results showed that the bending mode and the dent geometry had a strong influence on the plastic collapse behaviour. Moment-bending angle curves obtained from computer simulation were evaluated with a variety of factors. A dent whose depth was 5% of the outer diameter did not reduce the load-carrying capacity of a pipe. The load-carrying capacity was higher with an opening bending mode than with a closing bending mode regardless of dent depth.

  12. Genetic Loci Governing Grain Yield and Root Development under Variable Rice Cultivation Conditions

    Directory of Open Access Journals (Sweden)

    Margaret Catolos

    2017-10-01

    Full Text Available Drought is the major abiotic stress to rice grain yield under unpredictable changing climatic scenarios. The widely grown, high yielding but drought susceptible rice varieties need to be improved by unraveling the genomic regions controlling traits enhancing drought tolerance. The present study was conducted with the aim to identify quantitative trait loci (QTLs for grain yield and root development traits under irrigated non-stress and reproductive-stage drought stress in both lowland and upland situations. A mapping population consisting of 480 lines derived from a cross between Dular (drought-tolerant and IR64-21 (drought susceptible was used. QTL analysis revealed three major consistent-effect QTLs for grain yield (qDTY1.1, qDTY1.3, and qDTY8.1 under non-stress and reproductive-stage drought stress conditions, and 2 QTLs for root traits (qRT9.1 for root-growth angle and qRT5.1 for multiple root traits, i.e., seedling-stage root length, root dry weight and crown root number. The genetic locus qDTY1.1 was identified as hotspot for grain yield and yield-related agronomic and root traits. The study identified significant positive correlations among numbers of crown roots and mesocotyl length at the seedling stage and root length and root dry weight at depth at later stages with grain yield and yield-related traits. Under reproductive stage drought stress, the grain yield advantage of the lines with QTLs ranged from 24.1 to 108.9% under upland and 3.0–22.7% under lowland conditions over the lines without QTLs. The lines with QTL combinations qDTY1.3+qDTY8.1 showed the highest mean grain yield advantage followed by lines having qDTY1.1+qDTY8.1 and qDTY1.1+qDTY8.1+qDTY1.3, across upland/lowland reproductive-stage drought stress. The identified QTLs for root traits, mesocotyl length, grain yield and yield-related traits can be immediately deployed in marker-assisted breeding to develop drought tolerant high yielding rice varieties.

  13. Genetically modified parthenocarpic eggplants: improved fruit productivity under both greenhouse and open field cultivation.

    Directory of Open Access Journals (Sweden)

    Pandolfini Tiziana

    2002-04-01

    Full Text Available Abstract Background Parthenocarpy, or fruit development in the absence of fertilization, has been genetically engineered in eggplant and in other horticultural species by using the DefH9-iaaM gene. The iaaM gene codes for tryptophan monoxygenase and confers auxin synthesis, while the DefH9 controlling regions drive expression of the gene specifically in the ovules and placenta. A previous greenhouse trial for winter production of genetically engineered (GM parthenocarpic eggplants demonstrated a significant increase (an average of 33% increase in fruit production concomitant with a reduction in cultivation costs. Results GM parthenocarpic eggplants have been evaluated in three field trials. Two greenhouse spring trials have shown that these plants outyielded the corresponding untransformed genotypes, while a summer trial has shown that improved fruit productivity in GM eggplants can also be achieved in open field cultivation. Since the fruits were always seedless, the quality of GM eggplant fruits was improved as well. RT-PCR analysis demonstrated that the DefH9-iaaM gene is expressed during late stages of fruit development. Conclusions The DefH9-iaaM parthenocarpic gene is a biotechnological tool that enhances the agronomic value of all eggplant genotypes tested. The main advantages of DefH9-iaaM eggplants are: i improved fruit productivity (at least 30–35% under both greenhouse and open field cultivation; ii production of good quality (marketable fruits during different types of cultivation; iii seedless fruit with improved quality. Such advantages have been achieved without the use of either male or female sterility genes.

  14. Genetic and agronomic assessment of cob traits in corn under low and normal nitrogen management conditions.

    Science.gov (United States)

    Jansen, Constantin; Zhang, Yongzhong; Liu, Hongjun; Gonzalez-Portilla, Pedro J; Lauter, Nick; Kumar, Bharath; Trucillo-Silva, Ignacio; Martin, Juan Pablo San; Lee, Michael; Simcox, Kevin; Schussler, Jeff; Dhugga, Kanwarpal; Lübberstedt, Thomas

    2015-07-01

    Exploring and understanding the genetic basis of cob biomass in relation to grain yield under varying nitrogen management regimes will help breeders to develop dual-purpose maize. With rising energy demands and costs for fossil fuels, alternative energy from renewable sources such as maize cobs will become competitive. Maize cobs have beneficial characteristics for utilization as feedstock including compact tissue, high cellulose content, and low ash and nitrogen content. Nitrogen is quantitatively the most important nutrient for plant growth. However, the influence of nitrogen fertilization on maize cob production is unclear. In this study, quantitative trait loci (QTL) have been analyzed for cob morphological traits such as cob weight, volume, length, diameter and cob tissue density, and grain yield under normal and low nitrogen regimes. 213 doubled-haploid lines of the intermated B73 × Mo17 (IBM) Syn10 population have been resequenced for 8575 bins, based on SNP markers. A total of 138 QTL were found for six traits across six trials using composite interval mapping with ten cofactors and empirical comparison-wise thresholds (P = 0.001). Despite moderate to high repeatabilities across trials, few QTL were consistent across trials and overall levels of explained phenotypic variance were lower than expected some of the cob trait × trial combinations (R (2) = 7.3-43.1 %). Variation for cob traits was less affected by nitrogen conditions than by grain yield. Thus, the economics of cob usage under low nitrogen regimes is promising.

  15. Effect of additional minor elements on accumulation behavior of point defects under electron irradiation in austenitic stainless steels

    International Nuclear Information System (INIS)

    Sekio, Yoshihiro; Yamashita, Shinichiro; Takahashi, Heishichiro; Sakaguchi, Norihito

    2014-01-01

    Addition of minor elements to a base alloy is often applied with the aim of mitigating void swelling by decreasing the vacancy diffusivity and flux which influence vacancy accumulation behavior. However, the comparative evaluations of parameters, such as the diffusivity and flux, between a base alloy and modified alloys with specific additives have not been studied in detail. In this study, type 316 austenitic stainless steel as a base alloy and type 316 austenitic stainless steels modified with vanadium (V) or zirconium (Zr) additions were used to perform evaluations from the changes of widths of the void denuded zone (VDZ) formed near a random grain boundary during electron irradiation because these widths depend on vacancy diffusivity and flux. The formations of VDZs were observed in in-situ observations during electron irradiation at 723 K and the formed VDZ widths were measured from the transmission electron microscopic images after electron irradiation. As a result, the VDZs were formed in both steels without and with V, and respective widths were ∼119 and ∼100 nm. On the other hand, the VDZ formation was not observed clearly in the steel with Zr. From the measured VDZ widths in the steels without and with V addition, the estimated ratio of the vacancy diffusivity in the steel with V to that in the steel without V was about 0.50 and the estimated ratio of the vacancy flux in the steel with V to that in the steel without V was about 0.71. This result suggests that the effect of additional minor elements on vacancy accumulation behaviors under electron irradiation could be estimated from evaluations of the VDZ width changes among steels with and without minor elements. Especially, because void swelling is closely related with the vacancy diffusion process, the VDZ width changes would also be reflected on void swelling behavior. (author)

  16. Genetics

    International Nuclear Information System (INIS)

    Hubitschek, H.E.

    1975-01-01

    Progress is reported on the following research projects: genetic effects of high LET radiations; genetic regulation, alteration, and repair; chromosome replication and the division cycle of Escherichia coli; effects of radioisotope decay in the DNA of microorganisms; initiation and termination of DNA replication in Bacillus subtilis; mutagenesis in mouse myeloma cells; lethal and mutagenic effects of near-uv radiation; effect of 8-methoxypsoralen on photodynamic lethality and mutagenicity in Escherichia coli; DNA repair of the lethal effects of far-uv; and near uv irradiation of bacterial cells

  17. Simultaneous Estimation of Mixing Rates and Genetic Drift Under Successive Sampling of Genetic Markers With Application to the Mud Crab (Scylla paramamosain) in Japan

    OpenAIRE

    Kitakado, Toshihide; Kitada, Shuichi; Obata, Yasuhiro; Kishino, Hirohisa

    2006-01-01

    In stock enhancement programs, it is important to assess mixing rates of released individuals in stocks. For this purpose, genetic stock identification has been applied. The allele frequencies in a composite population are expressed as a mixture of the allele frequencies in the natural and released populations. The estimation of mixing rates is possible, under successive sampling from the composite population, on the basis of temporal changes in allele frequencies. The allele frequencies in t...

  18. A multi-method approach to the molecular diagnosis of overt and borderline 11p15.5 defects underlying Silver-Russell and Beckwith-Wiedemann syndromes.

    Science.gov (United States)

    Russo, Silvia; Calzari, Luciano; Mussa, Alessandro; Mainini, Ester; Cassina, Matteo; Di Candia, Stefania; Clementi, Maurizio; Guzzetti, Sara; Tabano, Silvia; Miozzo, Monica; Sirchia, Silvia; Finelli, Palma; Prontera, Paolo; Maitz, Silvia; Sorge, Giovanni; Calcagno, Annalisa; Maghnie, Mohamad; Divizia, Maria Teresa; Melis, Daniela; Manfredini, Emanuela; Ferrero, Giovanni Battista; Pecile, Vanna; Larizza, Lidia

    2016-01-01

    Multiple (epi)genetic defects affecting the expression of the imprinted genes within the 11p15.5 chromosomal region underlie Silver-Russell (SRS) and Beckwith-Wiedemann (BWS) syndromes. The molecular diagnosis of these opposite growth disorders requires a multi-approach flowchart to disclose known primary and secondary (epi)genetic alterations; however, up to 20 and 30 % of clinically diagnosed BWS and SRS cases remain without molecular diagnosis. The complex structure of the 11p15 region with variable CpG methylation and low-rate mosaicism may account for missed diagnoses. Here, we demonstrate the relevance of complementary techniques for the assessment of different CpGs and the importance of testing multiple tissues to increase the SRS and BWS detection rate. Molecular testing of 147 and 450 clinically diagnosed SRS and BWS cases provided diagnosis in 34 SRS and 185 BWS patients, with 9 SRS and 21 BWS cases remaining undiagnosed and herein referred to as "borderline." A flowchart including complementary techniques and, when applicable, the analysis of buccal swabs, allowed confirmation of the molecular diagnosis in all borderline cases. Comparison of methylation levels by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) in borderline and control cases defined an interval of H19/IGF2:IG-DMR loss of methylation that was distinct between "easy to diagnose" and "borderline" cases, which were characterized by values ≤mean -3 standard deviations (SDs) compared to controls. Values ≥mean +1 SD at H19/IGF2: IG-DMR were assigned to borderline hypermethylated BWS cases and those ≤mean -2 SD at KCNQ1OT1: TSS-DMR to hypomethylated BWS cases; these were supported by quantitative pyrosequencing or Southern blot analysis. Six BWS cases suspected to carry mosaic paternal uniparental disomy of chromosome 11 were confirmed by SNP array, which detected mosaicism till 10 %. Regarding the clinical presentation, borderline SRS were representative

  19. Comparative transcriptome analyses reveal the genetic basis underlying the immune function of three amphibians' skin.

    Science.gov (United States)

    Fan, Wenqiao; Jiang, Yusong; Zhang, Meixia; Yang, Donglin; Chen, Zhongzhu; Sun, Hanchang; Lan, Xuelian; Yan, Fan; Xu, Jingming; Yuan, Wanan

    2017-01-01

    Skin as the first barrier against external invasions plays an essential role for the survival of amphibians on land. Understanding the genetic basis of skin function is significant in revealing the mechanisms underlying immunity of amphibians. In this study, we de novo sequenced and comparatively analyzed skin transcriptomes from three different amphibian species, Andrias davidianus, Bufo gargarizans, and Rana nigromaculata Hallowell. Functional classification of unigenes in each amphibian showed high accordance, with the most represented GO terms and KEGG pathways related to basic biological processes, such as binding and metabolism and immune system. As for the unigenes, GO and KEGG distributions of conserved orthologs in each species were similar, with the predominantly enriched pathways including RNA polymerase, nucleotide metabolism, and defense. The positively selected orthologs in each amphibian were also similar, which were primarily involved in stimulus response, cell metabolic, membrane, and catalytic activity. Furthermore, a total of 50 antimicrobial peptides from 26 different categories were identified in the three amphibians, and one of these showed high efficiency in inhibiting the growth of different bacteria. Our understanding of innate immune function of amphibian skin has increased basis on the immune-related unigenes, pathways, and antimicrobial peptides in amphibians.

  20. Comparative transcriptome analyses reveal the genetic basis underlying the immune function of three amphibians’ skin

    Science.gov (United States)

    Zhang, Meixia; Yang, Donglin; Chen, Zhongzhu; Lan, Xuelian; Yan, Fan; Xu, Jingming; Yuan, Wanan

    2017-01-01

    Skin as the first barrier against external invasions plays an essential role for the survival of amphibians on land. Understanding the genetic basis of skin function is significant in revealing the mechanisms underlying immunity of amphibians. In this study, we de novo sequenced and comparatively analyzed skin transcriptomes from three different amphibian species, Andrias davidianus, Bufo gargarizans, and Rana nigromaculata Hallowell. Functional classification of unigenes in each amphibian showed high accordance, with the most represented GO terms and KEGG pathways related to basic biological processes, such as binding and metabolism and immune system. As for the unigenes, GO and KEGG distributions of conserved orthologs in each species were similar, with the predominantly enriched pathways including RNA polymerase, nucleotide metabolism, and defense. The positively selected orthologs in each amphibian were also similar, which were primarily involved in stimulus response, cell metabolic, membrane, and catalytic activity. Furthermore, a total of 50 antimicrobial peptides from 26 different categories were identified in the three amphibians, and one of these showed high efficiency in inhibiting the growth of different bacteria. Our understanding of innate immune function of amphibian skin has increased basis on the immune-related unigenes, pathways, and antimicrobial peptides in amphibians. PMID:29267366

  1. Defects and defect processes in nonmetallic solids

    CERN Document Server

    Hayes, W

    2004-01-01

    This extensive survey covers defects in nonmetals, emphasizing point defects and point-defect processes. It encompasses electronic, vibrational, and optical properties of defective solids, plus dislocations and grain boundaries. 1985 edition.

  2. Genetics

    DEFF Research Database (Denmark)

    Christensen, Kaare; McGue, Matt

    2016-01-01

    The sequenced genomes of individuals aged ≥80 years, who were highly educated, self-referred volunteers and with no self-reported chronic diseases were compared to young controls. In these data, healthy ageing is a distinct phenotype from exceptional longevity and genetic factors that protect...

  3. The underlying mechanisms of genetic innovation and speciation in the family Corynebacteriaceae: A phylogenomics approach.

    Science.gov (United States)

    Zhi, Xiao-Yang; Jiang, Zhao; Yang, Ling-Ling; Huang, Ying

    2017-02-01

    The pangenome of a bacterial species population is formed by genetic reduction and genetic expansion over the long course of evolution. Gene loss is a pervasive source of genetic reduction, and (exogenous and endogenous) gene gain is the main driver of genetic expansion. To understand the genetic innovation and speciation of the family Corynebacteriaceae, which cause a wide range of serious infections in humans and animals, we analyzed the pangenome of this family, and reconstructed its phylogeny using a phylogenomics approach. Genetic variations have occurred throughout the whole evolutionary history of the Corynebacteriaceae. Gene loss has been the primary force causing genetic changes, not only in terms of the number of protein families affected, but also because of its continuity on the time series. The variation in metabolism caused by these genetic changes mainly occurred for membrane transporters, two-component systems, and metabolism related to amino acids and carbohydrates. Interestingly, horizontal gene transfer (HGT) not only caused changes related to pathogenicity, but also triggered the acquisition of antimicrobial resistance. The Darwinian theory of evolution did not adequately explain the effects of dispersive HGT and/or gene loss in the evolution of the Corynebacteriaceae. These findings provide new insight into the evolution and speciation of Corynebacteriaceae and advance our understanding of the genetic innovation in microbial populations. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease

    DEFF Research Database (Denmark)

    Baillie, J Kenneth; Bretherick, Andrew; Haley, Christopher S

    2018-01-01

    Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns...... the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes...... in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn's disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely...

  5. The genetic basis underlying variation in production of the flavour compound diacetyl by Lactobacillus rhamnosus strains in milk.

    Science.gov (United States)

    Lo, Raquel; Ho, Van Thi Thuy; Bansal, Nidhi; Turner, Mark S

    2018-01-16

    Diacetyl and the closely related compound acetoin impart desirable buttery flavour and odour to many foods including cheese and are generated through the metabolism of citrate by lactic acid bacteria (LAB). To increase the levels of these compounds, adjunct cultures capable of producing them can be added to cheese fermentations. In this study, we compared the diacetyl and acetoin producing abilities of 13 Lactobacillus rhamnosus strains from cheese sources. Diacetyl and acetoin production was found to be a common feature of Lb. rhamnosus grown in milk, with 12 strains producing these compounds. Whole genome sequencing of four strains revealed that genes encoding the citrate metabolising pathway present in other LAB are conserved in Lb. rhamnosus. One strain was, however, totally defective in diacetyl and acetoin production. This was likely due to an inability to produce the diacetyl/acetoin precursor compound acetolactate resulting from a frameshift mutation in the acetolactate synthase (als) gene. Complementation of this defective strain with a complete als gene from a diacetyl producing strain restored production of diacetyl and acetoin to levels equivalent to naturally high producing strains. Introduction of the same als-containing plasmid into the probiotic Lb. rhamnosus strain GG also increased diacetyl and acetoin levels. In model cheesemaking experiments, the als-complemented strain produced very high levels of diacetyl and acetoin over 35days of ripening. These findings identify the genetic basis for natural variation in production of a key cheese flavour compound in Lb. rhamnosus strains. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Modelled in vivo HIV fitness under drug selective pressure and estimated genetic barrier towards resistance are predictive for virological response

    DEFF Research Database (Denmark)

    Deforche, Koen; Cozzi-Lepri, Alessandro; Theys, Kristof

    2008-01-01

    BACKGROUND: A method has been developed to estimate a fitness landscape experienced by HIV-1 under treatment selective pressure as a function of the genotypic sequence thereby also estimating the genetic barrier to resistance. METHODS: We evaluated the performance of two estimated fitness landsca...

  7. 75 FR 68911 - Regulations Under the Genetic Information Nondiscrimination Act of 2008

    Science.gov (United States)

    2010-11-09

    ... covered entities, however, might engage in conduct that could cause an employer to discriminate. For... disease or disorder. But just as the number of genetic tests increases, so do the concerns of the general... efforts to develop new medicines and treatments for genetic diseases and disorders would be slowed or...

  8. A Dynamic Programming-Based Sustainable Inventory-Allocation Planning Problem with Carbon Emissions and Defective Item Disposal under a Fuzzy Random Environment

    Directory of Open Access Journals (Sweden)

    Kai Kang

    2018-01-01

    Full Text Available There is a growing concern that business enterprises focus primarily on their economic activities and ignore the impact of these activities on the environment and the society. This paper investigates a novel sustainable inventory-allocation planning model with carbon emissions and defective item disposal over multiple periods under a fuzzy random environment. In this paper, a carbon credit price and a carbon cap are proposed to demonstrate the effect of carbon emissions’ costs on the inventory-allocation network costs. The percentage of poor quality products from manufacturers that need to be rejected is assumed to be fuzzy random. Because of the complexity of the model, dynamic programming-based particle swarm optimization with multiple social learning structures, a DP-based GLNPSO, and a fuzzy random simulation are proposed to solve the model. A case is then given to demonstrate the efficiency and effectiveness of the proposed model and the DP-based GLNPSO algorithm. The results found that total costs across the inventory-allocation network varied with changes in the carbon cap and that carbon emissions’ reductions could be utilized to gain greater profits.

  9. Defect formation in aqueous environment: Theoretical assessment of boron incorporation in nickel ferrite under conditions of an operating pressurized-water nuclear reactor (PWR)

    Science.gov (United States)

    Rák, Zs.; Bucholz, E. W.; Brenner, D. W.

    2015-06-01

    A serious concern in the safety and economy of a pressurized water nuclear reactor is related to the accumulation of boron inside the metal oxide (mostly NiFe2O4 spinel) deposits on the upper regions of the fuel rods. Boron, being a potent neutron absorber, can alter the neutron flux causing anomalous shifts and fluctuations in the power output of the reactor core. This phenomenon reduces the operational flexibility of the plant and may force the down-rating of the reactor. In this work an innovative approach is used to combine first-principles calculations with thermodynamic data to evaluate the possibility of B incorporation into the crystal structure of NiFe2O4 , under conditions typical to operating nuclear pressurized water nuclear reactors. Analyses of temperature and pH dependence of the defect formation energies indicate that B can accumulate in NiFe2O4 as an interstitial impurity and may therefore be a major contributor to the anomalous axial power shift observed in nuclear reactors. This computational approach is quite general and applicable to a large variety of solids in equilibrium with aqueous solutions.

  10. Osteoporotic vertebral fractures during pregnancy: be aware of a potential underlying genetic cause.

    Science.gov (United States)

    Campos-Obando, Natalia; Oei, Ling; Hoefsloot, Lies H; Kiewiet, Rosalie M; Klaver, Caroline C W; Simon, Marleen E H; Zillikens, M Carola

    2014-04-01

    Although the baby growing in its mother's womb needs calcium for skeletal development, osteoporosis and fractures very rarely occur during pregnancy. A 27-year-old woman in the seventh month of her first pregnancy contracted midthoracic back pain after lifting an object. The pain was attributed to her pregnancy, but it remained postpartum. Her past medical history was uneventful, except for severely reduced vision of her left eye since birth. Family history revealed that her maternal grandmother had postmenopausal osteoporosis and her half-brother had three fractures during childhood after minor trauma. Her height was 1.58 m; she had no blue sclerae or joint hyperlaxity. Laboratory examination including serum calcium, phosphate, alkaline phosphatase, creatinine, β-carboxyterminal cross-linking telopeptide of type I collagen, 25-hydroxyvitamin D, and TSH was normal. Multiple thoracic vertebral fractures were diagnosed on x-ray examination, and dual-energy x-ray absorptiometry scanning showed severe osteoporosis (Z-scores: L2-L4, -5.6 SD; femur neck, -3.9 SD). DNA analyses revealed two compound heterozygous missense mutations in LRP5. The patient's mother carried one of the LRP5 mutations and was diagnosed with osteoporosis. Her half-brother, treated with cabergoline for a microprolactinoma, also had osteoporosis of the lumbar spine on dual-energy x-ray absorptiometry and carried the same LRP5 mutation. The patient was treated with risedronate for 2.5 years. Bone mineral density and back pain improved. She stopped bisphosphonate use 6 months before planning a second pregnancy. Our patient was diagnosed with osteoporosis pseudoglioma syndrome/familial exudative vitreoretinopathy. Potential underlying genetic causes should be considered in pregnancy-associated osteoporosis with implications for patients and relatives. More studies regarding osteoporosis treatment preceding conception are desirable.

  11. Likelihood for transcriptions in a genetic regulatory system under asymmetric stable Lévy noise

    Science.gov (United States)

    Wang, Hui; Cheng, Xiujun; Duan, Jinqiao; Kurths, Jürgen; Li, Xiaofan

    2018-01-01

    This work is devoted to investigating the evolution of concentration in a genetic regulation system, when the synthesis reaction rate is under additive and multiplicative asymmetric stable Lévy fluctuations. By focusing on the impact of skewness (i.e., non-symmetry) in the probability distributions of noise, we find that via examining the mean first exit time (MFET) and the first escape probability (FEP), the asymmetric fluctuations, interacting with nonlinearity in the system, lead to peculiar likelihood for transcription. This includes, in the additive noise case, realizing higher likelihood of transcription for larger positive skewness (i.e., asymmetry) index β, causing a stochastic bifurcation at the non-Gaussianity index value α = 1 (i.e., it is a separating point or line for the likelihood for transcription), and achieving a turning point at the threshold value β≈-0.5 (i.e., beyond which the likelihood for transcription suddenly reversed for α values). The stochastic bifurcation and turning point phenomena do not occur in the symmetric noise case (β = 0). While in the multiplicative noise case, non-Gaussianity index value α = 1 is a separating point or line for both the MFET and the FEP. We also investigate the noise enhanced stability phenomenon. Additionally, we are able to specify the regions in the whole parameter space for the asymmetric noise, in which we attain desired likelihood for transcription. We have conducted a series of numerical experiments in "regulating" the likelihood of gene transcription by tuning asymmetric stable Lévy noise indexes. This work offers insights for possible ways of achieving gene regulation in experimental research.

  12. The evolutionary genetics of the genes underlying phenotypic associations for loblolly pine (Pinus taeda, Pinaceae).

    Science.gov (United States)

    Eckert, Andrew J; Wegrzyn, Jill L; Liechty, John D; Lee, Jennifer M; Cumbie, W Patrick; Davis, John M; Goldfarb, Barry; Loopstra, Carol A; Palle, Sreenath R; Quesada, Tania; Langley, Charles H; Neale, David B

    2013-12-01

    A primary goal of evolutionary genetics is to discover and explain the genetic basis of fitness-related traits and how this genetic basis evolves within natural populations. Unprecedented technological advances have fueled the discovery of genetic variants associated with ecologically relevant phenotypes in many different life forms, as well as the ability to scan genomes for deviations from selectively neutral models of evolution. Theoretically, the degree of overlap between lists of genomic regions identified using each approach is related to the genetic architecture of fitness-related traits and the strength and type of natural selection molding variation at these traits within natural populations. Here we address for the first time in a plant the degree of overlap between these lists, using patterns of nucleotide diversity and divergence for >7000 unique amplicons described from the extensive expressed sequence tag libraries generated for loblolly pine (Pinus taeda L.) in combination with the >1000 published genetic associations. We show that loci associated with phenotypic traits are distinct with regard to neutral expectations. Phenotypes measured at the whole plant level (e.g., disease resistance) exhibit an approximately twofold increase in the proportion of adaptive nonsynonymous substitutions over the genome-wide average. As expected for polygenic traits, these signals were apparent only when loci were considered at the level of functional sets. The ramifications of this result are discussed in light of the continued efforts to dissect the genetic basis of quantitative traits.

  13. Genetic diversity of Vietnamese lowland rice germplasms as revealed by SSR markers in relation to seedling vigour under submergence

    Directory of Open Access Journals (Sweden)

    Hien Thi Thu Vu

    2016-01-01

    Full Text Available In the direct-seeding rice cultivation system, seedling vigour is one of the most important traits for stable stand establishment during early seedling stages, particularly under submergence that is caused by temporal flash flood. We studied the genetic diversity in a set of 40 Vietnamese lowland rice varieties using 30 simple sequence repeat (SSR markers covering all rice chromosomes. A total of 111 alleles were detected, with a mean of 3.7 alleles per locus. The number of polymorphic alleles detected by each SSR marker ranged from 2 to 6. The fragment size of a given SSR locus varied between 85 and 650 bp and the frequency of a major allele at each locus ranged from 32.5% to 76.9%. Polymorphism information content value varied from 0.355 to 0.774 with an average of 0.594. The genetic similarity calculated between pairs of rice varieties ranged from 0.03 to 0.97 with an average of 0.27. According to a constructed dendrogram of unweighted pair group method with arithmetic mean based on the SSR marker analysis, the tested rice varieties were clustered into two major groups consisting of five subgroups. Significant correlations existed between the mean genetic similarity and the mean seedling vigour estimated by shoot length under submergence among the tested varieties. Our results suggested usefulness of the SSR marker system to assess genetic diversity in Vietnamese rice germplasms in relation to their seedling vigour under submergence.

  14. Fetal abdominal wall defects.

    Science.gov (United States)

    Prefumo, Federico; Izzi, Claudia

    2014-04-01

    The most common fetal abdominal wall defects are gastroschisis and omphalocele, both with a prevalence of about three in 10,000 births. Prenatal ultrasound has a high sensitivity for these abnormalities already at the time of the first-trimester nuchal scan. Major unrelated defects are associated with gastroschisis in about 10% of cases, whereas omphalocele is associated with chromosomal or genetic abnormalities in a much higher proportion of cases. Challenges in management of gastroschisis are related to the prevention of late intrauterine death, and the prediction and treatment of complex forms. With omphalocele, the main difficulty is the exclusion of associated conditions, not all diagnosed prenatally. An outline of the postnatal treatment of abdominal wall defects is given. Other rarer forms of abdominal wall defects are pentalogy of Cantrell, omphalocele, bladder exstrophy, imperforate anus, spina bifida complex, prune-belly syndrome, body stalk anomaly, and bladder and cloacal exstrophy; they deserve multidisciplinary counselling and management. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Persistent increase of plasma butyryl/isobutyrylcarnitine concentrations as marker of SCAD defect and ethylmalonic encephalopathy

    DEFF Research Database (Denmark)

    Merinero, B; Perez-Cerda, C; Ruiz Sala, P

    2007-01-01

    High concentrations of butyryl/isobutyrylcarnitine (C(4)-carnitine) in plasma with increase of ethylmalonic acid (EMA) in urine point to different genetic entities, and further investigations are required to differentiate the possible underlying defect. Here we report three unrelated cases, two...

  16. A Shared Genetic Propensity Underlies Experiences of Bullying Victimization in Late Childhood and Self-Rated Paranoid Thinking in Adolescence

    Science.gov (United States)

    Shakoor, Sania; McGuire, Phillip; Cardno, Alastair G.; Freeman, Daniel; Plomin, Robert; Ronald, Angelica

    2015-01-01

    Background: Bullying is a risk factor for developing psychotic experiences (PEs). Whether bullying is associated with particular PEs, and the extent to which genes and environments influence the association, are unknown. This study investigated which specific PEs in adolescence are associated with earlier bullying victimization and the genetic and environmental contributions underlying their association. Method: Participants were 4826 twin pairs from a longitudinal community-based twin study in England and Wales who reported on their bullying victimization at the age of 12 years. Measures of specific PEs (self-rated Paranoia, Hallucinations, Cognitive disorganization, Grandiosity, Anhedonia, and parent-rated Negative Symptoms) were recorded at age of 16 years. Results: Childhood bullying victimization was most strongly associated with Paranoia in adolescence (r = .26; P bullying victimization and Paranoia were both heritable (35% and 52%, respectively) with unique environmental influences (39% and 48%, respectively), and bullying victimization showed common environmental influences (26%). The association between bullying victimization and Paranoia operated almost entirely via genetic influences (bivariate heritability = 93%), with considerable genetic overlap (genetic correlation = .55). Conclusion: In contrast to the assumed role of bullying victimization as an environmental trigger, these data suggest that bullying victimization in late childhood is particularly linked to self-rated Paranoia in adolescence via a shared genetic propensity. Clinically, individuals with a history of bullying victimization are predicted to be particularly susceptible to paranoid symptoms. PMID:25323579

  17. A shared genetic propensity underlies experiences of bullying victimization in late childhood and self-rated paranoid thinking in adolescence.

    Science.gov (United States)

    Shakoor, Sania; McGuire, Phillip; Cardno, Alastair G; Freeman, Daniel; Plomin, Robert; Ronald, Angelica

    2015-05-01

    Bullying is a risk factor for developing psychotic experiences (PEs). Whether bullying is associated with particular PEs, and the extent to which genes and environments influence the association, are unknown. This study investigated which specific PEs in adolescence are associated with earlier bullying victimization and the genetic and environmental contributions underlying their association. Participants were 4826 twin pairs from a longitudinal community-based twin study in England and Wales who reported on their bullying victimization at the age of 12 years. Measures of specific PEs (self-rated Paranoia, Hallucinations, Cognitive disorganization, Grandiosity, Anhedonia, and parent-rated Negative Symptoms) were recorded at age of 16 years. Childhood bullying victimization was most strongly associated with Paranoia in adolescence (r = .26; P bullying victimization and Paranoia were both heritable (35% and 52%, respectively) with unique environmental influences (39% and 48%, respectively), and bullying victimization showed common environmental influences (26%). The association between bullying victimization and Paranoia operated almost entirely via genetic influences (bivariate heritability = 93%), with considerable genetic overlap (genetic correlation = .55). In contrast to the assumed role of bullying victimization as an environmental trigger, these data suggest that bullying victimization in late childhood is particularly linked to self-rated Paranoia in adolescence via a shared genetic propensity. Clinically, individuals with a history of bullying victimization are predicted to be particularly susceptible to paranoid symptoms. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

  18. Persistency of Prediction Accuracy and Genetic Gain in Synthetic Populations Under Recurrent Genomic Selection.

    Science.gov (United States)

    Müller, Dominik; Schopp, Pascal; Melchinger, Albrecht E

    2017-03-10

    Recurrent selection (RS) has been used in plant breeding to successively improve synthetic and other multiparental populations. Synthetics are generated from a limited number of parents [Formula: see text] but little is known about how [Formula: see text] affects genomic selection (GS) in RS, especially the persistency of prediction accuracy ([Formula: see text]) and genetic gain. Synthetics were simulated by intermating [Formula: see text]= 2-32 parent lines from an ancestral population with short- or long-range linkage disequilibrium ([Formula: see text]) and subjected to multiple cycles of GS. We determined [Formula: see text] and genetic gain across 30 cycles for different training set ( TS ) sizes, marker densities, and generations of recombination before model training. Contributions to [Formula: see text] and genetic gain from pedigree relationships, as well as from cosegregation and [Formula: see text] between QTL and markers, were analyzed via four scenarios differing in (i) the relatedness between TS and selection candidates and (ii) whether selection was based on markers or pedigree records. Persistency of [Formula: see text] was high for small [Formula: see text] where predominantly cosegregation contributed to [Formula: see text], but also for large [Formula: see text] where [Formula: see text] replaced cosegregation as the dominant information source. Together with increasing genetic variance, this compensation resulted in relatively constant long- and short-term genetic gain for increasing [Formula: see text] > 4, given long-range LD A in the ancestral population. Although our scenarios suggest that information from pedigree relationships contributed to [Formula: see text] for only very few generations in GS, we expect a longer contribution than in pedigree BLUP, because capturing Mendelian sampling by markers reduces selective pressure on pedigree relationships. Larger TS size ([Formula: see text]) and higher marker density improved persistency of

  19. Persistency of Prediction Accuracy and Genetic Gain in Synthetic Populations Under Recurrent Genomic Selection

    Directory of Open Access Journals (Sweden)

    Dominik Müller

    2017-03-01

    Full Text Available Recurrent selection (RS has been used in plant breeding to successively improve synthetic and other multiparental populations. Synthetics are generated from a limited number of parents ( Np , but little is known about how Np affects genomic selection (GS in RS, especially the persistency of prediction accuracy (rg , g ^ and genetic gain. Synthetics were simulated by intermating Np= 2–32 parent lines from an ancestral population with short- or long-range linkage disequilibrium (LDA and subjected to multiple cycles of GS. We determined rg , g ^ and genetic gain across 30 cycles for different training set (TS sizes, marker densities, and generations of recombination before model training. Contributions to rg , g ^ and genetic gain from pedigree relationships, as well as from cosegregation and LDA between QTL and markers, were analyzed via four scenarios differing in (i the relatedness between TS and selection candidates and (ii whether selection was based on markers or pedigree records. Persistency of rg , g ^ was high for small Np , where predominantly cosegregation contributed to rg , g ^ , but also for large Np , where LDA replaced cosegregation as the dominant information source. Together with increasing genetic variance, this compensation resulted in relatively constant long- and short-term genetic gain for increasing Np > 4, given long-range LDA in the ancestral population. Although our scenarios suggest that information from pedigree relationships contributed to rg , g ^ for only very few generations in GS, we expect a longer contribution than in pedigree BLUP, because capturing Mendelian sampling by markers reduces selective pressure on pedigree relationships. Larger TS size (NTS and higher marker density improved persistency of rg , g ^ and hence genetic gain, but additional recombinations could not increase genetic gain.

  20. Mapping QTL for Seed Germinability under Low Temperature Using a New High-Density Genetic Map of Rice

    Directory of Open Access Journals (Sweden)

    Ningfei Jiang

    2017-07-01

    Full Text Available Mapping major quantitative trait loci (QTL responsible for rice seed germinability under low temperature (GULT can provide valuable genetic source for improving cold tolerance in rice breeding. In this study, 124 rice backcross recombinant inbred lines (BRILs derived from a cross indica cv. Changhui 891 and japonica cv. 02428 were genotyped through re-sequencing technology. A bin map was generated which includes 3057 bins covering distance of 1266.5 cM with an average of 0.41 cM between markers. On the basis of newly constructed high-density genetic map, six QTL were detected ranging from 40 to 140 kb on Nipponbare genome. Among these, two QTL qCGR8 and qGRR11 alleles shared by 02428 could increase GULT and seed germination recovery rate after cold stress, respectively. However, qNGR1 and qNGR4 may be two major QTL affecting indica Changhui 891germination under normal condition. QTL qGRR1 and qGRR8 affected the seed germination recovery rate after cold stress and the alleles with increasing effects were shared by the Changhui 891 could improve seed germination rate after cold stress dramatically. These QTL could be a highly valuable genetic factors for cold tolerance improvement in rice lines. Moreover, the BRILs developed in this study will serve as an appropriate choice for mapping and studying genetic basis of rice complex traits.

  1. Evolutionary divergence of the genetic architecture underlying photoperiodism in the pitcher-plant mosquito, Wyeomyia smithii.

    Science.gov (United States)

    Lair, K P; Bradshaw, W E; Holzapfel, C M

    1997-12-01

    We determine the contribution of composite additive, dominance, and epistatic effects to the genetic divergence of photoperiodic response along latitudinal, altitudinal, and longitudinal gradients in the pitcher-plant mosquito, Wyeomyia smithii. Joint scaling tests of crosses between populations showed widespread epistasis as well as additive and dominance differences among populations. There were differences due to epistasis between an alpine population in North Carolina and populations in Florida, lowland North Carolina, and Maine. Longitudinal displacement resulted in differences due to epistasis between Florida and Alabama populations separated by 300 km but not between Maine and Wisconsin populations separated by 2000 km. Genetic differences between New Jersey and Ontario did not involve either dominance or epistasis and we estimated the minimum number of effective factors contributing to a difference in mean critical photoperiod of 5 SD between them as nE = 5. We propose that the genetic similarity of populations within a broad northern region is due to their more recent origin since recession of the Laurentide Ice Sheet and that the unique genetic architecture of each population is the result of both mutation and repeated migration-founder-flush episodes during the dispersal of W. smithii in North America. Our results suggest that differences in composite additive and dominance effects arise early in the genetic divergence of populations while differences due to epistasis accumulate after more prolonged isolation.

  2. Neural circuit architecture defects in a Drosophila model of Fragile X syndrome are alleviated by minocycline treatment and genetic removal of matrix metalloproteinase

    Directory of Open Access Journals (Sweden)

    Saul S. Siller

    2011-09-01

    Fragile X syndrome (FXS, caused by loss of the fragile X mental retardation 1 (FMR1 product (FMRP, is the most common cause of inherited intellectual disability and autism spectrum disorders. FXS patients suffer multiple behavioral symptoms, including hyperactivity, disrupted circadian cycles, and learning and memory deficits. Recently, a study in the mouse FXS model showed that the tetracycline derivative minocycline effectively remediates the disease state via a proposed matrix metalloproteinase (MMP inhibition mechanism. Here, we use the well-characterized Drosophila FXS model to assess the effects of minocycline treatment on multiple neural circuit morphological defects and to investigate the MMP hypothesis. We first treat Drosophila Fmr1 (dfmr1 null animals with minocycline to assay the effects on mutant synaptic architecture in three disparate locations: the neuromuscular junction (NMJ, clock neurons in the circadian activity circuit and Kenyon cells in the mushroom body learning and memory center. We find that minocycline effectively restores normal synaptic structure in all three circuits, promising therapeutic potential for FXS treatment. We next tested the MMP hypothesis by assaying the effects of overexpressing the sole Drosophila tissue inhibitor of MMP (TIMP in dfmr1 null mutants. We find that TIMP overexpression effectively prevents defects in the NMJ synaptic architecture in dfmr1 mutants. Moreover, co-removal of dfmr1 similarly rescues TIMP overexpression phenotypes, including cellular tracheal defects and lethality. To further test the MMP hypothesis, we generated dfmr1;mmp1 double null mutants. Null mmp1 mutants are 100% lethal and display cellular tracheal defects, but co-removal of dfmr1 allows adult viability and prevents tracheal defects. Conversely, co-removal of mmp1 ameliorates the NMJ synaptic architecture defects in dfmr1 null mutants, despite the lack of detectable difference in MMP1 expression or gelatinase activity between the single

  3. Genetic predisposition for beta cell fragility underlies type 1 and type 2 diabetes.

    Science.gov (United States)

    Dooley, James; Tian, Lei; Schonefeldt, Susann; Delghingaro-Augusto, Viviane; Garcia-Perez, Josselyn E; Pasciuto, Emanuela; Di Marino, Daniele; Carr, Edward J; Oskolkov, Nikolay; Lyssenko, Valeriya; Franckaert, Dean; Lagou, Vasiliki; Overbergh, Lut; Vandenbussche, Jonathan; Allemeersch, Joke; Chabot-Roy, Genevieve; Dahlstrom, Jane E; Laybutt, D Ross; Petrovsky, Nikolai; Socha, Luis; Gevaert, Kris; Jetten, Anton M; Lambrechts, Diether; Linterman, Michelle A; Goodnow, Chris C; Nolan, Christopher J; Lesage, Sylvie; Schlenner, Susan M; Liston, Adrian

    2016-05-01

    Type 1 (T1D) and type 2 (T2D) diabetes share pathophysiological characteristics, yet mechanistic links have remained elusive. T1D results from autoimmune destruction of pancreatic beta cells, whereas beta cell failure in T2D is delayed and progressive. Here we find a new genetic component of diabetes susceptibility in T1D non-obese diabetic (NOD) mice, identifying immune-independent beta cell fragility. Genetic variation in Xrcc4 and Glis3 alters the response of NOD beta cells to unfolded protein stress, enhancing the apoptotic and senescent fates. The same transcriptional relationships were observed in human islets, demonstrating the role of beta cell fragility in genetic predisposition to diabetes.

  4. Genetic variation underlying resistance to infectious hematopoietic necrosis virus in a steelhead trout (Oncorhynchus mykiss) population

    Science.gov (United States)

    Brieuc, Marine S. O.; Purcell, Maureen K.; Palmer, Alexander D.; Naish, Kerry A.

    2015-01-01

    Understanding the mechanisms of host resistance to pathogens will allow insights into the response of wild populations to the emergence of new pathogens. Infectious hematopoietic necrosis virus (IHNV) is endemic to the Pacific Northwest and infectious to Pacific salmon and trout (Oncorhynchus spp.). Emergence of the M genogroup of IHNV in steelhead trout O. mykiss in the coastal streams of Washington State, between 2007 and 2011, was geographically heterogeneous. Differences in host resistance due to genetic change were hypothesized to be a factor influencing the IHNV emergence patterns. For example, juvenile steelhead trout losses at the Quinault National Fish Hatchery (QNFH) were much lower than those at a nearby facility that cultures a stock originally derived from the same source population. Using a classical quantitative genetic approach, we determined the potential for the QNFH steelhead trout population to respond to selection caused by the pathogen, by estimating the heritability for 2 traits indicative of IHNV resistance, mortality (h2 = 0.377 (0.226 - 0.550)) and days to death (h2 = 0.093 (0.018 - 0.203)). These results confirm that there is a genetic basis for resistance and that this population has the potential to adapt to IHNV. Additionally, genetic correlation between days to death and fish length suggests a correlated response in these traits to selection. Reduction of genetic variation, as well as the presence or absence of resistant alleles, could affect the ability of populations to adapt to the pathogen. Identification of the genetic basis for IHNV resistance could allow the assessment of the susceptibility of other steelhead populations.

  5. Vertebral defect, anal atresia, cardiac defect, tracheoesophageal fistula/esophageal atresia, renal defect, and limb defect association with Mayer-Rokitansky-Küster-Hauser syndrome in co-occurrence

    DEFF Research Database (Denmark)

    Bjørsum-Meyer, Thomas; Herlin, Morten; Qvist, Niels

    2016-01-01

    Background: The vertebral defect, anal atresia, cardiac defect, tracheoesophageal fistula/esophageal atresia, renal defect, and limb defect association and Mayer-Rokitansky-Küster-Hauser syndrome are rare conditions. We aimed to present two cases with the vertebral defect, anal atresia, cardiac...... defect, tracheoesophageal fistula/esophageal atresia, renal defect, and limb defect association and Mayer-Rokitansky-Küster-Hauser co-occurrence from our local surgical center and through a systematic literature search detect published cases. Furthermore, we aimed to collect existing knowledge...... in the embryopathogenesis and genetics in order to discuss a possible link between the vertebral defect, anal atresia, cardiac defect, tracheoesophageal fistula/esophageal atresia, renal defect, and limb defect association and Mayer-Rokitansky-Küster-Hauser syndrome. Case presentation: Our first case was a white girl...

  6. Brief Communication: Quantitative- and molecular-genetic differentiation in humans and chimpanzees: implications for the evolutionary processes underlying cranial diversification.

    Science.gov (United States)

    Weaver, Timothy D

    2014-08-01

    Estimates of the amount of genetic differentiation in humans among major geographic regions (e.g., Eastern Asia vs. Europe) from quantitative-genetic analyses of cranial measurements closely match those from classical- and molecular-genetic markers. Typically, among-region differences account for ∼10% of the total variation. This correspondence is generally interpreted as evidence for the importance of neutral evolutionary processes (e.g., genetic drift) in generating among-region differences in human cranial form, but it was initially surprising because human cranial diversity was frequently assumed to show a strong signature of natural selection. Is the human degree of similarity of cranial and DNA-sequence estimates of among-region genetic differentiation unusual? How do comparisons with other taxa illuminate the evolutionary processes underlying cranial diversification? Chimpanzees provide a useful starting point for placing the human results in a broader comparative context, because common chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) are the extant species most closely related to humans. To address these questions, I used 27 cranial measurements collected on a sample of 861 humans and 263 chimpanzees to estimate the amount of genetic differentiation between pairs of groups (between regions for humans and between species or subspecies for chimpanzees). Consistent with previous results, the human cranial estimates are quite similar to published DNA-sequence estimates. In contrast, the chimpanzee cranial estimates are much smaller than published DNA-sequence estimates. It appears that cranial differentiation has been limited in chimpanzees relative to humans. © 2014 Wiley Periodicals, Inc.

  7. Efficacy of Rosuvastatin in Children With Homozygous Familial Hypercholesterolemia and Association With Underlying Genetic Mutations

    NARCIS (Netherlands)

    Stein, Evan A.; Dann, Eldad J.; Wiegman, Albert; Skovby, Flemming; Gaudet, Daniel; Sokal, Etienne; Charng, Min-Ji; Mohamed, Mafauzy; Luirink, Ilse; Raichlen, Joel S.; Sundén, Mattias; Carlsson, Stefan C.; Raal, Frederick J.; Kastelein, John J. P.

    2017-01-01

    BACKGROUND Homozygous familial hypercholesterolemia (HoFH), a rare genetic disorder, is characterized by extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) and accelerated atherosclerotic cardiovascular disease. Statin treatment starts at diagnosis, but no statin has been

  8. Genetic Factors Underlying the Risk of Thalidomide-Related Neuropathy in Patients With Multiple Myeloma

    NARCIS (Netherlands)

    Johnson, David C.; Corthals, Sophie L.; Walker, Brian A.; Ross, Fiona M.; Gregory, Walter M.; Dickens, Nicholas J.; Lokhorst, Henk M.; Goldschmidt, Hartmut; Davies, Faith E.; Durie, Brian G. M.; Van Ness, Brian; Child, J. Anthony; Sonneveld, Pieter; Morgan, Gareth J.

    2011-01-01

    Purpose To indentify genetic variation that can modulate and predict the risk of developing thalidomide-related peripheral neuropathy (TrPN). Patients and Methods We analyzed DNA from 1,495 patients with multiple myeloma. Using a custom-built single nucleotide polymorphism (SNP) array, we tested the

  9. Genetic and environmental contributions underlying stability in Childhood Obsessive-Compulsive Behavior.

    NARCIS (Netherlands)

    van Grootheest, D.S.; Bartels, M.; Cath, D.C.; Beekman, A.T.F.; Hudziak, J.; Boomsma, D.I.

    2007-01-01

    Background: Little is known about the stability of obsessive-compulsive (OC) behavior during childhood. The objective of this study is to determine the developmental stability of pediatric OC behavior and the genetic and environmental influences on stability in a large population-based twin sample.

  10. Virus-host co-evolution under a modified nuclear genetic code

    Directory of Open Access Journals (Sweden)

    Derek J. Taylor

    2013-03-01

    Full Text Available Among eukaryotes with modified nuclear genetic codes, viruses are unknown. However, here we provide evidence of an RNA virus that infects a fungal host (Scheffersomyces segobiensis with a derived nuclear genetic code where CUG codes for serine. The genomic architecture and phylogeny are consistent with infection by a double-stranded RNA virus of the genus Totivirus. We provide evidence of past or present infection with totiviruses in five species of yeasts with modified genetic codes. All but one of the CUG codons in the viral genome have been eliminated, suggesting that avoidance of the modified codon was important to viral adaptation. Our mass spectroscopy analysis indicates that a congener of the host species has co-opted and expresses a capsid gene from totiviruses as a cellular protein. Viral avoidance of the host’s modified codon and host co-option of a protein from totiviruses suggest that RNA viruses co-evolved with yeasts that underwent a major evolutionary transition from the standard genetic code.

  11. Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease.

    Science.gov (United States)

    Baillie, J Kenneth; Bretherick, Andrew; Haley, Christopher S; Clohisey, Sara; Gray, Alan; Neyton, Lucile P A; Barrett, Jeffrey; Stahl, Eli A; Tenesa, Albert; Andersson, Robin; Brown, J Ben; Faulkner, Geoffrey J; Lizio, Marina; Schaefer, Ulf; Daub, Carsten; Itoh, Masayoshi; Kondo, Naoto; Lassmann, Timo; Kawai, Jun; Mole, Damian; Bajic, Vladimir B; Heutink, Peter; Rehli, Michael; Kawaji, Hideya; Sandelin, Albin; Suzuki, Harukazu; Satsangi, Jack; Wells, Christine A; Hacohen, Nir; Freeman, Thomas C; Hayashizaki, Yoshihide; Carninci, Piero; Forrest, Alistair R R; Hume, David A

    2018-03-01

    Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcriptional activity. Accordingly, shared transcriptional activity (coexpression) may help prioritise loci associated with a given trait, and help to identify underlying biological processes. Using cap analysis of gene expression (CAGE) profiles of promoter- and enhancer-derived RNAs across 1824 human samples, we have analysed coexpression of RNAs originating from trait-associated regulatory regions using a novel quantitative method (network density analysis; NDA). For most traits studied, phenotype-associated variants in regulatory regions were linked to tightly-coexpressed networks that are likely to share important functional characteristics. Coexpression provides a new signal, independent of phenotype association, to enable fine mapping of causative variants. The NDA coexpression approach identifies new genetic variants associated with specific traits, including an association between the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn's disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely to respond differently to pharmacological therapy. Together, these findings enable a deeper biological understanding of the causal basis of complex traits.

  12. Genetics and Genomics of Congenital Heart Disease

    Science.gov (United States)

    Zaidi, Samir; Brueckner, Martina

    2017-01-01

    Congenital heart disease is the most common birth defect, and due to major advances in medical and surgical management, there are now more adults living with CHD than children. Until recently, the cause of the majority of CHD was unknown. Advances in genomic technologies have discovered the genetic etiology of a significant fraction of CHD, while at the same time pointing to remarkable complexity in CHD genetics. This review will focus on the evidence for genetic causes underlying CHD and discuss data supporting both monogenic and complex genetic mechanisms underlying CHD. The discoveries from CHD genetic studies draw attention to biological pathways that simultaneously open the door to a better understanding of cardiac development, and impact clinical care of CHD patients. Finally, we address clinical genetic evaluation of patients and families affected by CHD. PMID:28302740

  13. Defect creation under UV irradiation of CsI:Pb crystals in Pb 2+ -induced absorption bands investigated by luminescence methods

    Czech Academy of Sciences Publication Activity Database

    Babin, V.; Kalder, K.; Krasnikov, A.; Nikl, Martin; Nitsch, Karel; Zazubovich, S.

    2002-01-01

    Roč. 234, č. 2 (2002), s. 689-700 ISSN 0370-1972 Grant - others:NATO(XX) SfP 973510 Institutional research plan: CEZ:AV0Z1010914 Keywords : CsI:Pb crystal * luminescence * thermoluminescence * defect creation * UV irradiation Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 0.930, year: 2002

  14. Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease.

    Science.gov (United States)

    Imhann, Floris; Vich Vila, Arnau; Bonder, Marc Jan; Fu, Jingyuan; Gevers, Dirk; Visschedijk, Marijn C; Spekhorst, Lieke M; Alberts, Rudi; Franke, Lude; van Dullemen, Hendrik M; Ter Steege, Rinze W F; Huttenhower, Curtis; Dijkstra, Gerard; Xavier, Ramnik J; Festen, Eleonora A M; Wijmenga, Cisca; Zhernakova, Alexandra; Weersma, Rinse K

    2018-01-01

    Patients with IBD display substantial heterogeneity in clinical characteristics. We hypothesise that individual differences in the complex interaction of the host genome and the gut microbiota can explain the onset and the heterogeneous presentation of IBD. Therefore, we performed a case-control analysis of the gut microbiota, the host genome and the clinical phenotypes of IBD. Stool samples, peripheral blood and extensive phenotype data were collected from 313 patients with IBD and 582 truly healthy controls, selected from a population cohort. The gut microbiota composition was assessed by tag-sequencing the 16S rRNA gene. All participants were genotyped. We composed genetic risk scores from 11 functional genetic variants proven to be associated with IBD in genes that are directly involved in the bacterial handling in the gut: NOD2 , CARD9 , ATG16L1 , IRGM and FUT2 . Strikingly, we observed significant alterations of the gut microbiota of healthy individuals with a high genetic risk for IBD: the IBD genetic risk score was significantly associated with a decrease in the genus Roseburia in healthy controls (false discovery rate 0.017). Moreover, disease location was a major determinant of the gut microbiota: the gut microbiota of patients with colonic Crohn's disease (CD) is different from that of patients with ileal CD, with a decrease in alpha diversity associated to ileal disease (p=3.28×10 -13 ). We show for the first time that genetic risk variants associated with IBD influence the gut microbiota in healthy individuals. Roseburia spp are acetate-to-butyrate converters, and a decrease has already been observed in patients with IBD. 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/.

  15. Genetic Analysis for Some of Morphological Traits in Bread Wheat under Drought Stress Condition Using Generations Mean Analysis

    Directory of Open Access Journals (Sweden)

    Jamileh Abedi

    2015-06-01

    Full Text Available Perception of genes action controlling of quantitative traits is very important in genetic breeding methods the plant populations. to study and estimate the parameters of genetic and appointment the best genetically model for justification the genetic changing some of traits the bread wheat under drought stress condition, parents (P1 & P2 and F3, F4, F5 generations together the four control cultivars (Kharchia, Gaspard, Moghan and Mahuti were evaluated by generation mean analysis using a agoment design including six blocks. Generation mean analysis was performed for all traits with Mather and Jinks model using joint scaling test. Three parameter model [m d h] provided the best fit for all traits expect harvest index, main spike grain weight, number of grain per plant, Total spike weight of plant with significant at 5% and 1% levels . Though additive and dominance effect both had interfered in controlling often the traits but with attention to difference effects and variety component was determined that dominance is more impressive than additive effect for traits of number of tiller, main spike weight, grain yield and grain number of main spike. Therefore will benefit using of these traits in the collection and to improve these traits hybridization would be much efficient than the selection strategies. In this study additive Ч additive epistasis effect only observed for traits of Total spike weight of plant, number of grain per plant, main spike grain weight and harvest index and other traits hadn’t any epistasis effect that it was demonstration lack of existence the genes reciprocal effect in the inheritance studied traits. Therefore we can suggest that the selection strategies perform in terminal generations and additive Ч additive epistasis effect would be confirmed in selection under self-pollination condition.

  16. Genetic variation underlying renal uric acid excretion in Hispanic children: the Viva La Familia Study.

    Science.gov (United States)

    Chittoor, Geetha; Haack, Karin; Mehta, Nitesh R; Laston, Sandra; Cole, Shelley A; Comuzzie, Anthony G; Butte, Nancy F; Voruganti, V Saroja

    2017-01-17

    Reduced renal excretion of uric acid plays a significant role in the development of hyperuricemia and gout in adults. Hyperuricemia has been associated with chronic kidney disease and cardiovascular disease in children and adults. There are limited genome-wide association studies associating genetic polymorphisms with renal urate excretion measures. Therefore, we investigated the genetic factors that influence the excretion of uric acid and related indices in 768 Hispanic children of the Viva La Familia Study. We performed a genome-wide association analysis for 24-h urinary excretion measures such as urinary uric acid/urinary creatinine ratio, uric acid clearance, fractional excretion of uric acid, and glomerular load of uric acid in SOLAR, while accounting for non-independence among family members. All renal urate excretion measures were significantly heritable (p uric acid clearance with a single nucleotide polymorphism (SNP) in zinc finger protein 446 (ZNF446) (rs2033711 (A/G), MAF: 0.30). The minor allele (G) was associated with increased uric acid clearance. Also, we found suggestive associations of uric acid clearance with SNPs in ZNF324, ZNF584, and ZNF132 (in a 72 kb region of 19q13; p <1 × 10 -6 , MAFs: 0.28-0.31). For the first time, we showed the importance of 19q13 region in the regulation of renal urate excretion in Hispanic children. Our findings indicate differences in inherent genetic architecture and shared environmental risk factors between our cohort and other pediatric and adult populations.

  17. Defects of mitochondrial DNA replication.

    Science.gov (United States)

    Copeland, William C

    2014-09-01

    Mitochondrial DNA is replicated by DNA polymerase γ in concert with accessory proteins such as the mitochondrial DNA helicase, single-stranded DNA binding protein, topoisomerase, and initiating factors. Defects in mitochondrial DNA replication or nucleotide metabolism can cause mitochondrial genetic diseases due to mitochondrial DNA deletions, point mutations, or depletion, which ultimately cause loss of oxidative phosphorylation. These genetic diseases include mitochondrial DNA depletion syndromes such as Alpers or early infantile hepatocerebral syndromes, and mitochondrial DNA deletion disorders, such as progressive external ophthalmoplegia, ataxia-neuropathy, or mitochondrial neurogastrointestinal encephalomyopathy. This review focuses on our current knowledge of genetic defects of mitochondrial DNA replication (POLG, POLG2, C10orf2, and MGME1) that cause instability of mitochondrial DNA and mitochondrial disease. © The Author(s) 2014.

  18. Exploring the genetics and non-cell autonomous mechanisms underlying ALS/FTLD.

    Science.gov (United States)

    Chen, Hongbo; Kankel, Mark W; Su, Susan C; Han, Steve W S; Ofengeim, Dimitry

    2018-03-01

    Although amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, was first described in 1874, a flurry of genetic discoveries in the last 10 years has markedly increased our understanding of this disease. These findings have not only enhanced our knowledge of mechanisms leading to ALS, but also have revealed that ALS shares many genetic causes with another neurodegenerative disease, frontotemporal lobar dementia (FTLD). In this review, we survey how recent genetic studies have bridged our mechanistic understanding of these two related diseases and how the genetics behind ALS and FTLD point to complex disorders, implicating non-neuronal cell types in disease pathophysiology. The involvement of non-neuronal cell types is consistent with a non-cell autonomous component in these diseases. This is further supported by studies that identified a critical role of immune-associated genes within ALS/FTLD and other neurodegenerative disorders. The molecular functions of these genes support an emerging concept that various non-autonomous functions are involved in neurodegeneration. Further insights into such a mechanism(s) will ultimately lead to a better understanding of potential routes of therapeutic intervention. Facts ALS and FTLD are severe neurodegenerative disorders on the same disease spectrum. Multiple cellular processes including dysregulation of RNA homeostasis, imbalance of proteostasis, contribute to ALS/FTLD pathogenesis. Aberrant function in non-neuronal cell types, including microglia, contributes to ALS/FTLD. Strong neuroimmune and neuroinflammatory components are associated with ALS/FTLD patients. Open Questions Why can patients with similar mutations have different disease manifestations, i.e., why do C9ORF72 mutations lead to motor neuron loss in some patients while others exhibit loss of neurons in the frontotemporal lobe? Do ALS causal mutations result in microglial dysfunction and contribute to ALS/FTLD pathology? How do microglia

  19. Coagulation defects.

    Science.gov (United States)

    Soliman, Doreen E; Broadman, Lynn M

    2006-09-01

    The present understanding of the coagulation process emphasizes the final common pathway and the proteolytic systems that result in the degradation of formed clots and the prevention of unwanted clot formations, as well as a variety of defense systems that include tissue repair, autoimmune processes, arteriosclerosis, tumor growth, the spread of metastases, and defense systems against micro-organisms. This article discusses diagnosis and management of some of the most common bleeding disorders. The goals are to provide a simple guide on how best to manage patients afflicted with congenital or acquired clotting abnormalities during the perioperative period, present a brief overview of the methods of testing and monitoring the coagulation defects, and discuss the appropriate pharmacologic or blood component therapies for each disease.

  20. Distinct genetic architecture underlies the emergence of sleep loss and prey-seeking behavior in the Mexican cavefish.

    Science.gov (United States)

    Yoshizawa, Masato; Robinson, Beatriz G; Duboué, Erik R; Masek, Pavel; Jaggard, James B; O'Quin, Kelly E; Borowsky, Richard L; Jeffery, William R; Keene, Alex C

    2015-02-20

    Sleep is characterized by extended periods of quiescence and reduced responsiveness to sensory stimuli. Animals ranging from insects to mammals adapt to environments with limited food by suppressing sleep and enhancing their response to food cues, yet little is known about the genetic and evolutionary relationship between these processes. The blind Mexican cavefish, Astyanax mexicanus is a powerful model for elucidating the genetic mechanisms underlying behavioral evolution. A. mexicanus comprises an extant ancestral-type surface dwelling morph and at least five independently evolved cave populations. Evolutionary convergence on sleep loss and vibration attraction behavior, which is involved in prey seeking, have been documented in cavefish raising the possibility that enhanced sensory responsiveness underlies changes in sleep. We established a system to study sleep and vibration attraction behavior in adult A. mexicanus and used high coverage quantitative trait loci (QTL) mapping to investigate the functional and evolutionary relationship between these traits. Analysis of surface-cave F2 hybrid fish and an outbred cave population indicates that independent genetic factors underlie changes in sleep/locomotor activity and vibration attraction behavior. High-coverage QTL mapping with genotyping-by-sequencing technology identify two novel QTL intervals that associate with locomotor activity and include the narcolepsy-associated tp53 regulating kinase. These QTLs represent the first genomic localization of locomotor activity in cavefish and are distinct from two QTLs previously identified as associating with vibration attraction behavior. Taken together, these results localize genomic regions underlying sleep/locomotor and sensory changes in cavefish populations and provide evidence that sleep loss evolved independently from enhanced sensory responsiveness.

  1. DGAT1 underlies large genetic variation in milk-fat composition of dairy cows.

    Science.gov (United States)

    Schennink, A; Stoop, W M; Visker, M H P W; Heck, J M L; Bovenhuis, H; van der Poel, J J; van Valenberg, H J F; van Arendonk, J A M

    2007-10-01

    Dietary fat may play a role in the aetiology of many chronic diseases. Milk and milk-derived foods contribute substantially to dietary fat, but have a fat composition that is not optimal for human health. We measured the fat composition of milk samples in 1918 Dutch Holstein Friesian cows in their first lactation and estimated genetic parameters for fatty acids. Substantial genetic variation in milk-fat composition was found: heritabilities were high for short- and medium-chain fatty acids (C4:0-C16:0) and moderate for long-chain fatty acids (saturated and unsaturated C18). We genotyped 1762 cows for the DGAT1 K232A polymorphism, which is known to affect milk-fat percentage, to study the effect of the polymorphism on milk-fat composition. We found that the DGAT1 K232A polymorphism has a clear influence on milk-fat composition. The DGAT1 allele that encodes lysine (K) at position 232 (232K) is associated with more saturated fat; a larger fraction of C16:0; and smaller fractions of C14:0, unsaturated C18 and conjugated linoleic acid (P < 0.001). We conclude that selective breeding can make a significant contribution to change the fat composition of cow's milk.

  2. BAYESIAN PREDICTION OF GENETIC PARAMETERS IN Eucalyptus globulus CLONES UNDER WATER SUPPLY CONDITIONS

    Directory of Open Access Journals (Sweden)

    Freddy Mora

    2013-06-01

    Full Text Available http://dx.doi.org/10.5902/198050989297A Bayesian analysis of genetic parameters for growth traits at twelve months after planting was carried out in twenty nine Eucalyptus globulus clones in southern Chile. Two different environmental conditions were considered: 1 Non-irrigation and; 2 Plants were irrigated with a localized irrigation system. The Bayesian approach was performed using Gibbs sampling algorithm in a clone-environment interaction model. Inheritability values ​​were high in the water supply condition (posterior mode: H2=0.41, 0.36 and 0.39 for height, diameter and sectional area, respectively, while in the environment without irrigation, the inheritabilities were significantly lower, which was confirmed by the Bayesian credible intervals (95% probability. The posterior mode of the genetic correlation between sites was positive and high for all traits (r=0.7, 0.65 and 0.8, for height, diameter and sectional area, respectively and according to the credible interval, it was statistically different from zero, indicating a non-significant interaction.

  3. Assessment of Genetics Understanding. Under What Conditions Do Situational Features Have an Impact on Measures?

    Science.gov (United States)

    Schmiemann, Philipp; Nehm, Ross H.; Tornabene, Robyn E.

    2017-12-01

    Understanding how situational features of assessment tasks impact reasoning is important for many educational pursuits, notably the selection of curricular examples to illustrate phenomena, the design of formative and summative assessment items, and determination of whether instruction has fostered the development of abstract schemas divorced from particular instances. The goal of our study was to employ an experimental research design to quantify the degree to which situational features impact inferences about participants' understanding of Mendelian genetics. Two participant samples from different educational levels and cultural backgrounds (high school, n = 480; university, n = 444; Germany and USA) were used to test for context effects. A multi-matrix test design was employed, and item packets differing in situational features (e.g., plant, animal, human, fictitious) were randomly distributed to participants in the two samples. Rasch analyses of participant scores from both samples produced good item fit, person reliability, and item reliability and indicated that the university sample displayed stronger performance on the items compared to the high school sample. We found, surprisingly, that in both samples, no significant differences in performance occurred among the animal, plant, and human item contexts, or between the fictitious and "real" item contexts. In the university sample, we were also able to test for differences in performance between genders, among ethnic groups, and by prior biology coursework. None of these factors had a meaningful impact upon performance or context effects. Thus some, but not all, types of genetics problem solving or item formats are impacted by situational features.

  4. Intelligence : shared genetic basis between Mendelian disorders and a polygenic trait

    NARCIS (Netherlands)

    Franić, Sanja; Groen-Blokhuis, Maria M; Dolan, Conor V; Kattenberg, Mathijs V; Pool, René; Xiao, Xiangjun; Scheet, Paul A; Ehli, Erik A; Davies, Gareth E; van der Sluis, Sophie; Abdellaoui, Abdel; Hansell, Narelle K; Martin, Nicholas G; Hudziak, James J; van Beijsterveldt, Catherina E M; Swagerman, Suzanne C; Hulshoff Pol, Hilleke E; de Geus, Eco J C; Bartels, Meike; Ropers, H Hilger; Hottenga, Jouke-Jan; Boomsma, Dorret I

    2015-01-01

    Multiple inquiries into the genetic etiology of human traits indicated an overlap between genes underlying monogenic disorders (eg, skeletal growth defects) and those affecting continuous variability of related quantitative traits (eg, height). Extending the idea of a shared genetic basis between a

  5. Two case reports of an unusual association between Klippel-Feil syndrome and amyotrophic lateral sclerosis: Do they share same genetic defect?

    Directory of Open Access Journals (Sweden)

    Koneru Lakshmi Umamaheshwar

    2013-01-01

    Full Text Available Klippel-Feil syndrome (KFS is an unusual skeletal disorder characterized by congenital fusion of two or more cervical vertebrae which can be sporadic or familial. KFS emerges to be a failure of the normal segmentation and fusion of the mesodermal somites during 3 rd and 8 th weeks of embryonic development. The triad of low posterior hairline, short neck, and restricted neck motion is present only in 50% and often associated with scoliosis, spina bifida, Sprengel′s deformity, cervical ribs, deafness, cleft palate, renal anomalies, congenital heart defects, and so on because of heterogeneous nature of the disease. The significance of KFS lies in the secondary effects produced on the nervous system, which usually presents with features of progressive cord and brain stem compression with relatively minor trauma. We here report two cases of KFS presented in association with amyotrophic lateral sclerosis. Only two such cases have been described in the literature in 1954 and 1975.

  6. Physical and genetic mapping of the CMT4A locus and exclusion of PMP-2 as the defect in CMT4A

    Energy Technology Data Exchange (ETDEWEB)

    Othmane, K.B.; Loeb, D.; Roses, A.D.; Pericak-Vance, M.A.; Vance, J.M. [Duke Univ. Medical Center, Durham, NC (United States)] [and others

    1995-07-20

    We have previously localized one form of the autosomal recessive Charcot-Marie-Tooth disease type 4 (CMT4A) to a 5-cM region of chromosome 8q13-q21. We now report the formation of a 7-Bp YAC contig spanning the region. This contig was used to map nine additional microsatellites and six STSs to this region, and subsequent haplotype analysis has narrowed the CMT4A flanking interval to less than 1 cM. In addition, using SSCP and our physical map, we have demonstrated that the myelin protein PMP-2, mapped by FISH to this region, is not the defect in CMT4A. 27 refs., 3 figs., 1 tab.

  7. Human ATP-binding cassette transporter 1 (ABC1): Genomic organization and identification of the genetic defect in the original Tangier disease kindred

    Science.gov (United States)

    Remaley, Alan T.; Rust, Stephan; Rosier, Marie; Knapper, Cathy; Naudin, Laurent; Broccardo, Cyril; Peterson, Katherine M.; Koch, Christine; Arnould, Isabelle; Prades, Catherine; Duverger, Nicholas; Funke, Harald; Assman, Gerd; Dinger, Maria; Dean, Michael; Chimini, Giovanna; Santamarina-Fojo, Silvia; Fredrickson, Donald S.; Denefle, Patrice; Brewer, H. Bryan

    1999-01-01

    Tangier disease is characterized by low serum high density lipoproteins and a biochemical defect in the cellular efflux of lipids to high density lipoproteins. ABC1, a member of the ATP-binding cassette family, recently has been identified as the defective gene in Tangier disease. We report here the organization of the human ABC1 gene and the identification of a mutation in the ABC1 gene from the original Tangier disease kindred. The organization of the human ABC1 gene is similar to that of the mouse ABC1 gene and other related ABC genes. The ABC1 gene contains 49 exons that range in size from 33 to 249 bp and is over 70 kb in length. Sequence analysis of the ABC1 gene revealed that the proband for Tangier disease was homozygous for a deletion of nucleotides 3283 and 3284 (TC) in exon 22. The deletion results in a frameshift mutation and a premature stop codon starting at nucleotide 3375. The product is predicted to encode a nonfunctional protein of 1,084 aa, which is approximately half the size of the full-length ABC1 protein. The loss of a Mnl1 restriction site, which results from the deletion, was used to establish the genotype of the rest of the kindred. In summary, we report on the genomic organization of the human ABC1 gene and identify a frameshift mutation in the ABC1 gene of the index case of Tangier disease. These results will be useful in the future characterization of the structure and function of the ABC1 gene and the analysis of additional ABC1 mutations in patients with Tangier disease. PMID:10535983

  8. Genetics Home Reference: CHOPS syndrome

    Science.gov (United States)

    ... Defects Patient Support and Advocacy Resources (4 links) American Heart Association Contact a Family: Heart Defects The Arc: For People with Intellectual and Developmental Disabilities University of Kansas Genetics Education Center Resource List: ...

  9. Ambient-temperature diffusion and gettering of Pt atoms in GaN with surface defect region under 60Co gamma or MeV electron irradiation

    Science.gov (United States)

    Hou, Ruixiang; Li, Lei; Fang, Xin; Xie, Ziang; Li, Shuti; Song, Weidong; Huang, Rong; Zhang, Jicai; Huang, Zengli; Li, Qiangjie; Xu, Wanjing; Fu, Engang; Qin, G. G.

    2018-01-01

    Generally, the diffusion and gettering of impurities in GaN needs high temperature. Calculated with the ambient-temperature extrapolation value of the high temperature diffusivity of Pt atoms in GaN reported in literature, the time required for Pt atoms diffusing 1 nm in GaN at ambient temperature is about 19 years. Therefore, the ambient-temperature diffusion and gettering of Pt atoms in GaN can hardly be observed. In this work, the ambient-temperature diffusion and gettering of Pt atoms in GaN is reported for the first time. It is demonstrated by use of secondary ion mass spectroscopy that in the condition of introducing a defect region on the GaN film surface by plasma, and subsequently, irradiated by 60Co gamma-ray or 3 MeV electrons, the ambient-temperature diffusion and gettering of Pt atoms in GaN can be detected. It is more obvious with larger irradiation dose and higher plasma power. With a similar surface defect region, the ambient-temperature diffusion and gettering of Pt atoms in GaN stimulated by 3 MeV electron irradiation is more marked than that stimulated by gamma irradiation. The physical mechanism of ambient-temperature diffusion and gettering of Pt atoms in a GaN film with a surface defect region stimulated by gamma or MeV electron irradiation is discussed.

  10. Genetic and Molecular Mechanisms Underlying Symbiotic Specificity in Legume-Rhizobium Interactions

    Directory of Open Access Journals (Sweden)

    Qi Wang

    2018-03-01

    Full Text Available Legumes are able to form a symbiotic relationship with nitrogen-fixing soil bacteria called rhizobia. The result of this symbiosis is to form nodules on the plant root, within which the bacteria can convert atmospheric nitrogen into ammonia that can be used by the plant. Establishment of a successful symbiosis requires the two symbiotic partners to be compatible with each other throughout the process of symbiotic development. However, incompatibility frequently occurs, such that a bacterial strain is unable to nodulate a particular host plant or forms nodules that are incapable of fixing nitrogen. Genetic and molecular mechanisms that regulate symbiotic specificity are diverse, involving a wide range of host and bacterial genes/signals with various modes of action. In this review, we will provide an update on our current knowledge of how the recognition specificity has evolved in the context of symbiosis signaling and plant immunity.

  11. Genetic and epigenetic mechanisms underlying arsenic-associated diabetes mellitus: a perspective of the current evidence.

    Science.gov (United States)

    Martin, Elizabeth M; Stýblo, Miroslav; Fry, Rebecca C

    2017-05-01

    Chronic exposure to arsenic has been associated with the development of diabetes mellitus (DM), a disease characterized by hyperglycemia resulting from dysregulation of glucose homeostasis. This review summarizes four major mechanisms by which arsenic induces diabetes, namely inhibition of insulin-dependent glucose uptake, pancreatic β-cell damage, pancreatic β-cell dysfunction and stimulation of liver gluconeogenesis that are supported by both in vivo and in vitro studies. Additionally, the role of polymorphic variants associated with arsenic toxicity and disease susceptibility, as well as epigenetic modifications associated with arsenic exposure, are considered in the context of arsenic-associated DM. Taken together, in vitro, in vivo and human genetic/epigenetic studies support that arsenic has the potential to induce DM phenotypes and impair key pathways involved in the regulation of glucose homeostasis.

  12. Genetic subdivision and candidate genes under selection in North American grey wolves.

    Science.gov (United States)

    Schweizer, Rena M; vonHoldt, Bridgett M; Harrigan, Ryan; Knowles, James C; Musiani, Marco; Coltman, David; Novembre, John; Wayne, Robert K

    2016-01-01

    Previous genetic studies of the highly mobile grey wolf (Canis lupus) found population structure that coincides with habitat and phenotype differences. We hypothesized that these ecologically distinct populations (ecotypes) should exhibit signatures of selection in genes related to morphology, coat colour and metabolism. To test these predictions, we quantified population structure related to habitat using a genotyping array to assess variation in 42 036 single-nucleotide polymorphisms (SNPs) in 111 North American grey wolves. Using these SNP data and individual-level measurements of 12 environmental variables, we identified six ecotypes: West Forest, Boreal Forest, Arctic, High Arctic, British Columbia and Atlantic Forest. Next, we explored signals of selection across these wolf ecotypes through the use of three complementary methods to detect selection: FST /haplotype homozygosity bivariate percentilae, bayescan, and environmentally correlated directional selection with bayenv. Across all methods, we found consistent signals of selection on genes related to morphology, coat coloration, metabolism, as predicted, as well as vision and hearing. In several high-ranking candidate genes, including LEPR, TYR and SLC14A2, we found variation in allele frequencies that follow environmental changes in temperature and precipitation, a result that is consistent with local adaptation rather than genetic drift. Our findings show that local adaptation can occur despite gene flow in a highly mobile species and can be detected through a moderately dense genomic scan. These patterns of local adaptation revealed by SNP genotyping likely reflect high fidelity to natal habitats of dispersing wolves, strong ecological divergence among habitats, and moderate levels of linkage in the wolf genome. © 2015 John Wiley & Sons Ltd.

  13. Invariability of Central Metabolic Flux Distribution in Shewanella oneidensis MR-1 Under Environmental or Genetic Perturbations

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Yinjie; Martin, Hector Garcia; Deutschbauer, Adam; Feng, Xueyang; Huang, Rick; Llora, Xavier; Arkin, Adam; Keasling, Jay D.

    2009-04-21

    An environmentally important bacterium with versatile respiration, Shewanella oneidensis MR-1, displayed significantly different growth rates under three culture conditions: minimal medium (doubling time {approx} 3 hrs), salt stressed minimal medium (doubling time {approx} 6 hrs), and minimal medium with amino acid supplementation (doubling time {approx}1.5 hrs). {sup 13}C-based metabolic flux analysis indicated that fluxes of central metabolic reactions remained relatively constant under the three growth conditions, which is in stark contrast to the reported significant changes in the transcript and metabolite profiles under various growth conditions. Furthermore, ten transposon mutants of S. oneidensis MR-1 were randomly chosen from a transposon library and their flux distributions through central metabolic pathways were revealed to be identical, even though such mutational processes altered the secondary metabolism, for example, glycine and C1 (5,10-Me-THF) metabolism.

  14. Genetic Architecture of Natural Variation Underlying Adult Foraging Behavior That Is Essential for Survival of Drosophila melanogaster.

    Science.gov (United States)

    Lee, Yuh Chwen G; Yang, Qian; Chi, Wanhao; Turkson, Susie A; Du, Wei A; Kemkemer, Claus; Zeng, Zhao-Bang; Long, Manyuan; Zhuang, Xiaoxi

    2017-05-01

    Foraging behavior is critical for the fitness of individuals. However, the genetic basis of variation in foraging behavior and the evolutionary forces underlying such natural variation have rarely been investigated. We developed a systematic approach to assay the variation in survival rate in a foraging environment for adult flies derived from a wild Drosophila melanogaster population. Despite being such an essential trait, there is substantial variation of foraging behavior among D. melanogaster strains. Importantly, we provided the first evaluation of the potential caveats of using inbred Drosophila strains to perform genome-wide association studies on life-history traits, and concluded that inbreeding depression is unlikely a major contributor for the observed large variation in adult foraging behavior. We found that adult foraging behavior has a strong genetic component and, unlike larval foraging behavior, depends on multiple loci. Identified candidate genes are enriched in those with high expression in adult heads and, demonstrated by expression knock down assay, are involved in maintaining normal functions of the nervous system. Our study not only identified candidate genes for foraging behavior that is relevant to individual fitness, but also shed light on the initial stage underlying the evolution of the behavior. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  15. RAD-QTL Mapping Reveals Both Genome-Level Parallelism and Different Genetic Architecture Underlying the Evolution of Body Shape in Lake Whitefish (Coregonus clupeaformis) Species Pairs.

    Science.gov (United States)

    Laporte, Martin; Rogers, Sean M; Dion-Côté, Anne-Marie; Normandeau, Eric; Gagnaire, Pierre-Alexandre; Dalziel, Anne C; Chebib, Jobran; Bernatchez, Louis

    2015-05-21

    Parallel changes in body shape may evolve in response to similar environmental conditions, but whether such parallel phenotypic changes share a common genetic basis is still debated. The goal of this study was to assess whether parallel phenotypic changes could be explained by genetic parallelism, multiple genetic routes, or both. We first provide evidence for parallelism in fish shape by using geometric morphometrics among 300 fish representing five species pairs of Lake Whitefish. Using a genetic map comprising 3438 restriction site-associated DNA sequencing single-nucleotide polymorphisms, we then identified quantitative trait loci underlying body shape traits in a backcross family reared in the laboratory. A total of 138 body shape quantitative trait loci were identified in this cross, thus revealing a highly polygenic architecture of body shape in Lake Whitefish. Third, we tested for evidence of genetic parallelism among independent wild populations using both a single-locus method (outlier analysis) and a polygenic approach (analysis of covariation among markers). The single-locus approach provided limited evidence for genetic parallelism. However, the polygenic analysis revealed genetic parallelism for three of the five lakes, which differed from the two other lakes. These results provide evidence for both genetic parallelism and multiple genetic routes underlying parallel phenotypic evolution in fish shape among populations occupying similar ecological niches. Copyright © 2015 Laporte et al.

  16. Novel genetic loci underlying human intracranial volume identified through genome-wide association

    NARCIS (Netherlands)

    Adams, Hieab H H; Hibar, Derrek P; Chouraki, Vincent; Stein, Jason L; Nyquist, Paul A; Rentería, Miguel E; Trompet, Stella; Arias-Vasquez, Alejandro; Seshadri, Sudha; Desrivières, Sylvane; Beecham, Ashley H; Jahanshad, Neda; Wittfeld, Katharina; Van der Lee, Sven J; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S; Armstrong, Nicola J; Athanasiu, Lavinia; Axelsson, Tomas; Beiser, Alexa; Bernard, Manon; Bis, Joshua C; Blanken, Laura M E; Blanton, Susan H; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brickman, Adam M; Carmichael, Owen; Chakravarty, M Mallar; Chauhan, Ganesh; Chen, Qiang; Ching, Christopher R K; Cuellar-Partida, Gabriel; Braber, Anouk Den; Doan, Nhat Trung; Ehrlich, Stefan; Filippi, Irina; Ge, Tian; Giddaluru, Sudheer; Goldman, Aaron L; Gottesman, Rebecca F; Greven, Corina U; Grimm, Oliver; Griswold, Michael E; Guadalupe, Tulio; Hass, Johanna; Haukvik, Unn K; Hilal, Saima; Hofer, Edith; Hoehn, David; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Liao, Jiemin; Liewald, David C M; Lopez, Lorna M; Luciano, Michelle; Macare, Christine; Marquand, Andre; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; Mazoyer, Bernard; McKay, David R; McWhirter, Rebekah; Milaneschi, Yuri; Mirza-Schreiber, Nazanin; Muetzel, Ryan L; Maniega, Susana Muñoz; Nho, Kwangsik; Nugent, Allison C; Loohuis, Loes M Olde; Oosterlaan, Jaap; Papmeyer, Martina; Pappa, Irene; Pirpamer, Lukas; Pudas, Sara; Pütz, Benno; Rajan, Kumar B; Ramasamy, Adaikalavan; Richards, Jennifer S; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rommelse, Nanda; Rose, Emma J; Royle, Natalie A; Rundek, Tatjana; Sämann, Philipp G; Satizabal, Claudia L; Schmaal, Lianne; Schork, Andrew J; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V; Sprooten, Emma; Strike, Lachlan T; Teumer, Alexander; Thomson, Russell; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Meer, Dennis; Van Donkelaar, Marjolein M J; Van Eijk, Kristel R; Van Erp, Theo G M; Van Rooij, Daan; Walton, Esther; Westlye, Lars T; Whelan, Christopher D; Windham, Beverly G; Winkler, Anderson M; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Xu, Bing; Yanek, Lisa R; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P; Agartz, Ingrid; Aggarwal, Neelum T; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A; Arepalli, Sampath; Assareh, Amelia A; Barral, Sandra; Bastin, Mark E; Becker, Diane M; Becker, James T; Bennett, David A; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I; Brodaty, Henry; Brouwer, Rachel M; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cahn, Wiepke; Calhoun, Vince D; Cannon, Dara M; Cavalleri, Gianpiero L; Chen, Christopher; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Dale, Anders M; Davies, Gareth E; De Geus, Eco J C; De Jager, Philip L; de Zubicaray, Greig I; Delanty, Norman; Depondt, Chantal; DeStefano, Anita L; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Espeseth, Thomas; Evans, Denis A; Fedko, Iryna O; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E; Fleischman, Debra A; Ford, Ian; Foroud, Tatiana M; Fox, Peter T; Francks, Clyde; Fukunaga, Masaki; Gibbs, J Raphael; Glahn, David C; Gollub, Randy L; Göring, Harald H H; Grabe, Hans J; Green, Robert C; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Hansell, Narelle K; Hardy, John; Hartman, Catharina A; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G; Heslenfeld, Dirk J; Ho, Beng-Choon; Hoekstra, Pieter J; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Pol, Hilleke E Hulshoff; Ikeda, Masashi; Ikram, M Kamran; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G; Jukema, J Wouter; Kahn, René S; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L; Longstreth, W T; Lopez, Oscar L; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S; McDonald, Colm; McIntosh, Andrew M; McMahon, Katie L; McMahon, Francis J; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Mosley, Thomas H; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Nalls, Michael A; Nauck, Matthias; Nichols, Thomas E; Niessen, Wiro J; Nöthen, Markus M; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L; Ophoff, Roel A; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W J H; Pike, G Bruce; Potkin, Steven G; Psaty, Bruce M; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L; Romanczuk-Seiferth, Nina; Rotter, Jerome I; Ryten, Mina; Sacco, Ralph L; Sachdev, Perminder S; Saykin, Andrew J; Schmidt, Reinhold; Schofield, Peter R; Sigurdsson, Sigurdur; Simmons, Andy; Singleton, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soininen, Hilkka; Srikanth, Velandai; Steen, Vidar M; Stott, David J; Sussmann, Jessika E; Thalamuthu, Anbupalam; Tiemeier, Henning; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Tzourio, Christophe; Uitterlinden, Andre G; Hernández, Maria C Valdés; Van der Brug, Marcel; Van der Lugt, Aad; Van der Wee, Nic J A; Van Duijn, Cornelia M; Van Haren, Neeltje E M; Van T Ent, Dennis; Van Tol, Marie-Jose; Vardarajan, Badri N; Veltman, Dick J; Vernooij, Meike W; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M; Wassink, Thomas H; Weale, Michael E; Weinberger, Daniel R; Weiner, Michael W; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y; Wright, Clinton B; Zielke, H Ronald; Zonderman, Alan B; Deary, Ian J; DeCarli, Charles; Schmidt, Helena; Martin, Nicholas G; De Craen, Anton J M; Wright, Margaret J; Launer, Lenore J; Schumann, Gunter; Fornage, Myriam; Franke, Barbara; Debette, Stéphanie; Medland, Sarah E; Ikram, M Arfan; Thompson, Paul M

    2016-01-01

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously

  17. Genetic control of protein, oil and fatty acids content under partial ...

    African Journals Online (AJOL)

    The purpose of the present study was to map quantitative trait locus (QTLs) associated with percentage of seed protein, oil and fatty acids content under different conditions in a population of recombinant inbred lines (RILs) of sunflower. Three independent field experiments were conducted with well-, partial-irrigated and ...

  18. An assessment of yield gains under climate change due to genetic modification of pearl millet.

    Science.gov (United States)

    Singh, Piara; Boote, K J; Kadiyala, M D M; Nedumaran, S; Gupta, S K; Srinivas, K; Bantilan, M C S

    2017-12-01

    Developing cultivars with traits that can enhance and sustain productivity under climate change will be an important climate smart adaptation option. The modified CSM-CERES-Pearl millet model was used to assess yield gains by modifying plant traits determining crop maturity duration, potential yield and tolerance to drought and heat in pearl millet cultivars grown at six locations in arid (Hisar, Jodhpur, Bikaner) and semi-arid (Jaipur, Aurangabad and Bijapur) tropical India and two locations in semi-arid tropical West Africa (Sadore in Niamey and Cinzana in Mali). In all the study locations the yields decreased when crop maturity duration was decreased by 10% both in current and future climate conditions; however, 10% increase in crop maturity significantly (pclimate situations in India and West Africa. Drought tolerance imparted the lowest yield gain at Aurangabad (6%), the highest at Sadore (30%) and intermediate at the other locations under current climate. Under climate change the contribution of drought tolerance to the yield of cultivars either increased or decreased depending upon changes in rainfall of the locations. Yield benefits of heat tolerance substantially increased under climate change at most locations, having the greatest effects at Bikaner (17%) in India and Sadore (13%) in West Africa. Aurangabad and Bijapur locations had no yield advantage from heat tolerance due to their low temperature regimes. Thus drought and heat tolerance in pearl millet increased yields under climate change in both the arid and semi-arid tropical climates with greater benefit in relatively hotter environments. This study will assists the plant breeders in evaluating new promising plant traits of pearl millet for adapting to climate change at the selected locations and other similar environments. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Tuning to the significant: neural and genetic processes underlying affective enhancement of visual perception and memory.

    Science.gov (United States)

    Markovic, Jelena; Anderson, Adam K; Todd, Rebecca M

    2014-02-01

    Emotionally arousing events reach awareness more easily and evoke greater visual cortex activation than more mundane events. Recent studies have shown that they are also perceived more vividly and that emotionally enhanced perceptual vividness predicts memory vividness. We propose that affect-biased attention (ABA) - selective attention to emotionally salient events - is an endogenous attentional system tuned by an individual's history of reward and punishment. We present the Biased Attention via Norepinephrine (BANE) model, which unifies genetic, neuromodulatory, neural and behavioural evidence to account for ABA. We review evidence supporting BANE's proposal that a key mechanism of ABA is locus coeruleus-norepinephrine (LC-NE) activity, which interacts with activity in hubs of affective salience networks to modulate visual cortex activation and heighten the subjective vividness of emotionally salient stimuli. We further review literature on biased competition and look at initial evidence for its potential as a neural mechanism behind ABA. We also review evidence supporting the role of the LC-NE system as a driving force of ABA. Finally, we review individual differences in ABA and memory including differences in sensitivity to stimulus category and valence. We focus on differences arising from a variant of the ADRA2b gene, which codes for the alpha2b adrenoreceptor as a way of investigating influences of NE availability on ABA in humans. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Climate change underlies global demographic, genetic, and cultural transitions in pre-Columbian southern Peru.

    Science.gov (United States)

    Fehren-Schmitz, Lars; Haak, Wolfgang; Mächtle, Bertil; Masch, Florian; Llamas, Bastien; Cagigao, Elsa Tomasto; Sossna, Volker; Schittek, Karsten; Isla Cuadrado, Johny; Eitel, Bernhard; Reindel, Markus

    2014-07-01

    Several archaeological studies in the Central Andes have pointed at the temporal coincidence of climatic fluctuations (both long- and short-term) and episodes of cultural transition and changes of socioeconomic structures throughout the pre-Columbian period. Although most scholars explain the connection between environmental and cultural changes by the impact of climatic alterations on the capacities of the ecosystems inhabited by pre-Columbian cultures, direct evidence for assumed demographic consequences is missing so far. In this study, we address directly the impact of climatic changes on the spatial population dynamics of the Central Andes. We use a large dataset of pre-Columbian mitochondrial DNA sequences from the northern Rio Grande de Nasca drainage (RGND) in southern Peru, dating from ∼840 BC to 1450 AD. Alternative demographic scenarios are tested using Bayesian serial coalescent simulations in an approximate Bayesian computational framework. Our results indicate migrations from the lower coastal valleys of southern Peru into the Andean highlands coincident with increasing climate variability at the end of the Nasca culture at ∼640 AD. We also find support for a back-migration from the highlands to the coast coincident with droughts in the southeastern Andean highlands and improvement of climatic conditions on the coast after the decline of the Wari and Tiwanaku empires (∼1200 AD), leading to a genetic homogenization in the RGND and probably southern Peru as a whole.

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

    Science.gov (United States)

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

    2018-01-25

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

  2. Resonance control of a silicon micro-ring resonator modulator under high-speed operation using the intrinsic defect-mediated photocurrent.

    Science.gov (United States)

    Wang, Zhao; Paez, Dixon; El-Rahman, Ahmed I Abd; Wang, Peng; Dow, Liam; Cartledge, John C; Knights, Andrew P

    2017-10-02

    A method to stabilize the resonance wavelength of a depletion-type silicon micro-ring resonator modulator during high-speed operation is described. The method utilizes the intrinsic defect-mediated photo-absorption of a silicon waveguide and results in a modulator chip fabrication process that is free of heterogeneous integration (for example using germanium), thus significantly reducing the complexity and cost of manufacture. Residual defects, present after p-n junction formation, are found to produce an adequate photocurrent for use as a feedback signal, while an integrated heater is used to compensate for thermal drift via closed-loop control. The photocurrent is measured by a source-meter, which simultaneously provides a DC bias to the integrated heater during high-speed operation. A drop-port or an integrated extrinsic detector is not needed. This feedback control method is experimentally demonstrated via a computer-aided proportional-integral-differential loop. The resonance locking is validated for 12.5 Gb/s intensity modulation in a back-to-back bit-error-rate measurement. The stabilization method described is not limited to a specific modulator design and is compatible with speeds greatly in excess of 12.5 Gb/s, in contrast to the bandwidth limitation of other stabilization methods that rely on intrinsic photo-carrier generation through non-linear processes such as two-photon-absorption. Further, the use of intrinsic defects present after standard fabrication insures that no excess loss is associated with this stabilization method.

  3. Genetic parameters of rumination time and feed efficiency traits in primiparous Holstein cows under research and commercial conditions.

    Science.gov (United States)

    Byskov, M V; Fogh, A; Løvendahl, P

    2017-12-01

    Feed efficiency has the potential to be improved both through feeding, management, and breeding. Including feed efficiency in a selection index is limited by the fact that dry matter intake (DMI) recording is only feasible under research facilities, resulting in small data sets and, consequently, uncertain genetic parameter estimates. As a result, the need to record DMI indicator traits on a larger scale exists. Rumination time (RT), which is already recorded in commercial dairy herds by a sensor-based system, has been suggested as a potential DMI indicator. However, RT can only be a DMI indicator if it is heritable, correlates with DMI, and if the genetic parameters of RT in commercial herd settings are similar to those in research facilities. Therefore, the objective of our study was to estimate genetic parameters for RT and the related traits of DMI in primiparous Holstein cows, and to compare genetic parameters of rumination data between a research herd and 72 commercial herds. The estimated heritability values were all moderate for DMI (0.32-0.49), residual feed intake (0.23-0.36), energy-corrected milk (ECM) yield (0.49-0.70), and RT (0.14-0.44) found in the research herd. The estimated heritability values for ECM were lower for the commercial herds (0.08-0.35) than that for the research herd. The estimated heritability values for RT were similar for the 2 herd types (0.28-0.32). For the research herd, we found negative individual level correlations between RT and DMI (-0.24 to -0.09) and between RT and RFI (-0.34 to -0.03), and we found both positive and negative correlations between RT and ECM (-0.08 to 0.09). For the commercial herds, genetic correlations between RT and ECM were both positive and negative (-0.27 to 0.10). In conclusion, RT was not found to be a suitable indicator trait for feed intake and only a weak indicator of feed efficiency. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  4. Novel genetic loci underlying human intracranial volume identified through genome-wide association

    OpenAIRE

    Adams, Hieab HH; Hibar, Derrek P; Chouraki, Vincent; Stein, Jason L; Nyquist, Paul A; Renter��a, Miguel E; Trompet, Stella; Arias-Vasquez, Alejandro; Seshadri, Sudha; Desrivi��res, Sylvane; Beecham, Ashley H; Jahanshad, Neda; Wittfeld, Katharina; Van der Lee, Sven J; Abramovic, Lucija

    2016-01-01

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjus...

  5. Rapid Genetic Adaptation during the First Four Months of Survival under Resource Exhaustion.

    Science.gov (United States)

    Avrani, Sarit; Bolotin, Evgeni; Katz, Sophia; Hershberg, Ruth

    2017-07-01

    Many bacteria, including the model bacterium Escherichia coli can survive for years within spent media, following resource exhaustion. We carried out evolutionary experiments, followed by whole genome sequencing of hundreds of evolved clones to study the dynamics by which E. coli adapts during the first 4 months of survival under resource exhaustion. Our results reveal that bacteria evolving under resource exhaustion are subject to intense selection, manifesting in rapid mutation accumulation, enrichment in functional mutation categories and extremely convergent adaptation. In the most striking example of convergent adaptation, we found that across five independent populations adaptation to conditions of resource exhaustion occurs through mutations to the three same specific positions of the RNA polymerase core enzyme. Mutations to these three sites are strongly antagonistically pleiotropic, in that they sharply reduce exponential growth rates in fresh media. Such antagonistically pleiotropic mutations, combined with the accumulation of additional mutations, severely reduce the ability of bacteria surviving under resource exhaustion to grow exponentially in fresh media. We further demonstrate that the three positions at which these resource exhaustion mutations occur are conserved for the ancestral E. coli allele, across bacterial phyla, with the exception of nonculturable bacteria that carry the resource exhaustion allele at one of these positions, at very high frequencies. Finally, our results demonstrate that adaptation to resource exhaustion is not limited by mutational input and that bacteria are able to rapidly adapt under resource exhaustion in a temporally precise manner through allele frequency fluctuations. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  6. Role of genetics in adapting forests under climate change: lessons learned from common garden experiments in central Europe

    Science.gov (United States)

    Chakraborty, Debojyoti; Schueler, Silvio

    2017-04-01

    Adaptive management aiming at reducing vulnerability and enhancing the resilience of forested ecosystems is a key to preserving the potential of forests to provide multiple ecosystem services under climate change. Planting alternative or non native tree species adapted to future conditions and also utilizing the genetic variation within tree species has also been suggested as an important adaptive management strategy under climate change. Therefore, knowledge on suitable provenances/populations is a key issue. Provenance trial experiments, where several populations of a species are planted in a particular climate or throughout an appropriate climatic gradient offers a great opportunity to understand adaptive genetic variation within a tree species. These trials were primarily established, for identifying populations with desired growth and fitness characteristics. Due to the increasing interest in climate change, such trials were revisited to understand the relation between growth performance and climate and to recommend suitable populations for future conditions. Here we present the lessons learned from provenance trials of Norway spruce and Douglas -fir in central Europe. With data from provenance trials planted across a wide range of environmental conditions in central Europe we developed multivariate models, Universal Response Functions (URFs). The URFs predict growth performance as a function of climate of planting locations (i.e. environmental factors) and provenance/ population origin (i.e. genetic factors). The flexibility of the URFs as a decision making tool is remarkable. The model can be used as to identify suitable planting material for a give site, and vice versa and also as a species distribution model (SDM) with integrated genetic variation. Under current and climate change scenarios, the URFs were applied to predict populations with higher growth performance in central Europe and also as species distribution models for Douglas-fir (Pseudotsuga

  7. Optimization of wear behavior of electroless Ni-P-W coating under dry and lubricated conditions using genetic algorithm (GA

    Directory of Open Access Journals (Sweden)

    Arkadeb Mukhopadhyay

    2016-12-01

    Full Text Available The present study aims to investigate the tribological behavior of Ni-P-W coating under dry and lubricated condition. The coating is deposited onto mild steel (AISI 1040 specimens by the electroless method using a sodium hypophosphite based alkaline bath. Coating characterization is done to investigate the effect of microstructure on its performance. The change in microhardness is observed to be quite significant after annealing the deposits at 400°C for 1h. A pin–on–disc type tribo-tester is used to investigate the tribological behavior of the coating under dry and lubricated conditions. The experimental design formulation is based on Taguchi’s orthogonal array. The design parameters considered are the applied normal load, sliding speed and sliding duration while the response parameter is wear depth. Multiple regression analysis is employed to obtain a quadratic model of the response variables with the main design parameters under considerations. A high value of coefficient of determination of 95.3% and 87.5% of wear depth is obtained under dry and lubricated conditions, respectively which indicate good correlation between experimental results and the multiple regression models. Analysis of variance at a confidence level of 95% shows that the models are statistically significant. Finally, the quadratic equations are used as objective functions to obtain the optimal combination of tribo testing parameters for minimum wear depth using genetic algorithm (GA.

  8. Cellular, Molecular, and Genetic Substrates Underlying the Impact of Nicotine on Learning

    Science.gov (United States)

    Gould, Thomas J.; Leach, Prescott T.

    2013-01-01

    deficits in learning, and 4) the role of genetics and developmental stage (i.e., adolescence) in these effects. PMID:23973448

  9. On the underlying assumptions of threshold Boolean networks as a model for genetic regulatory network behavior.

    Science.gov (United States)

    Tran, Van; McCall, Matthew N; McMurray, Helene R; Almudevar, Anthony

    2013-01-01

    Boolean networks (BoN) are relatively simple and interpretable models of gene regulatory networks. Specifying these models with fewer parameters while retaining their ability to describe complex regulatory relationships is an ongoing methodological challenge. Additionally, extending these models to incorporate variable gene decay rates, asynchronous gene response, and synergistic regulation while maintaining their Markovian nature increases the applicability of these models to genetic regulatory networks (GRN). We explore a previously-proposed class of BoNs characterized by linear threshold functions, which we refer to as threshold Boolean networks (TBN). Compared to traditional BoNs with unconstrained transition functions, these models require far fewer parameters and offer a more direct interpretation. However, the functional form of a TBN does result in a reduction in the regulatory relationships which can be modeled. We show that TBNs can be readily extended to permit self-degradation, with explicitly modeled degradation rates. We note that the introduction of variable degradation compromises the Markovian property fundamental to BoN models but show that a simple state augmentation procedure restores their Markovian nature. Next, we study the effect of assumptions regarding self-degradation on the set of possible steady states. Our findings are captured in two theorems relating self-degradation and regulatory feedback to the steady state behavior of a TBN. Finally, we explore assumptions of synchronous gene response and asynergistic regulation and show that TBNs can be easily extended to relax these assumptions. Applying our methods to the budding yeast cell-cycle network revealed that although the network is complex, its steady state is simplified by the presence of self-degradation and lack of purely positive regulatory cycles.

  10. Population size drives industrial Saccharomyces cerevisiae alcoholic fermentation and is under genetic control.

    Science.gov (United States)

    Albertin, Warren; Marullo, Philippe; Aigle, Michel; Dillmann, Christine; de Vienne, Dominique; Bely, Marina; Sicard, Delphine

    2011-04-01

    Alcoholic fermentation (AF) conducted by Saccharomyces cerevisiae has been exploited for millennia in three important human food processes: beer and wine production and bread leavening. Most of the efforts to understand and improve AF have been made separately for each process, with strains that are supposedly well adapted. In this work, we propose a first comparison of yeast AFs in three synthetic media mimicking the dough/wort/grape must found in baking, brewing, and wine making. The fermentative behaviors of nine food-processing strains were evaluated in these media, at the cellular, populational, and biotechnological levels. A large variation in the measured traits was observed, with medium effects usually being greater than the strain effects. The results suggest that human selection targeted the ability to complete fermentation for wine strains and trehalose content for beer strains. Apart from these features, the food origin of the strains did not significantly affect AF, suggesting that an improvement program for a specific food processing industry could exploit the variability of strains used in other industries. Glucose utilization was analyzed, revealing plastic but also genetic variation in fermentation products and indicating that artificial selection could be used to modify the production of glycerol, acetate, etc. The major result was that the overall maximum CO(2) production rate (V(max)) was not related to the maximum CO(2) production rate per cell. Instead, a highly significant correlation between V(max) and the maximum population size was observed in all three media, indicating that human selection targeted the efficiency of cellular reproduction rather than metabolic efficiency. This result opens the way to new strategies for yeast improvement.

  11. Population Size Drives Industrial Saccharomyces cerevisiae Alcoholic Fermentation and Is under Genetic Control▿†‡

    Science.gov (United States)

    Albertin, Warren; Marullo, Philippe; Aigle, Michel; Dillmann, Christine; de Vienne, Dominique; Bely, Marina; Sicard, Delphine

    2011-01-01

    Alcoholic fermentation (AF) conducted by Saccharomyces cerevisiae has been exploited for millennia in three important human food processes: beer and wine production and bread leavening. Most of the efforts to understand and improve AF have been made separately for each process, with strains that are supposedly well adapted. In this work, we propose a first comparison of yeast AFs in three synthetic media mimicking the dough/wort/grape must found in baking, brewing, and wine making. The fermentative behaviors of nine food-processing strains were evaluated in these media, at the cellular, populational, and biotechnological levels. A large variation in the measured traits was observed, with medium effects usually being greater than the strain effects. The results suggest that human selection targeted the ability to complete fermentation for wine strains and trehalose content for beer strains. Apart from these features, the food origin of the strains did not significantly affect AF, suggesting that an improvement program for a specific food processing industry could exploit the variability of strains used in other industries. Glucose utilization was analyzed, revealing plastic but also genetic variation in fermentation products and indicating that artificial selection could be used to modify the production of glycerol, acetate, etc. The major result was that the overall maximum CO2 production rate (Vmax) was not related to the maximum CO2 production rate per cell. Instead, a highly significant correlation between Vmax and the maximum population size was observed in all three media, indicating that human selection targeted the efficiency of cellular reproduction rather than metabolic efficiency. This result opens the way to new strategies for yeast improvement. PMID:21357433

  12. Microbial and genetic ecology of tropical Vertisols under intensive chemical farming.

    Science.gov (United States)

    Malhotra, Jaya; Aparna, K; Dua, Ankita; Sangwan, Naseer; Trimurtulu, N; Rao, D L N; Lal, Rup

    2015-01-01

    There are continued concerns on unscientific usage of chemical fertilizers and pesticides, particularly in many developing countries leading to adverse consequences for soil biological quality and agricultural sustainability. In farmers' fields in tropical Vertisols of peninsular India, "high" fertilizer and pesticide usage at about 2.3 times the recommended rates in black gram (Vigna mungo) did not have a deleterious effect on the abundance of culturable microorganisms, associative nitrogen fixers, nitrifiers, and 16S rRNA gene diversity compared to normal rates. However, "very high" application at about five times the fertilizers and 1.5 times pesticides in chilies (Capsicum annuum) adversely affected the populations of fungi, actinomycetes, and ammonifiers, along with a drastic change in the eubacterial community profile and diversity over normal rates. Actinobacteria were dominant in black gram normal (BG1) (47%), black gram high (BG2) (36%), and chili normal (CH1) (30%) and were least in chili very high (CH2) (14%). Geodermatophilus formed 20% of Actinobacteria in BG1 but disappeared in BG2, CH1, and CH2. Asticcacaulis dominated at "very high" input site (CH2). Diversity of nitrogen fixers was completely altered; Dechloromonas and Anaeromyxobacter were absent in BG1 but proliferated well in BG2. There was reduction in rhizobial nifH sequences in BG2 by 46%. Phylogenetic differences characterized by UniFrac and principal coordinate analysis showed that BG2 and CH2 clustered together depicting a common pattern of genetic shift, while BG1 and CH1 fell at different axis. Overall, there were adverse consequences of "very high" fertilizer and pesticide usage on soil microbial diversity and function in tropical Vertisols.

  13. Neural Tube Defects

    Science.gov (United States)

    Neural tube defects are birth defects of the brain, spine, or spinal cord. They happen in the ... that she is pregnant. The two most common neural tube defects are spina bifida and anencephaly. In ...

  14. Association mapping of loci controlling genetic and environmental interaction of soybean flowering time under various photo-thermal conditions.

    Science.gov (United States)

    Mao, Tingting; Li, Jinyu; Wen, Zixiang; Wu, Tingting; Wu, Cunxiang; Sun, Shi; Jiang, Bingjun; Hou, Wensheng; Li, Wenbin; Song, Qijian; Wang, Dechun; Han, Tianfu

    2017-05-26

    Soybean (Glycine max (L.) Merr.) is a short day plant. Its flowering and maturity time are controlled by genetic and environmental factors, as well the interaction between the two factors. Previous studies have shown that both genetic and environmental factors, mainly photoperiod and temperature, control flowering time of soybean. Additionally, these studies have reported gene × gene and gene × environment interactions on flowering time. However, the effects of quantitative trait loci (QTL) in response to photoperiod and temperature have not been well evaluated. The objectives of the current study were to identify the effects of loci associated with flowering time under different photo-thermal conditions and to understand the effects of interaction between loci and environment on soybean flowering. Different photoperiod and temperature combinations were obtained by adjusting sowing dates (spring sowing and summer sowing) or day-length (12 h, 16 h). Association mapping was performed on 91 soybean cultivars from different maturity groups (MG000-VIII) using 172 SSR markers and 5107 SNPs from the Illumina SoySNP6K iSelectBeadChip. The effects of the interaction between QTL and environments on flowering time were also analysed using the QTXNetwork. Large-effect loci were detected on Gm 11, Gm 16 and Gm 20 as in previous reports. Most loci associated with flowering time are sensitive to photo-thermal conditions. Number of loci associated with flowering time was more under the long day (LD) than under the short day (SD) condition. The variation of flowering time among the soybean cultivars mostly resulted from the epistasis × environment and additive × environment interactions. Among the three candidate loci, i.e. Gm04_4497001 (near GmCOL3a), Gm16_30766209 (near GmFT2a and GmFT2b) and Gm19_47514601 (E3 or GmPhyA3), the Gm04_4497001 may be the key locus interacting with other loci for controlling soybean flowering time. The effects of loci associated

  15. Genetic drift evolution under vaccination pressure among H5N1 Egyptian isolates

    Directory of Open Access Journals (Sweden)

    Afifi Manal A

    2011-06-01

    Egypt. Egyptian H5N1-AIVs are constantly undergoing genetic changes and reveal a complex pattern of drifts. These findings raise the concerns about the value of using influenza vaccines in correlation with the development of antigenic drift in influenza epidemics.

  16. Genetically modified corn on fall armyworm and earwig populations under field conditions

    Directory of Open Access Journals (Sweden)

    Marina Regina Frizzas

    2014-02-01

    Full Text Available The effects of corn MON810 on the Spodoptera frugiperda (J.E. Smith and the earwig Doru luteipes (Scudder were tested under field conditions in Brazil. Results from MON810 corn fields were compared with those fields of conventional corn with and without the application of insecticides in four harvests in the region of Barretos, SP. It was assessed the damage to S. frugiperda via direct counts of the number of fall armyworms and adults and nymphs of the predator D. luteipes on corn plants. The rate of S. frugiperda damage and the average numbers of larvae (large and small were lower in the MON810 corn field relative to the control plot. There were no differences (P>0.05 between treatments regarding the predator abundance in corn plants. The second crop season ("safrinha" showed the greatest extent of S. frugiperda damage and the lowest average abundance of earwigs. MON810 was effective in controlling S. frugiperda and abundance of predator D. luteipes was similar in the three treatments under field conditions.

  17. Encephalocele and associated skull defects | Komolafe | West ...

    African Journals Online (AJOL)

    Encephalocele is a common congenital problem in the practice of Neurosurgery worldwide, with varying sizes of the underlying skull defects. This study was carried out to determine the size of the problem; to assess whether the skull defects are being under-managed or not; and also to determine those patients that will ...

  18. Virulence Differences among Melissococcus plutonius Strains with Different Genetic Backgrounds in Apis mellifera Larvae under an Improved Experimental Condition.

    Science.gov (United States)

    Nakamura, Keiko; Yamazaki, Yuko; Shiraishi, Akiyo; Kobayashi, Sota; Harada, Mariko; Yoshiyama, Mikio; Osaki, Makoto; Okura, Masatoshi; Takamatsu, Daisuke

    2016-09-14

    European foulbrood (EFB) caused by Melissococcus plutonius is an important bacterial disease of honeybee larvae. M. plutonius strains can be grouped into three genetically distinct groups (CC3, CC12 and CC13). Because EFB could not be reproduced in artificially reared honeybee larvae by fastidious strains of CC3 and CC13 previously, we investigated a method to improve experimental conditions using a CC3 strain and found that infection with a potassium-rich diet enhanced proliferation of the fastidious strain in larvae at the early stage of infection, leading to the appearance of clear clinical symptoms. Further comparison of M. plutonius virulence under the conditions revealed that the representative strain of CC12 was extremely virulent and killed all tested bees before pupation, whereas the CC3 strain was less virulent than the CC12 strain, and a part of the infected larvae pupated. In contrast, the tested CC13 strain was avirulent, and as with the non-infected control group, most of the infected brood became adult bees, suggesting differences in the insect-level virulence among M. plutonius strains with different genetic backgrounds. These strains and the improved experimental infection method to evaluate their virulence will be useful tools for further elucidation of the pathogenic mechanisms of EFB.

  19. Interspecific Hybridization in Pilot Whales and Asymmetric Genetic Introgression in Northern Globicephala melas under the Scenario of Global Warming.

    Science.gov (United States)

    Miralles, Laura; Oremus, Marc; Silva, Mónica A; Planes, Serge; Garcia-Vazquez, Eva

    2016-01-01

    Pilot whales are two cetacean species (Globicephala melas and G. macrorhynchus) whose distributions are correlated with water temperature and partially overlap in some areas like the North Atlantic Ocean. In the context of global warming, distribution range shifts are expected to occur in species affected by temperature. Consequently, a northward displacement of the tropical pilot whale G. macrorynchus is expected, eventually leading to increased secondary contact areas and opportunities for interspecific hybridization. Here, we describe genetic evidences of recurrent hybridization between pilot whales in northeast Atlantic Ocean. Based on mitochondrial DNA sequences and microsatellite loci, asymmetric introgression of G. macrorhynchus genes into G. melas was observed. For the latter species, a significant correlation was found between historical population growth rate estimates and paleotemperature oscillations. Introgressive hybridization, current temperature increases and lower genetic variation in G. melas suggest that this species could be at risk in its northern range. Under increasing environmental and human-mediated stressors in the North Atlantic Ocean, it seems recommendable to develop a conservation program for G. melas.

  20. Study of clustering point defects under irradiation in dilute iron alloys; Etude de la formation sous irradiation des amas de defauts ponctuels dans les alliages ferritiques faiblement allies

    Energy Technology Data Exchange (ETDEWEB)

    Duong-Hardouin Duparc, T.H.A

    1998-12-31

    In low copper steels for nuclear reactor pressure vessel, point defect clustering plays an important role in hardening. These clusters are very small and invisible by transmission electron microscopy. In order to study the hardening component which results from the clustering of freely migrating point defects, we irradiated in a high voltage electron microscope Fe, the FeCu{sub 0.13%}, FeP{sub 0.015%} and FeN{sub 33ppm} alloys and the complex FeMn{sub 1.5%}Ni{sub 0.8%}Cu{sub 0.13%}P{sub 0.01%} alloy the composition of which is close to the matrix of pressure vessel steel. We studied the nucleation of dislocation loops and their growth velocity. The observations and the analyses have shown that in the complex model alloy, the interstitial dislocation loops are smaller and their density is more important than for the others alloys. The diffusion coefficients of interstitials and vacancies are obtained with the help of a simplified model. The densities of dislocation loops and their growth velocities obtained experimentally are reproduced by means of a cluster dynamics model we have developed. This is achieved self-consistently by using as a first trial the approximated coefficients obtained with the simplified model. The results of calculations have shown that the binding energy of di-interstitials must be very important in the binary iron alloys and only 0.95 eV in iron. Copper, nitrogen and phosphorus stabilize di-interstitials in iron. Finally the distribution of interstitial loops at 290 deg C and at 2.10{sup -9} dpa/s is calculated with the diffusion coefficient of point defects adjusted in FeCu. A distribution of small loops appears which gives an increase of hardening estimated to 10 Hv instead of 33 Hv experimentally observed. This low value can be improved by assuming in agreement with molecular dynamics simulations that a little fraction of di-interstitials is created at 2.5 MeV. (author) 111 refs.

  1. Electrical fingerprint of pipeline defects

    International Nuclear Information System (INIS)

    Mica, Isabella; Polignano, Maria Luisa; Marco, Cinzia De

    2004-01-01

    Pipeline defects are dislocations that connect the source region of the transistor with the drain region. They were widely reported to occur in CMOS, BiCMOS devices and recently in SOI technologies. They can reduce device yield either by affecting the devices functionality or by increasing the current consumption under stand-by conditions. In this work the electrical fingerprint of these dislocations is studied, its purpose is to enable us to identify these defects as the ones responsible for device failure. It is shown that the pipeline defects are responsible for a leakage current from source to drain in the transistors. This leakage has a resistive characteristic and it is lightly modulated by the body bias. It is not sensitive to temperature; vice versa the off-current of a good transistor exhibits the well-known exponential dependence on 1/T. The emission spectrum of these defects was studied and compared with the spectrum of a good transistor. The paper aims to show that the spectrum of a defective transistor is quite peculiar; it shows well defined peaks, whereas the spectrum of a good transistor under saturation conditions is characterized by a broad spectral light emission distribution. Finally the deep-level transient spectroscopy (DLTS) is tried on defective diodes

  2. Hormonal and genetic influences underlying arousal as it drives sex and aggression in animal and human brains.

    Science.gov (United States)

    Mong, Jessica A; Pfaff, Donald W

    2003-01-01

    Estrogen treatment induces transcription and increases excitability and reproductive behavior. Estrogens provide the structural basis for increased synaptic activity and greater behavior-facilitating output. Administration of progesterone amplifies the effect of estrogens on mating behavior. The role of GnRH is to synchronize reproductive behavior with the ovulatory surge of LH. A causal connection can be charted from one individual gene to human social behavior, but only via six causal links. Glia, meninges and neurons may participate, under the influence of sex hormones, in the direction of sex behavior. Neural and genetic mechanisms for motivation may lead to biological understanding of functions that apply to the most primitive aspects of human mental functioning. With respect to aggression, besides testosterone and its metabolites, serotonergic projections to the forebrain play an important role.

  3. Genetic Counseling: MedlinePlus Health Topic

    Science.gov (United States)

    ... it if you Have a personal or family history of a genetic condition or birth defect Are pregnant or planning to be pregnant ... GO MEDICAL ENCYCLOPEDIA Genetic counseling Related Health Topics Birth Defects Family History Genetic Disorders Genetic Testing Prenatal Testing National Institutes ...

  4. Accumulation patterns of proper point defects in thermo-regulating coatings based on ZnO for space vehicles under electron irradiation

    International Nuclear Information System (INIS)

    Mikhajlov, M.M.; Sharafutdinova, V.V.

    1998-01-01

    The expansion of the band of the induced absorption of zinc oxide powders and thermo-regulating coatings based on ZnO for space vehicles is carried out after the 30 keV electron irradiation. Singularities of the growth of the intensity of individual components as a function of the accelerated electron flow are studied. It is found that power and exponential dependences with one or two components are characteristic for different color centers and different thermo-regulating coatings. The kinetics of the accumulation of free electrons is characterized by the maximum value of the electron flows at which the generation of color centers on pre-radiation defects is realized by the radiolysis of the pigment lattice

  5. Defect formation and desorption of metal atoms from alkali halide crystals under low energy electron bombardment studied by optical absorption and mass spectroscopy

    International Nuclear Information System (INIS)

    Seifert, N.R.

    1993-04-01

    This work presents an extensive investigation of electronically induced desorption of ground-state alkali atoms from alkali halides and for the first time correlates directly the desorption with the stability and spatial distribution of the defects formed during bombardment. The electron impact results in the formation of stable F-centers and F-center clusters in the bulk of the crystals. In striking contrast a significant metallization of the surface is observed. Even at temperatures as low as 90 deg C the metallization is achieved within the time resolution of our detection system, which can only be explained by the rapid diffusion of hot holes. Superimposed to the fast and short diffusion of hot holes is the slow F-center diffusion. Measuring the distribution of defects with low energy ion sputtering techniques indicates that at least in the case of LiF the observed diffusion constant of F-centers agrees with values derived by using methods different from that applied here. At low temperatures the formation of F-center clusters and metal on the surface dominates. Colloid formation clearly requires higher temperatures (typically around 200 deg C). This is a strong evidence that efficient F-center diffusion is necessary for the formation of metallic particles (colloids) in the bulk of the crystals. Desorption of alkali atoms from alkali halides at temperatures around room temperature is due to weakly bound alkali atoms. For elevated temperatures the stability of the metallic clusters in the bulk of the crystals (i.e. colloids) are the rate limiting process. (author)

  6. The ultrastructure and genetic traits of plants under the condition of hypobaric and hypoxia

    Science.gov (United States)

    Guo, Shuangsheng; Tang, Yongkang; Wang, Shulei; Cheng, Quanyong; Zhao, Qi

    This study analyzed the cellular, sub-cellular and molecular levels, particle composition and volume changes of Indian lettuce under the conditions of hypobaric and hypoxia. Firstly, in the hypobaric and hypoxia conditions, two kinds of sample showed a decrease in the num-ber of cells, the increase in volume and the deflation in nuclear size. Secondly, Significant changes of the chloroplast ultrastructure have taken place in the two conditions. Thirdly, in the hypoxia condition, the chloroplast grana lamellae fractured and aggregated, which caused the chloroplasts to enlarge, their lamellae to reduce,become vaguer and finally to disintegrate. Fourthly, the volume change and aggregation of the chloroplasts induced mitochondria to ap-proach the chloroplasts. Fifthly, cytoskeleton immunofluorescence positioning results showed that the microtubules had decreased in number, shortened in length and gathered in the vicinity of the nucleus. In addition, total leaf DNA-sequence alignment found no rbcl gene mutation in the extreme conditions. Keywords: Chloroplast Ultrastructure Cytoskeleton rbcl gene Indian lettuce

  7. A Behavioral Genetic Model of the Mechanisms Underlying the Link Between Obesity and Symptoms of ADHD.

    Science.gov (United States)

    Patte, Karen A; Davis, Caroline A; Levitan, Robert D; Kaplan, Allan S; Carter-Major, Jacqueline; Kennedy, James L

    2016-01-21

    The ADHD-obesity link has been suggested to result from a shared underlying basis of suboptimal dopamine (DA); however, this theory conflicts evidence that an amplified DA signal increases the risk for overeating and weight gain. A model was tested in which ADHD symptoms, predicted by hypodopaminergic functioning in the prefrontal cortex, in combination with an enhanced appetitive drive, predict hedonic eating and, in turn, higher body mass index (BMI). DRD2 and DRD4 markers were genotyped. The model was tested using structural equation modeling in a nonclinical sample (N = 421 adults). The model was a good fit to the data. Controlling for education, all parameter estimates were significant, except for the DRD4-ADHD symptom pathway. The significant indirect effect indicates that overeating mediated the ADHD symptoms-BMI association. Results support the hypothesis that overeating and elevated DA in the ventral striatum-representative of a greater reward response-contribute to the ADHD symptom-obesity relationship. © The Author(s) 2016.

  8. Application of multi-objective optimization based on genetic algorithm for sustainable strategic supplier selection under fuzzy environment

    Directory of Open Access Journals (Sweden)

    Muhammad Hashim

    2017-05-01

    Full Text Available Purpose:  The incorporation of environmental objective into the conventional supplier selection practices is crucial for corporations seeking to promote green supply chain management (GSCM. Challenges and risks associated with green supplier selection have been broadly recognized by procurement and supplier management professionals. This paper aims to solve a Tetra “S” (SSSS problem based on a fuzzy multi-objective optimization with genetic algorithm in a holistic supply chain environment. In this empirical study, a mathematical model with fuzzy coefficients is considered for sustainable strategic supplier selection (SSSS problem and a corresponding model is developed to tackle this problem. Design/methodology/approach: Sustainable strategic supplier selection (SSSS decisions are typically multi-objectives in nature and it is an important part of green production and supply chain management for many firms. The proposed uncertain model is transferred into deterministic model by applying the expected value mesurement (EVM and genetic algorithm with weighted sum approach for solving the multi-objective problem. This research focus on a multi-objective optimization model for minimizing lean cost, maximizing sustainable service and greener product quality level. Finally, a mathematical case of textile sector is presented to exemplify the effectiveness of the proposed model with a sensitivity analysis. Findings: This study makes a certain contribution by introducing the Tetra ‘S’ concept in both the theoretical and practical research related to multi-objective optimization as well as in the study of sustainable strategic supplier selection (SSSS under uncertain environment. Our results suggest that decision makers tend to select strategic supplier first then enhance the sustainability. Research limitations/implications: Although the fuzzy expected value model (EVM with fuzzy coefficients constructed in present research should be helpful for

  9. Application of multi-objective optimization based on genetic algorithm for sustainable strategic supplier selection under fuzzy environment

    Energy Technology Data Exchange (ETDEWEB)

    Hashim, M.; Nazam, M.; Yao, L.; Baig, S.A.; Abrar, M.; Zia-ur-Rehman, M.

    2017-07-01

    The incorporation of environmental objective into the conventional supplier selection practices is crucial for corporations seeking to promote green supply chain management (GSCM). Challenges and risks associated with green supplier selection have been broadly recognized by procurement and supplier management professionals. This paper aims to solve a Tetra “S” (SSSS) problem based on a fuzzy multi-objective optimization with genetic algorithm in a holistic supply chain environment. In this empirical study, a mathematical model with fuzzy coefficients is considered for sustainable strategic supplier selection (SSSS) problem and a corresponding model is developed to tackle this problem. Design/methodology/approach: Sustainable strategic supplier selection (SSSS) decisions are typically multi-objectives in nature and it is an important part of green production and supply chain management for many firms. The proposed uncertain model is transferred into deterministic model by applying the expected value mesurement (EVM) and genetic algorithm with weighted sum approach for solving the multi-objective problem. This research focus on a multi-objective optimization model for minimizing lean cost, maximizing sustainable service and greener product quality level. Finally, a mathematical case of textile sector is presented to exemplify the effectiveness of the proposed model with a sensitivity analysis. Findings: This study makes a certain contribution by introducing the Tetra ‘S’ concept in both the theoretical and practical research related to multi-objective optimization as well as in the study of sustainable strategic supplier selection (SSSS) under uncertain environment. Our results suggest that decision makers tend to select strategic supplier first then enhance the sustainability. Research limitations/implications: Although the fuzzy expected value model (EVM) with fuzzy coefficients constructed in present research should be helpful for solving real world

  10. Application of multi-objective optimization based on genetic algorithm for sustainable strategic supplier selection under fuzzy environment

    International Nuclear Information System (INIS)

    Hashim, M.; Nazam, M.; Yao, L.; Baig, S.A.; Abrar, M.; Zia-ur-Rehman, M.

    2017-01-01

    The incorporation of environmental objective into the conventional supplier selection practices is crucial for corporations seeking to promote green supply chain management (GSCM). Challenges and risks associated with green supplier selection have been broadly recognized by procurement and supplier management professionals. This paper aims to solve a Tetra “S” (SSSS) problem based on a fuzzy multi-objective optimization with genetic algorithm in a holistic supply chain environment. In this empirical study, a mathematical model with fuzzy coefficients is considered for sustainable strategic supplier selection (SSSS) problem and a corresponding model is developed to tackle this problem. Design/methodology/approach: Sustainable strategic supplier selection (SSSS) decisions are typically multi-objectives in nature and it is an important part of green production and supply chain management for many firms. The proposed uncertain model is transferred into deterministic model by applying the expected value mesurement (EVM) and genetic algorithm with weighted sum approach for solving the multi-objective problem. This research focus on a multi-objective optimization model for minimizing lean cost, maximizing sustainable service and greener product quality level. Finally, a mathematical case of textile sector is presented to exemplify the effectiveness of the proposed model with a sensitivity analysis. Findings: This study makes a certain contribution by introducing the Tetra ‘S’ concept in both the theoretical and practical research related to multi-objective optimization as well as in the study of sustainable strategic supplier selection (SSSS) under uncertain environment. Our results suggest that decision makers tend to select strategic supplier first then enhance the sustainability. Research limitations/implications: Although the fuzzy expected value model (EVM) with fuzzy coefficients constructed in present research should be helpful for solving real world

  11. A genetic screen for mutants defective in IAA1-LUC degradation in Arabidopsis thaliana reveals an important requirement for TOPOISOMERASE6B in auxin physiology.

    Science.gov (United States)

    Gilkerson, Jonathan; Callis, Judy

    2014-01-01

    Many plant growth and developmental processes are modulated by the hormone auxin. Auxin-modulated proteolysis of Aux/IAAs, a family of transcriptional repressors, represents a major mode of auxin action. Auxin facilitates the interaction of Aux/IAAs with TIR1/AFB F-box proteins, promoting their ubiquitination by the SCF(TIR1/AFB) ubiquitin E3 ligase leading to subsequent degradation by the 26S proteasome. To identify new genes regulating Aux/IAA proteolysis in Arabidopsis thaliana, we took a genetic approach, identifying individuals with altered degradation of an IAA1-luciferase fusion protein (IAA1-LUC). A mutant with 2-fold slower IAA1-LUC degradation rate compared with wild-type was isolated. Positional cloning identified the mutant as an allele of TOPOISOMERASE6B, named top6b-7. TOP6B encodes a subunit of a plant and archea-specific enzyme regulating endoreduplication, DNA damage repair and transcription in plants. T-DNA insertion alleles (top6b-8 and top6b-9) were also analyzed. top6b-7 seedlings are less sensitive to exogenous auxin than wild-type siblings in primary root growth assays, and experiments with DR5:GUS. Additionally, top6b-7 seedlings have a 40% reduction in the amount of endogenous IAA. These data suggest that increased IAA1-LUC half-life in top6b-7 probably results from a combination of both lower endogenous IAA levels and reduced sensitivity to auxin.

  12. Mechanisms and genetic factors underlying co-use of nicotine and alcohol or other drugs of abuse.

    Science.gov (United States)

    Cross, Sarah J; Lotfipour, Shahrdad; Leslie, Frances M

    2017-03-01

    Concurrent use of tobacco and alcohol or psychostimulants represents a major public health concern, with use of one substance influencing consumption of the other. Co-abuse of these drugs leads to substantial negative health outcomes, reduced cessation, and high economic costs, but the underlying mechanisms are poorly understood. Epidemiological data suggest that tobacco use during adolescence plays a particularly significant role. Adolescence is a sensitive period of development marked by major neurobiological maturation of brain regions critical for reward processing, learning and memory, and executive function. Nicotine exposure during this time produces a unique and long-lasting vulnerability to subsequent substance use, likely via actions at cholinergic, dopaminergic, and serotonergic systems. In this review, we discuss recent clinical and preclinical data examining the genetic factors and mechanisms underlying co-use of nicotine and alcohol or cocaine and amphetamines. We evaluate the critical role of nicotinic acetylcholine receptors throughout, and emphasize the dearth of preclinical studies assessing concurrent drug exposure. We stress important age and sex differences in drug responses, and highlight a brief, low-dose nicotine exposure paradigm that may better model early use of tobacco products. The escalating use of e-cigarettes among youth necessitates a closer look at the consequences of early adolescent nicotine exposure on subsequent alcohol and drug abuse.

  13. Lactic Acid Bacteria Protects Caenorhabditis elegans from Toxicity of Graphene Oxide by Maintaining Normal Intestinal Permeability under different Genetic Backgrounds

    Science.gov (United States)

    Zhao, Yunli; Yu, Xiaoming; Jia, Ruhan; Yang, Ruilong; Rui, Qi; Wang, Dayong

    2015-11-01

    Lactic acid bacteria (LAB) is safe and useful for food and feed fermentation. We employed Caenorhabditis elegans to investigate the possible beneficial effect of LAB (Lactobacillus bulgaricus) pretreatment against toxicity of graphene oxide (GO) and the underlying mechanisms. LAB prevented GO toxicity on the functions of both primary and secondary targeted organs in wild-type nematodes. LAB blocked translocation of GO into secondary targeted organs through intestinal barrier by maintaining normal intestinal permeability in wild-type nematodes. Moreover, LAB prevented GO damage on the functions of both primary and secondary targeted organs in exposed nematodes with mutations of susceptible genes (sod-2, sod-3, gas-1, and aak-2) to GO toxicity by sustaining normal intestinal permeability. LAB also sustained the normal defecation behavior in both wild-type nematodes and nematodes with mutations of susceptible genes. Therefore, the beneficial role of LAB against GO toxicity under different genetic backgrounds may be due to the combinational effects on intestinal permeability and defecation behavior. Moreover, the beneficial effects of LAB against GO toxicity was dependent on the function of ACS-22, homologous to mammalian FATP4 to mammalian FATP4. Our study provides highlight on establishment of pharmacological strategy to protect intestinal barrier from toxicity of GO.

  14. Prediction of composite fatigue life under variable amplitude loading using artificial neural network trained by genetic algorithm

    Science.gov (United States)

    Rohman, Muhamad Nur; Hidayat, Mas Irfan P.; Purniawan, Agung

    2018-04-01

    Neural networks (NN) have been widely used in application of fatigue life prediction. In the use of fatigue life prediction for polymeric-base composite, development of NN model is necessary with respect to the limited fatigue data and applicable to be used to predict the fatigue life under varying stress amplitudes in the different stress ratios. In the present paper, Multilayer-Perceptrons (MLP) model of neural network is developed, and Genetic Algorithm was employed to optimize the respective weights of NN for prediction of polymeric-base composite materials under variable amplitude loading. From the simulation result obtained with two different composite systems, named E-glass fabrics/epoxy (layups [(±45)/(0)2]S), and E-glass/polyester (layups [90/0/±45/0]S), NN model were trained with fatigue data from two different stress ratios, which represent limited fatigue data, can be used to predict another four and seven stress ratios respectively, with high accuracy of fatigue life prediction. The accuracy of NN prediction were quantified with the small value of mean square error (MSE). When using 33% from the total fatigue data for training, the NN model able to produce high accuracy for all stress ratios. When using less fatigue data during training (22% from the total fatigue data), the NN model still able to produce high coefficient of determination between the prediction result compared with obtained by experiment.

  15. Is Hypospadias Associated with Prenatal Exposure to Endocrine Disruptors? A French Collaborative Controlled Study of a Cohort of 300 Consecutive Children Without Genetic Defect.

    Science.gov (United States)

    Kalfa, Nicolas; Paris, Françoise; Philibert, Pascal; Orsini, Mattea; Broussous, Sylvie; Fauconnet-Servant, Nadège; Audran, Françoise; Gaspari, Laura; Lehors, Hélène; Haddad, Myriam; Guys, Jean-Michel; Reynaud, Rachel; Alessandrini, Pierre; Merrot, Thierry; Wagner, Kathy; Kurzenne, Jean-Yves; Bastiani, Florence; Bréaud, Jean; Valla, Jean-Stéphane; Lacombe, Gérard Morisson; Dobremez, Eric; Zahhaf, Amel; Daures, Jean-Pierre; Sultan, Charles

    2015-12-01

    Numerous studies have focused on the association between endocrine-disrupting chemicals (EDCs) and hypospadias. Phenotype variability, the absence of representative comparison groups and concomitant genetic testing prevent any definitive conclusions. To identify the role of occupational and environmental exposures to EDCs in nongenetic isolated hypospadias. A total of 408 consecutive children with isolated hypospadias and 302 normal boys were prospectively included (2009-2014) in a multi-institutional study in the south of France, the area of the country with the highest prevalence of hypospadias surgery. In patients without AR, SRD5A2, and MAMLD1 mutations, parental occupational and professional exposures to EDCs were evaluated based on European questionnaire QLK4-1999-01422 and a validated job-exposure matrix for EDCs. Environmental exposure was estimated using the zip code, the type of surrounding hazards, and distance from these hazards. Multivariate analysis was performed. Fetal exposure to EDCs around the window of genital differentiation was more frequent in the case of hypospadias (40.00% vs 17.55%, odds ratio 3.13, 95% confidence interval 2.11-4.65). The substances were paints/solvents/adhesives (16.0%), detergents (11.0%), pesticides (9.0%), cosmetics (5.6%), and industrial chemicals (4.0%). Jobs with exposure were more frequent in mothers of hypospadiac boys (19.73% vs 10.26%, p=0.0019), especially cleaners, hairdressers, beauticians, and laboratory workers. Paternal job exposure was more frequent in the cases of hypospadias (40.13% vs 27.48%, p=0.02). Industrial areas, incinerators, and waste areas were more frequent within a 3-km radius for mothers of hypospadiac boys (13.29% vs. 6.64%, phypospadias through occupational and environmental exposure during fetal life. The association of various types of exposures may increase this risk. Our multi-institutional study showed that parental professional, occupational, and environmental exposures to chemical

  16. Quantitative trait loci in hop (Humulus lupulus L.) reveal complex genetic architecture underlying variation in sex, yield and cone chemistry.

    Science.gov (United States)

    McAdam, Erin L; Freeman, Jules S; Whittock, Simon P; Buck, Emily J; Jakse, Jernej; Cerenak, Andreja; Javornik, Branka; Kilian, Andrzej; Wang, Cai-Hong; Andersen, Dave; Vaillancourt, René E; Carling, Jason; Beatson, Ron; Graham, Lawrence; Graham, Donna; Darby, Peter; Koutoulis, Anthony

    2013-05-30

    genetic control of traits of current economic and breeding significance in hop and demonstrate the complex genetic architecture underlying variation in these traits. The linkage information obtained in this study, based on transferable markers, can be used to facilitate the validation of QTL, crucial to the success of MAS.

  17. Magnetoencephalography signals are influenced by skull defects.

    Science.gov (United States)

    Lau, S; Flemming, L; Haueisen, J

    2014-08-01

    Magnetoencephalography (MEG) signals had previously been hypothesized to have negligible sensitivity to skull defects. The objective is to experimentally investigate the influence of conducting skull defects on MEG and EEG signals. A miniaturized electric dipole was implanted in vivo into rabbit brains. Simultaneous recording using 64-channel EEG and 16-channel MEG was conducted, first above the intact skull and then above a skull defect. Skull defects were filled with agar gels, which had been formulated to have tissue-like homogeneous conductivities. The dipole was moved beneath the skull defects, and measurements were taken at regularly spaced points. The EEG signal amplitude increased 2-10 times, whereas the MEG signal amplitude reduced by as much as 20%. The EEG signal amplitude deviated more when the source was under the edge of the defect, whereas the MEG signal amplitude deviated more when the source was central under the defect. The change in MEG field-map topography (relative difference measure, RDM(∗)=0.15) was geometrically related to the skull defect edge. MEG and EEG signals can be substantially affected by skull defects. MEG source modeling requires realistic volume conductor head models that incorporate skull defects. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  18. Proposta de uma metodologia para avaliação de defeitos de soldadura na manutenção de equipamentos sob pressão Proposed methodology to evaluate welding defects during maintenance of equipments under pressure

    Directory of Open Access Journals (Sweden)

    Paulo Silva

    2011-06-01

    Full Text Available A utilização de técnicas avançadas de controlo não destrutivo como o Time of Flight Detection (ToFD e o Phased Array para inspeção em manutenção de reservatórios de pressão permite a caracterização de numerosos defeitos não detectados durante a construção, como defeitos planares, cuja detecção por radiografia depende da sua orientação. Estas técnicas têm conduzido a um aumento substancial da fiabilidade dos equipamentos, uma vez que a detecção de defeitos num estágio inicial de desenvolvimento permite planear as intervenções, reduzir paragens e tempos não produtivos. Os defeitos de fabrico são identificados nas inspeções de manutenção pelo fato das técnicas usadas serem mais precisas e as áreas inspecionadas maiores do que as requeridas após construção. Alguns defeitos são facilmente classificados como tendo origem no fabrico e construção, mas outros não conseguem distinguir-se dos provocados pelas condições de serviço. Neste sentido, a decisão importante a tomar é a de avaliar se a evolução do defeito é possível de ocorrer, baseada no conhecimento das condições de serviço, do material, da dimensão e localização do defeito. Este artigo pretende fazer uma proposta de metodologia de avaliação de defeitos baseada num conjunto substancial de casos industriais de modo a apoiar o pessoal técnico nas fases de decisão em manutenção, inspeção e reparação de defeitos em juntas soldadas em reservatórios de pressão de processo.The use of advanced non-destructive techniques like ToFD and Phased Array to perform maintenance inspections of pressure vessels enables the characterization of numerous defects not detectable during the construction, as planar defects, whose detection by radiography is highly dependent on its orientation. These techniques lead to a substantial increase in reliability of equipments, since, the early detection of defects under development allows the planning of

  19. Vertebral defect, anal atresia, cardiac defect, tracheoesophageal fistula/esophageal atresia, renal defect, and limb defect association with Mayer-Rokitansky-Küster-Hauser syndrome in co-occurrence: two case reports and a review of the literature.

    Science.gov (United States)

    Bjørsum-Meyer, Thomas; Herlin, Morten; Qvist, Niels; Petersen, Michael B

    2016-12-21

    The vertebral defect, anal atresia, cardiac defect, tracheoesophageal fistula/esophageal atresia, renal defect, and limb defect association and Mayer-Rokitansky-Küster-Hauser syndrome are rare conditions. We aimed to present two cases with the vertebral defect, anal atresia, cardiac defect, tracheoesophageal fistula/esophageal atresia, renal defect, and limb defect association and Mayer-Rokitansky-Küster-Hauser co-occurrence from our local surgical center and through a systematic literature search detect published cases. Furthermore, we aimed to collect existing knowledge in the embryopathogenesis and genetics in order to discuss a possible link between the vertebral defect, anal atresia, cardiac defect, tracheoesophageal fistula/esophageal atresia, renal defect, and limb defect association and Mayer-Rokitansky-Küster-Hauser syndrome. Our first case was a white girl delivered by caesarean section at 37 weeks of gestation; our second case was a white girl born at a gestational age of 40 weeks. A co-occurrence of vertebral defect, anal atresia, cardiac defect, tracheoesophageal fistula/esophageal atresia, renal defect, and limb defect association and Mayer-Rokitansky-Küster-Hauser syndrome was diagnosed in both cases. We performed a systematic literature search in PubMed ((VACTERL) OR (VATER)) AND ((MRKH) OR (Mayer-Rokitansky-Küster-Hauser) OR (mullerian agenesis) OR (mullerian aplasia) OR (MURCS)) without limitations. A similar search was performed in Embase and the Cochrane library. We added two cases from our local center. All cases (n = 9) presented with anal atresia and renal defect. Vertebral defects were present in eight patients. Rectovestibular fistula was confirmed in seven patients. Along with the uterovaginal agenesis, fallopian tube aplasia appeared in five of nine cases and in two cases ovarian involvement also existed. The co-occurrence of the vertebral defect, anal atresia, cardiac defect, tracheoesophageal fistula/esophageal atresia, renal

  20. Temporal stability in the genetic structure of Sarcoptes scabiei under the host-taxon law: empirical evidences from wildlife-derived Sarcoptes mite in Asturias, Spain

    Science.gov (United States)

    2011-01-01

    Background Implicitly, parasite molecular studies assume temporal genetic stability. In this study we tested, for the first time to our knowledge, the extent of changes in genetic diversity and structure of Sarcoptes mite populations from Pyrenean chamois (Rupicapra pyrenaica) in Asturias (Spain), using one multiplex of 9 microsatellite markers and Sarcoptes samples from sympatric Pyrenean chamois, red deer (Cervus elaphus), roe deer (Capreolus capreolus) and red fox (Vulpes vulpes). Results The analysis of an 11-years interval period found little change in the genetic diversity (allelic diversity, and observed and expected heterozygosity). The temporal stability in the genetic diversity was confirmed by population structure analysis, which was not significantly variable over time. Population structure analysis revealed temporal stability in the genetic diversity of Sarcoptes mite under the host-taxon law (herbivore derived- and carnivore derived-Sarcoptes mite) among the sympatric wild animals from Asturias. Conclusions The confirmation of parasite temporal genetic stability is of vital interest to allow generalizations to be made, which have further implications regarding the genetic structure, epidemiology and monitoring protocols of the ubiquitous Sarcoptes mite. This could eventually be applied to other parasite species. PMID:21794141

  1. Temporal stability in the genetic structure of Sarcoptes scabiei under the host-taxon law: empirical evidences from wildlife-derived Sarcoptes mite in Asturias, Spain

    Directory of Open Access Journals (Sweden)

    Rossi Luca

    2011-07-01

    Full Text Available Abstract Background Implicitly, parasite molecular studies assume temporal genetic stability. In this study we tested, for the first time to our knowledge, the extent of changes in genetic diversity and structure of Sarcoptes mite populations from Pyrenean chamois (Rupicapra pyrenaica in Asturias (Spain, using one multiplex of 9 microsatellite markers and Sarcoptes samples from sympatric Pyrenean chamois, red deer (Cervus elaphus, roe deer (Capreolus capreolus and red fox (Vulpes vulpes. Results The analysis of an 11-years interval period found little change in the genetic diversity (allelic diversity, and observed and expected heterozygosity. The temporal stability in the genetic diversity was confirmed by population structure analysis, which was not significantly variable over time. Population structure analysis revealed temporal stability in the genetic diversity of Sarcoptes mite under the host-taxon law (herbivore derived- and carnivore derived-Sarcoptes mite among the sympatric wild animals from Asturias. Conclusions The confirmation of parasite temporal genetic stability is of vital interest to allow generalizations to be made, which have further implications regarding the genetic structure, epidemiology and monitoring protocols of the ubiquitous Sarcoptes mite. This could eventually be applied to other parasite species.

  2. Temporal stability in the genetic structure of Sarcoptes scabiei under the host-taxon law: empirical evidences from wildlife-derived Sarcoptes mite in Asturias, Spain.

    Science.gov (United States)

    Alasaad, Samer; Oleaga, Álvaro; Casais, Rosa; Rossi, Luca; Min, Annarita Molinar; Soriguer, Ramón C; Gortázar, Christian

    2011-07-27

    Implicitly, parasite molecular studies assume temporal genetic stability. In this study we tested, for the first time to our knowledge, the extent of changes in genetic diversity and structure of Sarcoptes mite populations from Pyrenean chamois (Rupicapra pyrenaica) in Asturias (Spain), using one multiplex of 9 microsatellite markers and Sarcoptes samples from sympatric Pyrenean chamois, red deer (Cervus elaphus), roe deer (Capreolus capreolus) and red fox (Vulpes vulpes). The analysis of an 11-years interval period found little change in the genetic diversity (allelic diversity, and observed and expected heterozygosity). The temporal stability in the genetic diversity was confirmed by population structure analysis, which was not significantly variable over time. Population structure analysis revealed temporal stability in the genetic diversity of Sarcoptes mite under the host-taxon law (herbivore derived- and carnivore derived-Sarcoptes mite) among the sympatric wild animals from Asturias. The confirmation of parasite temporal genetic stability is of vital interest to allow generalizations to be made, which have further implications regarding the genetic structure, epidemiology and monitoring protocols of the ubiquitous Sarcoptes mite. This could eventually be applied to other parasite species. © 2011 Alasaad et al; licensee BioMed Central Ltd.

  3. The Genetics Underlying Natural Variation in the Biotic Interactions of Arabidopsis thaliana: The Challenges of Linking Evolutionary Genetics and Community Ecology.

    Science.gov (United States)

    Roux, F; Bergelson, J

    2016-01-01

    In the context of global change, predicting the responses of plant communities in an ever-changing biotic environment calls for a multipronged approach at the interface of evolutionary genetics and community ecology. However, our understanding of the genetic basis of natural variation involved in mediating biotic interactions, and associated adaptive dynamics of focal plants in their natural communities, is still in its infancy. Here, we review the genetic and molecular bases of natural variation in the response to biotic interactions (viruses, bacteria, fungi, oomycetes, herbivores, and plants) in the model plant Arabidopsis thaliana as well as the adaptive value of these bases. Among the 60 identified genes are a number that encode nucleotide-binding site leucine-rich repeat (NBS-LRR)-type proteins, consistent with early examples of plant defense genes. However, recent studies have revealed an extensive diversity in the molecular mechanisms of defense. Many types of genetic variants associate with phenotypic variation in biotic interactions, even among the genes of large effect that tend to be identified. In general, we found that (i) balancing selection rather than directional selection explains the observed patterns of genetic diversity within A. thaliana and (ii) the cost/benefit tradeoffs of adaptive alleles can be strongly dependent on both genomic and environmental contexts. Finally, because A. thaliana rarely interacts with only one biotic partner in nature, we highlight the benefit of exploring diffuse biotic interactions rather than tightly associated host-enemy pairs. This challenge would help to improve our understanding of coevolutionary quantitative genetics within the context of realistic community complexity. © 2016 Elsevier Inc. All rights reserved.

  4. Progression of Left Ventricular Dysfunction and Remodelling under Optimal Medical Therapy in CHF Patients: Role of Individual Genetic Background

    Directory of Open Access Journals (Sweden)

    Marzia Rigolli

    2011-01-01

    Full Text Available Background. Neurohormonal systems play an important role in chronic heart failure (CHF. Due to interindividual heterogeneity in the benefits of therapy, it may be hypothesized that polymorphisms of neurohormonal systems may affect left ventricular (LV remodelling and systolic function. We aimed to assess whether genetic background of maximally treated CHF patients predicts variations in LV systolic function and volumes. Methods and Results. We prospectively studied 131 CHF outpatients on optimal treatment for at least six months. Echocardiographic evaluations were performed at baseline and after 12 months. Genotype analysis for ACE I/D, β1adrenergic receptor (AR Arg389Gly, β2AR Arg16Gly, and β2AR Gln27Glu polymorphisms was performed. No differences in baseline characteristics were detected among subgroups. ACE II was a significant predictor of improvement of LV end-diastolic and end-systolic volume (=.003 and =.002, respectively but not of LV ejection fraction (LVEF; β1AR389 GlyGly was related to improvement of LVEF (=.02 and LV end-systolic volume (=.01. The predictive value of polymorphisms remained after adjustment for other clinically significant predictors (<.05 for all. Conclusions. ACE I/D and β1AR Arg389Gly polymorphisms are independent predictors of reverse remodeling and systolic function recovery in CHF patients under optimal treatment.

  5. Expression profiling of a genetic animal model of depression reveals novel molecular pathways underlying depressive-like behaviours.

    Directory of Open Access Journals (Sweden)

    Ekaterini Blaveri

    2010-09-01

    Full Text Available The Flinders model is a validated genetic rat model of depression that exhibits a number of behavioural, neurochemical and pharmacological features consistent with those observed in human depression.In this study we have used genome-wide microarray expression profiling of the hippocampus and prefrontal/frontal cortex of Flinders Depression Sensitive (FSL and control Flinders Depression Resistant (FRL lines to understand molecular basis for the differences between the two lines. We profiled two independent cohorts of Flinders animals derived from the same colony six months apart, each cohort statistically powered to allow independent as well as combined analysis. Using this approach, we were able to validate using real-time-PCR a core set of gene expression differences that showed statistical significance in each of the temporally distinct cohorts, representing consistently maintained features of the model. Small but statistically significant increases were confirmed for cholinergic (chrm2, chrna7 and serotonergic receptors (Htr1a, Htr2a in FSL rats consistent with known neurochemical changes in the model. Much larger gene changes were validated in a number of novel genes as exemplified by TMEM176A, which showed 35-fold enrichment in the cortex and 30-fold enrichment in hippocampus of FRL animals relative to FSL.These data provide significant insights into the molecular differences underlying the Flinders model, and have potential relevance to broader depression research.

  6. Distribution network design under demand uncertainty using genetic algorithm and Monte Carlo simulation approach: a case study in pharmaceutical industry

    Science.gov (United States)

    Izadi, Arman; Kimiagari, Ali Mohammad

    2014-05-01

    Distribution network design as a strategic decision has long-term effect on tactical and operational supply chain management. In this research, the location-allocation problem is studied under demand uncertainty. The purposes of this study were to specify the optimal number and location of distribution centers and to determine the allocation of customer demands to distribution centers. The main feature of this research is solving the model with unknown demand function which is suitable with the real-world problems. To consider the uncertainty, a set of possible scenarios for customer demands is created based on the Monte Carlo simulation. The coefficient of variation of costs is mentioned as a measure of risk and the most stable structure for firm's distribution network is defined based on the concept of robust optimization. The best structure is identified using genetic algorithms and 14 % reduction in total supply chain costs is the outcome. Moreover, it imposes the least cost variation created by fluctuation in customer demands (such as epidemic diseases outbreak in some areas of the country) to the logistical system. It is noteworthy that this research is done in one of the largest pharmaceutical distribution firms in Iran.

  7. Finding Risk Groups by Optimizing Artificial Neural Networks on the Area under the Survival Curve Using Genetic Algorithms.

    Directory of Open Access Journals (Sweden)

    Jonas Kalderstam

    Full Text Available We investigate a new method to place patients into risk groups in censored survival data. Properties such as median survival time, and end survival rate, are implicitly improved by optimizing the area under the survival curve. Artificial neural networks (ANN are trained to either maximize or minimize this area using a genetic algorithm, and combined into an ensemble to predict one of low, intermediate, or high risk groups. Estimated patient risk can influence treatment choices, and is important for study stratification. A common approach is to sort the patients according to a prognostic index and then group them along the quartile limits. The Cox proportional hazards model (Cox is one example of this approach. Another method of doing risk grouping is recursive partitioning (Rpart, which constructs a decision tree where each branch point maximizes the statistical separation between the groups. ANN, Cox, and Rpart are compared on five publicly available data sets with varying properties. Cross-validation, as well as separate test sets, are used to validate the models. Results on the test sets show comparable performance, except for the smallest data set where Rpart's predicted risk groups turn out to be inverted, an example of crossing survival curves. Cross-validation shows that all three models exhibit crossing of some survival curves on this small data set but that the ANN model manages the best separation of groups in terms of median survival time before such crossings. The conclusion is that optimizing the area under the survival curve is a viable approach to identify risk groups. Training ANNs to optimize this area combines two key strengths from both prognostic indices and Rpart. First, a desired minimum group size can be specified, as for a prognostic index. Second, the ability to utilize non-linear effects among the covariates, which Rpart is also able to do.

  8. Interventricular communication in complete atrioventricular septal defect

    NARCIS (Netherlands)

    Suzuki, K.; Ho, S. Y.; Anderson, R. H.; Becker, A. E.; Neches, W. H.; Tatsuno, K.; Mimori, S.

    1998-01-01

    Little attention has been paid to whether the interventricular communication in complete atrioventricular septal defect is different beneath the superior and inferior bridging leaflets, a feature of obvious surgical significance. We searched for a defect under the bridging leaflets and examined the

  9. Indicators for Building Process without Final Defects -

    DEFF Research Database (Denmark)

    Jørgensen, Kirsten; Rasmussen, Grane Mikael Gregaard; Thuesen, Christian Langhoff

    2011-01-01

    This article introduces the preliminary data analysis, as well as the underlying theories and methods for identifying the indicators for building process without final defects. Since 2004, the Benchmark Centre for the Danish Construction Sector (BEC) has collected information about legal defects...

  10. Views on abortion: a comparison of female genetic counselors and women from the general population.

    Science.gov (United States)

    Woltanski, Amelia R; Cragun, Ryan T; Myers, Melanie F; Cragun, Deborah L

    2009-02-01

    While literature characterizing individual genetic counselors' abortion attitudes is sparse, the National Society of Genetic Counselors takes a clear stance for reproductive autonomy. To determine genetic counselors' views, this study compared (1) genetic counselors' abortion attitudes to those of women from the general population and (2) genetic counselors' professional abortion attitudes to their personal abortion attitudes. Genetic counselors were invited to complete an online survey. Response rate was 44.3% (709/1,601). Compared to women from the general population, female genetic counselors were significantly more likely to agree abortion should be an option in all cases (p abortion attitudes. Although the vast majority of genetic counselors agree that abortion should be available, they are significantly less likely to personally consider abortion under all circumstances presented (p < .001), and the percentage of genetic counselors who would consider terminating in the case of a severe birth defect is similar to studies of other women.

  11. MODEL-ASSISTED ESTIMATION OF THE GENETIC VARIABILITY IN PHYSIOLOGICAL PARAMETERS RELATED TO TOMATO FRUIT GROWTH UNDER CONTRASTED WATER CONDITIONS

    Directory of Open Access Journals (Sweden)

    Dario Constantinescu

    2016-12-01

    Full Text Available Drought stress is a major abiotic stres threatening plant and crop productivity. In case of fleshy fruits, understanding Drought stress is a major abiotic stress threatening plant and crop productivity. In case of fleshy fruits, understanding mechanisms governing water and carbon accumulations and identifying genes, QTLs and phenotypes, that will enable trade-offs between fruit growth and quality under Water Deficit (WD condition is a crucial challenge for breeders and growers. In the present work, 117 recombinant inbred lines of a population of Solanum lycopersicum were phenotyped under control and WD conditions. Plant water status, fruit growth and composition were measured and data were used to calibrate a process-based model describing water and carbon fluxes in a growing fruit as a function of plant and environment. Eight genotype-dependent model parameters were estimated using a multiobjective evolutionary algorithm in order to minimize the prediction errors of fruit dry and fresh mass throughout fruit development. WD increased the fruit dry matter content (up to 85 % and decreased its fresh weight (up to 60 %, big fruit size genotypes being the most sensitive. The mean normalized root mean squared errors of the predictions ranged between 16-18 % in the population. Variability in model genotypic parameters allowed us to explore diverse genetic strategies in response to WD. An interesting group of genotypes could be discriminated in which i the low loss of fresh mass under WD was associated with high active uptake of sugars and low value of the maximum cell wall extensibility, and ii the high dry matter content in control treatment (C was associated with a slow decrease of mass flow. Using 501 SNP markers genotyped across the genome, a QTL analysis of model parameters allowed to detect three main QTLs related to xylem and phloem conductivities, on chromosomes 2, 4 and 8. The model was then applied to design ideotypes with high dry matter

  12. Defect of the Eyelids.

    Science.gov (United States)

    Lu, Guanning Nina; Pelton, Ron W; Humphrey, Clinton D; Kriet, John David

    2017-08-01

    Eyelid defects disrupt the complex natural form and function of the eyelids and present a surgical challenge. Detailed knowledge of eyelid anatomy is essential in evaluating a defect and composing a reconstructive plan. Numerous reconstructive techniques have been described, including primary closure, grafting, and a variety of local flaps. This article describes an updated reconstructive ladder for eyelid defects that can be used in various permutations to solve most eyelid defects. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Environmental impacts of genetic improvement in growth rate and feed conversion in fish farming under density and nitrogen limitation

    NARCIS (Netherlands)

    Besson, M.; Aubin, J.; Arendonk, van J.A.M.; Komen, H.; Poelman, M.; Quillet, E.; Vandeputte, M.; Boer, de I.J.M.

    2014-01-01

    Many environmental impacts can be attributed to fish farming and there is a need to explore new ways of reducing environmental impacts, such as fish genetic improvement. The environmental consequences of genetic improvement in thermal growth coefficient (TGC) and in feed conversion ratio (FCR) were

  14. An aid to the diagnosis of genetic disorders underlying adult-onset renal failure : a literature review

    NARCIS (Netherlands)

    Joosten, H.; Strunk, A. L. M.; Meijer, S.; Boers, J. E.; Aries, M.J.H.; Abbes, A. P.; Engel, H.; Beukhof, J. R.

    Several genetic disorders can present in adult patients with renal insufficiency. Genetic renal disease other than ADPKD accounts for ESRD in 3% of the adult Dutch population. Because of this low prevalence and their clinical heterogeneity most adult nephrologists are less familiar with these

  15. Genetic Gains in Yield and Yield Related Traits under Drought Stress and Favorable Environments in a Maize Population Improved Using Marker Assisted Recurrent Selection

    Directory of Open Access Journals (Sweden)

    Folusho Bankole

    2017-05-01

    Full Text Available The objective of marker assisted recurrent selection (MARS is to increase the frequency of favorable marker alleles in a population before inbred line extraction. This approach was used to improve drought tolerance and grain yield (GY in a biparental cross of two elite drought tolerant lines. The testcrosses of randomly selected 50 S1 lines from each of the three selection cycles (C0, C1, C2 of the MARS population, parental testcrosses and the cross between the two parents (F1 were evaluated under drought stress (DS and well watered (WW well as under rainfed conditions to determine genetic gains in GY and other agronomic traits. Also, the S1 lines derived from each selection types were genotyped with single nucleotide polymorphism (SNP markers. Testcrosses derived from C2 produced significantly higher grain field under DS than those derived from C0 with a relative genetic gain of 7% per cycle. Also, the testcrosses of S1 lines from C2 showed an average genetic gain of 1% per cycle under WW condition and 3% per cycle under rainfed condition. Molecular analysis revealed that the frequency of favorable marker alleles increased from 0.510 at C0 to 0.515 at C2, while the effective number of alleles (Ne per locus decreased from C0 (1.93 to C2 (1.87. Our results underscore the effectiveness of MARS for improvement of GY under DS condition.

  16. Genetic structure of coexisting wild and managed agave populations: implications for the evolution of plants under domestication.

    Science.gov (United States)

    Figueredo, Carmen Julia; Casas, Alejandro; González-Rodríguez, Antonio; Nassar, Jafet M; Colunga-GarcíaMarín, Patricia; Rocha-Ramírez, Víctor

    2015-10-03

    Domestication is a continuous evolutionary process guided by humans. This process leads to divergence in characteristics such as behaviour, morphology or genetics, between wild and managed populations. Agaves have been important resources for Mesoamerican peoples since prehistory. Some species are domesticated and others vary in degree of domestication. Agave inaequidens Koch is used in central Mexico to produce mescal, and a management gradient from gathered wild and silvicultural populations, as well as cultivated plantations, has been documented. Significant morphological differences were reported among wild and managed populations, and a high phenotypic variation in cultivated populations composed of plants from different populations. We evaluated levels of genetic diversity and structure associated with management, hypothesizing that high morphological variation would be accompanied by high genetic diversity in populations with high gene flow and low genetic structure among managed and unmanaged populations. Wild, silvicultural and cultivated populations were studied, collecting tissue of 19-30 plants per population. Through 10 nuclear microsatellite loci, we compared population genetic parameters. We analysed partition of variation associated with management categories to estimate gene flow among populations. Agave inaequidens exhibits high levels of genetic diversity (He = 0.707) and moderate genetic structure (FST = 0.112). No differences were found in levels of genetic diversity among wild (He = 0.704), silviculturally managed (He = 0.733) and cultivated (He = 0.698) populations. Bayesian analysis indicated that five genetic clusters best fit the data, with genetic groups corresponding to habitats where populations grow rather than to management. Migration rates ranged from zero between two populations to markedly high among others (M = 0.73-35.25). Natural mechanisms of gene flow and the dynamic management of agave propagules among populations favour gene

  17. Genetic defects of cytochrome c oxidase assembly

    Czech Academy of Sciences Publication Activity Database

    Pecina, Petr; Houšťková, H.; Hansíková, H.; Zeman, J.; Houštěk, Josef

    2004-01-01

    Roč. 53, Suppl. 1 (2004), s. S213-S223 ISSN 0862-8408 R&D Projects: GA ČR GA303/03/0749 Institutional research plan: CEZ:AV0Z5011922 Keywords : cytochrome c oxidase * mitochondrial disorders Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 1.140, year: 2004

  18. Transcriptome analysis deciphers evolutionary mechanisms underlying genetic differentiation between coastal and offshore anchovy populations in the Bay of Biscay

    KAUST Repository

    Montes, Iratxe

    2016-09-13

    Morphometry and otolith microchemistry point to the existence of two populations of the European anchovy (Engraulis encrasicolus) in the Bay of Biscay: one in open seawaters, and a yet unidentified population in coastal waters. To test this hypothesis, we assembled a large number of samples from the region, including 587 juveniles and spawning adults from offshore and coastal waters, and 264 fish from other locations covering most of the species’ European range. These samples were genotyped for 456 exonic SNPs that provide a robust way to decipher adaptive processes in these populations. Two genetically differentiated populations of anchovy inhabit the Bay of Biscay with different population dynamics: (1) a large offshore population associated with marine waters included in the wide-shelf group, and (2) a coastal metapopulation adapted to estuarine environments in the Bay of Biscay and North Sea included in the narrow-shelf group. Transcriptome analysis identified neutral and adaptive evolutionary processes underlying differentiation between these populations. Reduced gene flow between offshore and coastal populations in the Bay of Biscay appears to result from divergence between two previously isolated gene pools adapted to contrasting habitats and now in secondary contact. Eleven molecular markers appear to mark divergent selection between the ecotypes, and a majority of these markers are associated with salinity variability. Ecotype differences at two outlier genes, TSSK6 and basigin, may hinder gamete compatibility between the ecotypes and reinforce reproductive isolation. Additionally, possible convergent evolution between offshore and coastal populations in the Bay of Biscay has been detected for the syntaxin1B-otoferlin gene system, which is involved in the control of larval buoyancy. Further study of exonic markers opens the possibility of understanding the mechanisms of adaptive divergence between European anchovy populations. © 2016, Springer

  19. An iterative genetic and dynamical modelling approach identifies novel features of the gene regulatory network underlying melanocyte development.

    Science.gov (United States)

    Greenhill, Emma R; Rocco, Andrea; Vibert, Laura; Nikaido, Masataka; Kelsh, Robert N

    2011-09-01

    The mechanisms generating stably differentiated cell-types from multipotent precursors are key to understanding normal development and have implications for treatment of cancer and the therapeutic use of stem cells. Pigment cells are a major derivative of neural crest stem cells and a key model cell-type for our understanding of the genetics of cell differentiation. Several factors driving melanocyte fate specification have been identified, including the transcription factor and master regulator of melanocyte development, Mitf, and Wnt signalling and the multipotency and fate specification factor, Sox10, which drive mitf expression. While these factors together drive multipotent neural crest cells to become specified melanoblasts, the mechanisms stabilising melanocyte differentiation remain unclear. Furthermore, there is controversy over whether Sox10 has an ongoing role in melanocyte differentiation. Here we use zebrafish to explore in vivo the gene regulatory network (GRN) underlying melanocyte specification and differentiation. We use an iterative process of mathematical modelling and experimental observation to explore methodically the core melanocyte GRN we have defined. We show that Sox10 is not required for ongoing differentiation and expression is downregulated in differentiating cells, in response to Mitfa and Hdac1. Unexpectedly, we find that Sox10 represses Mitf-dependent expression of melanocyte differentiation genes. Our systems biology approach allowed us to predict two novel features of the melanocyte GRN, which we then validate experimentally. Specifically, we show that maintenance of mitfa expression is Mitfa-dependent, and identify Sox9b as providing an Mitfa-independent input to melanocyte differentiation. Our data supports our previous suggestion that Sox10 only functions transiently in regulation of mitfa and cannot be responsible for long-term maintenance of mitfa expression; indeed, Sox10 is likely to slow melanocyte differentiation in the

  20. UPDATED MOLECULAR GENETICS AND PATHOGENESIS OF ICHTHYOSES

    Science.gov (United States)

    AKIYAMA, MASASHI

    2011-01-01

    ABSTRACT Research into the molecular genetics and pathomechanisms of ichthyoses have advanced considerably, resulting in the identification of several causative genes and molecules underlying the disease. In 2009, the First Ichthyosis Consensus Conference was held to establish a consensus for the nomenclature and classification of inherited ichthyoses, by which an international consensus for the classification of inherited ichthyosis was achieved. In this review, the pathogeneses of various ichthyoses are summarized based on their revised classification and terminology. Skin barrier defects are involved in the pathogenesis of various types of ichthyosis. The known causative molecules underlying ichthyosis include ABCA12, lipoxygenase-3, 12R-lipoxygenase, CYP4F22, ichthyin and steroid sulfatase, all of which are thought to be related to the intercellular lipid layers. ABCA12 is a known keratinocyte lipid transporter associated with lipid transport in lamellar granules and a loss of ABCA12 function leads to defective lipid transport in the keratinocytes, resulting in the most severe, harlequin ichthyosis phenotype. Other causative molecules for ichthyoses are transglutaminase 1, keratins and filaggrin. Transglutaminase 1 plays a role in cornified cell envelope formation. Keratins 1, 10 and 2 are involved in the keratin network of suprabasal keratinocytes and filaggrin is essential for the formation of keratohyalin granules. It is important to obtain information concerning genetic defects and to elucidate ichthyotic disease pathomechanisms for the establishment of an effective therapy and beneficial genetic counseling, including a prenatal diagnosis for families affected by ichthyotic disease. PMID:21928690

  1. The genetics of rheumatoid arthritis and the need for animal models to find and understand the underlying genes

    OpenAIRE

    Jirholt, Johan; Lindqvist, Anna-Karin B; Holmdahl, Rikard

    2000-01-01

    The causes of rheumatoid arthritis (RA) are largely unknown. However, RA is most probably a multifactorial disease with contributions from genetic and environmental factors. Searches for genes that influence RA have been conducted in both human and experimental model materials. Both types of study have confirmed the polygenic inheritance of the disease. It has become clear that the features of RA complicate the human genetic studies. Animal models are therefore valuable tools for identifying ...

  2. LETM1 haploinsufficiency causes mitochondrial defects in cells from humans with Wolf-Hirschhorn syndrome: implications for dissecting the underlying pathomechanisms in this condition

    Directory of Open Access Journals (Sweden)

    Lesley Hart

    2014-05-01

    Full Text Available Wolf-Hirschhorn syndrome (WHS represents an archetypical example of a contiguous gene deletion disorder – a condition comprising a complex set of developmental phenotypes with a multigenic origin. Epileptic seizures, intellectual disability, growth restriction, motor delay and hypotonia are major co-morbidities in WHS. Haploinsufficiency of LETM1, which encodes a mitochondrial inner-membrane protein functioning in ion transport, has been proposed as an underlying pathomechanism, principally for seizures but also for other core features of WHS, including growth and motor delay. Growing evidence derived from several model organisms suggests that reduced LETM1 expression is associated with some element of mitochondrial dysfunction. Surprisingly, LETM1-dependent mitochondrial functional deficits have not previously been described in cells from individuals with WHS. Here, using a unique panel of WHS-patient-derived cell lines with deletions of differing sizes, incorporating LETM1 or not, we show, for the first time, that LETM1 expression is reduced in mitochondria isolated from WHS-patient cells. Furthermore, we show that this is associated with distinct mitochondrial phenotypes, including altered intracellular [Ca2+] levels, dysfunctional mitochondrial transition-pore opening, hyperpolarization and superoxide leakage from resting mitochondria. Interestingly, we find that these phenotypes segregate with seizures in our WHS cohort. Our findings identify novel cellular phenotypes in WHS attributable to a 50% reduction in LETM1 expression level; these phenotypes could underlie and/or contribute to some of the core clinical features of this condition.

  3. LETM1 haploinsufficiency causes mitochondrial defects in cells from humans with Wolf-Hirschhorn syndrome: implications for dissecting the underlying pathomechanisms in this condition.

    Science.gov (United States)

    Hart, Lesley; Rauch, Anita; Carr, Antony M; Vermeesch, Joris R; O'Driscoll, Mark

    2014-05-01

    Wolf-Hirschhorn syndrome (WHS) represents an archetypical example of a contiguous gene deletion disorder - a condition comprising a complex set of developmental phenotypes with a multigenic origin. Epileptic seizures, intellectual disability, growth restriction, motor delay and hypotonia are major co-morbidities in WHS. Haploinsufficiency of LETM1, which encodes a mitochondrial inner-membrane protein functioning in ion transport, has been proposed as an underlying pathomechanism, principally for seizures but also for other core features of WHS, including growth and motor delay. Growing evidence derived from several model organisms suggests that reduced LETM1 expression is associated with some element of mitochondrial dysfunction. Surprisingly, LETM1-dependent mitochondrial functional deficits have not previously been described in cells from individuals with WHS. Here, using a unique panel of WHS-patient-derived cell lines with deletions of differing sizes, incorporating LETM1 or not, we show, for the first time, that LETM1 expression is reduced in mitochondria isolated from WHS-patient cells. Furthermore, we show that this is associated with distinct mitochondrial phenotypes, including altered intracellular [Ca(2+)] levels, dysfunctional mitochondrial transition-pore opening, hyperpolarization and superoxide leakage from resting mitochondria. Interestingly, we find that these phenotypes segregate with seizures in our WHS cohort. Our findings identify novel cellular phenotypes in WHS attributable to a 50% reduction in LETM1 expression level; these phenotypes could underlie and/or contribute to some of the core clinical features of this condition.

  4. Birth Defects in the Newborn Population: Race and Ethnicity

    Directory of Open Access Journals (Sweden)

    Alexander C. Egbe

    2015-06-01

    Conclusion: This is a comprehensive description of racial differences in the risk of birth defects in the United States. Observed racial differences in the risk of birth defects may be related to genetic susceptibilities, to cultural or social differences that could modify exposures, or to the many potential combinations between susceptibilities and exposures.

  5. Singlet oxygen triggers chloroplast rupture and cell death in the zeaxanthin epoxidase defective mutant aba1 of Arabidopsis thaliana under high light stress.

    Science.gov (United States)

    Sánchez-Corrionero, Álvaro; Sánchez-Vicente, Inmaculada; González-Pérez, Sergio; Corrales, Ascensión; Krieger-Liszkay, Anja; Lorenzo, Óscar; Arellano, Juan B

    2017-09-01

    The two Arabidopsis thaliana mutants, aba1 and max4, were previously identified as sharing a number of co-regulated genes with both the flu mutant and Arabidopsis cell suspension cultures exposed to high light (HL). On this basis, we investigated whether aba1 and max4 were generating high amounts of singlet oxygen ( 1 O 2 ) and activating 1 O 2 -mediated cell death. Thylakoids of aba1 produced twice as much 1 O 2 as thylakoids of max4 and wild type (WT) plants when illuminated with strong red light. 1 O 2 was measured using the spin probe 2,2,6,6-tetramethyl-4-piperidone hydrochloride. 77-K chlorophyll fluorescence emission spectra of thylakoids revealed lower aggregation of the light harvesting complex II in aba1. This was rationalized as a loss of connectivity between photosystem II (PSII) units and as the main cause for the high yield of 1 O 2 generation in aba1. Up-regulation of the 1 O 2 responsive gene AAA-ATPase was only observed with statistical significant in aba1 under HL. Two early jasmonate (JA)-responsive genes, JAZ1 and JAZ5, encoding for two repressor proteins involved in the negative feedback regulation of JA signalling, were not up-regulated to the WT plant levels. Chloroplast aggregation followed by chloroplast rupture and eventual cell death was observed by confocal imaging of the fluorescence emission of leaf cells of transgenic aba1 plants expressing the chimeric fusion protein SSU-GFP. Cell death was not associated with direct 1 O 2 cytotoxicity in aba1, but rather with a delayed stress response. In contrast, max4 did not show evidence of 1 O 2 -mediated cell death. In conclusion, aba1 may serve as an alternative model to other 1 O 2 -overproducing mutants of Arabidopsis for investigating 1 O 2 -mediated cell death. Copyright © 2017 Elsevier GmbH. All rights reserved.

  6. An Underlying Common Factor, Influenced by Genetics and Unique Environment, Explains the Covariation Between Major Depressive Disorder, Generalized Anxiety Disorder, and Burnout: A Swedish Twin Study.

    Science.gov (United States)

    Mather, Lisa; Blom, Victoria; Bergström, Gunnar; Svedberg, Pia

    2016-12-01

    Depression and anxiety are highly comorbid due to shared genetic risk factors, but less is known about whether burnout shares these risk factors. We aimed to examine whether the covariation between major depressive disorder (MDD), generalized anxiety disorder (GAD), and burnout is explained by common genetic and/or environmental factors. This cross-sectional study included 25,378 Swedish twins responding to a survey in 2005-2006. Structural equation models were used to analyze whether the trait variances and covariances were due to additive genetics, non-additive genetics, shared environment, and unique environment. Univariate analyses tested sex limitation models and multivariate analysis tested Cholesky, independent pathway, and common pathway models. The phenotypic correlations were 0.71 (0.69-0.74) between MDD and GAD, 0.58 (0.56-0.60) between MDD and burnout, and 0.53 (0.50-0.56) between GAD and burnout. Heritabilities were 45% for MDD, 49% for GAD, and 38% for burnout; no statistically significant sex differences were found. A common pathway model was chosen as the final model. The common factor was influenced by genetics (58%) and unique environment (42%), and explained 77% of the variation in MDD, 69% in GAD, and 44% in burnout. GAD and burnout had additive genetic factors unique to the phenotypes (11% each), while MDD did not. Unique environment explained 23% of the variability in MDD, 20% in GAD, and 45% in burnout. In conclusion, the covariation was explained by an underlying common factor, largely influenced by genetics. Burnout was to a large degree influenced by unique environmental factors not shared with MDD and GAD.

  7. Correlation between Focal Nodular Low Signal Changes in Hoffa’s Fat Pad Adjacent to Anterior Femoral Cartilage and Focal Cartilage Defect Underlying This Region and Its Possible Implication

    Directory of Open Access Journals (Sweden)

    Chermaine Deepa Antony

    2016-01-01

    Full Text Available Purpose. This study investigates the association between focal nodular mass with low signal in Hoffa’s fat pad adjacent to anterior femoral cartilage of the knee (FNMHF and focal cartilage abnormality in this region. Method. The magnetic resonance fast imaging employing steady-state acquisition sequence (MR FIESTA sagittal and axial images of the B1 and C1 region (described later of 148 patients were independently evaluated by two reviewers and categorized into four categories: normal, FNMHF with underlying focal cartilage abnormality, FNMHF with normal cartilage, and cartilage abnormality with no FNMHF. Results. There was a significant association (p=0.00 between FNMHF and immediate adjacent focal cartilage abnormality with high interobserver agreement. The absence of focal nodular lesions next to the anterior femoral cartilage has a very high negative predictive value for chondral injury (97.8%. Synovial biopsy of focal nodular lesion done during arthroscopy revealed some fibrocollagenous tissue and no inflammatory cells. Conclusion. We postulate that the FNMHF adjacent to the cartilage defects is a form of normal healing response to the cartilage damage. One patient with FHMHF and underlying cartilage abnormality was rescanned six months later. In this patient, the FNMHF disappeared and normal cartilage was observed in the adjacent region which may support this theory.

  8. Developmental genetic analysis of fruit shape traits under different environmental conditions in sponge gourd (Luffa cylindrical (L Roem. Violales, Cucurbitaceae

    Directory of Open Access Journals (Sweden)

    Sheng Zhang

    2008-01-01

    Full Text Available Analysis of genetic main effects and genotype × environment (GE interaction effects for the fruit shape traits fruit length and fruit circumference in the sponge gourd (Luffa cylindrical (L Roem. Violales, Cucurbitaceae was conducted for diallel cross data from two planting seasons. A genetic model including fruit direct effects and maternal effects and unconditional and conditional variances analysis was used to evaluate the development of the fruit at four maturation stages. The variance analysis results indicated that fruit length and circumference were simultaneously affected by fruit direct genetic effects and maternal effects as well as GE interaction effects. Fruit direct genetic effects were relatively more important for both fruit shape traits during the whole developmental period. Gene activation was mostly due to additive effects at the first maturation stage and dominance effects were mainly active during the other three stages. The fruit shape trait correlation coefficients due to different genetic effects and the phenotypic correlation coefficients varied significantly for the various maturation stages. The results indicate that it is relatively easy to improve the two fruit shape traits for market purposes by carefully selecting the parents at the first maturation stage 3 days after flowering instead of at fruit economic maturation.

  9. Genetic Dissection of Bioenergy-Related Traits in Sweet Sorghum (Sorghum bicolor) under Danish Agro-Climatic Conditions

    DEFF Research Database (Denmark)

    Mocoeur, Anne Raymonde Joelle

    plant for sequencing in 2009 promoting it as a C4 model plant. Among the very diverse genetic resources available for sorghum, sweet sorghum plants; amassing large quantities of juice-rich and sugar-rich stem, grain and vegetative biomass; have been enlightened as bioenergy crop as it can produced from...... a single plant food, feed and fuel. Sweet sorghum has gained interest in Europe to replace maize, for biogas and bioenergy productions, but this versatile crop is sensitive to chilling temperatures and little breeding efforts have been done toward its cold acclimation. The state-of-art of using...... in Denmark using a panel of genetic and genomic tools. A large bi-parental QTL mapping study was carried out by using several mapping populations progenies, derived from a cross between a sweet and grain sorghum and they were grown and phenotyped in China and Denmark. The genetic map used for this bi...

  10. Topological defect dynamics in operando battery nanoparticles

    Science.gov (United States)

    Ulvestad, Andrew; Meng, Shirley; Shpyrko, Oleg

    2015-03-01

    Topological defects are ubiquitous in physics and manifest themselves as magnetic monopoles in quantum field theories and crystallographic imperfections in condensed matter systems. In the latter, the defect properties determine many of the material's properties and as such represent substantial novel opportunities for design and optimization of desired functionalities through deliberate defect engineering and manipulation. However, this approach of ``defect choreography'' currently suffers from the lack of suitable nanoscale probes to track buried single defects in-situ and in-operando. Here we report 3D imaging of single edge dislocations and their motion in an individual nanoparticle under operando conditions in a Lithium ion battery. We further observe the dislocation act as a nucleation point during the structural phase transformation. We find that the region near the dislocation enters a negative Poisson's ratio, or auxetic, regime at high voltage. Dislocation imaging is thus a powerful nanotechnology and it opens a new, powerful avenue for facilitating improvement of nanostructured devices.

  11. The genetics of rheumatoid arthritis and the need for animal models to find and understand the underlying genes.

    Science.gov (United States)

    Jirholt, J; Lindqvist, A B; Holmdahl, R

    2001-01-01

    The causes of rheumatoid arthritis (RA) are largely unknown. However, RA is most probably a multifactorial disease with contributions from genetic and environmental factors. Searches for genes that influence RA have been conducted in both human and experimental model materials. Both types of study have confirmed the polygenic inheritance of the disease. It has become clear that the features of RA complicate the human genetic studies. Animal models are therefore valuable tools for identifying genes and determining their pathogenic role in the disease. This is probably the fastest route towards unravelling the pathogenesisis of RA and developing new therapies.

  12. Defects in semiconductors

    CERN Document Server

    Romano, Lucia; Jagadish, Chennupati

    2015-01-01

    This volume, number 91 in the Semiconductor and Semimetals series, focuses on defects in semiconductors. Defects in semiconductors help to explain several phenomena, from diffusion to getter, and to draw theories on materials' behavior in response to electrical or mechanical fields. The volume includes chapters focusing specifically on electron and proton irradiation of silicon, point defects in zinc oxide and gallium nitride, ion implantation defects and shallow junctions in silicon and germanium, and much more. It will help support students and scientists in their experimental and theoret

  13. Why increased nuchal translucency is associated with congenital heart disease: a systematic review on genetic mechanisms

    NARCIS (Netherlands)

    Burger, N.B.; Bekker, M.N.; Groot, C.J. de; Christoffels, V.M.; Haak, M.C.

    2015-01-01

    This overview provides insight into the underlying genetic mechanism of the high incidence of cardiac defects in fetuses with increased nuchal translucency (NT). Nuchal edema, the morphological equivalent of increased NT, is likely to result from abnormal lymphatic development and is strongly

  14. Daf-2, Daf-16 and Daf-23: Genetically Interacting Genes Controlling Dauer Formation in Caenorhabditis Elegans

    OpenAIRE

    Gottlieb, S.; Ruvkun, G.

    1994-01-01

    Under conditions of high population density and low food, Caenorhabditis elegans forms an alternative third larval stage, called the dauer stage, which is resistant to desiccation and harsh environments. Genetic analysis of some dauer constitutive (Daf-c) and dauer defective (Daf-d) mutants has revealed a complex pathway that is likely to function in particular neurons and/or responding tissues. Here we analyze the genetic interactions between three genes which comprise a branch of the dauer ...

  15. Genetic Variation of Morphological Traits and Transpiration in an Apple Core Collection under Well-Watered Conditions: Towards the Identification of Morphotypes with High Water Use Efficiency.

    Directory of Open Access Journals (Sweden)

    Gerardo Lopez

    Full Text Available Water use efficiency (WUE is a quantitative measurement which improvement is a major issue in the context of global warming and restrictions in water availability for agriculture. In this study, we aimed at studying the variation and genetic control of WUE and the respective role of its components (plant biomass and transpiration in a perennial fruit crop. We explored an INRA apple core collection grown in a phenotyping platform to screen one-year-old scions for their accumulated biomass, transpiration and WUE under optimal growing conditions. Plant biomass was decompose into morphological components related to either growth or organ expansion. For each trait, nine mixed models were evaluated to account for the genetic effect and spatial heterogeneity inside the platform. The Best Linear Unbiased Predictors of genetic values were estimated after model selection. Mean broad-sense heritabilities were calculated from variance estimates. Heritability values indicated that biomass (0.76 and WUE (0.73 were under genetic control. This genetic control was lower in plant transpiration with an heritability of 0.54. Across the collection, biomass accounted for 70% of the WUE variability. A Hierarchical Ascendant Classification of the core collection indicated the existence of six groups of genotypes with contrasting morphology and WUE. Differences between morphotypes were interpreted as resulting from differences in the main processes responsible for plant growth: cell division leading to the generation of new organs and cell elongation leading to organ dimension. Although further studies will be necessary on mature trees with more complex architecture and multiple sinks such as fruits, this study is a first step for improving apple plant material for the use of water.

  16. Genetic Background and Environment Influence the Effects of Mutations in pykF and Help Reveal Mechanisms Underlying Their Benefit

    Science.gov (United States)

    2015-08-01

    environment interactions characterize the evolution of drug resistance in yeast. Genetics 192:241–252. Gompel, N., and B. Prud’homme. 2009. The causes...3314–3323. 84 Walk, S. T., E. W. Alm, D. M. Gordon, J. L. Ram, G. A. Toranzos, J. M. Tiedje, and T. S. Whittam. 2009. Cryptic lineages of the genus

  17. Indirect Genetic Effects and the Spread of Infectious Disease: Are We Capturing the Full Heritable Variation Underlying Disease Prevalence?

    NARCIS (Netherlands)

    Lipschutz-Powell, D.; Woolliams, J.A.; Bijma, P.; Doeschl-Wilson, A.B.

    2012-01-01

    Reducing disease prevalence through selection for host resistance offers a desirable alternative to chemical treatment. Selection for host resistance has proven difficult, however, due to low heritability estimates. These low estimates may be caused by a failure to capture all the relevant genetic

  18. Genetic variability in elite barley genotypes based on the agro-morphological characteristics evaluated under irrigated system

    Directory of Open Access Journals (Sweden)

    Renato Fernando Amabile

    Full Text Available ABSTRACT Recently, researches have shown that the Brazilian savannah has a great potential to supply the demand for barley grains. The purpose of this study was to assess the genetic variability in 39 elite barley (Hordeum vulgare L. genotypes based on the agro-morphological traits of a crop irrigated in the savannah system. An irrigation experiment in the design of complete randomized block with four replicates was conducted at Federal District - Brazil. The evaluated traits were: distance from the last knot to the rachis, distance from the flag leaf to rachis, spike length, number of grains by ear, flag leaf area, plant height, silking, lodging, grain yield, thousand-seed weight, protein content and grain commercial classification. After using analysis of variance the means were used to estimate the genetic dissimilarity among all genotypes pairs based on the Mahalanobis’ generalized distance. Cluster analysis using genetic distance matrix was performed having Unweighted Pair Group Method using Arithmetic Means method (UPGMA as the criteria. Highly significant differences were found among the genotypes for all traits evaluated. The high coefficient of genetic variation indicates the possibility of having genetic gains for all traits. The traits that most contributed to the variability were the flag leaf area and silking, while the protein content and lodging were the traits that contributed the least. Based on the cluster analysis, at least three major groups of similarity were found. There was a clustering trend of two and six-rowed materials. The most divergent genotypes were PFC 2005123, Antártica-1, Nandi and FM 404.

  19. Genetic improvement of under-utilized and neglected crops in low income food deficit countries through irradiation and related techniques. Proceedings of a final research coordination meeting

    International Nuclear Information System (INIS)

    2004-11-01

    The majority of the world's food is produced from only a few crops, and yet many neglected and under-utilized crops are extremely important for food production in low income food deficit countries (LIFDCs). As the human population grows at an alarming rate in LIFDCs, food availability has declined and is also affected due to environmental factors, lack of improvement of local crop species, erosion of genetic diversity and dependence on a few crop species for food supply. Neglected crops are traditionally grown by farmers in their centres of origin or centres of diversity, where they are still important for the subsistence of local communities, and maintained by socio-cultural preferences and traditional uses. These crops remain inadequately characterised and, until very recently, have been largely ignored by research and conservation. Farmers are losing these crops because they are less competitive with improved major crop species. Radiation-induced mutation techniques have successfully been used that benefited the most genetic improvement of 'major crops' and their know-how have a great potential for enhancing the use of under-utilized and neglected species and speeding up their domestication and crop improvement. The FAO/IAEA efforts on genetic improvement of under-utilized and neglected species play a strategic role in complementing the work that is being carried out worldwide in their promotion. This CRP entitled Genetic Improvement of Under-utilized and Neglected Crops in LIFDCs through Irradiation and Related Techniques was initiated in 1998 with an overall objective to improve food security, enhance nutritional balance, and promote sustainable agriculture in LIFDCs. Specific objectives addressed major constraints to productivity of neglected and under-utilized crops by genetic improvement with radiation-induced mutations and biotechnology in order to enhance economic viability and sustain crop species diversity, and in future to benefit small farmers. This

  20. Defects in hardwood timber

    Science.gov (United States)

    Roswell D. Carpenter; David L. Sonderman; Everette D. Rast; Martin J. Jones

    1989-01-01

    Includes detailed information on all common defects that may aRect hardwood trees and logs. Relationships between manufactured products and those forms of round material to be processed from the tree for conversion into marketable products are discussed. This handbook supersedes Agriculture Handbook No. 244, Grade defects in hardwood timber and logs, by C.R. Lockard, J...

  1. Craniotomy Frontal Bone Defect

    African Journals Online (AJOL)

    2018-03-01

    Mar 1, 2018 ... with cosmetic deformity of fore head (Figure 1), and he claimed that he could not get job because of ... 1: Pre-operative forontal view of patient. Figure 2: Intra operative photography of defect (A) reconstructed defect (B) ... with a cosmetic deformity of forehead on left side. (4nA and B). He was a candidate for.

  2. Genetic control and combining ability of flag leaf area and relative water content traits of bread wheat cultivars under drought stress condition

    Directory of Open Access Journals (Sweden)

    Golparvar Ahmad Reza

    2013-01-01

    Full Text Available In order to compare mode of inheritance, combining ability, heterosis and gene action in genetic control of traits flag leaf area, relative water content and grain filling rate of bread wheat under drought stress, a study was conducted on 8 cultivars using of Griffing’s method2 in fixed model. Mean square of general combining ability was significant also for all traits and mean square of specific combining ability was significant also for all traits except relative water content of leaf which show importance of both additive and dominant effects of genes in heredity of these traits under stress. GCA to SCA mean square ratio was significant for none of traits. Results of this study showed that non additive effects of genes were more important than additive effect for all traits. According to results we can understand that genetic improvement of mentioned traits will have low genetic efficiency by selection from the best crosses of early generations. Then it is better to delay selection until advanced generations and increase in heritability of these traits.

  3. Genetic architecture and functional characterization of genes underlying the rapid diversification of male external genitalia between Drosophila simulans and Drosophila mauritiana.

    Science.gov (United States)

    Tanaka, Kentaro M; Hopfen, Corinna; Herbert, Matthew R; Schlötterer, Christian; Stern, David L; Masly, John P; McGregor, Alistair P; Nunes, Maria D S

    2015-05-01

    Male sexual characters are often among the first traits to diverge between closely related species and identifying the genetic basis of such changes can contribute to our understanding of their evolutionary history. However, little is known about the genetic architecture or the specific genes underlying the evolution of male genitalia. The morphology of the claspers, posterior lobes, and anal plates exhibit striking differences between Drosophila mauritiana and D. simulans. Using QTL and introgression-based high-resolution mapping, we identified several small regions on chromosome arms 3L and 3R that contribute to differences in these traits. However, we found that the loci underlying the evolution of clasper differences between these two species are independent from those that contribute to posterior lobe and anal plate divergence. Furthermore, while most of the loci affect each trait in the same direction and act additively, we also found evidence for epistasis between loci for clasper bristle number. In addition, we conducted an RNAi screen in D. melanogaster to investigate if positional and expression candidate genes located on chromosome 3L, are also involved in genital development. We found that six of these genes, including components of Wnt signaling and male-specific lethal 3 (msl3), regulate the development of genital traits consistent with the effects of the introgressed regions where they are located and that thus represent promising candidate genes for the evolution these traits. Copyright © 2015 by the Genetics Society of America.

  4. Joint genetic and network analyses identify loci associated with root growth under NaCl stress in Arabidopsis thaliana.

    Science.gov (United States)

    Kobayashi, Yuriko; Sadhukhan, Ayan; Tazib, Tanveer; Nakano, Yuki; Kusunoki, Kazutaka; Kamara, Mohamed; Chaffai, Radhouane; Iuchi, Satoshi; Sahoo, Lingaraj; Kobayashi, Masatomo; Hoekenga, Owen A; Koyama, Hiroyuki

    2016-04-01

    Plants have evolved a series of tolerance mechanisms to saline stress, which perturbs physiological processes throughout the plant. To identify genetic mechanisms associated with salinity tolerance, we performed linkage analysis and genome-wide association study (GWAS) on maintenance of root growth of Arabidopsis thaliana in hydroponic culture with weak and severe NaCl toxicity. The top 200 single-nucleotide polymorphisms (SNPs) determined by GWAS could cumulatively explain approximately 70% of the variation observed at each stress level. The most significant SNPs were linked to the genes of ATP-binding cassette B10 and vacuolar proton ATPase A2. Several known salinity tolerance genes such as potassium channel KAT1 and calcium sensor SOS3 were also linked to SNPs in the top 200. In parallel, we constructed a gene co-expression network to independently verify that particular groups of genes work together to a common purpose. We identify molecular mechanisms to confer salt tolerance from both predictable and novel physiological sources and validate the utility of combined genetic and network analysis. Additionally, our study indicates that the genetic architecture of salt tolerance is responsive to the severity of stress. These gene datasets are a significant information resource for a following exploration of gene function. © 2015 John Wiley & Sons Ltd.

  5. Cardiac Defects and Results of Cardiac Surgery in 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Carotti, Adriano; Digilio, Maria Cristina; Piacentini, Gerardo; Saffirio, Claudia; Di Donato, Roberto M.; Marino, Bruno

    2008-01-01

    Specific types and subtypes of cardiac defects have been described in children with 22q11.2 deletion syndrome as well as in other genetic syndromes. The conotruncal heart defects occurring in patients with 22q11.2 deletion syndrome include tetralogy of Fallot, pulmonary atresia with ventricular septal defect, truncus arteriosus, interrupted aortic…

  6. Fungal Genetics and Functional Diversity of Microbial Communities in the Soil under Long-Term Monoculture of Maize Using Different Cultivation Techniques

    Directory of Open Access Journals (Sweden)

    Anna Gałązka

    2018-01-01

    Full Text Available Fungal diversity in the soil may be limited under natural conditions by inappropriate environmental factors such as: nutrient resources, biotic and abiotic factors, tillage system and microbial interactions that prevent the occurrence or survival of the species in the environment. The aim of this paper was to determine fungal genetic diversity and community level physiological profiling of microbial communities in the soil under long-term maize monoculture. The experimental scheme involved four cultivation techniques: direct sowing (DS, reduced tillage (RT, full tillage (FT, and crop rotation (CR. Soil samples were taken in two stages: before sowing of maize (DSBS-direct sowing, RTBS-reduced tillage, FTBS-full tillage, CRBS-crop rotation and the flowering stage of maize growth (DSF-direct sowing, RTF-reduced tillage, FTF-full tillage, CRF-crop rotation. The following plants were used in the crop rotation: spring barley, winter wheat and maize. The study included fungal genetic diversity assessment by ITS-1 next generation sequencing (NGS analyses as well as the characterization of the catabolic potential of microbial communities (Biolog EcoPlates in the soil under long-term monoculture of maize using different cultivation techniques. The results obtained from the ITS-1 NGS technique enabled to classify and correlate the fungi species or genus to the soil metabolome. The research methods used in this paper have contributed to a better understanding of genetic diversity and composition of the population of fungi in the soil under the influence of the changes that have occurred in the soil under long-term maize cultivation. In all cultivation techniques, the season had a great influence on the fungal genetic structure in the soil. Significant differences were found on the family level (P = 0.032, F = 3.895, genus level (P = 0.026, F = 3.313 and on the species level (P = 0.033, F = 2.718. This study has shown that: (1 fungal diversity was changed

  7. Transcriptional profiling of human breast cancer cells cultured under microgravity conditions revealed the key role of genetic gravity sensors previously detected in Drosophila melanogaster

    Science.gov (United States)

    Valdivia-Silva, Julio E.; Lavan, David; Diego Orihuela-Tacuri, M.; Sanabria, Gabriela

    2016-07-01

    Currently, studies in Drosophila melanogaster has shown emerging evidence that microgravity stimuli can be detected at the genetic level. Analysis of the transcriptome in the pupal stage of the fruit flies under microgravity conditions versus ground controls has suggested the presence of a few candidate genes as "gravity sensors" which are experimentally validated. Additionally, several studies have shown that microgravity causes inhibitory effects in different types of cancer cells, although the genes involved and responsible for these effects are still unknown. Here, we demonstrate that the genes suggested as the sensors of gravitational waves in Drosophila melanogaster and their human counterpart (orthologous genes) are highly involved in carcinogenesis, proliferation, anti-apoptotic signals, invasiveness, and metastatic potential of breast cancer cell tumors. The transcriptome analyses suggested that the observed inhibitory effect in cancer cells could be due to changes in the genetic expression of these candidates. These results encourage the possibility of new therapeutic targets managed together and not in isolation.

  8. Physiological basis of genetic variation in leaf photosynthesis among rice (Oryza sativa L.) introgression lines under drought and well-watered conditions

    Science.gov (United States)

    Yin, Xinyou

    2012-01-01

    To understand the physiological basis of genetic variation and resulting quantitative trait loci (QTLs) for photosynthesis in a rice (Oryza sativa L.) introgression line population, 13 lines were studied under drought and well-watered conditions, at flowering and grain filling. Simultaneous gas exchange and chlorophyll fluorescence measurements were conducted at various levels of incident irradiance and ambient CO2 to estimate parameters of a model that dissects photosynthesis into stomatal conductance (g s), mesophyll conductance (g m), electron transport capacity (J max), and Rubisco carboxylation capacity (V cmax). Significant genetic variation in these parameters was found, although drought and leaf age accounted for larger proportions of the total variation. Genetic variation in light-saturated photosynthesis and transpiration efficiency (TE) were mainly associated with variation in g s and g m. One previously mapped major QTL of photosynthesis was associated with variation in g s and g m, but also in J max and V cmax at flowering. Thus, g s and g m, which were demonstrated in the literature to be responsible for environmental variation in photosynthesis, were found also to be associated with genetic variation in photosynthesis. Furthermore, relationships between these parameters and leaf nitrogen or dry matter per unit area, which were previously found across environmental treatments, were shown to be valid for variation across genotypes. Finally, the extent to which photosynthesis rate and TE can be improved was evaluated. Virtual ideotypes were estimated to have 17.0% higher photosynthesis and 25.1% higher TE compared with the best genotype investigated. This analysis using introgression lines highlights possibilities of improving both photosynthesis and TE within the same genetic background. PMID:22888131

  9. Traffic jam in the primitive streak: the role of defective mesoderm migration in birth defects.

    Science.gov (United States)

    Herion, Nils J; Salbaum, J Michael; Kappen, Claudia

    2014-08-01

    Gastrulation is the process in which the three germ layers are formed that contribute to the formation of all major tissues in the developing embryo. We here review mouse genetic models in which defective gastrulation leads to mesoderm insufficiencies in the embryo. Depending on severity of the abnormalities, the outcomes range from incompatible with embryonic survival to structural birth defects, such as heart defects, spina bifida, or caudal dysgenesis. The combined evidence from the mutant models supports the notion that these congenital anomalies can originate from perturbations of mesoderm specification, epithelial-mesenchymal transition, and mesodermal cell migration. Knowledge about the molecular pathways involved may help to improve strategies for the prevention of major structural birth defects. © 2014 Wiley Periodicals, Inc.

  10. Multiscale crystal defect dynamics: A coarse-grained lattice defect model based on crystal microstructure

    Science.gov (United States)

    Lyu, Dandan; Li, Shaofan

    2017-10-01

    Crystal defects have microstructure, and this microstructure should be related to the microstructure of the original crystal. Hence each type of crystals may have similar defects due to the same failure mechanism originated from the same microstructure, if they are under the same loading conditions. In this work, we propose a multiscale crystal defect dynamics (MCDD) model that models defects by considering its intrinsic microstructure derived from the microstructure or material genome of the original perfect crystal. The main novelties of present work are: (1) the discrete exterior calculus and algebraic topology theory are used to construct a scale-up (coarse-grained) dual lattice model for crystal defects, which may represent all possible defect modes inside a crystal; (2) a higher order Cauchy-Born rule (up to the fourth order) is adopted to construct atomistic-informed constitutive relations for various defect process zones, and (3) an hierarchical strain gradient theory based finite element formulation is developed to support an hierarchical multiscale cohesive (process) zone model for various defects in a unified formulation. The efficiency of MCDD computational algorithm allows us to simulate dynamic defect evolution at large scale while taking into account atomistic interaction. The MCDD model has been validated by comparing of the results of MCDD simulations with that of molecular dynamics (MD) in the cases of nanoindentation and uniaxial tension. Numerical simulations have shown that MCDD model can predict dislocation nucleation induced instability and inelastic deformation, and thus it may provide an alternative solution to study crystal plasticity.

  11. Screening Tests for Birth Defects

    Science.gov (United States)

    ... Advocacy For Patients About ACOG Screening Tests for Birth Defects Home For Patients Search FAQs Screening Tests ... FAQ165, April 2014 PDF Format Screening Tests for Birth Defects Pregnancy What is a birth defect? What ...

  12. Genetic causes of congenital brain malformations in epilepsy patients

    DEFF Research Database (Denmark)

    Møller, Rikke Steensbjerre

    2008-01-01

    The search for genetic causes of congenital brain malformations, severe epilepsy and mental retardation plays an important role in neuropediatrics and neurology. Disclosure of the aetiology of the intellectual disabilities, seizures and the underlying brain malformation may be of psychological...... genes for developmental brain defects. The overall aim of the present study has been to identify new candidate genes or predisposing factors involved in congenital brain malformations in epilepsy patients....

  13. Usage of analytical diagnostics when evaluating functional surface material defects

    Directory of Open Access Journals (Sweden)

    R. Frischer

    2015-10-01

    Full Text Available There are occurring defects due to defects mechanisms on parts of production devices surfaces. Outer defects pronouncement is changing throw the time with unequal speed. This variability of defect’s mechanism development cause that is impossible to evaluate technical state of the device in any moment, without the necessary underlying information. Proposed model is based on analytical diagnostics basis. Stochastic model with usage of Weibull probability distribution can assign probability of function surface defect occurrence on the operational information in any moment basis. The knowledge of defect range limiting moment, then enable when and in what range will be necessary to make renewal.

  14. Genetics Home Reference: spondylocostal dysostosis

    Science.gov (United States)

    ... Tube Defects Health Topic: Scoliosis Health Topic: Spina Bifida Health Topic: Spine Injuries and Disorders Genetic and Rare Diseases Information Center (1 link) Spondylocostal dysostosis ... Educational Resources (7 links) Cleveland Clinic: ...

  15. [Anti-HBV effects of genetically engineered replication-defective HBV with combined expression of antisense RNA and dominant negative mutants of core protein and construction of first-generation packaging cell line for HBV vector].

    Science.gov (United States)

    Sun, Dian Xing; Hu, Da Rong; Wu, Guang Hui; Hu, Xue Ling; Li, Juan; Fan, Gong Ren

    2002-08-01

    To explore the possibility of using HBV as a gene delivery vector, and to test the anti-HBV effects by intracellular combined expression of antisense RNA and dominant negative mutants of core protein. Full length of mutant HBV genome, which expresses core-partial P fusion protein and/or antisense RNA, was transfected into HepG2.2.15 cell lines. Positive clones were selected and mixed in respective groups with hygromycin in the culture medium. HBsAg and HBeAg, which exist in the culture medium, were tested by ELISA method. Intracellular HBc related HBV DNA was examined by dot blot hybridization. The existence of recombinant HBV virion in the culture medium was examined by PCR. Free of packaging signal, HBV genome, which express the HBV structural proteins including core, pol and preS/S proteins, was inserted into pCI-neo vector. HepG2 cell lines were employed to transfect with the construct. G418 selection was done at the concentration of 400mug/ml in the culture medium. The G418-resistant clones with the best expression of HBsAg and HBcAg were theoretically considered as packaging cell lines and propagated under the same conditions. It was transfected with plasmid pMEP-CPAS and then selected with G418 and hygromycin in the culture medium. The existence of recombinant HBV virion in the culture medium was examined by PCR. The mean inhibitory rates of HBsAg were 2.74% 3.83%, 40.08 2.05% (t=35.5, PDNA were 0, 82.0%, 59.9%, and 96.6%, respectively. Recombinant HB virion was detectable in the culture medium of all the three treatment groups. G418-resistant HBV packaging cell line, which harbored an HBV mutant whose packaging signal had been deleted, was generated. Expression of HBsAg and HBcAg was detectable. Transfected with plasmid pMEP-CPAS, it was found to secrete recombinant HB virion and no wild-type HBV was detectable in the culture medium. It has stronger anti-HBV effects by combined expression of antisense RNA and dominant negative mutants than by individual

  16. Blood flow patterns underlie developmental heart defects.

    Science.gov (United States)

    Midgett, Madeline; Thornburg, Kent; Rugonyi, Sandra

    2017-03-01

    Although cardiac malformations at birth are typically associated with genetic anomalies, blood flow dynamics also play a crucial role in heart formation. However, the relationship between blood flow patterns in the early embryo and later cardiovascular malformation has not been determined. We used the chicken embryo model to quantify the extent to which anomalous blood flow patterns predict cardiac defects that resemble those in humans and found that restricting either the inflow to the heart or the outflow led to reproducible abnormalities with a dose-response type relationship between blood flow stimuli and the expression of cardiac phenotypes. Constricting the outflow tract by 10-35% led predominantly to ventricular septal defects, whereas constricting by 35-60% most often led to double outlet right ventricle. Ligation of the vitelline vein caused mostly pharyngeal arch artery malformations. We show that both cardiac inflow reduction and graded outflow constriction strongly influence the development of specific and persistent abnormal cardiac structure and function. Moreover, the hemodynamic-associated cardiac defects recapitulate those caused by genetic disorders. Thus our data demonstrate the importance of investigating embryonic blood flow conditions to understand the root causes of congenital heart disease as a prerequisite to future prevention and treatment. NEW & NOTEWORTHY Congenital heart defects result from genetic anomalies, teratogen exposure, and altered blood flow during embryonic development. We show here a novel "dose-response" type relationship between the level of blood flow alteration and manifestation of specific cardiac phenotypes. We speculate that abnormal blood flow may frequently underlie congenital heart defects. Copyright © 2017 the American Physiological Society.

  17. A Population Genomics Approach to Assessing the Genetic Basis of Within-Host Microevolution Underlying Recurrent Cryptococcal Meningitis Infection

    Directory of Open Access Journals (Sweden)

    Johanna Rhodes

    2017-04-01

    Full Text Available Recurrence of meningitis due to Cryptococcus neoformans after treatment causes substantial mortality in HIV/AIDS patients across sub-Saharan Africa. In order to determine whether recurrence occurred due to relapse of the original infecting isolate or reinfection with a different isolate weeks or months after initial treatment, we used whole-genome sequencing (WGS to assess the genetic basis of infection in 17 HIV-infected individuals with recurrent cryptococcal meningitis (CM. Comparisons revealed a clonal relationship for 15 pairs of isolates recovered before and after recurrence showing relapse of the original infection. The two remaining pairs showed high levels of genetic heterogeneity; in one pair we found this to be a result of infection by mixed genotypes, while the second was a result of nonsense mutations in the gene encoding the DNA mismatch repair proteins MSH2, MSH5, and RAD5. These nonsense mutations led to a hypermutator state, leading to dramatically elevated rates of synonymous and nonsynonymous substitutions. Hypermutator phenotypes owing to nonsense mutations in these genes have not previously been reported in C. neoformans, and represent a novel pathway for rapid within-host adaptation and evolution of resistance to first-line antifungal drugs.

  18. A Population Genomics Approach to Assessing the Genetic Basis of Within-Host Microevolution Underlying Recurrent Cryptococcal Meningitis Infection.

    Science.gov (United States)

    Rhodes, Johanna; Beale, Mathew A; Vanhove, Mathieu; Jarvis, Joseph N; Kannambath, Shichina; Simpson, John A; Ryan, Anthea; Meintjes, Graeme; Harrison, Thomas S; Fisher, Matthew C; Bicanic, Tihana

    2017-04-03

    Recurrence of meningitis due to Cryptococcus neoformans after treatment causes substantial mortality in HIV/AIDS patients across sub-Saharan Africa. In order to determine whether recurrence occurred due to relapse of the original infecting isolate or reinfection with a different isolate weeks or months after initial treatment, we used whole-genome sequencing (WGS) to assess the genetic basis of infection in 17 HIV-infected individuals with recurrent cryptococcal meningitis (CM). Comparisons revealed a clonal relationship for 15 pairs of isolates recovered before and after recurrence showing relapse of the original infection. The two remaining pairs showed high levels of genetic heterogeneity; in one pair we found this to be a result of infection by mixed genotypes, while the second was a result of nonsense mutations in the gene encoding the DNA mismatch repair proteins MSH2 , MSH5 , and RAD5 These nonsense mutations led to a hypermutator state, leading to dramatically elevated rates of synonymous and nonsynonymous substitutions. Hypermutator phenotypes owing to nonsense mutations in these genes have not previously been reported in C. neoformans , and represent a novel pathway for rapid within-host adaptation and evolution of resistance to first-line antifungal drugs. Copyright © 2017 Rhodes et al.

  19. Genetic Diversity Underlying the Envelope Glycoproteins of Hepatitis C Virus: Structural and Functional Consequences and the Implications for Vaccine Design

    Directory of Open Access Journals (Sweden)

    Alexander W. Tarr

    2015-07-01

    Full Text Available In the 26 years since the discovery of Hepatitis C virus (HCV a major global research effort has illuminated many aspects of the viral life cycle, facilitating the development of targeted antivirals. Recently, effective direct-acting antiviral (DAA regimens with >90% cure rates have become available for treatment of chronic HCV infection in developed nations, representing a significant advance towards global eradication. However, the high cost of these treatments results in highly restricted access in developing nations, where the disease burden is greatest. Additionally, the largely asymptomatic nature of infection facilitates continued transmission in at risk groups and resource constrained settings due to limited surveillance. Consequently a prophylactic vaccine is much needed. The HCV envelope glycoproteins E1 and E2 are located on the surface of viral lipid envelope, facilitate viral entry and are the targets for host immunity, in addition to other functions. Unfortunately, the extreme global genetic and antigenic diversity exhibited by the HCV glycoproteins represents a significant obstacle to vaccine development. Here we review current knowledge of HCV envelope protein structure, integrating knowledge of genetic, antigenic and functional diversity to inform rational immunogen design.

  20. Genetic progress in the UNB-2U population of popcorn under recurrent selection in Rio de Janeiro, Brazil.

    Science.gov (United States)

    Ribeiro, R M; do Amaral Júnior, A T; Gonçalves, L S A; Candido, L S; Silva, T R C; Pena, G F

    2012-05-15

    As part of the Universidade Estadual do Norte Fluminense recurrent selection program of popcorn, we evaluated full-sib families of the sixth cycle of recurrent selection and estimated genetic progress for grain yield and expansion capacity. We assessed 200 full-sib families for 10 agronomic traits, in a randomized block design, with two replications within sets in two environments: Campos dos Goytacazes and Itaocara, in the State of Rio de Janeiro, Brazil. There were significant differences for families/"sets" for all traits, indicating genetic variability that could be exploited in future cycles. In the selection of superior progenies, the Mulamba and Mock index gave the best gains for popping expansion (PE) and grain yield (GY), with values of 10.97 and 15.30%, respectively, using random economic weights. By comparing the evolution of the means obtained for PE and GY in the cycles C(0), C(1), C(2), C(3), C(4), C(5), and predicted for C(6), a steady increase was observed for both PE and GY, with the addition of 1.71 mL/g (R(2) = 0.93) and 192.87 kg/ha (R(2) = 0.88), respectively, in each cycle. Given the good performance of this popcorn population in successive cycles of intrapopulation recurrent selection, we expect that a productive variety with high expansion capacity will soon be available for producers in the north and northwest regions of Rio de Janeiro State, Brazil.

  1. Application of the distributed genetic algorithm for in-core fuel optimization problems under parallel computational environment

    International Nuclear Information System (INIS)

    Yamamoto, Akio; Hashimoto, Hiroshi

    2002-01-01

    The distributed genetic algorithm (DGA) is applied for loading pattern optimization problems of the pressurized water reactors. A basic concept of DGA follows that of the conventional genetic algorithm (GA). However, DGA equally distributes candidates of solutions (i.e. loading patterns) to several independent ''islands'' and evolves them in each island. Communications between islands, i.e. migrations of some candidates between islands are performed with a certain period. Since candidates of solutions independently evolve in each island while accepting different genes of migrants, premature convergence in the conventional GA can be prevented. Because many candidate loading patterns should be evaluated in GA or DGA, the parallelization is efficient to reduce turn around time. Parallel efficiency of DGA was measured using our optimization code and good efficiency was attained even in a heterogeneous cluster environment due to dynamic distribution of the calculation load. The optimization code is based on the client/server architecture with the TCP/IP native socket and a client (optimization) module and calculation server modules communicate the objects of loading patterns each other. Throughout the sensitivity study on optimization parameters of DGA, a suitable set of the parameters for a test problem was identified. Finally, optimization capability of DGA and the conventional GA was compared in the test problem and DGA provided better optimization results than the conventional GA. (author)

  2. Single Ventricle Defects

    Science.gov (United States)

    ... heart defects along with pulmonary atresia. (Children with tetralogy of Fallot who also have pulmonary atresia may have treatment similar to others with tetralogy of Fallot.) How does it affect the heart? An opening ...

  3. Repairing Nanoparticle Surface Defects

    NARCIS (Netherlands)

    Marino, Emanuele; Kodger, Thomas E.; Crisp, R.W.; Timmerman, Dolf; MacArthur, Katherine E.; Heggen, Marc; Schall, Peter

    2017-01-01

    Solar devices based on semiconductor nanoparticles require the use of conductive ligands; however, replacing the native, insulating ligands with conductive metal chalcogenide complexes introduces structural defects within the crystalline nanostructure that act as traps for charge carriers. We

  4. Neural tube defects

    Directory of Open Access Journals (Sweden)

    M.E. Marshall

    1981-09-01

    Full Text Available Neural tube defects refer to any defect in the morphogenesis of the neural tube, the most common types being spina bifida and anencephaly. Spina bifida has been recognised in skeletons found in north-eastern Morocco and estimated to have an age of almost 12 000 years. It was also known to the ancient Greek and Arabian physicians who thought that the bony defect was due to the tumour. The term spina bifida was first used by Professor Nicolai Tulp of Amsterdam in 1652. Many other terms have been used to describe this defect, but spina bifida remains the most useful general term, as it describes the separation of the vertebral elements in the midline.

  5. Working Towards a Risk Prediction Model for Neural Tube Defects

    Science.gov (United States)

    Agopian, A.J.; Lupo, Philip J.; Tinker, Sarah C.; Canfield, Mark A.; Mitchell, Laura E.

    2015-01-01

    BACKGROUND Several risk factors have been consistently associated with neural tube defects (NTDs). However, the predictive ability of these risk factors in combination has not been evaluated. METHODS To assess the predictive ability of established risk factors for NTDs, we built predictive models using data from the National Birth Defects Prevention Study, which is a large, population-based study of nonsyndromic birth defects. Cases with spina bifida or anencephaly, or both (n = 1239), and controls (n = 8494) were randomly divided into separate training (75% of cases and controls) and validation (remaining 25%) samples. Multivariable logistic regression models were constructed with the training samples. The predictive ability of these models was evaluated in the validation samples by assessing the area under the receiver operator characteristic curves. An ordinal predictive risk index was also constructed and evaluated. In addition, the ability of classification and regression tree (CART) analysis to identify subgroups of women at increased risk for NTDs in offspring was evaluated. RESULTS The predictive ability of the multivariable models was poor (area under the receiver operating curve: 0.55 for spina bifida only, 0.59 for anencephaly only, and 0.56 for anencephaly and spina bifida combined). The predictive abilities of the ordinal risk indexes and CART models were also low. CONCLUSION Current established risk factors for NTDs are insufficient for population-level prediction of a women’s risk for having affected offspring. Identification of genetic risk factors and novel nongenetic risk factors will be critical to establishing models, with good predictive ability, for NTDs. PMID:22253139

  6. [Fetal atrioventricular septal defect associated with Patau and Edwards syndromes, as well as trisomy 22].

    Science.gov (United States)

    Cesko, I; Hajdú, J; Marton, T; Tóth-Pál, E; Papp, C; Papp, Z

    1998-05-03

    The atrioventricular septal defect is usually associated with trisomy 21 and it may be observed in the heterotaxia syndromes. Atrioventricular septal defect may be associated with 8p deletion. There are reported cases of familial atrioventricular septal defect. Atrioventicular septal defect is rarely associated with other chromosomal abnormalities. We are reporting three unusual cases of atrioventricular septal defect that were associated with trisomy 13, 18 and 22. This association may be due to effect of genetic loci on the 13, 18 and 22 chromosome which could play the role in the development and fusion of endocardial cushion and atrioventricular septal defect.

  7. Defects in medical X-ray equipment

    International Nuclear Information System (INIS)

    Eder, H.; Wahl, H.; Troeger, W.

    1979-01-01

    A careful estimate of the effects on the genetically significant radiation load shows that it is in the same order of magnitude as the increase in the skin dose area product. This is to say that of the genetically significant radiation dose of about 500 mJ/kg (50 mrem) per year and person due to medical X-ray diagnostics, about 75 mJ/kg (7.5 mrem) are due to serious defects in X-ray equipment. (orig.) [de

  8. Point defects dynamics in a stress field

    International Nuclear Information System (INIS)

    Smetniansky de De Grande, Nelida.

    1989-01-01

    The dependence of anisotropic defect diffusion on stress is studied for a hexagonal close packed (hcp) material under irradiation and uniaxially stressed. The diffusion is described as a discrete process of thermally activated jumps. It is shown that the presence of an external stress field enhances the intrinsic anisotropic diffusion, being this variation determined by the defect dipole tensors' symmetry in the equilibrium and saddle point configurations. Also, the point defect diffusion equations to sinks, like edge dislocations and spherical cavities, are solved and the sink strengths are calculated. The conclusion is that the dynamics of the interaction between defects and sinks is controlled by the changes in diffusivity induced by stress fields. (Author) [es

  9. Selection for long and short sleep duration in Drosophila melanogaster reveals the complex genetic network underlying natural variation in sleep.

    Science.gov (United States)

    Harbison, Susan T; Serrano Negron, Yazmin L; Hansen, Nancy F; Lobell, Amanda S

    2017-12-01

    Why do some individuals need more sleep than others? Forward mutagenesis screens in flies using engineered mutations have established a clear genetic component to sleep duration, revealing mutants that convey very long or short sleep. Whether such extreme long or short sleep could exist in natural populations was unknown. We applied artificial selection for high and low night sleep duration to an outbred population of Drosophila melanogaster for 13 generations. At the end of the selection procedure, night sleep duration diverged by 9.97 hours in the long and short sleeper populations, and 24-hour sleep was reduced to 3.3 hours in the short sleepers. Neither long nor short sleeper lifespan differed appreciably from controls, suggesting little physiological consequences to being an extreme long or short sleeper. Whole genome sequence data from seven generations of selection revealed several hundred thousand changes in allele frequencies at polymorphic loci across the genome. Combining the data from long and short sleeper populations across generations in a logistic regression implicated 126 polymorphisms in 80 candidate genes, and we confirmed three of these genes and a larger genomic region with mutant and chromosomal deficiency tests, respectively. Many of these genes could be connected in a single network based on previously known physical and genetic interactions. Candidate genes have known roles in several classic, highly conserved developmental and signaling pathways-EGFR, Wnt, Hippo, and MAPK. The involvement of highly pleiotropic pathway genes suggests that sleep duration in natural populations can be influenced by a wide variety of biological processes, which may be why the purpose of sleep has been so elusive.

  10. Dissection of Genetic Factors underlying Wheat Kernel Shape and Size in an Elite × Nonadapted Cross using a High Density SNP Linkage Map

    Directory of Open Access Journals (Sweden)

    Ajay Kumar

    2016-03-01

    Full Text Available Wheat kernel shape and size has been under selection since early domestication. Kernel morphology is a major consideration in wheat breeding, as it impacts grain yield and quality. A population of 160 recombinant inbred lines (RIL, developed using an elite (ND 705 and a nonadapted genotype (PI 414566, was extensively phenotyped in replicated field trials and genotyped using Infinium iSelect 90K assay to gain insight into the genetic architecture of kernel shape and size. A high density genetic map consisting of 10,172 single nucleotide polymorphism (SNP markers, with an average marker density of 0.39 cM/marker, identified a total of 29 genomic regions associated with six grain shape and size traits; ∼80% of these regions were associated with multiple traits. The analyses showed that kernel length (KL and width (KW are genetically independent, while a large number (∼59% of the quantitative trait loci (QTL for kernel shape traits were in common with genomic regions associated with kernel size traits. The most significant QTL was identified on chromosome 4B, and could be an ortholog of major rice grain size and shape gene or . Major and stable loci also were identified on the homeologous regions of Group 5 chromosomes, and in the regions of (6A and (7A genes. Both parental genotypes contributed equivalent positive QTL alleles, suggesting that the nonadapted germplasm has a great potential for enhancing the gene pool for grain shape and size. This study provides new knowledge on the genetic dissection of kernel morphology, with a much higher resolution, which may aid further improvement in wheat yield and quality using genomic tools.

  11. Arlequin suite ver 3.5: a new series of programs to perform population genetics analyses under Linux and Windows.

    Science.gov (United States)

    Excoffier, Laurent; Lischer, Heidi E L

    2010-05-01

    We present here a new version of the Arlequin program available under three different forms: a Windows graphical version (Winarl35), a console version of Arlequin (arlecore), and a specific console version to compute summary statistics (arlsumstat). The command-line versions run under both Linux and Windows. The main innovations of the new version include enhanced outputs in XML format, the possibility to embed graphics displaying computation results directly into output files, and the implementation of a new method to detect loci under selection from genome scans. Command-line versions are designed to handle large series of files, and arlsumstat can be used to generate summary statistics from simulated data sets within an Approximate Bayesian Computation framework. © 2010 Blackwell Publishing Ltd.

  12. Influence of genetic diversity on cause and effect relationships in lens culinaris germplasm under rain-fed eco-agricultural system

    International Nuclear Information System (INIS)

    Ilyas, M.; Arshad, M.; Ghafoor, A.

    2014-01-01

    Due to emerging demands of organic foods, lentil, one of the most primitive legumes was investigated for genetic diversity including cause and effect relationships among various clusters under eco-agricultural system. The 73 lentil genotypes were investigated for qualitative and quantitative traits to identify the potential lines under rain-fed conditions for organic farming using no chemical fertilizers for crop production. Variation existed for all the qualitative traits including orange cotyledon colour in 27 genotypes which is a preferred trait by Asian consumers including Pakistan. Five clusters revealed that average intra-clusters distances were more or less similar, whereas inter-cluster distance indicated higher level of genetic diversity. First three PCs contributed more than 3/4 of the variability and the results were in coordination with clustering pattern amongst 73 genotypes. The populations contributing the first PC were late in maturity possessed higher number of branches, pods, better biomass and grain yield. The PC/sub 2/ was more contributed by seeds pod-1 and seed diameter, whereas pod length and harvest index contributed 13% variability. The cause and effect relationships indicated differential response for selection of lentil genotypes suitable for eco-agricultural system within each cluster. (author)

  13. Anomalous rapid defect annihilation in self-assembled nanopatterns by defect melting.

    Science.gov (United States)

    Kim, Bong Hoon; Park, So Jung; Jin, Hyeong Min; Kim, Ju Young; Son, Seung-Woo; Kim, Myung-Hyun; Koo, Chong Min; Shin, Jonghwa; Kim, Jaeup U; Kim, Sang Ouk

    2015-02-11

    Molecular self-assembly commonly suffers from dense structural defect formation. Spontaneous defect annihilation in block copolymer (BCP) self-assembly is particularly retarded due to significant energy barrier for polymer chain diffusion and structural reorganization. Here we present localized defect melting induced by blending short neutral random copolymer chain as an unusual method to promote the defect annihilation in BCP self-assembled nanopatterns. Chemically neutral short random copolymer chains blended with BCPs are specifically localized and induce local disordered states at structural defect sites in the self-assembled nanopatterns. Such localized "defect melting" relieves the energy penalty for polymer diffusion and morphology reorganization such that spontaneous defect annihilation by mutual coupling is anomalously accelerated upon thermal annealing. Interestingly, neutral random copolymer chain blending also causes morphology-healing self-assembly behavior that can generate large-area highly ordered 10 nm scale nanopattern even upon poorly defined defective prepatterns. Underlying mechanisms of the unusual experimental findings are thoroughly investigated by three-dimensional self-consistent field theory calculation.

  14. Defect sizing using automated ultrasonic inspection techniques at RNL

    International Nuclear Information System (INIS)

    Rogerson, A.; Highmore, P.J.; Poulter, L.N.J.

    1983-10-01

    RNL has developed and applied automated wide-beam pulse-echo and time-of-flight techniques with synthetic aperture processing for sizing defects in clad thick-section weldments and nozzle corner regions. These techniques were amongst those used in the four test plate inspections making up the UKAEA Defect Detection Trials. In this report a critical appraisal is given of the sizing procedures adopted by RNL in these inspections. Several factors influencing sizing accuracy are discussed and results from particular defects highlighted. The time-of-flight technique with colour graphics data display is shown to be highly effective in imaging near-vertical buried defects and underclad defects of height greater than 5 mm. Early characterisation of any identified defect from its ultrasonic response under pulse-echo inspection is seen as a desirable aid to the selection of an appropriate advanced sizing technique for buried defects. (author)

  15. Structure Defect Property Relationships in Binary Intermetallics

    Science.gov (United States)

    Medasani, Bharat; Ding, Hong; Chen, Wei; Persson, Kristin; Canning, Andrew; Haranczyk, Maciej; Asta, Mark

    2015-03-01

    Ordered intermetallics are light weight materials with technologically useful high temperature properties such as creep resistance. Knowledge of constitutional and thermal defects is required to understand these properties. Vacancies and antisites are the dominant defects in the intermetallics and their concentrations and formation enthalpies could be computed by using first principles density functional theory and thermodynamic formalisms such as dilute solution method. Previously many properties of the intermetallics such as melting temperatures and formation enthalpies were statistically analyzed for large number of intermetallics using structure maps and data mining approaches. We undertook a similar exercise to establish the dependence of the defect properties in binary intermetallics on the underlying structural and chemical composition. For more than 200 binary intermetallics comprising of AB, AB2 and AB3 structures, we computed the concentrations and formation enthalpies of vacancies and antisites in a small range of stoichiometries deviating from ideal stoichiometry. The calculated defect properties were datamined to gain predictive capabilities of defect properties as well as to classify the intermetallics for their suitability in high-T applications. Supported by the US DOE under Contract No. DEAC02-05CH11231 under the Materials Project Center grant (Award No. EDCBEE).

  16. Modeling of constructed wetland performance in BOD5removal for domestic wastewater under changes in relative humidity using genetic programming.

    Science.gov (United States)

    Sankararajan, Vanitha; Neelakandhan, Nampoothiri; Chandrasekaran, Sivapragasam

    2017-04-01

    Despite the extensive use of constructed wetland (CW) as an effective method for domestic wastewater treatment, there is lack of clarity in arriving at well-defined design guidelines. This is particularly due to the fact that the design of CW is dependent on many inter-connected parameters which interact in a complex manner. Consequently, different researchers in the past have tried to address different aspects of this complexity. In this study, an attempt is made to model the influence of relative humidity (RH) in the effectiveness of BOD 5 removal. Since it is an accepted fact that plants respond to change in humidity, it is necessary to take this parameter into consideration particularly when the CW is to be designed involving changes in relative humidity over a shorter time horizon (say a couple of months). This study reveals that BOD 5out depends on the ratio of BOD 5in and relative humidity. An attempt is also made to model the outlet BOD 5 using genetic programming with inlet BOD 5 and relative humidity as input parameters.

  17. Estimating genetic potential of biofuel forest hardwoods to withstand metal toxicity in industrial effluent under dry tropical conditions.

    Science.gov (United States)

    Manzoor, S A; Mirza, S N; Zubair, M; Nouman, W; Hussain, S B; Mehmood, S; Irshad, A; Sarwar, N; Ammar, A; Iqbal, M F; Asim, A; Chattha, M U; Chattha, M B; Zafar, A; Abid, R

    2015-08-14

    Biofuel tree species are recognized as a promising alternative source of fuel to conventional forms. Additionally, these tree species are also effective in accumulating toxic heavy metals present in some industrial effluents. In developing countries such as Pakistan, the use of biofuel tree species is gaining popularity not only for harvesting economical and environmentally friendly biofuel, but also to sequester poisonous heavy metals from industrial wastewater. This study was aimed at evaluating the genetic potential of two biofuel species, namely, Jatropha curcas and Pongamia pinnata, to grow when irrigated with industrial effluent from the Pak-Arab Fertilizer Factory Multan, Southern Punjab, Pakistan. The growth performances of one-year-old seedlings of both species were compared in soil with adverse physiochemical properties. It was found that J. curcas was better able to withstand the toxicity of the heavy metals present in the fertilizer factory effluent. J. curcas showed maximum gain in height, diameter, and biomass production in soil irrigated with 75% concentrated industrial effluent. In contrast, P. pinnata showed a significant reduction in growth in soil irrigated with more than 50% concentrated industrial effluent, indicating that this species is less tolerant to higher toxicity levels of industrial effluent. This study identifies J. curcas as a promising biofuel tree species that can be grown using industrial wastewater.

  18. Genetic variants associated with the root system architecture of oilseed rape (Brassica napus L.) under contrasting phosphate supply.

    Science.gov (United States)

    Wang, Xiaohua; Chen, Yanling; Thomas, Catherine L; Ding, Guangda; Xu, Ping; Shi, Dexu; Grandke, Fabian; Jin, Kemo; Cai, Hongmei; Xu, Fangsen; Yi, Bin; Broadley, Martin R; Shi, Lei

    2017-08-01

    Breeding crops with ideal root system architecture for efficient absorption of phosphorus is an important strategy to reduce the use of phosphate fertilizers. To investigate genetic variants leading to changes in root system architecture, 405 oilseed rape cultivars were genotyped with a 60K Brassica Infinium SNP array in low and high P environments. A total of 285 single-nucleotide polymorphisms were associated with root system architecture traits at varying phosphorus levels. Nine single-nucleotide polymorphisms corroborate a previous linkage analysis of root system architecture quantitative trait loci in the BnaTNDH population. One peak single-nucleotide polymorphism region on A3 was associated with all root system architecture traits and co-localized with a quantitative trait locus for primary root length at low phosphorus. Two more single-nucleotide polymorphism peaks on A5 for root dry weight at low phosphorus were detected in both growth systems and co-localized with a quantitative trait locus for the same trait. The candidate genes identified on A3 form a haplotype 'BnA3Hap', that will be important for understanding the phosphorus/root system interaction and for the incorporation into Brassica napus breeding programs. © The Author 2017. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

  19. [Extending preimplantation genetic diagnosis to HLA typing: the Paris experience].

    Science.gov (United States)

    Steffann, J; Frydman, N; Burlet, P; Gigarel, N; Feyereisen, E; Kerbrat, V; Tachdjian, G; Munnich, A; Frydman, R

    2005-10-01

    Preimplantation genetic diagnosis (PGD) consists in the genetic analysis of one or two cells. These cells (blastomeres) are sampled from embryos, obtained by in vitro fertilization, at the third day of development. Since 1998, the bioethical laws (1994) and their decrees restricted PGD practices in France, strictly to the avoidance of the birth of a child affected with a genetic defect. In parallel, works on blood cord transplantation, taken at the birth of a compatible HLA sibling, showed very encouraging results, particularly for the treatment of Fanconi anemia. In 2001, Verlinsky et al., have reported the first PGD for Fanconi anaemia combined with HLA typing, allowing the birth of a healthy child, HLA-identical with his affected sister. The "designer baby" concept was born. The French law, which allowed PGD under specific conditions, i.e. when the genetic defect has been characterized in one parent at least, recently extended PGD to HLA typing when embryos are at risk of a genetic disorder. Article L.2131-4-1 (August 2004) allows the practice of HLA typing for PGD embryos when an elder sibling is affected with a genetic disorder and need stem cell transplantation. The HLA-matched offspring resulting from PGD can give cord blood at birth to supply the necessary therapy. This double selection give rise to serious ethical problems, but technical difficulties and legal restrictions will probably limit the development of such a procedure.

  20. Defects in middle ear cavitation cause conductive hearing loss in the Tcof1 mutant mouse.

    Science.gov (United States)

    Richter, Carol A; Amin, Susan; Linden, Jennifer; Dixon, Jill; Dixon, Michael J; Tucker, Abigail S

    2010-04-15

    Conductive hearing loss (CHL) is one of the most common forms of human deafness. Despite this observation, a surprising gap in our understanding of the mechanisms underlying CHL remains, particularly with respect to the molecular mechanisms underlying middle ear development and disease. Treacher Collins syndrome (TCS) is an autosomal dominant disorder of facial development that results from mutations in the gene TCOF1. CHL is a common feature of TCS but the causes of the hearing defect have not been studied. In this study, we have utilized Tcof1 mutant mice to dissect the developmental mechanisms underlying CHL. Our results demonstrate that effective cavitation of the middle ear is intimately linked to growth of the auditory bulla, the neural crest cell-derived structure that encapsulates all middle ear components, and that defects in these processes have a profoundly detrimental effect on hearing. This research provides important insights into a poorly characterized cause of human deafness, and provides the first mouse model for the study of middle ear cavity defects, while also being of direct relevance to a human genetic disorder.

  1. DEFECTS SIMULATION OF ROLLING STRIP

    OpenAIRE

    Rudolf Mišičko; Tibor Kvačkaj; Martin Vlado; Lucia Gulová; Miloslav Lupták; Jana Bidulská

    2009-01-01

    The defects in the continuous casting slabs can be developed or kept down in principle by rolling technology, especially depend to sort, size and distribution of primary defects, as well as used of rolling parameters. Scope of the article is on observation behavior artificial surface and undersurface defects (scores) without filler (surface defects) and filling by oxides and casting powder (subsurface defects). First phase of hot rolling process have been done by software simulation DEFORM 3D...

  2. Defective Glycinergic Synaptic Transmission in Zebrafish Motility Mutants

    OpenAIRE

    Hirata, Hiromi; Carta, Eloisa; Yamanaka, Iori; Harvey, Robert J.; Kuwada, John Y.

    2010-01-01

    Glycine is a major inhibitory neurotransmitter in the spinal cord and brainstem. Recently, in vivo analysis of glycinergic synaptic transmission has been pursued in zebrafish using molecular genetics. An ENU mutagenesis screen identified two behavioral mutants that are defective in glycinergic synaptic transmission. Zebrafish bandoneon (beo) mutants have a defect in glrbb, one of the duplicated glycine receptor (GlyR) β subunit genes. These mutants exhibit a loss of glycinergic synaptic ...

  3. Quantum computing with defects

    Science.gov (United States)

    Varley, Joel

    2011-03-01

    The development of a quantum computer is contingent upon the identification and design of systems for use as qubits, the basic units of quantum information. One of the most promising candidates consists of a defect in diamond known as the nitrogen-vacancy (NV-1) center, since it is an individually-addressable quantum system that can be initialized, manipulated, and measured with high fidelity at room temperature. While the success of the NV-1 stems from its nature as a localized ``deep-center'' point defect, no systematic effort has been made to identify other defects that might behave in a similar way. We provide guidelines for identifying other defect centers with similar properties. We present a list of physical criteria that these centers and their hosts should meet and explain how these requirements can be used in conjunction with electronic structure theory to intelligently sort through candidate systems. To elucidate these points, we compare electronic structure calculations of the NV-1 center in diamond with those of several deep centers in 4H silicon carbide (SiC). Using hybrid functionals, we report formation energies, configuration-coordinate diagrams, and defect-level diagrams to compare and contrast the properties of these defects. We find that the NC VSi - 1 center in SiC, a structural analog of the NV-1 center in diamond, may be a suitable center with very different optical transition energies. We also discuss how the proposed criteria can be translated into guidelines to discover NV analogs in other tetrahedrally coordinated materials. This work was performed in collaboration with J. R. Weber, W. F. Koehl, B. B. Buckley, A. Janotti, C. G. Van de Walle, and D. D. Awschalom. This work was supported by ARO, AFOSR, and NSF.

  4. The plant pathogen Pseudomonas syringae pv. tomato is genetically monomorphic and under strong selection to evade tomato immunity.

    Directory of Open Access Journals (Sweden)

    Rongman Cai

    2011-08-01

    Full Text Available Recently, genome sequencing of many isolates of genetically monomorphic bacterial human pathogens has given new insights into pathogen microevolution and phylogeography. Here, we report a genome-based micro-evolutionary study of a bacterial plant pathogen, Pseudomonas syringae pv. tomato. Only 267 mutations were identified between five sequenced isolates in 3,543,009 nt of analyzed genome sequence, which suggests a recent evolutionary origin of this pathogen. Further analysis with genome-derived markers of 89 world-wide isolates showed that several genotypes exist in North America and in Europe indicating frequent pathogen movement between these world regions. Genome-derived markers and molecular analyses of key pathogen loci important for virulence and motility both suggest ongoing adaptation to the tomato host. A mutational hotspot was found in the type III-secreted effector gene hopM1. These mutations abolish the cell death triggering activity of the full-length protein indicating strong selection for loss of function of this effector, which was previously considered a virulence factor. Two non-synonymous mutations in the flagellin-encoding gene fliC allowed identifying a new microbe associated molecular pattern (MAMP in a region distinct from the known MAMP flg22. Interestingly, the ancestral allele of this MAMP induces a stronger tomato immune response than the derived alleles. The ancestral allele has largely disappeared from today's Pto populations suggesting that flagellin-triggered immunity limits pathogen fitness even in highly virulent pathogens. An additional non-synonymous mutation was identified in flg22 in South American isolates. Therefore, MAMPs are more variable than expected differing even between otherwise almost identical isolates of the same pathogen strain.

  5. COE loss-of-function analysis reveals a genetic program underlying maintenance and regeneration of the nervous system in planarians.

    Directory of Open Access Journals (Sweden)

    Martis W Cowles

    2014-10-01

    Full Text Available Members of the COE family of transcription factors are required for central nervous system (CNS development. However, the function of COE in the post-embryonic CNS remains largely unknown. An excellent model for investigating gene function in the adult CNS is the freshwater planarian. This animal is capable of regenerating neurons from an adult pluripotent stem cell population and regaining normal function. We previously showed that planarian coe is expressed in differentiating and mature neurons and that its function is required for proper CNS regeneration. Here, we show that coe is essential to maintain nervous system architecture and patterning in intact (uninjured planarians. We took advantage of the robust phenotype in intact animals to investigate the genetic programs coe regulates in the CNS. We compared the transcriptional profiles of control and coe RNAi planarians using RNA sequencing and identified approximately 900 differentially expressed genes in coe knockdown animals, including 397 downregulated genes that were enriched for nervous system functional annotations. Next, we validated a subset of the downregulated transcripts by analyzing their expression in coe-deficient planarians and testing if the mRNAs could be detected in coe+ cells. These experiments revealed novel candidate targets of coe in the CNS such as ion channel, neuropeptide, and neurotransmitter genes. Finally, to determine if loss of any of the validated transcripts underscores the coe knockdown phenotype, we knocked down their expression by RNAi and uncovered a set of coe-regulated genes implicated in CNS regeneration and patterning, including orthologs of sodium channel alpha-subunit and pou4. Our study broadens the knowledge of gene expression programs regulated by COE that are required for maintenance of neural subtypes and nervous system architecture in adult animals.

  6. COE loss-of-function analysis reveals a genetic program underlying maintenance and regeneration of the nervous system in planarians.

    Science.gov (United States)

    Cowles, Martis W; Omuro, Kerilyn C; Stanley, Brianna N; Quintanilla, Carlo G; Zayas, Ricardo M

    2014-10-01

    Members of the COE family of transcription factors are required for central nervous system (CNS) development. However, the function of COE in the post-embryonic CNS remains largely unknown. An excellent model for investigating gene function in the adult CNS is the freshwater planarian. This animal is capable of regenerating neurons from an adult pluripotent stem cell population and regaining normal function. We previously showed that planarian coe is expressed in differentiating and mature neurons and that its function is required for proper CNS regeneration. Here, we show that coe is essential to maintain nervous system architecture and patterning in intact (uninjured) planarians. We took advantage of the robust phenotype in intact animals to investigate the genetic programs coe regulates in the CNS. We compared the transcriptional profiles of control and coe RNAi planarians using RNA sequencing and identified approximately 900 differentially expressed genes in coe knockdown animals, including 397 downregulated genes that were enriched for nervous system functional annotations. Next, we validated a subset of the downregulated transcripts by analyzing their expression in coe-deficient planarians and testing if the mRNAs could be detected in coe+ cells. These experiments revealed novel candidate targets of coe in the CNS such as ion channel, neuropeptide, and neurotransmitter genes. Finally, to determine if loss of any of the validated transcripts underscores the coe knockdown phenotype, we knocked down their expression by RNAi and uncovered a set of coe-regulated genes implicated in CNS regeneration and patterning, including orthologs of sodium channel alpha-subunit and pou4. Our study broadens the knowledge of gene expression programs regulated by COE that are required for maintenance of neural subtypes and nervous system architecture in adult animals.

  7. Reduction in Defect Content of ODS Alloys

    Energy Technology Data Exchange (ETDEWEB)

    Ritherdon, J

    2001-05-15

    The work detailed within this report is a continuation of earlier work carried out under contract number 1DX-SY382V. The earlier work comprises a literature review of the sources and types of defects found principally in Fe-based ODS alloys as well as experimental work designed to identify defects in the prototype ODS-Fe{sub 3}Al alloy, deduce their origins and to recommend methods of defect reduction. The present work is an extension of the experimental work already reported and concentrates on means of reduction of defects already identified rather than the search for new defect types. This report also includes results gathered during powder separation trials, conducted by the University of Groningen, Netherlands and coordinated by the University of Liverpool, involving the separation of different metallic powders in terms of their differing densities. The scope and objectives of the present work were laid out in the technical proposal ''Reduction in Defect Content in ODS Alloys-III''. All the work proposed in the ''Statement of Work'' section of the technical proposal has been carried out and all work extra to the ''Statement of Work'' falls within the context of an ODS-Fe{sub 3}Al alloy of improved overall quality and potential creep performance in the consolidated form. The outturn of the experimental work performed is reported in the following sections.

  8. Structure defects in cementite

    International Nuclear Information System (INIS)

    Schmitt, Bernard

    1971-01-01

    After a presentation of experimental techniques (elaboration principles, elaboration techniques, and investigation techniques for cementite thin layers and iron-carbon massive alloys), the author of this research thesis reports the study of cementite structure (interatomic distance, description and representation), reports the study of iron-carbon thin layers (structure, influence of silicon, defects), reports the study of perfect and imperfect dislocations and of plane defects in cementite. The author also reports hardness measurements, and discusses the relationships between cementite and other iron carbides

  9. On the use of genetic algorithm to optimize industrial assets lifecycle management under safety and budget constraints

    International Nuclear Information System (INIS)

    Lonchampt, J.; Fessart, K.

    2013-01-01

    The purpose of this paper is to describe the method and tool dedicated to optimize investments planning for industrial assets. These investments may either be preventive maintenance tasks, asset enhancements or logistic investments such as spare parts purchases. The two methodological points to investigate in such an issue are: 1. The measure of the profitability of a portfolio of investments 2. The selection and planning of an optimal set of investments 3. The measure of the risk of a portfolio of investments The measure of the profitability of a set of investments in the IPOP tool is synthesised in the Net Present Value indicator. The NPV is the sum of the differences of discounted cash flows (direct costs, forced outages...) between the situations with and without a given investment. These cash flows are calculated through a pseudo-Markov reliability model representing independently the components of the industrial asset and the spare parts inventories. The component model has been widely discussed over the years but the spare part model is a new one based on some approximations that will be discussed. This model, referred as the NPV function, takes for input an investments portfolio and gives its NPV. The second issue is to optimize the NPV. If all investments were independent, this optimization would be an easy calculation, unfortunately there are two sources of dependency. The first one is introduced by the spare part model, as if components are indeed independent in their reliability model, the fact that several components use the same inventory induces a dependency. The second dependency comes from economic, technical or logistic constraints, such as a global maintenance budget limit or a safety requirement limiting the residual risk of failure of a component or group of component, making the aggregation of individual optimum not necessary feasible. The algorithm used to solve such a difficult optimization problem is a genetic algorithm. After a description

  10. Genetic evidence that induction of root Fe(III) chelate reductase activity is necessary for iron uptake under iron deficiency.

    Science.gov (United States)

    Yi, Y; Guerinot, M L

    1996-11-01

    Reduction of Fe(III) to Fe(II) by Fe(III) chelate reductase is thought to be an obligatory step in iron uptake as well as the primary factor in making iron available for absorption by all plants except grasses. Fe(III) chelate reductase has also been suggested to play a more general role in the regulation of cation absorption. In order to experimentally address the importance of Fe(III) chelate reductase activity in the mineral nutrition of plants, three Arabidopsis thaliana mutans (frd1-1, frd1-2 and frd1-3), that do not show induction of Fe(III) chelate reductase activity under iron-deficient growth conditions, have been isolated and characterized. These mutants are still capable of acidifying the rhizosphere under iron-deficiency and accumulate more Zn and Mn in their shoots relative to wild-type plants regardless of iron status. frd1 mutants do not translocate radiolabeled iron to the shoots when roots are presented with a tightly chelated form of Fe(III). These results: (1) confirm that iron must be reduced before it can be transported, (2) show that Fe(III) reduction can be uncoupled from proton release, the other major iron-deficiency response, and (3) demonstrate that Fe(III) chelate reductase activity per se is not necessarily responsible for accumulation of cations previously observed in pea and tomato mutants with constitutively high levels of Fe(III) chelate reductase activity.

  11. Genetics of osteoporosis

    NARCIS (Netherlands)

    S.H. Ralston (Stuart); A.G. Uitterlinden (André)

    2010-01-01

    textabstractOsteoporosis is a common disease with a strong genetic component characterized by reduced bone mass, defects in the microarchitecture of bone tissue, and an increased risk of fragility fractures. Twin and family studies have shown high heritability of bone mineral density (BMD) and other

  12. Genetic determinants of facial clefting

    DEFF Research Database (Denmark)

    Jugessur, Astanand; Shi, Min; Gjessing, Håkon Kristian

    2009-01-01

    BACKGROUND: Facial clefts are common birth defects with a strong genetic component. To identify fetal genetic risk factors for clefting, 1536 SNPs in 357 candidate genes were genotyped in two population-based samples from Scandinavia (Norway: 562 case-parent and 592 control-parent triads; Denmark...

  13. Genetic-Phenotypic Variability and Correlation between Morphology-Anatomy-Physiology Characteristics and Dry Matter Yield of Polyploidized Forage Grasses under Aluminum Stressed Condition

    Directory of Open Access Journals (Sweden)

    S Anwar

    2007-01-01

    Full Text Available The study was conducted with the aim to know the genetic-phenotypic variability (heritability value, and correlation between morphology-anatomy-physiology characters and dry matter yield (DMY of polyploidized forage grasses under aluminum (Al stressed condition. A total of 16 forage grass genotypes (polyploid and diploid Brachiaria brizantha, Brachiaria decumbens, Setaria sphacelata, Setaria splendida, Panicum muticum, Panicum maximum, Pennisetum purpureum, and Pennisetum purpupoides were subjected to Al-stressed (16 mM Al2(SO43. The treatments were allotted to a Randomized Completely Block Design with monofactorial pattern (genotypes and 5 blocks in each treatment. The morphology-anatomy-physiology characteristics evaluated were plant height, leaf number, tiller number, leaf color, chlorophyll content, stomata number, chloroplast number, leaf nitrate reductase activity, dry matter, wet matter yield, dry matter yield, stress tolerance index and pH media. Results showed the polyploidization increased stress tolerance index of grasses. The genetic-phenotypic variability (heritability value estimates for all morphology-anatomy-physiology characteristics were high. Most morphology-anatomy-physiology characteristics, except leaf number, chlorophyll content and chloroplast number, had significant correlation to dry matter yield. In conclusion, evaluation on selection progress of dry matter yield of forage grasses can be effectively done by selection for yield of wet matter, plant height, leaf color, branch number, stomata number, leaf nitrate reductase activity, pH media, and dry matter simultaneously. (Animal Production 9(1: 23-29 (2007

  14. Prediction of crack growth direction by Strain Energy Sih's Theory on specimens SEN under tension-compression biaxial loading employing Genetic Algorithms

    International Nuclear Information System (INIS)

    Rodriguez-MartInez R; Lugo-Gonzalez E; Urriolagoitia-Calderon G; Urriolagoitia-Sosa G; Hernandez-Gomez L H; Romero-Angeles B; Torres-San Miguel Ch

    2011-01-01

    Crack growth direction has been studied in many ways. Particularly Sih's strain energy theory predicts that a fracture under a three-dimensional state of stress spreads in direction of the minimum strain energy density. In this work a study for angle of fracture growth was made, considering a biaxial stress state at the crack tip on SEN specimens. The stress state applied on a tension-compression SEN specimen is biaxial one on crack tip, as it can observed in figure 1. A solution method proposed to obtain a mathematical model considering genetic algorithms, which have demonstrated great capacity for the solution of many engineering problems. From the model given by Sih one can deduce the density of strain energy stored for unit of volume at the crack tip as dW = [1/2E(σ 2 x + σ 2 y ) - ν/E(σ x σy)]dV (1). From equation (1) a mathematical deduction to solve in terms of θ of this case was developed employing Genetic Algorithms, where θ is a crack propagation direction in plane x-y. Steel and aluminium mechanical properties to modelled specimens were employed, because they are two of materials but used in engineering design. Obtained results show stable zones of fracture propagation but only in a range of applied loading.

  15. Quantum computing with defects.

    Science.gov (United States)

    Weber, J R; Koehl, W F; Varley, J B; Janotti, A; Buckley, B B; Van de Walle, C G; Awschalom, D D

    2010-05-11

    Identifying and designing physical systems for use as qubits, the basic units of quantum information, are critical steps in the development of a quantum computer. Among the possibilities in the solid state, a defect in diamond known as the nitrogen-vacancy (NV(-1)) center stands out for its robustness--its quantum state can be initialized, manipulated, and measured with high fidelity at room temperature. Here we describe how to systematically identify other deep center defects with similar quantum-mechanical properties. We present a list of physical criteria that these centers and their hosts should meet and explain how these requirements can be used in conjunction with electronic structure theory to intelligently sort through candidate defect systems. To illustrate these points in detail, we compare electronic structure calculations of the NV(-1) center in diamond with those of several deep centers in 4H silicon carbide (SiC). We then discuss the proposed criteria for similar defects in other tetrahedrally coordinated semiconductors.

  16. Defects in semiconductor nanostructures

    Indian Academy of Sciences (India)

    sizes were less than 100 Si atoms due to computational limitations. An interesting parallel is that current first principles calculations alluded to in §5 are size ham- pered for similar reasons. These 'defect molecule' calculations were probably the first studies in SN. We believe that a perusal of this 'ancient' scientific literature.

  17. Production of point defects

    International Nuclear Information System (INIS)

    Zuppiroli, L.

    1975-01-01

    Vacancies at thermodynamic equilibrium and the annealing of these defects are studied first, after which electron irradiations are dealt with. The displacement threshold energy concept is introduced. Part three concerns heavy ion and neutron irradiations. Displacement cascades and the thermal spike concept are discussed [fr

  18. Defects in flexoelectric solids

    Science.gov (United States)

    Mao, Sheng; Purohit, Prashant K.

    2015-11-01

    A solid is said to be flexoelectric when it polarizes in proportion to strain gradients. Since strain gradients are large near defects, we expect the flexoelectric effect to be prominent there and decay away at distances much larger than a flexoelectric length scale. Here, we quantify this expectation by computing displacement, stress and polarization fields near defects in flexoelectric solids. For point defects we recover some well known results from strain gradient elasticity and non-local piezoelectric theories, but with different length scales in the final expressions. For edge dislocations we show that the electric potential is a maximum in the vicinity of the dislocation core. We also estimate the polarized line charge density of an edge dislocation in an isotropic flexoelectric solid which is in agreement with some measurements in ice. We perform an asymptotic analysis of the crack tip fields in flexoelectric solids and show that our results share some features from solutions in strain gradient elasticity and piezoelectricity. We also compute the energy release rate for cracks using simple crack face boundary conditions and use them in classical criteria for crack growth to make predictions. Our analysis can serve as a starting point for more sophisticated analytic and computational treatments of defects in flexoelectric solids which are gaining increasing prominence in the field of nanoscience and nanotechnology.

  19. Semiconductor Nanowires: Defects Update

    Science.gov (United States)

    Kavanagh, Karen L.

    2008-05-01

    Structural defects commonly observed in semiconducting nanowires by electron microscopy will be reviewed and their origins discussed. Their effects on electrical and optical properties will be illustrated with examples from GaSb, InAs, and ZnSe nanowires grown by MOCVD and MBE.

  20. Quo Vadis, Medical Genetics?

    Science.gov (United States)

    Czeizel, Andrew E.

    The beginning of human genetics and its medical part: medical genetics was promising in the early decades of this century. Many genetic diseases and defects with Mendelian origin were identified and it helped families with significant genetic burden to limit their child number. Unfortunately this good start was shadowed by two tragic events. On the one hand, in the 1930s and early 1940s the German fascism brought about the dominance of an unscientific eugenics to mask vile political crimes. People with genetic diseases-defects were forced to sterilisation and several of them were killed. On the other hand, in the 1950s lysenkoism inhibitied the evolution of genetics in the Soviet Union and their satelite countries. Lysenko's doctrine declared genetics as a product of imperialism and a guilty science, therefore leading geneticists were ousted form their posts and some of them were executed or put in prison. Past decades genetics has resulted fantastic new results and achieved a leading position within the natural sciences. To my mind, however, the expected wider use of new eugenics indicates a new tragedy and this Cassandra's prediction is the topic of this presentation.

  1. Genetic Dissection of Root Morphological Traits Related to Nitrogen Use Efficiency in Brassica napus L. under Two Contrasting Nitrogen Conditions

    Directory of Open Access Journals (Sweden)

    Jie Wang

    2017-09-01

    Full Text Available As the major determinant for nutrient uptake, root system architecture (RSA has a massive impact on nitrogen use efficiency (NUE. However, little is known the molecular control of RSA as related to NUE in rapeseed. Here, a rapeseed recombinant inbred line population (BnaZNRIL was used to investigate root morphology (RM, an important component for RSA and NUE-related traits under high-nitrogen (HN and low-nitrogen (LN conditions by hydroponics. Data analysis suggested that RM-related traits, particularly root size had significantly phenotypic correlations with plant dry biomass and N uptake irrespective of N levels, but no or little correlation with N utilization efficiency (NUtE, providing the potential to identify QTLs with pleiotropy or specificity for RM- and NUE-related traits. A total of 129 QTLs (including 23 stable QTLs, which were repeatedly detected at least two environments or different N levels were identified and 83 of them were integrated into 22 pleiotropic QTL clusters. Five RM-NUE, ten RM-specific and three NUE-specific QTL clusters with same directions of additive-effect implied two NUE-improving approaches (RM-based and N utilization-based directly and provided valuable genomic regions for NUE improvement in rapeseed. Importantly, all of four major QTLs and most of stable QTLs (20 out of 23 detected here were related to RM traits under HN and/or LN levels, suggested that regulating RM to improve NUE would be more feasible than regulating N efficiency directly. These results provided the promising genomic regions for marker-assisted selection on RM-based NUE improvement in rapeseed.

  2. Fitting Analysis using Differential evolution Optimization (FADO):. Spectral population synthesis through genetic optimization under self-consistency boundary conditions

    Science.gov (United States)

    Gomes, J. M.; Papaderos, P.

    2017-07-01

    The goal of population spectral synthesis (pss; also referred to as inverse, semi-empirical evolutionary- or fossil record approach) is to decipher from the spectrum of a galaxy the mass, age and metallicity of its constituent stellar populations. This technique, which is the reverse of but complementary to evolutionary synthesis, has been established as fundamental tool in extragalactic research. It has been extensively applied to large spectroscopic data sets, notably the SDSS, leading to important insights into the galaxy assembly history. However, despite significant improvements over the past decade, all current pss codes suffer from two major deficiencies that inhibit us from gaining sharp insights into the star-formation history (SFH) of galaxies and potentially introduce substantial biases in studies of their physical properties (e.g., stellar mass, mass-weighted stellar age and specific star formation rate). These are I) the neglect of nebular emission in spectral fits, consequently; II) the lack of a mechanism that ensures consistency between the best-fitting SFH and the observed nebular emission characteristics of a star-forming (SF) galaxy (e.g., hydrogen Balmer-line luminosities and equivalent widths-EWs, shape of the continuum in the region around the Balmer and Paschen jump). In this article, we present fado (Fitting Analysis using Differential evolution Optimization) - a conceptually novel, publicly available pss tool with the distinctive capability of permitting identification of the SFH that reproduces the observed nebular characteristics of a SF galaxy. This so-far unique self-consistency concept allows us to significantly alleviate degeneracies in current spectral synthesis, thereby opening a new avenue to the exploration of the assembly history of galaxies. The innovative character of fado is further augmented by its mathematical foundation: fado is the first pss code employing genetic differential evolution optimization. This, in conjunction

  3. 7 CFR 51.1564 - External defects.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false External defects. 51.1564 Section 51.1564 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946...

  4. 49 CFR 213.113 - Defective rails.

    Science.gov (United States)

    2010-10-01

    ..., oriented in or near the transverse plane, due to incomplete penetration of the weld metal between the rail ends, lack of fusion between weld and rail end metal, entrainment of slag or sand, under-bead or other shrinkage cracking, or fatigue cracking. Weld defects may originate in the rail head, web, or base, and in...

  5. Point defects in group IV semiconductors

    CERN Document Server

    Pizzini, S

    2017-01-01

    Aim of this book is to focus on the properties of defects in semiconductors of the fourth group under a physico-chemical approach, capable to demonstrate whether the full acknowledgement of their chemical nature could account for several problems encountered in practice or would suggest further experimental or theoretical accomplishments.

  6. 7 CFR 51.1565 - Internal defects.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Internal defects. 51.1565 Section 51.1565 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946...

  7. Defects and Disorder in the Drosophila Eye

    Science.gov (United States)

    Kim, Sangwoo; Carthew, Richard; Hilgenfeldt, Sascha

    Cell division and differentiation tightly control the regular pattern in the normal eye of the Drosophila fruit fly while certain genetic mutations introduce disorder in the form of topological defects. Analyzing data from pupal retinas, we develop a model based on Voronoi construction that explains the defect statistics as a consequence of area variation of individual facets (ommatidia). The analysis reveals a previously unknown systematic long-range area variation that spans the entire eye, with distinct effects on topological disorder compared to local fluctuations. The internal structure of the ommatidia and the stiffness of their interior cells also plays a crucial role in the defect generation. Accurate predictions of the correlation between the area variation and the defect density in both normal and mutant animals are obtained without free parameters. This approach can potentially be applied to cellular systems in many other contexts to identify size-topology correlations near the onset of symmetry breaking. This work has been supported by the NIH (GM098077) and the NSF (Grant No. 1504301).

  8. Emerging new tools to study and treat muscle pathologies: genetics and molecular mechanisms underlying skeletal muscle development, regeneration, and disease.

    Science.gov (United States)

    Crist, Colin

    2017-01-01

    Skeletal muscle is the most abundant tissue in our body, is responsible for generating the force required for movement, and is also an important thermogenic organ. Skeletal muscle is an enigmatic tissue because while on the one hand, skeletal muscle regeneration after injury is arguably one of the best-studied stem cell-dependent regenerative processes, on the other hand, skeletal muscle is still subject to many degenerative disorders with few therapeutic options in the clinic. It is important to develop new regenerative medicine-based therapies for skeletal muscle. Future therapeutic strategies should take advantage of rapidly developing technologies enabling the differentiation of skeletal muscle from human pluripotent stem cells, along with precise genome editing, which will go hand in hand with a steady and focused approach to understanding underlying mechanisms of skeletal muscle development, regeneration, and disease. In this review, I focus on highlighting the recent advances that particularly have relied on developmental and molecular biology approaches to understanding muscle development and stem cell function. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  9. Electronic structure of point defects in semiconductors

    International Nuclear Information System (INIS)

    Bruneval, Fabien

    2014-01-01

    This 'Habilitation a diriger des Recherches' memoir presents most of my scientific activities during the past 7 years, in the field of electronic structure calculations of defects in solids. Point defects (vacancies, interstitials, impurities) in functional materials are a key parameter to determine if these materials will actually fill the role they have been assigned or not. Indeed, the presence of defects cannot be avoided when the temperature is increased or when the material is subjected to external stresses, such as irradiation in the nuclear reactors and in artificial satellites with solar radiations. However, in many cases, defects are introduced in the materials on purpose to tune the electronic transport, optical or even magnetic properties. This procedure is called the doping of semiconductors, which is the foundation technique for transistors, diodes, or photovoltaic cells. However, doping is not always straightforward and unexpected features may occur, such as doping asymmetry or Fermi level pinning, which can only be explained by complex phenomena involving different types of defects or complexes of defects. In this context, the calculations of electronic structure ab initio is an ideal tool to complement the experimental observations, to gain the understanding of phenomena at the atomic level, and even to predict the properties of defects. The power of the ab initio calculations comes from their ability to describe any system of electrons and nuclei without any specific adjustment. But although there is a strong need for numerical simulations in this field, the ab initio calculations for defects are still under development as of today. The work presented in this memoir summarizes my contributions to methodological developments on this subject. These developments have followed two main tracks. The first topic is the better understanding of the unavoidable finite size effects. Indeed, defects in semiconductors or insulators are generally present in

  10. 49 CFR 232.15 - Movement of defective equipment.

    Science.gov (United States)

    2010-10-01

    ... under this part only if all of the following conditions are met: (1) The defective car or locomotive is... line of the railroad where the car or locomotive was first found to be defective or is the nearest... for cars or locomotives with brakes cut out en route, the following additional requirements are met...

  11. Genetic causes of congenital diaphragmatic hernia

    Science.gov (United States)

    Wynn, Julia; Yu, Lan; Chung, Wendy K.

    2014-01-01

    Congenital diaphragmatic hernia (CDH) is a moderately prevalent birth defect that, despite advances in neonatal care, is still a significant cause of infant death, and surviving patients have significant morbidity. The goal of ongoing research to elucidate the genetic causes of CDH is to develop better treatment and ultimately prevention. CDH is a complex developmental defect that is etiologically heterogeneous. This review summarizes the recurrent genetic causes of CDH including aneuploidies, chromosome copy number variants, and single gene mutations. It also discusses strategies for genetic evaluation and genetic counseling in an era of rapidly evolving technologies in clinical genetic diagnostics. PMID:25447988

  12. Study on the intrinsic defects in tin oxide with first-principles method

    Science.gov (United States)

    Sun, Yu; Liu, Tingyu; Chang, Qiuxiang; Ma, Changmin

    2018-04-01

    First-principles and thermodynamic methods are used to study the contribution of vibrational entropy to defect formation energy and the stability of the intrinsic point defects in SnO2 crystal. According to thermodynamic calculation results, the contribution of vibrational entropy to defect formation energy is significant and should not be neglected, especially at high temperatures. The calculated results indicate that the oxygen vacancy is the major point defect in undoped SnO2 crystal, which has a higher concentration than that of the other point defect. The property of negative-U is put forward in SnO2 crystal. In order to determine the most stable defects much clearer under different conditions, the most stable intrinsic defect as a function of Fermi level, oxygen partial pressure and temperature are described in the three-dimensional defect formation enthalpy diagrams. The diagram visually provides the most stable point defects under different conditions.

  13. Ventricular Septal Defect (For Teens)

    Science.gov (United States)

    ... have a heart defect should avoid getting body piercings. Piercing increases the possibility that bacteria can get into ... damage heart valves. If you're considering a piercing and you have a heart defect, talk to ...

  14. Congenital Heart Defects (For Parents)

    Science.gov (United States)

    ... diagnosed until the teen years — or even adulthood. Newborn Screening Newborns in the U.S. are screened at ... Has a Heart Defect Coarctation of the Aorta Arrhythmias Mitral Valve Prolapse Atrial Septal Defect Ventricular Septal ...

  15. DECOMPOSTION OF GENETICALLY ENGINEERED TOBACCO UNDER FIELD CONDITIONS: PERSISTENCE OF THE PROTEINASE INHIBITOR I PRODUCT AND EFFECTS OF SOIL MICROBIAL RESPIRATION AND PROTOZOA, NEMATODE AND MICROARTHR

    Science.gov (United States)

    1. To evaluate the potential effects of genetically engineered (transgenic) plants on soil ecosystems, litterbags containing leaves of non-engineered (parental) and transgenic tobacco plants were buried in field plots. The transgenic tobacco plants were genetically engineered to ...

  16. Defects in Quantum Computers.

    Science.gov (United States)

    Gardas, Bartłomiej; Dziarmaga, Jacek; Zurek, Wojciech H; Zwolak, Michael

    2018-03-14

    The shift of interest from general purpose quantum computers to adiabatic quantum computing or quantum annealing calls for a broadly applicable and easy to implement test to assess how quantum or adiabatic is a specific hardware. Here we propose such a test based on an exactly solvable many body system-the quantum Ising chain in transverse field-and implement it on the D-Wave machine. An ideal adiabatic quench of the quantum Ising chain should lead to an ordered broken symmetry ground state with all spins aligned in the same direction. An actual quench can be imperfect due to decoherence, noise, flaws in the implemented Hamiltonian, or simply too fast to be adiabatic. Imperfections result in topological defects: Spins change orientation, kinks punctuating ordered sections of the chain. The number of such defects quantifies the extent by which the quantum computer misses the ground state, and is, therefore, imperfect.

  17. Reconstructions of eyelid defects

    Directory of Open Access Journals (Sweden)

    Nirmala Subramanian

    2011-01-01

    Full Text Available Eyelids are the protective mechanism of the eyes. The upper and lower eyelids have been formed for their specific functions by Nature. The eyelid defects are encountered in congenital anomalies, trauma, and postexcision for neoplasm. The reconstructions should be based on both functional and cosmetic aspects. The knowledge of the basic anatomy of the lids is a must. There are different techniques for reconstructing the upper eyelid, lower eyelid, and medial and lateral canthal areas. Many a times, the defects involve more than one area. For the reconstruction of the lid, the lining should be similar to the conjunctiva, a cover by skin and the middle layer to give firmness and support. It is important to understand the availability of various tissues for reconstruction. One layer should have the vascularity to support the other layer which can be a graft. A proper plan and execution of it is very important.

  18. Benign gastric filling defect

    Energy Technology Data Exchange (ETDEWEB)

    Oh, K. K.; Lee, Y. H.; Cho, O. K.; Park, C. Y. [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1979-06-15

    The gastric lesion is a common source of complaints to Orientals, however, evaluation of gastric symptoms and laboratory examination offer little specific aid in the diagnosis of gastric diseases. Thus roentgenography of gastrointestinal tract is one of the most reliable method for detail diagnosis. On double contract study of stomach, gastric filling defect is mostly caused by malignant gastric cancer, however, other benign lesions can cause similar pictures which can be successfully treated by surgery. 66 cases of benign causes of gastric filling defect were analyzed at this point of view, which was verified pathologically by endoscope or surgery during recent 7 years in Yensei University College of Medicine, Severance Hospital. The characteristic radiological picture of each disease was discussed for precise radiologic diagnosis. 1. Of total 66 cases, there were 52 cases of benign gastric tumor 10 cases of gastric varices, 5 cases of gastric bezoar, 5 cases of corrosive gastritis, 3 cases of granulomatous disease and one case of gastric hematoma. 2. The most frequent causes of benign tumors were adenomatous polyp (35/42) and the next was leiomyoma (4/42). Others were one of case of carcinoid, neurofibroma and cyst. 3. Characteristic of benign adenomatous polyp were relatively small in size, smooth surface and were observed that large size, benign polyp was frequently type IV lesion with a stalk. 4. Submucosal tumors such as leiomyoma needed differential diagnosis with polypoid malignant cancer. However, the characteristic points of differentiation was well circumscribed smooth margined filling defect without definite mucosal destruction on surface. 5. Gastric varices showed multiple lobulated filling defected especially on gastric fundus that changed its size and shape by respiration and posture of patients. Same varices lesions on esophagus and history of liver disease were helpful for easier diagnosis. 6. Gastric bezoar showed well defined movable mass

  19. Benign gastric filling defect

    International Nuclear Information System (INIS)

    Oh, K. K.; Lee, Y. H.; Cho, O. K.; Park, C. Y.

    1979-01-01

    The gastric lesion is a common source of complaints to Orientals, however, evaluation of gastric symptoms and laboratory examination offer little specific aid in the diagnosis of gastric diseases. Thus roentgenography of gastrointestinal tract is one of the most reliable method for detail diagnosis. On double contract study of stomach, gastric filling defect is mostly caused by malignant gastric cancer, however, other benign lesions can cause similar pictures which can be successfully treated by surgery. 66 cases of benign causes of gastric filling defect were analyzed at this point of view, which was verified pathologically by endoscope or surgery during recent 7 years in Yensei University College of Medicine, Severance Hospital. The characteristic radiological picture of each disease was discussed for precise radiologic diagnosis. 1. Of total 66 cases, there were 52 cases of benign gastric tumor 10 cases of gastric varices, 5 cases of gastric bezoar, 5 cases of corrosive gastritis, 3 cases of granulomatous disease and one case of gastric hematoma. 2. The most frequent causes of benign tumors were adenomatous polyp (35/42) and the next was leiomyoma (4/42). Others were one of case of carcinoid, neurofibroma and cyst. 3. Characteristic of benign adenomatous polyp were relatively small in size, smooth surface and were observed that large size, benign polyp was frequently type IV lesion with a stalk. 4. Submucosal tumors such as leiomyoma needed differential diagnosis with polypoid malignant cancer. However, the characteristic points of differentiation was well circumscribed smooth margined filling defect without definite mucosal destruction on surface. 5. Gastric varices showed multiple lobulated filling defected especially on gastric fundus that changed its size and shape by respiration and posture of patients. Same varices lesions on esophagus and history of liver disease were helpful for easier diagnosis. 6. Gastric bezoar showed well defined movable mass

  20. Different responsiveness to a high-fat/cholesterol diet in two inbred mice and underlying genetic factors: a whole genome microarray analysis

    Directory of Open Access Journals (Sweden)

    Jin Gang

    2009-10-01

    Full Text Available Abstract Background To investigate different responses to a high-fat/cholesterol diet and uncover their underlying genetic factors between C57BL/6J (B6 and DBA/2J (D2 inbred mice. Methods B6 and D2 mice were fed a high-fat/cholesterol diet for a series of time-points. Serum and bile lipid profiles, bile acid yields, hepatic apoptosis, gallstones and atherosclerosis formation were measured. Furthermore, a whole genome microarray was performed to screen hepatic genes expression profile. Quantitative real-time PCR, western blot and TUNEL assay were conducted to validate microarray data. Results After fed the high-fat/cholesterol diet, serum and bile total cholesterol, serum cholesterol esters, HDL cholesterol and Non-HDL cholesterol levels were altered in B6 but not significantly changed in D2; meanwhile, biliary bile acid was decreased in B6 but increased in D2. At the same time, hepatic apoptosis, gallstones and atherosclerotic lesions occurred in B6 but not in D2. The hepatic microarray analysis revealed distinctly different genes expression patterns between B6 and D2 mice. Their functional pathway groups included lipid metabolism, oxidative stress, immune/inflammation response and apoptosis. Quantitative real time PCR, TUNEL assay and western-blot results were consistent with microarray analysis. Conclusion Different genes expression patterns between B6 and D2 mice might provide a genetic basis for their distinctive responses to a high-fat/cholesterol diet, and give us an opportunity to identify novel pharmaceutical targets in related diseases in the future.

  1. A Partial Backlogging Inventory Model for Deteriorating Item under Fuzzy Inflation and Discounting over Random Planning Horizon: A Fuzzy Genetic Algorithm Approach

    Directory of Open Access Journals (Sweden)

    Dipak Kumar Jana

    2013-01-01

    Full Text Available An inventory model for deteriorating item is considered in a random planning horizon under inflation and time value money. The model is described in two different environments: random and fuzzy random. The proposed model allows stock-dependent consumption rate and shortages with partial backlogging. In the fuzzy stochastic model, possibility chance constraints are used for defuzzification of imprecise expected total profit. Finally, genetic algorithm (GA and fuzzy simulation-based genetic algorithm (FSGA are used to make decisions for the above inventory models. The models are illustrated with some numerical data. Sensitivity analysis on expected profit function is also presented. Scope and Purpose. The traditional inventory model considers the ideal case in which depletion of inventory is caused by a constant demand rate. However, to keep sales higher, the inventory level would need to remain high. Of course, this would also result in higher holding or procurement cost. Also, in many real situations, during a longer-shortage period some of the customers may refuse the management. For instance, for fashionable commodities and high-tech products with short product life cycle, the willingness for a customer to wait for backlogging is diminishing with the length of the waiting time. Most of the classical inventory models did not take into account the effects of inflation and time value of money. But in the past, the economic situation of most of the countries has changed to such an extent due to large-scale inflation and consequent sharp decline in the purchasing power of money. So, it has not been possible to ignore the effects of inflation and time value of money any more. The purpose of this paper is to maximize the expected profit in the random planning horizon.

  2. Public health approach to birth defects: the Argentine experience.

    Science.gov (United States)

    Bidondo, María Paz; Groisman, Boris; Barbero, Pablo; Liascovich, Rosa

    2015-04-01

    Birth defects are a global problem, but their impact is particularly severe in low and middle income countries, where the conditions for prevention, treatment, and rehabilitation are more critical. The epidemiological transition in the infant mortality causes, and the concern of the community and the mass media about the teratogenic risk of environmental pollutants, has made health authorities aware of the importance of birth defects in Argentina. The objective of this paper is to outline those actions specifically taken in Argentina aimed at the prevention of birth defects at a national level. Firstly, we focus on birth defects in Argentina on a general basis, and then we present different laws and actions taken in terms of surveillance and public health programs, primary, secondary, and tertiary prevention. Finally, we present the Teratology Information Service "Fetal Health Line", and the genetic services organization and health professionals training by the National Center of Medical Genetics and the National Program of Genetics Network. In conclusion, in the country, several programs focus on different approaches to the problem, and the challenge is to coordinate the teamwork between them. Finally, we list tips to address birth defects from the public health perspective.

  3. Defects in an active nematic confined to a toroid

    Science.gov (United States)

    Ellis, Perry; Pearce, Dan; Giomi, Luca; Fernandez-Nieves, Alberto

    Active materials are driven far from the ground state by the motion of their constituent particles, thereby making them inherently non-equilibrium materials. For an active nematic, this results in a continuous creation and annihilation of +/- 1 / 2 defect pairs. Here, we confine an active nematic to the surface of a toroid and show that the topological charge of the defects couples to the Gaussian curvature of the underlying surface. However, in our experiments this defect unbinding happens on average, illustrating that despite subtle differences, the role of activity is reminiscent of the role of temperature in conventional nematics. This is confirmed by computer simulations which clearly illustrate that defect unbinding depends on activity. Overall, our results illustrate the role of confinement and curvature on the defect behavior of active nematic liquid crystals. PWE is supported by FLAMEL under Grant NSF 1258425.

  4. Thyroid gland development and defects.

    Science.gov (United States)

    Kratzsch, Juergen; Pulzer, Ferdinand

    2008-02-01

    During the functional ontogenesis of the thyroid gland an increasing number of transcription factors play fundamental roles in thyroid-cell differentiation, maintenance of the differentiated state, and thyroid-cell proliferation. The early growth and development of the fetal thyroid appears to be generally independent of thyroid-stimulating hormone (TSH). TSH and thyroxine (T4) levels increase from the 12th week of gestation until delivery, whereas triiodothyronine (T3) levels remain relatively low. At birth, a cold-stimulated short-lived TSH surge is observed, followed by a TSH decrease until day 3 or 4 of life by T4 feedback inhibition. Disorders of thyroid gland development and/or function are relatively common, affecting approximately one newborn infant in 2000-4000. The most prevalent disease, congenital hypothyroidism, is frequently caused by genetic defects of transcription factors involved in the development of the thyroid or pituitary gland. A major cause of congenital hyperthyroidism is the transplacental passage of stimulating thyrotropin antibodies from the mother to the fetus. Hypothyroxinaemia or hypotriiodthyroninaemia is frequently observed in preterm infants with or without severe non-thyroidal illness. Whereas congenital hypo- and hyperthyroidism may be treated successfully with T4 or thyrostatic drugs, there is still insufficient evidence on whether the use of T4 for treatment of the latter condition results in changes in neonatal morbidity or reductions in neurodevelopmental impairment.

  5. [Vascular disruption birth defects are not associated to chromosomal alterations].

    Science.gov (United States)

    Pachajoa, Harry; Ariza, Yoseth; Isaza, Carolina; Méndez, Fabián

    2015-11-01

    It is estimated that 2 to 35 of newborns present a congenital malformation. Some publications suggest that vascular disruption birth defects are not associated with chromosomal alterations detected by conventional karyotype. to determine the frequency of chromosomal alterations detected by high resolution G banded karyotype in patients with vascular disruption birth defects in a Colombian population (South America). transversal study. Population: a sample of patients identified by an epidemiological surveillance system of congenital malformations in a reference hospital in Cali, Colombia. 41 cases of vascular disruption birth defects were identified during a 36 month period; in a descending order those were: transverse reduction defects, hydranencephaly and gastroschisis. Two expert cytogenetists performed independent evaluation of the genetic material of the patients, and no chromosomal alterations detectable by G banded karyotype were identified. It is recommended that genetic counseling in cases of defects by vascular disruption is carried out taking into account the empirical recurrence risks reported for each one the types of defects by vascular disruption and the use of karyotype should be limited to cases with other malformations or chromosomal abnormality suspected by phenotype.

  6. Thermal properties of defective fullerene

    Science.gov (United States)

    Li, Jian; Zheng, Dong-Qin; Zhong, Wei-Rong

    2016-09-01

    We have investigated the thermal conductivity of defective fullerene (C60) by using the nonequilibrium molecular dynamics (MD) method. It is found that the thermal conductivity of C60 with one defect is lower than the thermal conductivity of perfect C60. However, double defects in C60 have either positive or negative influence on the thermal conductivity, which depends on the positions of the defects. The phonon spectra of perfect and defective C60 are also provided to give corresponding supports. Our results can be extended to long C60 chains, which is helpful for the thermal management of C60.

  7. Melanoma genetics

    DEFF Research Database (Denmark)

    Read, Jazlyn; Wadt, Karin A W; Hayward, Nicholas K

    2015-01-01

    Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence of herita......Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence...... in a combined total of approximately 50% of familial melanoma cases, the underlying genetic basis is unexplained for the remainder of high-density melanoma families. Aside from the possibility of extremely rare mutations in a few additional high penetrance genes yet to be discovered, this suggests a likely...... polygenic component to susceptibility, and a unique level of personal melanoma risk influenced by multiple low-risk alleles and genetic modifiers. In addition to conferring a risk of cutaneous melanoma, some 'melanoma' predisposition genes have been linked to other cancers, with cancer clustering observed...

  8. Autosomal recessive ichthyosis with limb reduction defect: A simple ...

    African Journals Online (AJOL)

    Ichthyosis is a genetically and phenotypically heterogeneous disease that can be isolated and restricted to the skin manifestations or associated with extracutaneous symptoms. One of which is limb reduction defect known as CHILD syndrome; a rare inborn error of metabolism of cholesterol biosynthesis that is usually ...

  9. Prevalence of spermatozoa morphologic defects from Zebu bulls ...

    African Journals Online (AJOL)

    Bulls are keys to fertility and genetic improvement of the total herd. Spermatozoa quality is among of major components for evaluation of bulls to be used as breeding bulls. This study was therefore carried out to determine the prevalence of spermatozoa defects in Tanzania shorthorn breeding bulls, and to determine if the ...

  10. Point defects in nickel

    International Nuclear Information System (INIS)

    Peretto, P.

    1969-01-01

    The defects in electron irradiated nickel (20 deg. K) or neutron irradiated nickel (28 deg. K) are studied by simultaneous analysis using the magnetic after-effect, electron microscopy and electrical resistivity recovery. We use zone refined nickel (99.999 per cent) which, for some experiments, is alloyed with a small amount of iron (for example 0.1 per cent Fe). The temperature dependant electrical recovery may be divided in four stages. The sub-stages I B (31 deg. K), I C (42 deg. K), I D (from to 57 deg. K) and I E (62 deg. K) of stage I are due to the disappearance of single interstitials into vacancies. The interstitial defect has a split configuration with a migration energy of about 0.15 eV. In the close pair which disappears in stage I B the interstitial is found to be in a 3. neighbour position whilst in stage I D it is near the direction from the vacancy. In stage I E there is no longer any interaction between the interstitial and the vacancy. The stage II is due to more complicated interstitial defects: di-interstitials for stage II B (84 deg. K) and larger and larger interstitial loops for the following sub-stages. The loops may be seen by electron microscopy. Impurities can play the role of nucleation centers for the loops. Stages III A (370 deg. K) and III B (376 deg. K) are due to two types of di-vacancies. During stage IV (410 deg. K) the single vacancies migrate. Vacancy type loops and interstitial type loops grow concurrently and disappear at about 800 deg. K as observed by electron microscopy. (author) [fr

  11. Single ventricle cardiac defect

    International Nuclear Information System (INIS)

    Eren, B.; Turkmen, N.; Fedakar, R.; Cetin, V.

    2010-01-01

    Single ventricle heart is defined as a rare cardiac abnormality with a single ventricle chamber involving diverse functional and physiological defects. Our case is of a ten month-old baby boy who died shortly after admission to the hospital due to vomiting and diarrhoea. Autopsy findings revealed cyanosis of finger nails and ears. Internal examination revealed; large heart, weighing 60 grams, single ventricle, without a septum and upper membranous part. Single ventricle is a rare pathology, hence, this paper aims to discuss this case from a medico-legal point of view. (author)

  12. Feline genetics: clinical applications and genetic testing.

    Science.gov (United States)

    Lyons, Leslie A

    2010-11-01

    DNA testing for domestic cat diseases and appearance traits is a rapidly growing asset for veterinary medicine. Approximately 33 genes contain 50 mutations that cause feline health problems or alterations in the cat's appearance. A variety of commercial laboratories can now perform cat genetic diagnostics, allowing both the veterinary clinician and the private owner to obtain DNA test results. DNA is easily obtained from a cat via a buccal swab with a standard cotton bud or cytological brush, allowing DNA samples to be easily sent to any laboratory in the world. The DNA test results identify carriers of the traits, predict the incidence of traits from breeding programs, and influence medical prognoses and treatments. An overall goal of identifying these genetic mutations is the correction of the defect via gene therapies and designer drug therapies. Thus, genetic testing is an effective preventative medicine and a potential ultimate cure. However, genetic diagnostic tests may still be novel for many veterinary practitioners and their application in the clinical setting needs to have the same scrutiny as any other diagnostic procedure. This article will review the genetic tests for the domestic cat, potential sources of error for genetic testing, and the pros and cons of DNA results in veterinary medicine. Highlighted are genetic tests specific to the individual cat, which are a part of the cat's internal genome. Copyright © 2010 Elsevier Inc. All rights reserved.

  13. Phase instability in crystals under irradiation

    International Nuclear Information System (INIS)

    Martin, G.

    1975-01-01

    A diffusion term is introduced in the standard chemical rate model of the defect population in crystals under irradiation. For point defect generation rates larger than a critical value (g*), the uniform point defect population is shown to be unstable with respect to spatial fluctuations of the point defect concentration. g* is temperature dependent. Severala effects including the nucleation of arrays of point defect clusters, or radiation induced precipitation may occur above the instability threshold. Defect-defect interaction potentials play a crucial role in the numerical value of this threshold [fr

  14. On determining defects identity in carbon nanotubes using charge probes

    Energy Technology Data Exchange (ETDEWEB)

    Kostyrko, T. [Faculty of Physics, A. Mickiewicz University, ul. Umultowska 85, 61-614 Poznań (Poland); García-Suárez, V.M. [Departamento de Física, Universidad de Oviedo, 33007 Oviedo (Spain); Nanomaterials and Nanotechnology Research Center (CINN), Oviedo (Spain); Wawrzyniak-Adamczewska, M., E-mail: mwaw@amu.edu.pl [Faculty of Physics, A. Mickiewicz University, ul. Umultowska 85, 61-614 Poznań (Poland); Ferrer, J. [Departamento de Física, Universidad de Oviedo, 33007 Oviedo (Spain); Nanomaterials and Nanotechnology Research Center (CINN), Oviedo (Spain)

    2016-06-15

    Highlights: • Conductance maps in defected carbon nanotube were computed using an ab initio method. • H-passivation can transform a vacancy from a donor type to an acceptor type defect. • Means to use a point charge probe to identify defect types in carbon nanotubes were shown. • Carbon nanotubes with defects can be applied as static charge detectors in nanoscale. - Abstract: A metallic carbon nanotube with point-like defects under influence of a local potential due to a point charge probe is theoretically studied. A combination of density functional theory and the Landauer–Büttiker formalism is used to compute the electronic conductance in the zero-voltage limit. From a collection of the results obtained by varying the probe position around different defects the conductance maps are created. The analysis of the conductance maps allows us to formulate conditions under which several point-like defects (the Stone–Wales defect, a simple carbon vacancy, hydrogen-passivated vacancies) can be distinguished and identified in experiments with the help of scanning probe microscopy.

  15. Birth Defects in India: Magnitude, Public Health Impact and Prevention

    Directory of Open Access Journals (Sweden)

    Anita Kar

    2014-07-01

    Full Text Available Birth defects refer to a group of diverse congenital conditions, which are responsible for stillbirths, neonatal deaths, chronic medical conditions and disability. Due to their low prevalence and high mortality, birth defects are not considered to be a significant health problem in India. Various data however identify that India may harbour a significant burden of birth defects, and that these conditions may be responsible for a considerable proportion of neonatal deaths in India. Although it is widely assumed that survival of patients with birth defects is low, data suggests that in 2002, there were nearly six million Indians living with impairments arising at birth. These data urge the need for implementation of a national birth defects programme in India, with a strong component of prevention. The need for significant research investments to understand the epidemiology and public health impact of birth defects in India is identified. Translation research, transcending the disciplines of medicine, public health and genetics is required to develop a low cost birth defects service as a component of the existing maternal and child health programme.

  16. Epigenetic understanding of gene-environment interactions in psychiatric disorders: a new concept of clinical genetics

    OpenAIRE

    Kubota, Takeo; Miyake, Kunio; Hirasawa, Takae

    2012-01-01

    Abstract Epigenetics is a mechanism that regulates gene expression independently of the underlying DNA sequence, relying instead on the chemical modification of DNA and histone proteins. Although environmental and genetic factors were thought to be independently associated with disorders, several recent lines of evidence suggest that epigenetics bridges these two factors. Epigenetic gene regulation is essential for normal development, thus defects in epigenetics cause various rare congenital ...

  17. Enhancement of lipid productivity in oleaginous Colletotrichum fungus through genetic transformation using the yeast CtDGAT2b gene under model-optimized growth condition.

    Directory of Open Access Journals (Sweden)

    Prabuddha Dey

    Full Text Available Oleaginous fungi are of special interest among microorganisms for the production of lipid feedstocks as they can be cultured on a variety of substrates, particularly waste lingocellulosic materials, and few fungal strains are reported to accumulate inherently higher neutral lipid than bacteria or microalgae. Previously, we have characterized an endophytic filamentous fungus Colletotrichum sp. DM06 that can produce total lipid ranging from 34% to 49% of its dry cell weight (DCW upon growing with various carbon sources and nutrient-stress conditions. In the present study, we report on the genetic transformation of this fungal strain with the CtDGAT2b gene, which encodes for a catalytically efficient isozyme of type-2 diacylglycerol acyltransferase (DGAT from oleaginous yeast Candida troplicalis SY005. Besides the increase in size of lipid bodies, total lipid titer by the transformed Colletotrichum (lipid content ∼73% DCW was found to be ∼1.7-fold more than the wild type (lipid content ∼38% DCW due to functional activity of the CtDGAT2b transgene when grown under standard condition of growth without imposition of any nutrient-stress. Analysis of lipid fractionation revealed that the neutral lipid titer in transformants increased up to 1.8-, 1.6- and 1.5-fold compared to the wild type when grown under standard, nitrogen stress and phosphorus stress conditions, respectively. Lipid titer of transformed cells was further increased to 1.7-fold following model-based optimization of culture conditions. Taken together, ∼2.9-fold higher lipid titer was achieved in Colletotrichum fungus due to overexpression of a rate-limiting crucial enzyme of lipid biosynthesis coupled with prediction-based bioprocess optimization.

  18. Cancer predisposition in children: genetics, phenotypes & screening

    NARCIS (Netherlands)

    Hopman, S.M.J.

    2014-01-01

    This thesis describes the genetic, phenotypic and screening aspects of tumor predisposition syndromes in childhood cancer patients. In tumor predisposition syndromes, the same constitutional molecular defects that lead to the clinical phenotype predispose the patient to develop specific cancers.

  19. Dipole defects in beryl

    International Nuclear Information System (INIS)

    Holanda, B A; Cordeiro, R C; Blak, A R

    2010-01-01

    Dipole defects in gamma irradiated and thermally treated beryl (Be 3 Al 2 Si 6 O 18 ) samples have been studied using the Thermally Stimulated Depolarization Currents (TSDC) technique. TSDC experiments were performed in pink (morganite), green (emerald), blue (aquamarine) and colourless (goshenite) natural beryl. TSDC spectra present dipole peaks at 190K, 220K, 280K and 310K that change after gamma irradiation and thermal treatments. In morganite samples, for thermal treatments between 700K and 1100K, the 280K peak increase in intensity and the band at 220K disappears. An increase of the 280K peak and a decrease of the 190K peak were observed in the TSDC spectra of morganite after a gamma irradiation of 25kGy performed after the thermal treatments. In the case of emerald samples, thermal treatments enhanced the 280K peak and gamma irradiation partially destroyed this band. The goshenite TSDC spectra present only one band at 280K that is not affected either by thermal treatments or by gamma irradiation. All the observed peaks are of dipolar origin because the intensity of the bands is linearly dependent on the polarization field, behaviour of dipole defects. The systematic study, by means of TSDC measurements, of ionizing irradiation effects and thermal treatments in these crystals makes possible a better understanding of the role played by the impurities in beryl crystals.

  20. High Defect Tolerance in Lead Halide Perovskite CsPbBr3.

    Science.gov (United States)

    Kang, Jun; Wang, Lin-Wang

    2017-01-19

    The formation energies and charge-transition levels of intrinsic point defects in lead halide perovskite CsPbBr 3 are studied from first-principles calculations. It is shown that the formation energy of dominant defect under Br-rich growth condition is much lower than that under moderate or Br-poor conditions. Thus avoiding the Br-rich condition can help to reduce the defect concentration. Interestingly, CsPbBr 3 is found to be highly defect-tolerant in terms of its electronic structure. Most of the intrinsic defects induce shallow transition levels. Only a few defects with high formation energies can create deep transition levels. Therefore, CsPbBr 3 can maintain its good electronic quality despite the presence of defects. Such defect tolerance feature can be attributed to the lacking of bonding-antibonding interaction between the conduction bands and valence bands.

  1. Syndromes and Disorders Associated with Omphalocele (III: Single Gene Disorders, Neural Tube Defects, Diaphragmatic Defects and Others

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2007-06-01

    Full Text Available Omphalocele can be associated with single gene disorders, neural tube defects, diaphragmatic defects, fetal valproate syndrome, and syndromes of unknown etiology. This article provides a comprehensive review of omphalocele-related disorders: otopalatodigital syndrome type II; Melnick–Needles syndrome; Rieger syndrome; neural tube defects; Meckel syndrome; Shprintzen–Goldberg omphalocele syndrome; lethal omphalocele-cleft palate syndrome; cerebro-costo-mandibular syndrome; fetal valproate syndrome; Marshall–Smith syndrome; fibrochondrogenesis; hydrolethalus syndrome; Fryns syndrome; omphalocele, diaphragmatic defects, radial anomalies and various internal malformations; diaphragmatic defects, limb deficiencies and ossification defects of skull; Donnai–Barrow syndrome; CHARGE syndrome; Goltz syndrome; Carpenter syndrome; Toriello–Carey syndrome; familial omphalocele; Cornelia de Lange syndrome; C syndrome; Elejalde syndrome; Malpuech syndrome; cervical ribs, Sprengel anomaly, anal atresia and urethral obstruction; hydrocephalus with associated malformations; Kennerknecht syndrome; lymphedema, atrial septal defect and facial changes; and craniosynostosis- mental retardation syndrome of Lin and Gettig. Perinatal identification of omphalocele should alert one to the possibility of omphalocele-related disorders and familial inheritance and prompt a thorough genetic counseling for these disorders.

  2. Interaction between solute atoms and radiation defects in Fe-Ni-Si and Fe-Mn-Si alloys under irradiation with proton ions at low-temperature

    Energy Technology Data Exchange (ETDEWEB)

    Murakami, Kenta, E-mail: murakami@tokai.t.u-tokyo.ac.jp [Nuclear Professional School, School of Engineering, The University of Tokyo, 2-22 Shirakata-Shirane, Tokai-mura, Ibaraki, 319-1188 (Japan); Iwai, Takeo, E-mail: iwai@med.id.yamagata-u.ac.jp [Faculty of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata, Yamagata-shi, 990-9585 (Japan); Abe, Hiroaki [Nuclear Professional School, School of Engineering, The University of Tokyo, 2-22 Shirakata-Shirane, Tokai-mura, Ibaraki, 319-1188 (Japan); Sekimura, Naoto, E-mail: sekimura@n.t.u-tokyo.ac.jp [Department of Nuclear Engineering and Management, School of Engineering, The University of Tokyo, 7-3-1, Tokyo, Hongo, Bunkyo, 113-8656 (Japan)

    2016-12-15

    Isochronal annealing followed by residual resistivity measurements at 12 K was performed in Fe-0.6Ni-0.6Si and Fe-1.5Mn-0.6Si alloys irradiated with 1 MeV proton ions below 70 K, and recovery stages were compared with those of Fe–0.6Ni and Fe–1.5Mn. The effects of silicon addition in the Fe-Ni alloy was observed as the appearance of a new recovery stage at 282–372 K, presumably corresponding to clustering of solute atoms in matrix, and as a change in mixed dumbbell migration at 122–142 K. Silicon addition mitigated the manganese effect in Fe–Mn alloy that is obstructing the recovery of radiation defects. Reduction of resistivity in Fe-Mn-Si alloy also suggested formation of small solute atom clusters.

  3. Hyaluronic acid in calves defects correction

    Directory of Open Access Journals (Sweden)

    Lorenzo Rosset

    2014-09-01

    Full Text Available Aim: Since the advent of fillers, new techniques are continuously developed for different uses. In this study, we evaluated the use of hyaluronic acid for calf augmentation. Methods: A total of 42 patients were enrolled in this study. All of them underwent augmentation procedure in our centers under local anesthesia, the operations were completed within 1 h with a prompt correction of the defects. Results: Thirty-nine patients were satisfied with the treatment (93%, while three had complications, local infection, and lumps, that were resolved quickly (7%. Conclusion: Macrofillers can be injected into the calf to correct any defects. The advantages include short duration of treatment; the procedure performed under local anesthesia and limited side-effects that resolve promptly. This study suggests the use of biocompatible macrofillers for the augmentation of not only calves, but also for augmentation of breast and buttocks.

  4. Topological defects in extended inflation

    International Nuclear Information System (INIS)

    Copeland, E.J.; Kolb, E.W.; Chicago Univ., IL; Liddle, A.R.

    1990-04-01

    We consider the production of topological defects, especially cosmic strings, in extended inflation models. In extended inflation, the Universe passes through a first-order phase transition via bubble percolation, which naturally allows defects to form at the end of inflation. The correlation length, which determines the number density of the defects, is related to the mean size of bubbles when they collide. This mechanism allows a natural combination of inflation and large-scale structure via cosmic strings. 18 refs

  5. Diaphragmatic defect in trisomy 13

    International Nuclear Information System (INIS)

    Reinbold, W.D.; Reinwein, H.; Back, E.

    1986-01-01

    Congenital diaphragmatic defect is often combined with other malformations that are severe or fatal. The rare finding of a congenital diaphragmatic defect in a newborn with trisomy 13 is reported. The newborn died within 2 days. Postmortem examination showed typical malformations due to trisomy 13 besides a diaphragmatic defect of left retrosternal position. Karyotype revealed a 13/14 translocation of trisomy 13. (orig.) [de

  6. Topological defects in extended inflation

    International Nuclear Information System (INIS)

    Copeland, E.J.; Kolb, E.W.; Liddle, A.R.

    1990-01-01

    We consider the production of topological defects, especially cosmic strings, in extended-inflation models. In extended inflation, the Universe passes through a first-order phase transition via bubble percolation, which naturally allows defects to form at the end of inflation. The correlation length, which determines the number density of the defects, is related to the mean size of the bubbles when they collide. This mechanism allows a natural combination of inflation and large-scale structure via cosmic strings

  7. Advances in genetic therapeutic strategies for Duchenne muscular dystrophy.

    Science.gov (United States)

    Guiraud, Simon; Chen, Huijia; Burns, David T; Davies, Kay E

    2015-12-01

    What is the topic of this review? This review highlights recent progress in genetically based therapies targeting the primary defect of Duchenne muscular dystrophy. What advances does it highlight? Over the last two decades, considerable progress has been made in understanding the mechanisms underlying Duchenne muscular dystrophy, leading to the development of genetic therapies. These include manipulation of the expression of the gene or related genes, the splicing of the gene and its translation, and replacement of the gene using viral approaches. Duchenne muscular dystrophy is a lethal X-linked disorder caused by mutations in the dystrophin gene. In the absence of the dystrophin protein, the link between the cytoskeleton and extracellular matrix is destroyed, and this severely compromises the strength, flexibility and stability of muscle fibres. The devastating consequence is progressive muscle wasting and premature death in Duchenne muscular dystrophy patients. There is currently no cure, and despite exhaustive palliative care, patients are restricted to a wheelchair by the age of 12 years and usually succumb to cardiac or respiratory complications in their late 20s. This review provides an update on the current genetically based therapies and clinical trials that target or compensate for the primary defect of this disease. These include dystrophin gene-replacement strategies, genetic modification techniques to restore dystrophin expression, and modulation of the dystrophin homologue, utrophin, as a surrogate to re-establish muscle function. © 2015 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

  8. Genetic variation in carbon isotope discrimination and its relationship to growth under field conditions in full-sib families of Picea mariana

    Science.gov (United States)

    Lawrence B. Flanagan; Kurt H. Johnsen

    1995-01-01

    Measurements of the stable carbon isotope composition of leaf tissue were made on Picea mariana (Mill.) B.S.P. trees from four full-sib families grown on three different field sites at the Petawawa National Forestry Institute, Ontario, Canada. The four families chosen exhibited genetic variation for growth characteristics. Genetic...

  9. Positron studies of defected metals, metallic surfaces

    International Nuclear Information System (INIS)

    Bansil, A.

    1991-01-01

    Specific problems proposed under this project included the treatment of electronic structure and momentum density in various disordered and defected systems. Since 1987, when the new high-temperature superconductors were discovered, the project focused extensively on questions concerning the electronic structure and Fermiology of high-T c superconductors, in particular, (i) momentum density and positron experiments, (ii) angle-resolved photoemission intensities, (iii) effects of disorder and substitutions in the high-T c 's

  10. A criterion and mechanism for power ramp defects

    International Nuclear Information System (INIS)

    Garlick, A.; Gravenor, J.G.

    1978-02-01

    The problem of power ramp defects in water reactor fuel pins is discussed in relation to results recently obtained from ramp experiments in the Steam Generating Heavy Water Reactor. Cladding cracks in the defected fuel pins were similar, both macro- and micro structurally, to those in unirradiated Zircaloy exposed to iodine stress-corrosion cracking (scc) conditions. Furthermore, when the measured stress levels for scc in short-term tests were taken as a criterion for ramp defects, UK fuel modelling codes were found to give a useful indication of defect probability under reactor service conditions. The likelihood of sticking between fuel and cladding is discussed and evidence presented which suggests that even at power a degree of adhesion may be expected in some fuel pins. The ramp defect mechanism is discussed in terms of fission product scc, initiation being by intergranular penetration and propagation by cleavage when suitably orientated grains are exposed to large dilatational stresses ahead of the main crack. (author)

  11. The relationship between reaction kinetics and mutagenic action of monofunctional alkylating agents in higher eukaryotic systems. IV. The effects of the excision-defective mei-9L1 and mus(2)201D1 mutants on alkylation-induced genetic damage in Drosophila.

    Science.gov (United States)

    Vogel, E W; Dusenbery, R L; Smith, P D

    1985-04-01

    Repair-defective mutants of Drosophila melanogaster which identify two major DNA excision repair loci have been examined for their effects on alkylation-induced mutagenesis using the sex-linked recessive lethal assay as a measure of genotoxic endpoint. The alkylating agents (AAs) chosen for comparative analysis were selected on the basis of their reaction kinetics with DNA and included MMS, EMS, MNU, DMN, ENU, DEN and ENNG. Repair-proficient males were treated with the AAs and mated with either excision-defective mei-9L1 or mus(2)201D1 females or appropriate excision-proficient control females. The results of the present work suggest that a qualitative and quantitative relationship exists between the nature and the extent of chemical modification of DNA and the induction of of genetic alterations. The presence of either excision-defective mutant can enhance the frequency of mutation (hypermutability) and this hypermutability can be correlated with the Swain-Scott constant S of specific AAs such that as the SN1 character of the DNA alkylation reaction increases, the difference in response between repair-deficient and repair-proficient females decreases. The order of hypermutability of AAs with mei-9L1 relative to mei-9+ is MMS greater than MNU greater than DMN = EMS greater than iPMS = ENU = DEN = ENNG. When the percentage of lethal mutations induced in mei-9L1 females are plotted against those determined for control females, straight lines of different slopes are obtained. These mei-9L1/mei-9+ indices are: MMS = 7.6, MNU = 5.4, DMN = 2.4, EMS = 2.4 and iPMS = ENU = DEN = ENNG = 1. An identical order of hypermutability with