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Sample records for modeling catecholaminergic polymorphic

  1. Catecholaminergic polymorphic ventricular tachycardia in 2012

    Directory of Open Access Journals (Sweden)

    Christian van der Werf

    2011-12-01

    Full Text Available Catecholaminergic polymorphic ventricular tachycardia (CPVT is a rare, potentially lethal inherited arrhythmia syndrome characterized by stress or emotion-induced ventricular arrhythmias. CPVT was first described in 1960, while the genetic basis underlying this syndrome was discovered in 2001. The past decade has seen substantial advances in understanding the pathophysiology of CPVT. In addition, significant advances have been made in elucidating clinical characteristics of CPVT patients and new treatment options have become available. Here, we review current literature on CPVT to present state-of-the-art knowledge on the subject of the genetic basis, pathophysiology, clinical presentation, diagnosis, treatment and prognosis.

  2. Current topics in catecholaminergic polymorphic ventricular tachycardia

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    Naokata Sumitomo, MD, PhD

    2016-10-01

    Full Text Available Catecholaminergic polymorphic ventricular tachycardia (CPVT is induced by emotions or exercise in patients without organic heart disease and may be polymorphic or bidirectional in nature. The prognosis of CPVT is not good, and therefore prevention of sudden death is of utmost importance. Genetic variants of CPVT include RyR2, CASQ2, CALM2, TRD, and possibly KCNJ2 and ANK2 gene mutations. Hypotheses that suggest the causes of CPVT include weakened binding of FKBP12.6 and RyR2, a store overload-induced Ca2+ release (SOICR, unzipping of intramolecular domain interactions in RyR2, and molecular and functional abnormalities caused by mutations in the CASQ2 gene. The incidence of an RyR2 anomaly in CPVTs is about 35–79%, whereas anomalies in the CASQ2 gene account for 3–5% CPVTs. The ping-pong theory, suggesting that reciprocating delayed after depolarization induces bigeminy of the right and left bundle branches, may explain the pathogenesis of bidirectional ventricular tachycardia. Flecainide, carvedilol, left sympathetic nerve denervation, and catheter ablation of the PVC may serve as new therapeutic strategies for CPVT while gene-therapy may be applied to some types of CPVT in the future. Although, not all sudden cardiac deaths in CPVT patients are currently preventable, new medical and interventional therapies may improve CPVT prognosis.

  3. [Catecholaminergic polymorphic ventricular tachycardia is a rare inherited heart disease.

    DEFF Research Database (Denmark)

    Holst, Anders Gaarsdal; Tfelt-Hansen, 1jacob; Olesen, Morten S

    2010-01-01

    Catecholaminergic polymorphic ventricular tachycardia is a rare inherited heart disease, which can lead to life-threatening ventricular arrhythmias in patients with a structurally normal heart. The age of onset is usually between two and 12 years and the initial symptom is frequently syncope...

  4. Catecholaminergic polymorphic ventricular tachycardia: important messages from case reports

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    van der Werf, Christian; Wilde, Arthur A. M.

    2011-01-01

    This editorial refers to 'Germline and somatic mosaicism for a mutation of the ryanodine receptor type 2 gene: implication for genetic counselling and patient caring' by N. Roux-Buisson et al., on page 130 and 'Efficacy of flecainide in a patient with catecholaminergic polymorphic ventricular

  5. Postexertional Supraventricular Tachycardia in Children with Catecholaminergic Polymorphic Ventricular Tachycardia

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    Scott D. N. Else

    2012-01-01

    Full Text Available Catecholaminergic polymorphic ventricular tachycardia (CPVT is a severe arrhythmia associated with sudden death in the young. It is caused by defective calcium handling in ventricular myocytes. The association of supraventricular tachycardia (SVT with CPVT is described in the literature, occurring in the lead-up to ventricular tachycardia during exercise testing. We describe three cases of SVT that were initiated in the recovery period of exercise testing in children with CPVT.

  6. Bidirectional Ventricular Tachycardia: A Hallmark of Catecholaminergic Polymorphic Ventricular Tachycardia

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    Dr. Francisco Femenia, MD

    2012-03-01

    Full Text Available Catecholaminergic polymorphic ventricular tachycardia is a familial cardiac arrhythmia that is related to RYR2 or CASQ2 gene mutation. It occurs in patients with structurally normal heart and causes exercise-emotion triggered syncope and sudden cardiac death. We present a 13 year-old girl with recurrent episodes of exercise-related syncope and prior history of sudden death in a first degree relative.

  7. Catecholaminergic polymorphic ventricular tachycardia: An exciting new era

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    Shashank P Behere

    2016-01-01

    Full Text Available Catecholaminergic polymorphic ventricular tachycardia (CPVT is a highly malignant inheritable cardiac channelopathy. The past decade and a half has provided exciting new discoveries elucidating the genetic etiology and pathophysiology of CPVT. This review of the current literature on CPVT aims to summarize the state of the art in our understanding of the genetic etiology and the molecular pathogenesis of CPVT, and how these relate to our current approach to diagnosis and management. We will also shed light on groundbreaking new work that will continue to refine the management of CPVT in the future. As our knowledge of CPVT continues to grow, further studies will yield a better understanding of the efficacy and pitfalls of established diagnostic approaches and therapies as well as help shape newer diagnostic and treatment strategies. Two separate searches were run on the National Center for Biotechnology Information's (NCBI website. The first used the medical subject headings (MeSH database using the term “catecholaminergic polymorphic ventricular tachycardia” that was run on the PubMed database using the age filter (birth to 18 years, and it yielded 58 results. The second search using the MeSH database with the search term “catecholaminergic polymorphic ventricular tachycardia,” applying no filters yielded 178 results. The abstracts of all these articles were studied and the articles were categorized and organized. Articles of relevance were read in full. As and where applicable, relevant references and citations from the primary articles were further explored and read in full.

  8. Molecular diagnostics of catecholaminergic polymorphic ventricular tachycardia using denaturing high-performance liquid chromatography and sequencing

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    Postma, Alex V.; Bhuiyan, Zahurul A.; Bikker, Hennie

    2006-01-01

    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disease characterized by adrenergic-induced arrhythmias in the form of bidirectional and PVT. CPVT is a distinct clinical entity associated with a high mortality rate of up to 50% by the age of 30 yr. Recently, the

  9. Catecholaminergic polymorphic ventricular tachycardia. An important diagnosis in children with syncope and normal heart

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    Luiz Roberto Leite

    2001-01-01

    Full Text Available Syncope in children is primarily related to vagal hyperreactivity, but ventricular tachycardia (VT way rarely be seen. Catecholaminergic polymorphic VT is a rare entity that can occur in children without heart disease and with a normal QT interval, which may cause syncope and sudden cardiac death. In this report, we describe the clinical features, treatment, and clinical follow-up of three children with syncope associated with physical effort or emotion and cathecolaminergic polymorphic VT. Symptoms were controlled with beta-blockers, but one patient died suddenly in the fourth year of follow-up. Despite the rare occurrence, catecholaminergic polymorphic VT is an important cause of syncope and sudden death in children with no identified heart disease and normal QT interval.

  10. Clinical and genetic profile of catecholaminergic polymorphic ventricular tachycardia in Hong Kong Chinese children.

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    Yu, T C; Liu, A Py; Lun, K S; Chung, B Hy; Yung, T C

    2016-08-01

    To report our experience in the management of catecholaminergic polymorphic ventricular tachycardia in Hong Kong Chinese children. This case series study was conducted in a tertiary paediatric cardiology centre in Hong Kong. All paediatric patients diagnosed at our centre with catecholaminergic polymorphic ventricular tachycardia from January 2008 to October 2014 were included. Ten patients (five females and five males) were identified. The mean age at presentation and at diagnosis were 11.0 (standard deviation, 2.9) years and 12.5 (2.8) years, respectively. The mean delay time from first presentation to diagnosis was 1.5 (standard deviation, 1.3) years. They presented with recurrent syncope and six patients had a history of aborted cardiac arrest. Four patients were initially misdiagnosed to have epilepsy. Catecholaminergic polymorphic ventricular tachycardia was diagnosed by electrocardiogram at cardiac arrest (n=2), or provocation test, either by catecholamine infusion test (n=6) or exercise test (n=2). Mutations of the RyR2 gene were confirmed in six patients. Nine patients were commenced on beta-blockers after diagnosis. Despite medications, three patients developed aborted or resuscitated cardiac arrest (n=2) and syncope (n=1). Left cardiac sympathetic denervation was performed in five patients and an implantable cardioverter defibrillator was implanted in another. There was no mortality during follow-up. Catecholaminergic polymorphic ventricular tachycardia should be considered in children who present with recurrent syncope during exercise or emotional stress. Despite beta-blocker treatment, recurrent ventricular arrhythmias occur and may result in cardiac arrest.

  11. Catecholaminergic polymorphic ventricular tachycardia in a 3-year-old with occult myocarditis.

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    Bryant, Randall M; Redfearn, Sharon P; Marangi, Don; Davenport, Joseph P; Kuntz, Sean T; Schowengerdt, Kenneth O

    2002-10-01

    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare clinical entity in children. Occult myocarditis has not been previously implicated as an etiologic agent. A 3-year-old female presents with a presumed breath-holding spell and is found to have ventricular fibrillation requiring DC cardioversion. An invasive electrophysiological study was performed demonstrating the absence of inducible ventricular arrhythmias. Low dose epinephrine confirmed the presence CPVT. Right ventricular endomyocardial biopsies sent for polymerase chain reaction (PCR) analysis demonstrated the presence of adenoviral DNA. The authors hypothesize that occult myocarditis may be the inciting agent for CPVT in children.

  12. Guidelines for the diagnosis and management of Catecholaminergic Polymorphic Ventricular Tachycardia.

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    Pflaumer, Andreas; Davis, Andrew M

    2012-02-01

    Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is an inherited arrhythmia syndrome, characterised by polymorphic ventricular tachycardia induced by adrenergic stress. CPVT can be caused by mutations the cardiac ryanodine receptor gene (RYR2) or mutations in the cardiac calsequestrin gene CASQ2. Structural heart disease is usually absent and the baseline ECG is usually normal. Patients with CPVT often present with exercise- or emotion induced syncope, the first presentation can also be sudden cardiac death. Besides removal of triggers treatment with beta blockers is currently a class I indication in clinically diagnosed patients. Beta blockage should be titrated up to an effective level. The addition of flecainide seems to be a promising approach in patients where arrhythmias are not completely suppressed by beta blockers. A cardioverter-defibrillator (ICD) or left cervical sympathetic denervation might be considered under special circumstances. Genetic counselling is recommended and all first degree relatives should be properly evaluated. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  13. Integration of 60 000 exomes and ACMG guidelines question the role of Catecholaminergic Polymorphic Ventricular Tachycardia associated variants

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    Paludan-Müller, Christian; Ahlberg, Gustav; Ghouse, Jonas

    2017-01-01

    Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is a highly lethal cardiac arrhythmia disease occurring during exercise or psychological stress. CPVT has an estimated prevalence of 1:10 000 and has mainly been associated with variants in calcium regulating genes. Identification...... of potential false-positive pathogenic variants was conducted by searching The Exome Aggregation Consortium (ExAC) database (n=60 706) for variants reported to be associated with CPVT. The pathogenicity of the interrogated variants was assessed using guidelines from the American College of Medical Genetics...... and Genomics (ACMG) and in silico prediction tools. Thirty-eight out of 246 variants (15%) previously associated with CPVT were identified in the ExAC database. We predicted the CPVT prevalence to be 1:132. The ACMG standards classified 29% of ExAC variants as pathogenic or likely pathogenic. The in silico...

  14. Hormonal modulation of catecholaminergic neurotransmission in a prenatal stress model.

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    Pallarés, María Eugenia; Antonelli, Marta C

    2015-01-01

    Our laboratory has a long-standing interest in the effects of prenatal stress (PS) on various neurotransmitter pathways and the morphology of the developing brain as well as in behavioural aspects of the offspring. Employing a commonly used PS paradigm in which the dams were subjected to restraint stress during the last week of gestation, we observed that several of these pathways were altered in the offspring brain. In this chapter, we will summarize and discuss the results obtained with the main catecholaminergic pathways, namely dopamine (DA) and norepinephrine (NE). In our hands, PS produces an increase in dopamine D2-type receptors in limbic areas, a decreased DA release after amphetamine stimulation in prefrontal cortex (PFC) and an increase in NE release in the same area of the adult offspring brain. In addition, DA uptake is altered at prepubertal stages that persist through adulthood. However, the expression of the step-limiting enzyme of the DA synthesis, tyrosine hydroxylase (TH), is only impaired at early stages of development after PS in the neuronal bodies. At the nuclear regulation level, dopaminergic transcription factors Nurr1 and Ptx3 showed a high vulnerability to PS showing changes along the lifespan. It was striking to observe that many impairments observed in most of these pathways differed depending on whether they were tested before or after puberty indicating a particular sensitivity of the systems to variations in gonadal hormones peaks. In fact, we observed that PS induced long-term effects on the male offspring reproductive system and spermatogenesis development, particularly by inducing a long-term imbalance of circulating sexual hormone levels. Our findings suggest that PS exerts long-term effects on various neurotransmitter pathways altering the normal connectivity between brain areas. Since the developing forebrain was shown to be influenced by androgen exposure, and PS was shown to disrupt prenatal testosterone surges, our results

  15. Characterization of a novel mutation in the cardiac ryanodine receptor that results in catecholaminergic polymorphic ventricular tachycardia

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    Jiang, Dawei; Jones, Peter P; Davis, Darryl R; Gow, Robert; Green, Martin S; Birnie, David H; Chen, SR Wayne

    2010-01-01

    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disease that manifests as syncope or sudden death during high adrenergic tone in the absence of structural heart defects. It is primarily caused by mutations in the cardiac ryanodine receptor (RyR2). The mechanism by which these mutations cause arrhythmia remains controversial, with discrepant findings related to the role of the RyR2 binding protein FKBP12.6. The purpose of this study was to characterize a novel RyR2 mutation identified in a kindred with clinically diagnosed CPVT. Single-strand conformational polymorphism analysis and direct DNA sequencing were used to screen the RyR2 gene for mutations. Site-directed mutagenesis was employed to introduce the mutation into the mouse RyR2 cDNA. The impact of the mutation on the interaction between RyR2 and a 12.6 kDa FK506 binding protein (FKBP12.6) was determined by immunoprecipitation and immunoblotting and its effect on RyR2 function was characterized by single cell Ca2+ imaging and [3H]ryanodine binding. A novel CPVT mutation, E189D, was identified. The E189D mutation does not alter the affinity of the channel for FKBP12.6, but it increases the propensity for store-overload-induced Ca2+ release (SOICR). Furthermore, the E189D mutation enhances the basal channel activity of RyR2 and its sensitivity to activation by caffeine. The E189D RyR2 mutation is causative for CPVT and functionally increases the propensity for SOICR without altering the affinity for FKBP12.6. These observations strengthen the notion that enhanced SOICR, but not altered FKBP12.6 binding, is a common mechanism by which RyR2 mutations cause arrhythmias. PMID:20676041

  16. Flecainide Reduces Ventricular Arrhythmias in Patients With Genotype RyR2-positive Catecholaminergic Polymorphic Ventricular Tachycardia.

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    Wangüemert Pérez, Fernando; Hernández Afonso, Julio Salvador; Groba Marco, María Del Val; Caballero Dorta, Eduardo; Álvarez Acosta, Luis; Campuzano Larrea, Oscar; Pérez, Guillermo; Brugada Terradellas, Josep; Brugada Terradellas, Ramón

    2018-03-01

    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by polymorphic or bidirectional ventricular arrhythmias (VA) triggered by physical or emotional stress in young people with a structurally normal heart. Beta-blockers are the cornerstone of treatment, while flecainide has recently been incorporated into the therapeutic arsenal. The aim of this study was to report our experience with this drug. The cohort included 174 genotype-positive CPVT-patients from 7 families. We collected data from patients who were receiving flecainide and analyzed the indications, adverse effects and dosage, clinical events, VA and arrhythmic window during exercise testing, and implantable cardioverter-defibrillator (ICD) shocks during follow-up. Eighteen patients (10.4%) received flecainide; 17 patients in combination with beta-blockers, and 1 patient as monotherapy due to beta-blocker intolerance. None of the patients presented side effects. In 13 patients (72.2%) the indication was the persistence of exercise-induced VA and in 5 patients (27.7%) persistent ICD-shocks, despite on beta-blockers. After flecainide initiation, the exercise-induced VA quantitative score was reduced by more than 50% in 66.7% of the members of family 1 (32.76 ± 84.06 vs 74.38 ± 153.86; P = .018). The arrhythmic window was reduced (5.8 ± 11.9 bpm vs 19.69 ± 21.27 bpm; P = .007), and 4 of 5 patients with appropriate ICD shocks experienced no further shocks in the follow-up. In CPVT-patients flecainide reduces clinical events, exercise-induced VA, the arrhythmic window, and ICD shocks, with good tolerance. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  17. Non-ventricular, Clinical, and Functional Features of the RyR2(R420Q) Mutation Causing Catecholaminergic Polymorphic Ventricular Tachycardia.

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    Domingo, Diana; Neco, Patricia; Fernández-Pons, Elena; Zissimopoulos, Spyros; Molina, Pilar; Olagüe, José; Suárez-Mier, M Paz; Lai, F Anthony; Gómez, Ana M; Zorio, Esther

    2015-05-01

    Catecholaminergic polymorphic ventricular tachycardia is a malignant disease, due to mutations in proteins controlling Ca(2+) homeostasis. While the phenotype is characterized by polymorphic ventricular arrhythmias under stress, supraventricular arrhythmias may occur and are not fully characterized. Twenty-five relatives from a Spanish family with several sudden deaths were evaluated with electrocardiogram, exercise testing, and optional epinephrine challenge. Selective RyR2 sequencing in an affected individual and cascade screening in the rest of the family was offered. The RyR2(R420Q) mutation was generated in HEK-293 cells using site-directed mutagenesis to conduct in vitro functional studies. The exercise testing unmasked catecholaminergic polymorphic ventricular tachycardia in 8 relatives (sensitivity = 89%; positive predictive value = 100%; negative predictive value = 93%), all of them carrying the heterozygous RyR2(R420Q) mutation, which was also present in the proband and a young girl without exercise testing, a 91% penetrance at the end of the follow-up. Remarkably, sinus bradycardia, atrial and junctional arrhythmias, and/or giant post-effort U-waves were identified in patients. Upon permeabilization and in intact cells, the RyR2(R420Q) expressing cells showed a smaller peak of Ca(2+) release than RyR2 wild-type cells. However, at physiologic intracellular Ca(2+) concentration, equivalent to the diastolic cytosolic concentration, the RyR2(R420Q) released more Ca(2+) and oscillated faster than RyR2 wild-type cells. The missense RyR2(R420Q) mutation was identified in the N-terminus of the RyR2 gene in this highly symptomatic family. Remarkably, this mutation is associated with sinus bradycardia, atrial and junctional arrhythmias, and giant U-waves. Collectively, functional heterologous expression studies suggest that the RyR2(R420Q) behaves as an aberrant channel, as a loss- or gain-of-function mutation depending on cytosolic intracellular Ca(2

  18. The catecholaminergic nerve plexus of Holothuroidea

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    Díaz-Balzac, Carlos A.; Mejías, Wigberto; Jiménez, Luis B.

    2010-01-01

    Catecholamines have been extensively reported to be present in most animal groups, including members of Echinodermata. In this study, we investigated the presence and distribution of catecholaminergic nerves in two members of the Holothuroidea, Holothuria glaberrima (Selenka, 1867) (Aspidochirotida, Holothuroidea) and Holothuria mexicana (Ludwig, 1875) (Aspidochirotida, Holothuroidea), by using induced fluorescence for catecholamines on tissue sections and immunohistochemistry with an antibody that recognizes tyrosine hydroxylase. The presence of a catecholaminergic nerve plexus similar in distribution and extension to those previously reported in other members of Echinodermata was observed. This plexus, composed of cells and fibers, is found in the ectoneural component of the echinoderm nervous system and is continuous with the circumoral nerve ring and the radial nerves, tentacular nerves, and esophageal plexus. In addition, fluorescent nerves in the tube feet are continuous with the catecholaminergic components of the radial nerve cords. This is the first comprehensive report on the presence and distribution of catecholamines in the nervous system of Holothuroidea. The continuity and distribution of the catecholaminergic plexus strengthen the notion that the catecholaminergic cells are interneurons, since these do not form part of the known sensory or motor circuits and the fluorescence is confined to organized nervous tissue. PMID:20827375

  19. Impaired mTORC2 signaling in catecholaminergic neurons exaggerates high fat diet-induced hyperphagia

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    Olga I. Dadalko

    2015-09-01

    Conclusions: Our data support a model in which mTORC2 signaling within catecholaminergic neurons constrains consumption of a high-fat diet, while disruption causes high-fat diet-specific exaggerated hyperphagia. In parallel, impaired mTORC2 signaling leads to aberrant striatal DA neurotransmission, which has been associated with obesity in human and animal models, as well as with escalating substance abuse. These data suggest that defects localized to the catecholaminergic pathways are capable of overriding homeostatic circuits, leading to obesity, metabolic impairment, and aberrant DA-dependent behaviors.

  20. Modafinil as a catecholaminergic agent: empirical evidence and unanswered questions

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    Jonathan P Wisor

    2013-10-01

    Full Text Available Modafinil, in its two clinical formulations (Provigil® and Nuvigil®, is a widely prescribed wake-promoting therapeutic agent. It binds competitively to the cell membrane dopamine transporter and is dependent on catecholaminergic (dopaminergic and adrenergic signaling for its wake-promoting effects. The clinical spectrum of effects for modafinil is distinct from the effects seen with other catecholaminergic agents. Relative to other commonly used agents that act through catecholaminergic mechanisms, modafinil has a relatively low abuse potential, produces wakefulness with an attenuated compensatory sleep recovery thereafter, and does not ameliorate cataplexy in narcolepsy. These clinically relevant phenomenological differences between modafinil and agents such as amphetamines and cocaine do not eliminate catecholaminergic effects as a possible mediator of its wake-promoting action; they merely reflect its unique pharmacological profile. Modafinil is an exceptionally weak, but apparently very selective, dopamine transporter inhibitor. The pharmacodynamic response to modafinil, as measured by dopamine levels in brain microdialysate, is protracted relative to other agents that act via catecholaminergic mechanisms. The conformational constraints on the interaction of modafinil with the dopamine transporter—and probably, as a consequence, its effects on trace amine receptor signaling in the catecholaminergic cell—are unique among catecholaminergic agents. These unique pharmacological properties of modafinil should be considered both in seeking to thoroughly understand its putatively elusive mechanism of action and in the design of novel therapeutic agents.

  1. [Catecholaminergic polymorphic ventricular tachycardia is a rare inherited heart disease.

    DEFF Research Database (Denmark)

    Holst, Anders Gaarsdal; Tfelt-Hansen, 1jacob; Olesen, Morten S

    2010-01-01

    or cardiac arrest. The arrhythmias are usually triggered by exercise or emotional affection. The diagnosis is often made using exercise electrocardiogram, which typically triggers arrhythmias. The treatment consists of beta blockers, frequently in combination with implantation of a cardioverter...

  2. Deletion of Rictor in catecholaminergic neurons alters locomotor activity and ingestive behavior.

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    Kaska, Sophia; Brunk, Rebecca; Bali, Vedrana; Kechner, Megan; Mazei-Robison, Michelle S

    2017-05-01

    While the etiology of depression is not fully understood, increasing evidence from animal models suggests a role for the ventral tegmental area (VTA) in pathogenesis. In this paper, we investigate the potential role of VTA mechanistic target of rapamycin 2 (TORC2) signaling in mediating susceptibility to chronic social defeat stress (CSDS), a well-established mouse model of depression. Utilizing genetic and viral knockout of Rictor (rapamycin-insensitive companion of target of rapamycin), a requisite component of TORC2, we demonstrate that decreasing Rictor-dependent TORC2 signaling in catecholaminergic neurons, or within the VTA specifically, does not alter susceptibility to CSDS. Opiate abuse and mood disorders are often comorbid, and previous data demonstrate a role for VTA TORC2 in mediating opiate reward. Thus, we also investigated its potential role in mediating changes in opiate reward following CSDS. Catecholaminergic deletion of Rictor increases water, sucrose, and morphine intake but not preference in a two-bottle choice assay in stress-naïve mice, and these effects are maintained after stress. VTA-specific knockout of Rictor increases water and sucrose intake after physical CSDS, but does not alter consummatory behavior in the absence of stress. These findings suggest a novel role for TORC2 in mediating stress-induced changes in consummatory behaviors that may contribute to some aspects of mood disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. The catecholaminergic-cholinergic balance hypothesis of bipolar disorder revisited

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    van Enkhuizen, Jordy; Janowsky, David S; Olivier, Berend; Minassian, Arpi; Perry, William; Young, Jared W; Geyer, Mark A

    2014-01-01

    Bipolar disorder is a unique illness characterized by fluctuations between mood states of depression and mania. Originally, an adrenergic-cholinergic balance hypothesis was postulated to underlie these different affective states. In this review, we update this hypothesis with recent findings from human and animal studies, suggesting that a catecholaminergic-cholinergic hypothesis may be more relevant. Evidence from neuroimaging studies, neuropharmacological interventions, and genetic associations support the notion that increased cholinergic functioning underlies depression, whereas increased activations of the catecholamines (dopamine and norepinephrine) underlie mania. Elevated functional acetylcholine during depression may affect both muscarinic and nicotinic acetylcholine receptors in a compensatory fashion. Increased functional dopamine and norepinephrine during mania on the other hand may affect receptor expression and functioning of dopamine reuptake transporters. Despite increasing evidence supporting this hypothesis, a relationship between these two neurotransmitter systems that could explain cycling between states of depression and mania is missing. Future studies should focus on the influence of environmental stimuli and genetic susceptibilities that may affect the catecholaminergic-cholinergic balance underlying cycling between the affective states. Overall, observations from recent studies add important data to this revised balance theory of bipolar disorder, renewing interest in this field of research. PMID:25107282

  4. Risk of catecholaminergic crisis following glucocorticoid administration in patients with an adrenal mass: a literature review

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    Barrett, C.; Uum, S.H. van; Lenders, J.W.M.

    2015-01-01

    BACKGROUND: Glucocorticoids as diagnostic or therapeutic agents have been reported to carry an increased risk of catecholaminergic crisis (CC) in patients with pheochromocytoma or paraganglioma (PPGL). METHODS: We searched literature databases using the following terms: pheochromocytoma,

  5. Glucocorticoids, master modulators of the thymic catecholaminergic system?

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    I. Pilipović

    Full Text Available There is evidence that the major mediators of stress, i.e., catecholamines and glucocorticoids, play an important role in modulating thymopoiesis and consequently immune responses. Furthermore, there are data suggesting that glucocorticoids influence catecholamine action. Therefore, to assess the putative relevance of glucocorticoid-catecholamine interplay in the modulation of thymopoiesis we analyzed thymocyte differentiation/maturation in non-adrenalectomized and andrenalectomized rats subjected to treatment with propranolol (0.4 mg·100 g body weight-1·day-1 for 4 days. The effects of β-adrenoceptor blockade on thymopoiesis in non-adrenalectomized rats differed not only quantitatively but also qualitatively from those in adrenalectomized rats. In adrenalectomized rats, besides a more efficient thymopoiesis [judged by a more pronounced increase in the relative proportion of the most mature single-positive TCRαβhigh thymocytes as revealed by two-way ANOVA; for CD4+CD8- F (1,20 = 10.92, P < 0.01; for CD4-CD8+ F (1,20 = 7.47, P < 0.05], a skewed thymocyte maturation towards the CD4-CD8+ phenotype, and consequently a diminished CD4+CD8-/CD4-CD8+ mature TCRαβhigh thymocyte ratio (3.41 ± 0.21 in non-adrenalectomized rats vs 2.90 ± 0.31 in adrenalectomized rats, P < 0.05 were found. Therefore, we assumed that catecholaminergic modulation of thymopoiesis exhibits a substantial degree of glucocorticoid-dependent plasticity. Given that glucocorticoids, apart from catecholamine synthesis, influence adrenoceptor expression, we also hypothesized that the lack of adrenal glucocorticoids affected not only β-adrenoceptor- but also α-adrenoceptor-mediated modulation of thymopoiesis.

  6. Determination of solubility profiles of eflucimibe polymorphs: experimental and modeling.

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    Teychene, S; Autret, J M; Biscans, B

    2006-04-01

    This work presents the determination of the phase diagram of two polymorphs of Eflucimibe in pure solvents and solvent mixtures at different temperatures. Solid phase changes were analysed by Differential Scanning Calorimetry. Solubility measurements show that the solubility of the two forms are very similar. Experimental data obtained in ethanol, reported in a Van t'Hoff plot, exhibit a transition temperature around 265 K. A single maximum is observed when solubility is plotted against the solubility parameters of solvents or solvent mixture and it is not related to a solid phase change. This phenomenon, known as a positive synergetic effect, has been explained in term of evolution of solute-solvents polar interactions. Several thermodynamics models (UNIFAC, UNIQUAC, Wilson, Scatchard Hildebrand ... ) were tested in order to predict the Liquid-Solid Equilibrium for this system. The semi empirical model UNIQUAC gives the best fit. The results obtained are in good agreement with the experimental data (mean deviation lower than 5%) and the solubility maximum found experimentally for each polymorph is also well described.

  7. Modeling dynamic beta-gamma polymorphic transition in Tin

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    Chauvin, Camille; Montheillet, Frank; Petit, Jacques; CEA Gramat Collaboration; EMSE Collaboration

    2015-06-01

    Solid-solid phase transitions in metals have been studied by shock waves techniques for many decades. Recent experiments have investigated the transition during isentropic compression experiments and shock-wave compression and have highlighted the strong influence of the loading rate on the transition. Complementary data obtained with velocity and temperature measurements around the polymorphic transition beta-gamma of Tin on gas gun experiments have displayed the importance of the kinetics of the transition. But, even though this phenomenon is known, modeling the kinetic remains complex and based on empirical formulations. A multiphase EOS is available in our 1D Lagrangian code Unidim. We propose to present the influence of various kinetic laws (either empirical or involving nucleation and growth mechanisms) and their parameters (Gibbs free energy, temperature, pressure) on the transformation rate. We compare experimental and calculated velocities and temperature profiles and we underline the effects of the empirical parameters of these models.

  8. Cholinergic and catecholaminergic neurons relay striatal information to the optic tectum in amphibians

    NARCIS (Netherlands)

    Marin, O.; Smeets, W.J.A.J.; Munoz, M.; Sanchez-Camacho, C.; Pena, A.S.; Lopez, J.M.; Gonzalez, A.

    1999-01-01

    In the amphibians Rana perezi and Xenopus laevis, the involvement of cholinergic and catecholaminergic neurons in the relay of basal ganglia inputs to the tectum was investigated. Tract-tracing experiments, in which anterograde tracers were applied to the basal ganglia and retrograde tracers to the

  9. Unfolded Protein Response Is Activated in the Hearts of Catecholaminergic Polymorphic Ventricular Tachycardia (Cpvt Mice

    Directory of Open Access Journals (Sweden)

    Bakiu Rigers

    2014-10-01

    Full Text Available Izoforma 2 kalsekvestrina (CSQ2 je glavni kalcijum-vezujući protein sarkoplazmatskog retikuluma (SR i nalazi se kako u srčanom tako i u skeletnom mišiću. CSQ2 deluje kao kalcijumski receptor koji reguliše oslobađanje Ca2+ jona iz SR, putem interakcije sa triadinom, junktinom i rianodinskim receptorom. Različite mutacije csq2 gena mogu da izazovu poremećaje u oslobađanju Ca2+ i time kontraktilne funkcije, čime doprinose ravoju aritmija i iznenadnoj srčanoj smrti mladih osoba koje boluju od kateholaminergičke polimorfne ventrikularne tahikardije (CPVT. Razvojem transgenetskih miševa sa CSG2 point mutacijom (R33Q i CPVT-om, primećen je drastičan pad nivoa mutiranog proteina. Prateći biomolekularni pristup, nekoliko analiza je izvedeno, koristeći tretman različitim antitelima, sa ciljem da se otkrije kada počinje smanjenje nivoa CSQ2, rasvetli mehanizam uključen u redukciju CSQ2 i ispita da li prisustvo mutiranih proteina utiče i na druge proteine. Rezultati ove studije su pokazali da se nivoi mutiranih CSQ2 smanjuju ubrzo nakon rodjenja, što je udruženo sa smanjenim nivoom ostalih značajnih proteina SR, uključujući triadin (TD. Takođe je primećeno da odgovor nesavijenih proteina može biti povezan sa ushodnom regulacijom proteina i aktivacijom ATF-6 zavisnog signalnog puta. Prisustvo R33Q mutacije je izazvalo smanjenje nivoa CSQ2 putem aktivacije odgovora nesavijenih proteina i posledične proteozomalne degradacije.

  10. Nationwide experience of catecholaminergic polymorphic ventricular tachycardia caused by RyR2 mutations

    DEFF Research Database (Denmark)

    Broendberg, Anders Krogh; Nielsen, Jens Cosedis; Bjerre, Jesper

    2017-01-01

    probands, 18 symptomatic and 10 asymptomatic relatives with a RyR2 mutation. Twenty (87%) probands and 10 (36%) relatives had severe presenting symptoms (sudden cardiac death (SCD), aborted SCD (ASCD) or syncope).As compared with symptomatic relatives, probands had lower age at onset of symptoms (16 years...... of the 28 ICD treated patients (7%). No patients receiving treatment died during follow-up (57 months (IQR, 32-139)). Multifocal atrial tachycardia was the predominant symptom in five patients. CONCLUSIONS: In a national cohort of RyR2 mutation-positive CPVT patients, SCD, ASCD and syncope were presenting...

  11. Descending supraspinal pathways in amphibians. II. Distribution and origin of the catecholaminergic innervation of the spinal cord.

    NARCIS (Netherlands)

    Sanchez-Camacho, C.; Marin, O.; Smeets, W.J.; Donkelaar, H.J. ten; Gonzalez, A.

    2001-01-01

    Immunohistochemical studies with antibodies against tyrosine hydroxylase, dopamine, and noradrenaline have revealed that the spinal cord of anuran, urodele, and gymnophionan (apodan) amphibians is abundantly innervated by catecholaminergic (CA) fibers and terminals. Because intraspinal cells occur

  12. Rheumatoid arthritis: identifying and characterising polymorphisms using rat models

    Science.gov (United States)

    2016-01-01

    ABSTRACT Rheumatoid arthritis is a chronic inflammatory joint disorder characterised by erosive inflammation of the articular cartilage and by destruction of the synovial joints. It is regulated by both genetic and environmental factors, and, currently, there is no preventative treatment or cure for this disease. Genome-wide association studies have identified ∼100 new loci associated with rheumatoid arthritis, in addition to the already known locus within the major histocompatibility complex II region. However, together, these loci account for only a modest fraction of the genetic variance associated with this disease and very little is known about the pathogenic roles of most of the risk loci identified. Here, we discuss how rat models of rheumatoid arthritis are being used to detect quantitative trait loci that regulate different arthritic traits by genetic linkage analysis and to positionally clone the underlying causative genes using congenic strains. By isolating specific loci on a fixed genetic background, congenic strains overcome the challenges of genetic heterogeneity and environmental interactions associated with human studies. Most importantly, congenic strains allow functional experimental studies be performed to investigate the pathological consequences of natural genetic polymorphisms, as illustrated by the discovery of several major disease genes that contribute to arthritis in rats. We discuss how these advances have provided new biological insights into arthritis in humans. PMID:27736747

  13. MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration

    OpenAIRE

    Cebrián, Carolina; Zucca, Fabio A.; Mauri, Pierluigi; Steinbeck, Julius A.; Studer, Lorenz; Scherzer, Clemens R.; Kanter, Ellen; Budhu, Sadna; Mandelbaum, Jonathan; Vonsattel, Jean P.; Zecca, Luigi; Loike, John D.; Sulzer, David

    2014-01-01

    Subsets of rodent neurons are reported to express major histocompatibilty complex class I (MHC-I), but such expression has not been reported in normal adult human neurons. Here we provide evidence from immunolabel, RNA expression, and mass spectrometry analysis of postmortem samples that human catecholaminergic substantia nigra and locus coeruleus neurons express MHC-I, and that this molecule is inducible in human stem cell derived dopamine (DA) neurons. Catecholamine murine cultured neurons ...

  14. Logistic regression models for polymorphic and antagonistic pleiotropic gene action on human aging and longevity

    DEFF Research Database (Denmark)

    Tan, Qihua; Bathum, L; Christiansen, L

    2003-01-01

    In this paper, we apply logistic regression models to measure genetic association with human survival for highly polymorphic and pleiotropic genes. By modelling genotype frequency as a function of age, we introduce a logistic regression model with polytomous responses to handle the polymorphic...... situation. Genotype and allele-based parameterization can be used to investigate the modes of gene action and to reduce the number of parameters, so that the power is increased while the amount of multiple testing minimized. A binomial logistic regression model with fractional polynomials is used to capture...

  15. MIDBRAIN CATECHOLAMINERGIC NEURONS CO-EXPRESS α-SYNUCLEIN AND TAU IN PROGRESSIVE SUPRANUCLEAR PALSY

    Directory of Open Access Journals (Sweden)

    María Elena eErro Aguirre

    2015-03-01

    Full Text Available Objective: To analyze the frequency and distribution of α-synuclein deposits in progressive supranuclear palsy (PSP.Methods: The brains of 25 cases of pathologically confirmed PSP were evaluated with immunohistochemistry for α-synuclein and tau. Multiple immunofluorescent stains were applied to analyze the expression of tau and α-synuclein aggregates in catecholaminergic neurons. Patients’ clinical symptoms were retrospectively recorded. Results: Deposits α-synuclein in the form of typical Lewy bodies (LBs were only found in two PSP cases (8% that fulfilled the clinical subtype of PSP known as Richardson’s syndrome (RS. LBs were present in the locus ceruleus, substantia nigra pars compacta, basal forebrain, amygdala and cingulated cortex in a distribution mimicking that of Parkinson’s disease. Triple-immunolabeling revealed co-expression of α-synuclein and tau proteins in some tyrosine hydroxilase-positive neurons of the locus ceruleus and substantia nigra pars compacta.Conclusions: There is no apparent clinical correlation between the presence of LBs in PSP. Tau protein co-aggregate with α-synuclein in catecholaminergic neurons of PSP brains suggesting a synergistic interaction between the two proteins. This is in keeping with the current view of neurodegenerative disorders as ‘misfolded protein diseases’.

  16. Catecholaminergic Regulation of Learning Rate in a Dynamic Environment

    Science.gov (United States)

    Jepma, Marieke; Nassar, Matthew R.; Rangel-Gomez, Mauricio; Meeter, Martijn; Nieuwenhuis, Sander

    2016-01-01

    Adaptive behavior in a changing world requires flexibly adapting one’s rate of learning to the rate of environmental change. Recent studies have examined the computational mechanisms by which various environmental factors determine the impact of new outcomes on existing beliefs (i.e., the ‘learning rate’). However, the brain mechanisms, and in particular the neuromodulators, involved in this process are still largely unknown. The brain-wide neurophysiological effects of the catecholamines norepinephrine and dopamine on stimulus-evoked cortical responses suggest that the catecholamine systems are well positioned to regulate learning about environmental change, but more direct evidence for a role of this system is scant. Here, we report evidence from a study employing pharmacology, scalp electrophysiology and computational modeling (N = 32) that suggests an important role for catecholamines in learning rate regulation. We found that the P3 component of the EEG—an electrophysiological index of outcome-evoked phasic catecholamine release in the cortex—predicted learning rate, and formally mediated the effect of prediction-error magnitude on learning rate. P3 amplitude also mediated the effects of two computational variables—capturing the unexpectedness of an outcome and the uncertainty of a preexisting belief—on learning rate. Furthermore, a pharmacological manipulation of catecholamine activity affected learning rate following unanticipated task changes, in a way that depended on participants’ baseline learning rate. Our findings provide converging evidence for a causal role of the human catecholamine systems in learning-rate regulation as a function of environmental change. PMID:27792728

  17. Enhanced catecholaminergic and serotoninergic activity in rat brain from weaning to sexual maturity: rationale for prophylactic (-)deprenyl (selegiline) medication.

    Science.gov (United States)

    Knoll, J; Miklya, I

    1995-01-01

    Food deprived rats in the late developmental phase of life (2 months of age) are significantly more active than those in the early postdevelopmental phase (4 months of age), pointing to enhanced catecholaminergic activity during the developmental phase. We therefore measured the resting release of dopamine from the striatum, substantia nigra and tuberculum olfactorium, and of noradrenaline from the locus coeruleus, as an indicator of the basic activity of catecholaminergic neurons in the brain, in 2,4,8,16 and 32 weeks old male and female rats. We also measured the release of serotonin from the raphe. Both in male and female rats, the resting release of transmitters from brain catecholaminergic and serotoninergic neurons between weaning and the end of the 2nd month of age, i.e. during the crucial developmental phase of their life, was significantly higher than either before or after that period, signalling a transition from a developmental to a postdevelopmental (aging) phase of life and indicating that safe and effective measures are needed to maintain the catecholaminergic system at a higher activity level during the postdevelopmental phase. Daily administration of low doses (0.01-0.25 mg/kg) of (-)deprenyl for 21 days significantly enhances the resting release of catecholamines and diminishes that of serotonin, providing a rationale for prophylactic medication with this drug during the postdevelopmental lifespan. We also show that (-)methamphetamine, the parent compound of (-)deprenyl and (-)1-phenyl-2-propylaminopentane (PPAP), a deprenyl analogue free of MAO-B inhibitory potency but otherwise possessing the same pharmacological profile as (-)deprenyl, act similarly, furnishing direct evidence that enhancement of catecholaminergic activity in the brain by multiple, small dose administration of (-)deprenyl is unrelated to MAO-B inhibition.

  18. Analysis of the Catecholaminergic Phenotype in Human SH-SY5Y and BE(2-M17 Neuroblastoma Cell Lines upon Differentiation.

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    Roberta Filograna

    Full Text Available Human cell lines are often used to investigate cellular pathways relevant for physiological or pathological processes or to evaluate cell toxicity or protection induced by different compounds, including potential drugs. In this study, we analyzed and compared the differentiating activities of three agents (retinoic acid, staurosporine and 12-O-tetradecanoylphorbol-13-acetate on the human neuroblastoma SH-SY5Y and BE(2-M17 cell lines; the first cell line is largely used in the field of neuroscience, while the second is still poorly characterized. After evaluating their effects in terms of cell proliferation and morphology, we investigated their catecholaminergic properties by assessing the expression profiles of the major genes involved in catecholamine synthesis and storage and the cellular concentrations of the neurotransmitters dopamine and noradrenaline. Our results demonstrate that the two cell lines possess similar abilities to differentiate and acquire a neuron-like morphology. The most evident effects in SH-SY5Y cells were observed in the presence of staurosporine, while in BE(2-M17 cells, retinoic acid induced the strongest effects. Undifferentiated SH-SY5Y and BE(2-M17 cells are characterized by the production of both NA and DA, but their levels are considerably higher in BE(2-M17 cells. Moreover, the NAergic phenotype appears to be more pronounced in SH-SY5Y cells, while BE(2-M17 cells have a more prominent DAergic phenotype. Finally, the catecholamine concentration strongly increases upon differentiation induced by staurosporine in both cell lines. In conclusion, in this work the catecholaminergic phenotype of the human BE(2-M17 cell line upon differentiation was characterized for the first time. Our data suggest that SH-SY5Y and BE(2-M17 represent two alternative cell models for the neuroscience field.

  19. Catecholaminergic System of Invertebrates: Comparative and Evolutionary Aspects in Comparison With the Octopaminergic System.

    Science.gov (United States)

    Gallo, Valentina P; Accordi, Fiorenza; Chimenti, Claudio; Civinini, Annalena; Crivellato, Enrico

    2016-01-01

    In this review we examined the catecholaminergic system of invertebrates, starting from protists and getting to chordates. Different techniques used by numerous researchers revealed, in most examined phyla, the presence of catecholamines dopamine, noradrenaline, and adrenaline or of the enzymes involved in their synthesis. The catecholamines are generally linked to the nervous system and they can act as neurotransmitters, neuromodulators, and hormones; moreover they play a very important role as regards the response to a large number of stress situations. Nevertheless, in some invertebrate phyla belonging to Protostoma, the monoamine octopamine is the main biogenic amine. The presence of catecholamines in some protists suggests a role as intracellular or interorganismal signaling molecules and an ancient origin of their synthetic pathways. The catecholamines appear also involved in the regulation of bioluminescence and in the control of larval development and metamorphosis in some marine invertebrate phyla. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. A General Model of Negative Frequency Dependent Selection Explains Global Patterns of Human ABO Polymorphism

    Science.gov (United States)

    Villanea, Fernando A.; Safi, Kristin N.; Busch, Jeremiah W.

    2015-01-01

    The ABO locus in humans is characterized by elevated heterozygosity and very similar allele frequencies among populations scattered across the globe. Using knowledge of ABO protein function, we generated a simple model of asymmetric negative frequency dependent selection and genetic drift to explain the maintenance of ABO polymorphism and its loss in human populations. In our models, regardless of the strength of selection, models with large effective population sizes result in ABO allele frequencies that closely match those observed in most continental populations. Populations must be moderately small to fall out of equilibrium and lose either the A or B allele (Ne ≤ 50) and much smaller (Ne ≤ 25) for the complete loss of diversity, which nearly always involved the fixation of the O allele. A pattern of low heterozygosity at the ABO locus where loss of polymorphism occurs in our model is consistent with small populations, such as Native American populations. This study provides a general evolutionary model to explain the observed global patterns of polymorphism at the ABO locus and the pattern of allele loss in small populations. Moreover, these results inform the range of population sizes associated with the recent human colonization of the Americas. PMID:25946124

  1. A General Model of Negative Frequency Dependent Selection Explains Global Patterns of Human ABO Polymorphism.

    Directory of Open Access Journals (Sweden)

    Fernando A Villanea

    Full Text Available The ABO locus in humans is characterized by elevated heterozygosity and very similar allele frequencies among populations scattered across the globe. Using knowledge of ABO protein function, we generated a simple model of asymmetric negative frequency dependent selection and genetic drift to explain the maintenance of ABO polymorphism and its loss in human populations. In our models, regardless of the strength of selection, models with large effective population sizes result in ABO allele frequencies that closely match those observed in most continental populations. Populations must be moderately small to fall out of equilibrium and lose either the A or B allele (N(e ≤ 50 and much smaller (N(e ≤ 25 for the complete loss of diversity, which nearly always involved the fixation of the O allele. A pattern of low heterozygosity at the ABO locus where loss of polymorphism occurs in our model is consistent with small populations, such as Native American populations. This study provides a general evolutionary model to explain the observed global patterns of polymorphism at the ABO locus and the pattern of allele loss in small populations. Moreover, these results inform the range of population sizes associated with the recent human colonization of the Americas.

  2. Catecholaminergic and cholinergic systems of mouse brain are modulated by LMN diet, rich in theobromine, polyphenols and polyunsaturated fatty acids.

    Science.gov (United States)

    Fernández-Fernández, Laura; Esteban, Gerard; Giralt, Mercedes; Valente, Tony; Bolea, Irene; Solé, Montse; Sun, Ping; Benítez, Susana; Morelló, José Ramón; Reguant, Jordi; Ramírez, Bartolomé; Hidalgo, Juan; Unzeta, Mercedes

    2015-04-01

    The possible modulatory effect of the functional LMN diet, rich in theobromine, polyphenols and polyunsaturated fatty acids, on the catecholaminergic and cholinergic neurotransmission, affecting cognition decline during aging has been studied. 129S1/SvlmJ mice were fed for 10, 20, 30 and 40 days with either LMN or control diets. The enzymes involved in catecholaminergic and cholinergic metabolism were determined by both immunohistological and western blot analyses. Noradrenalin, dopamine and other metabolites were quantified by HPLC analysis. Theobromine, present in cocoa, the main LMN diet component, was analysed in parallel using SH-SY5Y and PC12 cell lines. An enhanced modulatory effect on both cholinergic and catecholaminergic transmissions was observed on 20 day fed mice. Similar effect was observed with theobromine, besides its antioxidant capacity inducing SOD-1 and GPx expression. The enhancing effect of the LMN diet and theobromine on the levels of acetylcholine-related enzymes, dopamine and specially noradrenalin confirms the beneficial role of this diet on the "cognitive reserve" and hence a possible reducing effect on cognitive decline underlying aging and Alzheimer's disease.

  3. Loss of catecholaminergic neuromodulation of persistent forms of hippocampal synaptic plasticity with increasing age

    Directory of Open Access Journals (Sweden)

    Hannah Twarkowski

    2016-09-01

    Full Text Available Neuromodulation by means of the catecholaminergic system is a key component of motivation-driven learning and behaviorally modulated hippocampal synaptic plasticity. In particular, dopamine acting on D1/D5 receptors and noradrenaline acting on beta-adrenergic receptors exert a very potent regulation of forms of hippocampal synaptic plasticity that last for very long-periods of time (>24h, and occur in conjunction with novel spatial learning. Antagonism of these receptors not only prevents long-term potentiation (LTP and long-term depression (LTD, but prevents the memory of the spatial event that, under normal circumstances, leads to the perpetuation of these plasticity forms. Spatial learning behavior that normally comes easily to rats, such as object-place learning and spatial reference learning, becomes increasingly impaired with aging. Middle-aged animals display aging-related deficits of specific, but not all, components of spatial learning, and one possibility is that this initial manifestation of decrements in learning ability that become manifest in middle-age relate to changes in motivation, attention and/or the regulation by neuromodulatory systems of these behavioral states.Here, we compared the regulation by dopaminergic D1/D5 and beta-adrenergic receptors of persistent LTP in young (2-4 month old and middle-aged (8-14 month old rats. We observed in young rats, that weak potentiation that typically lasts for ca. 2h could be strengthened into persistent (>24h LTP by pharmacological activation of either D1/D5 or beta-adrenergic receptors. By contrast, no such facilitation occurred in middle-aged rats. This difference was not related to an ostensible learning deficit: a facilitation of weak potentiation into LTP by spatial learning was possible both in young and middle-aged rats. It was also not directly linked to deficits in LTP: strong afferent stimulation resulted in equivalent LTP in both age groups. We postulate that this change in

  4. The VIS-AD data model: Integrating metadata and polymorphic display with a scientific programming language

    Science.gov (United States)

    Hibbard, William L.; Dyer, Charles R.; Paul, Brian E.

    1994-01-01

    The VIS-AD data model integrates metadata about the precision of values, including missing data indicators and the way that arrays sample continuous functions, with the data objects of a scientific programming language. The data objects of this data model form a lattice, ordered by the precision with which they approximate mathematical objects. We define a similar lattice of displays and study visualization processes as functions from data lattices to display lattices. Such functions can be applied to visualize data objects of all data types and are thus polymorphic.

  5. Controversies in Cardiovascular Research: Induced pluripotent stem cell-derived cardiomyocytes – boutique science or valuable arrhythmia model?

    Science.gov (United States)

    Knollmann, Björn C

    2013-01-01

    As part of the series on Controversies in Cardiovascular Research, the article reviews the strengths and limitations of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) as models of cardiac arrhythmias. Specifically, the article attempts to answer the following questions: Which clinical arrhythmias can be modeled by iPSC-CM? How well can iPSC-CM model adult ventricular myocytes? What are the strengths and limitations of published iPSC-CM arrhythmia models? What new mechanistic insight has been gained? What is the evidence that would support using iPSC-CM to personalize anti-arrhythmic drug therapy? The review also discusses the pros and cons of using the iPSC-CM technology for modeling specific genetic arrhythmia disorders such as long QT syndrome, Brugada Syndrome or Catecholaminergic Polymorphic Ventricular Tachycardia. PMID:23569106

  6. Risk of catecholaminergic crisis following glucocorticoid administration in patients with an adrenal mass: a literature review.

    Science.gov (United States)

    Barrett, Catherine; van Uum, Stan H M; Lenders, Jacques W M

    2015-11-01

    Glucocorticoids as diagnostic or therapeutic agents have been reported to carry an increased risk of catecholaminergic crisis (CC) in patients with pheochromocytoma or paraganglioma (PPGL). We searched literature databases using the following terms: pheochromocytoma, paraganglioma, adrenal incidentaloma, steroids, glucocorticoids, dexamethasone suppression test (DST), hypertensive crisis, cosyntropin and CRH. From all published case reports (1962-2013), we reviewed medical history, presenting symptoms, dose and route of steroid administration, location and size of adrenal mass, biochemical phenotype and outcome. Twenty-five case reports describing a CC were identified. Three patients with an adrenal incidentaloma suffered a CC following high-dose DST, and in one case, this was fatal. In two of these patients, biochemical testing missed the diagnosis, and in the third, a DST was done despite elevated urinary metanephrines. No CC has been reported for patients undergoing a low-dose DST. Three of 16 patients who received therapeutic glucocorticoids and four of six patients following cosyntropin testing died. No specific biochemical phenotype was related to adverse events. Although a causal relationship cannot be established from this review, it seems prudent to exclude a PPGL in patients with a large incidentaloma or when high-dose DST is considered in a patient with an incidentaloma of any size. Our literature review does not support the need for biochemical testing for PPGL prior to a low-dose (1 mg) DST. Finally, before starting therapeutic glucocorticoids, any clinical signs or symptoms of a potential PPGL should prompt reliable biochemical testing to rule out a PPGL. © 2015 John Wiley & Sons Ltd.

  7. Non-antipsychotic catecholaminergic drugs for antipsychotic-induced tardive dyskinesia.

    Science.gov (United States)

    El-Sayeh, Hany G; Rathbone, John; Soares-Weiser, Karla; Bergman, Hanna

    2018-01-18

    Tardive dyskinesia (TD) is a disabling movement disorder associated with the prolonged use of antipsychotic medication. Several strategies have been examined in the treatment of TD. Currently, however, there is no clear evidence of the effectiveness of these drugs in TD and they have been associated with many side effects. One particular strategy would be to use pharmaceutical agents which are known to influence the catecholaminergic system at various junctures. 1. To determine the effects of any of the following drugs for antipsychotic-induced TD in people with schizophrenia or other chronic mental illnesses.i. Drugs which influence the noradrenergic system.ii. Dopamine receptor agonists.iii. Dopamine receptor antagonists.iv. Dopamine-depletor drugs.v. Drugs that increase the production or release of dopamine.2. To examine whether any improvement occurred with short periods of intervention (less than 6 weeks) and, if this did occur, whether this effect was maintained at longer periods of follow-up.3. To examine if there was a differential effect for the various compounds.4. To examine whether the use of non-antipsychotic catecholaminergic drugs are most effective in those with more recent onset TD (less than five years). We retrieved 712 references from searching the Cochrane Schizophrenia Group Trials Register (July 2015 and April 2017). We also inspected references of all identified studies for further trials and contacted authors of trials for additional information. We selected studies if they were randomised controlled trials focusing on people with schizophrenia or other chronic mental illnesses and antipsychotic-induced tardive dyskinesia. We compared the use of catecholaminergic interventions versus placebo, no intervention, or any other intervention for the treatment of antipsychotic-induced tardive dyskinesia. We independently extracted data from these trials and we estimated risk ratios (RRs) with 95% confidence intervals (CIs). We assumed that people

  8. Modeling polymorphic transformation of rotating bacterial flagella in a viscous fluid

    Science.gov (United States)

    Ko, William; Lim, Sookkyung; Lee, Wanho; Kim, Yongsam; Berg, Howard C.; Peskin, Charles S.

    2017-06-01

    The helical flagella that are attached to the cell body of bacteria such as Escherichia coli and Salmonella typhimurium allow the cell to swim in a fluid environment. These flagella are capable of polymorphic transformation in that they take on various helical shapes that differ in helical pitch, radius, and chirality. We present a mathematical model of a single flagellum described by Kirchhoff rod theory that is immersed in a fluid governed by Stokes equations. We perform numerical simulations to demonstrate two mechanisms by which polymorphic transformation can occur, as observed in experiments. First, we consider a flagellar filament attached to a rotary motor in which transformations are triggered by a reversal of the direction of motor rotation [L. Turner et al., J. Bacteriol. 182, 2793 (2000), 10.1128/JB.182.10.2793-2801.2000]. We then consider a filament that is fixed on one end and immersed in an external fluid flow [H. Hotani, J. Mol. Biol. 156, 791 (1982), 10.1016/0022-2836(82)90142-5]. The detailed dynamics of the helical flagellum interacting with a viscous fluid is discussed and comparisons with experimental and theoretical results are provided.

  9. High performing rats are more sensitive toward catecholaminergic activity enhancer (CAE) compounds than their low performing peers.

    Science.gov (United States)

    Knoll, J; Knoll, B; Miklya, I

    1996-01-01

    Two breeds of rats, Charles River Wistar [Crl(Wi)Br.] and HSD Wistar [Wistar per LATI (Budapest) Br.], with remarkable difference in learning performance were selected. The rats were trained in the shuttle box with 100 trials per day and the number of conditioned avoidance responses (CARs), the escape failures (EFs) to the unconditioned stimulus and the intersignal reactions (IRs) were counted and evaluated by multi-way analysis of variance (ANOVA). Rats of the Crl (Wi) breed proved to be the 'low performing' (LP) animals and rats of the Wistar per LATI (Budapest) breed the 'high performing' (HP) ones. The HP rats produced higher number of CARs (pPPAP], which enhances action potential-transmitter release coupling in the catecholaminergic neurons, fully antagonized in a dose of 1 mg/kg, tetrabenazine-induced learning depression in HP rats and this dose was ineffective in LP rats. The findings were regarded as further support for the view that endogenous CAE substances regulate catecholaminergic activity in the brain and (-)PPAP acts via this regulation.

  10. Age and duration of inflammatory environment differentially affect the neuroimmune response and catecholaminergic neurons in the midbrain and brainstem.

    Science.gov (United States)

    Bardou, Isabelle; Kaercher, Roxanne M; Brothers, Holly M; Hopp, Sarah C; Royer, Sarah; Wenk, Gary L

    2014-05-01

    Neuroinflammation and degeneration of ascending catecholaminergic systems occur early in the neurodegenerative process. Age and the duration of a pro-inflammatory environment induced by continuous intraventricular lipopolysaccharide (LPS) differentially affect the expression profile of pro- and anti-inflammatory genes and proteins as well as the number of activated microglia (express major histocompatibility complex II; MHC II) and the integrity and density of ascending catecholaminergic neural systems originating from the locus coeruleus (LC) and substantia nigra pars compacta (SNpc) in rats. LPS infusion increased gene expression and/or protein levels for both pro- and anti-inflammatory biomarkers. Although LPS infusion stimulated a robust increase in IL-1ß gene and protein expression, this increase was blunted with age. LPS infusion also increased the density of activated microglia cells throughout the midbrain and brainstem. Corresponding to the development of a pro-inflammatory environment, LC and SNpc neurons immunopositive for tyrosine-hydroxylase (the rate-limiting synthetic enzyme for dopamine and norepinephrine) decreased in number, along with a decrease in tyrosine-hydroxylase gene expression in the midbrain and/or brainstem region. Our data support the concept that continuous exposure to a pro-inflammatory environment drives exaggerated changes in the production and release of inflammatory mediators that interact with age to impair functional capacity of the SNpc and LC. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. The distribution and morphological characteristics of catecholaminergic cells in the diencephalon and midbrain of the bottlenose dolphin (Tursiops truncatus).

    Science.gov (United States)

    Manger, Paul R; Fuxe, Kjell; Ridgway, Sam H; Siegel, Jerome M

    2004-01-01

    The present study describes the distribution and cellular morphology of catecholaminergic neurons in the diencephalon and midbrain of the bottlenose dolphin (Tursiops truncatus). Tyrosine hydroxylase immunohistochemistry was used to visualize these putatively dopaminergic neurons. The standard A1-A17, C1-C3, nomenclature is used for expediency; however, the neuroanatomical names of the various nuclei have also been given. Dolphins exhibit certain tyrosine hydroxylase immunoreactive (TH-ir) catecholaminergic neuronal groups in the midbrain (A8, A9, A10) and diencephalon (A11, A12, A14), however, no neuronal clusters clearly corresponding to the A13 and A15 groups could be identified. The subdivisions of these neuronal groups are in general agreement with those of other mammals, but there is a high degree of species specificity. First, three TH-ir neuronal groups not identified in other species were found: in the ventral lateral peri-aqueductal gray matter, posterior dorsal hypothalamus, and rostral mesencephalic raphe. Second, the normal components of the substantia nigra (A9 or pars compacta, A9 lateral or pars lateralis, A9 ventral or pars reticulata) were extremely cell sparse, but there was a substantial expansion of the A9 medial and A10 lateral subdivisions forming an impressive 'ventral wing' in the posterior substantia nigra. The findings of this and previous studies suggest a distinct evolutionary trend occurring in the neuromodulatory systems in mammals. The results are discussed in relation to motor control, thermoregulation, unihemispheric sleep, and dolphin cognition. Copyright 2004 S. Karger AG, Basel

  12. Modeling genetic imprinting effects of DNA sequences with multilocus polymorphism data

    Directory of Open Access Journals (Sweden)

    Staud Roland

    2009-08-01

    Full Text Available Abstract Single nucleotide polymorphisms (SNPs represent the most widespread type of DNA sequence variation in the human genome and they have recently emerged as valuable genetic markers for revealing the genetic architecture of complex traits in terms of nucleotide combination and sequence. Here, we extend an algorithmic model for the haplotype analysis of SNPs to estimate the effects of genetic imprinting expressed at the DNA sequence level. The model provides a general procedure for identifying the number and types of optimal DNA sequence variants that are expressed differently due to their parental origin. The model is used to analyze a genetic data set collected from a pain genetics project. We find that DNA haplotype GAC from three SNPs, OPRKG36T (with two alleles G and T, OPRKA843G (with alleles A and G, and OPRKC846T (with alleles C and T, at the kappa-opioid receptor, triggers a significant effect on pain sensitivity, but with expression significantly depending on the parent from which it is inherited (p = 0.008. With a tremendous advance in SNP identification and automated screening, the model founded on haplotype discovery and statistical inference may provide a useful tool for genetic analysis of any quantitative trait with complex inheritance.

  13. Distribution and morphology of putative catecholaminergic and serotonergic neurons in the medulla oblongata of a sub-adult giraffe, Giraffa camelopardalis.

    Science.gov (United States)

    Badlangana, N Ludo; Bhagwandin, Adhil; Fuxe, Kjell; Manger, Paul R

    2007-11-01

    The current study details the nuclear parcellation and appearance of putative catecholaminergic and serotonergic neurons within the medulla oblongata of a sub-adult giraffe, using immunohistochemistry for tyrosine hydroxylase and serotonin. We hypothesized that the unusual phenotype of the giraffe, this being the long neck and potential axonal lengthening of these neurons, may pose specific problems in terms of the efficient functioning of these systems, as several groups of catecholaminergic and serotonergic neurons, especially of the medulla, are known to project to the entire spinal cord. This specific challenge may lead to observable differences in the nuclear parcellation and morphology of these systems in the giraffe. Our personal observations in the giraffe reveal that, as with other Artiodactyls, the spinal cord extends to the caudal end of the sacral vertebrae. Within the giraffe medulla we found evidence for five putative catecholaminergic (neurons containing tyrosine hydroxylase) and five serotonergic nuclei. In terms of both morphological appearance of the neurons and nuclear parcellation we did not find any evidence for features that may be considered affected by the phenotype of the giraffe. The nuclear parcellation and appearance of both the putative catecholaminergic and serotonergic systems in the medulla of the giraffe studied are strikingly similar to that seen in previous studies of other Artiodactyls. We interpret these findings in terms of a growing literature detailing order specific phylogenetic constraints in the evolution of these neuromodulatory systems.

  14. Family Polymorphism

    DEFF Research Database (Denmark)

    Ernst, Erik

    2001-01-01

    This paper takes polymorphism to the multi-object level. Traditional inheritance, polymorphism, and late binding interact nicely to provide both flexibility and safety — when a method is invoked on an object via a polymorphic reference, late binding ensures that we get the appropriate implementat......This paper takes polymorphism to the multi-object level. Traditional inheritance, polymorphism, and late binding interact nicely to provide both flexibility and safety — when a method is invoked on an object via a polymorphic reference, late binding ensures that we get the appropriate...

  15. Mechanistic Studies and Modeling Reveal the Origin of Differential Inhibition of Gag Polymorphic Viruses by HIV-1 Maturation Inhibitors.

    Science.gov (United States)

    Lin, Zeyu; Cantone, Joseph; Lu, Hao; Nowicka-Sans, Beata; Protack, Tricia; Yuan, Tian; Yang, Hong; Liu, Zheng; Drexler, Dieter; Regueiro-Ren, Alicia; Meanwell, Nicholas A; Cockett, Mark; Krystal, Mark; Lataillade, Max; Dicker, Ira B

    2016-11-01

    HIV-1 maturation inhibitors (MIs) disrupt the final step in the HIV-1 protease-mediated cleavage of the Gag polyprotein between capsid p24 capsid (CA) and spacer peptide 1 (SP1), leading to the production of infectious virus. BMS-955176 is a second generation MI with improved antiviral activity toward polymorphic Gag variants compared to a first generation MI bevirimat (BVM). The underlying mechanistic reasons for the differences in polymorphic coverage were studied using antiviral assays, an LC/MS assay that quantitatively characterizes CA/SP1 cleavage kinetics of virus like particles (VLPs) and a radiolabel binding assay to determine VLP/MI affinities and dissociation kinetics. Antiviral assay data indicates that BVM does not achieve 100% inhibition of certain polymorphs, even at saturating concentrations. This results in the breakthrough of infectious virus (partial antagonism) regardless of BVM concentration. Reduced maximal percent inhibition (MPI) values for BVM correlated with elevated EC50 values, while rates of HIV-1 protease cleavage at CA/SP1 correlated inversely with the ability of BVM to inhibit HIV-1 Gag polymorphic viruses: genotypes with more rapid CA/SP1 cleavage kinetics were less sensitive to BVM. In vitro inhibition of wild type VLP CA/SP1 cleavage by BVM was not maintained at longer cleavage times. BMS-955176 exhibited greatly improved MPI against polymorphic Gag viruses, binds to Gag polymorphs with higher affinity/longer dissociation half-lives and exhibits greater time-independent inhibition of CA/SP1 cleavage compared to BVM. Virological (MPI) and biochemical (CA/SP1 cleavage rates, MI-specific Gag affinities) data were used to create an integrated semi-quantitative model that quantifies CA/SP1 cleavage rates as a function of both MI and Gag polymorph. The model outputs are in accord with in vitro antiviral observations and correlate with observed in vivo MI efficacies. Overall, these findings may be useful to further understand antiviral

  16. Organization of cholinergic, putative catecholaminergic and serotonergic nuclei in the diencephalon, midbrain and pons of sub-adult male giraffes.

    Science.gov (United States)

    Bux, Faiza; Bhagwandin, Adhil; Fuxe, Kjell; Manger, Paul R

    2010-05-01

    The current study describes the nuclear organization and neuronal morphology of the cholinergic, putative catecholaminergic and serotonergic systems within the diencephalon, midbrain and pons of the giraffe using immunohistochemistry for choline acetyltransferase, tyrosine hydroxylase and serotonin. The giraffe has a unique phenotype (the long neck), a large brain (over 500 g) and is a non-domesticated animal, while previous studies examining the brains of other Artiodactyls have all been undertaken on domesticated animals. The aim of the present study was to investigate possible differences in the nuclear organization and neuronal morphology of the above-mentioned systems compared to that seen in other Artiodactyls and mammals. The nuclear organization of all three systems within the giraffe brain was similar to that of other Artiodactyls. Some features of interest were noted for the giraffe and in comparison to other mammals studied. The cholinergic neuronal somata of the laterodorsal tegmental nucleus were slightly larger than those of the pedunculopontine tegmental nucleus, a feature not described in other mammals. The putative catecholaminergic system of the giraffe appeared to lack an A15 dorsal nucleus, which is commonly seen in other mammals but absent in the Artiodactyls, had a large and expanded substantia nigra pars reticulata (A9 ventral), a small diffuse portion of the locus coerueleus (A6d), an expansive subcoeruleus (A7sc and A7d), and lacked the A4 nucleus of the locus coeruleus complex. The nuclear organization of the serotonergic system of the giraffe was identical to that seen in all other eutherian mammals studied to date. These observations in the giraffe demonstrate that despite significant changes in life history, phenotype, brain size and time of divergence, species within the same order show the same nuclear organization of the systems investigated. Copyright (c) 2009 Elsevier B.V. All rights reserved.

  17. Multiple single nucleotide polymorphism analysis using penalized regression in nonlinear mixed-effect pharmacokinetic models.

    Science.gov (United States)

    Bertrand, Julie; Balding, David J

    2013-03-01

    Studies on the influence of single nucleotide polymorphisms (SNPs) on drug pharmacokinetics (PK) have usually been limited to the analysis of observed drug concentration or area under the concentration versus time curve. Nonlinear mixed effects models enable analysis of the entire curve, even for sparse data, but until recently, there has been no systematic method to examine the effects of multiple SNPs on the model parameters. The aim of this study was to assess different penalized regression methods for including SNPs in PK analyses. A total of 200 data sets were simulated under both the null and an alternative hypothesis. In each data set for each of the 300 participants, a PK profile at six sampling times was simulated and 1227 genotypes were generated through haplotypes. After modelling the PK profiles using an expectation maximization algorithm, genetic association with individual parameters was investigated using the following approaches: (i) a classical stepwise approach, (ii) ridge regression modified to include a test, (iii) Lasso and (iv) a generalization of Lasso, the HyperLasso. Penalized regression approaches are often much faster than the stepwise approach. There are significantly fewer true positives for ridge regression than for the stepwise procedure and HyperLasso. The higher number of true positives in the stepwise procedure was accompanied by a higher count of false positives (not significant). We find that all approaches except ridge regression show similar power, but penalized regression can be much less computationally demanding. We conclude that penalized regression should be preferred over stepwise procedures for PK analyses with a large panel of genetic covariates.

  18. Modeling the competition between polymorphic phases: highlights on the effect of Ostwald ripening

    Czech Academy of Sciences Publication Activity Database

    Tahri, Y.; Kožíšek, Zdeněk; Gagniere, E.; Chabanon, E.; Bounahmidi, T.; Mangin, D.

    2016-01-01

    Roč. 16, č. 10 (2016), s. 5689-5697 ISSN 1528-7483 R&D Projects: GA MŠk LD15004 Institutional support: RVO:68378271 Keywords : phase transitions * nucleation * polymorphic systems Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 4.055, year: 2016

  19. Modelling the contribution of family history and variation in single nucleotide polymorphisms to risk of schizophrenia

    DEFF Research Database (Denmark)

    Agerbo, Esben; Mortensen, Preben Bo; Wiuf, Carsten

    2012-01-01

    Epidemiological studies indicate that having any family member with schizophrenia increases the risk of schizophrenia in the probands. However, genome-wide association studies (GWAS) have accounted for little of this variation. The aim of this study was to use a population-based sample to explore...... the influence of single-nucleotide polymorphisms (SNPs) on the excess schizophrenia risk in offspring of parents with a psychotic, bipolar affective or other psychiatric disorder....

  20. The BDNF Val66Met Polymorphism Interacts with Maternal Parenting Influencing Adolescent Depressive Symptoms: Evidence of Differential Susceptibility Model.

    Science.gov (United States)

    Zhang, Leilei; Li, Zhi; Chen, Jie; Li, Xinying; Zhang, Jianxin; Belsky, Jay

    2016-03-01

    Although depressive symptoms are common during adolescence, little research has examined gene-environment interaction on youth depression. This study chose the brain-derived neurotrophic factor (BDNF) gene, tested the interaction between a functional polymorphism resulting amino acid substitution of valine (Val) to methionine (Met) in the proBDNF protein at codon 66 (Val66Met), and maternal parenting on youth depressive symptoms in a sample of 780 community adolescents of Chinese Han ethnicity (aged 11-17, M = 13.6, 51.3 % females). Participants reported their depressive symptoms and perceived maternal parenting. Results indicated the BDNF Val66Met polymorphism significantly moderated the influence of maternal warmth-reasoning, but not harshness-hostility, on youth depressive symptoms. Confirmatory model evaluation indicated that the interaction effect involving warmth-reasoning conformed to the differential-susceptibility rather than diathesis-stress model of person-X-environment interaction. Thus, Val carriers experienced less depressive symptoms than Met homozygotes when mothering was more positive but more symptoms when mothering was less positive. The findings provided evidence in support of the differential susceptibility hypothesis of youth depressive symptoms and shed light on the importance of examining the gene-environment interaction from a developmental perspective.

  1. Use of latent class models to accommodate inter-laboratory variation in assessing genetic polymorphisms associated with disease risk

    Directory of Open Access Journals (Sweden)

    Walter Stephen D

    2008-08-01

    Full Text Available Abstract Background Researchers wanting to study the association of genetic factors with disease may encounter variability in the laboratory methods used to establish genotypes or other traits. Such variability leads to uncertainty in determining the strength of a genotype as a risk factor. This problem is illustrated using data from a case-control study of cervical cancer in which some subjects were independently assessed by different laboratories for the presence of a genetic polymorphism. Inter-laboratory agreement was only moderate, which led to a very wide range of empirical odds ratios (ORs with the disease, depending on how disagreements were treated. This paper illustrates the use of latent class models (LCMs and to estimate OR while taking laboratory accuracy into account. Possible LCMs are characterised in terms of the number of laboratory measurements available, and if their error rates are assumed to be differential or non-differential by disease status and/or laboratory. Results The LCM results give maximum likelihood estimates of laboratory accuracy rates and the OR of the genetic variable and disease, and avoid the ambiguities of the empirical results. Having allowed for possible measurement error in the expure, the LCM estimates of exposure – disease associations are typically stronger than their empirical equivalents. Also the LCM estimates exploit all the available data, and hence have relatively low standard errors. Conclusion Our approach provides a way to evaluate the association of a polymorphism with disease, while taking laboratory measurement error into account. Ambiguities in the empirical data arising from disagreements between laboratories are avoided, and the estimated polymorphism-disease association is typically enhanced.

  2. Anti-inflammatory effects of cell-based therapy with tyrosine hydroxylase-positive catecholaminergic cells in experimental arthritis.

    Science.gov (United States)

    Jenei-Lanzl, Zsuzsa; Capellino, Silvia; Kees, Frieder; Fleck, Martin; Lowin, Torsten; Straub, Rainer H

    2015-02-01

    Studies in rheumatoid arthritis (RA), osteoarthritis (OA) and mice with arthritis demonstrated tyrosine hydroxylase-positive (TH(+)) cells in arthritic synovium and parallel loss of sympathetic nerve fibres. The exact function of TH(+) cells and mode of TH induction are not known. Synovial cells of RA/OA were isolated and cultured under normoxic/hypoxic conditions with/without stimulating enzyme cofactors of TH and inhibitors of TH. We studied TH expression and release of cytokines/catecholamines. In vivo function was tested by cell therapy with TH(+) neuronal precursor cells (TH(+) neuronal cells) in DBA/1 mice with collagen type II-induced arthritis (CIA). Compared with normoxic conditions, hypoxia increased TH protein expression and catecholamine synthesis and decreased release of tumour necrosis factor (TNF) in OA/RA synovial cells. This inhibitory effect on TNF was reversed by TH inhibition with α-methyl-para-tyrosine (αMPT), which was particularly evident under hypoxic conditions. Incubation with specific TH cofactors (tetrahydrobiopterin and Fe(2+)) increased hypoxia-induced inhibition of TNF, which was also reversed by αMPT. To address a possible clinical role of TH(+) cells, murine TH(+) neuronal cells were generated from mesenchymal stem cells. TH(+) neuronal cells exhibited a typical catecholaminergic phenotype. Adoptive transfer of TH(+) neuronal cells markedly reduced CIA in mice, and 6-hydroxydopamine, which depletes TH(+) cells, reversed this effect. The anti-inflammatory effect of TH(+) neuronal cells on experimental arthritis has been presented for the first time. In RA/OA, TH(+) synovial cells have TH-dependent anti-inflammatory capacities, which are augmented under hypoxia. Using generated TH(+) neuronal cells might open new avenues for cell-based therapy. 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.

  3. (-)Deprenyl and (-)1-phenyl-2-propylaminopentane, [(-)PPAP], act primarily as potent stimulants of action potential-transmitter release coupling in the catecholaminergic neurons.

    Science.gov (United States)

    Knoll, J; Miklya, I; Knoll, B; Markó, R; Kelemen, K

    1996-01-01

    The activity of the catecholaminergic neurons in the rat brain is enhanced significantly 30 min after the subcutaneous injection of very small doses of (-)deprenyl (threshold doses: 0.01 mg/kg for noradrenergic neurons and 0.025 mg/kg for dopaminergic neurons). As a catecholaminergic activity enhancer (CAE) substance (-)deprenyl is about ten times more potent than its parent compound, (-)methamphetamine. While the (+)methamphetamine is 3-5 times more potent than (-)methamphetammine in releasing catecholamines, the (-)methamphetamine is the more potent CAE substance. The mechanism of the CAE effect of (-)deprenyl and (-)PPAP, a deprenyl-derived substance devoid of MAO inhibitory potency, was studied in rats by measuring: a) the release of catecholamines from striatum, substantia nigra, tuberculum olfactorium and locus coeruleus; b) the stimulation induced release of 3H-noradrenaline from the isolated brain stem; and c) the antagonistic effect against tetrabenazine-induced depression of learning in the shuttle box. The CAE effect was found to be unrelated: a) to the inhibition of MAO activity; b) to the inhibition of presynaptic catecholamine receptors; c) to the inhibition of the uptake of catecholamines; and d) to the release of catecholamines. It was concluded that (-)deprenyl and (-)PPAP act primarily as potent stimulants of action potential-transmitter release coupling in the catecholaminergic neurons of the brain. We show that both (-)deprenyl and (-)PPAP enhance the inward Ca2+ current in sino-auricular fibers of the frog heart. (-)PPAP was much more potent than either (+)PPAP or (-)deprenyl in this test.

  4. Exposure to advertisement calls of reproductive competitors activates vocal-acoustic and catecholaminergic neurons in the plainfin midshipman fish, Porichthys notatus.

    Directory of Open Access Journals (Sweden)

    Christopher L Petersen

    Full Text Available While the neural circuitry and physiology of the auditory system is well studied among vertebrates, far less is known about how the auditory system interacts with other neural substrates to mediate behavioral responses to social acoustic signals. One species that has been the subject of intensive neuroethological investigation with regard to the production and perception of social acoustic signals is the plainfin midshipman fish, Porichthys notatus, in part because acoustic communication is essential to their reproductive behavior. Nesting male midshipman vocally court females by producing a long duration advertisement call. Females localize males by their advertisement call, spawn and deposit all their eggs in their mate's nest. As multiple courting males establish nests in close proximity to one another, the perception of another male's call may modulate individual calling behavior in competition for females. We tested the hypothesis that nesting males exposed to advertisement calls of other males would show elevated neural activity in auditory and vocal-acoustic brain centers as well as differential activation of catecholaminergic neurons compared to males exposed only to ambient noise. Experimental brains were then double labeled by immunofluorescence (-ir for tyrosine hydroxylase (TH, an enzyme necessary for catecholamine synthesis, and cFos, an immediate-early gene product used as a marker for neural activation. Males exposed to other advertisement calls showed a significantly greater percentage of TH-ir cells colocalized with cFos-ir in the noradrenergic locus coeruleus and the dopaminergic periventricular posterior tuberculum, as well as increased numbers of cFos-ir neurons in several levels of the auditory and vocal-acoustic pathway. Increased activation of catecholaminergic neurons may serve to coordinate appropriate behavioral responses to male competitors. Additionally, these results implicate a role for specific catecholaminergic

  5. Distribution of Fos-Like Immunoreactivity, Catecholaminergic and Serotoninergic Neurons Activated by the Laryngeal Chemoreflex in the Medulla Oblongata of Rats.

    Directory of Open Access Journals (Sweden)

    Xiaolu Wang

    Full Text Available The laryngeal chemoreflex (LCR induces apnea, glottis closure, bradycardia and hypertension in young and maturing mammals. We examined the distribution of medullary nuclei that are activated by the LCR and used immunofluorescent detection of Fos protein as a cellular marker for neuronal activation to establish that the medullary catecholaminergic and serotoninergic neurons participate in the modulation of the LCR. The LCR was elicited by the infusion of KCl-HCl solution into the laryngeal lumen of adult rats in the experimental group, whereas the control group received the same surgery but no infusion. In comparison, the number of regions of Fos-like immunoreactivity (FLI that were activated by the LCR significantly increased in the nucleus of the solitary tract (NTS, the vestibular nuclear complex (VNC, the loose formation of the nucleus ambiguus (AmbL, the rostral ventral respiratory group (RVRG, the ventrolateral reticular complex (VLR, the pre-Bötzinger complex (PrBöt, the Bötzinger complex (Böt, the spinal trigeminal nucleus (SP5, and the raphe obscurus nucleus (ROb bilaterally from the medulla oblongata. Furthermore, 12.71% of neurons with FLI in the dorsolateral part of the nucleus of the solitary tract (SolDL showed tyrosine hydroxylase-immunoreactivity (TH-ir, catecholaminergic, and 70.87% of neurons with FLI in the ROb were serotoninergic. Our data demonstrated the distribution of medullary nuclei that were activated by the LCR, and further demonstrated that catecholaminergic neurons of the SolDL and serotoninergic neurons of the ROb were activated by the LCR, indicating the potential central pathway of the LCR.

  6. Rapid metabolism of exogenous angiotensin II by catecholaminergic neuronal cells in culture media.

    Science.gov (United States)

    Basu, Urmi; Seravalli, Javier; Madayiputhiya, Nandakumar; Adamec, Jiri; Case, Adam J; Zimmerman, Matthew C

    2015-02-01

    Angiotensin II (AngII) acts on central neurons to increase neuronal firing and induce sympathoexcitation, which contribute to the pathogenesis of cardiovascular diseases including hypertension and heart failure. Numerous studies have examined the precise AngII-induced intraneuronal signaling mechanism in an attempt to identify new therapeutic targets for these diseases. Considering the technical challenges in studying specific intraneuronal signaling pathways in vivo, especially in the cardiovascular control brain regions, most studies have relied on neuronal cell culture models. However, there are numerous limitations in using cell culture models to study AngII intraneuronal signaling, including the lack of evidence indicating the stability of AngII in culture media. Herein, we tested the hypothesis that exogenous AngII is rapidly metabolized in neuronal cell culture media. Using liquid chromatography-tandem mass spectrometry, we measured levels of AngII and its metabolites, Ang III, Ang IV, and Ang-1-7, in neuronal cell culture media after administration of exogenous AngII (100 nmol/L) to a neuronal cell culture model (CATH.a neurons). AngII levels rapidly declined in the media, returning to near baseline levels within 3 h of administration. Additionally, levels of Ang III and Ang-1-7 acutely increased, while levels of Ang IV remained unchanged. Replenishing the media with exogenous AngII every 3 h for 24 h resulted in a consistent and significant increase in AngII levels for the duration of the treatment period. These data indicate that AngII is rapidly metabolized in neuronal cell culture media, and replenishing the media at least every 3 h is needed to sustain chronically elevated levels. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  7. Kinetic modeling for thermal dehydration of ferrous oxalate dihydrate polymorphs: a combined model for induction period-surface reaction-phase boundary reaction.

    Science.gov (United States)

    Ogasawara, Haruka; Koga, Nobuyoshi

    2014-04-03

    In this study, ferrous oxalate dihydrate polymorph particles, α- and β-phases, with square bipyramidal and quadratic prismatic shapes, respectively, were synthesized. Thermal dehydration of the samples was subjected to kinetic study as a typical reaction that indicates a significant induction period and a sigmoidal mass-loss behavior. On the basis of the formal kinetic analysis of the mass-loss traces recorded under isothermal, nonisothermal, and constant transformation rate conditions and the morphological observations of the surface textures of the partially reacted sample particles, a combined kinetic model for the induction period-surface reaction-phase boundary reaction was developed. The sigmoidal mass-loss behavior after the significant induction period under isothermal conditions was satisfactorily simulated by the combined kinetic model. The kinetic parameters for the component processes of induction period, surface reaction, and phase boundary reaction were separately determined from the kinetic simulation. The differences in the kinetic behaviors of the induction period and the phase boundary reaction between α- and β-phase samples were well described by the kinetic parameters. The applicability of the combined kinetic model to practical systems was demonstrated through characterizing the physicogeometrical kinetics of the thermal dehydration of ferrous oxalate dihydrate polymorphs.

  8. Genome-wide analysis of intraspecific DNA polymorphism in 'Micro-Tom', a model cultivar of tomato (Solanum lycopersicum).

    Science.gov (United States)

    Kobayashi, Masaaki; Nagasaki, Hideki; Garcia, Virginie; Just, Daniel; Bres, Cécile; Mauxion, Jean-Philippe; Le Paslier, Marie-Christine; Brunel, Dominique; Suda, Kunihiro; Minakuchi, Yohei; Toyoda, Atsushi; Fujiyama, Asao; Toyoshima, Hiromi; Suzuki, Takayuki; Igarashi, Kaori; Rothan, Christophe; Kaminuma, Eli; Nakamura, Yasukazu; Yano, Kentaro; Aoki, Koh

    2014-02-01

    Tomato (Solanum lycopersicum) is regarded as a model plant of the Solanaceae family. The genome sequencing of the tomato cultivar 'Heinz 1706' was recently completed. To accelerate the progress of tomato genomics studies, systematic bioresources, such as mutagenized lines and full-length cDNA libraries, have been established for the cultivar 'Micro-Tom'. However, these resources cannot be utilized to their full potential without the completion of the genome sequencing of 'Micro-Tom'. We undertook the genome sequencing of 'Micro-Tom' and here report the identification of single nucleotide polymorphisms (SNPs) and insertion/deletions (indels) between 'Micro-Tom' and 'Heinz 1706'. The analysis demonstrated the presence of 1.23 million SNPs and 0.19 million indels between the two cultivars. The density of SNPs and indels was high in chromosomes 2, 5 and 11, but was low in chromosomes 6, 8 and 10. Three known mutations of 'Micro-Tom' were localized on chromosomal regions where the density of SNPs and indels was low, which was consistent with the fact that these mutations were relatively new and introgressed into 'Micro-Tom' during the breeding of this cultivar. We also report SNP analysis for two 'Micro-Tom' varieties that have been maintained independently in Japan and France, both of which have served as standard lines for 'Micro-Tom' mutant collections. Approximately 28,000 SNPs were identified between these two 'Micro-Tom' lines. These results provide high-resolution DNA polymorphic information on 'Micro-Tom' and represent a valuable contribution to the 'Micro-Tom'-based genomics resources.

  9. Tissue and Animal Models of Sudden Cardiac Death

    Science.gov (United States)

    Sallam, Karim; Li, Yingxin; Sager, Philip T.; Houser, Steven R.; Wu, Joseph C.

    2015-01-01

    Sudden Cardiac Death (SCD) is a common cause of death in patients with structural heart disease, genetic mutations or acquired disorders affecting cardiac ion channels. A wide range of platforms exist to model and study disorders associated with SCD. Human clinical studies are cumbersome and are thwarted by the extent of investigation that can be performed on human subjects. Animal models are limited by their degree of homology to human cardiac electrophysiology including ion channel expression. Most commonly used cellular models are cellular transfection models, which are able to mimic the expression of a single ion channel offering incomplete insight into changes of the action potential profile. Induced pluripotent stem cell derived Cardiomyocytes (iPSC-CMs) resemble, but are not identical, to adult human cardiomyocytes, and provide a new platform for studying arrhythmic disorders leading to SCD. A variety of platforms exist to phenotype cellular models including conventional and automated patch clamp, multi-electrode array, and computational modeling. iPSC-CMs have been used to study Long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy and other hereditary cardiac disorders. Although iPSC-CMs are distinct from adult cardiomyocytes, they provide a robust platform to advance the science and clinical care of SCD. PMID:26044252

  10. Preparation and evaluation of famotidine polymorphs.

    Science.gov (United States)

    Nagaraju, Ravouru; Prathusha, Ande Penchala; Subhash Chandra Bose, Penjury; Kaza, Rajesh; Bharathi, Koganti

    2010-06-01

    The main objective of this study was to compare the behaviour of drug release among the famotidine polymorphs prepared by using various additives and solvents, by solvent evaporation method. The famotidine polyvinyl pyrrolidone polymorphs with different concentrations (0.5, 1 and 1.5%) were prepared by using solvent evaporation method. In these polymorphs of different concentrations 1% w/v polymorphs showed better release. Similarly, famotidine polymorphs of Tween 80 with different concentrations, polyethylene glycol 1% w/v and methanol was prepared. Famotidine polymorphs prepared the PVP (1% w/v) showed better drug release and solubility. DSC, FTIR, SEM and XRD studies were carried out. DSC studies revealed that PVP polymorphs were found to stable compared to other polymorphs. FTIR studies of the polymorphs prepared indicated that there was an interaction found in all polymorphs except PVP polymorphs indicating the absence of drug-additive interaction. SEM studies of PVP and methanol polymorphs revealed that they are tabular and prismatic and columnar respectively. These changes in morphology were due to variations in face dimensions and also properties of additives and solvent used in the preparation. XRD studies revealed that there is an increase in crystallinity in methanol polymorphs when compared to PVP polymorphs and pure drug. The mechanism of drug release was determined using zero order, first order and Hixon-Crowel equations. From the drug release kinetics these polymorphs followed first order and Hixon-Crowel release kinetics, exhibited fair linearity in their dissolution data. Further, in vivo studies were carried out for the evaluation of antiulcer activity. Based upon the drug release pattern and its kinetics only two of the prepared polymorphs of famotidine i.e. famotidine PVP polymorphs and famotidine methanol polymorphs were selected for animal studies. Antiulcer studies were carried out using pylorus ligation model and estimation of antioxidant

  11. Modelling the PKPD of oxycodone in experimental pain - Impact of opioid receptor polymorphisms

    DEFF Research Database (Denmark)

    Olsen, Rasmus; Foster, David J R; Upton, Richard N

    2016-01-01

    in healthy volunteers. Pain tolerance data from muscle pressure (n=36), visceral pressure (n=54) and skin pinch (n=34) were included. Genetic associations with 18 opioid-receptor SNPs were explored using a stepwise covariate approach. Model simulations were performed using the estimated model parameters...

  12. Assessment of the genotoxicity of heavy metals in Phaseolus vulgaris L. as a model plant system by Random Amplified Polymorphic DNA (RAPD) analysis.

    Science.gov (United States)

    Gjorgieva, Darinka; Kadifkova-Panovska, Tatjana; Mitrev, Saša; Kovacevik, Biljana; Kostadinovska, Emilija; Bačeva, Katerina; Stafilov, Trajče

    2012-01-01

    Impact assessments of environmental pollutants are important in eco-genotoxicology. A random amplified polymorphic DNA (RAPD) technique was used to detect genotoxicity-induced DNA damage in Phaseolus vulgaris L. from heavy metals at two different concentrations. The results from six 10-base pair (bp) random RAPD primers with 60-70% GC content used, showed a total of 295 RAPD fragments of 700-4000 bp in molecular size in the seedlings of untreated and treated samples, of which only 163 fragments were polymorphic. Polymorphisms became evident as the disappearance and/or appearance of DNA fragments in treated samples compared to the control. A dendrogram constructed using the Numerical Taxonomy and Multivariate Analysis System (NTSYSps), showed that the control group merged with groups treated with CuSO(4)·5H(2)O (150 mg L(-1)) and MnSO(4)·H(2)O (150 mg L(-1)) in a separate cluster. These groups were linked with all of the other samples treated with metals at concentrations of 150 mg L(-1) and CuSO(4)·5H(2)O and Cd(NO(3))(2) at concentrations of 350 mg L(-1). Finally, the samples treated with metals at concentrations of 350 mg L(-1) together with NiSO(4) at the concentration of 150 mg L(-1), clustered separately. The DNA polymorphism detected by RAPD analysis offered a useful biomarker assay for the detection of toxic chemicals genotoxicity in plant model systems.

  13. Polymorphic ethyl alcohol as a model system for the quantitative study of glassy behaviour

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, H.E.; Schober, H.; Gonzalez, M.A. [Institut Max von Laue - Paul Langevin (ILL), 38 - Grenoble (France); Bermejo, F.J.; Fayos, R.; Dawidowski, J. [Consejo Superior de Investigaciones Cientificas, Madrid (Spain); Ramos, M.A.; Vieira, S. [Universidad Autonoma de Madrid (Spain)

    1997-04-01

    The nearly universal transport and dynamical properties of amorphous materials or glasses are investigated. Reasonably successful phenomenological models have been developed to account for these properties as well as the behaviour near the glass-transition, but quantitative microscopic models have had limited success. One hindrance to these investigations has been the lack of a material which exhibits glass-like properties in more than one phase at a given temperature. This report presents results of neutron-scattering experiments for one such material ordinary ethyl alcohol, which promises to be a model system for future investigations of glassy behaviour. (author). 8 refs.

  14. Uniqueness of polymorphism for a discrete, selection-migration model with genetic dominance

    Science.gov (United States)

    James F. Selgrade; James H. Roberds

    2009-01-01

    The migration into a natural population of a controlled population, e.g., a transgenic population, is studied using a one island selection-migration model. A 2-dimensional system of nonlinear difference equations describes changes in allele frequency and population size between generations. Biologically reasonable conditions are obtained which guarantee the existence...

  15. Oxygen Adsorption on β-Cristobalite Polymorph: Ab Initio Modeling and Semiclassical Time-Dependent Dynamics

    Science.gov (United States)

    Rutigliano, M.; Zazza, C.; Sanna, N.; Pieretti, A.; Mancini, G.; Barone, V.; Cacciatore, M.

    2009-10-01

    The adsorption dynamics of atomic oxygen on a model β-cristobalite silica surface has been studied by combining ab initio electronic structure calculations with a molecular dynamics semiclassical approach. We have evaluated the interaction potential of atomic and molecular oxygen interacting with an active Si site of a model β-cristobalite surface by performing DFT electronic structure calculations. As expected, O is strongly chemisorbed, Eb = 5.57 eV, whereas molecular oxygen can be weakly adsorbed with a high-energy barrier to the adsorption state of ˜2 eV. The binding energies calculated for silica clusters of different sizes have revealed the local nature of the O,O2-silica interaction. Semiclassical collision dynamic calculations show that O is mainly adsorbed in single-bounce collisions, with a smaller probability for adsorption via a multicollision mechanism. The probability for adsorption/desorption (reflected) collisions at the three impact energies is small but not negligible at the higher energy considered in the trajectory calculations, about Pr = 0.2 at Ekin = 0.8 eV. The calculations give evidence of a complex multiphonon excitation-deexcitation mechanism underlying the dynamics of stable adsorption and inelastic reflection collisions.

  16. Genome-wide single nucleotide polymorphisms (SNPs) for a model invasive ascidian Botryllus schlosseri.

    Science.gov (United States)

    Gao, Yangchun; Li, Shiguo; Zhan, Aibin

    2018-04-01

    Invasive species cause huge damages to ecology, environment and economy globally. The comprehensive understanding of invasion mechanisms, particularly genetic bases of micro-evolutionary processes responsible for invasion success, is essential for reducing potential damages caused by invasive species. The golden star tunicate, Botryllus schlosseri, has become a model species in invasion biology, mainly owing to its high invasiveness nature and small well-sequenced genome. However, the genome-wide genetic markers have not been well developed in this highly invasive species, thus limiting the comprehensive understanding of genetic mechanisms of invasion success. Using restriction site-associated DNA (RAD) tag sequencing, here we developed a high-quality resource of 14,119 out of 158,821 SNPs for B. schlosseri. These SNPs were relatively evenly distributed at each chromosome. SNP annotations showed that the majority of SNPs (63.20%) were located at intergenic regions, and 21.51% and 14.58% were located at introns and exons, respectively. In addition, the potential use of the developed SNPs for population genomics studies was primarily assessed, such as the estimate of observed heterozygosity (H O ), expected heterozygosity (H E ), nucleotide diversity (π), Wright's inbreeding coefficient (F IS ) and effective population size (Ne). Our developed SNP resource would provide future studies the genome-wide genetic markers for genetic and genomic investigations, such as genetic bases of micro-evolutionary processes responsible for invasion success.

  17. A multifactor dimensionality reduction-logistic regression model of gene polymorphisms and an environmental interaction analysis in cancer research.

    Science.gov (United States)

    Wu, Yazhou; Zhang, Ling; Liu, Ling; Zhang, Yanqi; Zhao, Zengwei; Liu, Xiaoyu; Yi, Dong

    2011-01-01

    Analysis of interactions between genes and the environment with complex multifactorial human disease faces important challenges. Limitations of parametric-statistical methods for detection of gene effects that are dependent solely or partially on interactions with other genes or environmental exposures are key problems. The aim of the study was to investigate the use of multifactor dimensionality reduction (MDR) and logistic regression models to analyze the effects of interactions between complex disease genes with other genes and with environmental factors and to compare the results of these two methods in interaction analysis. In this case-control study, the two methods were applied to analog data of samples from 486 cancer patients and 514 control individuals by computer simulation, including 4 environment factors (E1~E4) and 8 gene polymorphism factors (G1~G8). Non-conditional logistic regression was used to analyze risk factors for cancer, and MDR and logistic regression were employed to analyze interactions under various conditions. MDR could find high-level interactions between genes and the environment (E3*G1*G7), but it could not find a main effect; conversely, logistic regression better analyzed the main effects (E3, G1, and G4) but was limited in its analysis of high-level interactions (E3*G1*G7). The results of these two methods with analog data show that the gene G1 site, the G4 site, E3, and the E3*G1*G7 interaction may be risk factors for occurrence of cancer. MDR and logistic regression, which are the two complementary methods, can be combined to analyze gene-gene (gene-environment) interactions with good results. This approach should help to determine the causes of diseases, such as chronic non-transmittable diseases like cancer.

  18. Qualitative and simultaneous quantitative analysis of cimetidine polymorphs by ultraviolet-visible and shortwave near-infrared diffuse reflectance spectroscopy and multivariate calibration models.

    Science.gov (United States)

    Feng, Yuyan; Li, Xiangling; Xu, Kailin; Zou, Huayu; Li, Hui; Liang, Bing

    2015-02-01

    The object of the present study was to investigate the feasibility of applying ultraviolet-visible and shortwave near-infrared diffuse reflectance spectroscopy (UV-vis-SWNIR DRS) coupled with chemometrics in qualitative and simultaneous quantitative analysis of drug polymorphs, using cimetidine as a model drug. Three polymorphic forms (A, B and D) and a mixed crystal (M1) of cimetidine, obtained by preparation under different crystallization conditions, were characterized by microscopy, X-ray powder diffraction (XRPD) and infrared spectroscopy (IR). The discriminant models of four forms (A, B, D and M1) were established by discriminant partial least squares (PLS-DA) using different pretreated spectra. The R and RMSEP of samples in the prediction set by discriminant model with original spectra were 0.9959 and 0.1004. Among the quantitative models of binary mixtures (A and D) established by partial least squares (PLS) and least squares-support vector machine (LS-SVM) with different pretreated spectra, the LS-SVM models based on original and MSC spectra had better prediction effect with a R of 1.0000 and a RMSEP of 0.0134 for form A, and a R of 1.0000 and a RMSEP of 0.0024 for form D. For ternary mixtures, the established PLS quantitative models based on normalized spectra had relatively better prediction effect for forms A, B and D with R of 0.9901, 0.9820 and 0.9794 and RMSEP of 0.0471, 0.0529 and 0.0594, respectively. This research indicated that UV-vis-SWNIR DRS can be used as a simple, rapid, nondestructive qualitative and quantitative method for the analysis of drug polymorphs. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Effects of Fat Polymorphic Transformation and Nonfat Particle Size Distribution on the Surface Changes of Untempered Model Chocolate, Based on Solid Cocoa Mass.

    Science.gov (United States)

    Zhao, Huanhuan; Young, Ashley K; James, Bryony J

    2018-04-01

    This study aims to understand the bloom process in untempered chocolate by investigating the polymorphic transformation of cocoa butter and changes in chocolate surface. Cocoa mass with varying particle size distributions (PSD) were used to produce untempered model chocolate. Optical microscopy showed that during 25 d of storage, the chocolate surface gradually became honeycombed in appearance with dark spots surrounded by white sandy bloom areas. In conjunction with X-ray diffraction this indicates that the polymorphic transformation of form IV cocoa butter to more stable form V crystals caused the observed surface changes with the most significant changes occurring within 6 d. As bloom developed the surface whiteness increased, but the PSD of nonfat particles showed limited impact on the changes in whiteness. Moreover, scanning electron microscopy showed separated fat crystals on fat-rich dark spots and empty spaces between particles in bloom areas suggesting redistribution of fat in the chocolate matrix. The results reported in this work can facilitate the understanding of fat bloom formation in untempered chocolate with respect to the changes in microstructure and surface appearances. It also contributes to show the details of IV-to-V polymorphic transformation in the fat phase as time went by. © 2018 Institute of Food Technologists®.

  20. HLA-DR polymorphisms influence in vivo responses to staphylococcal toxic shock syndrome toxin-1 in a transgenic mouse model.

    Science.gov (United States)

    Krogman, A; Tilahun, A; David, C S; Chowdhary, V R; Alexander, M P; Rajagopalan, G

    2017-01-01

    Toxic shock syndrome toxin-1 (TSST-1) is a potent superantigen produced by Staphylococcus aureus. In addition to menstrual and nonmenstrual toxic shock syndromes, TSST-1 is also implicated in the immunopathogenesis of pneumonia, infective endocarditis, neonatal exanthematous disease, and atopic dermatitis among others. Superantigens first bind to major histocompatibility complex (MHC) class II molecules and then activate a large proportion of T cells by cross-linking their T cell receptor. As binding to MHC class II molecules is a critical step in the robust activation of the immune system by TSST-1 and other superantigens, polymorphic variations between different HLA-DR alleles could potentially influence the magnitude of immune activation and immunopathology caused by TSST-1. As TSST-1 is highly toxic to humans and given that multiple variations of alleles of HLA-DR and HLA-DQ are expressed in each individual, it is difficult to determine how HLA-DR polymorphisms quantitatively and qualitatively impact immune activation caused by TSST-1 in humans. However, such investigations can be conducted on transgenic mice lacking all endogenous MHC class II molecules and expressing specific HLA class II alleles. Therefore, transgenic mice expressing different HLA-DRB1 alleles (HLA-DRB1*15:01, HLA-DRB1*15:02, HLA-DRB1*03:01, HLA-DRB1*04:01), and sharing HLA-A1*01:01 chain, were systemically challenged with purified TSST-1 and multiple immune parameters were assessed. Among the HLA-DR alleles, mice expressing HLA-DRB1*15:01 allele elicited a significantly higher serum cytokine/chemokine response; greater splenic T cell expansion and most severe organ pathology. Our study highlights the potential utility of human leukocyte antigen (HLA) transgenic mice in understanding the impact of HLA polymorphisms on the outcomes of diseases caused by TSST-1 and other superantigens. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Abnormal Ca2+ homeostasis, atrial arrhythmogenesis and sinus node dysfunction in murine hearts modelling RyR2 modification

    Directory of Open Access Journals (Sweden)

    Yanmin eZhang

    2013-06-01

    Full Text Available RyR2 mutations are implicated in catecholaminergic polymorphic ventricular tachycardia thought to result from altered myocyte Ca2+ homeostasis reflecting inappropriate ‘leakiness’ of RyR2-Ca2+ release channels arising from increases in their basal activity, alterations in their phosphorylation, or defective interactions with other molecules or ions. The latter include calstabin, calsequestrin-2, Mg2+, and extraluminal or intraluminal Ca2+. Recent clinical studies additionally associate RyR2 abnormalities with atrial arrhythmias including atrial tachycardia, fibrillation and standstill, and sinus node dysfunction. Some RyR2 mutations associated with CPVT in mouse models also show such arrhythmias that similarly correlate with altered Ca2+ homeostasis. Some examples show evidence for increased Ca2+/calmodulin-dependent protein kinase II phosphorylation of RyR2. A homozygotic RyR2-P2328S variant demonstrates potential arrhythmic substrate resulting from reduced conduction velocity in addition to delayed afterdepolarizations and ectopic action potential firing. Finally, one model with an increased RyR2 activity in the sino-atrial node shows decreased automaticity in the presence of Ca2+-dependent decreases in ICa,L and diastolic sarcoplasmic reticular Ca2+ depletion.

  2. An alternative to the search for single polymorphisms: toward molecular personality scales for the five-factor model.

    Science.gov (United States)

    McCrae, Robert R; Scally, Matthew; Terracciano, Antonio; Abecasis, Gonçalo R; Costa, Paul T

    2010-12-01

    There is growing evidence that personality traits are affected by many genes, all of which have very small effects. As an alternative to the largely unsuccessful search for individual polymorphisms associated with personality traits, the authors identified large sets of potentially related single nucleotide polymorphisms (SNPs) and summed them to form molecular personality scales (MPSs) with from 4 to 2,497 SNPs. Scales were derived from two thirds of a large (N = 3,972) sample of individuals from Sardinia who completed the Revised NEO Personality Inventory (P. T. Costa, Jr., & R. R. McCrae, 1992) and were assessed in a genomewide association scan. When MPSs were correlated with the phenotype in the remaining one third of the sample, very small but significant associations were found for 4 of the 5e personality factors when the longest scales were examined. These data suggest that MPSs for Neuroticism, Openness to Experience, Agreeableness, and Conscientiousness (but not Extraversion) contain genetic information that can be refined in future studies, and the procedures described here should be applicable to other quantitative traits. PsycINFO Database Record (c) 2010 APA, all rights reserved.

  3. Polymorphic Embedding of DSLs

    DEFF Research Database (Denmark)

    Hofer, Christian; Ostermann, Klaus; Rendel, Tillmann

    2008-01-01

    propose polymorphic embedding of DSLs, where many different interpretations of a DSL can be provided as reusable components, and show how polymorphic embedding can be realized in the programming language Scala. With polymorphic embedding, the static type-safety, modularity, composability and rapid...... prototyping of pure embedding are reconciled with the flexibility attainable by external toolchains....

  4. Polymorphisms associated with the risk of lung cancer in a healthy Mexican Mestizo population: application of the additive model for cancer

    Directory of Open Access Journals (Sweden)

    Rebeca Pérez-Morales

    2011-01-01

    Full Text Available Lung cancer is the leading cause of cancer mortality in Mexico and worldwide. In the past decade, there has been an increase in the number of lung cancer cases in young people, which suggests an important role for genetic background in the etiology of this disease. In this study, we genetically characterized 16 polymorphisms in 12 low penetrance genes (AhR, CYP1A1, CYP2E1, EPHX1, GSTM1, GSTT1, GSTPI, XRCC1, ERCC2, MGMT, CCND1 and TP53 in 382 healthy Mexican Mestizos as the first step in elucidating the genetic structure of this population and identifying high risk individuals. All of the genotypes analyzed were in Hardy-Weinberg equilibrium, but different degrees of linkage were observed for polymorphisms in the CYP1A1 and EPHX1 genes. The genetic variability of this population was distributed in six clusters that were defined based on their genetic characteristics. The use of a polygenic model to assess the additive effect of low penetrance risk alleles identified combinations of risk genotypes that could be useful in predicting a predisposition to lung cancer. Estimation of the level of genetic susceptibility showed that the individual calculated risk value (iCRV ranged from 1 to 16, with a higher iCRV indicating a greater genetic susceptibility to lung cancer.

  5. Effects of pre-experience of social exclusion on hypothalamus-pituitary-adrenal axis and catecholaminergic responsiveness to public speaking stress.

    Directory of Open Access Journals (Sweden)

    Ulrike Weik

    Full Text Available BACKGROUND: Being socially excluded is associated with a variety of psychological changes and with an increased risk of disease. Today, the immediate physiological consequences of being socially excluded are not well understood. In two recent studies employing a standardized exclusion paradigm (Cyberball we found social exclusion in this virtual game did not alter cortisol secretion directly. However, exclusion pre-experience suppresses the normal cortisol response to public speaking stress in women. The present study aims to replicate our previous finding and further elucidate it by analyzing for the first time whether this alteration of cortisol-responsiveness is associated to ACTH and whether the catecholaminergic system is affected as well. METHODS: Women were randomly assigned to Cyberball-induced exclusion (SE, n = 22 or inclusion (SI, n = 21, respectively. Immediately afterwards they were subjected to public speaking stress. Salivary cortisol, plasma ACTH, catecholamines and estradiol were assessed as were psychological distress and mood. RESULTS: Cyberball exclusion led to a highly significant immediate increase in negative affect in excluded women. After public speaking negative affect in included women increased as well and groups no longer differed. We replicate our previous finding of cortisol non-responsiveness to public speaking stress after exclusion pre-experience and find this effect to be significantly correlated with ACTH alterations. No such effects are observed for catecholamines. CONCLUSIONS: We replicated our previous study result of a suppressed cortisol stress response after a short exclusion experience via Cyberball, thereby underlining the profound effects of social exclusion on a subsequent cortisol stress response. This further demonstrates that these alterations are associated with ACTH. Lack of effects on catecholamines is discussed in view of the tend-and-befriend hypothesis but also from a methodological

  6. Changes in the Cholinergic, Catecholaminergic, Orexinergic and Serotonergic Structures Forming Part of the Sleep Systems of Adult Mice Exposed to Intrauterine Alcohol

    Directory of Open Access Journals (Sweden)

    Oladiran I. Olateju

    2017-11-01

    Full Text Available We examined the effect of chronic prenatal alcohol exposure on certain neuronal systems involved with the sleep-wake cycle of C57BL/6J mice exposed to prenatal alcohol once they had reached 56 days post-natal. Pregnant mice were exposed to alcohol, through oral gavage, on gestational days 7–16, with recorded blood alcohol concentration (BACs averaging 1.84 mg/ml (chronic alcohol group, CA. Two control groups, an oral gavage sucrose control group (chronic alcohol control group, CAc and a non-treated control group (NTc, were also examined. At 56 days post-natal, the pups from each group were sacrificed and the whole brain sectioned in a coronal plane and immunolabeled for cholineacetyltransferase (ChAT, tyrosine hydroxylase (TH, serotonin (5HT and orexin-A (OxA which labels cholinergic, catecholaminergic, serotonergic and orexinergic structures respectively. The overall nuclear organization and neuronal morphology were identical in all three groups studied, and resemble that previously reported for laboratory rodents. Quantification of the estimated numbers of ChAT immunopositive (+ neurons of the pons, the TH+ neurons of the pons and the OxA+ neurons of the hypothalamus showed no statistically significant difference between the three experimental groups. The stereologically estimated areas and volumes of OxA+ neurons in the CA group were statistically significantly larger than the groups not exposed to prenatal alcohol, but the ChAT+ neurons in the CA group were statistically significantly smaller. The density of orexinergic boutons in the anterior cingulate cortex was lower in the CA group than the other groups. No statistically significant difference was found in the area and volume of TH+ neurons between the three experimental groups. These differences are discussed in relation to the sleep disorders recorded in children with fetal alcohol spectrum disorder (FASD.

  7. Effects of pre-experience of social exclusion on hypothalamus-pituitary-adrenal axis and catecholaminergic responsiveness to public speaking stress.

    Science.gov (United States)

    Weik, Ulrike; Kuepper, Yvonne; Hennig, Juergen; Deinzer, Renate

    2013-01-01

    Being socially excluded is associated with a variety of psychological changes and with an increased risk of disease. Today, the immediate physiological consequences of being socially excluded are not well understood. In two recent studies employing a standardized exclusion paradigm (Cyberball) we found social exclusion in this virtual game did not alter cortisol secretion directly. However, exclusion pre-experience suppresses the normal cortisol response to public speaking stress in women. The present study aims to replicate our previous finding and further elucidate it by analyzing for the first time whether this alteration of cortisol-responsiveness is associated to ACTH and whether the catecholaminergic system is affected as well. Women were randomly assigned to Cyberball-induced exclusion (SE, n = 22) or inclusion (SI, n = 21), respectively. Immediately afterwards they were subjected to public speaking stress. Salivary cortisol, plasma ACTH, catecholamines and estradiol were assessed as were psychological distress and mood. Cyberball exclusion led to a highly significant immediate increase in negative affect in excluded women. After public speaking negative affect in included women increased as well and groups no longer differed. We replicate our previous finding of cortisol non-responsiveness to public speaking stress after exclusion pre-experience and find this effect to be significantly correlated with ACTH alterations. No such effects are observed for catecholamines. We replicated our previous study result of a suppressed cortisol stress response after a short exclusion experience via Cyberball, thereby underlining the profound effects of social exclusion on a subsequent cortisol stress response. This further demonstrates that these alterations are associated with ACTH. Lack of effects on catecholamines is discussed in view of the tend-and-befriend hypothesis but also from a methodological perspective.

  8. The hypoalgesic effect of oxycodone in human experimental pain models in relation to the CYP2D6 oxidation polymorphism

    DEFF Research Database (Denmark)

    Zwisler, Stine T; Enggaard, Thomas P; Noehr-Jensen, Lene

    2009-01-01

    Oxycodone is O-demethylated by CYP2D6 to oxymorphone which is a potent micro-receptor agonist. The CYP2D6 oxidation polymorphism divides the Caucasian population in two phenotypes: approximately 8% with no enzyme activity, poor metabolizers (PM) and the remainder with preserved CYP2D6 activity...... including 33 (16 EM and 17 PM) healthy volunteers. Pain tests were performed before and 1, 2, 3 and 4 hr after medication and included pain detection and tolerance thresholds to single electrical sural nerve stimulation, pain summation threshold to repetitive electrical sural nerve stimulation and the cold...... = 0.037, a difference of 10%, CI: 1%-20%) for PM compared with EM. In the cold pressor test, there was less reduction in pain AUC on oxycodone for PM compared with EM (14% vs. 26%, P = 0.012, a difference of 12%, CI: 3%-22%). The plasma oxymorphone/oxycodone ratio was significantly lower in PM...

  9. Association of the functional V158M catechol-O-methyl-transferase polymorphism with panic disorder in women.

    Science.gov (United States)

    Domschke, Katharina; Freitag, Christine M; Kuhlenbäumer, Gregor; Schirmacher, Anja; Sand, Philipp; Nyhuis, Peter; Jacob, Christian; Fritze, Jürgen; Franke, Petra; Rietschel, Marcella; Garritsen, Henk S; Fimmers, Rolf; Nöthen, Markus M; Lesch, Klaus-Peter; Stögbauer, Florian; Deckert, Jürgen

    2004-06-01

    Panic disorder is an anxiety disorder with an estimated heritability of up to 48%. Pharmacological and genetic studies suggest that genes coding for proteins involved in the catecholaminergic system might be relevant for the pathogenesis of the disease. In the present study, we genotyped a single nucleotide polymorphism (472G/A=V158M) in the coding region of the catechol-O-methyl-transferase (COMT) gene in 115 patients with panic disorder and age- and sex-matched controls. Association analysis revealed a significant excess of the more active COMT allele (472G=V158) in patients with panic disorder (p=0.04), particularly in female patients (p=0.01), but not in male patients (p=1.0). The assessment of a possible interaction of the COMT polymorphism with a previously reported functional 30-bp VNTR in the monoamine oxidase A promoter (MAOALPR) in female patients did not yield significant results. Our data support a role of the 472G/A (V158M) COMT polymorphism or a nearby locus in the pathogenesis of panic disorder in women.

  10. Toxicity of chlorpyrifos and chlorpyrifos oxon in a transgenic mouse model of the human paraoxonase (PON1) Q192R polymorphism

    Energy Technology Data Exchange (ETDEWEB)

    Cole, Toby B.; Walter, Betsy J.; Shih, Diana M.; Tward, Aaron D.; Lusis, Aldons J.; Timchalk, Chuck; Richter, Rebecca J.; Costa, Lucio G.; Furlong, Clement E.

    2005-08-01

    The Q192R polymorphism of paraoxonase (PON1) has been shown to affect hydrolysis of organophosphorus compounds. The Q192 and R192 alloforms exhibit equivalent catalytic efficiencies of hydrolysis for diazoxon, the oxon form of the pesticide (DZ). However, the R192 alloform has a higher catalytic efficiency of hydrolysis than does the Q192 alloform for chlorpyrifos oxon (CPO), the oxon form of the pesticide chlorpyrifos (CPS). The current study examined the relevance of these observations for in-vivo exposures to chlorpyrifos and chlorpyrifos oxon. Methods Using a transgenic mouse model we examined the relevance of the Q192R polymorphism for exposure to CPS and CPO in vivo. Transgenic mice were generated that expressed either human PON1Q192 or PON1R192 at equivalent levels, in the absence of endogenous mouse PON1. Dose-response and time course experiments were performed on adult mice exposed dermally to CPS or CPO. Morbidity and acetylcholinesterase (AChE) activity in the brain and diaphragm were determined in the first 24 h following exposure. Results Mice expressing PON1Q192 were significantly more sensitive to CPO, and to a lesser extent CPS, than were mice expressing PON1R192. The time course of inhibition following exposure to 1.2 mg/kg CPO revealed maximum inhibition of brain AChE at 6?12 h, with PON1R192, PON1Q192, and PON1? /? mice exhibiting 40, 70 and 85% inhibition, respectively, relative to control mice. The effect of PON1 removal on the dose?response curve for CPS exposure was remarkably consistent with a PBPK/PD model of CPS exposure. Conclusion These results indicate that individuals expressing only the PON1Q192 allele would be more sensitive to the adverse effects of CPO or CPS exposure, especially if they are expressing a low level of plasma PON1Q192.

  11. Polymorphism of iron at high pressure: A 3D phase-field model for displacive transitions with finite elastoplastic deformations

    Science.gov (United States)

    Vattré, A.; Denoual, C.

    2016-07-01

    A thermodynamically consistent framework for combining nonlinear elastoplasticity and multivariant phase-field theory is formulated at large strains. In accordance with the Clausius-Duhem inequality, the Helmholtz free energy and time-dependent constitutive relations give rise to displacive driving forces for pressure-induced martensitic phase transitions in materials. Inelastic forces are obtained by using a representation of the energy landscape that involves the concept of reaction pathways with respect to the point group symmetry operations of crystal lattices. On the other hand, additional elastic forces are derived for the most general case of large strains and rotations, as well as nonlinear, anisotropic, and different elastic pressure-dependent properties of phases. The phase-field formalism coupled with finite elastoplastic deformations is implemented into a three-dimensional Lagrangian finite element approach and is applied to analyze the iron body-centered cubic (α-Fe) into hexagonal close-packed (ɛ-Fe) phase transitions under high hydrostatic compression. The simulations exhibit the major role played by the plastic deformation in the morphological and microstructure evolution processes. Due to the strong long-range elastic interactions between variants without plasticity, a forward α → ɛ transition is energetically unfavorable and remains incomplete. However, plastic dissipation releases considerably the stored strain energy, leading to the α ↔ ɛ ↔α‧ (forward and reverse) polymorphic phase transformations with an unexpected selection of variants.

  12. Polymorphous computing fabric

    Science.gov (United States)

    Wolinski, Christophe Czeslaw [Los Alamos, NM; Gokhale, Maya B [Los Alamos, NM; McCabe, Kevin Peter [Los Alamos, NM

    2011-01-18

    Fabric-based computing systems and methods are disclosed. A fabric-based computing system can include a polymorphous computing fabric that can be customized on a per application basis and a host processor in communication with said polymorphous computing fabric. The polymorphous computing fabric includes a cellular architecture that can be highly parameterized to enable a customized synthesis of fabric instances for a variety of enhanced application performances thereof. A global memory concept can also be included that provides the host processor random access to all variables and instructions associated with the polymorphous computing fabric.

  13. Prediction of serotonin transporter promoter polymorphism genotypes from single nucleotide polymorphism arrays using machine learning methods.

    Science.gov (United States)

    Lu, Ake Tzu-Hui; Bakker, Steven; Janson, Esther; Cichon, Sven; Cantor, Rita M; Ophoff, Roel A

    2012-08-01

    The serotonin transporter gene (SLC6A4) and its promoter (5-HTTLPR) polymorphism have been the focus of a large number of association studies of behavioral traits and psychiatric disorders. However, large-scale genotyping of the polymorphism has been very difficult. We report the development and validation of a 5-HTTLPR genotype prediction model. The single nucleotide polymorphisms (SNPs) from the 2000 kb region surrounding 5-HTTLPR were used to construct a prediction model through a newly developed machine learning method, multicategory vertex discriminant analysis with 2147 individuals from the Northern Finnish Birth Cohort genotyped with the Illumina 370K SNP array and manually genotyped for 5-HTTLPR polymorphism. The prediction model was applied to SNP genotypes in a Dutch/German schizophrenia case-control sample of 3318 individuals to test the association of the polymorphism with schizophrenia. The prediction model of eight SNPs achieved a 92.4% accuracy rate and a 0.98±0.01 area under the receiving operating characteristic. Evidence for an association of the polymorphism with schizophrenia was observed (P=0.05, odds ratio=1.105). This prediction model provides an effective substitute of manually genotyped 5-HTTLPR alleles, providing a new approach for large scale association studies of this polymorphism.

  14. The PPCD1 mouse: characterization of a mouse model for posterior polymorphous corneal dystrophy and identification of a candidate gene.

    Directory of Open Access Journals (Sweden)

    Anna L Shen

    2010-08-01

    Full Text Available The PPCD1 mouse, a spontaneous mutant that arose in our mouse colony, is characterized by an enlarged anterior chamber resulting from metaplasia of the corneal endothelium and blockage of the iridocorneal angle by epithelialized corneal endothelial cells. The presence of stratified multilayered corneal endothelial cells with abnormal patterns of cytokeratin expression are remarkably similar to those observed in human posterior polymorphous corneal dystrophy (PPCD and the sporadic condition, iridocorneal endothelial syndrome. Affected eyes exhibit epithelialized corneal endothelial cells, with inappropriate cytokeratin expression and proliferation over the iridocorneal angle and posterior cornea. We have termed this the "mouse PPCD1" phenotype and mapped the mouse locus for this phenotype, designated "Ppcd1", to a 6.1 Mbp interval on Chromosome 2, which is syntenic to the human Chromosome 20 PPCD1 interval. Inheritance of the mouse PPCD1 phenotype is autosomal dominant, with complete penetrance on the sensitive DBA/2J background and decreased penetrance on the C57BL/6J background. Comparative genome hybridization has identified a hemizygous 78 Kbp duplication in the mapped interval. The endpoints of the duplication are located in positions that disrupt the genes Csrp2bp and 6330439K17Rik and lead to duplication of the pseudogene LOC100043552. Quantitative reverse transcriptase-PCR indicates that expression levels of Csrp2bp and 6330439K17Rik are decreased in eyes of PPCD1 mice. Based on the observations of decreased gene expression levels, association with ZEB1-related pathways, and the report of corneal opacities in Csrp2bp(tm1a(KOMPWtsi heterozygotes and embryonic lethality in nulls, we postulate that duplication of the 78 Kbp segment leading to haploinsufficiency of Csrp2bp is responsible for the mouse PPCD1 phenotype. Similarly, CSRP2BP haploinsufficiency may lead to human PPCD.

  15. Genetic variation and effects of candidate-gene polymorphisms on coagulation properties, curd firmness modeling and acidity in milk from Brown Swiss cows.

    Science.gov (United States)

    Cecchinato, A; Chessa, S; Ribeca, C; Cipolat-Gotet, C; Bobbo, T; Casellas, J; Bittante, G

    2015-07-01

    The aims of this study were to estimate the genetic variation of traditional milk coagulation properties (MCPs), milk acidity, curd firmness (CF) modeled on time t (CF(t) ; comprising: RCT(eq), rennet coagulation time estimated from the equation; CF(P), the asymptotic potential curd firmness; k(CF), the curd firming instant rate constant; and k(SR), the syneresis instant rate constant) and maximum CF traits (MCF; comprising CF(max), the maximum CF value; and tmax, the time of attainment). Furthermore, we investigated 96 single nucleotide polymorphisms (SNPs) from 54 candidate genes, testing their associations with the above-listed traits. Milk and blood samples were collected from 1271 cows (each sampled once) from 85 herds. Genotyping was performed using a custom Illumina VeraCode GoldenGate approach. A Bayesian linear animal model (including the effects of herd, days in milk, parity and additive polygenic effects) was used to estimate the genetic parameters of the studied traits. The same model with the addition of the SNP genotype effect was used for our association analysis. The heritability estimates of CF t and the MCF traits (RCT(eq)=0.258; k(CF)=0.230; CF(max)=0.191; t(max)=0.278) were similar to those obtained using traditional MCPs (0.187 to 0.267), except for the lower estimates for CF(P) (0.064) and k(SR) (0.077). A total of 13 of the 51 tested SNPs had relevant additive effects on at least one trait. We observed associations between MCPs and SNPs in the genes encoding ATP-binding cassette sub-family G member 2 (ABCG2), chemokine ligand 2 (CCL2), growth hormone 1 (GH1), prolactin (PRL) and toll-like receptor 2 (TLR2). Whereas, CF(t) and the MCF traits were associated with polymorphisms in the α-s1-casein (CSN1S1), β-casein (CSN2), GH1, oxidized low-density lipoprotein receptor 1 (OLR1), phospholipase C β1 (PLCB1), PRL and signal transducer and activator of transcription 5A (STAT5A) genes.

  16. Typing polymorphic recursion

    OpenAIRE

    Figueiredo, Lucília Camarão de; Camarão, Carlos

    2001-01-01

    This paper discusses some advantages of supporting polymorphic recursión in programming languages and describes a decidable type inference algorithm for typing polymorphic and possibly mutually recursive definitions, using Haskell to provide an executable high level specification of the algorithm.

  17. A mixed integer linear programming model to reconstruct phylogenies from single nucleotide polymorphism haplotypes under the maximum parsimony criterion.

    Science.gov (United States)

    Catanzaro, Daniele; Ravi, Ramamoorthi; Schwartz, Russell

    2013-01-23

    Phylogeny estimation from aligned haplotype sequences has attracted more and more attention in the recent years due to its importance in analysis of many fine-scale genetic data. Its application fields range from medical research, to drug discovery, to epidemiology, to population dynamics. The literature on molecular phylogenetics proposes a number of criteria for selecting a phylogeny from among plausible alternatives. Usually, such criteria can be expressed by means of objective functions, and the phylogenies that optimize them are referred to as optimal. One of the most important estimation criteria is the parsimony which states that the optimal phylogeny T∗for a set H of n haplotype sequences over a common set of variable loci is the one that satisfies the following requirements: (i) it has the shortest length and (ii) it is such that, for each pair of distinct haplotypes hi,hj∈H, the sum of the edge weights belonging to the path from hi to hj in T∗ is not smaller than the observed number of changes between hi and hj. Finding the most parsimonious phylogeny for H involves solving an optimization problem, called the Most Parsimonious Phylogeny Estimation Problem (MPPEP), which is NP-hard in many of its versions. In this article we investigate a recent version of the MPPEP that arises when input data consist of single nucleotide polymorphism haplotypes extracted from a population of individuals on a common genomic region. Specifically, we explore the prospects for improving on the implicit enumeration strategy of implicit enumeration strategy used in previous work using a novel problem formulation and a series of strengthening valid inequalities and preliminary symmetry breaking constraints to more precisely bound the solution space and accelerate implicit enumeration of possible optimal phylogenies. We present the basic formulation and then introduce a series of provable valid constraints to reduce the solution space. We then prove that these

  18. The serotonin transporter gene polymorphism (5HTTLPR) moderates the effect of adolescent environmental conditions on self-esteem in young adulthood: A structural equation modeling approach

    Science.gov (United States)

    Jonassaint, Charles R.; Ashley-Koch, Allison; Whitfield, Keith E.; Hoyle, Rick H.; Richman, Laura Smart; Siegler, Ilene C.; Royal, Charmaine D.; Williams, Redford

    2013-01-01

    Here we examine the effects of both self-reported and independent observer-reported environmental risk indices, the serotonin transporter gene promoter (5HTTLPR) polymorphism, and their interaction on self-esteem. This trait was assessed during early and mid adolescence (mean age = 14 and 16.5, respectively) and young adulthood (mean age = 21.8) in a prospective cohort of 1214 unrelated participants in the Longitudinal Study of Adolescent Health (Add Health). Using structural equation modeling we identified a gene–environment (G × E) interaction using observer-report but not self-report measures of environmental stress exposure during adolescence: 5HTTLPR genotype and observer-reports of home and neighborhood quality (HNQ) during adolescence interacted to predict self-esteem levels in young adulthood (p adolescence reported lower self-esteem in young adulthood than those with a good HNQ during adolescence. In contrast, among individuals with the l/l genotype, adolescent HNQ did not predict adulthood self-esteem. Genes may moderate the effect of adolescent environmental conditions on adulthood self-esteem. PMID:22659377

  19. The serotonin transporter gene polymorphism (5HTTLPR) moderates the effect of adolescent environmental conditions on self-esteem in young adulthood: a structural equation modeling approach.

    Science.gov (United States)

    Jonassaint, Charles R; Ashley-Koch, Allison; Whitfield, Keith E; Hoyle, Rick H; Richman, Laura Smart; Siegler, Ilene C; Royal, Charmaine D; Williams, Redford

    2012-09-01

    Here we examine the effects of both self-reported and independent observer-reported environmental risk indices, the serotonin transporter gene promoter (5HTTLPR) polymorphism, and their interaction on self-esteem. This trait was assessed during early and mid adolescence (mean age=14 and 16.5, respectively) and young adulthood (mean age=21.8) in a prospective cohort of 1214 unrelated participants in the Longitudinal Study of Adolescent Health (Add Health). Using structural equation modeling we identified a gene-environment (G×E) interaction using observer-report but not self-report measures of environmental stress exposure during adolescence: 5HTTLPR genotype and observer-reports of home and neighborhood quality (HNQ) during adolescence interacted to predict self-esteem levels in young adulthood (padolescence reported lower self-esteem in young adulthood than those with a good HNQ during adolescence. In contrast, among individuals with the l/l genotype, adolescent HNQ did not predict adulthood self-esteem. Genes may moderate the effect of adolescent environmental conditions on adulthood self-esteem. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Insights into the Molecular Mechanisms Underlying Mammalian P2X7 Receptor Functions and Contributions in Diseases, Revealed by Structural Modeling and Single Nucleotide Polymorphisms

    Science.gov (United States)

    Jiang, Lin-Hua; Baldwin, Jocelyn M.; Roger, Sebastien; Baldwin, Stephen A.

    2013-01-01

    The mammalian P2X7 receptors (P2X7Rs), a member of the ionotropic P2X receptor family with distinctive functional properties, play an important part in mediating extracellular ATP signaling in health and disease. A clear delineation of the molecular mechanisms underlying the key receptor properties, such as ATP-binding, ion permeation, and large pore formation of the mammalian P2X7Rs, is still lacking, but such knowledge is crucial for a better understanding of their physiological functions and contributions in diseases and for development of therapeutics. The recent breakthroughs in determining the atomic structures of the zebrafish P2X4.1R in the closed and ATP-bound open states have provided the long-awaited structural information. The human P2RX7 gene is abundant with non-synonymous single nucleotide polymorphisms (NS-SNPs), which generate a repertoire of human P2X7Rs with point mutations. Characterizations of the NS-SNPs identified in patients of various disease conditions and the resulting mutations have informed previously unknown molecular mechanisms determining the mammalian P2X7R functions and diseases. In this review, we will discuss the new insights into such mechanisms provided by structural modeling and recent functional and genetic linkage studies of NS-SNPs. PMID:23675347

  1. Insights into the molecular mechanisms underlying mammalian P2X7 receptor functions and contributions in diseases, revealed by structural modeling and single nucleotide polymorphisms

    Directory of Open Access Journals (Sweden)

    Lin-Hua eJiang

    2013-05-01

    Full Text Available The mammalian P2X7 receptors (P2X7Rs, a member of the ionotropic P2X receptor family with distinctive functional properties, play an important part in mediating extracellular ATP signaling in health and disease. A clear delineation of the molecular mechanisms underlying the key receptor properties, such as ATP-binding, ion permeation, and large pore formation of the mammalian P2X7Rs, is still lacking, but such knowledge is crucial for a better understanding of their physiological functions and contributions in diseases and for development of therapeutics. The recent breakthroughs in determining the atomic structures of the zebrafish P2X4.1R in the closed and ATP-bound open states have provided the long-awaited structural information. The human P2RX7 gene is abundant with non-synonymous single nucleotide polymorphisms (NS-SNPs, which generate a repertoire of human P2X7Rs with point mutations. Characterizations of the NS-SNPs identified in patients of various disease conditions and the resulting mutations have informed previously unknown molecular mechanisms determining the mammalian P2X7R functions and diseases. In this review, we will discuss the new insights into such mechanisms provided by structural modeling and recent functional and genetic linkage studies of NS-SNPs.

  2. Evidence for Karyotype Polymorphism in the Free-Living Flatworm, Macrostomum lignano, a Model Organism for Evolutionary and Developmental Biology

    NARCIS (Netherlands)

    Zadesenets, Kira S.; Vizoso, Dita B.; Schlatter, Aline; Konopatskaia, Irina D.; Berezikov, Eugene; Scharer, Lukas; Rubtsov, Nikolay B.

    2016-01-01

    Over the past decade, the free-living flatworm Macrostomum lignano has been successfully used in many areas of biology, including embryology, stem cells, sexual selection, bioadhesion and aging. The increased use of this powerful laboratory model, including the establishment of genomic resources and

  3. CDKN2A region polymorphism and genetic susceptibility to melanoma in the melim swine model of familial melanoma

    Czech Academy of Sciences Publication Activity Database

    Chalony, C.; Renard, C.; Naulleas, V. S.; Crechet, F.; Leplatt, J. J.; Tricaud, Y.; Horák, Vratislav; Gruand, J.; Le Roy, P.; Frelat, G.; Geffrotin, C.

    2003-01-01

    Roč. 103, č. 5 (2003), s. 631-635 ISSN 0020-7136 R&D Projects: GA AV ČR KSK5011112; GA ČR GA524/01/0162; GA AV ČR IBS5045113 Institutional research plan: CEZ:AV0Z5045916 Keywords : melim swine model Subject RIV: ED - Physiology Impact factor: 4.375, year: 2003

  4. Evidence for Karyotype Polymorphism in the Free-Living Flatworm, Macrostomum lignano, a Model Organism for Evolutionary and Developmental Biology

    OpenAIRE

    Zadesenets, Kira S.; Vizoso, Dita B.; Schlatter, Aline; Konopatskaia, Irina D.; Berezikov, Eugene; Scharer, Lukas; Rubtsov, Nikolay B.

    2016-01-01

    Over the past decade, the free-living flatworm Macrostomum lignano has been successfully used in many areas of biology, including embryology, stem cells, sexual selection, bioadhesion and aging. The increased use of this powerful laboratory model, including the establishment of genomic resources and tools, makes it essential to have a detailed description of the chromosome organization of this species, previously suggested to have a karyotype with 2n = 8 and one pair of large and three pairs ...

  5. Influence of interleukin-1 gene polymorphism on the outcome of supportive periodontal therapy explored by a multi-factorial periodontal risk assessment model (PRA).

    Science.gov (United States)

    Persson, G Rutger; Matuliené, Giedré; Ramseier, Christoph A; Persson, Rigmor E; Tonetti, Maurizio S; Lang, Niklaus P

    2003-01-01

    Multi-factorial risk models have been proposed to enhance the ability to predict risk for the progression of treated chronic periodontitis. to study if the outcomes of supportive periodontal therapy (SPT) based on a multi-factorial periodontal risk assessment are influenced by IL-1 gene polymorphism (IP) status. Information about the IP and smoking status, clinical periodontal conditions and age related bone level measurements were used to calculate a peridontal risk assessment model (PRA). The surface area of this diagram was calculated for 224 subjects who had participated in an SPT program over four years. Baseline and 4-year follow-up data were studied in relation to the IP status. Positive IP tests were obtained for 80/224 (35.7%) of the subjects. At baseline the mean PRA for the IP positive group was 79.9 units, which at year four had increased to 81.3 units (mean diff: 1.4 units, S.D.+/-16.5, pPRA for the IP negative group was 44.2 and 38.6 units, respectively. This difference was statistically significant (mean diff: 5.6, S.D.+/-16.1, pPRA over the four-year period (PRA difference: 7.04, t=3.01, pPRA included bleeding on probing at baseline, IP status, proportional alveolar bone loss in relation to the age, and gender. The PRA allowed the assessment of the outcomes of SPT therapy. Subjects with positive IP did not respond to individualized SPT as favorably as did IP negative subjects.

  6. Induced pluripotent stem cell derived cardiomyocytes as models for cardiac arrhythmias

    Directory of Open Access Journals (Sweden)

    Maaike eHoekstra

    2012-08-01

    Full Text Available Cardiac arrhythmias are a major cause of morbidity and mortality. In younger patients, the majority of sudden cardiac deaths have an underlying Mendelian genetic cause. Over the last 15 years, enormous progress has been made in identifying the distinct clinical phenotypes and in studying the basic cellular and genetic mechanisms associated with the primary Mendelian (monogenic arrhythmia syndromes. Investigation of the electrophysiological consequences of an ion channel mutation is ideally done in the native cardiomyocyte environment. However, the majority of such studies so far have relied on heterologous expression systems in which single ion channel genes are expressed in non-cardiac cells. In some cases, transgenic mouse models haven been generated, but these also have significant shortcomings, primarily related to species differences.The discovery that somatic cells can be reprogrammed to pluripotency as induced pluripotent stem cells (iPSC has generated much interest since it presents an opportunity to generate patient- and disease-specific cell lines from which normal and diseased human cardiomyocytes can be obtained These genetically diverse human model systems can be studied in vitro and used to decipher mechanisms of disease and identify strategies and reagents for new therapies. Here we review the present state of the art with respect to cardiac disease models already generated using IPSC technology and which have been (partially characterized.Human iPSC (hiPSC models have been described for the cardiac arrhythmia syndromes, including LQT1, LQT2, LQT3-Brugada Syndrome, LQT8/Timothy syndrome and catecholaminergic polymorphic ventricular tachycardia. In most cases, the hiPSC-derived cardiomyoctes recapitulate the disease phenotype and have already provided opportunities for novel insight into cardiac pathophysiology. It is expected that the lines will be useful in the development of pharmacological agents for the management of these

  7. Nucleotide polymorphism in the 5.8S nrDNA gene and internal transcribed spacers in Phakopsora pachyrhizi viewed from structural models.

    Science.gov (United States)

    Freire, Maíra Cristina Menezes; da Silva, Maria Roméria; Zhang, Xuecheng; Almeida, Álvaro Manuel Rodrigues; Stacey, Gary; de Oliveira, Luiz Orlando

    2012-02-01

    The assessment of nucleotide polymorphisms in environmental samples of obligate pathogens requires DNA amplification through the polymerase chain reaction (PCR) and bacterial cloning of PCR products prior to sequencing. The drawback of this strategy is that it can give rise to false polymorphisms owing to DNA polymerase misincorporation during PCR or bacterial cloning. We investigated patterns of nucleotide polymorphism in the internal transcribed spacer (ITS) region for Phakopsora pachyrhizi, an obligate biotrophic fungus that causes the Asian soybean rust. Field-collected samples of P. pachyrhizi were obtained from all major soybean production areas worldwide, including Brazil and the United States. Bacterially-cloned, PCR products were obtained using a high fidelity DNA polymerase. A total of 370 ITS sequences that were subjected to an array of complementary sequence analyses, which included analyses of secondary structure stability, the pattern of nucleotide polymorphisms, GC content, and the presence of conserved motifs. The sequences exhibited features of functional rRNAs. Overall, polymorphisms took place within less conserved motives, such as loops and bulges; alternatively, they gave rise to non-canonical G-U pairs within conserved regions of double stranded helices. We discuss the usefulness of structural analyses to filter out putative 'suspicious' bacterially cloned ITS sequences, thus keeping artificially-induced sequence variation to a minimum. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Evidence for Karyotype Polymorphism in the Free-Living Flatworm, Macrostomum lignano, a Model Organism for Evolutionary and Developmental Biology.

    Science.gov (United States)

    Zadesenets, Kira S; Vizoso, Dita B; Schlatter, Aline; Konopatskaia, Irina D; Berezikov, Eugene; Schärer, Lukas; Rubtsov, Nikolay B

    2016-01-01

    Over the past decade, the free-living flatworm Macrostomum lignano has been successfully used in many areas of biology, including embryology, stem cells, sexual selection, bioadhesion and aging. The increased use of this powerful laboratory model, including the establishment of genomic resources and tools, makes it essential to have a detailed description of the chromosome organization of this species, previously suggested to have a karyotype with 2n = 8 and one pair of large and three pairs of small metacentric chromosomes. We performed cytogenetic analyses for chromosomes of one commonly used inbred line of M. lignano (called DV1) and uncovered unexpected chromosome number variation in the form of aneuploidies of the largest chromosomes. These results prompted us to perform karyotypic studies in individual specimens of this and other lines of M. lignano reared under laboratory conditions, as well as in freshly field-collected specimens from different natural populations. Our analyses revealed a high frequency of aneuploids and in some cases other numerical and structural chromosome abnormalities in laboratory-reared lines of M. lignano, and some cases of aneuploidy were also found in freshly field-collected specimens. Moreover, karyological analyses were performed in specimens of three further species: Macrostomum sp. 8 (a close relative of M. lignano), M. spirale and M. hystrix. Macrostomum sp. 8 showed a karyotype that was similar to that of M. lignano, with tetrasomy for its largest chromosome being the most common karyotype, while the other two species showed a simpler karyotype that is more typical of the genus Macrostomum. These findings suggest that M. lignano and Macrostomum sp. 8 can be used as new models for studying processes of partial genome duplication in genome evolution.

  9. Evidence for Karyotype Polymorphism in the Free-Living Flatworm, Macrostomum lignano, a Model Organism for Evolutionary and Developmental Biology.

    Directory of Open Access Journals (Sweden)

    Kira S Zadesenets

    Full Text Available Over the past decade, the free-living flatworm Macrostomum lignano has been successfully used in many areas of biology, including embryology, stem cells, sexual selection, bioadhesion and aging. The increased use of this powerful laboratory model, including the establishment of genomic resources and tools, makes it essential to have a detailed description of the chromosome organization of this species, previously suggested to have a karyotype with 2n = 8 and one pair of large and three pairs of small metacentric chromosomes. We performed cytogenetic analyses for chromosomes of one commonly used inbred line of M. lignano (called DV1 and uncovered unexpected chromosome number variation in the form of aneuploidies of the largest chromosomes. These results prompted us to perform karyotypic studies in individual specimens of this and other lines of M. lignano reared under laboratory conditions, as well as in freshly field-collected specimens from different natural populations. Our analyses revealed a high frequency of aneuploids and in some cases other numerical and structural chromosome abnormalities in laboratory-reared lines of M. lignano, and some cases of aneuploidy were also found in freshly field-collected specimens. Moreover, karyological analyses were performed in specimens of three further species: Macrostomum sp. 8 (a close relative of M. lignano, M. spirale and M. hystrix. Macrostomum sp. 8 showed a karyotype that was similar to that of M. lignano, with tetrasomy for its largest chromosome being the most common karyotype, while the other two species showed a simpler karyotype that is more typical of the genus Macrostomum. These findings suggest that M. lignano and Macrostomum sp. 8 can be used as new models for studying processes of partial genome duplication in genome evolution.

  10. Complex relationships between occupation, environment, DNA adducts, genetic polymorphisms and bladder cancer in a case-control study using a structural equation modeling.

    Directory of Open Access Journals (Sweden)

    Stefano Porru

    Full Text Available DNA adducts are considered an integrate measure of carcinogen exposure and the initial step of carcinogenesis. Their levels in more accessible peripheral blood lymphocytes (PBLs mirror that in the bladder tissue. In this study we explore whether the formation of PBL DNA adducts may be associated with bladder cancer (BC risk, and how this relationship is modulated by genetic polymorphisms, environmental and occupational risk factors for BC. These complex interrelationships, including direct and indirect effects of each variable, were appraised using the structural equation modeling (SEM analysis. Within the framework of a hospital-based case/control study, study population included 199 BC cases and 213 non-cancer controls, all Caucasian males. Data were collected on lifetime smoking, coffee drinking, dietary habits and lifetime occupation, with particular reference to exposure to aromatic amines (AAs and polycyclic aromatic hydrocarbons (PAHs. No indirect paths were found, disproving hypothesis on association between PBL DNA adducts and BC risk. DNA adducts were instead positively associated with occupational cumulative exposure to AAs (p = 0.028, whereas XRCC1 Arg 399 (p<0.006 was related with a decreased adduct levels, but with no impact on BC risk. Previous findings on increased BC risk by packyears (p<0.001, coffee (p<0.001, cumulative AAs exposure (p = 0.041 and MnSOD (p = 0.009 and a decreased risk by MPO (p<0.008 were also confirmed by SEM analysis. Our results for the first time make evident an association between occupational cumulative exposure to AAs with DNA adducts and BC risk, strengthening the central role of AAs in bladder carcinogenesis. However the lack of an association between PBL DNA adducts and BC risk advises that these snapshot measurements are not representative of relevant exposures. This would envisage new scenarios for biomarker discovery and new challenges such as repeated measurements at different

  11. Inferring polymorphism-induced regulatory gene networks active in human lymphocyte cell lines by weighted linear mixed model analysis of multiple RNA-Seq datasets.

    Directory of Open Access Journals (Sweden)

    Wensheng Zhang

    Full Text Available Single-nucleotide polymorphisms (SNPs contribute to the between-individual expression variation of many genes. A regulatory (trait-associated SNP is usually located near or within a (host gene, possibly influencing the gene's transcription or/and post-transcriptional modification. But its targets may also include genes that are physically farther away from it. A heuristic explanation of such multiple-target interferences is that the host gene transfers the SNP genotypic effects to the distant gene(s by a transcriptional or signaling cascade. These connections between the host genes (regulators and the distant genes (targets make the genetic analysis of gene expression traits a promising approach for identifying unknown regulatory relationships. In this study, through a mixed model analysis of multi-source digital expression profiling for 140 human lymphocyte cell lines (LCLs and the genotypes distributed by the international HapMap project, we identified 45 thousands of potential SNP-induced regulatory relationships among genes (the significance level for the underlying associations between expression traits and SNP genotypes was set at FDR < 0.01. We grouped the identified relationships into four classes (paradigms according to the two different mechanisms by which the regulatory SNPs affect their cis- and trans- regulated genes, modifying mRNA level or altering transcript splicing patterns. We further organized the relationships in each class into a set of network modules with the cis- regulated genes as hubs. We found that the target genes in a network module were often characterized by significant functional similarity, and the distributions of the target genes in three out of the four networks roughly resemble a power-law, a typical pattern of gene networks obtained from mutation experiments. By two case studies, we also demonstrated that significant biological insights can be inferred from the identified network modules.

  12. Modeling single nucleotide polymorphisms in the human AKR1C1 and AKR1C2 genes: implications for functional and genotyping analyses.

    Directory of Open Access Journals (Sweden)

    Jonathan W Arthur

    2010-12-01

    Full Text Available Enzymes encoded by the AKR1C1 and AKR1C2 genes are responsible for the metabolism of progesterone and 5α-dihydrotestosterone (DHT, respectively. The effect of amino acid substitutions, resulting from single nucleotide polymorphisms (SNPs in the AKR1C2 gene, on the enzyme kinetics of the AKR1C2 gene product were determined experimentally by Takashi et al. In this paper, we used homology modeling to predict and analyze the structure of AKR1C1 and AKR1C2 genetic variants. The experimental reduction in enzyme activity in the AKR1C2 variants F46Y and L172Q, as determined by Takahashi et al., is predicted to be due to increased instability in cofactor binding, caused by disruptions to the hydrogen bonds between NADP and AKR1C2, resulting from the insertion of polar residues into largely non-polar environments near the site of cofactor binding. Other AKR1C2 variants were shown to involve either conservative substitutions or changes taking place on the surface of the molecule and distant from the active site, confirming the experimental finding of Takahashi et al. that these variants do not result in any statistically significant reduction in enzyme activity. The AKR1C1 R258C variant is predicted to have no effect on enzyme activity for similar reasons. Thus, we provide further insight into the molecular mechanism of the enzyme kinetics of these proteins. Our data also highlight previously reported difficulties with online databases.

  13. The pattern of polymorphism in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    2005-07-01

    Full Text Available We resequenced 876 short fragments in a sample of 96 individuals of Arabidopsis thaliana that included stock center accessions as well as a hierarchical sample from natural populations. Although A. thaliana is a selfing weed, the pattern of polymorphism in general agrees with what is expected for a widely distributed, sexually reproducing species. Linkage disequilibrium decays rapidly, within 50 kb. Variation is shared worldwide, although population structure and isolation by distance are evident. The data fail to fit standard neutral models in several ways. There is a genome-wide excess of rare alleles, at least partially due to selection. There is too much variation between genomic regions in the level of polymorphism. The local level of polymorphism is negatively correlated with gene density and positively correlated with segmental duplications. Because the data do not fit theoretical null distributions, attempts to infer natural selection from polymorphism data will require genome-wide surveys of polymorphism in order to identify anomalous regions. Despite this, our data support the utility of A. thaliana as a model for evolutionary functional genomics.

  14. A predictive model of the association between gene polymorphism and the risk of noise-induced hearing loss caused by gunfire noise

    Directory of Open Access Journals (Sweden)

    Ben-Chih Yuan

    2012-01-01

    Conclusion: In this study, we found that although loud noise could usually result in hearing damage, the clinical characteristics of hearing loss were irrelevant to gunfire noise. The gene polymorphisms provide predictors for us to evaluate the risk of NIHL prior to gunshot training.

  15. Fat mass and obesity-associated (FTO) gene polymorphisms are associated with physical activity, food intake, eating behaviors, psychological health, and modeled change in body mass index in overweight/obese Caucasian adults.

    Science.gov (United States)

    Harbron, Janetta; van der Merwe, Lize; Zaahl, Monique G; Kotze, Maritha J; Senekal, Marjanne

    2014-08-06

    The fat mass and obesity-associated (FTO) gene is currently recognized as the most robust predictor of polygenic obesity. We investigated associations between the FTO rs1421085 and rs17817449 polymorphisms and the FTO rs1421085-rs17817449 haplotype and dietary intake, eating behavior, physical activity, and psychological health, as well as the effect of these associations on BMI. N = 133 treatment seeking overweight/obese Caucasian adults participated in this study. Genotyping was performed from whole blood samples. Weight and height was measured and a non-quantified food frequency questionnaire was completed to assess food group intake. Validated questionnaires were completed to assess physical activity (Baecke questionnaire), psychological health (General Health questionnaire, Rosenburg self-esteem scale and Beck Depression Inventory), and eating behavior (Three Factor Eating questionnaire). The risk alleles of the FTO polymorphisms were associated with poorer eating behaviors (higher hunger, internal locus for hunger, and emotional disinhibition scores), a higher intake of high fat foods and refined starches and more depressive symptoms. The modeled results indicate that interactions between the FTO polymorphisms or haplotypes and eating behavior, psychological health, and physical activity levels may be associated with BMI. The clinical significance of these results for implementation as part of weight management interventions needs further investigation.

  16. Fat Mass and Obesity-Associated (FTO Gene Polymorphisms Are Associated with Physical Activity, Food Intake, Eating Behaviors, Psychological Health, and Modeled Change in Body Mass Index in Overweight/Obese Caucasian Adults

    Directory of Open Access Journals (Sweden)

    Janetta Harbron

    2014-08-01

    Full Text Available The fat mass and obesity-associated (FTO gene is currently recognized as the most robust predictor of polygenic obesity. We investigated associations between the FTO rs1421085 and rs17817449 polymorphisms and the FTO rs1421085–rs17817449 haplotype and dietary intake, eating behavior, physical activity, and psychological health, as well as the effect of these associations on BMI. N = 133 treatment seeking overweight/obese Caucasian adults participated in this study. Genotyping was performed from whole blood samples. Weight and height was measured and a non-quantified food frequency questionnaire was completed to assess food group intake. Validated questionnaires were completed to assess physical activity (Baecke questionnaire, psychological health (General Health questionnaire, Rosenburg self-esteem scale and Beck Depression Inventory, and eating behavior (Three Factor Eating questionnaire. The risk alleles of the FTO polymorphisms were associated with poorer eating behaviors (higher hunger, internal locus for hunger, and emotional disinhibition scores, a higher intake of high fat foods and refined starches and more depressive symptoms. The modeled results indicate that interactions between the FTO polymorphisms or haplotypes and eating behavior, psychological health, and physical activity levels may be associated with BMI. The clinical significance of these results for implementation as part of weight management interventions needs further investigation.

  17. Estimating relative stability of polymorphs by generation of configurational free energy phase diagram

    DEFF Research Database (Denmark)

    Upadhyay, Pratik Pankaj; Dantuluri, Ajay K; Kumar, Lokesh

    2012-01-01

    , a new methodology for assessing thermodynamic T(t) of two polymorphs has been developed. Configurational free energy (G(c) ) of amorphous with respect to each polymorph was calculated to determine the T(t) . This method was used to determine the T(t) and polymorphic relationship of two model drugs...

  18. A model of cardiac ryanodine receptor gating predicts experimental Ca2+-dynamics and Ca2+-triggered arrhythmia in the long QT syndrome

    Science.gov (United States)

    Wilson, Dan; Ermentrout, Bard; Němec, Jan; Salama, Guy

    2017-09-01

    Abnormal Ca2+ handling is well-established as the trigger of cardiac arrhythmia in catecholaminergic polymorphic ventricular tachycardia and digoxin toxicity, but its role remains controversial in Torsade de Pointes (TdP), the arrhythmia associated with the long QT syndrome (LQTS). Recent experimental results show that early afterdepolarizations (EADs) that initiate TdP are caused by spontaneous (non-voltage-triggered) Ca2+ release from Ca2+-overloaded sarcoplasmic reticulum (SR) rather than the activation of the L-type Ca2+-channel window current. In bradycardia and long QT type 2 (LQT2), a second, non-voltage triggered cytosolic Ca2+ elevation increases gradually in amplitude, occurs before overt voltage instability, and then precedes the rise of EADs. Here, we used a modified Shannon-Puglisi-Bers model of rabbit ventricular myocytes to reproduce experimental Ca2+ dynamics in bradycardia and LQT2. Abnormal systolic Ca2+-oscillations and EADs caused by SR Ca2+-release are reproduced in a modified 0-dimensional model, where 3 gates in series control the ryanodine receptor (RyR2) conductance. Two gates control RyR2 activation and inactivation and sense cytosolic Ca2+ while a third gate senses luminal junctional SR Ca2+. The model predicts EADs in bradycardia and low extracellular [K+] and cessation of SR Ca2+-release terminate salvos of EADs. Ca2+-waves, systolic cell-synchronous Ca2+-release, and multifocal diastolic Ca2+ release seen in subcellular Ca2+-mapping experiments are observed in the 2-dimensional version of the model. These results support the role of SR Ca2+-overload, abnormal SR Ca2+-release, and the subsequent activation of the electrogenic Na+/Ca2+-exchanger as the mechanism of TdP. The model offers new insights into the genesis of cardiac arrhythmia and new therapeutic strategies.

  19. Formation of Piroxicam Polymorphism in Solution Crystallization

    DEFF Research Database (Denmark)

    Bruun Hansen, Thomas; Qu, Haiyan

    2015-01-01

    Recently, new insights into crystallization prior to actual nucleation have shown interesting results for drugs showing differences in hydrogen bonding or orientation in various polymorphic forms. On the basis of this concept, piroxicam was chosen as a model compound because the two common forms, I...... also explored, and new insights into polymorphic control are documented and discussed. The crystal landscape was mapped for cooling crystallization of piroxicam from acetone/water mixtures (0.5 K/min) and for antisolvent crystallization from acetone with water as the antisolvent. Varying cooling rates...

  20. Metal Ion Controlled Polymorphism of a Peptide

    DEFF Research Database (Denmark)

    Hemmingsen, Lars Bo Stegeager; Jancso, Attila; Szunyogh, Daniel

    2011-01-01

    , …) in the peptide, and the ligand and structural preferences of the metal ion (in our studies Zn2+, Cd2+, Hg2+, Cu+/2+). Simultaneously, new species such as metal ion bridged ternary complexes or even oligomers may be formed. In recent previous studies we have observed similar polymorphism of zinc finger model...

  1. Study of obesity associated proopiomelanocortin gene polymorphism

    African Journals Online (AJOL)

    ... fasting glucose, fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR) and fasting lipid profiles, and higher frequency of occurrence of non alcoholic fatty liver disease and BED. Allelic frequencies of POMC gene 9 bp insertional polymorphism were comparable in patients and controls (p= 0.956).

  2. Teaching polymorphism early

    DEFF Research Database (Denmark)

    2005-01-01

    Is it possible to teach dynamic polymorphism early? What techniques could facilitate teaching it in Java. This panel will bring together people who have considered this question and attempted to implement it in various ways, some more completely than others. It will also give participants...

  3. Single Nucleotide Polymorphism

    DEFF Research Database (Denmark)

    Børsting, Claus; Pereira, Vania; Andersen, Jeppe Dyrberg

    2014-01-01

    Single nucleotide polymorphisms (SNPs) are the most frequent DNA sequence variations in the genome. They have been studied extensively in the last decade with various purposes in mind. In this chapter, we will discuss the advantages and disadvantages of using SNPs for human identification...

  4. Polymorphs of Pridopidine Hydrochloride

    DEFF Research Database (Denmark)

    Zimmermann, A.; Frostrup, B.; Bond, A. D.

    2012-01-01

    Pridopidine hydrochloride (Huntexil, Neuro-Search A/S, Ballerup, Denmark) is a dopaminergic stabilizer, currently in development for the treatment of motor symptoms associated with Huntington's disease. In this study, two polymorphic forms are characterized, forms I and II. The crystal structures...

  5. Mouse Model of the OPRM1 (A118G) Polymorphism: Differential Heroin Self-Administration Behavior Compared with Wild-Type Mice

    Science.gov (United States)

    Zhang, Yong; Picetti, Roberto; Butelman, Eduardo R; Ho, Ann; Blendy, Julie A; Kreek, Mary Jeanne

    2015-01-01

    Mu-opioid receptors (MOPRs) are the target of heroin and other prescription opioids, which are currently responsible for massive addiction morbidity in the US. The gene coding for the human MOPR (OPRM1) has an important functional single nucleotide polymorphism (SNP), A118G. The OPRM1 A118G genotype results in substantially increased risk of heroin addiction in humans; however, the neurobiological mechanism for this increased risk is not fully understood. This study examined heroin self-administration (SA) behavior in A112G (G/G) mice, harboring a functionally equivalent SNP in Oprm1 with a similar amino acid substitution, in extended (4 h) SA sessions. Adult male and female G/G mice and ‘wild-type' litter mates (A/A) were allowed to self-administer heroin (0.25 mg/kg/unit dose, FR1 with a nose poke response) for 4 h/day, for 10 consecutive days. Half of the mice then continued in a heroin dose–response study, while extinction from heroin SA was studied in the other half. In vivo microdialysis was used to measure acute heroin-induced increases of striatal dopamine in the GG vs AA genotypes. Male and female G/G mice responded for heroin significantly more (and thus had greater intake) than A/A mice, in the initial 10 days of heroin SA, and in the subsequent dose–response study. There were no significant differences in extinction of SA between the A/A and G/G mice. Heroin-induced increases in striatal dopamine levels are higher in the GG mice than in the AA mice. Both male and female G/G mice self-administered more heroin than did A/A mice over a 10-day period, possibly because of the greater increases of heroin-induced striatal dopamine in the GG mice. Furthermore, G/G male mice escalated the amount of heroin self-administration across 10 extended-access sessions more than A/A male mice did. These are the first studies to examine the acquisition of heroin SA in this mouse model. These studies may lead to a better understanding of the neurobiological and

  6. Validation of in vitro cell models used in drug metabolism and transport studies; genotyping of cytochrome P450, phase II enzymes and drug transporter polymorphisms in the human hepatoma (HepG2), ovarian carcinoma (IGROV-1) and colon carcinoma (CaCo-2, LS180) cell lines

    International Nuclear Information System (INIS)

    Brandon, Esther F.A.; Bosch, Tessa M.; Deenen, Maarten J.; Levink, Rianne; Wal, Everdina van der; Meerveld, Joyce B.M. van; Bijl, Monique; Beijnen, Jos H.; Schellens, Jan H.M.; Meijerman, Irma

    2006-01-01

    Human cell lines are often used for in vitro biotransformation and transport studies of drugs. In vivo, genetic polymorphisms have been identified in drug-metabolizing enzymes and ABC-drug transporters leading to altered enzyme activity, or a change in the inducibility of these enzymes. These genetic polymorphisms could also influence the outcome of studies using human cell lines. Therefore, the aim of our study was to pharmacogenotype four cell lines frequently used in drug metabolism and transport studies, HepG2, IGROV-1, CaCo-2 and LS180, for genetic polymorphisms in biotransformation enzymes and drug transporters. The results indicate that, despite the presence of some genetic polymorphisms, no real effects influencing the activity of metabolizing enzymes or drug transporters in the investigated cell lines are expected. However, this characterization will be an aid in the interpretation of the results of biotransformation and transport studies using these in vitro cell models

  7. Polymorphism of phosphoric oxide

    Science.gov (United States)

    Hill, W.L.; Faust, G.T.; Hendricks, S.B.

    1943-01-01

    The melting points and monotropic relationship of three crystalline forms of phosphoric oxide were determined by the method of quenching. Previous vapor pressure data are discussed and interpreted to establish a pressure-temperature diagram (70 to 600??) for the one-component system. The system involves three triple points, at which solid, liquid and vapor (P4O10) coexist in equilibrium, namely: 420?? and 360 cm., 562?? and 43.7 cm. and 580?? and 55.5 cm., corresponding to the hexagonal, orthorhombic and stable polymorphs, respectively, and at least two distinct liquids, one a stable polymer of the other, which are identified with the melting of the stable form and the hexagonal modification, respectively. Indices of refraction of the polymorphs and glasses were determined. The density and the thermal, hygroscopic and structural properties of the several phases are discussed.

  8. On the polymorphism of griseofulvin: identification of two additional polymorphs.

    Science.gov (United States)

    Mahieu, Aurelien; Willart, Jean-Francois; Dudognon, Emeline; Eddleston, Mark D; Jones, William; Danède, Florence; Descamps, Marc

    2013-02-01

    In this paper, we present an investigation of the polymorphism of griseofulvin. In addition to the only reported crystalline form (form I), two new polymorphic forms (II and III) have been identified and characterized by differential scanning calorimetry and powder X-ray diffraction. Reasons why these two polymorphs were isolated during the present study, but not detected during the numerous previous studies on this drug, are also discussed. Copyright © 2012 Wiley Periodicals, Inc.

  9. Koka: Programming with Row Polymorphic Effect Types

    Directory of Open Access Journals (Sweden)

    Daan Leijen

    2014-06-01

    Full Text Available We propose a programming model where effects are treated in a disciplined way, and where the potential side-effects of a function are apparent in its type signature. The type and effect of expressions can also be inferred automatically, and we describe a polymorphic type inference system based on Hindley-Milner style inference. A novel feature is that we support polymorphic effects through row-polymorphism using duplicate labels. Moreover, we show that our effects are not just syntactic labels but have a deep semantic connection to the program. For example, if an expression can be typed without an _exn_ effect, then it will never throw an unhandled exception. Similar to Haskell's `runST` we show how we can safely encapsulate stateful operations. Through the state effect, we can also safely combine state with let-polymorphism without needing either imperative type variables or a syntactic value restriction. Finally, our system is implemented fully in a new language called Koka and has been used successfully on various small to medium-sized sample programs ranging from a Markdown processor to a tier-splitted chat application. You can try out Koka live at www.rise4fun.com/koka/tutorial.

  10. Lifted Java: A Minimal Calculus for Translation Polymorphism

    DEFF Research Database (Denmark)

    Ingesman, Matthias Diehn; Ernst, Erik

    2011-01-01

    as a single object which has both types. In the terminology of Object Teams this is called translation polymorphism. In both Object Teams and CaesarJ the type system of the Java programming language has been extended to support this through the use of advanced language features. However, so far the soundness...... of translation polymorphism has not been proved. This paper presents a simple model that extends Featherweight Java with the core operations of translation polymorphism, provides a Coq proof that its type system is sound, and shows that the ambiguity problem associated with the so-called smart lifting mechanism...

  11. Crystallization and Polymorphism of Felodipine

    DEFF Research Database (Denmark)

    Surov, A. O.; Solanko, K. A.; Bond, A. D.

    2012-01-01

    Two previously known polymorphs (forms I and II) and two new polymorphs (forms III and IV) of the calcium-channel blocker felodipine were obtained during attempts to cocrystallize the compound with a variety of potential cocrystal formers. A correlation was observed between the polymorphic outcome...... and the effective pH value in the presence of the cocrystal former, and it was possible subsequently to produce the four polymorphs by pH adjustment using H2SO4(aq) or NaOH(aq). This suggests that there is no distinct "structure-directing" role for the molecular additives present during the cocrystallization trials...

  12. [Impact of gene-environment interaction between the C (-344) T polymorphism of CYP11B2 and drinking index on the risk of hypertension under multifactor dimensionality reduction model in Chinese Mongolian population].

    Science.gov (United States)

    Pan, Xing-qiang; Liu, Yong-yue; Zhang, Xian-yu; Zhang, Yong-hong; Xu, Qun; Qiu, Chang-chun; Tong, Wei-jun

    2009-09-01

    To explore the interaction between C (-344) T polymorphism of CYP11B2 and drinking index (DI) as well as their impact on the risk of hypertension in Chinese Mongolian population. A total of 1575 Mongolian people aged 20 and older including 562 hypertensive and 1013 normal-tensive from agricultural and pastoral areas in Tongliao city of Inner Mongolia, were included in this study. A cross-sectional survey was conducted to collect data by personal interview with local residents, using a standard questionnaire. Fasting blood samples were drawn and height, weight and blood pressure were measured. The variant genotypes of CYP11B2, ACE and eNOS were identified by PCR assays. Gene-environment interactions were analyzed, using multifactor dimensionality reduction (MDR) model. Based on the result of the best MDR model, a multiple logistic regression model was constructed as the final cause-effect interpretative model. The interaction between CYP11B2 variant genotype and drinking index appeared the best MDR model with statistical significance (chi(2) = 66.35, P or = 168), the genotype (TT) combining the drinking index (> or = 40), the genotype (TT) combining the drinking index (> or = 1) and the genotype (TC) combining the drinking index (> or = 90), were all risk factors of hypertension when comparing with genotype (CC) combining the drinking index (0), and the ORs (95%CI) appeared to be 2.07 (1.15 - 3.70), 2.35 (1.22 - 4.56), 2.05 (1.07 - 3.94) and 5.56 (2.54 - 12.18) respectively. Essential hypertension might positively be affected by the interaction of the C (-344) T polymorphism of CYP11B2 and the drinking index in Chinese Mongolian population.

  13. Association study of molecular polymorphisms in candidate genes related to stress responses with production and meat quality traits in pigs.

    Science.gov (United States)

    Terenina, E; Babigumira, B M; Le Mignon, G; Bazovkina, D; Rousseau, S; Salin, F; Bendixen, C; Mormede, P

    2013-02-01

    The hypothalamic-pituitary-adrenal (HPA) axis exerts a large range of effects on metabolism, the immune system, inflammatory processes, and brain functions. Together with the sympathetic nervous system, it is also the most important stress-responsive neuroendocrine system. Both systems influence production traits, carcass composition, and meat quality. The HPA axis may be a critical target for genetic selection of more robust animals. Indeed, numerous studies in various species have demonstrated the importance of genetic factors in shaping the individual HPA axis phenotype, and genetic polymorphism can be found at each level of the axis, including hormone production by the adrenal cortices under stimulation by adrenocorticotropic hormone (ACTH), hormone bioavailability, or receptor and postreceptor mechanisms. The aim of the present experiment was to extend these findings to the brain neurochemical systems involved in stress responses. To this end, a number of candidate genes were sequenced for molecular polymorphisms and their association was studied with stress neuroendocrine and production traits in a genetically diverse population consisting of 100 female pigs from an advanced intercross (F10-F12) between 2 highly divergent breeds, Large White (LW) and Meishan (MS). The LW breed has a high production potential for lean meat and a low HPA axis activity, and the MS breed has low growth rate, fat carcasses-but large litters of highly viable piglets-and a high HPA axis activity. Candidate genes were chosen in the catecholaminergic and serotonergic pathways, in the pituitary control of cortisol production, among genes previously demonstrated to be differentially expressed in ACTH-stimulated adrenal glands from LW and MS pigs, and in cortisol receptors. Sixty new polymorphisms were found. The association study with carcass and meat quality traits and with endocrine traits showed a number of significant results, such as monoamine oxidase (MAOA) polymorphisms with

  14. Structure of graphane polymorphs

    Science.gov (United States)

    Belenkova, T. E.; Greshyakov, V. A.; Chernov, V. M.; Belenkov, E. A.

    2017-11-01

    Calculations of the structure and electronic properties for five structural variations of graphane were performed within the framework of density functional theory (DFT) with generalized gradient approximations (GGA). The electron densities of states and band structure of graphene crystals have been calculated. It has been established that the band gap for graphane polymorphs varies from 5.50 eV to 5.65 eV. Sublimation energy of graphane layers with different structure was varying from 11.33 to 11.48 eV per C-H molecular group.

  15. Methylenetetrahydrofolate reductase (MTHFR) gene polymorphism ...

    African Journals Online (AJOL)

    Administrator

    2011-10-19

    Oct 19, 2011 ... Polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene are associated with abortion, early embryo loss and recurrent spontaneous abortion in human. However, information on the association between MTHFR polymorphism and cow abortion is scarce. In the present study, the effects.

  16. Methylenetetrahydrofolate reductase (MTHFR) gene polymorphism ...

    African Journals Online (AJOL)

    Polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene are associated with abortion, early embryo loss and recurrent spontaneous abortion in human. However, information on the association between MTHFR polymorphism and cow abortion is scarce. In the present study, the effects of MTHFR ...

  17. Association between Gene Polymorphisms and Pain Sensitivity Assessed in a Multi-Modal Multi-Tissue Human Experimental Model - An Explorative Study

    DEFF Research Database (Denmark)

    Nielsen, Lecia Møller; Olesen, Anne Estrup; Sato, Hiroe

    2016-01-01

    The genetic influence on sensitivity to noxious stimuli (pain sensitivity) remains controversial and needs further investigation. In the present study, the possible influence of polymorphisms in three opioid receptor (OPRM, OPRD and OPRK) genes and the catechol-O-methyltransferase (COMT) gene...... on pain sensitivity in healthy participants was investigated. Catechol-O-methyltransferase has an indirect effect on the mu opioid receptor by changing its activity through an altered endogenous ligand effect. Blood samples for genetic analysis were withdrawn in a multi-modal and multi-tissue experimental......, electrical and thermal visceral stimulations. A cold pressor test was also conducted. DNA was available from 38 of 40 participants. Compared to non-carriers of the COMT rs4680A allele, carriers reported higher bone pressure pain tolerance threshold (i.e. less pain) by up to 23.8% (p

  18. Per3 VNTR polymorphism and chronic heart failure.

    Science.gov (United States)

    Lipkova, Jolana; Bienertova-Vasku, Julie Anna; Spinarova, Lenka; Bienert, Petr; Hlavna, Marian; Pavkova Goldbergova, Monika; Parenica, Jiri; Spinar, Jindrich; Vasku, Anna

    2014-01-01

    The aim of this study was to investigate the relationship between gene Period3 (Per3) variable number tandem repeat (VNTR) polymorphism and chronic heart failure (CHF). The study subjects (372 patients of Caucasian origin with CHF and 332 healthy controls) were genotyped for Per3 VNTR polymorphism using an allele-specific PCR. No significant differences in genotype or Per3 VNTR allele frequencies were found between CHF cases and controls (Pg=0.30, Pa=0.52). No significant differences were uncovered either between CHF cases according to etiology (DCMP vs. IHD; Pg=0.87, Pa=0.91). In the multivariate regression modeling, no predictive function of VNTR Per3 polymorphism on ejection fraction or NYHA class, hyperlipidaemia or type II diabetes risk was found. Per3 VNTR polymorphism is not a major risk factor for chronic heart failure or a factor modulating the severity of the CHF in this population.

  19. Diabat Interpolation for Polymorph Free-Energy Differences.

    Science.gov (United States)

    Kamat, Kartik; Peters, Baron

    2017-02-02

    Existing methods to compute free-energy differences between polymorphs use harmonic approximations, advanced non-Boltzmann bias sampling techniques, and/or multistage free-energy perturbations. This work demonstrates how Bennett's diabat interpolation method ( J. Comput. Phys. 1976, 22, 245 ) can be combined with energy gaps from lattice-switch Monte Carlo techniques ( Phys. Rev. E 2000, 61, 906 ) to swiftly estimate polymorph free-energy differences. The new method requires only two unbiased molecular dynamics simulations, one for each polymorph. To illustrate the new method, we compute the free-energy difference between face-centered cubic and body-centered cubic polymorphs for a Gaussian core solid. We discuss the justification for parabolic models of the free-energy diabats and similarities to methods that have been used in studies of electron transfer.

  20. Social polymorphism in the sweat beeLasioglossum(Evylaeus)calceatum.

    Science.gov (United States)

    Davison, P J; Field, J

    Temperate-zone socially polymorphic sweat bees (Hymenoptera: Halictidae) are ideal model systems for elucidating the origins of eusociality, a major evolutionary transition. Bees express either social or solitary behaviour in different parts of their range, and social phenotype typically correlates with season length. Despite their obvious utility, however, socially polymorphic sweat bees have received relatively little attention with respect to understanding the origins of eusociality. Lasioglossum ( Evylaeus ) calceatum is a widespread sweat bee that is thought to be socially polymorphic, with important potential as an experimental model species. We first determined the social phenotype of L. calceatum at three sites located at different latitudes within the UK. We then investigated sociality in detail across two years at the southernmost site. We found that L. calceatum exhibits latitudinal social polymorphism within the UK; bees were solitary at our two northern sites but the majority of nests were social at our southern site. Sociality in the south was characterised by a relatively small mean of two and 3.5 workers per nest in each year, respectively, and a small to medium mean caste-size dimorphism of 6.6 %. Foundresses were smaller in our more northern and high altitude populations. Sociality is clearly less specialised than in some closely related obligately social species but probably more specialied than other polymorphic sweat bees. Our research provides a starting point for future experimental work to investigate mechanisms underlying social polymorphism in L . calceatum .

  1. Single Nucleotide Polymorphism

    DEFF Research Database (Denmark)

    Børsting, Claus; Pereira, Vania; Andersen, Jeppe Dyrberg

    2014-01-01

    and briefly describe the methods that are preferred for SNP typing in forensic genetics. In addition, we will illustrate how SNPs can be used as investigative leads in the police investigation by discussing the use of ancestry informative markers and forensic DNA phenotyping. Modern DNA sequencing......Single nucleotide polymorphisms (SNPs) are the most frequent DNA sequence variations in the genome. They have been studied extensively in the last decade with various purposes in mind. In this chapter, we will discuss the advantages and disadvantages of using SNPs for human identification...... technologies (also called next generation sequencing or NGS) have the potential to completely transform forensic genetic investigations as we know them today. Here, we will make a short introduction to NGS and explain how NGS may combine analysis of the traditional forensic genetic markers with analysis...

  2. Association with polymorphic marmoset cytochrome P450 2C19 of in vivo hepatic clearances of chirally separated R-omeprazole and S-warfarin using individual marmoset physiologically based pharmacokinetic models.

    Science.gov (United States)

    Kusama, Takashi; Toda, Akiko; Shimizu, Makiko; Uehara, Shotaro; Inoue, Takashi; Uno, Yasuhiro; Utoh, Masahiro; Sasaki, Erika; Yamazaki, Hiroshi

    2017-11-10

    1. Simulated clearances of R-warfarin and efavirenz were recently reported for individual cynomolgus monkeys genotyped for cytochrome P450 2C19 and 2C9, respectively. To expand and verify this modeling procedure, simulations of R/S-omeprazole and R/S-warfarin clearances after oral administrations in individual marmosets were performed using individual simplified physiologically based pharmacokinetic (PBPK) modeling consisting of gut, liver and central compartments. 2. Pharmacokinetics of R/S-omeprazole were chirally determined using the previously reported plasma microsamples in this study. The areas under the plasma concentration/time curves (AUC) of R-omeprazole and S-warfarin, but not S-omeprazole and R-warfarin, after oral administrations in the P450 2C19 homozygous mutant group were significantly higher than those in the wild-type group. These modeled hepatic intrinsic clearances were also significantly associated with the marmoset P450 2C19 genotypes. Other parameter values, e.g. absorption rate constants or systemic circulation volumes, were not likely determining factors. 3. The reported individual AUC values measured in 4-6 marmosets after oral R-omeprazole and S-warfarin administrations were significantly correlated with the AUC values predicted using the PBPK models after virtual administrations. 4. This study indicates that clearances of R-omeprazole, S-warfarin and related medicines associated with polymorphic P450 2C19 in individual marmosets can be simulated using simplified individual PBPK models.

  3. Methylenetetrahydrofolate reductase gene polymorphisms in Egyptian Turner Syndrome patients.

    Science.gov (United States)

    Ismail, Manal F; Zarouk, Waheba A; Ruby, Mona O; Mahmoud, Wael M; Gad, Randa S

    2015-01-01

    Folate metabolism dysfunctions can result in DNA hypomethylation and abnormal chromosome segregation. Two common polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) encoding gene (C677T and A1298C) reduce MTHFR activity, but when associated with aneuploidy, the results are conflicting. Turner Syndrome (TS) is an interesting model for investigating the association between MTHFR gene polymorphisms and nondisjunction because of the high frequency of chromosomal mosaicism in this syndrome. To investigate the association of MTHFR gene C677T and A1298C polymorphisms in TS patients and their mothers and to correlate these polymorphisms with maternal risk of TS offspring. MTHFR C677T and A1298C polymorphisms were genotyped in 33 TS patients, their mothers and 15 healthy females with their mothers as controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing technique. Genotype and allele frequencies of both C677T and A1298C were not significantly different between TS cases and controls. There were no significant differences in C677T genotype distribution between the TS mothers and controls (p=1). The MTHFR 1298AA and 1298AC genotypes were significantly increased in TS mothers Vs. control mothers (p=0.002). The C allele frequency of the A1298C polymorphism was significantly different between the TS mothers and controls (p=0.02). The association of A1298C gene polymorphism in TS patients was found to increase with increasing age of both mothers (p=0.026) and fathers (p=0.044) of TS cases. Our findings suggest a strong association between maternal MTHFR A1298C and risk of TS in Egypt.

  4. A monoclinic polymorph of theophylline

    Directory of Open Access Journals (Sweden)

    Shuo Zhang

    2011-12-01

    Full Text Available A monoclinic polymorph of theophylline, C7H8N4O2, has been obtained from a chloroform/methanol mixture by evaporation under ambient conditions. The new polymorph crystallizes with two molecules in the asymmetric unit. The structure features intermolecular N—H...O hydrogen bonds, resulting in the formation of dimers between two crystallographically different molecules; each molecule acts as both donor and acceptor.

  5. Diffuse Scattering as an Aid to the Understanding of Polymorphism in Pharmaceuticals

    Science.gov (United States)

    Welberry, T. R.; Chan, E. J.; Goossens, D. J.; Heerdegen, A. P.

    2012-05-01

    Polymorphism occurs when the same molecular compound can crystallize in more than one distinct crystal structure. Its study is a field of great interest and activity. This is largely driven by its importance in the pharmaceutical industry, but polymorphism is also an issue in the pigments, dyes, and explosives industries. The polymorph formed by a compound generally exerts a strong influence on its solid-state properties. The polymorphic form of a drug molecule may affect the ease of manufacture and processing, shelf life, and most significantly the rate of uptake of the molecule by the human body. They can even vary in toxicity; one polymorph may be safe, while a second may be toxic. In this review of recently published work, we show how diffuse scattering experiments coupled with Monte Carlo (MC) computer modeling can aid in the understanding of polymorphism. Examples of the two common pharmaceuticals, benzocaine and aspirin, both of which are bimorphic, at ambient temperatures, are discussed.

  6. Diffuse Scattering as an Aid to the Understanding of Polymorphism in Pharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Welberry, T.R.; Chan, E.J.; Goossens, D.J.; Heerdegen, A.P. (ANU)

    2012-04-30

    Polymorphism occurs when the same molecular compound can crystallize in more than one distinct crystal structure. Its study is a field of great interest and activity. This is largely driven by its importance in the pharmaceutical industry, but polymorphism is also an issue in the pigments, dyes, and explosives industries. The polymorph formed by a compound generally exerts a strong influence on its solid-state properties. The polymorphic form of a drug molecule may affect the ease of manufacture and processing, shelf life, and most significantly the rate of uptake of the molecule by the human body. They can even vary in toxicity; one polymorph may be safe, while a second may be toxic. In this review of recently published work, we show how diffuse scattering experiments coupled with Monte Carlo (MC) computer modeling can aid in the understanding of polymorphism. Examples of the two common pharmaceuticals, benzocaine and aspirin, both of which are bimorphic, at ambient temperatures, are discussed.

  7. Enteric bacterial metabolites propionic and butyric acid modulate gene expression, including CREB-dependent catecholaminergic neurotransmission, in PC12 cells--possible relevance to autism spectrum disorders.

    Directory of Open Access Journals (Sweden)

    Bistra B Nankova

    Full Text Available Alterations in gut microbiome composition have an emerging role in health and disease including brain function and behavior. Short chain fatty acids (SCFA like propionic (PPA, and butyric acid (BA, which are present in diet and are fermentation products of many gastrointestinal bacteria, are showing increasing importance in host health, but also may be environmental contributors in neurodevelopmental disorders including autism spectrum disorders (ASD. Further to this we have shown SCFA administration to rodents over a variety of routes (intracerebroventricular, subcutaneous, intraperitoneal or developmental time periods can elicit behavioral, electrophysiological, neuropathological and biochemical effects consistent with findings in ASD patients. SCFA are capable of altering host gene expression, partly due to their histone deacetylase inhibitor activity. We have previously shown BA can regulate tyrosine hydroxylase (TH mRNA levels in a PC12 cell model. Since monoamine concentration is known to be elevated in the brain and blood of ASD patients and in many ASD animal models, we hypothesized that SCFA may directly influence brain monoaminergic pathways. When PC12 cells were transiently transfected with plasmids having a luciferase reporter gene under the control of the TH promoter, PPA was found to induce reporter gene activity over a wide concentration range. CREB transcription factor(s was necessary for the transcriptional activation of TH gene by PPA. At lower concentrations PPA also caused accumulation of TH mRNA and protein, indicative of increased cell capacity to produce catecholamines. PPA and BA induced broad alterations in gene expression including neurotransmitter systems, neuronal cell adhesion molecules, inflammation, oxidative stress, lipid metabolism and mitochondrial function, all of which have been implicated in ASD. In conclusion, our data are consistent with a molecular mechanism through which gut related environmental signals

  8. A Prospective Cohort Study on IRS Gene Polymorphisms in Type 2 ...

    African Journals Online (AJOL)

    Insulin resistance status was determined using the homeostatic model assessment for insulin resistance (HOMA-IR) index. Results: IRS1 polymorphisms were associated with increased insulin resistance (X2 = 5.09, p = 0.023) in T2DM patients with severe/acute hyperglycemia. IRS2 polymorphisms were not associated with ...

  9. Association of lactase 13910 C/T polymorphism with bone mineral ...

    Indian Academy of Sciences (India)

    However, there was no significant association of LCT 13910 C/T polymorphism with BMD at lumbar spine and risk of vertebral fractures under all genetic contrast models (all P values were >0.05). The meta-analysis suggests that there are significant effects of LCT 13910 C/T polymorphism on BMD and fracture risk.

  10. Investigation of polymorphic transitions of piracetam induced during wet granulation.

    Science.gov (United States)

    Potter, Catherine B; Kollamaram, Gayathri; Zeglinski, Jacek; Whitaker, Darren A; Croker, Denise M; Walker, Gavin M

    2017-10-01

    Piracetam was investigated as a model API which is known to exhibit a number of different polymorphic forms. It is freely soluble in water so the possibility exists for polymorphic transformations to occur during wet granulation. Analysis of the polymorphic form present during lab-scale wet granulation, using water as a granulation liquid, was studied with powder X-ray diffraction and Raman spectroscopy as off-line and inline analysis tools respectively. Different excipients with a range of hydrophilicities, aqueous solubilities and molecular weights were investigated to examine their influence on these solution-mediated polymorphic transitions and experimental results were rationalised using molecular modelling. Our results indicated that as an increasing amount of water was added to the as-received piracetam FIII, a greater amount of the API dissolved which recrystallised upon drying to the metastable FII(6.403) via a monohydrate intermediary. Molecular level analysis revealed that the observed preferential transformation of monohydrate to FII is linked with a greater structural similarity between the monohydrate and FII polymorph in comparison to FIII. The application of Raman spectroscopy as a process analytical technology (PAT) tool to monitor the granulation process for the production of the monohydrate intermediate as a precursor to the undesirable metastable form was demonstrated. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Introduction to the polymorphic tracking code Fibre bundles, polymorphic Taylor types and "Exact tracking"

    CERN Document Server

    Schmidt, F; McIntosh, E

    2002-01-01

    This is a description of the basic ideas behind the ``Polymorphic Tracking Code'' or PTC. PTC is truly a ``kick code'' or symplectic integrator in the tradition of TRACYII, SixTrack, and TEAPOT. However it separates correctly the mathematical atlas of charts and the magnets at a structural level by implementing a ``restricted fibre bundle.'' The resulting structures allow backward propagation and recirculation, something not possible in standard tracking codes. Also PTC is polymorphic in handling real (single, double and even quadruple precision) and Taylor series. Therefore it has all the tools associated to the TPSA packages: Lie methods, Normal Forms, Cosy-Infinity capabilities, beam envelopes for radiation, etc., as well as parameter dependence on-the-fly. However PTC is an integrator, and as such, one must, generally, adhere to the Talman ``exactness'' view of modelling. Incidentally, it supports exact sector and rectangular bends as well. Of course, one can certainly bypass its integrator and the user i...

  12. The Genealogical Consequences of Fecundity Variance Polymorphism

    Science.gov (United States)

    Taylor, Jesse E.

    2009-01-01

    The genealogical consequences of within-generation fecundity variance polymorphism are studied using coalescent processes structured by genetic backgrounds. I show that these processes have three distinctive features. The first is that the coalescent rates within backgrounds are not jointly proportional to the infinitesimal variance, but instead depend only on the frequencies and traits of genotypes containing each allele. Second, the coalescent processes at unlinked loci are correlated with the genealogy at the selected locus; i.e., fecundity variance polymorphism has a genomewide impact on genealogies. Third, in diploid models, there are infinitely many combinations of fecundity distributions that have the same diffusion approximation but distinct coalescent processes; i.e., in this class of models, ancestral processes and allele frequency dynamics are not in one-to-one correspondence. Similar properties are expected to hold in models that allow for heritable variation in other traits that affect the coalescent effective population size, such as sex ratio or fecundity and survival schedules. PMID:19433628

  13. Polymorphous band structure model of gapping in the antiferromagnetic and paramagnetic phases of the Mott insulators MnO, FeO, CoO, and NiO

    Science.gov (United States)

    Trimarchi, Giancarlo; Wang, Zhi; Zunger, Alex

    2018-01-01

    The existence of band gaps in both the antiferromagnetic (AFM) and paramagnetic (PM) phases of the classic NaCl-structure Mott insulators MnO, FeO, CoO, and NiO is traditionally viewed and taught as a manifestation of strong correlation whereby insulation results from electrons moving across the lattice forming states with doubly occupied d orbitals on certain atomic sites and empty d orbitals on other sites. Within such theories, the gap of the AFM and PM phases of these oxides emerges even in the absence of spatial symmetry breaking. The need for such a correlated picture is partially based on the known failure of the commonly used band models for the PM phase that assume for such a spin disordered state the macroscopically averaged NaCl structure, where all transition metal (TM) sites are symmetry-equivalent (a monomorphous description), producing a gapless PM state with zero magnetic moments, in sharp conflict with experiment. Here, we seek to understand the minimum theoretical description needed to capture the leading descriptors of ground state Mott insulation in the classic, 3 d monoxide Mott systems—gapping and moment formation in the AFM and PM phase. As noted by previous authors, the spin-ordered AFM phase in these materials already shows in band theory a significant band gap when one doubles the NaCl unit cell by permitting different potentials for transition-metal atoms with different spins. For the spin-disordered PM phase, we allow analogously larger NaCl-type supercells where each TM site can have different spin direction and local bonding environments (i.e., disordered), yet the total spin is zero. Such a polymorphous description has the flexibility to acquire symmetry-breaking energy-lowering patterns that can lift the degeneracy of the d orbitals and develop large on-site magnetic moments without violating the global, averaged NaCl symmetry. Electrons are exchanged between spin-up and spin-down bands to create closed-shell insulating

  14. ASSOCIATION BETWEEN CYTOKINE GENE POLYMORPHISMS AND RECURRENT MISCARRIAGE

    Directory of Open Access Journals (Sweden)

    L A. Gordeeva

    2017-01-01

    Full Text Available Associations between IL1B (rs1143634, IL1RN (VNTR, intron 2, IL4 (VNTR, intron 3, TNFA (rs1800629, rs361525, IL6 (rs1800795, and IL10 (rs1800896 genetic polymorphisms in women with recurrent miscarriage (RM were analyzed. We studied DNA samples of 112 women with RM and 267 women with physiological pregnancy. The IL1RN, IL4 genotypes were identified by PCR techniques, the IL1B, IL6 gene polymorphisms were defined by means of RFLP approach. To detect TNFA and IL10 gene polymorphisms, TaqMan real-time PCR was used. The results have shown that polymorphic loci of IL1B, IL1RN, IL10, TNFA genes were not associated with RM, and early spontaneous abortion risk. The 2R allele of IL4 gene was found to be associated with higher RM risk (OR = 1.52; 95% CI = [1.08-2.14]; P-value (cor = 0.05, and G allele of IL6 gene was associated with a risk for > 3 early spontaneous abortions (OR = 2.10; 95% CI = [1.24-3.56]; P-value (cor = 0.05, in an additive inheritance model. Upon evaluation of the data obtained, one may conclude that the IL4 (VNTR intron 3 and IL6 (rs1800795 gene polymorphisms could influence the RM development. These results may be useful for assessment of molecular mechanisms underlying early spontaneous abortion.

  15. Association of polymorphism of the alpha 1-antitrypsin gene with ...

    African Journals Online (AJOL)

    In order to determine the relationship between the polymorphisms of the AAT gene and milk production traits and SCS, the General Linear Model (GLM) procedure from the Statistical Analysis Software was used. SNP5504 affected milk fat percentage, SNP8178 affected milk protein percentage and SNP5609 and SNP5624 ...

  16. Association of polymorphism in the alpha-1-antitrypsin gene with ...

    African Journals Online (AJOL)

    Sahand Rayaneh

    2014-06-11

    Jun 11, 2014 ... Association of polymorphism in the alpha-1-antitrypsin gene with milk production traits in ... Abstract. Alpha-1-antitrypsin (A1AT) as a strong protease inhibitor plays a major role in the protection of tissues ..... populations over generations; iii) Different statistical models used to analyse the data. For the traits ...

  17. Tumour necrosis factor alpha (TNF-α) genetic polymorphisms and ...

    Indian Academy of Sciences (India)

    Sensitivity analysis of the summary odds ratio coefficients on the association between TNF-α-308G/A polymorphism and AILD risk using a random effects model. (A allele vs G allele). Results were computed by omitting each study in turn. Error bars are 95% confidence interval. Journal of Genetics, Vol. 92, No. 3, December ...

  18. Prospects for inferring pairwise relationships with single nucleotide polymorphisms

    Science.gov (United States)

    Jeffery C. Glaubitz; O. Eugene, Jr. Rhodes; J. Andrew DeWoody

    2003-01-01

    An extraordinarily large number of single nucleotide polymorphisms (SNPs) are now available in humans as well as in other model organisms. Technological advancements may soon make it feasible to assay hundreds of SNPs in virtually any organism of interest. One potential application of SNPs is the determination of pairwise genetic relationships in populations without...

  19. Influence of thiopurine methyltransferase gene polymorphism on ...

    Indian Academy of Sciences (India)

    Azza A. G. Tantawy

    2017-11-28

    Nov 28, 2017 ... Thiopurine methyltransferase (TPMT) gene polymorphism regulates thiopurine therapeutic efficacy and toxicity. The ... assessment, haematological panel investigations and TPMT gene polymorphism for G238C, G460A and A719G alleles assessment .... TPMT polymorphism in Egyptian cancer patients.

  20. Structural Immaturity of Human iPSC-Derived Cardiomyocytes: In Silico Investigation of Effects on Function and Disease Modeling

    Science.gov (United States)

    Koivumäki, Jussi T.; Naumenko, Nikolay; Tuomainen, Tomi; Takalo, Jouni; Oksanen, Minna; Puttonen, Katja A.; Lehtonen, Šárka; Kuusisto, Johanna; Laakso, Markku; Koistinaho, Jari; Tavi, Pasi

    2018-01-01

    Background: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising experimental tool for translational heart research and drug development. However, their usability as a human adult cardiomyocyte model is limited by their functional immaturity. Our aim is to analyse quantitatively those characteristics and how they differ from adult CMs. Methods and Results: We have developed a novel in silico model with all essential functional electrophysiology and calcium handling features of hiPSC-CMs. Importantly, the virtual cell recapitulates the immature intracellular ion dynamics that are characteristic for hiPSC-CMs, as quantified based our in vitro imaging data. The strong “calcium clock” is a source for a dual function of excitation-contraction coupling in hiPSC-CMs: action potential and calcium transient morphology vary substantially depending on the activation sequence of underlying ionic currents and fluxes that is altered in spontaneous vs. paced mode. Furthermore, parallel simulations with hiPSC-CM and adult cardiomyocyte models demonstrate the central differences. Results indicate that hiPSC-CMs translate poorly the disease specific phenotypes of Brugada syndrome, long QT Syndrome and catecholaminergic polymorphic ventricular tachycardia, showing less robustness and greater tendency for arrhythmic events than adult CMs. Based on a comparative sensitivity analysis, hiPSC-CMs share some features with adult CMs, but are still functionally closer to prenatal CMs than adult CMs. A database analysis of 3000 hiPSC-CM model variants suggests that hiPSC-CMs recapitulate poorly fundamental physiological properties of adult CMs. Single modifications do not appear to solve this problem, which is mostly contributed by the immaturity of intracellular calcium handling. Conclusion: Our data indicates that translation of findings from hiPSC-CMs to human disease should be made with great caution. Furthermore, we established a

  1. Structural Immaturity of Human iPSC-Derived Cardiomyocytes: In Silico Investigation of Effects on Function and Disease Modeling

    Directory of Open Access Journals (Sweden)

    Jussi T. Koivumäki

    2018-02-01

    Full Text Available Background: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs have emerged as a promising experimental tool for translational heart research and drug development. However, their usability as a human adult cardiomyocyte model is limited by their functional immaturity. Our aim is to analyse quantitatively those characteristics and how they differ from adult CMs.Methods and Results: We have developed a novel in silico model with all essential functional electrophysiology and calcium handling features of hiPSC-CMs. Importantly, the virtual cell recapitulates the immature intracellular ion dynamics that are characteristic for hiPSC-CMs, as quantified based our in vitro imaging data. The strong “calcium clock” is a source for a dual function of excitation-contraction coupling in hiPSC-CMs: action potential and calcium transient morphology vary substantially depending on the activation sequence of underlying ionic currents and fluxes that is altered in spontaneous vs. paced mode. Furthermore, parallel simulations with hiPSC-CM and adult cardiomyocyte models demonstrate the central differences. Results indicate that hiPSC-CMs translate poorly the disease specific phenotypes of Brugada syndrome, long QT Syndrome and catecholaminergic polymorphic ventricular tachycardia, showing less robustness and greater tendency for arrhythmic events than adult CMs. Based on a comparative sensitivity analysis, hiPSC-CMs share some features with adult CMs, but are still functionally closer to prenatal CMs than adult CMs. A database analysis of 3000 hiPSC-CM model variants suggests that hiPSC-CMs recapitulate poorly fundamental physiological properties of adult CMs. Single modifications do not appear to solve this problem, which is mostly contributed by the immaturity of intracellular calcium handling.Conclusion: Our data indicates that translation of findings from hiPSC-CMs to human disease should be made with great caution. Furthermore, we

  2. HFE p.H63D polymorphism does not influence ALS phenotype and survival

    Science.gov (United States)

    Chiò, Adriano; Mora, Gabriele; Sabatelli, Mario; Caponnetto, Claudia; Lunetta, Christian; Traynor, Bryan J.; Johnson, Janel O.; Nalls, Mike A.; Calvo, Andrea; Moglia, Cristina; Borghero, Giuseppe; Monsurrò, Maria Rosaria; Bella, Vincenzo La; Volanti, Paolo; Simone, Isabella; Salvi, Fabrizio; Logullo, Francesco O.; Nilo, Riva; Giannini, Fabio; Mandrioli, Jessica; Tanel, Raffaella; Murru, Maria Rita; Mandich, Paola; Zollino, Marcella; Conforti, Francesca L.; Penco, Silvana

    2016-01-01

    It has been recently reported that the p.His63Asp polymorphism of the HFE gene accelerates disease progression both in the SOD1 transgenic mouse and in amyotrophic lateral sclerosis (ALS) patients. We have evaluated the effect of HFE p.His63Asp polymorphism on the phenotype in 1351 Italian ALS patients (232 of Sardinian ancestry). Patients were genotyped for the HFE p.His63Asp polymorphism (CC, GC, and GG). All patients were also assessed for C9ORF72, TARDBP, SOD1, and FUS mutations. Of the 1351 ALS patients, 363 (29.2%) were heterozygous (GC) for the p.His63Asp polymorphism and 30 (2.2%) were homozygous for the minor allele (GG). Patients with CC, GC, and GG polymorphisms did not significantly differ by age at onset, site of onset of symptoms, and survival; however, in SOD1 patients with CG or GG polymorphism had a significantly longer survival than those with a CC polymorphism. Differently from what observed in the mouse model of ALS, the HFE p.His63Asp polymorphism has no effect on ALS phenotype in this large series of Italian ALS patients. PMID:26174855

  3. Polymorphic Uncertain Linear Programming for Generalized Production Planning Problems

    Directory of Open Access Journals (Sweden)

    Xinbo Zhang

    2014-01-01

    Full Text Available A polymorphic uncertain linear programming (PULP model is constructed to formulate a class of generalized production planning problems. In accordance with the practical environment, some factors such as the consumption of raw material, the limitation of resource and the demand of product are incorporated into the model as parameters of interval and fuzzy subsets, respectively. Based on the theory of fuzzy interval program and the modified possibility degree for the order of interval numbers, a deterministic equivalent formulation for this model is derived such that a robust solution for the uncertain optimization problem is obtained. Case study indicates that the constructed model and the proposed solution are useful to search for an optimal production plan for the polymorphic uncertain generalized production planning problems.

  4. Genome-wide patterns of nucleotide polymorphism in domesticated rice

    DEFF Research Database (Denmark)

    Caicedo, Ana L; Williamson, Scott H; Hernandez, Ryan D

    2007-01-01

    Domesticated Asian rice (Oryza sativa) is one of the oldest domesticated crop species in the world, having fed more people than any other plant in human history. We report the patterns of DNA sequence variation in rice and its wild ancestor, O. rufipogon, across 111 randomly chosen gene fragments......, and use these to infer the evolutionary dynamics that led to the origins of rice. There is a genome-wide excess of high-frequency derived single nucleotide polymorphisms (SNPs) in O. sativa varieties, a pattern that has not been reported for other crop species. We developed several alternative models...... the dominant demographic model for domesticated species, cannot explain the derived nucleotide polymorphism site frequency spectrum in rice. Instead, a bottleneck model that incorporates selective sweeps, or a more complex demographic model that includes subdivision and gene flow, are more plausible...

  5. Exploring the role of the HNF-1αG319S polymorphism in β cell failure and youth-onset type 2 diabetes: Lessons from MODY and Hnf-1α-deficient animal models.

    Science.gov (United States)

    Jonasson, Michael E; Wicklow, Brandy A; Sellers, Elizabeth A C; Dolinsky, Vernon W; Doucette, Christine A

    2015-10-01

    The prevalence of youth-onset type 2 diabetes (T2D) is rapidly increasing worldwide, disproportionately affecting Indigenous youth with Oji-Cree heritage from central Canada. Candidate gene screening has uncovered a novel and private polymorphism in the Oji-Cree population in the hepatocyte nuclear factor-1 alpha (HNF-1α) gene, where a highly conserved glycine residue at position 319 is changed to a serine (termed HNF-1αG319S or simply G319S). Oji-Cree youth who carry one or two copies of the "S-allele" present at diagnosis with less obesity, reduced indicators of insulin resistance, and lower plasma insulin levels at diagnosis, suggestive of a primary defect in the insulin-secreting β cells. Few studies on the impact of the HNF-1αG319S variant on β cell function have been performed to date; however, much can be learned from other clinical phenotypes of HNF-1α-deficiency, including HNF-1α mutations that cause maturity-onset diabetes of the young 3 (MODY3). In addition, evaluation of Hnf-1α-deficient murine models reveals that HNF-1α plays a central role in the regulation of insulin secretion by regulating the expression of key genes involved in β cell glucose-sensing, mitochondrial function, and the maintenance of the β cell phenotype in differentiated β cells. The overall goal of this minireview is to explore the impact of HNF-1α-deficiency on the β cell to better inform future research into the mechanisms of β cell dysfunction in Oji-Cree youth with T2D.

  6. A Murine Model of Genetic and Environmental Neurotoxicant Action

    National Research Council Canada - National Science Library

    Richfield, Eric

    1999-01-01

    .... The major findings to date include the generation and characterization of transgenic lines of mice expressing alpha synuclein in catecholaminergic cell groups, their increased vulnerability to MPTP...

  7. Methylenetetrahydrofolate reductase A1298C polymorphism and diabetes risk: evidence from a meta-analysis.

    Science.gov (United States)

    Yan, Yulan; Liang, Hongjie; Yang, Shi; Wang, Jian; Xie, Li; Qin, Xue; Li, Shan

    2014-08-01

    The relationship between the methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism and the susceptibility of diabetes remains inclusive or controversial. For better understanding of the influence of MTHFR A1298C polymorphism on diabetes risk, we performed this meta-analysis. All related articles were identified through a search of PubMed, Embase, Chinese Biomedical Literature Database (CBM, Chinese), China National Knowledge Infrastructure (CNKI), and Wangfang Database (Chinese). The relationship between the MTHFR A1298C polymorphism and diabetes susceptibility was conducted by odds ratios (ORs) and 95% confidence intervals. Total of six studies with 897 cases and 852 controls were included in our meta-analysis. Overall, the significance associated was found between MTHFR A1298C polymorphism and the susceptibility of diabetes under recessive model (CC vs. OR=1.70, 95% CI=1.18-2.45, p=0.004). On the subgroup analysis according to ethnicity, the results indicated that MTHFR A1298C polymorphism has a significant association with diabetes in Asian population under dominant model (CC/AC vs. AA: OR=1.31, 95% CI=1.003-1.72, p=0.047). However, there was no association found between MTHFR A1298C polymorphism and diabetes susceptibility in Caucasians. The results indicated that the MTHFR A1298C polymorphism is a dangerous factor for diabetes, especially for Asians.

  8. The amount of DNA polymorphism when population size changes linearly.

    Science.gov (United States)

    Takahashi, Takuya; Tajima, Fumio

    2017-09-12

    Population size is one of the main factors that determine the amount of DNA polymorphism. We examined a model under which the population size changed linearly. Because of the simplicity of this model, we could analytically obtain the expectation of nucleotide diversity, E(π), and the expectation of the amount of DNA polymorphism, E(θ), based on the number of segregating sites. The results suggest that E(π) is larger than E(θ) when the population size decreased and that E(π) is smaller than E(θ) when the population size increased. The expected time to the most recent common ancestor could also be obtained under this model.

  9. Genetic Polymorphisms, Estrogens, and Breast Density

    National Research Council Canada - National Science Library

    Maskarinec, Gertraud

    2003-01-01

    .... We have completed two investigations that addressed the following specific aims: 1. To examine the association between polymorphism in genes coding for metabolism and biosynthesis of estrogens...

  10. CTLA-4 polymorphisms associate with breast cancer susceptibility in Asians: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Zhiming Dai

    2017-01-01

    Full Text Available Previous studies have investigated the association between cytotoxic T-lymphocyte antigen-4 (CTLA-4 polymorphisms and breast cancer susceptibility, but the results remained inconsistent. Therefore, we evaluated the relationship between four common CTLA-4 polymorphisms and breast cancer risk by a meta-analysis, aiming to derive a comprehensive and precise conclusion. We searched EMBASE, Pubmed, Web of Science, CNKI, and Wanfang databases until July 18th, 2016. Finally, ten eligible studies involving 4,544 breast cancer patients and 4,515 cancer-free controls were included; all these studies were from Asia. Odds ratio (OR and 95% confidence interval (CI were used to evaluate the breast cancer risk in five genetic models. The results indicated that the CTLA-4 +49A>G (rs231775 polymorphism had a significant association with decreased breast cancer risk in allelic, homozygous, dominant and recessive models. Also, the +6230G>A (rs3087243 polymorphism reduced breast cancer risk especially in the Chinese population under homozygous and recessive models. In contrast, the −1661A>G (rs4553808 polymorphism increased breast cancer risk in allelic, heterozygous and dominant models, whereas −1722 T>C (rs733618 did not relate to breast cancer risk. In conclusion, CTLA-4 polymorphisms significantly associate with breast cancer susceptibility in Asian populations, and different gene loci may have different effects on breast cancer development. Further large-scale studies including multi-racial populations are required to confirm our findings.

  11. Polymorphic Types in ACL2

    Directory of Open Access Journals (Sweden)

    Benjamin Selfridge

    2014-06-01

    Full Text Available This paper describes a tool suite for the ACL2 programming language which incorporates certain ideas from the Hindley-Milner paradigm of functional programming (as exemplified in popular languages like ML and Haskell, including a "typed" style of programming with the ability to define polymorphic types. These ideas are introduced via macros into the language of ACL2, taking advantage of ACL2's guard-checking mechanism to perform type checking on both function definitions and theorems. Finally, we discuss how these macros were used to implement features of Specware, a software specification and implementation system.

  12. Associations between interleukin-1 gene polymorphisms and coronary heart disease risk: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Liang Zhou

    Full Text Available OBJECTIVE: A great number of studies regarding the associations between IL-1B-511, IL-1B+3954 and IL-1RN VNTR polymorphisms within the IL-1gene cluster and coronary heart disease (CHD have been published. However, results have been inconsistent. In this study, a meta-analysis was performed to investigate the associations. METHODS: Published literature from PubMed and Embase databases were searched for eligible publications. Pooled odds ratios (ORs with 95% confidence intervals (CIs were calculated using random- or fixed- effect model. RESULTS: Thirteen studies (3,219 cases/2,445 controls for IL-1B-511 polymorphism, nine studies (1,828 cases/1,818 controls for IL-1B+3954 polymorphism and twelve studies (2,987 cases/ 2,208 controls for IL-1RN VNTR polymorphism were included in this meta analysis. The results indicated that both IL-1B-511 and IL-1B+3954 polymorphisms were not associated with CHD risk (IL-1B-511 T vs. C: OR = 0.98, 95%CI 0.87-1.09; IL-1B+3954 T vs. C: OR = 1.06, 95%CI 0.95-1.19. Similarly, there was no association between IL-1RN VNTR polymorphism and CHD risk (*2 vs. L: OR = 1.00, 95%CI 0.85-1.17. CONCLUSIONS: This meta-analysis suggested that there were no associations between IL-1 gene cluster polymorphisms and CHD.

  13. Association of TAP gene polymorphisms and risk of cervical intraepithelial neoplasia.

    Science.gov (United States)

    Natter, Camilla; Polterauer, Stephan; Rahhal-Schupp, Jasmin; Cacsire Castillo-Tong, Dan; Pils, Sophie; Speiser, Paul; Zeillinger, Robert; Heinze, Georg; Grimm, Christoph

    2013-01-01

    Transporter associated with antigen processing (TAP) is responsible for peptide loading onto class I major histocompatibility complex (MHC-I) molecules. TAP seems to facilitate the detection of HPV by MHC-I molecules and contributes to successful eradication of HPV. TAP polymorphisms could have an important impact on the course of HPV infection. The aim of this study is to evaluate the association between five TAP gene polymorphisms and the risk of CIN. Methods. This case-control study investigated five common TAP polymorphisms in TAP1 (1341 and 2254) and TAP2 (1135, 1693, and 1993) in 616 women with CIN and 206 controls. Associations between gene polymorphisms and risk of CIN were analysed by univariate and multivariable models. The combined effect of the five TAP gene polymorphisms on the risk for CIN was investigated by haplotype analysis. No significant difference in genotype distribution of the five TAP polymorphisms was observed in women with CIN and controls. Haplotype analysis revealed that women with haplotype mut-wt-wt-wt-wt (TAP polymorphisms t1135-t1341-t1693-t1993-t2254) had a significantly lower risk for CIN, compared to women with the haplotype wt-wt-wt-wt-wt (P = 0.006; OR 0.5 [0.35-0.84]). Identification of this haplotype combination could be used to identify women, less susceptible for development of CIN following HPV infection.

  14. Conformational polymorphs of a novel TCNQ derivative carrying an acetylene group

    Science.gov (United States)

    Iida, Yuki; Kataoka, Makoto; Okuno, Tsunehisa

    2018-01-01

    TCNQ is one of the most important organic acceptors and lots of its derivatives have been prepared. However the reports on their crystal polymorphs are limited to their complexes, and simple polymorphs of TCNQ derivatives are uncommon. We succeeded in preparation of a novel TCNQ derivative, 2,2'-(2-(prop-2-yn-1-yloxy)cyclohexa-2,5-diene-1,4-diylidene)dimalononitrile, having a propynyloxy group on a substituent. This compound was found to have two crystal polymorphs depending on a solvent for recrystallization. In polymorph I, dimeric hydrogen bonds are formed between acetylenic hydrogens and cyano nitrogens with the molecule in an inversion symmetry. While, in polymorph II, the molecules make intermolecular hydrogen bonds between acetylenic hydrogens and cyano nitrogens with the molecule in 21 symmetry, forming a hydrogen bonded molecular helix along the b axis. Besides patterns of the intermolecular hydrogen bonds, difference was recognized in conformation of propynyloxy group. The molecule has an anti conformation in polymorph I and a gauche conformation in polymorph II. DFT calculation indicates that the anti conformer is less stable than the gauche one. But a solvation model suggests the anti conformer is estimated to be more stable in a toluene solution.

  15. Association of TAP Gene Polymorphisms and Risk of Cervical Intraepithelial Neoplasia

    Directory of Open Access Journals (Sweden)

    Camilla Natter

    2013-01-01

    Full Text Available Background. Transporter associated with antigen processing (TAP is responsible for peptide loading onto class I major histocompatibility complex (MHC-I molecules. TAP seems to facilitate the detection of HPV by MHC-I molecules and contributes to successful eradication of HPV. TAP polymorphisms could have an important impact on the course of HPV infection. Objective. The aim of this study is to evaluate the association between five TAP gene polymorphisms and the risk of CIN. Methods. This case-control study investigated five common TAP polymorphisms in TAP1 (1341 and 2254 and TAP2 (1135, 1693, and 1993 in 616 women with CIN and 206 controls. Associations between gene polymorphisms and risk of CIN were analysed by univariate and multivariable models. The combined effect of the five TAP gene polymorphisms on the risk for CIN was investigated by haplotype analysis. Results. No significant difference in genotype distribution of the five TAP polymorphisms was observed in women with CIN and controls. Haplotype analysis revealed that women with haplotype mut-wt-wt-wt-wt (TAP polymorphisms t1135-t1341-t1693-t1993-t2254 had a significantly lower risk for CIN, compared to women with the haplotype wt-wt-wt-wt-wt (; OR 0.5 []. Conclusion. Identification of this haplotype combination could be used to identify women, less susceptible for development of CIN following HPV infection.

  16. Drift, admixture, and selection in human evolution: a study with DNA polymorphisms.

    OpenAIRE

    Bowcock, A M; Kidd, J R; Mountain, J L; Hebert, J M; Carotenuto, L; Kidd, K K; Cavalli-Sforza, L L

    1991-01-01

    Accuracy of evolutionary analysis of populations within a species requires the testing of a large number of genetic polymorphisms belonging to many loci. We report here a reconstruction of human differentiation based on 100 DNA polymorphisms tested in five populations from four continents. The results agree with earlier conclusions based on other classes of genetic markers but reveal that Europeans do not fit a simple model of independently evolving populations with equal evolutionary rates. ...

  17. Aldehyde Dehydrogenase 2 Polymorphism Is a Predictor of Smoking Cessation.

    Science.gov (United States)

    Masaoka, Hiroyuki; Gallus, Silvano; Ito, Hidemi; Watanabe, Miki; Yokomizo, Akira; Eto, Masatoshi; Matsuo, Keitaro

    2017-09-01

    Smoking cessation has been known to be associated with drinking behaviors, which are influenced by polymorphisms in genes encoding alcohol metabolizing enzymes. The aim was to evaluate the impact of aldehyde dehydrogenase 2 (ALDH2, rs671) and alcohol dehydrogenase 1B (ADH1B, rs1229984) polymorphisms together with drinking behaviors on smoking cessation. We conducted a cross-sectional study with 1137 former smokers and 1775 current smokers without any cancer at Aichi Cancer Center Hospital between 2001 and 2005. Unconditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for successful smoking cessation by comparing former smokers (quitters) with current smokers (non-quitters). Older age, lower amount of cumulative smoking exposure, lower number of cigarettes per day, younger age of smoking initiation, shorter smoking duration, longer time to first cigarette in the morning, and lower amount of drinking among ever drinkers were predictors of smoking cessation. After careful adjustment for age, sex, smoking patterns, and drinking status, the ORs for smoking cessation among subjects with ALDH2 Glu/Lys and Lys/Lys were 1.02 (95% CI 0.84-1.23) and 1.78 (95% CI 1.23-2.58) compared with those with ALDH2 Glu/Glu, respectively Mediation analyses confirmed that the effect of ALDH2 Lys/Lys on smoking cessation was independent by dinking behaviors. No statistically significant association between ADH1B polymorphism and smoking cessation was observed. In our Japanese population, ALDH2 polymorphism predicts smoking cessation, independent by drinking behaviors. Interventions for promoting smoking cessation by ALDH2 polymorphism may be useful in Asian populations. We newly show that subjects with ALDH2 Lys/Lys genotype in a functional polymorphism, rs671, are more likely to quit smoking than those with ALDH2 Glu allele in a Japanese population. Our finding suggests that ALDH2 polymorphism may be useful for promoting smoking

  18. Polymorphism

    Indian Academy of Sciences (India)

    of the cancer 'chronic myeloid leukemia'. Novartis invented imatinib in 1992 and patented it in 1993 in US and other countries. The company applied for a patent in India in 1998 for β-crystalline form of imatinib mesylate, which led to a legal scrutiny of Patents Act 1970. suggested that virtually 'every compound has different ...

  19. Influence of thiopurine methyltransferase gene polymorphism on ...

    Indian Academy of Sciences (India)

    Thiopurine methyltransferase (TPMT) gene polymorphism regulates thiopurine therapeutic efficacy and toxicity. The aim of this study was to determine the influence of TPMT gene polymorphism in Egyptian children with acute lymphoblastic leukaemia (ALL). Sixty-four patients with ALL, T lineage (27%) and pre-B phenotype ...

  20. MHC polymorphism under host-pathogen coevolution

    NARCIS (Netherlands)

    Borghans, J.A.M.; Beltman, J.B.; Boer, R.J. de

    2004-01-01

    The genes encoding major histocompatibility (MHC) molecules are among the most polymorphic genes known for vertebrates. Since MHC molecules play an important role in the induction of immune responses, the evolution of MHC polymorphism is often explained in terms of increased protection of hosts

  1. Methylenetetrahydrofolate reductase A1298C polymorphism and ...

    African Journals Online (AJOL)

    Methylenetetrahydrofolate reductase A1298C polymorphism and breast cancer risk: A meta analysis of 33 studies. ... were searched for case‑control studies relating the association between MTHFR A1298C polymorphism and BC risk and estimated summary odds ratios (ORs) with confidence intervals (CIs) for assessment.

  2. Hoare type theory, polymorphism and separation

    DEFF Research Database (Denmark)

    Nanevski, Alexandar; Morrisett, J. Gregory; Birkedal, Lars

    2008-01-01

    with higher-order functions and type polymorphism. We further show that in the presence of type polymorphism, it becomes possible to interpret the Hoare types in the “small footprint” manner, as advocated by separation logic, whereby specifications tightly describe the state required by the computation. We...

  3. Mechanism of unusual polymorph transformations in calcium ...

    Indian Academy of Sciences (India)

    research for many years. However, till date the ... Polymorph selection plays key role in biominerali- zation as the .... Mechanism of unusual polymorph transformations in calcium carbonate. 1401. In te n s ity. 2-Theta - Scale. 20. 30. 40. 50. 60. V. V110. V. V. V. V. V. Refluxed for 75 mins: 100% Aragonite. A221. A. A. A. A. A.

  4. Genetic polymorphism of serotonin transporter 5-HTTLPR ...

    Indian Academy of Sciences (India)

    insertion/deletion polymorphism in the 5 - flanking promoter region (5-HTTLPR). This gene has received considerable atten- tion in attempts to understand the molecular determinants of smoking. Therefore, in the present study, the relationship between genetic polymorphism of serotonin transporter in smoking behaviour is ...

  5. using random amplified polymorphic DNA (RAPD)

    African Journals Online (AJOL)

    To study the pattern of genetic diversity in 45 genotypes of common bean, 19 RAPD primers were used. Of 253 bands produced, 236 bands (94.22%) were polymorphic in which maximum number (20 polymorphic bands) were observed in the profiles of the primer OPB-07. Highest PIC value (0.79) was observed for the ...

  6. Energetics Underlying Twist Polymorphisms in Amyloid Fibrils

    NARCIS (Netherlands)

    Periole, Xavier; Huber, Thomas; Bonito-Oliva, Alessandra; Aberg, Karina C; van der Wel, Patrick C A; Sakmar, Thomas P; Marrink, Siewert J

    2018-01-01

    Amyloid fibrils are highly ordered protein aggregates associated with more than 40 human diseases. The exact conditions in which the fibrils are grown determine many types of reported fibril polymorphism, including different twist patterns. Twist-based polymorphs display unique mechanical properties

  7. gene polymorphism and its serum lev

    Indian Academy of Sciences (India)

    Navya

    Running title: Interleukin-10 gene polymorphism in metabolic syndrome. Keywords: ... polymorphisms, IL-10 -819 C >T and -592C >A were significantly associated with risk of metabolic syndrome. The mutant ..... Upon analysis for correlation of IL-10 serum level with clinico-biochemical characteristics of cases and controls,.

  8. Fat Mass and Obesity-Associated (FTO) Gene Polymorphisms Are Associated with Physical Activity, Food Intake, Eating Behaviors, Psychological Health, and Modeled Change in Body Mass Index in Overweight/Obese Caucasian Adults

    OpenAIRE

    Harbron, Janetta; Merwe, Lize van der; Zaahl, Monique; Kotze, Maritha; Senekal, Marjanne

    2014-01-01

    The fat mass and obesity-associated (FTO) gene is currently recognized as the most robust predictor of polygenic obesity. We investigated associations between the FTO rs1421085 and rs17817449 polymorphisms and the FTO rs1421085–rs17817449 haplotype and dietary intake, eating behavior, physical activity, and psychological health, as well as the effect of these associations on BMI. N = 133 treatment seeking overweight/obese Caucasian adults participated in this study. Genotyping was performed ...

  9. Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer susceptibility.

    Science.gov (United States)

    Xia, Lei-Zhou; Liu, Yi; Xu, Xiao-Zhou; Jiang, Peng-Cheng; Ma, Gui; Bu, Xue-Feng; Zhang, Yong-Jun; Yu, Feng; Xu, Ke-Sen; Li, Hua

    2014-08-28

    To identify the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and gastric cancer (GC) susceptibility. Systematic searches were performed on the electronic databases PubMed, ISI, Web of knowledge, CNKI and Wanfang, as well as manual searching of the references of the identified articles. A total of 26 papers were included in this meta-analysis. Overall and subgroup analyses were performed. Odds ratio (OR) and 95%CI were used to evaluate the associations between MTHFR polymorphisms and GC risk. The I (2) statistics were used to evaluate between-study heterogeneity. Sensitivity analysis was also performed. Increased risk was found for the MTHFR C677T polymorphism under four genetic models (TT + CT vs CC: OR = 1.23, P = 0.002; T vs C: OR = 1.15, P = 0.001; TT vs CC: OR = 1.37, P = 0.0005; TT vs CT + CC: OR = 1.17, P = 0.0008). Subgroup analysis by ethnicity suggested that C677T polymorphism conferred a risk of GC in eastern but not in western populations. Stratification by tumor site showed an association between the C677T polymorphism and gastric cardia cancer and non-cardia GC in the worldwide population and in eastern populations. Regardless of comparisons with controls or diffuse-type GC, a positive association was found for the C677T polymorphism and an increased risk of intestinal-type GC in the whole population and in western populations. With regard to the A1298C polymorphism, we found that genotype CC was significantly decreased and conferred protection against GC in eastern populations (CC vs AA: OR = 0.44, P = 0.03; CC vs AC + AA: OR = 0.46, P = 0.04). MTHFR C677T polymorphism is a risk factor for GC, and the A1298C polymorphism may be a protective factor against GC in eastern populations.

  10. Aspects and Polymorphism in AspectJ

    DEFF Research Database (Denmark)

    Lorenz, David Harel; Ernst, Erik

    2003-01-01

    There are two important points of view on inclusion or subtype polymorphism in object-oriented programs, namely polymorphic access and dynamic dispatch. These features are essential for object-oriented programming, and it is worthwhile to consider whether they are supported in aspect......-oriented programming (AOP). In AOP, pieces of crosscutting behavior are extracted from the base code and localized in aspects, losing as a result their polymorphic capabilities while introducing new and unexplored issues. In this paper, we explore what kinds of polymorphism AOP languages should support, using Aspect......J as the basis for the presentation. The results are not exclusive to AspectJ---aspectual polymorphism may make aspects in any comparable AOSD language more expressive and reusable across programs, while preserving safety....

  11. Association of polymorphisms in one-carbon metabolizing genes with breast cancer risk in Syrian women.

    Science.gov (United States)

    Lajin, Bassam; Alhaj Sakur, Amir; Ghabreau, Lina; Alachkar, Amal

    2012-08-01

    Dietary folate status as well as polymorphisms in one-carbon metabolism genes may affect the risk of breast cancer through aberrant DNA methylation and altered nucleotide synthesis and DNA repair. A large number of studies investigated the role of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms in breast cancer with inconsistent results. Association between multiple polymorphisms in one-carbon metabolism genes and breast cancer was not studied before in an Arab population. The purpose of the present study is to test the hypothesis that polymorphisms in one-carbon metabolism genes are associated with breast cancer susceptibility in Syrian breast cancer women patients. A total of 245 subjects (119 breast cancer women patients and 126 healthy controls) were genotyped for MTHFR C677T and A1298C and MTRR A66G polymorphisms. Association was tested for under numerous genetic models. A statistically significant association was found for MTHFR A1298C polymorphism especially under the allele contrast model (odds ratio (OR) = 1.68, 95% confidence interval (CI) (1.16-2.45), P = 0.006). On the other hand, no significant association was found for MTHFR C677T or MTRR A66G under any of the genetic models tested. The effects of the compound genotypes were also examined. The 66GG genotype was found to be protective against breast cancer when combined with the 677CT or 1298AC genotype (OR = 0.18, 95% CI (0.04-0.82), P = 0.014; OR = 0.3, 95% CI (0.08-1.11), P = 0.058). In conclusion, our study supports the hypothesis that polymorphisms in one-carbon gene metabolisms modulate the risk for breast cancer, particularly the A1298C polymorphism of the MTHFR gene.

  12. Key brainstem structures activated during hypoxic exposure in one-day-old mice highlight characteristics for modelling breathing network in premature infants

    Directory of Open Access Journals (Sweden)

    Fanny JOUBERT

    2016-12-01

    Full Text Available We mapped and characterized changes in the activity of brainstem cell groups under hypoxia in one-day-old newborn mice, an animal model in which the central nervous system at birth is particularly immature. The classical biphasic respiratory response characterized by transient hyperventilation, followed by severe ventilation decline, was associated with increased c-FOS immunoreactivity in brainstem cell groups: the nucleus of the solitary tract, ventral reticular nucleus of the medulla, retrotrapezoid/parafacial region, parapyramidal group, raphe magnus nucleus, lateral and medial parabrachial nucleus, and dorsal subcoeruleus nucleus. In contrast, the hypoglossal nucleus displayed decreased c-FOS immunoreactivity. There were fewer or no activated catecholaminergic cells activated in the medulla oblongata, whereas approximately 45% of the c-FOS-positive cells in the dorsal subcoeruleus were co-labelled. Approximately 30% of the c-FOS-positive cells in the parapyramidal group were serotoninergic, whereas only a small portion were labelled for serotonin in the raphe magnus nucleus. None of the c-FOS-positive cells in the retrotrapezoid/parafacial region were co-labelled for PHOX2B. Thus, the hypoxia-activated brainstem neuronal network of one-day-old mice is characterized by i the activation of catecholaminergic cells of the dorsal subcoeruleus nucleus, a structure implicated in the strong depressive pontine influence previously reported in the fetus but not in newborns, ii the weak activation of catecholaminergic cells of the ventral reticular nucleus of the medulla, an area involved in hypoxic hyperventilation, and iii the absence of PHOX2B-positive cells activated in the retrotrapezoid/parafacial region. Based on these results, one-day-old mice could highlight characteristics for modelling the breathing network of premature infants.

  13. Polymorphism of xenobiotic metabolizm genes

    International Nuclear Information System (INIS)

    Freidin, M. B.; Ten, I. A.; Sevostiyanova, N. v.; Kokorina, Y. I.; Slominskaya, F. M.; Tereshchenko, I. V.; Kolomiets, S. A.; Takhanov, R. M.

    2004-01-01

    The genes of xenobiotic metabolism enzymes genes, also called biotransformation genes or environmental genes seems to be an important factor of individual susceptibility of common diseases of different genesis including cancer. At the present time, a systematic accumulation of information on the role of these genes polymorphism in predisposition to different disorders is carried out worldwide. To investigate a significance of biotransformation genes for cancer disorders in West Siberia region, we studies a polymorphism of genes CYP2C19 (Small-RFLP, 1 and 2 alleles in exone 5), GSTTI, GSTMI (null and normal alleles in both genes) in 47 lung cancer (LC) patients, 269 women with breast cancer (BC), and 130 controls from Tomsk, Russia. All participants were Russians. The frequency of GSTM1 null genotype in LC patients was significantly higher than that in controls (0.608?0.071 vs. 0.162?0-032; p<1x10-7 by Fisher exact test), whereas the frequency of null genotype in BC women was significantly lower in comparison with control women (0.545?0.039 vs. 0.747?0.053: p=0.005 by Fisher exact test). The latter circumstance seems to be unexpected because a priori one suggest that just null genotype of GSTM1 is of a pathological nature. Frequencies of null genotypes of GSTN1 in LC patients and GSTT1 in BC women corresponded to those in controls. In LC patients frequencies of CYP2C19 alleles did not differ significantly from values control sample, whereas in BC women the frequency of CYP2C19 2 allele was higher than that in control (0.340?0.20 vs. 0.182?0.034, p=4,9x10-4 by Fisher exact test). This allele encodes a truncated non-functional protein being a major cause of poor metabolism of some drugs. Thus, the data obtained allow us to conclude that polymorphisms of GSTTi, GSTM1, and CYP2C19 genes are associated with cancer disorders in Russians from West Siberia Even so, their pathogenetic meaning is specific with respect the type of malignant pathology. (Author)

  14. Androgen Receptor Gene Polymorphism, Aggression, and Reproduction in Tanzanian Foragers and Pastoralists

    Science.gov (United States)

    Butovskaya, Marina L.; Lazebny, Oleg E.; Vasilyev, Vasiliy A.; Dronova, Daria A.; Karelin, Dmitri V.; Mabulla, Audax Z. P.; Shibalev, Dmitri V.; Shackelford, Todd K.; Fink, Bernhard; Ryskov, Alexey P.

    2015-01-01

    The androgen receptor (AR) gene polymorphism in humans is linked to aggression and may also be linked to reproduction. Here we report associations between AR gene polymorphism and aggression and reproduction in two small-scale societies in northern Tanzania (Africa)—the Hadza (monogamous foragers) and the Datoga (polygynous pastoralists). We secured self-reports of aggression and assessed genetic polymorphism of the number of CAG repeats for the AR gene for 210 Hadza men and 229 Datoga men (aged 17–70 years). We conducted structural equation modeling to identify links between AR gene polymorphism, aggression, and number of children born, and included age and ethnicity as covariates. Fewer AR CAG repeats predicted greater aggression, and Datoga men reported more aggression than did Hadza men. In addition, aggression mediated the identified negative relationship between CAG repeats and number of children born. PMID:26291982

  15. Association of OPN rs11730582 polymorphism with cancer risk: a meta-analysis

    Directory of Open Access Journals (Sweden)

    He LL

    2016-03-01

    Full Text Available Lanlan He,1,* Yong Wang2,* 1Emergency Department, Zhenjiang First People’s Hospital, Zhenjiang, People’s Republic of China; 2Department of Interventional Radiology and Vascular Surgery, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, People’s Republic of China *Both authors contributed equally to this work Purpose: Several molecular epidemiological studies have investigated the association between OPN rs11730582 C>T polymorphism and cancer risk, but the results are inconsistent. Hence, a meta-analysis was conducted to determine the association of this polymorphism with cancer risk. Materials and methods: The related articles were searched in PubMed, Embase, and Chinese National Knowledge Infrastructure databases. Pooled odds ratios and 95% confidence intervals were calculated to evaluate the strength of the associations. A random-effects model or fixed-effects model was employed depending on the heterogeneity. Results: A total of ten case-control studies involving 2,749 cancer cases and 3,398 controls were included in the meta-analysis. In overall analysis, OPN rs11730582 C>T polymorphism was not associated with cancer risk. In a stratified analysis by cancer type, no significant association was found between OPN rs11730582 C>T polymorphism and the risk of glioma, gastric cancer, and other cancers. Conclusion: This meta-analysis suggests that OPN rs11730582 C>T polymorphism is not associated with cancer susceptibility. Keywords: osteopontin, polymorphism, cancer, risk 

  16. Mebendazole crystal forms in tablet formulations. An ATR-FTIR/chemometrics approach to polymorph assignment.

    Science.gov (United States)

    Calvo, Natalia L; Kaufman, Teodoro S; Maggio, Rubén M

    2016-04-15

    Structural polymorphism of active pharmaceutical ingredients (API) is a relevant concern for the modern pharmaceutical industry, since different polymorphic forms may display dissimilar properties, critically affecting the performance of the corresponding drug products. Mebendazole (MEB) is a widely used broad spectrum anthelmintic drug of the benzimidazole class, which exhibits structural polymorphism (Forms A-C). Form C, which displays the best pharmaceutical profile, is the recommended one for clinical use. The polymorphs of MEB were prepared and characterized by spectroscopic, calorimetric and microscopic means. The polymorphs were employed to develop a suitable chemometrics-assisted sample display model based on the first two principal components of their ATR-FTIR spectra in the 4000-600 cm(-1) region. The model was internally and externally validated employing the leave-one-out procedure and an external validation set, respectively. Its suitability for revealing the polymorphic identity of MEB in tablets was successfully assessed analyzing commercial tablets under different physical forms (whole, powdered, dried, sieved and aged). It was concluded that the ATR-FTIR/PCA (principal component analysis) association is a fast, efficient and non-destructive technique for assigning the solid-state forms of MEB in its drug products, with minimum sample pre-treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Color plumage polymorphism and predator mimicry in brood parasites.

    Science.gov (United States)

    Trnka, Alfréd; Grim, Tomáš

    2013-05-10

    Plumage polymorphism may evolve during coevolution between brood parasites and their hosts if rare morph(s), by contravening host search image, evade host recognition systems better than common variant(s). Females of the parasitic common cuckoo (Cuculus canorus) are a classic example of discrete color polymorphism: gray females supposedly mimic the sparrowhawk (Accipiter nisus), while rufous females are believed to mimic the kestrel (Falco tinnunculus). Despite many studies on host responses to adult cuckoos comprehensive tests of the "hawk mimicry" and "kestrel mimicry" hypotheses are lacking so far. We tested these hypotheses by examining host responses to stuffed dummies of the sparrowhawk, kestrel, cuckoo and the innocuous turtle dove (Streptopelia turtur) as a control at the nest. Our experimental data from an aggressive cuckoo host, the great reed warbler (Acrocephalus arundinaceus), showed low effectiveness of cuckoo-predator mimicry against more aggressive hosts regardless of the type of model and the degree of perfection of the mimic. Specifically, warblers discriminated gray cuckoos from sparrowhawks but did not discriminate rufous cuckoos from kestrels. However, both gray and rufous cuckoos were attacked vigorously and much more than control doves. The ratio of aggression to gray vs. rufous cuckoo was very similar to the ratio between frequencies of gray vs. rufous cuckoo morphs in our study population. Overall, our data combined with previous results from other localities suggest polymorphism dynamics are not strongly affected by local predator model frequencies. Instead, hosts responses and discrimination abilities are proportional, other things being equal, to the frequency with which hosts encounter various cuckoo morphs near their nests. This suggests that female cuckoo polymorphism is a counter-adaptation to thwart a specific host adaptation, namely an ability to not be fooled by predator mimicry. We hypothesize the dangerousness of a particular

  18. Configurational entropy of hydrogen-disordered ice polymorphs

    International Nuclear Information System (INIS)

    Herrero, Carlos P.; Ramírez, Rafael

    2014-01-01

    The configurational entropy of several H-disordered ice polymorphs is calculated by means of a thermodynamic integration along a path between a totally H-disordered state and one fulfilling the Bernal-Fowler ice rules. A Monte Carlo procedure based on a simple energy model is used, so that the employed thermodynamic path drives the system from high temperatures to the low-temperature limit. This method turns out to be precise enough to give reliable values for the configurational entropy s th of different ice phases in the thermodynamic limit (number of molecules N → ∞). The precision of the method is checked for the ice model on a two-dimensional square lattice. Results for the configurational entropy are given for H-disordered arrangements on several polymorphs, including ices Ih, Ic, II, III, IV, V, VI, and XII. The highest and lowest entropy values correspond to ices VI and XII, respectively, with a difference of 3.3% between them. The dependence of the entropy on the ice structures has been rationalized by comparing it with structural parameters of the various polymorphs, such as the mean ring size. A particularly good correlation has been found between the configurational entropy and the connective constant derived from self-avoiding walks on the ice networks

  19. On polymorphism of dysprosium trichloride

    International Nuclear Information System (INIS)

    Zakiryanova, Irina D.; Khokhlov, Vladimir A.; Salyulev, Alexander B.; Korzun, Iraida V.

    2015-01-01

    For the first time, the structure of crystalline DyCl 3 over a wide temperature range from room temperature to melting point was studied by Raman spectroscopy. The phonon modes (cm -1 ) of dysprosium trichloride (monoclinic crystal lattice of AlCl 3 type, Z = 4, CN = 6) at room temperature are 257 (A 1g ), 201 (E g ), 112 (E g ), 88 (A 1g ), and 63 (E g ). The monoclinic structure of the crystalline DyCl 3 C 2h 3 symmetry was found to remain constant over the studied temperature range. No polymorphic transformation in the solid state was detected. Gravimetry, calorimetry, and mass spectrometry have been used in addition to support the conclusions made on the basis of Raman spectroscopic data.

  20. On polymorphism of dysprosium trichloride

    Energy Technology Data Exchange (ETDEWEB)

    Zakiryanova, Irina D.; Khokhlov, Vladimir A.; Salyulev, Alexander B.; Korzun, Iraida V. [RAS Ural Branch, Ekaterinburg (Russian Federation). Institute of High-Temperature Electrochemistry

    2015-07-01

    For the first time, the structure of crystalline DyCl{sub 3} over a wide temperature range from room temperature to melting point was studied by Raman spectroscopy. The phonon modes (cm{sup -1}) of dysprosium trichloride (monoclinic crystal lattice of AlCl{sub 3} type, Z = 4, CN = 6) at room temperature are 257 (A{sub 1g}), 201 (E{sub g}), 112 (E{sub g}), 88 (A{sub 1g}), and 63 (E{sub g}). The monoclinic structure of the crystalline DyCl{sub 3} C{sub 2h}{sup 3} symmetry was found to remain constant over the studied temperature range. No polymorphic transformation in the solid state was detected. Gravimetry, calorimetry, and mass spectrometry have been used in addition to support the conclusions made on the basis of Raman spectroscopic data.

  1. Polymorphism of dislocation core structures at the atomic scale.

    Science.gov (United States)

    Wang, Zhongchang; Saito, Mitsuhiro; McKenna, Keith P; Ikuhara, Yuichi

    2014-01-01

    Dislocation defects together with their associated strain fields and segregated impurities are of considerable significance in many areas of materials science. However, their atomic-scale structures have remained extremely challenging to resolve, limiting our understanding of these ubiquitous defects. Here, by developing a complex modelling approach in combination with bicrystal experiments and systematic atomic-resolution imaging, we are now able to pinpoint individual dislocation cores at the atomic scale, leading to the discovery that even simple magnesium oxide can exhibit polymorphism of core structures for a given dislocation species. These polymorphic cores are associated with local variations in strain fields, segregation of defects, and electronic states, adding a new dimension to understanding the properties of dislocations in real materials. The findings advance our fundamental understanding of basic behaviours of dislocations and demonstrate that quantitative prediction and characterization of dislocations in real materials is possible.

  2. Rotation-Induced Polymorphic Transitions in Bacterial Flagella

    Science.gov (United States)

    Vogel, Reinhard; Stark, Holger

    2013-04-01

    Bacteria propel themselves with the help of rotating helical flagella. They change their swimming direction during tumbling events in order to increase, for example, their supply of nutrients (chemotaxis). During tumbling a bacterial flagellum assumes different polymorphic states. Based on a continuum model for the motor-flagellum system, we demonstrate that a changing motor torque can initiate these polymorphic transformations. In particular, we investigate the run-and-stop tumble strategy of Rhodobacter sphaeroides which uses a coiled-to-normal transition in its single flagellum. We also show that torque reversal in single-flagellated Escherichia coli generates a normal-to-curly I transition as observed for tumbling E. coli that swim with a bundle of several flagella.

  3. Rhesus macaque IFITM3 gene polymorphisms and SIV infection.

    Directory of Open Access Journals (Sweden)

    Michael Winkler

    Full Text Available Interferon-induced transmembrane proteins (IFITMs have been recognized as important antiviral effectors of the innate immune system, both in cell culture and in infected humans. In particular, polymorphisms of the human IFITM3 gene have been shown to affect disease severity and progression in influenza A virus (FLUAV and human immunodeficiency virus (HIV infection, respectively. Rhesus macaques (Macaca mulatta are commonly used to model human infections and the experimental inoculation of these animals with simian immunodeficiency virus (SIV is one of the best models for HIV/AIDS in humans. However, information on the role of IFITM3 in SIV infection of rhesus macaques is currently lacking. We show that rhesus macaque (rh IFITM3 inhibits SIV and FLUAV entry in cell culture, although with moderately reduced efficiency as compared to its human counterpart. We further report the identification of 16 polymorphisms in the rhIFITM3 gene, three of which were exonic and synonymous while the remainder was located in non-coding regions. Employing previously characterized samples from two cohorts of SIV-infected rhesus macaques, we investigated the relationship between these rhIFITM3 polymorphisms and both AIDS-free survival time and virus load. In cohort 1, several intronic polymorphisms were significantly associated with virus load or survival. However, an association with both parameters was not observed and significance was lost in most cases when animals were stratified for the presence of MHC allele Mamu-A1*001. Moreover, no significant genotype-phenotype associations were detected in cohort 2. These results suggest that, although IFITM3 can inhibit SIV infection in cell culture, genetic variation in rhIFITM3 might have only a minor impact on the course of SIV infection in experimentally infected animals.

  4. The association between COMT Val158Met polymorphism and migraine risk: A meta-analysis.

    Science.gov (United States)

    Liao, Yao-Jun; Jiang, Jing-Ru; Jin, San-Qing

    2017-05-01

    Background The COMT Val158Met polymorphism has long been regarded as a risk factor for migraine. The possible association between COMT Val158Met polymorphism and migraine has been evaluated in several studies, but the results are not consistent. Therefore, we conduct this meta-analysis to address these issues. Methods The WEB OF SCIENCE and EMBASE databases were searched for eligible studies. The odds ratio (OR) with the corresponding 95% confidence interval (CI) was calculated to estimate the strength of the association between COMT Val158Met polymorphism and migraine. Results Five studies with 979 cases and 1870 controls were ultimately included in the present meta-analysis. The overall data showed no significant association between COMT Val158Met polymorphism and migraine in the multiplicative model (OR = 0.97, 95% CI: 0.78-1.21, p = 0.805) and dominant model (OR = 1.05, 95% CI: 0.75-1.48, p = 0.773), neither in the additive model (OR = 0.97, 95% CI: 0.77-1.23, p = 0.817) nor in the recessive model (OR = 0.88, 95% CI: 0.71-1.09, p = 0.246). In subgroup analysis, both for Caucasian and Asian populations, no statistically significant associations were observed in any genetic models. Conclusions Our meta-analysis suggested that the COMT Val158Met polymorphism was not associated with migraine risk.

  5. Effects of As2O3 on DNA methylation, genomic instability, and LTR retrotransposon polymorphism in Zea mays.

    Science.gov (United States)

    Erturk, Filiz Aygun; Aydin, Murat; Sigmaz, Burcu; Taspinar, M Sinan; Arslan, Esra; Agar, Guleray; Yagci, Semra

    2015-12-01

    Arsenic is a well-known toxic substance on the living organisms. However, limited efforts have been made to study its DNA methylation, genomic instability, and long terminal repeat (LTR) retrotransposon polymorphism causing properties in different crops. In the present study, effects of As2O3 (arsenic trioxide) on LTR retrotransposon polymorphism and DNA methylation as well as DNA damage in Zea mays seedlings were investigated. The results showed that all of arsenic doses caused a decreasing genomic template stability (GTS) and an increasing Random Amplified Polymorphic DNAs (RAPDs) profile changes (DNA damage). In addition, increasing DNA methylation and LTR retrotransposon polymorphism characterized a model to explain the epigenetically changes in the gene expression were also found. The results of this experiment have clearly shown that arsenic has epigenetic effect as well as its genotoxic effect. Especially, the increasing of polymorphism of some LTR retrotransposon under arsenic stress may be a part of the defense system against the stress.

  6. Absence of association between the INSIG2 gene polymorphism (rs7566605) and obesity in the European Youth Heart Study (EYHS)

    DEFF Research Database (Denmark)

    Vimaleswaran, Karani S; Franks, Paul W; Brage, Soren

    2009-01-01

    (930 boys and 1,073 girls) from the European Youth Heart Study (EYHS), a school-based, cross-sectional study of pre- and early pubertal children. The association between the polymorphism and obesity traits was tested using additive and recessive models adjusted for age, age-group, gender, maturity...... of this polymorphism with obesity traits. This polymorphism has been hypothesized to alter INSIG2 expression leading to inhibition of fatty acid and cholesterol synthesis. Hence, we investigated the association of the INSIG2 rs7566605 polymorphism with obesity- and lipid-related traits in Danish and Estonian children......, the polymorphism was not associated with overweight (P = 0.87) or obesity (P = 0.34). We also did not find association with waist circumference (WC), sum of four skinfolds, or with total cholesterol, triglycerides, low-density lipoprotein, or high-density lipoprotein. There were no gender-specific (P = 0.55), age...

  7. Diffusion Monte Carlo Study of Para-Diiodobenzene Polymorphism Revisited.

    Science.gov (United States)

    Hongo, Kenta; Watson, Mark A; Iitaka, Toshiaki; Aspuru-Guzik, Alán; Maezono, Ryo

    2015-03-10

    We revisit our investigation of the diffusion Monte Carlo (DMC) simulation of para-diiodobenzene (p-DIB) molecular crystal polymorphism. [See J. Phys. Chem. Lett. 2010, 1, 1789-1794.] We perform, for the first time, a rigorous study of finite-size effects and choice of nodal surface on the prediction of polymorph stability in molecular crystals using fixed-node DMC. Our calculations are the largest that are currently feasible using the resources of the K-computer and provide insights into the formidable challenge of predicting such properties from first principles. In particular, we show that finite-size effects can influence the trial nodal surface of a small (1 × 1 × 1) simulation cell considerably. Therefore, we repeated our DMC simulations with a 1 × 3 × 3 simulation cell, which is the largest such calculation to date. We used a density functional theory (DFT) nodal surface generated with the PBE functional, and we accumulated statistical samples with ∼6.4 × 10(5) core hours for each polymorph. Our final results predict a polymorph stability that is consistent with experiment, but they also indicate that the results in our previous paper were somewhat fortuitous. We analyze the finite-size errors using model periodic Coulomb (MPC) interactions and kinetic energy corrections, according to the CCMH scheme of Chiesa, Ceperley, Martin, and Holzmann. We investigate the dependence of the finite-size errors on different aspect ratios of the simulation cell (k-mesh convergence) in order to understand how to choose an appropriate ratio for the DMC calculations. Even in the most expensive simulations currently possible, we show that the finite size errors in the DMC total energies are much larger than the energy difference between the two polymorphs, although error cancellation means that the polymorph prediction is accurate. Finally, we found that the T-move scheme is essential for these massive DMC simulations in order to circumvent population explosions and

  8. Polymorphism Sequence - JSNP | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available List Contact us JSNP Polymorphism Sequence Data detail Data name Polymorphism Sequence DOI 10.18908/lsdba.nb...dc00114-001 Description of data contents Information on polymorphisms (SNPs and insertions/deletions) and th...se Name database name JSNP_SNP: single nucleotide polymorphism JSNP_InsDel_IND: insertion/deletion JSNP_InsD...ved allele observed 3' Flanking Sequence 3' flanking sequence Offset in Flanking Sequence position of the polymorphism...uence Accession No. accession No. of the sequence for polymorphism screening Offset in Record position of the polymorphism

  9. Association between polymorphisms in selected inflammatory response genes and the risk of prostate cancer

    Directory of Open Access Journals (Sweden)

    Chen J

    2016-01-01

    Full Text Available Jun Chen,1,* Xue-Ming Ying,2,* Xue-Ming Huang,3 Peng Huang,4 Shao-Cong Yan1 1Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, 2Department of Oncology, Jingdezhen City People’s Hospital, Jingdezhen, 3Department of Urology, Research Institute, The First Affiliated Hospital of Nanchang University, 4The Medical School of Nanchang University, School of Public Health, Nanchang, People’s Republic of China*These authors contributed equally to this workAbstract: Inflammation represents an important event which facilitates prostate carcinogenesis. Genetic variations in inflammatory response genes could affect the level and function of the protein products, resulting in the differential prostate cancer risk among carriers of different variants. This study attempted to investigate the association of IL-4 rs2243250, IL-6 rs10499563, IL-8 rs4073, as well as NFKBIA rs2233406 and rs3138053 polymorphisms with prostate cancer risk in the Chinese population. Genotyping of the polymorphisms was performed by using polymerase chain reaction-restriction fragment length polymorphism technique on 439 prostate cancer patients and 524 controls, and the association of each polymorphic genotype with prostate cancer risk was evaluated by using logistic regression analysis based on allele, heterozygous, and homozygous comparison models, with adjustment to age and smoking status. We showed that the C allele of IL-4 rs2243250 polymorphism could increase prostate cancer risk (heterozygous comparison model: odds ratio [OR] =1.434, 95% confidence interval [CI] =1.092–1.881, P=0.009; homozygous comparison model: OR =2.301, 95% CI =1.402–3.775, P=0.001; allele comparison model: OR =1.509, 95% CI =1.228–1.853, P<0.001. On the other hand, the C allele of rs10499563 polymorphism could decrease prostate cancer risk (heterozygous comparison model: OR =0.694, 95% CI =0.525–0.918, P=0.010; homozygous comparison model: OR =0.499, 95% CI =0

  10. FTO polymorphism, cardiorespiratory fitness, and obesity in Brazilian youth.

    Science.gov (United States)

    Reuter, Cézane Priscila; Rosane De Moura Valim, Andréia; Gaya, Anelise Reis; Borges, Tássia Silvana; Klinger, Elisa Inês; Possuelo, Lia Gonçalves; Franke, Silvia Isabel Rech; Kmetzsch, Lívia; Vainstein, Marilene Henning; Prá, Daniel; Burgos, Miria Suzana

    2016-05-01

    The aim of the present study was to evaluate the relationship between the rs9939609 fat mass and obesity-associated (FTO) polymorphism and cardiorespiratory fitness (CRF) with overweight/obesity outcomes in youth. This study included 420 youths, comprising 211 boys and 209 girls aged 7-17. Overweight/obesity were evaluated by body mass index (BMI), waist circumference (WC), and the percentage of fat (PF) according to two skinfold thickness measurements. Genotyping of the rs9939609 polymorphism was conducted using real-time Polymerase Chain Reaction (PCR) utilizing TaqMan(®) probes, and CRF was evaluated through a 9-minute run/walk test, categorized as fit or unfit. Logistic regression was utilized to evaluate a possible association between the polymorphism and CRF, with three obesity indicators evaluated. Individuals with the genotype risk (AA) of FTO polymorphism rs9939609 showed higher prevalence of overweight/obesity, as evaluated by BMI (OR: 3.21; CI: 1.71-6.05), WC (OR: 2.59; CI: 1.35-4.97), and PF (OR: 2.59; CI: 1.36-4.92). Additionally, students with the AA genotype in the unfit model had a significant odds ratio for obesity (OR: 4.40; CI: 1.83-10.61 for BMI; OR: 3.54; CI: 1.58-7.96 for WC), whereas we did not observe associations between the AA genotype with BMI and WC using the fit model. Conversely, PF was associated with the AA genotype only in the fit model (OR: 3.24; CI: 1.26-8.34). This study demonstrated that the rs9939609 (FTO) polymorphism showed a relationship with obesity in the population studied and an interaction with CRF. Students with low levels of CRF and the AA genotype have a higher risk of being overweight/obese. This association was not found in students with higher levels of CRF. Am. J. Hum. Biol. 28:381-386, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  11. Deletion polymorphism at chromosome 3q26.1 and oral squamous cell carcinoma

    Science.gov (United States)

    KAWACHI, HOMARE; SUGAHARA, KEISUKE; NAKAMURA, YASUTAKA; KATAKURA, AKIRA; MINAGUCHI, KIYOSHI; SHIBAHARA, TAKAHIKO

    2013-01-01

    Several recent studies have investigated DNA instability in malignancies including deletions and duplications of part of the chromosome using array-based comparative genomic hybridization (CGH) analysis. Using the same approach on oral squamous cell carcinoma (OSCC) tissue samples, we found a frequent deletion at chromosome 3q26.1 in OSCC patients; this polymorphism showed a gene frequency of 0.293–0.368 in healthy volunteers (n=60) and 0.129–0.195 in OSCC patients (n=54). Detailed analysis around the polymorphic region revealed the deletion breakage point. A significant association of gene frequency for the deletion polymorphism between healthy volunteers and patients implicated genetic factors related to this polymorphism in the development of OSCC. Currently, no gene is predicted to lie within the 3,606-kbp region around the polymorphism. Thus, although a single-gene model could not explain the occurrence of OSCC, we believe that examining this polymorphism could be useful in identifying risk factors for OSCC. PMID:23258604

  12. CDKN2B gene rs1063192 polymorphism decreases the risk of glaucoma.

    Science.gov (United States)

    Hu, Zhenxian; He, Chenliang

    2017-03-28

    The aim of this meta-analysis was to evaluate the association between cyclin-dependent kinase Inhibitor-2B (CDKN2B) gene rs1063192 polymorphism and glaucoma risk. We searched the databases of PubMed, and Embase. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by using fixed-effect or random-effect models. A total of 14 case-control studies involving 11,316 cases and 24,055 controls were included. Meta-analysis showed that CDKN2B gene rs1063192 polymorphism was associated with a decreased risk of glaucoma. Stratification analysis of ethnicity indicated that rs1063192 polymorphism decreased the risk of glaucoma among Caucasians and Asians. Stratification analysis by type of glaucoma revealed that rs1063192 polymorphism conferred a protective factor of primary open-angle glaucoma (POAG) and non-POAG. Stratification by source of controls uncovered an association between rs1063192 polymorphism and glaucoma in groups of population-based controls. In conclusion, this meta-analysis indicates that CDKN2B gene rs1063192 polymorphism is significantly associated with a decreased risk of glaucoma.

  13. [Association between HLA-DQA1 gene copy number polymorphisms and susceptibility to gastric cancer].

    Science.gov (United States)

    Huang, Li-ming; Cheng, Yan; Yu, Dian-ke; Zhai, Kan; Tan, Wen; Lin, Dong-xin

    2012-04-01

    To explore the association between HLA-DQA1 gene copy number polymorphisms and gastric cancer risk in Chinese population, and the interaction of those genes and environmental factors. The genotype of HLA-DQA1 gene copy number polymorphisms was determined in 343 patients with gastric cancer and 330 controls by quantitative polymerase chain reaction. Logistic regression model was used to evaluate the impact of this polymorphism on the risk of developing gastric cancer and the gene-environment interaction. Compared with 0 copy of HLA-DQA1 gene carriers, the 2 copies of HLA-DQA1 gene carriers had a significantly increased risk of gastric cancer (OR = 1.87, 95%CI = 1.15 - 3.06, P = 0.012). Gene-environment interaction of HLA-DQA1 gene copy number polymorphisms and Helicobacter pylori infection significantly increased the risk of gastric cancer in a multiplicative manner, with an OR of 3.89 (95%CI = 1.75 - 8.57, P = 0.001). HLA-DQA1 gene copy number polymorphism is associated with gastric cancer susceptibility, and there is a multiplicative gene-environment interaction between this polymorphism and Hp infection in the development of gastric cancer.

  14. Clinical Implications of the BIM Deletion Polymorphism in Advanced Lung Adenocarcinoma Treated With Gefitinib.

    Science.gov (United States)

    Yuan, Jupeng; Li, Bo; Zhang, Nasha; Zhu, Hui; Zhou, Liqing; Zhang, Li; Yang, Ming

    2018-02-19

    Proapoptotic protein Bcl-2-like 11 (BIM) is a crucial tumor suppressor gene in lung cancer development. A 2903-bp genomic deletion polymorphism is present in BIM intron 2, which alters RNA splicing and impairs the generation of the death-inducing isoform of BIM and resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). In the present study, we investigated the clinical implications of this genetic polymorphism in patients with advanced lung adenocarcinoma treated with gefitinib. After genotyping the BIM deletion polymorphism in 111 patients with stage IIIB or IV lung adenocarcinoma receiving gefitinib, the hazard ratio (HR) and 95% confidence interval (CI) for progression-free survival and overall survival were estimated using Cox proportional hazards models. Possession of ≥ 1 deletion allele of the BIM polymorphism was observed in 18.02% of the patients. The BIM deletion polymorphism was an independent indicator of a shorter PFS (7.5 months vs. 11.3 months; HR, 2.38; 95% CI, 1.30-4.34; P = .005) and shorter OS (9.9 months vs. 27.5 months; HR, 2.53; 95% CI, 1.37-4.65; P = .003). Additionally, patients carrying the BIM deletion allele were more likely to experience acquired gefitinib-resistant disease. Our results indicate that the BIM deletion polymorphism might be a promising germline biomarker for gefitinib treatment in Chinese patients with lung adenocarcinoma. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Identification of amplified fragment length polymorphism (AFLP ...

    African Journals Online (AJOL)

    Identification of amplified fragment length polymorphism (AFLP) fragments linked to soybean mosaic virus resistance gene in Glycine soja and conversion to a sequence characterized amplified regions (SCAR) marker for rapid selection.

  16. Polymorphous light eruption - some interesting aspects

    International Nuclear Information System (INIS)

    Corrales-Padilla, H.; Dominguez-Soto, L.; Hojyo-Tomoka, M.T.; Londono, F.; Vargas-Ocampo, F.

    1979-01-01

    A study of polymorphous light eruption (PLE) is Latin America is reported. The clinical lesions, the course, histopathology, differential diagnosis, pathogenesis, treatment and systemic photoprotection are discussed. Treatment with ultraviolet radiation is included. (C.F.)

  17. Complementary DNA-amplified fragment length polymorphism ...

    African Journals Online (AJOL)

    Complementary DNA-amplified fragment length polymorphism (AFLP-cDNA) analysis of differential gene expression from the xerophyte Ammopiptanthus mongolicus in response to cold, drought and cold together with drought.

  18. (ISSR) and randomly amplified polymorphic DNA

    African Journals Online (AJOL)

    ajl yemi

    2011-12-19

    Dec 19, 2011 ... The phylogenic relationship within four species of Polygonum (including Polygonum hyrcanicum Rech. f. (three samples), Polygonum persicaria Boiss & Bushe Boiss, Polygonum avicular L., and Polygonum hydropiper L. subsp. Hydropiper) was investigated by randomly amplified polymorphic DNA ...

  19. Estrogens, Genetic Polymorphisms and Breast Cancer Risk

    National Research Council Canada - National Science Library

    Okobia, Michael N; Bunker, Clareann H; Kuller, Lewis; Ferrell, Robert E; Anyanwu, Stanley N; Ezeome, Emmanuel R; Uche, Emmanuel E

    2004-01-01

    This study is aimed at evaluating the role of polymorphisms in the genes encoding enzymes responsible for the biosynthesis and degradation of estrogens and its metabolites in susceptibility to breast...

  20. DNA polymorphism analysis of Xanthomonas campestris pv ...

    African Journals Online (AJOL)

    strand conformation polymorphism (SSCP) techniques using M13 and 16S rRNA primers, respectively, for genotyping of the phytopathogenic bacterium Xanthomonas campestris pv. campestris was studied. RAPD provided a simple, rapid, and ...

  1. Single feature polymorphism discovery in rice.

    Directory of Open Access Journals (Sweden)

    Rajesh Kumar

    Full Text Available The discovery of nucleotide diversity captured as single feature polymorphism (SFP by using the expression array is a high-throughput and effective method in detecting genome-wide polymorphism. The efficacy of such method was tested in rice, and the results presented in the paper indicate high sensitivity in predicting SFP. The sensitivity of polymorphism detection was further demonstrated by the fact that no biasness was observed in detecting SFP with either single or multiple nucleotide polymorphisms. The high density SFP data that can be generated quite effectively by the current method has promise for high resolution genetic mapping studies, as physical location of features are well-defined on rice genome.

  2. CD16 and CD32 Gene Polymorphisms May Contribute to Risk of Idiopathic Thrombocytopenic Purpura

    Science.gov (United States)

    Xu, Jiannan; Zhao, Liyun; Zhang, Yan; Guo, Qingxu; Chen, Hui

    2016-01-01

    Background Epidemiological studies have evaluated the associations of CD16 158F>V and CD32 131H>R gene polymorphisms with the risk of idiopathic thrombocytopenic purpura (ITP). Material/Methods Published studies on CD16 158F>V and CD32 131H>R polymorphisms with susceptibility to ITP were systematically reviewed until April 1, 2014. The Cochrane Library Database, Medline, CINAHL, EMBASE, Web of Science, and Chinese Biomedical Database (CBM) were used to search for relevant studies and then a meta-analysis was conducted by using Stata 12.0 software in order to produce consistent statistical results. Results In total, 10 clinical case-control studies with 741 ITP patients and 1092 healthy controls were enrolled for quantitative data analysis. Results of this meta-analysis suggest that CD16 158F>V polymorphism had strong correlations with the susceptibility to ITP under 5 genetic models (all PR polymorphism and the susceptibility to ITP (all P>0.05). Subgroup analysis by ethnicity revealed that CD16 158F>V polymorphism was associated with the increased risk of ITP among both Caucasian and non-Caucasian populations. Nevertheless, no statistically significant correlations between CD32 131H>R polymorphism and the risk of ITP were observed among Caucasians and non-Caucasians (all P>0.05). Conclusions Our findings indicate that CD16 158F>V polymorphism may contribute to the increased risk of ITP, whereas CD32 131H>R polymorphism may not be an important risk factor for ITP. PMID:27315784

  3. Bulk segregant analysis using single nucleotide polymorphism microarrays.

    Directory of Open Access Journals (Sweden)

    Anthony Becker

    2011-01-01

    Full Text Available Bulk segregant analysis (BSA using microarrays, and extreme array mapping (XAM have recently been used to rapidly identify genomic regions associated with phenotypes in multiple species. These experiments, however, require the identification of single feature polymorphisms (SFP between the cross parents for each new combination of genotypes, which raises the cost of experiments. The availability of the genomic polymorphism data in Arabidopsis thaliana, coupled with the efficient designs of Single Nucleotide Polymorphism (SNP genotyping arrays removes the requirement for SFP detection and lowers the per array cost, thereby lowering the overall cost per experiment. To demonstrate that these approaches would be functional on SNP arrays and determine confidence intervals, we analyzed hybridizations of natural accessions to the Arabidopsis ATSNPTILE array and simulated BSA or XAM given a variety of gene models, populations, and bulk selection parameters. Our results show a striking degree of correlation between the genotyping output of both methods, which suggests that the benefit of SFP genotyping in context of BSA can be had with the cheaper, more efficient SNP arrays. As a final proof of concept, we hybridized the DNA from bulks of an F2 mapping population of a Sulfur and Selenium ionomics mutant to both the Arabidopsis ATTILE1R and ATSNPTILE arrays, which produced almost identical results. We have produced R scripts that prompt the user for the required parameters and perform the BSA analysis using the ATSNPTILE1 array and have provided them as supplemental data files.

  4. UGT polymorphisms and lamotrigine clearance during pregnancy

    DEFF Research Database (Denmark)

    Petrenaite, Vaiva; Öhman, Inger; Ekström, Lena

    2018-01-01

    OBJECTIVE: To evaluate the impact of maternal UGT1A4 and UGT2B7 genetic polymorphisms and sex of foetus on gestation-induced changes in lamotrigine (LTG) clearance during pregnancy and post-partum (PP). METHODS: Single nucleotide polymorphisms UGT1A4 142T > G, L48V (*3), UGT1A4 70C > A, P24T (*2)...

  5. Association between IL-1β polymorphisms and gastritis risk

    Science.gov (United States)

    Sun, Xiaoming; Cai, Hongxing; Li, Zhouru; Li, Shanshan; Yin, Wenjiang; Dong, Guokai; Kuai, Jinxia; He, Yihui; Jia, Jing

    2017-01-01

    Abstract Background: Helicobacter pylori (H. pylori) infection of the human stomach regularly leads to chronic gastric inflammation. The cytokine gene interleukin (IL)-1β has been implicated in influencing the pathology of inflammation induced by H. pylori infection. Currently, several studies have been carried out to investigate the association of IL-1β-511 (rs16944) and IL-1β-31 (rs1143627) polymorphisms with gastritis risk; however, the results are inconsistent and inconclusive. To assess the effect of IL-1β polymorphisms on gastritis susceptibility, we conducted a meta-analysis. Methods: Up to March 15, 2016, 2205 cases and 2289 controls were collected from 12 published case–control studies. Summarized odds ratios and corresponding 95% confidence intervals (CIs) for IL-1β-511 and IL-1β-31 polymorphisms and gastritis risk were estimated using fixed- or random-effects models when appropriate. Heterogeneity was assessed by chi-squared-based Q-statistic test, and the sources of heterogeneity were explored by subgroup analyses and logistic meta-regression analyses. Publication bias was evaluated by Begg funnel plot and Egger test. Sensitivity analyses were also performed. Results: The results provided evidences that the single nucleotide polymorphisms (SNPs) in IL-1β-31 might be associated with the gastritis risk, especially in the Caucasian population, while SNPs in the IL-1β-511 might not be. Conclusion: Our studies may be helpful in supplementing the disease monitoring of gastritis in the future, and additional studies to determine the exact molecular mechanisms might inspire interventions to protect the susceptible subgroups. PMID:28151895

  6. Association between matrix metalloproteinases polymorphisms and ovarian cancer risk: A meta-analysis and systematic review.

    Directory of Open Access Journals (Sweden)

    Xu-Ming Zhu

    Full Text Available Published data on the relationship between matrix metalloproteinases (MMPs polymorphisms and ovarian cancer risk have implicated inconclusive results. To evaluate the role of MMPs polymorphisms in ovarian cancer risk, a meta-analysis and systematic review were performed.MMPs polymorphisms which could be quantitatively synthesized were involved in meta-analysis. Five comparison models (homozygote model, heterozygote model, dominant model, recessive model, additive model were carried out, a subgroup analysis was performed to clarify heterogeneity source. The remaining polymorphisms which could not be quantitatively synthesized were involved in systematic review.10 articles with 20 studies were included in this paper. Among those studies, 8 studies involving MMP1 rs1799750 and MMP3 rs34093618 could be meta-analyzed and 12 studies involving 12 polymorphisms could not. Meta-analysis showed that no associations were found between MMP1 rs1799750 (homozygote model: OR = 0.93, 95%CI = 0.70-1.23, POR = 0.60; heterozygote model: OR = 1.09, 95%CI = 0.78-1.54, POR = 0.61; dominant model: OR = 1.02, 95%CI = 0.83-1.25, POR = 0.84; recessive model: OR = 0.95, 95%CI = 0.75-1.21, POR = 0.67; additive model: OR = 1.00, 95%CI = 0.85-1.17, POR = 0.99, MMP3 rs34093618 (homozygote model: OR = 1.25, 95%CI = 0.70-2.24, POR = 0.46; heterozygote model: OR = 1.08, 95%CI = 0.51-2.31, POR = 0.84; dominant model: OR = 0.97, 95%CI = 0.68-1.38, POR = 0.85; recessive model: OR = 1.12, 95%CI = 0.69-1.80, POR = 0.65; additive model: OR = 1.01, 95%CI = 0.79-1.31, POR = 0.91 and ovarian cancer. Furthermore, similar results were detected in subgroup analysis. The systematic review on 12 polymorphisms suggested that MMP2 C-735T, MMP7 A-181G, MMP8 rs11225395, MMP9 rs6094237, MMP12 rs2276109, MMP20 rs2292730, MMP20 rs12278250, MMP20 rs9787933 might have a potential effect on ovarian cancer risk.In summary, polymorphisms of MMPs might not be associated with ovarian cancer risk. However

  7. Heterozygote advantage fails to explain the high degree of polymorphism of the MHC

    DEFF Research Database (Denmark)

    de Boer, R.J.; Borghans, J.A.M.; Boven, M.

    2004-01-01

    Major histocompatibility (MHC) molecules are encoded by extremely polymorphic genes and play a crucial role in vertebrate immunity. Natural selection favors MHC heterozygous hosts because individuals heterozygous at the MHC can present a larger diversity of peptides from infectious pathogens than...... homozygous individuals. Whether or not heterozygote advantage is sufficient to account for a high degree of polymorphism is controversial, however. Using mathematical models we studied the degree of MHC polymorphism arising when heterozygote advantage is the only selection pressure. We argue that existing...... models are misleading in that the fitness of heterozygotes is not related to the MHC alleles they harbor. To correct for this, we have developed novel models in which the genotypic fitness of a host directly reflects the fitness contributions of its MHC alleles. The mathematical analysis suggests...

  8. Dispersal Polymorphisms in Invasive Fire Ants.

    Directory of Open Access Journals (Sweden)

    Jackson A Helms

    Full Text Available In the Found or Fly (FoF hypothesis ant queens experience reproduction-dispersal tradeoffs such that queens with heavier abdomens are better at founding colonies but are worse flyers. We tested predictions of FoF in two globally invasive fire ants, Solenopsis geminata (Fabricius, 1804 and S. invicta (Buren, 1972. Colonies of these species may produce two different monogyne queen types-claustral queens with heavy abdomens that found colonies independently, and parasitic queens with small abdomens that enter conspecific nests. Claustral and parasitic queens were similarly sized, but the abdomens of claustral queens weighed twice as much as those of their parasitic counterparts. Their heavier abdomens adversely impacted morphological predictors of flight ability, resulting in 32-38% lower flight muscle ratios, 55-63% higher wing loading, and 32-33% higher abdomen drag. In lab experiments maximum flight durations in claustral S. invicta queens decreased by about 18 minutes for every milligram of abdomen mass. Combining our results into a simple fitness tradeoff model, we calculated that an average parasitic S. invicta queen could produce only 1/3 as many worker offspring as a claustral queen, but could fly 4 times as long and have a 17- to 36-fold larger potential colonization area. Investigations of dispersal polymorphisms and their associated tradeoffs promises to shed light on range expansions in invasive species, the evolution of alternative reproductive strategies, and the selective forces driving the recurrent evolution of parasitism in ants.

  9. Polymorphism in Bacterial Flagella Suspensions

    Science.gov (United States)

    Schwenger, Walter J.

    Bacterial flagella are a type of biological polymer studied for its role in bacterial motility and the polymorphic transitions undertaken to facilitate the run and tumble behavior. The naturally rigid, helical shape of flagella gives rise to novel colloidal dynamics and material properties. This thesis studies methods in which the shape of bacterial flagella can be controlled using in vitro methods and the changes the shape of the flagella have on both single particle dynamics and bulk material properties. We observe individual flagellum in both the dilute and semidilute regimes to observe the effects of solvent condition on the shape of the filament as well as the effect the filament morphology has on reptation through a network of flagella. In addition, we present rheological measurements showing how the shape of filaments effects the bulk material properties of flagellar suspensions. We find that the individual particle dynamics in suspensions of flagella can vary with geometry from needing to reptate linearly via rotation for helical filaments to the prevention of long range diffusion for block copolymer filaments. Similarly, for bulk material properties of flagella suspensions, helical geometries show a dramatic enhancement in elasticity over straight filaments while block copolymers form an elastic gel without the aid of crosslinking agents.

  10. Utilising polymorphisms to achieve allele-specific genome editing in zebrafish

    Directory of Open Access Journals (Sweden)

    Samuel J. Capon

    2017-01-01

    Full Text Available The advent of genome editing has significantly altered genetic research, including research using the zebrafish model. To better understand the selectivity of the commonly used CRISPR/Cas9 system, we investigated single base pair mismatches in target sites and examined how they affect genome editing in the zebrafish model. Using two different zebrafish strains that have been deep sequenced, CRISPR/Cas9 target sites containing polymorphisms between the two strains were identified. These strains were crossed (creating heterozygotes at polymorphic sites and CRISPR/Cas9 complexes that perfectly complement one strain injected. Sequencing of targeted sites showed biased, allele-specific editing for the perfectly complementary sequence in the majority of cases (14/19. To test utility, we examined whether phenotypes generated by F0 injection could be internally controlled with such polymorphisms. Targeting of genes bmp7a and chordin showed reduction in the frequency of phenotypes in injected ‘heterozygotes’ compared with injecting the strain with perfect complementarity. Next, injecting CRISPR/Cas9 complexes targeting two separate sites created deletions, but deletions were biased to selected chromosomes when one CRISPR/Cas9 target contained a polymorphism. Finally, integration of loxP sequences occurred preferentially in alleles with perfect complementarity. These experiments demonstrate that single nucleotide polymorphisms (SNPs present throughout the genome can be utilised to increase the efficiency of in cis genome editing using CRISPR/Cas9 in the zebrafish model.

  11. [The value of 5-HTT gene polymorphism for the assessment and prediction of male adolescence violence].

    Science.gov (United States)

    Yu, Yue; Liu, Xiang; Yang, Zhen-xing; Qiu, Chang-jian; Ma, Xiao-hong

    2012-08-01

    To establish an adolescent violence crime prediction model, and to assess the value of serotonin transporter (5-HTT) gene polymorphism for the assessment and prediction of violent crime. Investigative tools were used to analyze the difference in personality dimensions, social support, coping styles, aggressiveness, impulsivity, and family condition scale between 223 adolescents with violence behavior and 148 adolescents without violence behavior. The distribution of 5-HTT gene polymorphisms (5-HTTLPR and 5-HTTVNTR) was compared between the two groups. The role of 5-HTT gene polymorphism on adolescent personality, impulsion and aggression scale also was also analyzed. Stepwise logistic regression was used to establish a predictive model for adolescent violent crime. Significant difference was found between the violence group and the control group on multiple dimensions of psychology and environment scales. However, no statistical difference was found with regard to the 5-HTT genotypes and alleles between adolescents with violent behaviors and normal controls. The rate of prediction accuracy was not significantly improved when 5-HTT gene polymorphism was taken into the model. The violent crime of adolescents was closely related with social and environmental factors. No association was found between 5-HTT polymorphisms and adolescent violence criminal behavior.

  12. Use of Germline Polymorphisms in Predicting Concurrent Chemoradiotherapy Response in Esophageal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Pei-Chun [Department of Statistics and Informatics Science, Providence University, Taiwan (China); Chen, Yen-Ching [Institute of Epidemiology Preventive Medicine, College of Public Health, National Taiwan University, Taiwan (China); Research Center for Gene, Environment, and Human Health, College of Public Health, National Taiwan University, Taiwan (China); Department of Public Health, Institute of Epidemiology, National Taiwan University, Taiwan (China); Lai, Liang-Chuan [Graduate Institute of Physiology, National Taiwan University, Taiwan (China); Tsai, Mong-Hsun [Institute of Biotechnology, National Taiwan University, Taiwan (China); Chen, Shin-Kuang [National Clinical Trial and Research Center, National Taiwan University Hospital, Taiwan (China); Yang, Pei-Wen; Lee, Yung-Chie [Department of Surgery, National Taiwan University Hospital, Taiwan (China); Hsiao, Chuhsing K. [Research Center for Gene, Environment, and Human Health, College of Public Health, National Taiwan University, Taiwan (China); Department of Public Health, Institute of Epidemiology, National Taiwan University, Taiwan (China); Bioinformatics and Biostatistics Core, Research Center for Medical Excellence, National Taiwan University, Taiwan (China); Lee, Jang-Ming, E-mail: jangming@ntuh.gov.tw [Department of Surgery, National Taiwan University Hospital, Taiwan (China); Chuang, Eric Y., E-mail: chuangey@ntu.edu.tw [National Clinical Trial and Research Center, National Taiwan University Hospital, Taiwan (China); Bioinformatics and Biostatistics Core, Research Center for Medical Excellence, National Taiwan University, Taiwan (China); Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taiwan (China)

    2012-04-01

    Purpose: To identify germline polymorphisms to predict concurrent chemoradiation therapy (CCRT) response in esophageal cancer patients. Materials and Methods: A total of 139 esophageal cancer patients treated with CCRT (cisplatin-based chemotherapy combined with 40 Gy of irradiation) and subsequent esophagectomy were recruited at the National Taiwan University Hospital between 1997 and 2008. After excluding confounding factors (i.e., females and patients aged {>=}70 years), 116 patients were enrolled to identify single nucleotide polymorphisms (SNPs) associated with specific CCRT responses. Genotyping arrays and mass spectrometry were used sequentially to determine germline polymorphisms from blood samples. These polymorphisms remain stable throughout disease progression, unlike somatic mutations from tumor tissues. Two-stage design and additive genetic models were adopted in this study. Results: From the 26 SNPs identified in the first stage, 2 SNPs were found to be significantly associated with CCRT response in the second stage. Single nucleotide polymorphism rs16863886, located between SGPP2 and FARSB on chromosome 2q36.1, was significantly associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.62-10.30) under additive models. Single nucleotide polymorphism rs4954256, located in ZRANB3 on chromosome 2q21.3, was associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.57-10.87). The predictive accuracy for CCRT response was 71.59% with these two SNPs combined. Conclusions: This is the first study to identify germline polymorphisms with a high accuracy for predicting CCRT response in the treatment of esophageal cancer.

  13. Methylenetetrahydrofolate reductase gene polymorphism and risk of chronic myelogenous leukemia: a meta-analysis.

    Science.gov (United States)

    Li, Chen; Yichao, Jin; Jiaxin, Lin; Yueting, Zhang; Qin, Lu; Tonghua, Yang

    2015-01-01

    Reported evidence supports a role for methylenetetrahydrofolate reductase (MTHFR) in the risk of chronic myelogenous leykemia (CML). However, these reports arrived at non-conclusive and even conflicting results regarding the association between two common MTHFR polymorphisms (C677T and A1298C) and CML risk. Thus, a meta-analysis was carried out to clarify a more precise association between these two polymorphisms and the CML risk by updating the available publications. Pooled odds ratios (OR) with corresponding 95% confidence interval (95% CI) and stratification analysis were performed to estimate the relationship between MTHFR polymorphisms and the risk of CML under different genetic comparison models. Data from the meta-analysis showed no significant association between MTHFR C677T polymorphism and CML risk. However, significant associations were found between MTHFR A1298C variants and CML risk under homozygous comparison model (CC vs AA, OR=1.62, 95% CI=1.11-2.36, p=0.01) and dominant comparison model (CC+AC vs AA, OR=1.68, 95% CI=1.17-2.43, p=0.005) in overall population; especially more obvious impacts were noticed for Asian populations in subgroup analysis for homozygous model (CC vs AA, OR=2.00, 95% CI=1.25-3.21, p=0.004) and dominant model (CC+AC vs AA, OR=2.49, 95% CI=1.42-4.36, p=0.001), but this did not apply in Caucasian populations. The results of this meta-analysis suggested no significant association between MTHFR C677T polymorphism and CML risk, while an increased CML risk was noticed for 1298C variant carriers, especially in Asian populations but not in Caucasian populations, which suggested ethnicity differences between MTHFR A1298C polymorphisms and risk of CML.

  14. Associations between the Genetic Polymorphisms of Osteopontin Promoter and Susceptibility to Cancer in Chinese Population: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Yulan Liu

    Full Text Available Several studies have been conducted to examine the associations between osteopontin (OPN promoter gene SPP1 polymorphisms with human cancers in Chinese population, but the results remain inconsistent. The aim of this meta-analysis is to clarify the associations between SPP1 polymorphisms and cancer susceptibility.All eligible case-control studies published up to March 2015 were identified by searching PubMed, Web of Science, Embase, and Cochrane Library without language restrictions. Pooled odds ratio (OR and 95% confidence interval (95% CI were calculated using fixed- or random-effect model.A total of 11 case-control studies were included; of those, there were eleven studies (3130 cases and 3828 controls for -443T>C polymorphism, ten studies (3019 cases and 3615 controls for -156G>GG polymorphism, eight studies (2258 cases and 2846 controls for -66T>G polymorphism. Overall, no evidence indicated that the -443 T>C polymorphism was associated with cancer risk (OR = 0.93, 95%CI 0.62-1.38 for dominant model, OR = 1.06, 95%CI 0.73-1.55 for recessive model, OR = 0.88, 95%CI 0.62-1.26 for CT vs TT model, OR = 1.03, 95%CI 0.61-1.73 for CC vs TT model. While, a significantly increase risk was found for -156 G>GG polymorphism (OR = 1.22, 95%CI 1.10-1.35 for dominant model, OR = 1.25, 95%CI 1.10-1.41 for recessive model, OR = 1.18, 95%CI 1.06-1.32 for GGG vs GG model, OR = 1.35, 95%CI 1.09-1.68 for GGGG vs GG model. For -66T>G polymorphism, we found a decrease risk of cancer (OR = 0.84, 95% CI 0.71-0.98 for dominant model, but this result changed (OR = 0.93, 95% CI 0.77-1.12 for dominant model when we excluded a study.This meta-analysis suggests that in Chinese population the -156G>GG polymorphism of SPP1 might be a risk factor for human cancers, while -443T>C mutation is not associated with cancer risk. For -66T>G polymorphism, it may be a protective factor for human cancers.

  15. Associations between a polymorphism in the hydroxysteroid (11-beta) dehydrogenase 1 gene, neuroticism and postpartum depression.

    Science.gov (United States)

    Iliadis, S I; Comasco, E; Hellgren, C; Kollia, N; Sundström Poromaa, I; Skalkidou, A

    2017-01-01

    This study examined the association between a single nucleotide polymorphism in the hydroxysteroid (11-beta) dehydrogenase 1 gene and neuroticism, as well as the possible mediatory role of neuroticism in the association between the polymorphism and postpartum depressive symptoms. 769 women received questionnaires containing the Edinburgh Postnatal Depression Scale (EPDS) at six weeks postpartum and demographic data at pregnancy week 17 and 32 and at six weeks postpartum, as well as the Swedish universities Scales of Personality at pregnancy week 32. Linear regression models showed an association between the GG genotype and depressive symptoms. When neuroticism was introduced in the model, it was associated with EPDS score, whereas the association between the GG genotype and EPDS became borderline significant. A path analysis showed that neuroticism had a mediatory role in the association between the polymorphism and EPDS score. The use of the EPDS, which is a self-reporting instrument. Neuroticism was associated with the polymorphism and had a mediatory role in the association between the polymorphism and postpartum depression. This finding elucidates the genetic background of neuroticism and postpartum depression. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Simultaneous Quantification of Three Polymorphic Forms of Carbamazepine in the Presence of Excipients Using Raman Spectroscopy

    Directory of Open Access Journals (Sweden)

    Marco Farias

    2014-09-01

    Full Text Available The occurrence of polymorphic transitions is a serious problem for pharmaceutical companies, because it can affect the bioavailability of the final product. With several known polymorphic forms carbamazepine is one of the most problematic drugs in this respect. Raman spectroscopy is a vibrational technique that is becoming very important in the pharmaceutical field, mainly due to its highly specific molecular fingerprint capabilities and easy use as a process analytical tool. However, multivariate methods are necessary both for identification and quantification. In this work an analytical methodology using Raman spectroscopy and interval Partial Least Squares Regression (iPLS, was developed in order to quantify mixtures of carbamazepine polymorphs in the presence of the most common excipients. The three polymorphs CBZ I, CBZ III and CBZ DH (which is a dihydrate were synthesized and characterized by PXRD and DSC. Subsequently, tablets were manufactured using excipients and 15 different mixtures of carbamazepine polymorphs. The iPLS model presented average prediction validation errors of 1.58%, 1.04% and 0.22% wt/wt, for CBZ I, CBZ III and CBZ DH, respectively, considering the whole mass of the tablet. The model presents a good prediction capacity and the proposed methodology could be used to perform quality control in final products.

  17. Dimer and cluster approach for the evaluation of electronic couplings governing charge transport: Application to two pentacene polymorphs

    Energy Technology Data Exchange (ETDEWEB)

    Canola, Sofia; Pecoraro, Claudia; Negri, Fabrizia

    2016-10-20

    Hole transport properties are modeled for two polymorphs of pentacene: the single crystal polymorph and the thin film polymorph relevant for organic thin-film transistor applications. Electronic couplings are evaluated in the standard dimer approach but also considering a cluster approach in which the central molecule is surrounded by a large number of molecules quantum-chemically described. The effective electronic couplings suitable for the parametrization of a tight-binding model are derived either from the orthogonalization scheme limited to HOMO orbitals and from the orthogonalization of the full basis of molecular orbitals. The angular dependent mobilities estimated for the two polymorphs using the predicted pattern of couplings display different anisotropy characteristics as suggested from experimental investigations.

  18. Methylenetetrahydrofolate reductase gene A1298C polymorphism in pediatric stroke--case-control and family-based study.

    Science.gov (United States)

    Balcerzyk, Anna; Niemiec, Paweł; Kopyta, Ilona; Emich-Widera, Ewa; Pilarska, Ewa; Pienczk-Ręcławowicz, Karolina; Kaciński, Marek; Wendorff, Janusz; Żak, Iwona

    2015-01-01

    Moderate hyperhomocysteinemia is one of the risk factors of pediatric stroke. Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme, which regulates homocysteine metabolism, and some polymorphisms of gene encoding this enzyme are associated with a decreased activity of the enzyme. The aim of the study was to assess an association between the A1298C polymorphism and pediatric stroke. We also evaluated a possible synergistic effect of A1298C and C677T polymorphisms of this gene. The study group consisted of 88 children after ischemic stroke, 142 of their parents and 111 controls. The A1298C polymorphism was genotyped using the restriction fragment length polymorphism method. We used 2 study designs: a case-control model and a family-based association test. The Statistica 7.1 and EpiInfo 6 softwares were used in all analyses. We did not observe any statistically significant differences either in the transmission of the A allele in the family-based test or in the frequency of the A allele in the patients group compared with the controls. We also did not notice any significant additive or synergistic effects between the A1298C and C677T polymorphisms. An analysis of the results obtained in this study and a critical review of previously published studies indicate that the A1298C polymorphism of the MTHFR gene is not related to ischemic stroke in children. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  19. The impact of a TSH receptor gene polymorphism on thyroid-related phenotypes in a healthy Danish twin population

    DEFF Research Database (Denmark)

    Hansen, Pia Skov; van der Deure, Wendy M; Peeters, Robin P

    2007-01-01

    OBJECTIVES: The Asp727Glu polymorphism in the TSH receptor (TSHR) gene is associated with serum TSH levels. However, the proportion of genetic variation accounted for by this polymorphism is unknown. In this study, we (1) examined the association of the Asp727Glu polymorphism with thyroid size...... between the TSHR-Asp727Glu polymorphism and measures of thyroid homeostasis were assessed and the effect of the polymorphism on the trait's phenotypic variability was quantified by incorporating the genotype information in structural equation modelling. RESULTS: The genotype distribution was Asp/Asp 84.......9%; Asp/Glu 14.5% and Glu/Glu 0.6%. Carriers of the TSHR-Glu727 allele had lower TSH levels (noncarriers vs. carriers: 1.78 +/- 0.93 vs. 1.60 +/- 0.84 mU/l, P = 0.04). Regression analysis showed an association between the TSHR-Asp727Glu polymorphism and serum TSH (P = 0.007). The polymorphism accounted...

  20. Association between CD14 gene polymorphisms and cancer risk: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Jun Wang

    Full Text Available BACKGROUND: Two polymorphisms, -260C/T and -651C/T, in the CD14 gene have been implicated in susceptibility to cancer. However, the results remain inconclusive. This meta-analysis aimed to investigate the association between the two polymorphisms and risk of cancer. METHODS: All eligible case-control studies published up to March 2014 were identified by searching PubMed, Web of Science, CNKI and WanFang database. Pooled odds ratio (OR with 95% confidence interval (CI were used to access the strength of this association in fixed- or random-effects model. RESULTS: 17 case-control studies from fourteen articles were included. Of those, there were 17 studies (4198 cases and 4194 controls for -260C/T polymorphism and three studies (832 cases and 1190 controls for -651C/T polymorphism. Overall, no significant associations between the two polymorphisms of CD14 gene and cancer risk were found. When stratified by ethnicity, cancer type and source of control, similar results were observed among them. In addition, in further subgroups analysis by Helicobacter pylori (H. pylori infection status and tumor location in gastric cancer subgroup, we found that the CD14 -260C/T polymorphism may increase the risk of gastric cancer in H. pylori-infected individuals. CONCLUSIONS: This meta-analysis suggests that the CD14 -260C/T polymorphism may increase the risk of gastric cancer in H. pylori-infected individuals. However, large and well-designed studies are warranted to validate our findings.

  1. Surfactant protein B gene polymorphism in preterm babies with respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    P.P.R. Lyra

    2011-01-01

    Full Text Available The etiology of respiratory distress syndrome (RDS is multifactorial and multigenic. Studies have suggested that polymorphisms and mutations in the surfactant protein B (SP-B gene are associated with the pathogenesis of RDS. The objectives of this study were to determine and compare the frequencies of SP-B gene polymorphisms in preterm babies with and without RDS. We studied 151 neonates: 79 preterm babies without RDS and 72 preterm newborns with RDS. The following four SP-B gene polymorphisms were analyzed: A/C at -18, C/T at 1580, A/G at 9306, and G/C at nucleotide 8714. The polymorphisms were detected by PCR amplification of genomic DNA and genotyping. The genotypes were determined using PCR-based converted restriction fragment length polymorphisms. The control group consisted of 42 (53% girls and 37 (47% boys. Weight ranged from 1170 to 3260 g and mean gestational age (GA was 33.9 weeks (range: 29 to 35 weeks and 6 days. The RDS group consisted of 31 (43% girls and 41 (57% boys. Weight ranged from 614 to 2410 g and mean GA was 32 weeks (range: 26 to 35 weeks. The logistic regression model showed that GA was the variable that most contributed to the occurrence of RDS. The AG genotype of the A/G polymorphism at position 9306 of the SP-B gene was a protective factor in this population (OR = 0.1681; 95%CI = 0.0426-0.6629. We did not detect differences in the frequencies of the other polymorphisms between the two groups of newborns.

  2. The effect of six polymorphisms in the Apolipoprotein B gene on parameters of lipid metabolism in a Danish population

    DEFF Research Database (Denmark)

    Bentzen, J; Jørgensen, T; Fenger, M

    2002-01-01

    on fasting levels of triglyceride, VLDL-, LDL-, HDL- and total cholesterol and on body mass index (BMI) in a cohort of 2656 Danes aged 40-70 years using a linear model correcting for the effects of gender, age, BMI, smoking, alcohol consumption and physical activity. The codon 2488 polymorphism was the most...... influential of the tested polymorphisms, significantly influencing triglyceride (P = 0.002), LDL-cholesterol (P triglyceride (P = 0.007) and VLDL-cholesterol (P = 0.001), while...

  3. Investigation of drug polymorphism: Case of artemisinin

    International Nuclear Information System (INIS)

    Horosanskaia, E.; Seidel-Morgenstern, A.; Lorenz, H.

    2014-01-01

    Highlights: • The Artemisinin dimorphic system was found to be enantiotropic. • The Orthorhombic modification is the form stable at low-temperatures and the triclinic modification the form stable at high-temperatures. • The polymorphic phase transition occurs at ∼130 °C. - Abstract: The polymorphism of the anti-malarial compound artemisinin was examined. The phase behavior of solid artemisinin has experimentally been investigated using differential scanning calorimetry and temperature-resolved X-Ray powder diffraction. In addition, complementary solution studies and suspension experiments were performed. The results clearly confirm the existence of two modifications of artemisinin, which are related enantiotropically. The orthorhombic modification is the thermodynamically stable form at low temperatures, while the triclinic form is the stable one at higher temperatures with a transition temperature of ∼130 °C. Problems associated with analysis of the polymorphic phase behavior are comprehensively addressed

  4. 2-(4-Fluorobenzylidenepropanedinitrile: monoclinic polymorph

    Directory of Open Access Journals (Sweden)

    Ahmed M. El-Agrody

    2013-04-01

    Full Text Available The title compound, C10H5FN2, is a monoclinic (P21/c polymorph of the previously reported triclinic (P-1 form [Antipin et al. (2003. J. Mol. Struct. 650, 1–20]. The 13 non-H atoms in the title polymorph are almost coplanar (r.m.s. deviation = 0.020 Å; a small twist between the fluorobenzene and dinitrile groups [C—C—C—C torsion angle = 175.49 (16°] is evident in the triclinic polymorph. In the crystal, C—H...N interactions lead to supramolecular layers parallel to (-101; these are connected by C—F...π interactions.

  5. Association between polymorphisms in interleukins and oral lichen planus

    Science.gov (United States)

    Shi, Quan; Zhang, Tong; Huo, Na; Huang, Yang; Xu, Juan; Liu, Hongchen

    2017-01-01

    Abstract Background: More and more studies have suggested that single-nucleotide polymorphisms (SNPs) in interleukin (IL) genes are correlated with an increased risk of developing oral lichen planus (OLP). However, these results were inconsistent. Therefore, the aim of this meta-analysis is to retrieve and comprehensively analyze all related clinical studies to investigate the association of ILs gene polymorphisms with the OLP risk. Methods: PubMed, Embase, and the Cochrane Library were searched for eligible studies to evaluate the association between IL polymorphisms and the OLP. The odds ratios (ORs) and 95% confidence intervals (CIs) from each study were pooled to estimate the strength of the association. Statistical analyses were performed by using STATA software. Results: In all 6 studies, including 4 SNPs (IL6-174G/C, IL10-592C/A, IL10-819C/T, and IL10-1082G/A), 362 OLP patients and 622 non-OLP control subjects from five different countries were investigated. As for the IL6-174G/C, IL10-819C/T, and IL10-1082G/A, no evidence was found to support the association between SNP and OLP susceptibility in any genetic models. However, as for IL10-592C/A, a significant relationship between them was identified in all of comparison models (C vs A: OR = 0.724, 95% CI = 0.585–0.897, P = 0.003; CC vs AA: OR = 0.447, 95% CI = 0.276–0.722, P = 0.001; AC vs AA: OR = 0.585, 95% CI = 0.387–0.883, P = 0.011; CC+AC vs AA: OR = 0.544, 95% CI = 0.365–0.809, P = 0.003; CC vs AA+AC: OR = 0.715, 95% CI = 0.515–0.994, P = 0.046). Conclusion: With the presently available evidence, this meta-analysis fails to show the statistical associations between IL6-174G/C, IL10-819C/T, and IL10-1082G/A and OLP susceptibility in any genetic models. However, the A allele and AA genotype in IL10-592C/A polymorphism may increase the risk of OLP. In the future, more well-designed studies with larger sample sizes are needed. PMID

  6. E-selectin gene polymorphisms and essential hypertension in Asian population: an updated meta-analysis.

    Directory of Open Access Journals (Sweden)

    Gaojun Cai

    Full Text Available Epidemiological studies have shown that E-selectin gene polymorphisms (A561C and C1839T may be associated with essential hypertension (EH, but the results are conflicting in different ethnic populations. Thus, we performed this meta-analysis to investigate a more authentic association between E-selectin gene polymorphisms and the risk of EH.We searched the relevant studies for the present meta-analysis from the following electronic databases: PubMed, Embase, Cochrane Library, Google Scholar, Web of Science, Wanfang Data, and China National Knowledge Infrastructure (CNKI. Odds ratios (OR with 95% confidence interval (CI were used to evaluate the strength of the association between E-selectin gene polymorphisms and EH susceptibility. The pooled ORs were performed for dominant model, allelic model and recessive model. The publication bias was examined by Begg's funnel plots and Egger's test.A total of eleven studies met the inclusion criteria. All studies came from Asians. Ten studies (12 cohorts evaluated the A561C polymorphism and EH risk, including 2,813 cases and 2,817 controls. The pooled OR was 2.280 (95%CI: 1.893-2.748, P<0.001 in dominant model, 5.284 (95%CI: 2.679-10.420, P<0.001 in recessive model and 2.359 (95%CI: 1.981-2.808, P = 0.001 in allelic model. Four studies (six cohorts evaluated C1839T polymorphism and EH risk, including 1,700 cases and 1,681 controls. The pooled OR was 0.785 (95%CI: 0.627-0.983, P = 0.035 in dominant model, 1.250 (95%CI: 0.336-4.652, P = 0.739 in recessive model and 0.805 (95%CI: 0.649-0.999, P = 0.049 in allelic model.The current meta-analysis concludes that the C allele of E-selectin A561C gene polymorphism might increase the EH risk in Asian population, whereas the T allele of E-selectin C1839T gene polymorphism might decrease the EH risk.

  7. The common polymorphism of apolipoprotein E

    DEFF Research Database (Denmark)

    Gerdes, Ulrik

    2003-01-01

    Apolipoprotein E (apoE) has important functions in systemic and local lipid transport, but also has other functions. The gene (APOE) shows a common polymorphism with three alleles--APOE*2, APOE*3, and APOE*4. Their frequencies vary substantially around the world, but APOE*3 is the most common...... from only 10-15% in southern Europe to 40-50% in the north. The gradient may be a trace of the demic expansion of agriculture that began about 10,000 years ago, but it may also reflect the possibility that APOE*4 carriers are less likely to develop vitamin D deficiency. The common APOE polymorphism...

  8. Polymorphic transformation of helical flagella of bacteria

    Science.gov (United States)

    Lim, Sookkyung; Howard Berg Collaboration; William Ko Collaboration; Yongsam Kim Collaboration; Wanho Lee Collaboration; Charles Peskin Collaboration

    2016-11-01

    Bacteria such as E. coli swim in an aqueous environment by utilizing the rotation of flagellar motors and alternate two modes of motility, runs and tumbles. Runs are steady forward swimming driven by bundles of flagellar filaments whose motors are turning CCW; tumbles involve a reorientation of the direction of swimming triggered by motor reversals. During tumbling, the helical flagellum undergoes polymorphic transformations, which is a local change in helical pitch, helical radius, and handedness. In this work, we investigate the underlying mechanism of structural conformation and how this polymorphic transition plays a role in bacterial swimming. National Science Foundation.

  9. Myeloperoxidase polymorphism, menopausal status, and breast cancer risk: an update meta-analysis.

    Directory of Open Access Journals (Sweden)

    Xue Qin

    Full Text Available Myeloperoxidase (MPO is a metabolic/oxidative lysosomal enzyme secreted by reactive neutrophils at the sites of inflamed organs and tissues during phagocytosis. MPO has been either directly or indirectly linked to neoplasia, which is a well-established risk factor for many types of cancer. A large number of studies have reported the role of MPO G-463A polymorphism regarding breast-cancer risk. However, the published findings are inconsistent. Therefore, we conducted a meta-analysis to determine more precise estimations for the relationship. Eligible studies were identified by searching several electronic databases for relevant reports published before June 2012. According to the inclusion criteria and exclusion criteria, a total of five eligible studies were included in the pooled analyses. When the five eligible studies concerning MPO G-463A polymorphism were pooled into this meta-analysis, there was no evidence found for a significant association between MPO G-463A polymorphism and breast-cancer risk in any genetic model. We also categorized by ethnicity (Caucasian or Asian for subgroup analysis; according to this subgroup analysis, we found no significant association between MPO G-463A polymorphism and breast-cancer risk in any genetic model. However, in the stratified analysis for the premenopausal group, women carrying the AA genotype were found to have a significantly reduced risk (OR = 0.56, 95% CI 0.34-0.94, p = 0.027. Under the recessive model, there was a significant association between MPO G-463A polymorphism and breast-cancer risk (OR = 0.57, 95% CI 0.34-0.93, p = 0.025. We conclude that MPO-G463A polymorphism might not be a good predictor of breast-cancer risk, though menopausal status modified women's risk of developing breast cancer.

  10. Glutathione S-transferase P1 gene polymorphisms and susceptibility ...

    Indian Academy of Sciences (India)

    matched and ethnicity-matched healthy controls (n = 200) were genotyped for polymorphisms in GSTP1 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Genotype distribution of g.313A>G and ...

  11. ADAM33 polymorphisms are associated with asthma and a distinctive palm dermatoglyphic pattern.

    Science.gov (United States)

    Xue, Weilin; Han, Wei; Zhou, Zhao-Shan

    2013-12-01

    A close correlation between asthma and palm dermatoglyphic patterns has been observed in previous studies, but the underlying genetic mechanisms have not been investigated. A disintegrin and metalloprotein‑33 (ADAM33) polymorphisms are important in the development of asthma and other atopic diseases. To investigate the underlying mechanisms of the association between asthma and distinctive palm dermatoglyphic patterns, thirteen ADAM33 single‑nucleotide polymorphisms (SNPs) were analyzed for the association between asthma and palm dermatoglyphic patterns in a population of 400 asthmatic patients and 200 healthy controls. Based on the results, five SNPs, rs44707 (codominant model, P=0.031; log‑additive model, P=0.0084), rs2787094 (overdominant model, P=0.049), rs678881 (codominant model, P=0.028; overdominant model, P=0.0083), rs677044 (codominant model, P=0.013; log‑additive model, P=0.0033) and rs512625 (dominant model, P=0.033), were associated with asthma in this population. Two SNPs, rs44707 (dominant model, P=0.042) and rs2787094 (codominant model, P=0.014; recessive model, P=0.0038), were observed in the asthma patients with the distinctive palm pattern. As rs44707 and rs2787094 are associated with asthma and a distinctive palm pattern, the data suggest that ADAM33 polymorphisms are correlated with asthma and may be the underlying genetic basis of the association between asthma and palm dermatoglyphic patterns.

  12. Association between maternal, fetal and paternal MTHFR gene C677T and A1298C polymorphisms and risk of recurrent pregnancy loss: a comprehensive evaluation.

    Science.gov (United States)

    Yang, Yi; Luo, Yunyao; Yuan, Jing; Tang, Yidan; Xiong, Lang; Xu, MangMang; Rao, XuDong; Liu, Hao

    2016-06-01

    Numerous studies have investigated the associations between methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms and risk of recurrent pregnancy loss (RPL); however, the results remain controversial. The aim of this study is to drive a more precise estimation of association between MTHFR gene polymorphisms and risk of RPL. We searched PubMed, EMBASE, Cochrane library, Web of Science and China Knowledge Resource Integrated Database for papers on MTHFR gene C677T and A1298C polymorphisms and RPL risk. The pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of association in the homozygous model, heterozygous model, dominant model, recessive model and an additive model. The software STATA (Version 13.0) was used for statistical analysis. Overall, 57 articles were included in the final meta-analysis. In maternal group the MTHFR C677T polymorphism showed pooled odds ratios for the homozygous comparison [OR = 2.285, 95 % CI (1.702, 3.067)] and the MTHFR A1298C polymorphism showed pooled odds ratios for recessive model [OR = 1.594, 95 % CI (1.136, 2.238)]. In fetal group the MTHFR C677T polymorphism showed pooled odds ratios for dominant model [OR = 1.037, 95 % CI (0.567, 1.894)] and the MTHFR A1298C polymorphism showed pooled odds ratios for dominant model [OR = 1.495, 95 % CI (1.102, 2.026)]. In summary, the results of our meta-analysis indicate that maternal and paternal MTHFR gene C677T and A1298C polymorphisms are associated with RPL. We also observed a significant association between fetal MTHFR A1298C polymorphism and RPL but not C677T.

  13. The ABO blood group is a trans-species polymorphism in primates.

    Science.gov (United States)

    Ségurel, Laure; Thompson, Emma E; Flutre, Timothée; Lovstad, Jessica; Venkat, Aarti; Margulis, Susan W; Moyse, Jill; Ross, Steve; Gamble, Kathryn; Sella, Guy; Ober, Carole; Przeworski, Molly

    2012-11-06

    The ABO histo-blood group, the critical determinant of transfusion incompatibility, was the first genetic polymorphism discovered in humans. Remarkably, ABO antigens are also polymorphic in many other primates, with the same two amino acid changes responsible for A and B specificity in all species sequenced to date. Whether this recurrence of A and B antigens is the result of an ancient polymorphism maintained across species or due to numerous, more recent instances of convergent evolution has been debated for decades, with a current consensus in support of convergent evolution. We show instead that genetic variation data in humans and gibbons as well as in Old World monkeys are inconsistent with a model of convergent evolution and support the hypothesis of an ancient, multiallelic polymorphism of which some alleles are shared by descent among species. These results demonstrate that the A and B blood groups result from a trans-species polymorphism among distantly related species and has remained under balancing selection for tens of millions of years-to date, the only such example in hominoids and Old World monkeys outside of the major histocompatibility complex.

  14. EVC gene polymorphisms and risks of isolated hypospadias - a preliminary study.

    Science.gov (United States)

    Kowal, Andrzej; Mostowska, Adrianna; Mydlak, Dariusz; Eberdt-Gołąbek, Bożena; Misztal, Matthew; Jagodziński, Paweł P; Hozyasz, Kamil K

    2015-01-01

    Hypospadias has a complex etiology with both genetic and environmental factors contributing to the condition. Urogenital abnormalities including hypospadias, are found in 22% of cases with Ellis van Creveld syndrome (EvC). Mutations in the EVC gene can cause major and minor anomalies, which form phenotypes that partially overlap with those present in EvC. The aim of this study was to evaluate the association between nucleotide variants of the EVC gene and the risk of hypospadias. Four single nucleotide polymorphisms (SNPs) of the EVC gene (rs3774856, rs2302075, rs1383180, rs7680768) were taken under investigation in 96 patients with isolated hypospadias and 284 matched controls. Genotyping of all polymorphisms was carried out by PCR and followed by appropriate restriction enzyme digestion (PCR-RFLP). Individuals homozygous for the SNP rs2302075 (p.Thr449Lys) showed an elevated risk for hypospadias. Haplotypes containing the rs2302075 variant also revealed modest associations with hypospadias, which did not survive multiple testing corrections. None of the other tested EVC polymorphisms displayed significant association with the risk of hypospadias, either in dominant or recessive inheritance models. The results of this study suggest that polymorphic variants of the EVC gene do not substantially contribute to the risk of hypospadias based on our study population. However, further studies should help to clarify the relationship between polymorphisms of EVC and hypospadias.

  15. EVC gene polymorphisms and risks of isolated hypospadias – a preliminary study

    Science.gov (United States)

    Kowal, Andrzej; Mostowska, Adrianna; Mydlak, Dariusz; Eberdt-Gołąbek, Bożena; Misztal, Matthew; Jagodziński, Paweł P.

    2015-01-01

    Introduction Hypospadias has a complex etiology with both genetic and environmental factors contributing to the condition. Urogenital abnormalities including hypospadias, are found in 22% of cases with Ellis van Creveld syndrome (EvC). Mutations in the EVC gene can cause major and minor anomalies, which form phenotypes that partially overlap with those present in EvC. The aim of this study was to evaluate the association between nucleotide variants of the EVC gene and the risk of hypospadias. Material and methods Four single nucleotide polymorphisms (SNPs) of the EVC gene (rs3774856, rs2302075, rs1383180, rs7680768) were taken under investigation in 96 patients with isolated hypospadias and 284 matched controls. Genotyping of all polymorphisms was carried out by PCR and followed by appropriate restriction enzyme digestion (PCR-RFLP). Results Individuals homozygous for the SNP rs2302075 (p.Thr449Lys) showed an elevated risk for hypospadias. Haplotypes containing the rs2302075 variant also revealed modest associations with hypospadias, which did not survive multiple testing corrections. None of the other tested EVC polymorphisms displayed significant association with the risk of hypospadias, either in dominant or recessive inheritance models. Conclusions The results of this study suggest that polymorphic variants of the EVC gene do not substantially contribute to the risk of hypospadias based on our study population. However, further studies should help to clarify the relationship between polymorphisms of EVC and hypospadias. PMID:26251756

  16. Comparative genome-wide polymorphic microsatellite markers in Antarctic penguins through next generation sequencing

    Science.gov (United States)

    Vianna, Juliana A.; Noll, Daly; Mura-Jornet, Isidora; Valenzuela-Guerra, Paulina; González-Acuña, Daniel; Navarro, Cristell; Loyola, David E.; Dantas, Gisele P. M.

    2017-01-01

    Abstract Microsatellites are valuable molecular markers for evolutionary and ecological studies. Next generation sequencing is responsible for the increasing number of microsatellites for non-model species. Penguins of the Pygoscelis genus are comprised of three species: Adélie (P. adeliae), Chinstrap (P. antarcticus) and Gentoo penguin (P. papua), all distributed around Antarctica and the sub-Antarctic. The species have been affected differently by climate change, and the use of microsatellite markers will be crucial to monitor population dynamics. We characterized a large set of genome-wide microsatellites and evaluated polymorphisms in all three species. SOLiD reads were generated from the libraries of each species, identifying a large amount of microsatellite loci: 33,677, 35,265 and 42,057 for P. adeliae, P. antarcticus and P. papua, respectively. A large number of dinucleotide (66,139), trinucleotide (29,490) and tetranucleotide (11,849) microsatellites are described. Microsatellite abundance, diversity and orthology were characterized in penguin genomes. We evaluated polymorphisms in 170 tetranucleotide loci, obtaining 34 polymorphic loci in at least one species and 15 polymorphic loci in all three species, which allow to perform comparative studies. Polymorphic markers presented here enable a number of ecological, population, individual identification, parentage and evolutionary studies of Pygoscelis, with potential use in other penguin species. PMID:28898354

  17. Vitamin D Receptor gene polymorphism may predict response to vitamin D intake and bone turnover

    Directory of Open Access Journals (Sweden)

    G Ahangari

    2010-01-01

    Full Text Available "n  "n Background and the purpose of the study:The molecular and functional basis of the VDR polymorphisms is fundamental to appreciate their potential clinical implications. The rationale of this study was to determine the level of serum vitamin D response to vitamin D intake in different genotypes of VDR (FokI polymorphism and its effect on the bone turnover in postmenopausal women.  Methods:The subjects for the study were 312 pre and post-menopausal women aged between 20-75 year randomly selected from the participants of Iranian multicenter osteoporosis study. After an overnight fast, 4ml of peripheral blood was taken and centrifuged to separate serum for measurement of serum parathyroid hormone, 25 hydroxyvitamin D, osteocalcin and cross laps. The FokI polymorphism in exon 2 of the VDR gene was detected by the polymerase chain reaction-restriction fragment length polymorphism Results and major conclusion: FOKI genotype predicted serum cross laps after adjustment for age, menopausal status, serum vitamin D (p<0.001 but did not find significant prediction regarding serum osteocalcin (p=0.3.Also in this model FOKI genotype predicted serum vitamin D after adjustment for age, menopausal status, calcium and vitamin D intake (p<0.001.VDR gene polymorphism may modifies response to vitamin D intake and predicts bone turnover.   "n 

  18. Association between MTHFR gene polymorphisms and the risk of autism spectrum disorders: a meta-analysis.

    Science.gov (United States)

    Pu, Danhua; Shen, Yiping; Wu, Jie

    2013-10-01

    Methylenetetrahydrofolate reductase (MTHFR) is essential for DNA biosynthesis and the epigenetic process of DNA methylation, and its gene polymorphisms have been implicated as risk factors for birth defects, neurological disorders, and cancers. However, reports on the association of MTHFR polymorphisms with autism spectrum disorders (ASD) are inconclusive. Therefore, we investigated the relationship of the MTHFR polymorphisms (C677T and A1298C) and the risk of ASD by meta-analysis. Up to December 2012, eight case-control studies involving 1672 patients with ASD and 6760 controls were included for meta-analysis. The results showed that the C677T polymorphism was associated with significantly increased ASD risk in all the comparison models [T vs. C allele (frequency of allele): odds ratio (OR) = 1.42, 95% confidence interval (CI): 1.09-1.85; CT vs. CC (heterozygote): OR = 1.48, 95% CI: 1.09-2.00; TT vs. CC (homozygote): OR = 1.86, 95% CI: 1.08-3.20; CT+TT vs. CC (dominant model): OR = 1.56, 95% CI: 1.12-2.18; and TT vs. CC+CT (recessive model): OR = 1.51, 95% CI: 1.02-2.22], whereas the A1298C polymorphism was found to be significantly associated with reduced ASD risk but only in a recessive model (CC vs. AA+AC: OR = 0.73, 95% CI: 0.56-0.97). In addition, we stratified the patient population based on whether they were from a country with food fortification of folic acid or not. The meta-analysis showed that the C677T polymorphism was found to be associated with ASD only in children from countries without food fortification. Our study indicated that the MTHFR C677T polymorphism contributes to increased ASD risk, and periconceptional folic acid may reduce ASD risk in those with MTHFR 677C>T polymorphism. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

  19. The association between MTHFR polymorphisms and cervical cancer risk: a system review and meta analysis.

    Science.gov (United States)

    Yi, Ke; Yang, LingYun; Lan, Zhu; Xi, MingRong

    2016-09-01

    Methylenetetrahydrofolate reductase (MTHFR) plays an important role in determining the proportions of folate coenzymes for DNA synthesis or DNA methylation. Published data on the association between the MTHFR polymorphisms and cervical risk are controversial. A meta-analysis was performed to assess whether the polymorphisms of MTHFR are associated with cervical cancer risk. Medline, Embase, China National Knowledge Infrastructure and Chinese Biomedicine Databases were searched to identify eligible studies. Pooled odds ratios (ORs) and 95 % confidence intervals (CIs) for MTHFR C677T and MTHFR A1298C polymorphisms and cervical cancer were appropriately derived from fixed-effects or random effects models. Five different ORs were calculated: (1) allele contrast (C vs. T), (2) homozygous comparison (CC vs. TT), (3) heterozygous comparison (CC vs. CT), (4) dominant model (CC vs. CT+TT) and (5) recessive model (CC+CT vs. TT). A total of 13 studies, which included 12 studies for MTHFR C677T (2332 cases and 3000 controls) and five studies for A1298C polymorphisms (677 cases and 1191 controls), were enrolled in this meta-analysis. The pooled analyses revealed that MTHFR C677T polymorphism was not associated with cervical cancer risk; while the A1298C polymorphism had a significant association with increased cervical cancer risk in allele contrast, heterozygote comparison and dominant model (A C, OR = 0.84, 95 % CI = 0.71-0.98; AA vs. CC OR = 0.72, 95 % CI = 0.59-0.89; AA vs. AC+CC, OR = 0.72, 95 % CI = 0.59-0.88). The significant associations between MTHFR A1298C polymorphism and cervical cancer were found among Asians and population-based case-control studies. This study indicated that the MTHFR C677T may be no associated with cervical cancer risk, and yet the MTHFR A1298C polymorphism may be a risk factor for cervical cancer.

  20. Crystallization of microparticulate pure polymorphs of active pharmaceutical ingredients using CO 2-expanded solvents

    OpenAIRE

    Veciana, J.; Sala, S.; Córdoba, A.; Moreno Calvo, E.; Elizondo, E.; Muntó, M.; Rojas, P.E.; Larrayoz Iriarte, María Angeles; Ventosa, N.

    2012-01-01

    The feasibility of the Depressurization of an Expanded Liquid Organic Solution (DELOS) method to process different active pharmaceutical ingredients (APIs) as finely divided powders with narrow particle size distribution, high crystallinity degree, high polymorphic purity, and free from residual solvent has been demonstrated. Cholesterol, acetylsalicylic acid (aspirin), naproxen, acetaminophen, and ibuprofen were chosen as model drugs. It has been demonstrated that the supersat...

  1. Meta-Analysis of the Association between Mir-196a-2 Polymorphism and Cancer Susceptibility

    International Nuclear Information System (INIS)

    Zhang, Huan; Su, Yu-liang; Yu, Herbert; Qian, Bi-yun

    2012-01-01

    MicroRNA plays a vital role in gene expression, and microRNA dysregulation is involved in carcinogenesis. The miR-196a-2 polymorphism rs11614913 is reportedly associated with cancer susceptibility. This meta-analysis was performed to assess the overall association of miR-196a-2 with cancer risk. A total of 27 independent case-control studies involving 10,435 cases and 12,075 controls were analyzed for the rs11614913 polymorphism. A significant association was found between rs11614913 polymorphism and cancer risk in four genetic models (CT vs. TT, OR=1.15, 95%CI=1.05–1.27; CC vs. TT, OR=1.23, 95%CI=1.08–1.39; Dominant model, OR=1.17, 95%CI=1.06–1.30; Additive model, OR=1.08, 95%CI=1.01–1.14). In the subgroup analysis of different tumor types, the C allele was associated with increased risk of lung, breast, and colorectal cancer, but not with liver, gastric, or esophageal cancer. In the subgroup analysis by ethnicity, a significantly increased risk of cancer was found among Asians in all genetic models, but no associations were found in the Caucasian subgroup. The meta-analysis demonstrated that the miR-196a-2 polymorphism is associated with cancer susceptibility, especially lung cancer, colorectal cancer, and breast cancer among Asian populations

  2. Transposition rates of Mycobacterium tuberculosis IS6110 restriction fragment length polymorphism patterns

    NARCIS (Netherlands)

    Eilers, Paul H. C.; van Soolingen, Dick; Thi Ngoc Lan, Nguyen; Warren, Rob M.; Borgdorff, Martien W.

    2004-01-01

    To determine the rate at which IS6110 restriction fragment length polymorphism (RFLP) patterns in Mycobacterium tuberculosis change over time, we applied a smooth nonparametric survival model to several data sets, including data from previous publications on the rate of change. The results strongly

  3. Avian Clock gene polymorphism : evidence for a latitudinal cline in allele frequencies

    NARCIS (Netherlands)

    Johnsen, A.; Fidler, A. E.; Kuhn, S.; Carter, K. L.; Hoffmann, A.; Barr, I. R.; Biard, C.; Charmantier, A.; Eens, M.; Korsten, P.; Siitari, H.; Tomiuk, J.; Kempenaers, B.

    2007-01-01

    In comparison with most animal behaviours, circadian rhythms have a well-characterized molecular genetic basis. Detailed studies of circadian clock genes in 'model' organisms provide a foundation for interpreting the functional and evolutionary significance of polymorphic circadian clock genes found

  4. Polymorphisms in VEGF-A are associated with COPD risk in the ...

    Indian Academy of Sciences (India)

    In this study, we examined and validated how common variants contribute to susceptibility to chronic obstructive pulmonarydisease (COPD) in the Han Chinese population. Here, we genotyped 18 nucleotide polymorphisms and evaluated their associationwith COPD using chi-square test and genetic model analysis (246 ...

  5. Polymorphisms of Selected DNA Repair Genes and Lung Cancer in Chromium Exposure.

    Science.gov (United States)

    Halasova, E; Matakova, T; Skerenova, M; Krutakova, M; Slovakova, P; Dzian, A; Javorkova, S; Pec, M; Kypusova, K; Hamzik, J

    2016-01-01

    Chromium is a well-known mutagen and carcinogen involved in lung cancer development. DNA repair genes play an important role in the elimination of genetic changes caused by chromium exposure. In the present study, we investigated the polymorphisms of the following DNA repair genes: XRCC3, participating in the homologous recombination repair, and hMLH1 and hMSH2, functioning in the mismatch repair. We focused on the risk the polymorphisms present in the development of lung cancer regarding the exposure to chromium. We analyzed 106 individuals; 45 patients exposed to chromium with diagnosed lung cancer and 61 healthy controls. Genotypes were determined by a PCR-RFLP method. We unravelled a potential for increased risk of lung cancer development in the hMLH1 (rs1800734) AA genotype in the recessive model. In conclusion, gene polymorphisms in the DNA repair genes underscores the risk of lung cancer development in chromium exposed individuals.

  6. Characterisation and cross-amplification of polymorphic microsatellite loci in ant-associated root-aphids

    DEFF Research Database (Denmark)

    Ivens, A.B.F.; Kronauer, Daniel Jan Christoph; Boomsma, J.J.

    2011-01-01

    Twenty-six polymorphic microsatellite loci were developed for four species of ant-associated root-aphids: Geoica utricularia, Forda marginata, Tetraneura ulmi and Anoecia corni. We found up to 9 alleles per locus, with an average of 4.8. We also report polymorphic cross-amplification of eleven...... of these markers between different pairs of study species. Furthermore, we tested previously published aphid microsatellites and found one locus developed for Pemphigus bursarius to be polymorphic in G. utricularia. These microsatellite markers will be useful to study the population structure of aphids associated...... with the ant Lasius flavus and possibly other ants. Such studies are relevant because: 1. L. flavus mounds and their associated flora and fauna are often key components in protected temperate grasslands, and 2. L. flavus and its diverse community of root-aphids provide an interesting model system for studying...

  7. Polymorphism, Intermolecular Interactions, and Spectroscopic Properties in Crystal Structures of Sulfonamides.

    Science.gov (United States)

    Sainz-Díaz, C Ignacio; Francisco-Márquez, Misaela; Soriano-Correa, Catalina

    2018-01-01

    The antibiotics family of sulfonamides has been used worldwide intensively in human therapeutics and farm livestock during decades. Intermolecular interactions of these sulfamides are important to understand their bioactivity and biodegradation. These interactions are also responsible for their supramolecular structures. The intermolecular interactions in the crystal polymorphs of the sulfonamides, sulfamethoxypyridazine, and sulfamethoxydiazine, as models of sulfonamides, have been studied by using quantum mechanical calculations. Different conformations in the sulphonamide molecules have been detected in the crystal polymorphs. Several intermolecular patterns have been studied to understand the molecular packing behavior in these antibiotics. Strong intermolecular hydrogen bonds and π-π interactions are the main driving forces for crystal packing in these sulfonamides. Different stability between polymorphs can explain the experimental behavior of these crystal forms. The calculated infrared spectroscopy frequencies explain the main intermolecular interactions in these crystals. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  8. Effects of CSN3 and LGB gene polymorphisms on production traits in beef cattle

    Directory of Open Access Journals (Sweden)

    Rogério A. Curi

    2005-01-01

    Full Text Available The objective of the present study was to estimate the allele and genotype frequencies of the CSN3/HinfI and LGB/HaeIII gene polymorphisms in beef cattle belonging to different genetic groups, and to determine the effects of these polymorphisms on growth and carcass traits in these animals, which are submitted to an intensive production model. Genotyping was performed on 79 Nelore, 30 Canchim (5/8 Charolais + 3/8 Zebu and 275 crossbred cattle originating from the crosses of Simmental (n = 30 and Angus (n = 245 sires with Nelore females. Body weight, weight gain, dressing percentage, longissimus dorsi area and backfat thickness were fitted using the GLM procedure, and least square means of the genotypes were compared by the F test. The results showed that the CSN3/HinfI and LGB/HaeIII polymorphisms did not have any effect on growth or carcass traits (p > 0.05.

  9. Analysis of three genetic polymorphisms in Malaysian essential ...

    African Journals Online (AJOL)

    Analysis of three genetic polymorphisms in Malaysian essential hypertensive and type 2 diabetic subjects. ... Genotyping of all the three polymorphisms was performed by PCR-RFLP method with the respective primers and restriction enzymes. The genotypic and allelic frequencies of the respective polymorphisms of the ...

  10. Upper petal lip colour polymorphism in Collinsia heterophylla ...

    Indian Academy of Sciences (India)

    Understanding the genetics of a polymorphic trait is important to predict its likely evolution. In Collinsia heterophylla, the upper petal lip colour can be either be white or white with a purple band, while the lower petal lip colour is invariably purple. Because the corolla is only partly polymorphic, the polymorphism can not have ...

  11. Analysis of TLR polymorphisms in typhoid patients and ...

    African Journals Online (AJOL)

    Ilakkia Sivaji

    2016-01-20

    Jan 20, 2016 ... implicated the genetic variations (polymorphisms) in TLR genes to influence the host susceptibility to infectious diseases. However, the available literature on TLR polymorphism and susceptibility to typhoid fever is unclear. Aim: This study aimed to investigate the polymorphism of TLRs 1, 2, 4 and 5 in ...

  12. Do prion protein gene polymorphisms induce apoptosis in non ...

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... Genetic variations such as single nucleotide polymorphisms (SNPs) in prion protein coding gene, Prnp, greatly affect susceptibility to prion diseases in mammals. Here, the coding region of Prnp was screened for polymorphisms in redeared turtle, Trachemys scripta. Four polymorphisms, L203V, N205I, ...

  13. Synchrotron X-ray diffuse scattering from a stable polymorphic material: terephthalic acid, C 8 H 6 O 4

    Energy Technology Data Exchange (ETDEWEB)

    Goossens, D. J.; Chan, E. J.

    2017-01-31

    Terephthalic acid (TPA, C8H6O4) is an industrially important chemical, one that shows polymorphism and disorder. Three polymorphs are known, two triclinic [(I) and (II)] and one monoclinic (III). Of the two triclinic polymorphs, (II) has been shown to be more stable in ambient conditions. This paper presents models of the local order of polymorphs (I) and (II), and compares the single-crystal diffuse scattering (SCDS) computed from the models with that observed from real crystals. TPA shows relatively weak and less-structured diffuse scattering than some other polymorphic materials, but it does appear that the SCDS is less well modelled by a purely harmonic model in polymorph (I) than in polymorph (II), according to the idea that the diffuse scattering is sensitive to anharmonicity that presages a structural phase transition. The work here verifies that displacive correlations are strong along the molecular chains and weak laterally, and that it is not necessary to allow the —COOH groups to librate to successfully model the diffuse scattering – keeping in mind that the data are from X-ray diffraction and not directly sensitive to H atoms.

  14. Association between MDR1 gene polymorphisms and Parkinson's disease in Asian and Caucasian populations: a meta-analysis.

    Science.gov (United States)

    Ahmed, Shiek S S J; Husain, R S Akram; Kumar, Suresh; Ramakrishnan, V

    2016-09-15

    Parkinson's disease (PD) is a complex neurodegenerative disease, its etiology is largely unknown. Studies demonstrate the association of genetic and environment factors in causing neuronal degeneration. Reports suggest that the multi-drug resistance gene (MDR1) plays a vital role in preventing the toxic substance in entering the brain, which is associated with PD. However, the association between the MDR1 polymorphisms (C1236T and C3435T) and its susceptibility to PD is inconclusive. Meta analysis was carried by retrieving literatures from databases to search the case-control studies on the associations between the MRD1 polymorphisms and PD. The pooled odds ratios (ORs) and its 95% confidence intervals (CIs) were calculated using fixed and random model to determine the association between the polymorphisms and PD susceptibility. Significant association was noticed for C1236T polymorphism and PD risk in the recessive model OR=0.80, 95% CI=0.66-0.97. Further, ethnicity based analysis showed significant association for C1236T in allelic model of Asian population and also in the recessive models of both Asian and Caucasian populations. However, insignificant associations were noticed for C3435T in all the four models. Overall, the analysis suggested that MDR1 C1236T polymorphism substantially contribute to Parkinson's disease in the recessive genetic model. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. The effect of six polymorphisms in the Apolipoprotein B gene on parameters of lipid metabolism in a Danish population

    DEFF Research Database (Denmark)

    Bentzen, J; Jørgensen, T; Fenger, M

    2002-01-01

    on fasting levels of triglyceride, VLDL-, LDL-, HDL- and total cholesterol and on body mass index (BMI) in a cohort of 2656 Danes aged 40-70 years using a linear model correcting for the effects of gender, age, BMI, smoking, alcohol consumption and physical activity. The codon 2488 polymorphism was the most...... influential of the tested polymorphisms, significantly influencing triglyceride (P = 0.002), LDL-cholesterol (P cholesterol (P = 0.006) and total cholesterol (P = 0.0001). The codon 2712 polymorphism had an impact on triglyceride (P = 0.007) and VLDL-cholesterol (P = 0.001), while...... the codon 71 polymorphism influenced LDL- and total cholesterol (P = 0.04 and P = 0.02, respectively). An interaction between smoking and codon 591 (P = 0.03) and smoking and codon 3611 (P = 0.02) on BMI was observed, as well as modest interactions between codon 3611 and codons 2488 and 2712 on lipid...

  16. Study on relationship between microsatellite polymorphism and ...

    African Journals Online (AJOL)

    Jane

    2010-12-13

    Dec 13, 2010 ... Image Analysis Software. Statistical analysis. Genetic polymorphism analysis. Allele frequencies were computed by gene counting ..... Wang GL, Mao XZ, George HD, Zhao ZS, Zhang LJ, Zeng YQ (2003). DNA tests in Hu sheep and Han sheep (small tail) showed the existence of Booroola (FecB) mutation, ...

  17. RESEARCH ARTICLE Analysis of polymorphisms and selective ...

    Indian Academy of Sciences (India)

    2017-01-27

    Jan 27, 2017 ... collected in Keningau, haplotypes K2, K9, K10, K11, K12, K13 and K14 were exclusively from Kudat while haplotypes K6 and K8 were found only from Kota Kinabalu. Haplotypes K4, K5 and K7 consisted of samples from all the three regions, indicating similar patterns of polymorphism from the different.

  18. Genetic polymorphism of serotonin transporter 5-HTTLPR ...

    Indian Academy of Sciences (India)

    ues to be the second major cause of death in the world. (WHO 2002) and it is associated with economic losses to ..... polymorphism with smoking behavior among adolescents. Am. J. Med. Genet. B. Neuropsychiatr. Genet. 135, 73–78. ... for the treatment of obesity. Curr. Drug Targets 6, 201–213. Heils A., Teufel A., Petri S., ...

  19. Isolation and characterization of polymorphic microsatellite markers ...

    African Journals Online (AJOL)

    Flax (Linum usitatissimum L.) is the third largest natural fiber crop and one of the five major oil crops in the world. ... These novel polymorphic microsatellite loci will be useful in genetic linkage map construction, germplasm classification and identification, gene identification and QTL mapping, and marker-assisted selection ...

  20. Characterization of novel polymorphic microsatellite markers from ...

    Indian Academy of Sciences (India)

    polymorphic microsatellite markers from the cDNA library of Japanese scallop Mizuhopecten yessoensis and cross-species amplification in bay scallop ... Keywords. microsatellite markers; cDNA library; Mizuhopecten yessoensis; Argopecten irradians. .... EST databases as a source for molecular markers: lessons from.

  1. LIG1 polymorphisms: the Indian scenario

    Indian Academy of Sciences (India)

    Elucidation of the genetic diversity and relatedness of the subpopulations of India may provide a unique resource for future analysis of genetic association of several critical community-specific complex diseases.We performed a comprehensive exploration of single nucleotide polymorphisms (SNPs) within the gene DNA ...

  2. Endothelial nitric oxide synthase gene polymorphisms associated ...

    African Journals Online (AJOL)

    Endothelial nitric oxide synthase (NOS3) is involved in key steps of immune response. Genetic factors predispose individuals to periodontal disease. This study's aim was to explore the association between NOS3 gene polymorphisms and clinical parameters in patients with periodontal disease. Genomic DNA was obtained ...

  3. Erythrocyte potassium and glutathione polymorphism determination ...

    African Journals Online (AJOL)

    Jane

    This research is aimed at determining the erythrocyte potassium and glutathione polymorphisms and also to identify the relationship among the various blood parameters in Saanen x Malta crossbred goat raised in Turkey. The allele gene frequencies of KH and KL associated with the potassium concentration.

  4. Erythrocyte potassium and glutathione polymorphism determination ...

    African Journals Online (AJOL)

    This research is aimed at determining the erythrocyte potassium and glutathione polymorphisms and also to identify the relationship among the various blood parameters in Saanen x Malta crossbred goat raised in Turkey. The allele gene frequencies of KH and KL associated with the potassium concentration were ...

  5. High-Pressure Polymorphism in Orthoamphiboles

    Science.gov (United States)

    Finkelstein, G. J.; Zhang, D.; Shelton, H.; Dera, P.

    2017-12-01

    Amphiboles are double-chain silicate minerals that are the structurally hydrated counterpart to single-chain, anhydrous pyroxenes. They may play an important role in the earth as a carrier for volatiles in subduction zones, as well as a generator for seismic anisotropy in the upper mantle. Recent work has described previously unrecognized high-pressure polymorphism at low temperatures in a variety of pyroxene minerals, which may be relevant for the structure and dynamics of thick, cold, subducted slabs. However, high-pressure polymorphism in amphiboles above a few GPa in pressure has not been well explored, and if similar polymorphism to pyroxenes exists in this mineral family, it may affect the extent and depth of volatile transport in amphiboles, as well as their rheological properties. At low temperatures and high pressures, orthopyroxenes undergo crystal structure transitions at lower pressures than clinopyroxenes (10-30 GPa vs. > 50 GPa), so for this study we have investigated polymorphism in the anthophyllite-gedrite (Al-free and Al rich) orthoamphibole solid solution series. Using neon gas-loaded diamond anvil cells, we compressed both phases to a maximum pressure of 31 GPa, and observed transitions to new monoclinic structures in both endmembers. In this presentation, we will discuss the details of these transitions and implications for the earth's interior.

  6. Methylenetetrahydrofolate Reductase C677T Polymorphism And ...

    African Journals Online (AJOL)

    for Coronary artery disease (CAD). This study included 65 subjects (40 cases & 25 controls). For all participants in this study total lipids profile, Apo A1, homoysteine, blood glucose, folic acid and genetic polymorphism of MTHFR were done. The percentage distribution of the different genotypes in the study population (all ...

  7. Association between the polymorphisms of matrix ...

    African Journals Online (AJOL)

    Nadia I Sewelam

    2013-02-23

    Feb 23, 2013 ... tion fragment length polymorphism (RFLP) for amplified genomic DNA. The frequencies of the com- ... Meanwhile, the race selection should be paid more atten- tion since the pathogenesis of a disease might have different bases in different racial population groups. У 2013 Ain Shams University. Production ...

  8. genes polymorphism on tacrolimus concentrations and dosage

    African Journals Online (AJOL)

    Marwa Helal

    2016-11-30

    Nov 30, 2016 ... transplant donors and recipients on blood level and dose requirements of oral tacrolimus, to help in designing an .... groups [11]. The aim of this pilot study is to assess the influence of ABCB1. (3435 C>T) and CYP3A5 (6986 A>G) genes polymorphisms of both donors and ..... liver graft rejection [24].

  9. Application of randomly amplified polymorphic DNA (RAPD ...

    African Journals Online (AJOL)

    Jane

    2011-10-10

    Oct 10, 2011 ... Polymerase chain reaction (PCR) based molecular markers have become increasingly popular for fingerprinting and cultivars identification since the development of PCR technology. (Saiki et al., 1988). RAPD-PCR (randomly amplified polymorphic DNA) was first conducted by Williams et al. (1990).

  10. Correlation between serum esterase polymorphism and production ...

    African Journals Online (AJOL)

    The polymorphism of serum esterase (Es) of Henan Yuxi fat-tailed sheep was detected through polyacrylamide gel electrophoresis (PAGE), and the correlation between serum esterase and productivity was analyzed. The research result indicated that there are two alleles on the Es loci of Henan Yuxi fat-tailed sheep: Es+ ...

  11. Chromosomal polymorphism in the Sporothrix schenckii complex.

    Science.gov (United States)

    Sasaki, Alexandre A; Fernandes, Geisa F; Rodrigues, Anderson M; Lima, Fábio M; Marini, Marjorie M; Dos S Feitosa, Luciano; de Melo Teixeira, Marcus; Felipe, Maria Sueli Soares; da Silveira, José Franco; de Camargo, Zoilo P

    2014-01-01

    Sporotrichosis is a polymorphic disease caused by a complex of thermodimorphic fungi including S. brasiliensis, S. schenckii sensu stricto (s. str.), S. globosa and S. luriei. Humans and animals can acquire the disease through traumatic inoculation of propagules into the subcutaneous tissue. Despite the importance of sporotrichosis as a disease that can take epidemic proportions there are just a few studies dealing with genetic polymorphisms and genomic architecture of these pathogens. The main objective of this study was to investigate chromosomal polymorphisms and genomic organization among different isolates in the S. schenckii complex. We used pulsed field gel electrophoresis (PFGE) to separate chromosomal fragments of isolated DNA, followed by probe hybridization. Nine loci (β-tubulin, calmodulin, catalase, chitin synthase 1, Internal Transcribed Spacer, Pho85 cyclin-dependent kinase, protein kinase C Ss-2, G protein α subunit and topoisomerase II) were mapped onto chromosomal bands of Brazilian isolates of S. schenckii s. str. and S. brasiliensis. Our results revealed the presence of intra and interspecies polymorphisms in chromosome number and size. The gene hybridization analysis showed that closely related species in phylogenetic analysis had similar genetic organizations, mostly due to identification of synteny groups in chromosomal bands of similar sizes. Our results bring new insights into the genetic diversity and genome organization among pathogenic species in the Sporothrix schenckii complex.

  12. Combined effect between two functional polymorphisms of ...

    Indian Academy of Sciences (India)

    A recent study in four populations (Ireland, UK, Australia and Finland) reported an allelic association between betaine/GABA transporter-1 (-1 or 612) and mesial temporal lobe epilepsy with hippocampal sclerosis. To demonstrate the association between 612 gene polymorphisms and TLE, TaqMan ...

  13. Effect of matrix metalloproteinase promoter polymorphisms on ...

    Indian Academy of Sciences (India)

    large-scale studies regarding gene–gene and gene–environment interactions are needed in the future. [Ye H., He Y., Wang J., Song T., Lan Z., Zhao Y. and Xi M. 2016 Effect of matrix metalloproteinase promoter polymorphisms on endometriosis and adenomyosis risk: evidence from a meta-analysis. J. Genet. 95, 611–619].

  14. Genetic Polymorphisms of Osteopontin in Association with ...

    African Journals Online (AJOL)

    Purpose: To determine the association of osteopontin (OPN) polymorphisms with ankylosing spondylitis (AS). Methods: A total of 120 cases diagnosed with AS and 106 age- and sex-matched healthy controls were recruited. All the patients were human leukocyte antigen (HLA)-B27 positive. Three single nucleotide ...

  15. Genetic diversity among sorghum landraces and polymorphism ...

    African Journals Online (AJOL)

    Microsatellites or simple sequence repeats (SSR) are playing an important role in molecular breeding. This investigation was undertaken to study the genetic diversity among local sorghum accessions from two different agro-ecological zones of Burkina Faso and to assess the polymorphism within local improved varieties ...

  16. Genetic polymorphism of serotonin transporter 5-HTTLPR ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 90; Issue 1. Genetic polymorphism of serotonin transporter 5-HTTLPR: involvement in smoking behaviour ... The present review examines the role of the serotonin transporter gene (5-HTT) in smoking behaviour and investigating studies that showed association of 5-HTT gene ...

  17. Endothelial nitric oxide synthase gene polymorphisms associated ...

    African Journals Online (AJOL)

    STORAGESEVER

    2010-05-24

    May 24, 2010 ... NOS3 gene polymorphisms and clinical parameters in patients with periodontal disease. Genomic DNA was obtained from the ... (Serrano et al., 2004),. Behcet's disease (Karasneh et al., 2005), diabetes (Monti ... EDTA-treated peripheral venous blood using the salting-out method. (Miller et al., 1988).

  18. Intraspecific chromosomal and genetic polymorphism in Brassica ...

    Indian Academy of Sciences (India)

    2014-04-16

    Apr 16, 2014 ... A. V., Lemesh V. A. and Muravenko O. V. 2014 Intraspecific chromosomal and genetic polymorphism in Brassica napus L. detected by cytogenetic and molecular markers. J. Genet. ...... Howell E. C., Kearsey M. J., Jones G. H., King G. J. and Armstrong. S. J. 2008 A and C genome distinction and ...

  19. Phenotypic characterisation and molecular polymorphism of ...

    African Journals Online (AJOL)

    The study of the phenotypic characterisation and molecular polymorphism of local chicken populations was carried out in Benin on 326 chickens of the Forest ecological area and 316 of the Savannah ecological area, all were 7 months old at least. The collection of blood for the molecular typing was achieved on 121 ...

  20. Eighteen polymorphic microsatellites for domestic pigeon Columba ...

    Indian Academy of Sciences (India)

    Indian Academy of Sciences. ONLINE RESOURCES. Eighteen polymorphic microsatellites for domestic pigeon Columba livia var. domestica developed by cross species amplification of chicken markers. MUKESH1, 2∗ and S. SATHYAKUMAR1. 1Wildlife Institute of India, P. O. Box 18, Chandrabani, Dehradun 248 001, ...

  1. Single-nucleotide polymorphisms in peroxisome proliferator ...

    Indian Academy of Sciences (India)

    However, association of these polymorphisms with the metabolic syndrome and its individual components has not been well investigated in the Indian population. The Indian population harbours the maximum number of diabetics in the world who are thus more susceptible to metabolic disorders. We screened a South ...

  2. MYO9B polymorphisms in multiple sclerosis

    DEFF Research Database (Denmark)

    Kemppinen, A.; Suvela, M.; Tienari, P.J.

    2009-01-01

    Single-nucleotide polymorphisms (SNPs) in the 3' region of myosin IXB (MYO9B) gene have recently been reported to associate with different inflammatory or autoimmune diseases. We monitored for the association of MYO9B variants to multiple sclerosis (MS) in four Northern European populations. First...

  3. LIG1 polymorphisms: the Indian scenario

    Indian Academy of Sciences (India)

    2014-08-14

    Aug 14, 2014 ... LIG1; MAF; SNP; HapMap. Journal of Genetics, Vol. 93, No. 2, August 2014. 459 ..... The CEPH population subgroup consists of 90 samples from 30 trios (two parents and one child) belonging to ..... studies on the association of LIG1 polymorphisms with any complex disorder within Indian subpopulations.

  4. Association between the polymorphisms of angiotensin converting ...

    African Journals Online (AJOL)

    Detailed history taking was done with stress on age, family history, menstrual, obstetric, medical and drug history. Physical examination including body mass index calculation was done. Histopathological examination was done for tumor grading and staging. Detection of ACE gene (I/D) polymorphism by PCR and AT1R ...

  5. Association between the polymorphisms of angiotensin converting ...

    African Journals Online (AJOL)

    Rania Mohamed El Sharkawy

    2014-01-07

    Jan 7, 2014 ... Detailed history taking was done with stress on age, family history, menstrual, obstetric, medical and drug history. Physical examination including body mass index calculation was done. Histopathological examination was done for tumor grading and staging. Detection of ACE gene (I/D) polymorphism by ...

  6. Complementary DNA-amplified fragment length polymorphism ...

    African Journals Online (AJOL)

    owner

    2011-05-09

    May 9, 2011 ... Complementary DNA-amplified fragment length polymorphism (cDNA-AFLP) technology was used to analyze ... that 9 of the studied expressed sequence tags (ESTs) are related to protein modification, 12 ESTs are involved in the .... primers were used during the first strand synthesis of our cDNA synthesis ...

  7. Phenotypic characterisation and molecular polymorphism of ...

    African Journals Online (AJOL)

    PRECIOUS

    2010-01-18

    Jan 18, 2010 ... The study of the phenotypic characterisation and molecular polymorphism of local chicken populations was carried out in Benin on 326 chickens of the Forest ecological area and 316 of the Savannah ecological area, all were 7 months old at least. The collection of blood for the molecular typing was.

  8. Random amplified polymorphic DNA based genetic characterization ...

    African Journals Online (AJOL)

    Random amplified polymorphic DNA based genetic characterization of four important species of Bamboo, found in Raigad district, Maharashtra State, India. ... Bambusoideae are differentiated from other members of the family by the presence of petiolate blades with parallel venation and stamens are three, four, six or more, ...

  9. Single-nucleotide polymorphisms in peroxisome proliferator ...

    Indian Academy of Sciences (India)

    Prakash

    the metabolic syndrome (MS) and type 2 diabetes. We also investigated the correlation of these two single-nucleotide polymorphisms (SNPs) with plasma resistin levels. The C1431T SNP was associated with higher levels of plasma resistin (P = 0.017). Furthermore, C1431T was associated with resistin in different tertiles.

  10. Isolation and characterization of polymorphic microsatellites for ...

    Indian Academy of Sciences (India)

    nothing is known about the life-history connections or migra- tions between silver pomfret in the Yellow Sea and China. Sea (Zhao et al. 2011). We all know that ... liminary study on the genetic diversity of four geographic populations of silver pomfret by means of random ampli- fied polymorphic DNA (RAPD) technique.

  11. Bovine gene polymorphisms related to fat deposition and meat tenderness

    Directory of Open Access Journals (Sweden)

    Marina R.S. Fortes

    2009-01-01

    Full Text Available Leptin, thyroglobulin and diacylglycerol O-acyltransferase play important roles in fat metabolism. Fat deposition has an influence on meat quality and consumers' choice. The aim of this study was to determine allele and genotype frequencies of polymorphisms of the bovine genes, which encode leptin (LEP, thyroglobulin (TG and diacylglycerol O-acyltransferase (DGAT1. A further objective was to establish the effects of these polymorphisms on meat characteristics. We genotyped 147 animals belonging to the Nelore (Bos indicus, Canchim (5/8 Bos taurus + 3/8 Bos indicus, Rubia Gallega X Nelore (1/2 Bos taurus + 1/2 Bos indicus, Brangus Three-way cross (9/16 Bos taurus + 7/16 Bos indicus and Braunvieh Three-way cross (3/4 Bos taurus + 1/4 Bos indicus breeds. Backfat thickness, total lipids, marbling score, ribeye area and shear force were fitted, using the General Linear Model (GLM procedure of the SAS software. The least square means of genotypes and genetic groups were compared using Tukey's test. Allele frequencies vary among the genetic groups, depending on Bos indicus versus Bos taurus influence. The LEP polymorphism segregates in pure Bos indicus Nelore animals, which is a new finding. The T allele of TG is fixed in Nelore, and DGAT1 segregates in all groups, but the frequency of allele A is lower in Nelore animals. The results showed no association between the genotypes and traits studied, but a genetic group effect on these traits was found. So, the genetic background remains relevant for fat deposition and meat tenderness, but the gene markers developed for Bos taurus may be insufficient for Bos indicus.

  12. Polymorphisms in signal transducer and activator of transcription 3 and lung function in asthma

    Directory of Open Access Journals (Sweden)

    Lazarus Ross

    2005-06-01

    Full Text Available Abstract Background Identifying genetic determinants for lung function is important in providing insight into the pathophysiology of asthma. Signal transducer and activator of transcription 3 is a transcription factor latent in the cytoplasm; the gene (STAT3 is activated by a wide range of cytokines, and may play a role in lung development and asthma pathogenesis. Methods We genotyped six single nucleotide polymorphisms (SNPs in the STAT3 gene in a cohort of 401 Caucasian adult asthmatics. The associations between each SNP and forced expiratory volume in 1 second (FEV1, as a percent of predicted, at the baseline exam were tested using multiple linear regression models. Longitudinal analyses involving repeated measures of FEV1 were conducted with mixed linear models. Haplotype analyses were conducted using imputed haplotypes. We completed a second association study by genotyping the same six polymorphisms in a cohort of 652 Caucasian children with asthma. Results We found that three polymorphisms were significantly associated with baseline FEV1: homozygotes for the minor alleles of each polymorphism had lower FEV1 than homozygotes for the major alleles. Moreover, these associations persisted when we performed an analysis on repeated measures of FEV1 over 8 weeks. A haplotypic analysis based on the six polymorphisms indicated that two haplotypes were associated with baseline FEV1. Among the childhood asthmatics, one polymorphism was associated with both baseline FEV1 and the repeated measures of FEV1 over 4 years. Conclusion Our results indicate that genetic variants in STAT3, independent of asthma treatment, are determinants of FEV1 in both adults and children with asthma, and suggest that STAT3 may participate in inflammatory pathways that have an impact on level of lung function.

  13. Glutathione enzyme and selenoprotein polymorphisms associate with mercury biomarker levels in Michigan dental professionals

    International Nuclear Information System (INIS)

    Goodrich, Jaclyn M.; Wang, Yi; Gillespie, Brenda; Werner, Robert; Franzblau, Alfred; Basu, Niladri

    2011-01-01

    Mercury is a potent toxicant of concern to both the general public and occupationally exposed workers (e.g., dentists). Recent studies suggest that several genes mediating the toxicokinetics of mercury are polymorphic in humans and may influence inter-individual variability in mercury accumulation. This work hypothesizes that polymorphisms in key glutathione synthesizing enzyme, glutathione s-transferase, and selenoprotein genes underlie inter-individual differences in mercury body burden as assessed by analytical mercury measurement in urine and hair, biomarkers of elemental mercury and methylmercury, respectively. Urine and hair samples were collected from a population of dental professionals (n = 515), and total mercury content was measured. Average urine (1.06 ± 1.24 ug/L) and hair mercury levels (0.49 ± 0.63 ug/g) were similar to national U.S. population averages. Taqman assays were used to genotype DNA from buccal swab samples at 15 polymorphic sites in genes implicated in mercury metabolism. Linear regression modeling assessed the ability of polymorphisms to modify the relationship between mercury biomarker levels and exposure sources (e.g., amalgams, fish consumption). Five polymorphisms were significantly associated with urine mercury levels (GSTT1 deletion), hair mercury levels (GSTP1-105, GSTP1-114, GSS 5′), or both (SEPP1 3′UTR). Overall, this study suggests that polymorphisms in selenoproteins and glutathione-related genes may influence elimination of mercury in the urine and hair or mercury retention following exposures to elemental mercury (via dental amalgams) and methylmercury (via fish consumption). -- Highlights: ► We explore the influence of 15 polymorphisms on urine and hair Hg levels. ► Urine and hair Hg levels in dental professionals were similar to the US population. ► GSTT1 and SEPP1 polymorphisms associated with urine Hg levels. ► Accumulation of Hg in hair following exposure from fish was modified by genotype. ► GSTP1, GSS

  14. Glutathione enzyme and selenoprotein polymorphisms associate with mercury biomarker levels in Michigan dental professionals

    Energy Technology Data Exchange (ETDEWEB)

    Goodrich, Jaclyn M.; Wang, Yi [Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109 (United States); Gillespie, Brenda [Department of Biostatistics, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109 (United States); Werner, Robert [Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109 (United States); Department of Physical Medicine and Rehabilitation, University of Michigan, 325 E. Eisenhower Parkway Suite 100, Ann Arbor, MI 48108 (United States); Franzblau, Alfred [Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109 (United States); Basu, Niladri, E-mail: niladri@umich.edu [Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109 (United States)

    2011-12-15

    Mercury is a potent toxicant of concern to both the general public and occupationally exposed workers (e.g., dentists). Recent studies suggest that several genes mediating the toxicokinetics of mercury are polymorphic in humans and may influence inter-individual variability in mercury accumulation. This work hypothesizes that polymorphisms in key glutathione synthesizing enzyme, glutathione s-transferase, and selenoprotein genes underlie inter-individual differences in mercury body burden as assessed by analytical mercury measurement in urine and hair, biomarkers of elemental mercury and methylmercury, respectively. Urine and hair samples were collected from a population of dental professionals (n = 515), and total mercury content was measured. Average urine (1.06 {+-} 1.24 ug/L) and hair mercury levels (0.49 {+-} 0.63 ug/g) were similar to national U.S. population averages. Taqman assays were used to genotype DNA from buccal swab samples at 15 polymorphic sites in genes implicated in mercury metabolism. Linear regression modeling assessed the ability of polymorphisms to modify the relationship between mercury biomarker levels and exposure sources (e.g., amalgams, fish consumption). Five polymorphisms were significantly associated with urine mercury levels (GSTT1 deletion), hair mercury levels (GSTP1-105, GSTP1-114, GSS 5 Prime ), or both (SEPP1 3 Prime UTR). Overall, this study suggests that polymorphisms in selenoproteins and glutathione-related genes may influence elimination of mercury in the urine and hair or mercury retention following exposures to elemental mercury (via dental amalgams) and methylmercury (via fish consumption). -- Highlights: Black-Right-Pointing-Pointer We explore the influence of 15 polymorphisms on urine and hair Hg levels. Black-Right-Pointing-Pointer Urine and hair Hg levels in dental professionals were similar to the US population. Black-Right-Pointing-Pointer GSTT1 and SEPP1 polymorphisms associated with urine Hg levels. Black

  15. Polymorphism of a polymer precursor: metastable glycolide polymorph recovered via large scale high-pressure experiments

    DEFF Research Database (Denmark)

    Hutchison, Ian B.; Delori, Amit; Wang, Xiao

    2015-01-01

    Using a large volume high-pressure press a new polymorph of an important precursor for biomedical polymers was isolated in gram quantities and used to seed crystallisation experiments at ambient pressure.......Using a large volume high-pressure press a new polymorph of an important precursor for biomedical polymers was isolated in gram quantities and used to seed crystallisation experiments at ambient pressure....

  16. Methylenetetrahydrofolate reductase (MTHFR polymorphisms and susceptibility for cervical lesions: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Shuyu Long

    Full Text Available BACKGROUND: The association between the methylenetetrahydrofolate reductase (MTHFR C677T/A1298C polymorphisms and the susceptibility to cervical lesions was unclear. This study was designed to investigate their precise association using a large-scale meta-analysis. METHODS: The previous 16 studies were identified by searching PubMed, Embase and CBM databases. The crude odds ratios and their corresponding 95% confidence intervals (CIs were used to estimate the association between the MTHFR C677T/A1298C polymorphisms and the susceptibility to the cervical lesions. The subgroup analyses were made on the following: pathological history, geographic region, ethnicity, source of controls and source of DNA for genotyping. RESULTS: Neither of the polymorphisms had a significant association with the susceptibility to the cervical lesions in all genetic models. Similar results were found in the subgroup analyses. No association was found between the MTHFR C677T polymorphism and the cervical lesions in the Asia or the America populations though a significant inverse association was found in the Europe population (additive model: P = 0.006, OR = 0.83, 95% CI = 0.72-0.95; CT vs. CC: P = 0.05, OR = 0.83, 95% CI = 0.69-1.00; TT vs. CC: P = 0.05, OR = 0.73, 95% CI = 0.53-1.00. Interestingly, women with the MTHFR A1298C polymorphisms had a marginally increased susceptibility to invasive cancer (ICC when compared with no carriers but no statistically significant difference in the dominant model (P = 0.06, OR = 1.21, 95% CI = 0.99-1.49 and AC vs. AA (P = 0.09, OR = 1.21, 95% CI = 0.97-1.51. CONCLUSIONS: The MTHFR C677T and A1298C polymorphisms may not increase the susceptibility to cervical lesions. However, the meta-analysis reveals a negative association between the MTHFR C677T polymorphisms and the cervical lesions, especially in the European populations. The marginal association between the MTHFR A1298C polymorphisms and the susceptibility to cervical cancer

  17. Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and susceptibility for cervical lesions: a meta-analysis.

    Science.gov (United States)

    Long, Shuyu; Yang, Xingliang; Liu, Xiaojiao; Yang, Pei

    2012-01-01

    The association between the methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphisms and the susceptibility to cervical lesions was unclear. This study was designed to investigate their precise association using a large-scale meta-analysis. The previous 16 studies were identified by searching PubMed, Embase and CBM databases. The crude odds ratios and their corresponding 95% confidence intervals (CIs) were used to estimate the association between the MTHFR C677T/A1298C polymorphisms and the susceptibility to the cervical lesions. The subgroup analyses were made on the following: pathological history, geographic region, ethnicity, source of controls and source of DNA for genotyping. Neither of the polymorphisms had a significant association with the susceptibility to the cervical lesions in all genetic models. Similar results were found in the subgroup analyses. No association was found between the MTHFR C677T polymorphism and the cervical lesions in the Asia or the America populations though a significant inverse association was found in the Europe population (additive model: P = 0.006, OR = 0.83, 95% CI = 0.72-0.95; CT vs. CC: P = 0.05, OR = 0.83, 95% CI = 0.69-1.00; TT vs. CC: P = 0.05, OR = 0.73, 95% CI = 0.53-1.00). Interestingly, women with the MTHFR A1298C polymorphisms had a marginally increased susceptibility to invasive cancer (ICC) when compared with no carriers but no statistically significant difference in the dominant model (P = 0.06, OR = 1.21, 95% CI = 0.99-1.49) and AC vs. AA (P = 0.09, OR = 1.21, 95% CI = 0.97-1.51). The MTHFR C677T and A1298C polymorphisms may not increase the susceptibility to cervical lesions. However, the meta-analysis reveals a negative association between the MTHFR C677T polymorphisms and the cervical lesions, especially in the European populations. The marginal association between the MTHFR A1298C polymorphisms and the susceptibility to cervical cancer requires a further study.

  18. Vascular endothelial growth factor (VEGF-634G/C) polymorphism and retinopathy of prematurity: a meta-analysis

    Science.gov (United States)

    Malik, Manzoor Ahmad; Shukla, Swati; Azad, Shorya Vardhan; Kaur, Jasbir

    2014-01-01

    Purpose Vascular endothelial growth factor polymorphism (VEGF-634G/C, rs 2010963) has been considered a risk factor for the development of retinopathy of prematurity (ROP). However, the results remain controversial. Therefore, the aim of the present meta-analysis was to determine the association between VEGF-634G/C polymorphism and ROP risk. Methods Published literature from PubMed and other databases were retrieved. All studies evaluating the association between VEGF-634G/C polymorphism and ROP risk were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random or fixed effects model. A total of six case-control studies including 355 cases and 471 controls were included. Results By pooling all the studies, we found that VEGF-634G/C polymorphism was not associated with ROP risk at co-dominant and allele levels and no association was also found in dominant and recessive models. While stratifying on ethnicity level no association was observed in Caucasian and Asian population. Discussion This meta-analysis suggests that VEGF-634G/C polymorphism may not be associated with ROP risk, the association between single VEGF-634G/C polymorphism and ROP risk awaits further investigation. PMID:25473347

  19. Polymorphism Control in Nanostructured Metal Oxides

    Science.gov (United States)

    Sood, Shantanu

    Polymorphic phase transformations are common to all nanocrystalline binary metal oxides. The polymorphic nature of such metal oxides makes available a large number of phases with differing crystal structures, each stable under certain conditions of temperature, pressure, and/or particle size. These different crystal structures translate to unique physical and chemical properties for each structural class of polymorphs. Thus predicting when polymorphic phase transitions are likely to occur becomes important to the synthesis of stable functional materials with desired properties. Theoretical calculations using a heuristic approach have resulted in an accurate estimation of the critical particle size predicting metastable to stable phase transitions. This formula is applied to different case studies: for anatase to rutile titania; gamma-Alumina to alpha-Alumina; and tetragonal to monoclinic zirconia. The theoretical values calculated have been seen to be very close to the experimental results from the literature. Manifestation of the effect of phase transitions in nanostructured metal oxides was provided in the study of metastable to stable phase transitions in WO3. Nanowires of tungsten trioxide have been synthesized in-situ inside an electron microscope. Such structure of tungsten trioxide result due to a metastable to stable phase transformation, from the cubic to the monoclinic phase. The transformation is massive and complete. The structures formed are unique one-dimensional nanowires. Such a method can be scaled inside any equipment equipped with an electron gun, for example lithography systems either using STEM or E-beam lithography. Another study on nanowire formation in binary metal oxides involved the synthesis of stable orthorhombic MoO3 by means of blend electrospinning. Both a traditional single jet electrospinning set up and a novel high-throughput process to get high aspect ratio nanowires. The latter is a jet-controlled and flow controlled

  20. Polymorphisms of glutathione S-transferase and methylenetetrahydrofolate reductase genes in Moldavian patients with ulcerative colitis: Genotype-phenotype correlation.

    Science.gov (United States)

    Varzari, Alexander; Deyneko, Igor V; Tudor, Elena; Turcan, Svetlana

    2016-02-01

    Glutathione S-transferases (GSTM1, GSTT1, and GSTP1) and methylenetetrahydrofolate reductase (MTHFR) are important enzymes for protection against oxidative stress. In addition, MTHFR has an essential role in DNA synthesis, repair, and methylation. Their polymorphisms have been implicated in the pathogenesis of ulcerative colitis (UC). The aim of the present study was to investigate the role of selected polymorphisms in these genes in the development of UC in the Moldavian population. In a case-control study including 128 UC patients and 136 healthy individuals, GSTM1 and GSTT1 genotypes (polymorphic deletions) were determined using multiplex polymerase chain reaction (PCR). The GSTP1 rs1695 (Ile105Val), MTHFR rs1801133 (C677T), and MTHFR rs1801131 (A1298C) polymorphisms were studied with restriction fragment length polymorphism (RFLP) analysis. Genotype-phenotype correlations were examined using logistic regression analysis. None of the genotypes, either alone or in combination, showed a strong association with UC. The case-only sub-phenotypic association analysis showed an association of the MTHFR rs1801133 polymorphism with the extent of UC under co-dominant (p corrected = 0.040) and recessive (p corrected = 0.020; OR = 0.15; CI = 0.04-0.63) genetic models. Also, an association between the MTHFR rs1801131 polymorphism and the severity of UC was reported for the over-dominant model (p corrected = 0.023; coefficient = 0.32; 95% CI = 0.10-0.54). The GST and MTHFR genotypes do not seem to be a relevant risk factor for UC in our sample. There was, however, evidence that variants in MTHFR may influence the clinical features in UC patients. Additional larger studies investigating the relationship between GST and MTHFR polymorphisms and UC are required.

  1. Meta-analysis of the association of MTHFR polymorphisms with multiple myeloma risk

    Science.gov (United States)

    Ma, Li-Min; Ruan, Lin-Hai; Yang, Hai-Ping

    2015-01-01

    The association of methylenetetrahydrofolate reductase (MTHFR) polymorphisms with multiple myeloma (MM) risk has been explored, but the results remain controversial. Thus, a meta-analysis was performed to provide a comprehensively estimate. The case-control studies about MTHFR C677T and A1298C polymorphisms with MM risk were collected by searching PubMed, Elsevier, China National Knowledge Infrastructure and Wanfang Databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to assess the strength of association. Overall, no significant association was found between MTHFR A1298C polymorphism and MM risk under all four genetic models (AC vs. AA, OR = 0.99, 95%CI = 0.82-1.20; CC vs. AA, OR = 1.14, 95%CI = 0.77-1.68; recessive model, OR = 1.10, 95%CI = 0.76-1.59; dominant model, OR = 1.01, 95%CI = 0.84-1.22). The risk was also not significantly altered for C677T polymorphism and MM in overall comparisons (CT vs. CC, OR = 1.04, 95%CI = 0.93-1.17; TT vs. CC, OR = 1.16, 95%CI = 0.98-1.37; recessive model, OR = 1.13, 95%CI = 0.98-1.32; dominant model, OR = 1.07, 95%CI = 0.96-1.20). In subgroup analyses by ethnicity, no significant association was observed in both Caucasians and Asians. This meta-analysis suggested that MTHFR polymorphisms were not associated with MM risk. PMID:26022785

  2. [Association of polymorphisms of NAPE-PLD and FAAH genes with schizophrenia in Chinese Han population].

    Science.gov (United States)

    Si, Peiru; Liu, Shulian; Tong, Dongxiao; Cheng, Meijin; Wang, Liwen; Cheng, Xiaoli

    2018-04-10

    To assess the association of polymorphisms of N-acyl-phosphatidylethanolamine-phospholipase D (DAPE-PLD) and fatty acid amide hydrolase (FAAH) genes, as well as their interaction, with schizophrenia. Polymorphisms of NAPE-PLD rs12540583 and FAAH rs324420, rs2295633, and rs6429600 were determined with PCR - restriction fragment length polymorphism assay and Sanger sequencing. The genotypes of 345 subjects of Han Chinese origin diagnosed with schizophrenia and a 403 controls were compared. The results were analyzed with SPSS 17.0, and the interaction of the two genes was analyzed using a multifactor dimensionality reduction (MDR) method. The frequency of NAPE-PLD rs12540583 polymorphism was significantly different between the two groups under both dominant and additive models (χ2=17.18 vs. χ2=18.94, P<0.0125). The frequencies of AC genotype and C allele of the patient group at rs12540583 were higher than those of the controls, and the interaction of NAPE-PLD and FAAH was associated with schizophrenia. A four-loci model (rs12540583, rs324420, rs2295633 and rs6429600) can best model the interaction between NAPE-PLD and FAAH. The AC genotype and C allele of NAPE-PLD rs12540583 locus are risk factors for schizophrenia, and the interaction between NAPE-PLD rs12540583 and FAAH rs324420, rs2295633 and rs6429600 is associated with schizophrenia.

  3. Genetic predisposition of IL-10 promoter polymorphisms with risk of multiple sclerosis: A meta-analysis.

    Science.gov (United States)

    Ramakrishnan, V; Akram Husain, R S; Ahmed, Shiek Ssj

    2017-05-15

    Interleukin-10 (IL-10) is a anti-inflammatory cytokine, which controls inflammation by inhibiting the synthesis of several cytokines produced by Th1 cells and macrophages. The association between Interleukin-10 promoter polymorphisms with the risk of multiple sclerosis (MS) remains inconclusive. In this study, a meta-analysis has been performed to assess the relationship between IL-10 gene polymorphisms rs1800896, rs1800871 and rs1800872 with the risk of MS. Nine case-control studies were selected involving 2755 participants. The association between the polymorphisms and MS was examined by the pooled odds ratios (ORs) with 95% confidence intervals (CIs) in allelic, homozygote, heterozygote, dominant and recessive genetic models. Of analyzed genetic models, the pooled ORs and CIs of each SNPs calculated based on random (I 2 >50) or fixed effects (I 2 0.05) of genetic predisposition with MS susceptibility across Asian and Caucasian populations. In addition, assessment based on funnel plot and Egger's linear regression test suggests no publication bias in all analyzed genetic models. Overall, our results demonstrated that rs1800896, rs1800871 and rs1800872 polymorphisms may not be the risk factor for the development of MS in both the populations. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Polymorphic transition of tin under shock wave compression: Experimental results

    Directory of Open Access Journals (Sweden)

    Sinatti F.

    2012-08-01

    Full Text Available In this work, the β-bct polymorphic transition in tin is investigated by means of plate impact experiments. The Sn target surface is observed in a partially released state obtained thanks to a transparent lithium fluoride (LiF anvil. We report both measurements of interface velocity and temperature obtained using Photon Doppler Velocimetry and IR optical pyrometer on shock-loaded tin from 8 to 16 GPa. We show that the Mabire Model EOS associated to the SCG plasticity model provides an overall good estimate of the velocity profiles. However, depnding on the shock amplitude, its prediction of the temperature profile may be less satisfactory, hence underlining the need for future improvements in terms of phase transition kinetics description.

  5. The role of predator selection on polymorphic aposematic poison frogs.

    Science.gov (United States)

    Noonan, Brice P; Comeault, Aaron A

    2009-02-23

    Demonstrations of interactions between diverse selective forces on bright coloration in defended species are rare. Recent work has suggested that not only do the bright colours of Neotropical poison frogs serve to deter predators, but they also play a role in sexual selection, with females preferring males similar to themselves. These studies report an interaction between the selective forces of mate choice and predation. However, evidence demonstrating phenotypic discrimination by potential predators on these polymorphic species is lacking. The possibility remains that visual (avian) predators possess an inherent avoidance of brightly coloured diurnal anurans and purifying selection against novel phenotypes within populations is due solely to non-random mating. Here, we examine the influence of predation on phenotypic variation in a polymorphic species of poison frog, Dendrobates tinctorius. Using clay models, we demonstrate a purifying role for predator selection, as brightly coloured novel forms are more likely to suffer an attack than both local aposematic and cryptic forms. Additionally, local aposematic forms are attacked, though infrequently, indicating ongoing testing/learning and a lack of innate avoidance. These results demonstrate predator-driven phenotypic purification within populations and suggest colour patterns of poison frogs may truly represent a 'magic trait'.

  6. XPA A23G polymorphism and risk of digestive system cancers: a meta-analysis.

    Science.gov (United States)

    He, Lei; Deng, Tao; Luo, Hesheng

    2015-01-01

    Several studies have reported an association between the A23G polymorphism (rs 1800975) in the xeroderma pigmentosum group A (XPA) gene and risk of digestive system cancers. However, the results are inconsistent. In this study, we performed a meta-analysis to assess the association between XPA A23G polymorphism and the risk of digestive system cancers. Relevant studies were identified using the PubMed, Web of Science, China National Knowledge Infrastructure, WanFang, and VIP databases up to August 30, 2014. The pooled odds ratio (OR) with a 95% confidence interval (CI) was calculated using the fixed or random effects model. A total of 18 case-control studies from 16 publications with 4,170 patients and 6,929 controls were included. Overall, no significant association was found between XPA A23G polymorphism and the risk of digestive system cancers (dominant model: GA + AA versus GG, OR 0.89, 95% CI 0.74-1.08; recessive model: AA versus GA + GG, OR 0.94, 95% CI 0.74-1.20; GA versus GG, OR 0.89, 95% CI 0.77-1.03; and AA versus GG, OR 0.87, 95% CI 0.64-1.19). When the analysis was stratified by ethnicity, similar results were observed among Asians and Caucasians in all genetic models. In stratified analysis based on tumor type, we also failed to detect any association between XPA A23G polymorphism and the risk of esophageal, gastric, or colorectal cancers. This meta-analysis indicates that the XPA A23G polymorphism is not associated with a risk of digestive system cancers.

  7. Association between UCP polymorphisms and adipokines with obesity in Mexican adolescents.

    Science.gov (United States)

    Sámano, Reyna; Huesca-Gómez, Claudia; López-Marure, Rebeca; Hernández-Cabrera, Ana-Karen; Rodríguez-Ventura, Ana; Tolentino, Maricruz; Morales, Rosa María; Gamboa, Ricardo

    2018-04-10

    It has been reported that the uncoupling proteins (UCPs) can contribute to energy metabolism, and are thus involved in the pathogenesis of obesity. The objective of the study was to analyze the association between UCP polymorphisms, clinical parameters and leptin and adiponectin plasma levels in an adolescent population with overweight and obesity. We analyzed the UCP1 -3826 C/T, UCP2-866 G/A, Ala55Val and UCP3 -55 C/T polymorphisms and the levels of adipokines in adolescents with normal weight and with overweight or obesity. The study included 270 students aged between 12 and 18 years categorized according to the percentiles from Mexico City. Adipokines levels were measured by immunoassay methods and the UCP polymorphisms were determined using Taqman real-time polymerase chain reaction (RT-PCR). No significant differences were found in the UCP polymorphisms in seven inheritance models studied. Most of the significant differences in the clinical parameters were found under a recessive model, the UCP2 -866 polymorphism was associated with diastolic blood pressure (p=0.008), triglycerides (p=0.045), low-density lipoprotein-cholesterol (LDL-C) (p=0.003), high-density lipoprotein-cholesterol (HDL-C) (p=0.050) and plasma levels of leptin (p<0.001). Also, the obese group was found to have higher leptin levels and lower adiponectin levels in GA+AA vs. GG (recessive model). This study demonstrated a direct relationship between the clinical characteristics and UCP2-866 in a recessive model, associated with high levels of leptin and decreased levels of adiponectin in an obese or overweight Mexican adolescent population.

  8. Tumour necrosis factor gene complex polymorphisms in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Ruse, Charlotte E; Hill, Maureen C; Tobin, Martin; Neale, Natalie; Connolly, Martin J; Parker, Stuart G; Wardlaw, Andrew J

    2007-02-01

    We aimed to examine the role of tumour necrosis factor gene complex polymorphisms in subjects with chronic obstructive pulmonary disease (COPD). We hypothesized that individuals possessing polymorphic variants associated with higher tumour necrosis factor (TNF) secretion would be more susceptible to and/or have more severe disease. Patients with COPD and population controls underwent detailed clinical phenotyping. Genotyping for the tumour necrosis factor-308 and the lymphotoxin alpha NcoI (LTalpha polymorphisms was carried out by 'blinded' laboratory staff. Three hundred and sixty one individuals (220 cases and 141 controls) were recruited. We showed an association between the LTalphaNcol polymorphism and forced vital capacity (FVC) in a population of older adults with and without COPD. The LTalphaNcol*2 allele was associated with poorer lung function, under a codominant model, with a fall in FVC (expressed as a percentage of its predicted value) of 3.7% for each copy of the LTalphaNcol*2 allele possessed (for FVC, regression coefficient (95% CI)=-3.73(-7.01 to -0.44), P=0.026; for FEV(1) regression coefficient=-3.56(-7.80 to 0.70), P=0.101. However, there was no difference in genotype distribution between the case and control populations. This study adds weight to the suggestion that the TNF gene complex is involved in physiological alterations (FVC) that may affect the development and severity of COPD. The absence of a significant association between the TNF gene-complex polymorphisms in this study does not rule out a modest effect of these polymorphisms on the risk of COPD, as much larger studies are needed to detect modest gene effects on binary disease endpoints.

  9. Polymorphism and methylation of the MC4R gene in obese and non-obese dogs.

    Science.gov (United States)

    Mankowska, Monika; Nowacka-Woszuk, Joanna; Graczyk, Aneta; Ciazynska, Paulina; Stachowiak, Monika; Switonski, Marek

    2017-08-01

    The dog is considered to be a useful biomedical model for human diseases and disorders, including obesity. One of the numerous genes associated with human polygenic obesity is MC4R, encoding the melanocortin 4 receptor. The aim of our study was to analyze polymorphisms and methylation of the canine MC4R in relation to adiposity. Altogether 270 dogs representing four breeds predisposed to obesity: Labrador Retriever (n = 187), Golden Retriever (n = 38), Beagle (n = 28) and Cocker Spaniel (n = 17), were studied. The dogs were classified into three groups: lean, overweight and obese, according to the 5-point Body Condition Score (BCS) scale. In the cohort of Labradors a complete phenotypic data (age, sex, neutering status, body weight and BCS) were collected for 127 dogs. The entire coding sequence as well as 5' and 3'-flanking regions of the studied gene were sequenced and six polymorphic sites were reported. Genotype frequencies differed considerably between breeds and Labrador Retrievers appeared to be the less polymorphic. Moreover, distribution of some polymorphic variants differed significantly (P C, c.868C>T and c.*33C>G) and Beagles (c.-435T>C and c.637G>T). On the contrary, in Labradors no association between the studied polymorphisms and BCS or body weight was observed. Methylation analysis, using bisulfite DNA conversion followed by Sanger sequencing, was carried out for 12 dogs with BCS = 3 and 12 dogs with BCS = 5. Two intragenic CpG islands, containing 19 cytosines, were analyzed and the methylation profile did not differ significantly between lean and obese animals. We conclude that an association of the MC4R gene polymorphism with dog obesity or body weight is unlikely, in spite of the fact that some associations were found in small cohorts of Beagles and Golden Retrievers. Also methylation level of this gene is not related with dog adiposity.

  10. MODULATING EFFECT OF THE −158 GΓ (C→T XMN-1 POLYMORPHISM IN INDIAN SICKLE CELL PATIENTS

    Directory of Open Access Journals (Sweden)

    Sanjay Pandey

    2012-01-01

    Full Text Available Xmn-1 polymorphism is a known factor, which increases fetal haemoglobin production. Among the inherited disorders of blood, thalassaemia and SCD constitutes a major bulk of genetic diseases in India.  Our aim was to verify the role of the Xmn I polymorphism as a modulating factor in sickle cell patients and frequency of the polymorphism in Indian sickle cell patients. Subjects were 60 sickles homozygous and 75 sickle beta thalassemia patients. 5 ml blood   samples collected from patients. Screening of sickle patients done by HPLC. An automated cell analyzer SYSMEX (K-4500 Model used to analyze the CBC of patients.Xmn1 polymorphism analysis done by PCR-RFLP and Statistical analysis was performed on GraphPad static’s software. t test applied to compare the means amongst group. Among the sickle homozygous 27 were   heterozygous (+/- and 19 were   homozygous (+/+ while 30 were heterozygous and 24 were homozygous in sickle β-thalassemia patients. Extremely significant differences (p-value <0.001 of hematological parameters seen among patient with xmn-1 carrier and without the xmn-1 carrier. In our cases the clinical symptom less frequent and higher HbF level with Xmn-1 carriers. Presence of Xmn-1 polymorphism in sickle patients with higher HbF that improve phenotypic presentation in the sickle cell patients. We conclude that the phenotype of Indian sickle cell patients influenced by Xmn-1 polymorphism.

  11. Quantitative assessment of the influence of tumor necrosis factor alpha polymorphism with gastritis and gastric cancer risk.

    Science.gov (United States)

    Li, Ming; Wang, Yinping; Gu, Yahong

    2014-02-01

    Tumor necrosis factor alpha (TNFA) is an important molecule in inflammatory, infectious, and tumoral processes. Inflammation is one of the early phases in the development of gastric cancer (GC). Therefore, several studies have examined the association of polymorphism in TNFA with gastritis and GC risk. A functional polymorphism, -308G>A (rs1800629), which is located in the promoter of TNFA gene, has been suggested to alter the production of TNF-α and influence cancer risk. To date, a number of studies have been carried out to investigate the relationship between the polymorphism and gastritis or GC susceptibility, but the results were conflicting. To investigate this inconsistency, we performed a meta-analysis of 36 studies for TNFA -308G>A polymorphism to evaluate the effect of TNFA on genetic susceptibility for gastritis and GC. An overall random-effects per-allele odds ratio of 1.16 (95 % confidence interval 1.04-1.29, P = 0.008) was found for the polymorphism. Significant results were also observed using dominant or recessive genetic models. In the subgroup analyses by ethnicity, significant results were found in Caucasians, whereas no significant associations were found among East Asians and other ethnic populations. No associations between the polymorphism and gastritis were observed. In addition, our data indicate that TNFA is involved in GC susceptibility and confers its effect primarily in diffuse type of tumors. Besides, -308G>A polymorphism was found to be significantly associated with both cardiac and noncardiac tumors. This meta-analysis demonstrated that the TNFA -308G>A polymorphism is a risk factor for developing GC, but the associations vary in different ethnic populations.

  12. The rs225017 polymorphism in the 3'UTR of the human DIO2 gene is associated with increased insulin resistance.

    Directory of Open Access Journals (Sweden)

    Leonardo B Leiria

    Full Text Available The Thr92Ala (rs225014 polymorphism in the type 2 deiodinase (DIO2 gene has been associated with insulin resistance (IR and decreased enzyme activity in human tissues but kinetic studies failed to detect changes in the mutant enzyme, suggesting that this variant might be a marker of abnormal DIO2 expression. Thus, we aimed to investigate whether other DIO2 polymorphisms, individually or in combination with the Thr92Ala, may contribute to IR. The entire coding-region of DIO2 gene was sequenced in 12 patients with type 2 diabetes mellitus (T2DM. Potentially informative variants were evaluated in 1077 T2DM patients and 516 nondiabetic subjects. IR was evaluated using the homeostasis model assessment (HOMA-IR index. DIO2 gene sequencing revealed no new mutation but 5 previously described single nucleotide polymorphisms (SNPs. We observed that all T2DM patients displaying high HOMA-IR index (n = 6 were homozygous for the rs225017 (T/A polymorphism. Further analysis showed that the median fasting plasma insulin and HOMA-IR of T2DM patients carrying the T/T genotype were higher than in patients carrying the A allele (P = 0.013 and P = 0.002, respectively. These associations were magnified in the presence of the Ala92Ala genotype of the Thr92Ala polymorphism. Moreover, the rs225017 and the Thr92Ala polymorphisms were in partial linkage disequilibrium (|D'| = 0.811; r2 = 0.365. In conclusion, the rs225017 polymorphism is associated with greater IR in T2DM and it seems to interact with the Thr92Ala polymorphism in the modulation of IR.

  13. Association of polymorphisms in the leptin and thyroglobulin genes with meat quality and carcass traits in beef cattle

    Directory of Open Access Journals (Sweden)

    Thiago Dutra de Carvalho

    2012-10-01

    Full Text Available The objective of the present study was to estimate the allelic and genotypic frequencies of the polymorphisms E2FB (AY138588.1: c.305C> T, located in the leptin gene (LEP, and TG5 (X05380.1:g.-422C>T, located in the thyroglobulin gene (TG, and evaluate the association of these polymorphisms in crossbred cattle of seven distinct genetic groups with the following traits: slaughter weight (SW, hot carcass weight (HCW, hot carcass yield (HCY, carcass fat thickness (CFT, ribeye area (REA, marbling (MARM and shear force (SF. The animals were genotyped using the PCR-RFLP (Polymorphism Chain Reaction-Restriction Fragment Length Polymorphism technique, using 201 products obtained from F1 Caracu × Nellore, Angus × Nellore and Valdostana × Nellore cows, mated to Canchim, Caracu and Red Angus bulls (only Caracu × Nellore cows were used with Red Angus bulls. The allelic and genotypic frequencies were compared using the Chi-squared test. Associations between the genotype of each polymorphism and the traits were analyzed using the General Linear Model (GLM of statistical software SAS. The least squares means of genotypes of the polymorphisms were compared using Student's t test. The E2FB polymorphism in the LEP gene was associated with CFT, showing the potential for use in national programs for genetic improvement of beef cattle, through the inclusion of SNP in genotyping commercial tests. The TG5 polymorphism in the TG gene was not associated with any of the evaluated traits and was considered ineffective for selection of beef cattle in Brazilian herds.

  14. Face and emotion expression processing and the serotonin transporter polymorphism 5-HTTLPR/rs22531.

    Science.gov (United States)

    Hildebrandt, A; Kiy, A; Reuter, M; Sommer, W; Wilhelm, O

    2016-06-01

    Face cognition, including face identity and facial expression processing, is a crucial component of socio-emotional abilities, characterizing humans as highest developed social beings. However, for these trait domains molecular genetic studies investigating gene-behavior associations based on well-founded phenotype definitions are still rare. We examined the relationship between 5-HTTLPR/rs25531 polymorphisms - related to serotonin-reuptake - and the ability to perceive and recognize faces and emotional expressions in human faces. For this aim we conducted structural equation modeling on data from 230 young adults, obtained by using a comprehensive, multivariate task battery with maximal effort tasks. By additionally modeling fluid intelligence and immediate and delayed memory factors, we aimed to address the discriminant relationships of the 5-HTTLPR/rs25531 polymorphisms with socio-emotional abilities. We found a robust association between the 5-HTTLPR/rs25531 polymorphism and facial emotion perception. Carriers of two long (L) alleles outperformed carriers of one or two S alleles. Weaker associations were present for face identity perception and memory for emotional facial expressions. There was no association between the 5-HTTLPR/rs25531 polymorphism and non-social abilities, demonstrating discriminant validity of the relationships. We discuss the implications and possible neural mechanisms underlying these novel findings. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  15. Polymorphisms in genes encoding the serotonin and dopamine pathways in two sisters with metachromatic leukodystrophy.

    Science.gov (United States)

    Kumperscak, H G; Dolzan, V; Videtic, A; Plesnicar, B K

    2008-01-01

    Metachromatic leukodystrophy (MLD) is a metabolic disease that has recently been investigated as a model for the study of psychosis. We report on two sisters with adult-type MLD who developed psychiatric symptomatology, but differed in their expression of psychotic and depressive symptoms. Association studies have indicated that polymorphisms in genes encoding the serotonin and dopamine transporters and receptors are related to the symptomatology of schizophrenia and/or depression; hence both sisters were genotyped for some of these candidate genes. The sisters shared dopamine receptor D(2) (DRD(2)) c.1047GG (p.311Ser/Ser) and c.-141Cins/ins polymorphisms, which are significantly associated with schizophrenia, but differed in the serotonin transporter gene-linked polymorphic region and serotonin receptor 1A (5-HT(1A)) c.-1019C to G polymorphisms, which may have increased the elder sister's susceptibility to depressive symptoms. Much bigger samples would be needed to gain enough statistical power to develop any hypotheses. This is the first report on genotyping MLD patients for candidate genes for psychiatric disorders, although MLD has been proposed as a model for schizophrenia.

  16. Hoare type theory, polymorphism and separation

    DEFF Research Database (Denmark)

    Nanevski, Alexandar; Morrisett, J. Gregory; Birkedal, Lars

    2008-01-01

    with higher-order functions and type polymorphism. We further show that in the presence of type polymorphism, it becomes possible to interpret the Hoare types in the “small footprint” manner, as advocated by separation logic, whereby specifications tightly describe the state required by the computation. We...... establish that HTT is sound and compositional, in the sense that separate verifications of individual program components suffice to ensure the correctness of the composite program....... to statically track and enforce correct use of side effects. The main feature of HTT is the Hoare type {P}x:A{Q} specifying computations with precondition P and postcondition Q that return a result of type A. Hoare types can be nested, combined with other types, and abstracted, leading to a smooth integration...

  17. Raman Identification of Polymorphs in Pentacene Films

    Directory of Open Access Journals (Sweden)

    Alberto Girlando

    2016-04-01

    Full Text Available We use Raman spectroscopy to characterize thin films of pentacene grown on Si/SiO x by Supersonic Molecular Beam Deposition (SuMBD. We find that films up to a thickness of about 781 Å (∼ 52 monolayers all belong to the so-called thin-film (TF phase. The appearance with strong intensity of some lattice phonons suggests that the films are characterized by good intra-layer order. A comparison of the Raman spectra in the lattice and CH bending spectral regions of the TF polymorph with the corresponding ones of the high-temperature (HT and low-temperature (LT bulk pentacene polymorphs provides a quick and nondestructive method to identify the different phases.

  18. C667T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene and susceptibility to myocardial infarction: A systematic review and meta-analysis.

    Science.gov (United States)

    Alizadeh, Shahab; Djafarian, Kurosh; Moradi, Sajjad; Shab-Bidar, Sakineh

    2016-08-15

    MTHFR C677T and A1298C polymorphisms have been reported to be associated with the risk of myocardial infarction (MI), although the results of previous studies have been inconsistent. The aim of this study was to explore whether these polymorphisms play a role in the genetic susceptibility to MI. A comprehensive search of MEDLINE and EMBASE databases was conducted for studies evaluating the association between the C667T and A1298C polymorphisms and MI risk. Odds ratios (OR) with 95% confidence intervals (CIs) were calculated to assess the strength of association in the dominant model, recessive model, allelic model, and genotypes contrast. A total of 47 studies were finally included in this meta-analysis. Overall, the results showed no statistically significant association between C667T and A1298C polymorphisms and MI risk. However, in subgroup analysis by ethnicity, the T allele of C677T polymorphism was associated with a 63% increased risk of MI compared with the C allele (T vs. C, OR=1. 63, 95%CI=1.15-2.10, fixed effects) in African populations, while compared to wild homozygote genotype, CT genotype was associated with a decreased risk of MI in North American populations (CT vs. CC, OR=0.81, 95%CI=0.64-0.98, fixed effects). Moreover, C677T polymorphism had a protective effect against MI risk under the dominant model (OR=0.93, 945%CI=0.87-0.99, fixed effects) in elderly (≥50) population. The A1298C polymorphism was not significantly associated with MI risk. Unlike A1298C polymorphism, C677T polymorphism was associated with risk of MI in African, North American, and elderly populations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Association between the TLR2 Arg753Gln polymorphism and the risk of sepsis: a meta-analysis.

    Science.gov (United States)

    Gao, Jun-wei; Zhang, An-qiang; Wang, Xiao; Li, Zhong-yun; Yang, Jian-hua; Zeng, Ling; Gu, Wei; Jiang, Jian-xin

    2015-11-30

    Recently, researchers in a number of studies have explored the association between the Toll-like receptor 2 (TLR2) Arg753Gln polymorphism and sepsis risk. However, the results were conflicting. In this meta-analysis, we aimed to confirm the effect of the TLR2 Arg753Gln polymorphism on sepsis risk. Relevant records up to 1 June 2015 were retrieved from the PubMed, Embase, and Web of Knowledge databases. The odds ratios with their corresponding 95 % confidence intervals were used to assess the association between the TLR2 Arg753Gln polymorphism and sepsis risk. The selection of a fixed or random effects model was made according to a heterogeneity test in total and subgroup analyses. Sensitivity analysis and publication bias test were performed to ensure the reliability of our results. A total of 12 studies with aggregate totals of 898 cases and 1517 controls met our inclusion criteria for meta-analysis. There were significant associations between the TLR2 Arg753Gln polymorphism and sepsis risk in overall analyses under two genetic models (the allele comparison and the dominant model). In addition, subgroup analyses based on age group, ethnicity, sepsis type, and source of control also showed a significant effect of the TLR2 Arg753Gln polymorphism on sepsis risk. Our present meta-analysis supports a direct effect of the TLR2 Arg753Gln polymorphism on sepsis risk, especially in Europeans. The TLR2 Arg753Gln polymorphism might be used as a relevant risk estimate for the development of sepsis. Studies with larger sample sizes and homogeneous groups of patients with sepsis are required for further analysis.

  20. Effect of matrix metalloproteinase promoter polymorphisms on ...

    Indian Academy of Sciences (India)

    endometriosis and adenomyosis risk: evidence from a meta-analysis. HUI YE1,2, YAZHOU HE1, ... between MMP-1 -1607 1G/2G MMP-2 -735 C/T, MMP-3 -1171 5A/6A and MMP-9 -1562 C/T polymorphisms and the risk of endometriosis and .... to estimate pooled ORs and 95% CIs if P value of Q test is <0.10, otherwise, the ...

  1. A novel multiplex analysis of filaggrin polymorphisms

    DEFF Research Database (Denmark)

    Meldgaard, Michael; Szecsi, Pal B; Carlsen, Berit C

    2012-01-01

    The filaggrin protein is expressed as profilaggrin mainly in stratum granulosum cells of the epidermis. The profilaggrin gene codes for 10-12 filaggrin repeats. The filaggrin protein is important for skin barrier function. Filaggrin deficiency due to functional null-polymorphisms affects 8-10% of......-10% of the people in Northern Europe and is a strong risk factor for several diseases. Here, we describe a novel method for efficient, multiplexed genotyping of variations in the profilaggrin gene....

  2. Highly polymorphic RFLP probes as diagnostic tools

    International Nuclear Information System (INIS)

    Donis-Keller, H.; Barker, D.F.; Knowlton, R.G.; Schumm, J.W.; Braman, J.C.; Green, P.

    1986-01-01

    In this paper, we describe the identification of highly polymorphic RFLP loci and their application to genotyping in humans and to mapping the CF gene to chromosome 7. We also report the construction of a high-resolution genetic map of chromosome 7 and summarize progress toward the development of a presymptomatic diagnostic test for CF that should be useful in virtually every case. 25 references, 7 figures, 5 tables

  3. The polymorphic, multilayered and networked urbanised territory

    DEFF Research Database (Denmark)

    Nielsen, Tom

    2015-01-01

    The discussion of the network city has in recent years been supplemented by an increasing interest in reconsidering the notion of territory. Looking into both geographical and urban design theories, we find examples of a focus on how the networks of the city not only connect them irreversibly...... in theory. The concept of The Polymorphic, Multilayered and Networked Urbanised Territory is introduced to grasp the reality experienced in European regions outside the largest and most potent versions of contemporary cities....

  4. Polymorphism of lipid self-assembly systems

    International Nuclear Information System (INIS)

    Takahashi, Hiroshi

    2002-01-01

    When lipid molecules are dispersed into an aqueous medium, various self-organized structures are formed, depending on conditions (temperature, concentration, etc), in consequence of the amphipathic nature of the molecules. In addition, lipid self-assembly systems exhibit polymorphic phase transition behavior. Since lipids are one of main components of biomembranes, studies on the structure and thermodynamic properties of lipid self-assembly systems are fundamentally important for the consideration of the stability of biomembranes. (author)

  5. Association between MTHFR A1298C polymorphism and male infertility: A meta-analysis.

    Science.gov (United States)

    Zhang, Qiang; Yin, Guo-Ying; Liu, Juan; Liang, Yue; Li, Yao-Yan; Zhao, Jing-Yu; Zhang, Li-Wen; Wang, Bai-Qi; Tang, Nai-Jun

    2017-04-01

    There have been several epidemiological studies evaluating the potential association between the methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism and the risk of male infertility. However, the results obtained were inconsistent. Therefore, we performed a meta-analysis to further examine the association between the MTHFR A1298C polymorphism and male infertility. A comprehensive search was conducted to identify all eligible studies from the online literature databases published prior to January 15th, 2016. A total of 20 studies with 4293 cases and 4507 controls were included. An odds ratio (OR) and a 95% confidence interval (95% CI) were calculated to assess the strength of the association. A cumulative meta-analysis, sensitivity analysis and assessment of the publication bias were also performed in this study. The results showed that in the overall analysis, the association between the MTHFR A1298C polymorphism and male infertility was not significant. A stratified analysis by ethnicity revealed a significant increase in the risk of male infertility in the Asian population with the MTHFR A1298C polymorphism (especially in the heterozygote model: OR=1.20, 95% CI=1.01-1.44, P=0.994; the dominant model: OR=1.23, 95% CI=1.04-1.45, P=0.996; and the allele model: OR=1.20, 95% CI=1.04-1.39, P=0.985) but not in the Caucasian population. In the stratified analyses, no significant association was observed between the different types of male infertility. This meta-analysis suggests the MTHFR A1298C polymorphism may be a potential risk factor for male infertility, especially in the Asian population.

  6. TLR9 polymorphisms and systemic lupus erythematosus risk: an update meta-analysis study.

    Science.gov (United States)

    Wang, Duan; Zhang, Chao; Zhou, Zongke; Pei, Fuxing

    2016-04-01

    It has been reported that the Toll-like receptor 9 (TLR9) gene polymorphisms may be associated with systemic lupus erythematosus (SLE) risk. However, some studies yielded conflicting results. Therefore, a comprehensive meta-analysis was performed to assess the precise association between TLR9 polymorphisms and SLE susceptibility. We performed a systematic search in PubMed, Embase (Ovid), China National Knowledge Internet, and Wanfang databases up to July 15, 2015. Odds ratio (OR) and 95 % confidence interval (CI) were used to pool the effect size. Statistical analyses were performed with STATA 11.0 software. In total, 21 studies from nineteen articles with 10,273 subjects were included in this meta-analysis. The overall results suggested that there was a statistically significant association between TLR9 rs187084 polymorphism and SLE risk observed in recessive model (TT vs. TC + CC: OR 1.17, 95 % CI 1.05-1.30, P = 0.005), codominant model (TT vs. CC: OR 1.22, 95 % CI 1.03-1.43, P = 0.019), and allele model (T vs. C: OR 1.15, 95 % CI 1.02-1.30, P = 0.020) in Asians. However, we found that there may be no significant association between the other three TLR9 polymorphisms and SLE risk in either Asians or non-Asians. In conclusion, the meta-analysis results suggested that TLR9 rs187084 polymorphism may increase the risk of SLE in Asians. However, no significant association between TLR9 SNPs (rs352139, rs352140, and rs5743836) and SLE risk was identified.

  7. New polymorphic variants of human blood clotting factor IX

    Energy Technology Data Exchange (ETDEWEB)

    Surin, V.L.; Luk`yanenko, A.V.; Tagiev, A.F.; Smirnova, O.V. [Hematological Research Center, Moscow (Russian Federation); Plutalov, O.V.; Berlin, Yu.A. [Shemyakin Institute of Bioorganic Chemistry, Moscow (Russian Federation)

    1995-04-01

    The polymorphism of Alu-repeats, which are located in the introns of the human factor IX gene (copies 1-3), was studied. To identify polymorphic variants, direct sequencing of PCR products that contained appropriate repeats was used. In each case, 20 unrelated X chromosomes were studied. A polymorphic Dra I site was found near the 3{prime}-end of Alu copy 3 within the region of the polyA tract. A PCR-based testing system with internal control of restriction hydrolysis was suggested. Testing 81 unrelated X chromosomes revealed that the frequency of the polymorphic Dra I site is 0.23. Taq I polymorphism, which was revealed in Alu copy 4 of factor IX gene in our previous work, was found to be closely linked to Dra I polymorphism. Studies in linkage between different types of polymorphisms of the factor IX gene revealed the presence of a rare polymorphism in intron a that was located within the same minisatellite region as the known polymorphic insertion 50 bp/Dde I. However, the size of the insertion in our case was 26 bp. Only one polymorphic variant was found among over 150 unrelated X chromosomes derived from humans from Moscow and its vicinity. 10 refs., 4 figs., 1 tab.

  8. The Association between MTHFR Gene Polymorphisms and Hepatocellular Carcinoma Risk: A Meta-Analysis

    Science.gov (United States)

    Deng, Yan; Huang, Shan; Xu, Juanjuan; Li, Haiwei; Li, Shan; Zhao, Jinmin

    2013-01-01

    Background The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and hepatocellular carcinoma (HCC) risk was inconsistent and underpowered. To clarify the effects of MTHFR gene polymorphisms on the risk of HCC, a meta-analysis of all available studies relating C677T and/or A1298C polymorphisms of MTHFR gene to the risk of HCC was conducted. Methods The authors searched PubMed, EMBASE, Cochrane Library, Web of Science, and Chinese Biomedical Literature database (CBM) for the period up to July 2012. Data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Metaregression and subgroup analyses were performed to identify the source of heterogeneity. Results Finally, 12 studies with 2,351 cases and 4,091 controls were included for C677T polymorphism and 6 studies with 1,333 cases and 1,878 controls were included for A1298C polymorphism. With respect to A1298C polymorphism, significantly decreased HCC risk was found in the overall population (CC vs. AA: OR = 0.660, 95%CI 0.460–0.946, P = 0.024; recessive model: OR = 0.667, 95%CI = 0.470–0.948, P = 0.024). In subgroup analyses, significantly decreased HCC risk was found in Asian population (CC vs. AA: OR = 0.647, 95%CI = 0.435–0.963; P = 0.032) and population-based studies (CC vs. AA: OR = 0.519, 95%CI = 0.327–0.823; P = 0.005). With respect to C677T polymorphism, no significant association with HCC risk was demonstrated in overall and stratified analyses. Conclusions We concluded that MTHFR A1298C polymorphism may play a protective role in the carcinogenesis of HCC. Further large and well-designed studies are needed to confirm this association. PMID:23457501

  9. The association between MTHFR gene polymorphisms and hepatocellular carcinoma risk: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Xue Qin

    Full Text Available BACKGROUND: The association between methylenetetrahydrofolate reductase (MTHFR gene polymorphisms and hepatocellular carcinoma (HCC risk was inconsistent and underpowered. To clarify the effects of MTHFR gene polymorphisms on the risk of HCC, a meta-analysis of all available studies relating C677T and/or A1298C polymorphisms of MTHFR gene to the risk of HCC was conducted. METHODS: The authors searched PubMed, EMBASE, Cochrane Library, Web of Science, and Chinese Biomedical Literature database (CBM for the period up to July 2012. Data were extracted by two independent authors and pooled odds ratio (OR with 95% confidence interval (CI was calculated. Metaregression and subgroup analyses were performed to identify the source of heterogeneity. RESULTS: Finally, 12 studies with 2,351 cases and 4,091 controls were included for C677T polymorphism and 6 studies with 1,333 cases and 1,878 controls were included for A1298C polymorphism. With respect to A1298C polymorphism, significantly decreased HCC risk was found in the overall population (CC vs. AA: OR = 0.660, 95%CI 0.460-0.946, P = 0.024; recessive model: OR = 0.667, 95%CI = 0.470-0.948, P = 0.024. In subgroup analyses, significantly decreased HCC risk was found in Asian population (CC vs. AA: OR = 0.647, 95%CI = 0.435-0.963; P = 0.032 and population-based studies (CC vs. AA: OR = 0.519, 95%CI = 0.327-0.823; P = 0.005. With respect to C677T polymorphism, no significant association with HCC risk was demonstrated in overall and stratified analyses. CONCLUSIONS: We concluded that MTHFR A1298C polymorphism may play a protective role in the carcinogenesis of HCC. Further large and well-designed studies are needed to confirm this association.

  10. Doppel gene polymorphisms in Portuguese sheep breeds: insights on ram fertility.

    Science.gov (United States)

    Pereira, R M; Mesquita, P; Batista, M; Baptista, M C; Barbas, J P; Pimenta, J; Santos, I C; Marques, M R; Vasques, M I; Silva Pereira, M; Santos Silva, F; Oliveira Sousa, M C; Fontes, C M G; Horta, A E M; Prates, J A M; Marques, C C

    2009-08-01

    Transgenic knockout of the gene encoding the prion-like protein Doppel leads to male infertility in mice. The precise role of Doppel in male fertility is still unclear, but sperm from Doppel-deficient mice appear to be unable to undergo the normal acrosome reaction necessary to penetrate the zona pellucida of the oocyte. The objective of this study was to characterize Doppel (Prnd) gene polymorphisms in eight Portuguese sheep breeds and to determine a possible relationship between these polymorphisms and ram fertility. Ovine genomic DNA of 364 animals of different breeds (Bordaleira entre Douro e Minho, Churra Badana, Churra Galega Mirandesa, Churra Mondegueira, Merino da Beira Baixa, Merino Branco, Saloia and Serra da Estrela) were analysed by multiple restriction fragment-single-strand conformation polymorphism (MRF-SSCP). This analysis revealed a synonymous substitution G-->A in codon 26 of Prnd gene. Churra Galega Mirandesa and Saloia breeds were more polymorphic (P=0.005 and P=0.04, respectively) than the overall population, while Serra da Estrela and Merino Branco animals were less polymorphic (P=0.007 and P=0.04). No polymorphism was found in Churra Mondegueira breed. Semen from 11 rams of Churra Galega Mirandesa breed (7 homozygous wildtype GG and 4 heterozygous GA) routinely used in the Portuguese Animal Germoplasm Bank was collected and frozen for fertility tests. A classification function was estimated, using data from post-swim-up semen motility and concentration and Day 6 embryo production rate, allowing the identification of the Doppel homozygous GG genotype with 86.7% of accuracy. This preliminary study detected the presence of only one polymorphism in codon 26 of Prnd gene in the Portuguese sheep breeds. In the polymorphic Churra Galega Mirandesa breed, GG genotype could be characterized through a model using three fertility traits, suggesting a relationship with male reproduction. Any future research should investigate not only AA genotype and its

  11. Solubility and dissolution studies of tibolone polymorphs

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    Rudy Bonfilio

    2018-03-01

    Full Text Available ABSTRACT Different solid forms of an active pharmaceutical ingredient can have distinct chemical and physical characteristics. In this work, we studied the solubility and dissolution properties of the described tibolone polymorphic forms (I and II. Both forms were successively recrystallized and characterized by powder X-ray diffraction and attenuated total reflection infrared spectroscopy. Equilibrium solubility and dissolution profiles were performed for both forms. Solubility studies demonstrated that form II is statistically more soluble in water, 0.01 mol L-1 HCl and pH 4.5 acetate buffer. The solubility of forms I and II were explained in terms of crystal packing. Dissolution tests of tablets showed a lower release of polymorphic form II than form I from tablets. The results showed an impact of polymorphism on the quality of tibolone tablets and suggest that tibolone forms I and II can show distinct interactions with pharmaceutical excipients used in tablets. Therefore, only form I is acceptable for the preparation of tablet forms. Based on our results, we propose the quality control on tibolone raw materials using X-ray diffraction analysis and attenuated total reflection infrared spectroscopy.

  12. Differential detectability of polymorphic warning signals under varying light environments.

    Science.gov (United States)

    Rojas, Bibiana; Rautiala, Petri; Mappes, Johanna

    2014-11-01

    The striking colour-pattern variation of some aposematic species is paradoxical because selection by predators is expected to favour signal uniformity. Although the mechanisms allowing for the maintenance of such variation are not well understood, possible explanations include both non-adaptive processes like drift and gene flow; and adaptive processes, such as an interaction between natural and sexual selection, spatial and temporal variation in selection, a link between behaviour or other fitness-related traits and phenotype, and predators' ability to generalise among different signals. Here we test whether warning-signal polymorphisms, such as that of dyeing poison frogs (Dendrobates tinctorius), could be maintained by differences in detectability among morphs. We did experiments in the wild using wax models with different aposematic colour patterns vs. cryptic ones, and examined the attack rates by wild predators over time. We also tested the detectability of different aposematic morphs by 'human predators' under different light environments. We found that cryptic frog models were attacked more than aposematic models, but there were no differences in bird attack rates towards the different aposematic morphs. However, we found that detectability of different morphs depends both on predator experience and light environment. We suggest that the interaction between differential detectability and signal efficiency among morphs in different light conditions could be a mechanism aiding to the maintenance of warning-signal polymorphisms. Our results highlight the importance of considering the light environment at which predators have their first encounters with aposematic prey for future studies on predation in the wild. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Study of the association between five polymorphisms and risk of hepatocellular carcinoma: A meta-analysis.

    Science.gov (United States)

    Yu, Jia-Yun; Hu, Fan; Du, Wei; Ma, Xue-Lei; Yuan, Kun

    2017-04-01

    Recently, several studies have investigated the association between polymorphisms in miR-146a rs2910164, miR-196a2 rs11614913, miR-499 rs3746444, miR-149 rs229283, miR-34b/c rs4938723, and hepatocellular carcinoma (HCC), which showed inconclusive results. A publication search was performed in PubMed, ExcerptaMedica Database, Chinese Biomedical Literature Database, and Chinese National Knowledge Infrastructure to collect relevant medical data published through February 2016. The aim of this study was to ascertain the association between HCC and micro-RNAs. A total of 21 studies were included in our study, which showed that miR-146a rs2910164 polymorphism has a significant association with HCC in the allele, recessive, and homozygous models overall [allele model: odds ratio (OR) = 0.927, 95% confidence interval (CI): 0.869-0.988, p = 0.02; recessive model: OR = 0.893, 95% CI: 0.814-0.981, p = 0.018; homozygous model: OR = 0.853, 95% CI: 0.744-0.978, p = 0.023] and in Asian populations (allele model: OR = 0.921, 95% CI: 0.863-0.983, p = 0.014; recessive model: OR = 0.893, 95% CI: 0.814-0.981, p = 0.019; homozygous model: OR = 0.851, 95% CI: 0.741-0.977, p = 0.022). For miR-196a2 rs11614913, significant statistical heterogeneity overall and in Asian populations was identified in the comparison of the allele, recessive, homozygous, and heterozygous models (overall: allele model: OR = 0.889, 95% CI: 0.842-0.94, p risk of HCC in Caucasians in all genetic models except for the heterozygous model (allele model: OR = 0.658, 95% CI: 0.49-0.885, p = 0.006; dominant model: OR = 0.641, 95% CI: 0.418-0.981, p = 0.041; recessive model: OR = 0.489, 95% CI: 0.278-0.862, p = 0.013; homozygous model: OR = 0.414, 95% CI: 0.222-0.772, p = 0.005). Only the recessive models produced a significant association between miR-499 rs3746444 polymorphism and HCC risk (recessive model: OR = 1.283, 95% CI: 1.008-1.632, p = 0.043). The analysis for mi

  14. Serine/threonine kinase 15 gene polymorphism and risk of digestive system cancers: A meta-analysis.

    Science.gov (United States)

    Luo, Jianfei; Yan, Ruicheng; Zou, Li

    2015-01-01

    Previous studies have reported an association between the two coding polymorphisms (91T>A and 169G>A) of the serine/threonine kinase 15 (STK15) gene and the risk of digestive system cancers; however, the results are inconsistent. In the present study, a meta-analysis was carried out to assess the association between the two STK15 polymorphisms and the risk of digestive system cancers. Relevant studies were identified using PubMed, Web of Science, China National Knowledge Infrastructure, WanFang and VIP databases up to February 18, 2014. The pooled odds ratio (OR) with a 95% confidence interval (CI) was calculated using the fixed or random effects model. A total of 15 case-control studies from 14 publications were included. Of these, 15 studies concerned the 91T>A polymorphism and included 7,619 cases and 7,196 controls and four studies concerned the 161G>A polymorphism and included 826 cases and 713 controls. A significantly increased risk of digestive system cancers was observed for the 91T>A polymorphism (recessive model: OR, 1.19; 95% CI, 1.07-1.31). In subgroup analysis by ethnicity, a significant association was detected in Asian populations (recessive model: OR, 1.21; 95% CI, 1.08-1.36) but not in Caucasian and mixed populations. Stratification by tumor type indicated that the 91T>A polymorphism was associated with an increased risk of esophageal and colorectal cancers under the recessive model (OR, 1.19; 95% CI, 1.03-1.38; and OR, 1.24; 95% CI, 1.04-1.46; respectively); however, no significant association was observed between the 169G>A polymorphism and the risk of digestive system cancers in any of the genetic models. Furthermore, in subgroup analysis by ethnicity, similar results were observed in the Asian and Caucasian populations. The present meta-analysis demonstrated that the STK15 gene 91T>A polymorphism, but not the 169G>A polymorphism, may be a risk factor for digestive system cancers, particularly for esophageal and colorectal cancers.

  15. Association between CD14 gene C-260T polymorphism and inflammatory bowel disease: a meta-analysis.

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    Zhengting Wang

    Full Text Available BACKGROUND: The gene encoding CD14 has been proposed as an IBD-susceptibility gene with its polymorphism C-260T being widely evaluated, yet with conflicting results. The aim of this study was to investigate the association between this polymorphism and IBD by conducting a meta-analysis. METHODOLOGY/PRINCIPAL FINDINGS: Seventeen articles met the inclusion criteria, which included a total of 18 case-control studies, including 1900 ulcerative colitis (UC cases, 2535 Crohn's disease (CD cases, and 4004 controls. Data were analyzed using STATA software. Overall, association between C-260T polymorphism and increased UC risk was significant in allelic comparison (odds ratio [OR]  =1.21, 95% confidence interval [CI]: 1.02-1.43; P=0.027, homozygote model (OR  =1.44, 95% CI: 1.03-2.01; P=0.033, as well as dominant model (OR  =1.36, 95% CI: 1.06-1.75; P=0.016. However, there was negative association between this polymorphism and CD risk across all genetic models. Subgroup analyses by ethnicity suggested the risk-conferring profiles of -260T allele and -260 TT genotype with UC in Asians, but not in Caucasians. There was a low probability of publication bias. CONCLUSIONS/SIGNIFICANCE: Expanding previous results of individual studies, our findings demonstrated that CD14 gene C-260T polymorphism might be a promising candidate marker in susceptibility to UC, especially in Asians.

  16. Effect of Plasminogen Activator Inhibitor-1 and Tissue Plasminogen Activator Polymorphisms on Susceptibility to Type 2 Diabetes in Malaysian Subjects

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    Zaid Al-Hamodi

    2012-01-01

    Full Text Available Elevated activity of plasminogen activator inhibitor-1 (PAI-1 and decreased tissue plasminogen activator (tPA activity are considered to be important risk factors for type 2 diabetes mellitus (T2DM and metabolic syndrome (MetS. The aim of this study was to investigate the association of the PAI-1 4G/5G and tPA Alu-repeat I/D polymorphisms with T2DM in Malaysian subjects. Serum insulin, coronary risk panel, plasma glucose, and PAI-1 4G/5G and tPA Alu-repeat I/D polymorphisms were studied in 303 T2DM subjects (227 with MetS and 76 without MetS and 131 normal subjects without diabetes and MetS. Statistical analysis showed that the dominant and additive models of PAI-1 4G/5G polymorphism showed a weak association with T2DM without MetS (OR=2.35, P=0.045; OR=1.67, P=0.058. On the other hand, the recessive model of the tPA Alu-repeat I/D polymorphism showed an association with T2DM with MetS (OR=3.32, P=0.013 whereas the dominant and additive models of the tPA Alu-repeat I/D polymorphism were not associated with T2DM either with or without MetS.

  17. Phenotypic evolution from genetic polymorphisms in a radial network architecture

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    Siegel Paul B

    2007-11-01

    Full Text Available Abstract Background The genetic architecture of a quantitative trait influences the phenotypic response to natural or artificial selection. One of the main objectives of genetic mapping studies is to identify the genetic factors underlying complex traits and understand how they contribute to phenotypic expression. Presently, we are good at identifying and locating individual loci with large effects, but there is a void in describing more complex genetic architectures. Although large networks of connected genes have been reported, there is an almost complete lack of information on how polymorphisms in these networks contribute to phenotypic variation and change. To date, most of our understanding comes from theoretical, model-based studies, and it remains difficult to assess how realistic their conclusions are as they lack empirical support. Results A previous study provided evidence that nearly half of the difference in eight-week body weight between two divergently selected lines of chickens was a result of four loci organized in a 'radial' network (one central locus interacting with three 'radial' loci that, in turn, only interacted with the central locus. Here, we study the relationship between phenotypic change and genetic polymorphism in this empirically detected network. We use a model-free approach to study, through individual-based simulations, the dynamic properties of this polymorphic and epistatic genetic architecture. The study provides new insights to how epistasis can modify the selection response, buffer and reveal effects of major loci leading to a progressive release of genetic variation. We also illustrate the difficulty of predicting genetic architecture from observed selection response, and discuss mechanisms that might lead to misleading conclusions on underlying genetic architectures from quantitative trait locus (QTL experiments in selected populations. Conclusion Considering both molecular (QTL and phenotypic (selection

  18. Survey and analysis of crystal polymorphism in organic structures

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    Kortney Kersten

    2018-03-01

    Full Text Available With the intention of producing the most comprehensive treatment of the prevalence of crystal polymorphism among structurally characterized materials, all polymorphic compounds flagged as such within the Cambridge Structural Database (CSD are analysed and a list of crystallographically characterized organic polymorphic compounds is assembled. Classifying these structures into subclasses of anhydrates, salts, hydrates, non-hydrated solvates and cocrystals reveals that there are significant variations in polymorphism prevalence as a function of crystal type, a fact which has not previously been recognized in the literature. It is also shown that, as a percentage, polymorphic entries are decreasing temporally within the CSD, with the notable exception of cocrystals, which continue to rise at a rate that is a constant fraction of the overall entries. Some phenomena identified that require additional scrutiny include the relative prevalence of temperature-induced phase transitions among organic salts and the paucity of polymorphism in crystals with three or more chemical components.

  19. Conformational flexibility and packing plausibility of repaglinide polymorphs

    Science.gov (United States)

    Rani, Dimpy; Goyal, Parnika; Chadha, Renu

    2018-04-01

    The present manuscript highlights the structural insight into the repaglinide polymorphs. The experimental screening for the possible crystal forms were carried out using various solvents, which generated three forms. The crystal structure of Form II and III was determined using PXRD pattern whereas structural analysis of Form I has already been reported. Form I, II and II was found to exist in P212121, PNA21 and P21/c space groups respectively. Conformational analysis was performed to account the conformational flexibility of RPG. The obtained conformers were further utilized to obtain the information about the crystal packing pattern of RPG polymorphs by polymorph prediction module. The lattice energy landscape, depicting the relationship between lattice energy and density of the polymorphs has been obtained for various possible polymorphs. The experimentally isolated polymorphs were successfully fitted into lattice energy landscape.

  20. Association between Factor V Gene Polymorphism and Risk of Ischemic Stroke: An Updated Meta-Analysis.

    Science.gov (United States)

    Alhazzani, Adel Ali; Kumar, Amit; Selim, Magdy

    2018-02-22

    Ischemic stroke is a complex, multifactorial, and polygenic disease. Reports on relationship between Factor V G1691A single nucleotide gene polymorphism and ischemic stroke have revealed inconsistent results. We conducted an updated meta-analysis to determine the role of Factor V single nucleotide gene polymorphism in ischemic stroke. We searched the literature using academic electronic databases that is, PubMed, Trip Data Base, EBSCO, and Google Scholar, last search up to September 2017. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from fixed or random effects models whichever applicable using software STATA version 13 (StataCorp LP, College Station, TX). Forty case-control studies met the inclusion criteria, which included 6860 cases and 18,025 controls. Altogether, 19 studies in young adults (age  40). Four studies did not report the mean age at recruitment. Significant association between Factor V G1691A gene polymorphism and risk of ischemic stroke were observed under dominant model (OR 1.40; 95% CI: 1.22 to 1.62, P value analysis suggested substantial association of Factor V gene polymorphism and risk of ischemic stroke in cases with onset at young age (OR 1.84; 95% CI: 1.47 to 2.30), but was not statistical significant in cases at old age (>40 years). Factor V G1691A single nucleotide gene polymorphism was associated with risk of ischemic stroke mainly in young adults. Further research with adequately powered prospective studies in homogenous subjects are required to determine the nature of association in young stroke. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  1. Association between TLR2 + 2477G/A polymorphism and bacterial meningitis: a meta-analysis.

    Science.gov (United States)

    Jin, Xiaochun; Yin, Shuzhou; Zhang, Youtao; Chen, Xu

    2018-02-19

    Toll-like receptor 2 (TLR2) is a key member of TLRs, which is crucial in the initial inflammatory response against bacteria. TLR2, is also the initial barrier against bacterial infection and plays an important role in recognising a variety of bacterial lipoproteins. Several studies have been performed to investigate the TLR2 + 2477G/A polymorphism and bacterial meningitis susceptibility. Unfortunately, the results of previous studies were controversial. Therefore, we performed a meta-analysis to derive a more precise estimation of the association. The association between the TLR2 + 2477G/A polymorphism and bacterial meningitis susceptibility was assessed by odds ratios together with their 95% confidence intervals (CI). Six studies were enrolled in the present meta-analysis. Overall, no significant association between TLR2 + 2477G/A polymorphism and bacterial meningitis risk were found under allele contrast (A vs. G: OR = 1.15, 95% CI = 0.93-1.43, P = 0.202), recessive genetic model (AA vs. OR = 1.12, 95% CI = 0.90-1.41, P = 0.313). The significant association was found between TLR2 + 2477G/A polymorphism and pneumococcal meningitis risk under allele contrast (A vs. G: OR = 1.54, 95% CI = 1.01-2.36, P = 0.046), recessive genetic model (AA vs. OR = 1.63, 95% CI = 1.03-2.57, P = 0.035). We conclude that TLR2 + 2477G/A polymorphism is not associated with meningococcal meningitis risk but contributes an increased risk of pneumococcal meningitis.

  2. Screening for, and management of, possible arrhythmogenic syndromes (channelopathies/ion channel diseases)

    DEFF Research Database (Denmark)

    Svendsen, Jesper Hastrup; Geelen, Peter; Svendsen, Jesper Hastrup

    2010-01-01

    This survey assesses the current management strategies for individuals with electrocardiographic features, suggesting an arrhythmogenic syndrome [including long QT syndrome (LQTS), Brugada syndrome (BS), catecholaminergic polymorphic ventricular tachycardia (CPVT) or short QT syndrome] or family ...

  3. Channelopathies as Causes of Sudden Cardiac Death

    NARCIS (Netherlands)

    Schwartz, Peter J.; Ackerman, Michael J.; Wilde, Arthur A. M.

    2017-01-01

    This article reviews the main clinical aspects of 3 channelopathies: the long QT syndrome, the catecholaminergic polymorphic ventricular tachycardia, and the Brugada syndrome. The text summarizes our views on clinical presentation and diagnosis, on risk stratification, and on therapy. Special

  4. Channelopathies, genetic testing and risk stratification

    NARCIS (Netherlands)

    Wilde, Arthur A. M.; Amin, Ahmad

    2017-01-01

    The cardiac channelopathies are a group of diseases with (disease-) specific electrocardiographic (ECG) characteristics and a disease-specific risk of sudden cardiac death (SCD). This group includes the Long QT Syndromes (LQTS), Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), Brugada

  5. Expanding spectrum of human RYR2-related disease: new electrocardiographic, structural, and genetic features

    NARCIS (Netherlands)

    Bhuiyan, Zahurul A.; van den Berg, Maarten P.; van Tintelen, J. Peter; Bink-Boelkens, Margreet T. E.; Wiesfeld, Ans C. P.; Alders, Marielle; Postma, Alex V.; van Langen, Irene; Mannens, Marcel M. A. M.; Wilde, Arthur A. M.

    2007-01-01

    BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia is a disease characterized by ventricular arrhythmias elicited exclusively under adrenergic stress. Additional features include baseline bradycardia and, in some patients, right ventricular fatty displacement. The clinical spectrum is

  6. Expanding spectrum of human RYR2-related disease - New electrocardiographic, structural, and genetic features

    NARCIS (Netherlands)

    Bhuiyan, Zahurul A.; van den Berg, Maarten P.; van Tintelen, J. Peter; Bink-Boelkens, Margreet T. E.; Wiesfeld, Ans C. P.; Alders, Marielle; Postma, Alex V.; van Langen, Irene; Mannens, Marcel M. A. M.; Wilde, Arthur A. M.

    2007-01-01

    Background - Catecholaminergic polymorphic ventricular tachycardia is a disease characterized by ventricular arrhythmias elicited exclusively under adrenergic stress. Additional features include baseline bradycardia and, in some patients, right ventricular fatty displacement. The clinical spectrum

  7. Association of LPP and TAGAP Polymorphisms with Celiac Disease Risk: A Meta-Analysis

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    Shi-Qi Huang

    2017-02-01

    Full Text Available Background: Lipoma preferred partner (LPP and T-cell activation Rho GTPase activating protein (TAGAP polymorphisms might influence the susceptibility to celiac disease. Therefore, we performed a meta-analysis by identifying relevant studies to estimate the risks of these polymorphisms on celiac disease. Methods: The PubMed, Web of Science and Embase databases were searched (up to October 2016 for LPP rs1464510 and TAGAP rs1738074 polymorphisms. Results: This meta-analysis included the same 7 studies for LPP rs1464510 and TAGAP rs1738074. The minor risk A allele at both rs1464510 and rs1738074 carried risks (odds ratios of 1.26 (95% CI: 1.22–1.30 and 1.17 (95% CI: 1.14–1.21, respectively, which contributed to increased risks in all celiac disease patients by 10.72% and 6.59%, respectively. The estimated lambdas were 0.512 and 0.496, respectively, suggesting that a co-dominant model would be suitable for both gene effects. Conclusions: This meta-analysis provides robust estimates that polymorphisms in LPP and TAGAP genes are potential risk factors for celiac disease in European and American. Prospective studies and more genome-wide association studies (GWAS are needed to confirm these findings, and some corresponding molecular biology experiments should be carried out to clarify the pathogenic mechanisms of celiac disease.

  8. Insertion-deletion polymorphisms (indels as genetic markers in natural populations

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    Johansson Malin

    2008-01-01

    Full Text Available Abstract Background We introduce the use of short insertion-deletion polymorphisms (indels for genetic analysis of natural populations. Results Sequence reads from light shot-gun sequencing efforts of different dog breeds were aligned to the dog genome reference sequence and gaps corresponding to indels were identified. One hundred candidate markers (4-bp indels were selected and genotyped in unrelated dogs (n = 7 and wolves (n = 18. Eighty-one and 76 out of 94 could be validated as polymorphic loci in the respective sample. Mean indel heterozygosity in a diverse set of wolves was 19%, and 74% of the loci had a minor allele frequency of >10%. Indels found to be polymorphic in wolves were subsequently genotyped in a highly bottlenecked Scandinavian wolf population. Fifty-one loci turned out to be polymorphic, showing their utility even in a population with low genetic diversity. In this population, individual heterozygosity measured at indel and microsatellite loci were highly correlated. Conclusion With an increasing amount of sequence information gathered from non-model organisms, we suggest that indels will come to form an important source of genetic markers, easy and cheap to genotype, for studies of natural populations.

  9. Intraspecific DNA methylation polymorphism in the non-edible oilseed plant castor bean

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    Shan He

    2017-10-01

    Full Text Available Investigation of the relationships of phenotypic and epigenetic variations might be a good way to dissect the genetic or molecular basis of phenotypic variation and plasticity in plants. Castor bean (Ricinus communis L., an important non-edible oilseed crop, is a mono-species genus plant in the family Euphorbiaceae. Since it displays rich phenotypic variations with low genetic diversity, castor bean is a good model to investigate the molecular basis of phenotypic and epigenetic variations. Cytosine DNA methylation represents a major molecular mechanism of epigenetic occurrence. In this study, epigenetic diversity of sixty landrace accessions collected worldwide was investigated using the methylation-sensitive amplification polymorphism (MSAP technique. Results showed that the epigenetic diversity (based on the polymorphism of DNA methylated loci exhibited a medium variation (Ne = 1.395, He = 0.242, I = 0.366 at the population level though the variation was great, ranging from 3.80% to 34.31% among accessions. Both population structure analysis and the phylogenetic construction (using the neighbor-joining criteria revealed that the two main clades were identified, but they did not display a distinct geographic structure. After inspecting the location of polymorphic methylated loci on genome we identified that the polymorphic methylated loci occur widely in nuclear and organelle genomes. This study provides new data to understand phenotypic and epigenetic variations in castor bean.

  10. Host erythrocyte polymorphisms and exposure to Plasmodium falciparum in Papua New Guinea

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    Imrie Heather J

    2008-01-01

    Full Text Available Abstract Background The protection afforded by human erythrocyte polymorphisms against the malaria parasite, Plasmodium falciparum, has been proposed to be due to reduced ability of the parasite to invade or develop in erythrocytes. If this were the case, variable levels of parasitaemia and rates of seroconversion to infected-erythrocyte variant surface antigens (VSA should be seen in different host genotypes. Methods To test this hypothesis, P. falciparum parasitaemia and anti-VSA antibody levels were measured in a cohort of 555 asymptomatic children from an area of intense malaria transmission in Papua New Guinea. Linear mixed models were used to investigate the effect of α+-thalassaemia, complement receptor-1 and south-east Asian ovalocytosis, as well as glucose-6-phosphate dehydrogenase deficiency and ABO blood group on parasitaemia and age-specific seroconversion to VSA. Results No host polymorphism showed a significant association with both parasite prevalence/density and age-specific seroconversion to VSA. Conclusion Host erythrocyte polymorphisms commonly found in Papua New Guinea do not effect exposure to blood stage P. falciparum infection. This contrasts with data for sickle cell trait and highlights that the above-mentioned polymorphisms may confer protection against malaria via distinct mechanisms.

  11. The association between PAI-1 -675 4G/5G polymorphism and type 2 diabetes mellitus.

    Science.gov (United States)

    Chen, L; Li, S-Y; Liu, M

    2017-08-15

    In this study, we aimed to analyze the association between plasminogen activator inhibitor 1 (PAI-1) -675 4G/5G polymorphism and type 2 diabetes mellitus (T2DM) risk. We included in 187 T2DM patients and 186 heathy controls between 2014 and 2017 from Tianjin Gong An Hospital, China. All patients and controls were ethnically Chinese Han population. The primers and polymerase chain reaction (PCR) conditions were performed. Results from this case-control study suggested that PAI-1 -675 4G/5G polymorphism was not associated with T2DM risk in four genetic models. Additionally, PAI-1 -675 4G/5G polymorphism was not associated with clinical and laboratory characteristics, such as age, gender, body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, triglycerides, and HbA1c. In conclusion, this case-control study suggested that PAI-1 -675 4G/5G polymorphism was not associated with T2DM risk in this population.

  12. Prothrombotic Gene Polymorphisms in Young Patients with Cerebrovascular Accident

    Directory of Open Access Journals (Sweden)

    Kuyaþ Hekimler Öztürk

    2013-07-01

    Full Text Available Aim: Cerebrovascular diseases are complex multifactorial disorders showing an increased incidence with increasing age and affected by genetic and environmental factors. Although risk factors for cerebrovascular diseases include age, sex, lineage, hypertension, diabetes mellitus, hypercholesterolemia; in young cerebrovascular patients below age 45, genetic factors may also contribute to the etiology. In this retrospective study, prothrombotic gene polymorphisms which are thought to be related with formation of disease in young adults with cerebrovascular accident (CVA were investigated. Material and Method: In the current study, Methylenetetrahydropholate Reductase (MTHFR C677T and A129C; Prothrombin (Factor II G20210A; Factor V Leiden G1691A prothrombotic gene polymorphisms were evaluated for 43 young patients under the age of 45 with cerebrovascular accident history. Result: For 43 young patients with cerebrovascular incident history, the frequency of following polymorphisms were determined as follows; MTHFR C677T polymorphism heterozygous frequency is 46.1%, homozygous frequency is 9.3%; MTHFR A1298C polymorphism heterozygous frequency is 39.47%, homozygous frequency is 26.31%; Prothrombin polymorphism heterozygous and homozygous frequency is 2.3%; FactorV Leiden polymorphism heterozygous frequency is 9.3%. Discussion: After evaluation the experimental results, we believe that MTHFR gene C677T and A1298C polymorphisms might be risk factors in CVAs. It was observed that cigarette usage, hypertension and existence of family story in addition to these polymorphisms increase the available risk.

  13. Amplified restriction fragment length polymorphism in parasite genetics.

    Science.gov (United States)

    Masiga, D K; Tait, A; Turner, C M

    2000-08-01

    The amplified restriction fragment length polymorphism (AFLP) technique is a relatively new method for the analysis of polymorphism that has not yet been widely used in parasitology. In this article, Dan Masiga, Andy Tait and Mike Turner provide a brief introduction to AFLP and illustrate how it can be used in the investigation of marker inheritance in genetic crosses and in the analysis of polymorphism of field populations. They also briefly highlight the strengths and weaknesses of AFLP in comparison with other methods for detecting polymorphism and conclude that AFLP is a very useful addition to the range of techniques available.

  14. Association between vitamin D receptor gene polymorphisms and breast cancer risk: a meta-analysis of 39 studies.

    Directory of Open Access Journals (Sweden)

    Kai Zhang

    Full Text Available BACKGROUND: The associations between vitamin D receptor (VDR gene polymorphisms and breast cancer risk were comprehensively investigated to clarify issues that remain controversial. METHODOLOGY/PRINCIPAL FINDINGS: An electronic search was conducted of several databases, including PubMed, the Cochrane library, Web of Science, EMBASE, CBM and CNKI, for papers that describe the association between Fok1, poly-A repeat, Bsm1, Taq1 or Apa1 polymorphisms of the VDR gene and breast cancer risk. Summary odds ratios and 95% confidence intervals (CI were estimated based on a fixed-effect model (FEM or random-effect model (REM, depending on the absence or presence of significant heterogeneity. A total of 39 studies met the inclusion criteria. A meta-analysis of high-quality studies showed that the Fok1 polymorphism of the VDR gene was associated with an increased risk of breast cancer (ff vs. Ff+FF, OR: 1.09, 95%CI: 1.02 to 1.16, p = 0.007. No significant associations were observed between the other polymorphisms and breast cancer risk. No positive results were detected by pooling the results of all relevant studies. CONCLUSION: A meta-analysis of high-quality studies demonstrated that the Fok1 polymorphism of the VDR gene was closely associated with breast cancer risk.

  15. ABO Gene Polymorphism and Thrombomodulin ?33G>A Polymorphism Were Not Risk Factors for Myocardial Infarction in Javanese Men

    OpenAIRE

    Lukitasari, Mifetika; Sadewa, Ahmad Hamim; Rohman, Mohammad Saifur

    2017-01-01

    Genetic factors contribute to about a half of coronary artery diseases. During the last several decades, some studies suggested that non-O blood group and thrombomodulin polymorphism ?33G>A are the risk factors of coronary artery disease especially in Asia. There was no prior study in Indonesia regarding this issue. Hence, this study was designed to investigate the correlation of ABO polymorphism and thrombomodulin polymorphism ?33G>A with the incidence of acute myocardial infarction (AMI). A...

  16. Association between methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphisms and essential hypertension: a systematic review and meta-analysis.

    Science.gov (United States)

    Wu, Yi-Le; Hu, Cai-Yun; Lu, Shan-Shan; Gong, Feng-Feng; Feng, Fang; Qian, Zhen-Zhong; Ding, Xiu-Xiu; Yang, Hui-Yun; Sun, Ye-Huan

    2014-12-01

    Many studies have investigated the role of 5,10-methylenetetrahydrofolate reductase gene (MTHFR) C677T/A1298C polymorphisms in essential hypertension (EH), but results are inconclusive. The purpose of this meta-analysis was to clarify the effects of MTHFR C677T/A1298C polymorphisms on the risk of EH. Electronic databases were searched to identify relevant studies published until January 2014. Data were extracted by two independent authors. Odds ratios (ORs) with 95%confidence intervals (CIs) were used to assess the association between MTHFR C677T/A1298C polymorphisms and the risk of EH using random effect models or fixed effect models. Finally,30 studies with 5207 cases and 5383 controls were included for C677T polymorphism and 6 studies with 1009 cases and 994 controls were included for A1298C polymorphism. Meta-analysis results indicated that MTHFR C677T polymorphism contributed to an increased risk of EH (for T vs. C: OR=1.30, 95%CI=1.18–1.43; for TT+CT vs. CC: OR=1.34, 95%CI=1.24–1.46; for TT vs. CC: OR=1.62, 95%CI=1.32–1.99; for TT vs. CT+CC: OR=1.41, 95%CI=1.26–1.59). However, no significant association was detected between MTHFR A1298C polymorphism and the risk of EH. This meta-analysis supports that MTHFR C677T polymorphism plays a role in developing EH. MTHFR A1298C polymorphism may not be associated with an increased risk of EH. Further large and well-designed studies are warranted to confirm these findings.

  17. Novel Processing of Ceramics with Polymorphic Control

    Science.gov (United States)

    Jodhani, Gagan

    Polymorphism is an important phenomenon exhibited by many materials, including ceramic oxides. The availability of multiple structural configurations for the same chemical composition opens the pathway to a large number of phases with distinct properties. The formation of the crystal structures can be directly correlated to the processing temperature and/or pressure as well as the particle size for nanomaterials. This work focuses on the tailored synthesis of the desired polymorphs of binary and ternary metal oxides through nanoscale processes with emphasis on flame spray pyrolysis. Flame spray pyrolysis (FSP) is a scalable nano-manufacturing process used for the synthesis of oxide based ceramics. The advantage of this process lies in ease of operation and inexpensive processing as well as the uniformity in the particle size distribution of the products. It is a rapid solidification process involving the atomization of precursor using high temperature gradients and low residence times in the flame. Thus, metastable polymorphs have successfully been synthesized by FSP. Although a wide variety of studies have been conducted on the synthesis and applications of ceramics via FSP there has been scarce knowledge on the actual dynamics of crystal structure formation during the process. Various solution parameters were studied to understand the particle and crystal structure formation for the FSP powders. The process parameters were kept the same; 1.5 slm methane and 3.0 slm O2 was used as fuel for the flame, 5slm oxygen was used as dispersion gas and the precursor was fed at 5ml/min. MoO3 was synthesized using different concentrations of precursor and the particle sizes obtained were correlated to the materials parameters such as solution concentration and amount of organic precursor solvent. Another study was conducted on formation of WO3 polymorphs using organic precursor salts dissolved in organic solvent. The solution was prepared to obtain low particle sizes and to

  18. Nucleosomes shape DNA polymorphism and divergence.

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    Sasha A Langley

    2014-07-01

    Full Text Available An estimated 80% of genomic DNA in eukaryotes is packaged as nucleosomes, which, together with the remaining interstitial linker regions, generate higher order chromatin structures [1]. Nucleosome sequences isolated from diverse organisms exhibit ∼10 bp periodic variations in AA, TT and GC dinucleotide frequencies. These sequence elements generate intrinsically curved DNA and help establish the histone-DNA interface. We investigated an important unanswered question concerning the interplay between chromatin organization and genome evolution: do the DNA sequence preferences inherent to the highly conserved histone core exert detectable natural selection on genomic divergence and polymorphism? To address this hypothesis, we isolated nucleosomal DNA sequences from Drosophila melanogaster embryos and examined the underlying genomic variation within and between species. We found that divergence along the D. melanogaster lineage is periodic across nucleosome regions with base changes following preferred nucleotides, providing new evidence for systematic evolutionary forces in the generation and maintenance of nucleosome-associated dinucleotide periodicities. Further, Single Nucleotide Polymorphism (SNP frequency spectra show striking periodicities across nucleosomal regions, paralleling divergence patterns. Preferred alleles occur at higher frequencies in natural populations, consistent with a central role for natural selection. These patterns are stronger for nucleosomes in introns than in intergenic regions, suggesting selection is stronger in transcribed regions where nucleosomes undergo more displacement, remodeling and functional modification. In addition, we observe a large-scale (∼180 bp periodic enrichment of AA/TT dinucleotides associated with nucleosome occupancy, while GC dinucleotide frequency peaks in linker regions. Divergence and polymorphism data also support a role for natural selection in the generation and maintenance of these

  19. Completed suicide, depression, and RELN polymorphisms.

    Science.gov (United States)

    Bučić, Marina; Pregelj, Peter; Zupanc, Tomaž; Videtič Paska, Alja

    2016-10-01

    Suicidal behavior is a complex phenomenon, an outcome of both environmental and genetic factors. In the present study, we looked for a potential association between suicide and the reelin gene as reelin has been associated previously with several psychiatric disorders, including depression. We analyzed three single nucleotide polymorphisms (SNPs) in the reelin gene, rs2965087, rs7341475, and rs362691, in a population of 483 suicide victims and 332 healthy controls, all Caucasians. An analysis was carried out according to sex and the method of suicide. In a group of 77 suicide victims with psychological autopsy data, suicide threats, suicide in the family, and number of depression symptoms were also considered. Analysis of all three polymorphisms did not confirm an association with suicide in general. However, for subjects included in psychological autopsy study, association with previous announcement of suicide in the group of subjects with TT genotype for polymorphism rs2965087 was determined. Furthermore, the results pointed to an association with reported suicide in the family of suicide victims in case of the TT genotype. In contrast, the number of depressive symptoms, besides suicidal threats, was lower in the group with the TT genotype. Psychological autopsies can be associated with recall bias and the sample was rather small and therefore underpowered. The present investigation, performed on a study sample from a population with one of the highest suicide rates in the world, indicated an association between rs2965087 in the reelin gene and the expression of suicidal threats a month before suicide in contrast to other symptoms of depression.

  20. KIAA0319 gene polymorphisms are associated with developmental dyslexia in Chinese Uyghur children

    Science.gov (United States)

    Zhao, Hua; Chen, Yun; Zhang, Bao-ping; Zuo, Peng-xiang

    2016-01-01

    The gene KIAA0319 has been reported to be associated with developmental dyslexia (DD) in previous studies, although the results have not always been consistent. However, few studies have been conducted in Uyghur populations. In the present study, we aimed to investigate the association of KIAA0319 polymorphisms and DD in individuals of Uyghurian descent. We used a custom-by-design 48-Plex SNPscan Kit to genotype 18 single-nucleotide polymorphisms (SNPs) of KIAA0319 in a group of 196 children with dyslexia and 196 controls of Uyghur descent aged 8–12 years. As a result, 7 SNPs (Pmin=0.001) of KIAA0319 had nominal significant differences between the cases and controls under specific genotypic models. The two SNPs rs6935076 (P=0.020 under dominant model; P=0.028 under additive model) and rs3756821 (P=0.021 under additive model) remained significantly associated with dyslexia after Bonferroni correction. Linkage disequilibrium analysis showed three blocks within KIAA0319, and only a 10-SNP haplotype in block 3 was present at significantly different frequencies in the dyslexic children and controls. This study indicated that genetic polymorphisms of KIAA0319 are associated with an increased risk of DD in the Uyghur population. PMID:27098879

  1. ABO Gene Polymorphism and Thrombomodulin -33G>A Polymorphism Were Not Risk Factors for Myocardial Infarction in Javanese Men.

    Science.gov (United States)

    Lukitasari, Mifetika; Sadewa, Ahmad Hamim; Rohman, Mohammad Saifur

    2017-01-01

    Genetic factors contribute to about a half of coronary artery diseases. During the last several decades, some studies suggested that non-O blood group and thrombomodulin polymorphism -33G>A are the risk factors of coronary artery disease especially in Asia. There was no prior study in Indonesia regarding this issue. Hence, this study was designed to investigate the correlation of ABO polymorphism and thrombomodulin polymorphism -33G>A with the incidence of acute myocardial infarction (AMI). A total of 192 subjects were enrolled in this case control study. AMI patients were diagnosed based on World Health Organization criteria. Healthy patients were subjects with AMI risk factor without any sign and symptoms of AMI. Patients with diabetes mellitus, cancer, and arrhythmia were excluded from this study. Genotyping for both polymorphisms was performed by PCR RFLP methods. The result of this study suggested that ABO polymorphism and thrombomodulin polymorphism -33G>A were not risk factors of AMI, p = 0.727 and p = 0.699, respectively. Furthermore, the analysis to identify the synergy of these polymorphisms failed to prove their correlation with AMI ( p = 0.118). Conclusively, this study showed that ABO polymorphism and thrombomodulin polymorphism -33G>A were not risk factors of AMI.

  2. Development of population pharmacokinetics model of icotinib with non-linear absorption characters in healthy Chinese volunteers to assess the CYP2C19 polymorphism and food-intake effect.

    Science.gov (United States)

    Hu, Pei; Chen, Jia; Liu, Dongyang; Zheng, Xin; Zhao, Qian; Jiang, Ji

    2015-07-01

    Icotinib is a potent and selective inhibitor of epidermal growth factor receptors (EGFR) approved to treat non-small cell lung cancer (NSCLC). However, its high variability may impede its application. The objectives of this analysis were to assess plasma pharmacokinetics and identify covariates that may explain variability in icotinib absorption and/or disposition following single dose of icotinib in healthy volunteers. Data from two clinical studies (n = 22) were analyzed. One study was designed as three-period and Latin-squared (six sequence) trial to evaluate dose proportionality, and the other one was designed as two-way crossover trial to evaluate food effect on pharmacokinetics (PK) characters. Icotinib concentrations in plasma were analyzed using non-linear mixed-effects model (NONMEM) method. The model was used to assess influence of food, demographic characteristics, measurements of blood biochemistry, and CYP2C19 genotype on PK characters of icotinib in humans. The final model was diagnosed by goodness-of-fit plots and evaluated by visual predictive check (VPC) and bootstrap methods. A two-compartment model with saturated absorption character was developed to capture icotinib pharmacokinetics. Typical value of clearance, distribution clearance, central volume of distribution, maximum absorption rate were 29.5 L/h, 24.9 L/h, 18.5 L, 122.2 L and 204,245 μg/h, respectively. When icotinib was administrated with food, bioavailability was estimated to be increased by 48%. Inter-occasion variability was identified to affect on maximum absorption rate constant in food-effect study. CL was identified to be significantly influenced by age, albumin concentration (ALB), and CYP2C19 genotype. No obvious bias was found by VPC and bootstrap methods. The developed model can capture icotinib pharmacokinetics well in healthy volunteers. Food intake can increase icotinib exposure. Three covariates, age, albumin concentration, and CYP2C19 genotype, were identified to

  3. Milk protein polymorphisms in Brazilian Zebu cattle

    OpenAIRE

    Silva, Ivana Tramontina da; Del Lama, Marco Antonio

    1997-01-01

    Five bovine milk protein polymorphisms were studied in Zebuine cattle raised in Brazil, through horizontal electrophoresis on starch gel containing urea and 2-mercaptoethanol, using basic and acidic buffer systems. Allelic frequencies for a-La, b-Lg, aS1-Cn, b-Cn and k-Cn loci were estimated in six Gyr herds (N = 283), six Guzerat herds (N = 205), one Nelore herd (N = 17) and one Sindi herd (N = 22), all from São Paulo or Minas Gerais State, Brazil. Genotypic frequencies observed for each loc...

  4. What Determines the Ice Polymorph in Clouds?

    Science.gov (United States)

    Hudait, Arpa; Molinero, Valeria

    2016-07-20

    Ice crystals in the atmosphere nucleate from supercooled liquid water and grow by vapor uptake. The structure of the ice polymorph grown has strong impact on the morphology and light scattering of the ice crystals, modulates the amount of water vapor in ice clouds, and can impact the molecular uptake and reactivity of atmospheric aerosols. Experiments and molecular simulations indicate that ice nucleated and grown from deeply supercooled liquid water is metastable stacking disordered ice. The ice polymorph grown from vapor has not yet been determined. Here we use large-scale molecular simulations to determine the structure of ice that grows as a result of uptake of water vapor in the temperature range relevant to cirrus and mixed-phase clouds, elucidate the molecular mechanism of the formation of ice at the vapor interface, and compute the free energy difference between cubic and hexagonal ice interfaces with vapor. We find that vapor deposition results in growth of stacking disordered ice only under conditions of extreme supersaturation, for which a nonequilibrium liquid layer completely wets the surface of ice. Such extreme conditions have been used to produce stacking disordered frost ice in experiments and may be plausible in the summer polar mesosphere. Growth of ice from vapor at moderate supersaturations in the temperature range relevant to cirrus and mixed-phase clouds, from 200 to 260 K, produces exclusively the stable hexagonal ice polymorph. Cubic ice is disfavored with respect to hexagonal ice not only by a small penalty in the bulk free energy (3.6 ± 1.5 J mol(-1) at 260 K) but also by a large free energy penalty at the ice-vapor interface (89.7 ± 12.8 J mol(-1) at 260 K). The latter originates in higher vibrational entropy of the hexagonal-terminated ice-vapor interface. We predict that the free energy penalty against the cubic ice interface should decrease strongly with temperature, resulting in some degree of stacking disorder in ice grown from

  5. Impact of the PPAR gamma-2 gene polymorphisms on the metabolic ...

    Indian Academy of Sciences (India)

    2016-08-04

    figure 1b). The lean women characterized by C1431C polymorphism had lower blood glucose concentrations (β=−0.2103,. Table 1. Polymorphisms of the PPARG gene investigated in the study. Polymorphism. SNP ID. Gene.

  6. Role of glutathione S-transferase P-1 (GSTP-1 gene polymorphism in COPD patients

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    Tarek F. El-Gazzar

    2016-10-01

    Conclusion: There is a significant association between GSTP1 gene polymorphism and the development of COPD, and smoking have a role in GSTP1 gene polymorphism. The polymorphism has no relation to disease severity.

  7. Intergenic Variable-Number Tandem-Repeat Polymorphism Upstream of rocA Alters Toxin Production and Enhances Virulence in Streptococcus pyogenes.

    Science.gov (United States)

    Zhu, Luchang; Olsen, Randall J; Horstmann, Nicola; Shelburne, Samuel A; Fan, Jia; Hu, Ye; Musser, James M

    2016-07-01

    Variable-number tandem-repeat (VNTR) polymorphisms are ubiquitous in bacteria. However, only a small fraction of them has been functionally studied. Here, we report an intergenic VNTR polymorphism that confers an altered level of toxin production and increased virulence in Streptococcus pyogenes The nature of the polymorphism is a one-unit deletion in a three-tandem-repeat locus upstream of the rocA gene encoding a sensor kinase. S. pyogenes strains with this type of polymorphism cause human infection and produce significantly larger amounts of the secreted cytotoxins S. pyogenes NADase (SPN) and streptolysin O (SLO). Using isogenic mutant strains, we demonstrate that deleting one or more units of the tandem repeats abolished RocA production, reduced CovR phosphorylation, derepressed multiple CovR-regulated virulence factors (such as SPN and SLO), and increased virulence in a mouse model of necrotizing fasciitis. The phenotypic effect of the VNTR polymorphism was nearly the same as that of inactivating the rocA gene. In summary, we identified and characterized an intergenic VNTR polymorphism in S. pyogenes that affects toxin production and virulence. These new findings enhance understanding of rocA biology and the function of VNTR polymorphisms in S. pyogenes. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  8. Interleukin-10 Polymorphisms in Association with Prognosis in Patients with B-Cell Lymphoma Treated by R-CHOP

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    Min Kyeong Kim

    2016-12-01

    Full Text Available Interleukin-10 (IL10 plays an important role in initiating and maintaining an appropriate immune response to non-Hodgkin lymphoma (NHL. Previous studies have revealed that the transcription of IL10 mRNA and its protein expression may be infl uenced by several single-nucleotide polymorphisms in the promoter and intron regions, including rs1800896, rs1800871, and rs1800872. However, the impact of polymorphisms of the IL10 gene on NHL prognosis has not been fully elucidated. Here, we investigated the association between IL10 polymorphisms and NHL prognosis. This study involved 112 NHL patients treated at the National Cancer Center, Korea. The median age was 57 years, and 70 patients (62.5% were men. Clinical characteristics, including age, performance status, stage, and extra-nodal involvement, as well as cell lineage and International Prognostic Index (IPI, were evaluated. A total of four polymorphisms in IL10 with heterozygous alleles were analyzed for hazard ratios of overall survival (OS and progression-free survival (PFS using Cox proportional hazards regression analysis. Diffuse large B-cell lymphoma was the most common histologic type (n = 83, followed by T-cell lymphoma (n = 18, mantle cell lymphoma (n = 6, and others (n = 5. Cell lineage, IPI, and extra-nodal involvement were predictors of prognosis. In the additive genetic model results for each IL10 polymorphism, the rs1800871 and rs1800872 polymorphisms represented a marginal association with OS (p = 0.09 and p = 0.06 and PFS (p = 0.05 and p = 0.08 in B-cell lymphoma patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP. These findings suggest that IL10 polymorphisms might be prognostic indicators for patients with B-cell NHL treated with R-CHOP.

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

    Directory of Open Access Journals (Sweden)

    Xue Qin

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

  10. Histone Deacetylase 3 Inhibition Overcomes BIM Deletion Polymorphism-Mediated Osimertinib Resistance in EGFR-Mutant Lung Cancer.

    Science.gov (United States)

    Tanimoto, Azusa; Takeuchi, Shinji; Arai, Sachiko; Fukuda, Koji; Yamada, Tadaaki; Roca, Xavier; Ong, S Tiong; Yano, Seiji

    2017-06-15

    Purpose: The BIM deletion polymorphism is associated with apoptosis resistance to EGFR tyrosine kinase inhibitors (EGFR-TKI), such as gefitinib and erlotinib, in non-small cell lung cancer (NSCLC) harboring EGFR mutations. Here, we investigated whether the BIM deletion polymorphism contributes to resistance against osimertinib, a third-generation EGFR-TKI. In addition, we determined the efficacy of a histone deacetylase (HDAC) inhibitor, vorinostat, against this form of resistance and elucidated the underlying mechanism. Experimental Design: We used EGFR -mutated NSCLC cell lines, which were either heterozygous or homozygous for the BIM deletion polymorphism, to evaluate the effect of osimertinib in vitro and in vivo Protein expression was examined by Western blotting. Alternative splicing of BIM mRNA was analyzed by RT-PCR. Results: EGFR -mutated NSCLC cell lines with the BIM deletion polymorphism exhibited apoptosis resistance to osimertinib in a polymorphism dosage-dependent manner, and this resistance was overcome by combined use with vorinostat. Experiments with homozygous BIM deletion-positive cells revealed that vorinostat affected the alternative splicing of BIM mRNA in the deletion allele, increased the expression of active BIM protein, and thereby induced apoptosis in osimertinib-treated cells. These effects were mediated predominantly by HDAC3 inhibition. In xenograft models, combined use of vorinostat with osimertinib could regress tumors in EGFR -mutated NSCLC cells homozygous for the BIM deletion polymorphism. Moreover, this combination could induce apoptosis even when tumor cells acquired EGFR -T790M mutations. Conclusions: These findings indicate the importance of developing HDAC3-selective inhibitors, and their combined use with osimertinib, for treating EGFR -mutated lung cancers carrying the BIM deletion polymorphism. Clin Cancer Res; 23(12); 3139-49. ©2016 AACR . ©2016 American Association for Cancer Research.

  11. Analysis of the relationship between interleukin polymorphisms within miRNA-binding regions and alcoholic liver disease.

    Science.gov (United States)

    Novo-Veleiro, I; Cieza-Borrella, C; Pastor, I; González-Sarmiento, Rogelio; Laso, F-J; Marcos, M

    2018-03-19

    Alcohol consumption promotes inflammation through the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB pathway, leading to organic damage. Some micro-RNA (miRNA) molecules modulate this inflammatory response by downregulating TLR4/NF-κB pathway mediators, like interleukins (ILs). Thus, polymorphisms within IL genes located near miRNA binding sites could modify the risk of ethanol-induced damage. The present study analyzed potential relationships between alcoholism or alcoholic liver disease (ALD) and IL12B 2124 G>T (rs1368439), IL16 5000 C>T (rs1131445), IL1R1 3114 C>T (rs3917328), and NFKB1 3400 A>G (rs4648143) polymorphisms. The study included 301 male alcoholic patients and 156 male healthy volunteers. Polymorphisms were genotyped using TaqMan ® PCR assays for allelic discrimination. Allele and genotype frequencies were compared between groups. Logistic regression analysis was performed to analyze the inheritance model. Analysis of the IL1R1 (rs3917328) polymorphism showed that the proportion of alleleT carriers (CT and TT genotypes) was higher in healthy controls (9.7%) than in alcoholic patients (6.5%; P=.042). However, multivariable logistic regression analyses did not yield a significant result. No differences between groups were found for other analyzed polymorphisms. Our study describes, for the first time, the expected frequencies of certain polymorphisms within miRNA-binding sites in alcoholic patients with and without ALD. Further studies should be developed to clarify the potential relevance of these polymorphisms in alcoholism and ALD development. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  12. Palm dermatoglyphs and interleukin-4 receptor polymorphisms in asthma.

    Science.gov (United States)

    Sun, Lixin; Xue, Weilin; Li, Jun; Zhou, Zhaoshan; Han, Wei

    2017-01-01

    Single nucleotide polymorphisms (SNPs) in the interleukin-4 receptor (IL-4R) gene have been identified as having a close association with asthma severity in different populations. In our previous studies, a close association between asthma and a distinctive palm dermatoglyphic pattern was observed; however, the clinical implication and underlying genetic mechanisms of this particular palm pattern have not been clarified. Whether this particular palm pattern is associated with asthma severity and IL-4R SNPs was assessed in the present study. A case cohort study was conducted in 400 patients with allergic asthma and in 200 healthy controls. DNA was extracted from peripheral blood leukocytes for analysis of 11 IL-4R SNPs associated with asthma via polymerase chain reaction. There are two SNPs, rs1805012 and rs3024608, which are associated with asthma (rs1805012, dominant model; P=0.03 and rs3024608, codominant model; P=0.029), and two SNPs, rs1805010 and rs3024608, which are associated with the positive palm pattern (rs1805010, log-additive model; P=0.031 and rs3024608, codominant model; P=0.016). The SNP of rs3024608 is associated with asthma and the positive palm pattern. Thus, genetic variation in IL-4R may be associated with the development of asthma and the distinctive palm pattern; however, further investigations are required to identify the connection between asthma and palm dermatoglyphic patterns.

  13. Tumor necrosis factor alpha rs1800629 polymorphism and risk of cervical lesions: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Min Li

    Full Text Available BACKGROUND: Tumor necrosis factor- alpha (TNF-α is an inflammatory cytokine which may play important role on the immune response may control the progression of cervical lesions. There is a possible association between TNF-α rs1800629 G/A polymorphism and cervical lesions, but previous studies report conflicting results. We performed a meta-analysis to comprehensively assess the association between TNF-α rs1800629 polymorphism and cervical lesions risk. METHODS: Literature searches of Pubmed, Embase, Web of Science, and Wanfang databases were performed for all publications on the association between TNF-α rs1800629 polymorphism and cervical lesions through December 15, 2012. The pooled odds ratios (ORs with their 95% confidence interval (95%CIs were calculated to assess the strength of the association. RESULTS: Twenty individual case-control studies from 19 publications with a total of 4,146 cases and 4,731 controls were finally included into the meta-analysis. Overall, TNF-α rs1800629 polymorphism was significantly associated with increased risk of cervical lesions under two main genetic comparison models (For A versus G: OR 1.22, 95%CI 1.04-1.44, P = 0.017; for AA versus GG: OR 1.32, 95%CI 1.02-1.71, P = 0.034. Subgroup analysis by ethnicity further showed that there was a significant association between TNF-α rs1800629 polymorphism and increased risk of cervical lesions in Caucasians but not in Asians. Subgroup analysis by the types of cervical lesions showed that there was a significant association between TNF-α rs1800629 polymorphism and increased risk of cervical cancer (For A versus G: OR 1.24, 95%CI 1.05-1.47, P = 0.011; for AA versus GG: OR 1.31, 95%CI 1.01-1.70, P = 0.043; for AA/GA versus GG: OR 1.25, 95%CI 1.01-1.54, P = 0.039. CONCLUSION: The meta-analysis suggests that TNF-α rs1800629 polymorphism is associated with increased risk of cervical lesions, especially in Caucasians.

  14. Sparse networks of directly coupled, polymorphic, and functional side chains in allosteric proteins.

    Science.gov (United States)

    Soltan Ghoraie, Laleh; Burkowski, Forbes; Zhu, Mu

    2015-03-01

    Recent studies have highlighted the role of coupled side-chain fluctuations alone in the allosteric behavior of proteins. Moreover, examination of X-ray crystallography data has recently revealed new information about the prevalence of alternate side-chain conformations (conformational polymorphism), and attempts have been made to uncover the hidden alternate conformations from X-ray data. Hence, new computational approaches are required that consider the polymorphic nature of the side chains, and incorporate the effects of this phenomenon in the study of information transmission and functional interactions of residues in a molecule. These studies can provide a more accurate understanding of the allosteric behavior. In this article, we first present a novel approach to generate an ensemble of conformations and an efficient computational method to extract direct couplings of side chains in allosteric proteins, and provide sparse network representations of the couplings. We take the side-chain conformational polymorphism into account, and show that by studying the intrinsic dynamics of an inactive structure, we are able to construct a network of functionally crucial residues. Second, we show that the proposed method is capable of providing a magnified view of the coupled and conformationally polymorphic residues. This model reveals couplings between the alternate conformations of a coupled residue pair. To the best of our knowledge, this is the first computational method for extracting networks of side chains' alternate conformations. Such networks help in providing a detailed image of side-chain dynamics in functionally important and conformationally polymorphic sites, such as binding and/or allosteric sites. © 2014 Wiley Periodicals, Inc.

  15. Association between the ERCC5 Asp1104His polymorphism and cancer risk: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Mei-Ling Zhu

    Full Text Available BACKGROUND: Excision repair cross complementing group 5 (ERCC5 or XPG plays an important role in regulating DNA excision repair, removal of bulky lesions caused by environmental chemicals or UV light. Mutations in this gene cause a rare autosomal recessive syndrome, and its functional single nucleotide polymorphisms (SNPs may alter DNA repair capacity phenotype and cancer risk. However, a series of epidemiological studies on the association between the ERCC5 Asp1104His polymorphism (rs17655, G>C and cancer susceptibility generated conflicting results. METHODOLOGY/PRINCIPAL FINDINGS: To derive a more precise estimation of the association between the ERCC5 Asp1104His polymorphism and overall cancer risk, we performed a meta-analysis of 44 published case-control studies, in which a total of 23,490 cases and 27,168 controls were included. To provide additional biological plausibility, we also assessed the genotype-gene expression correlation from the HapMap phase II release 23 data with 270 individuals from 4 ethnic populations. When all studies were pooled, we found no statistical evidence for a significantly increased cancer risk in the recessive genetic models (His/His vs. Asp/Asp: OR = 0.99, 95% CI: 0.92-1.06, P = 0.242 for heterogeneity or His/His vs. Asp/His + Asp/Asp: OR = 0.98, 95% CI: 0.93-1.03, P = 0.260 for heterogeneity, nor in further stratified analyses by cancer type, ethnicity, source of controls and sample size. In the genotype-phenotype correlation analysis from 270 individuals, we consistently found no significant correlation of the Asp1104His polymorphism with ERCC5 mRNA expression. CONCLUSIONS/SIGNIFICANCE: This meta-analysis suggests that it is unlikely that the ERCC5 Asp1104His polymorphism may contribute to individual susceptibility to cancer risk.

  16. Significant association of SREBP-2 genetic polymorphisms with avascular necrosis in the Korean population

    Directory of Open Access Journals (Sweden)

    Park Eui

    2008-10-01

    Full Text Available Abstract Background It is known that steroid usage and alcohol abuse are major etiological factors in the development of avascular necrosis (AVN, a bone disease that produces osteonecrosis of the femoral head. The facilitation of fat biosynthesis by steroids and alcohol disrupts the blood supply into the femoral head. SREBP-2 plays a central role in the maintenance of lipid homeostasis through stimulating expression of genes associated with cholesterol biosynthetic pathways. The aim of this study was to examine the association between the polymorphisms of the SREBP-2 gene and AVN susceptibility in the Korean population. Methods Four single nucleotide polymorphisms (SNP in the SREBP-2 gene, IVS1+8408 T>C (rs2267439, IVS3-342 G>T (rs2269657, IVS11+414 G>A (rs1052717 and IVS12-1667 G>A (rs2267443, were selected from public databases and genotyped in 443 AVN patients and 273 control subjects by using single-based extension (SBE genotyping. Results The minor allele (C frequency of rs2267439 showed a significant protective effect on AVN (P = 0.01, OR; 0.75, 95% CI; 0.604–0.935, and the genotype frequencies of this polymorphism were also different from the controls in all alternative analysis models (P range, 0.009–0.03, OR; 0.647–0.744. In contrast, rs1052717 and rs2267443 polymorphisms were significantly associated with AVN risk. Further analysis based on pathological etiology showed that the genotypes of rs2267439, rs1052717 and rs2267443 were also significantly associated with AVN susceptibility in each subgroup. Conclusion This study is the first report to evaluate the association between SREBP-2 gene polymorphisms and the susceptibility of AVN in the Korean population.

  17. Meta-analysis of microsomal epoxide hydrolase gene polymorphism and risk of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Jian-Hong Zhong

    Full Text Available BACKGROUND: Hepatocarcinogenesis is a complex process that may be influenced by many factors, including polymorphism in microsomal epoxide hydrolase (mEH. Previous work suggests an association between the Tyr113His and His139Arg mEH polymorphisms and susceptibility to hepatocellular carcinoma (HCC, but the results have been inconsistent. METHODS: PubMed, EMBASE, Google Scholar and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. A meta-analysis was performed to examine the association between Tyr113His and His139Arg mEH polymorphism and susceptibility to HCC. Odds ratios (ORs and 95% confidence intervals (95% CIs were calculated. RESULTS: Eleven studies were included in the meta-analysis, involving 1,696 HCC cases and 3,600 controls. The 113His- mEH allele was significantly associated with increased risk of HCC based on allelic contrast (OR = 1.35, 95% CI = 1.04-1.75, p = 0.02, homozygote comparison (OR = 1.65, 95% CI = 1.07-2.54, p = 0.02 and a recessive genetic model (OR = 1.54, 95% CI = 1.21-1.96, p<0.001, while individuals carrying the Arg139Arg mEH genotype had no association with increased or decreased risk of HCC. CONCLUSION: The 113His- allele polymorphism in mEH may be a risk factor for hepatocarcinogenesis, while the mEH 139Arg- allele may not be a risk or protective factor. There is substantial evidence that mEH polymorphisms interact synergistically with other genes and the environment to modulate risk of HCC. Further large and well-designed studies are needed to confirm these conclusions.

  18. Association between ADH1C and ALDH2 polymorphisms and alcoholism in a Turkish sample.

    Science.gov (United States)

    Ayhan, Yavuz; Gürel, Şeref Can; Karaca, Özgür; Zoto, Teuta; Hayran, Mutlu; Babaoğlu, Melih; Yaşar, Ümit; Bozkurt, Atilla; Dilbaz, Nesrin; Uluğ, Berna Diclenur; Demir, Başaran

    2015-04-01

    Polymorphisms in the genes encoding alcohol metabolizing enzymes are associated with alcohol dependence. To evaluate the association between the alcohol dehydrogenase 1C (ADH1C) Ile350Val and aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphisms and alcohol dependence in a Turkish sample. 235 individuals (115 alcohol-dependent patients and 120 controls) were genotyped for ADH1C and ALDH2 with PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism). Association between the polymorphisms and family history, daily and maximum amount of alcohol consumed was investigated. The associations between alcohol dependence, severity of consumption and family history and the polymorphisms were analyzed by chi-square or Fisher's exact test where necessary. Relationship between genotypes and dependence related features was evaluated using analysis of variance (ANOVA). The -350Val allele for ADH1C (ADH1C*2) was increased in alcohol-dependent patients (P = 0.05). In individuals with a positive family history, the genotype distribution differed significantly (P = 0.031) and more patients carried the Val allele compared with controls (P = 0.025). Genotyping of 162 participants did not reveal the -504Lys allele in ALDH2. These findings suggest that ADH1C*2 is associated with alcohol dependence in the Turkish population displaying a dominant inheritance model. ADH1C*2 allele may contribute to the variance in heritability of alcohol dependence. The ALDH2 -504Lys/Lys or Glu/Lys genotypes were not present in alcohol-dependent patients, similar to that seen in European populations and in contrast to the findings in the Asian populations.

  19. Phosphodiesterase 4D gene polymorphisms in sudden sensorineural hearing loss.

    Science.gov (United States)

    Chien, Chen-Yu; Tai, Shu-Yu; Wang, Ling-Feng; Hsi, Edward; Chang, Ning-Chia; Wang, Hsun-Mo; Wu, Ming-Tsang; Ho, Kuen-Yao

    2016-09-01

    The phosphodiesterase 4D (PDE4D) gene has been reported as a risk gene for ischemic stroke. The vascular factors are between the hypothesized etiologies of sudden sensorineural hearing loss (SSNHL), and this genetic effect might be attributed for its role in SSNHL. We hypothesized that genetic variants of the PDE4D gene are associated with susceptibility to SSNHL. We conducted a case-control study with 362 SSNHL cases and 209 controls. Three single nucleotide polymorphisms (SNPs) were selected. The genotypes were determined using TaqMan technology. Hardy-Weinberg equilibrium (HWE) was tested for each SNP, and genetic effects were evaluated according to three inheritance modes. We carried out sex-specific analysis to analyze the overall data. All three SNPs were in HWE. When subjects were stratified by sex, the genetic effect was only evident in females but not in males. The TT genotype of rs702553 exhibited an adjusted odds ratio (OR) of 3.83 (95 % confidence interval = 1.46-11.18) (p = 0.006) in female SSNHL. The TT genotype of SNP rs702553 was associated with female SSNHL under the recessive model (p = 0.004, OR 3.70). In multivariate logistic regression analysis, TT genotype of rs702553 was significantly associated with female SSNHL (p = 0.0043, OR 3.70). These results suggest that PDE4D gene polymorphisms influence the susceptibility for the development of SSNHL in the southern Taiwanese female population.

  20. Determining Candidate Single Nucleotide Polymorphisms in Acquired Laryngotracheal Stenosis.

    Science.gov (United States)

    Anis, Mursalin M; Krynetskaia, Natalia; Zhao, Zhigen; Krynetskiy, Evgeny; Soliman, Ahmed M S

    2018-03-01

    Despite wide adoption of strategies to prevent injury from prolonged intubation and tracheotomy, acquired laryngotracheal stenosis (ALTS) has not disappeared. ALTS' persistence may be due to patient factors that confer unique susceptibility for some. We sought to identify genetic markers in genes associated with wound healing that could be associated with ALTS. Case-control study. One hundred thirty-eight patients were recruited, 53 patients with ALTS and 85 control patients who underwent intubation or tracheotomy without evidence of ALTS. The patients' DNA was isolated from whole blood. Custom primers were designed, and the TaqMan assay employing allele-specific polymerase chain reaction was used to interrogate single nucleotide polymorphisms (SNPs) rs1799750, rs522616, rs2276109, rs2569190, rs1800469, and rs1024611 of candidate wound healing genes MMP1, MMP3, MMP12, CD14, TGFβ1, and MCP1, respectively. A logistic regression model was used to examine the association of candidate gene polymorphisms with the presence or absence of ALTS. All 138 patients were successfully genotyped. No significant association was found between candidate SNPs and development of ALTS in the overall group. However, subgroup analysis within each ethnicity identified SNPs that are associated with ALTS depending upon the ethnic background. Patient factors such as variations in wound healing due to functional SNPs may shed light on the development of ALTS. There may be a difference in susceptibility to developing ALTS in different ethnic backgrounds. These preliminary findings need to be corroborated in larger population studies. 3b. Laryngoscope, 128:E111-E116, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  1. Mutagenicity Assessment of Organophosphates using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism Assay

    OpenAIRE

    Bhinder, Preety; Chaudhry, Asha

    2013-01-01

    Objectives: In this study we have evaluated the mutagenicity of organophosphate pesticides acephate, chlorpyrifos, and profenofos using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay with the mosquito Culex quinquefasciatus taken as an experimental model. Materials and Methods: Second instar larvae were treated with LC20 of each pesticide for 24 h and mutations induced in the sequence of mitochondrial COII gene (690bp) were studied from restriction pattern...

  2. Estrogen receptor polymorphisms and incident dementia: the prospective 3C study.

    OpenAIRE

    Ryan, Joanne; Carrière, Isabelle; Carcaillon, Laure; Dartigues, Jean-Francois; Auriacombe, Sophie; Rouaud, Olivier; Berr, Claudine; Ritchie, Karen; Scarabin, Pierre-Yves; Ancelin, Marie-Laure

    2014-01-01

    International audience; BACKGROUND: Genetic variation in the estrogen receptor (ESR) may be associated with the incidence of Alzheimer's disease (AD), but this association could be modified by genetic and environmental factors. METHODS: The association between five ESR α (ESR1) and β (ESR2) polymorphisms with 7-year dementia incidence was examined among 6959 older men and women from the Three City Study using multivariate-adjusted Cox regression models with delayed entry. Gender, the apolipop...

  3. Plumage polymorphism and fitness in Swainson's hawks.

    Science.gov (United States)

    Briggs, C W; Collopy, M W; Woodbridge, B

    2011-10-01

    We examine the maintenance of a plumage polymorphism, variation in plumages among the same age and sex class within a population, in a population of Swainson's Hawks. We take advantage of 32 years of data to examine two prevalent hypotheses used to explain the persistence of morphs: apostatic selection and heterozygous advantage. We investigate differences in fitness among three morph classes of a melanistic trait in Swainson's Hawks: light (7% of the local breeding population), intermediate (57%) and dark (36%). Specifically, we examined morph differences in adult apparent survival, breeding success, annual number of fledglings produced, probability of offspring recruitment into the breeding population and lifetime reproductive success (LRS). If apostatic selection were a factor in maintaining morphs, we would expect that individuals with the least frequent morph would perform best in one or more of these fitness categories. Alternatively, if heterozygous advantage played a role in the maintenance of this polymorphism, we would expect heterozygotes (i.e. intermediate morphs) to have one or more increased rates in these categories. We found no difference in adult apparent survival between morph classes. Similarly, there were no differences in breeding success, nest productivity, LRS or probability of recruitment of offspring between parental morph. We conclude that neither apostatic selection nor heterozygous advantage appear to play a role in maintaining morphs in this population. © 2011 The Authors. Journal of Evolutionary Biology © 2011 European Society For Evolutionary Biology.

  4. Polymorphism in Br2 clathrate hydrates.

    Science.gov (United States)

    Goldschleger, I U; Kerenskaya, G; Janda, K C; Apkarian, V A

    2008-02-07

    The structure and composition of bromine clathrate hydrate has been controversial for more than 170 years due to the large variation of its observed stoichiometries. Several different crystal structures were proposed before 1997 when Udachin et al. (Udachin, K. A.; Enright, G. D.; Ratcliffe, C. I.; Ripmeester, J. A. J. Am. Chem. Soc. 1997, 119, 11481) concluded that Br2 forms only the tetragonal structure (TS-I). We show polymorphism in Br2 clathrate hydrates by identifying two distinct crystal structures through optical microscopy and resonant Raman spectroscopy on single crystals. After growing TS-I crystals from a liquid bromine-water solution, upon dropping the temperature slightly below -7 degrees C, new crystals of cubic morphology form. The new crystals, which have a limited thermal stability range, are assigned to the CS-II structure. The two structures are clearly distinguished by the resonant Raman spectra of the enclathrated Br2, which show long overtone progressions and allow the extraction of accurate vibrational parameters: omega(e) = 321.2 +/- 0.1 cm(-1) and omega(e)x(e) = 0.82 +/- 0.05 cm(-1) in TS-I and omega(e) = 317.5 +/- 0.1 cm(-1) and omega(e)x(e) = 0.70 +/- 0.1 cm(-1) in CS-II. On the basis of structural analysis, the discovery of the CS-II crystals implies stability of a large class of bromine hydrate structures and, therefore, polymorphism.

  5. Interleukin-10 promoter polymorphisms in myasthenia gravis.

    Science.gov (United States)

    Alseth, Espen Homleid; Nakkestad, Hanne Linda; Aarseth, Jan; Gilhus, Nils Erik; Skeie, Geir Olve

    2009-05-29

    Interleukin 10 (IL-10) is secreted by several hemopoietic cells and suppresses the Th1 mediated immune response, while stimulating B cell differentiation and the humoral immune response. IL-10 expression in Con A-stimulated peripheral blood mononuclear cells is related to three polymorphisms in the promoter region of the IL-10 gene; G/A at position -1082, T/C at position -819 and A/C at position -592. We analyzed the distribution of these IL-10 polymorphisms in 64 MG patients and 87 healthy blood donors to determine any influence on MG susceptibility. MG patients had a significantly higher frequency of the ACC/ACC haplotype (12.5% vs 3.4% in controls), as had the subgroups with late onset MG and thymomatous MG (20.0% and 21.4%, respectively). Early onset MG patients had a high frequency of the ATA/ATA haplotype (19.2% vs 3.4% in controls). Titin Ab-positive MG patients had high ACC/ACC (20.0%). This study indicates a direct link between IL-10 and MG pathogenesis, although the complex role of this multi-faceted cytokine in vivo is as yet not fully elucidated.

  6. Methylenetetrahydrofolate Reductase A1298C Polymorphism and Breast Cancer Risk: A Meta-analysis of 33 Studies.

    Science.gov (United States)

    Rai, V

    2014-11-01

    Methylenetetrahydrofolate reductase (MTHFR) enzyme is essential for DNA synthesis and DNA methylation, and its gene polymorphisms have been implicated as risk factors for birth defects, neurological disorders, and different types of cancers. Several studies have investigated the association between the MTHFR A1298C polymorphism and breast cancer (BC) risk, but the results were inconclusive. To assess the risk associated with MTHFR A1298C polymorphism, a comprehensive meta-analysis was performed. PubMed, Google Scholar, Elsevier and Springer Link databases were searched for case-control studies relating the association between MTHFR A1298C polymorphism and BC risk and estimated summary odds ratios (ORs) with confidence intervals (CIs) for assessment. Up to January 2014, 33 case-control studies involving 15,919 BC patients and 19,700 controls were included in the present meta-analysis. The results showed that the A1298C polymorphism was not associated with BC risk in all the five genetic models (C vs. A allele (allele contrast): OR = 0.99, 95% confidence interval (CI): 0.93-1.05; AC versus AA (heterozygote/codominant): OR = 0.97, 95% CI: 0.89-1.04; CC versus AA (homozygote): OR = 0.99, 95% CI: 0.91-1.06; CC + AC versus AA (dominant model): OR = 0.97, 95% CI: 0.90-1.05; and CC versus AC + AA (recessive model): OR = 0.99, 95% CI: 0.91-1.07). The present meta-analysis did not support any association between the MTHFR A1298C polymorphism and BC risk.

  7. Methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphisms and susceptibility to Parkinson's disease: a meta-analysis.

    Science.gov (United States)

    Wu, Yi-Le; Ding, Xiu-Xiu; Sun, Ye-Huan; Yang, Hui-Yun; Sun, Liang

    2013-12-15

    The association between the methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphisms and susceptibility to Parkinson's disease (PD) was controversial in previous studies. The present study was therefore designed to investigate a more reliable estimate. 15 studies were identified by a search of PubMed, EBMBASE, PDGENE, Elsevier, Springer Link, CBM (Chinese Biomedical Database), CNKI (Chinese National Knowledge Infrastructure), VIP (Chinese), and Wanfang (Chinese) databases, up to April 2013. Odds ratios (ORs) with corresponding 95% confidence interval (CI) were calculated using fixed effects model or random effects model. The subgroup analyses were made on the ethnicity. MTHFR C677T polymorphism had a significant association with susceptibility to PD in all genetic models (for T vs. C: OR=1.24, 95% CI=1.11-1.38; for TT+CT vs. CC: OR=1.27, 95% CI=1.10-1.46; for TT vs. CC: OR=1.56, 95% CI=1.22-1.98; for TT vs. CT+CC: OR=1.43, 95% CI=1.14-1.79). Subgroup analyses by ethnicity revealed that the association between the MTHFR C677T polymorphism and PD existed in Caucasian population and Asian population. However, no association was detected between the MTHFR A1298C polymorphism and PD. Results from this meta-analysis supported that the MTHFR C677T polymorphism was associated with an increased risk of PD. The MTHFR A1298C polymorphism may not increase the susceptibility to PD. Further studies are required to confirm our findings. © 2013.

  8. Association between NFKB1 −94ins/del ATTG Promoter Polymorphism and Cancer Susceptibility: An Updated Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Xiao Yang

    2014-01-01

    Full Text Available Nuclear factor-κB is associated with the pathogenesis of numerous malignancies, and the functional polymorphism −94ins/del ATTG (rs28362491 in the human NFKB1 gene is associated with cancer risk. Previous studies on the association between the −94ins/del ATTG polymorphism and cancer risk reported conflicting results. To clarify this relationship, we performed a meta-analysis of 21 case-control studies involving 6127 cases and 9238 controls. We used pooled odds ratios (ORs with their 95% confidence intervals (95% CIs to assess the association. We found that the NFKB1 promoter −94ins/del ATTG polymorphism was significantly associated with cancer risk in four genetic models (ins/ins versus del/del, OR = 1.47, 95% CI = 1.11–1.93; dominant model, OR = 1.26, 95% CI = 1.03–1.53; recessive model, OR = 1.26, 95% CI = 1.05–1.51; ins allele versus del allele, OR = 1.19, 95% CI = 1.05–1.35. Stratified analyses revealed a significant association between the polymorphism and ovarian, oral, and prostate cancers. Similar results were determined in an Asian population and not in a Caucasian population. Thus, our results suggested that the polymorphism can contribute to cancer risk. Moreover, the polymorphism can exert race- and cancer-specific effects on cancer risk. Further large-scale and functional studies are necessary to elucidate this possible effect.

  9. Head and neck cancer: genetic polymorphisms and folate metabolism.

    Science.gov (United States)

    Galbiatti, Ana Lívia Silva; Ruiz, Mariangela Torreglosa; Maniglia, José Victor; Raposo, Luis Sérgio; Pavarino-Bertelli, Erika Cristina; Goloni-Bertollo, Eny Maria

    2012-02-01

    Epidemiological evidence suggests that genetic variants encoding enzymes involved in folate metabolism may modulate HNSCC risk by altering DNA methylation synthesis and genomic estability. A review of the literature on genetic polymorphisms involved in folate metabolism and risk of head and neck cancer was carried out. An electronic search was made on the Medline database to select papers on head and neck cancer and polymorphisms involved in folate metabolism. The association between MTHFR C677T polymorphism and the risk of this tumor type was evaluated in nine studies; there was an association with this disease in three papers. The MTR A2756G and MTRR A66G and RFC1 A80G polymorphisms were also associated with increased risk for HNSCC. MTHFD1 G1958A polymorphism was not associated with increased risk of this disease; the evaluation results of the MTHFR A1298C polymorphism in this neoplasm were contradictory. Other polymorphisms involved in folate metabolism were not studied for this neoplasm. We conclude that polymorphisms involved in folate metabolism may modulate the risk of head and neck cancer, however, these results need to be demonstrated in different populations.

  10. Association of genetic polymorphism in GH gene with milk ...

    Indian Academy of Sciences (India)

    Association of genetic polymorphism in GH gene with milk production traits in Beijing Holstein cows ... Keywords. Beijing Holstein cows; growth hormone gene; genetic polymorphism; milk production traits ... I, II, and III). The A/A cows produced milk of higher protein content than of A/B individuals ( < 0.05 only in lactation II).

  11. Angiotensin-converting enzyme insertion/deletion polymorphism ...

    African Journals Online (AJOL)

    Background: The angiotensin-converting enzyme (ACE) I/D polymorphism has been reported to be associated with Kawasaki disease(KD) ,but studies to date present conflicting results. Objectives: The aim of this study is to derive a more precise estimation of the association between the ACE I/D polymorphism and KD risk.

  12. Apolipoprotein E gene polymorphism in Egyptian acute coronary ...

    African Journals Online (AJOL)

    Background: Apolipoprotein E (apo E) gene polymorphism was found to be associated with coronary artery disease in several studies. In this investigation, we aimed to study the association between apo E gene polymorphism and acute coronary syndrome in Egyptian population. Subjects and methods: The study included ...

  13. DNA polymorphism of butyrophilin gene by PCR-RFLP technique ...

    African Journals Online (AJOL)

    We used the polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) technique to screen for DNA polymorphism in 109 cattle. In all cattle, we amplified an 863 fragment consisting of part of exon 8. The amplified fragment digested with HaeIII restriction endonuclease and subjected to electrophoretic ...

  14. Analysis of bovine growth hormone gene polymorphism of local and ...

    African Journals Online (AJOL)

    Analysis of bovine growth hormone gene polymorphism of local and Holstein cattle breeds in Kerman province of Iran using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) ... African Journal of Biotechnology ... RFLPs in this segment were studied using AluI restriction enzyme.

  15. Effect of genetic and coexisting polymorphisms on platelet response ...

    Indian Academy of Sciences (India)

    Abstract. Polymorphisms of CYP2C19 are associated with platelet response to clopidogrel. This study was conducted to evaluate the contribution of the previously identified polymorphisms to the response of clopidogrel in a cohort of Chinese Han patients. A total of 222 acute coronary syndrome patients undergoing ...

  16. Fetal MTHFR C677T polymorphism confers no susceptibility to ...

    African Journals Online (AJOL)

    Maternal methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is reported as risk factor for Down syndrome (DS) pregnancy but fetal MTHFR C677T polymorphism was not well studied as risk factor for DS. Some studies were published, but results were controversial. Hence a meta-analysis of all published ...

  17. Alcohol consumption, alcohol dehydrogenase 3 polymorphism, and colorectal adenomas

    NARCIS (Netherlands)

    Tiemersma, E.W.; Wark, P.A.; Ocké, M.C.; Bunschoten, A.; Otten, M.H.; Kok, F.J.; Kampman, E.

    2003-01-01

    Alcohol is a probable risk factor with regard to colorectal neoplasm and is metabolized to the carcinogen acetaldehyde by the genetically polymorphic alcohol dehydrogenase 3 (ADH3) enzyme. We evaluated whether the association between alcohol and colorectal adenomas is modified by ADH3 polymorphism.

  18. Prevalence of thrombophilic gene polymorphisms (FVL G1691A and ...

    African Journals Online (AJOL)

    Background: Inherited thrombophilia may be caused by mutations, polymorphisms in a variety of genes mainly involved in haemostatic pathways. Aim of the study, was to find the prevalence of thrombophilic gene factor V Leiden (FVL) and methylene tetrahydrofolate reductase (MTHFR) gene polymorphism in patients with ...

  19. Male accessory gland secretory protein polymorphism in natural ...

    Indian Academy of Sciences (India)

    Male accessory gland secretory protein polymorphism was analysed in natural populations of Drosophila nasuta nasuta and D. sulfurigaster neonasuta for the first time, using SDS-PAGE to score polymorphism of these proteins in 2788 individuals of D. n. nasuta and 2232 individuals of D. s. neonasuta from 12 different ...

  20. Fc gamma receptor polymorphisms in relation to periodontitis

    NARCIS (Netherlands)

    Loos, BG; Leppers-Van de Straat, FGJ; Van de Winkel, JGJ; Van der Velden, U

    Objectives: Evidence suggests functional relevance for polymorphisms in Fcgamma R in relation to inflammatory and infectious diseases. The present aim was to investigate genetic polymorphisms in three Fcgamma R in relation to susceptibility and severity of periodontitis. Material and Methods: The

  1. Effects of human SAMHD1 polymorphisms on HIV-1 susceptibility

    International Nuclear Information System (INIS)

    White, Tommy E.; Brandariz-Nuñez, Alberto; Valle-Casuso, Jose Carlos; Knowlton, Caitlin; Kim, Baek; Sawyer, Sara L.; Diaz-Griffero, Felipe

    2014-01-01

    SAMHD1 is a human restriction factor that prevents efficient infection of macrophages, dendritic cells and resting CD4+ T cells by HIV-1. Here we explored the antiviral activity and biochemical properties of human SAMHD1 polymorphisms. Our studies focused on human SAMHD1 polymorphisms that were previously identified as evolving under positive selection for rapid amino acid replacement during primate speciation. The different human SAMHD1 polymorphisms were tested for their ability to block HIV-1, HIV-2 and equine infectious anemia virus (EIAV). All studied SAMHD1 variants block HIV-1, HIV-2 and EIAV infection when compared to wild type. We found that these variants did not lose their ability to oligomerize or to bind RNA. Furthermore, all tested variants were susceptible to degradation by Vpx, and localized to the nuclear compartment. We tested the ability of human SAMHD1 polymorphisms to decrease the dNTP cellular levels. In agreement, none of the different SAMHD1 variants lost their ability to reduce cellular levels of dNTPs. Finally, we found that none of the tested human SAMHD1 polymorphisms affected the ability of the protein to block LINE-1 retrotransposition. - Highlights: • Human SAMHD1 single-nucleotide polymorphisms block HIV-1 and HIV-2 infection. • SAMHD1 polymorphisms do not affect its ability to block LINE-1 retrotransposition. • SAMHD1 polymorphisms decrease the cellular levels of dNTPs

  2. Randomly amplified polymorphic DNA-polymerase chain reaction ...

    Indian Academy of Sciences (India)

    Genetic similarity and diversity of cultured catfish Silurus asotus populations collected from two areas in western Korea were examined using randomly amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR). Out of 20 random primers tested, 5 produced 1344 RAPD bands ranging from 8.2 to 13.6 polymorphic ...

  3. Human lymphocyte polymorphisms detected by quantitative two-dimensional electrophoresis

    International Nuclear Information System (INIS)

    Goldman, D.; Merril, C.R.

    1983-01-01

    A survey of 186 soluble lymphocyte proteins for genetic polymorphism was carried out utilizing two-dimensional electrophoresis of 14 C-labeled phytohemagglutinin (PHA)-stimulated human lymphocyte proteins. Nineteen of these proteins exhibited positional variation consistent with independent genetic polymorphism in a primary sample of 28 individuals. Each of these polymorphisms was characterized by quantitative gene-dosage dependence insofar as the heterozygous phenotype expressed approximately 50% of each allelic gene product as was seen in homozygotes. Patterns observed were also identical in monozygotic twins, replicate samples, and replicate gels. The three expected phenotypes (two homozygotes and a heterozygote) were observed in each of 10 of these polymorphisms while the remaining nine had one of the homozygous classes absent. The presence of the three phenotypes, the demonstration of gene-dosage dependence, and our own and previous pedigree analysis of certain of these polymorphisms supports the genetic basis of these variants. Based on this data, the frequency of polymorphic loci for man is: P . 19/186 . .102, and the average heterozygosity is .024. This estimate is approximately 1/3 to 1/2 the rate of polymorphism previously estimated for man in other studies using one-dimensional electrophoresis of isozyme loci. The newly described polymorphisms and others which should be detectable in larger protein surveys with two-dimensional electrophoresis hold promise as genetic markers of the human genome for use in gene mapping and pedigree analyses

  4. Study of simple sequence repeat (SSR) polymorphism for biotic ...

    African Journals Online (AJOL)

    home

    2013-10-02

    Oct 2, 2013 ... parents studied indicating the robust nature of microsatellites in revealing polymorphism. Based on this study, the large range of similarity values for related cultivars using microsatellites provides greater confidence for the assessment of simple sequence repeats (SSR) polymorphism. Key words: Simple ...

  5. Apelin rs2235306 polymorphism is not related to metabolic ...

    African Journals Online (AJOL)

    Eman T. Mehanna

    2014-11-27

    Nov 27, 2014 ... Abstract Background: Apelin is an adipokine that was identified to play a role in the control of glucose homeostasis. Apelin rs2235306 gene polymorphism was linked to insulin resistance and poor glycemic control. Aim of the study: To assess the relation of apelin rs2235306 polymorphism with metabolic ...

  6. Association between Tryptophan Hydroxylase 2 Gene Polymorphism and Completed Suicide

    Science.gov (United States)

    Fudalej, Sylwia; Ilgen, Mark; Fudalej, Marcin; Kostrzewa, Grazyna; Barry, Kristen; Wojnar, Marcin; Krajewski, Pawel; Blow, Frederic; Ploski, Rafal

    2010-01-01

    The association between suicide and a single nucleotide polymorphism (rs1386483) was examined in the recently identified tryptophan hydroxylase 2 (TPH2) gene. Blood samples of 143 suicide victims and 162 age- and sex-matched controls were examined. The frequency of the TT genotype in the TPH2 polymorphism was higher in suicide victims than in…

  7. Prion protein gene polymorphisms in Turkish native goat breeds

    Indian Academy of Sciences (India)

    HASAN MEYDAN

    Susceptibility to 'scrapie' disease in goats is influenced by polymorphisms of the prion protein (PRNP) gene. The aim of ... [Meydan H., Pehlivan E., Özkan M. M., Yildiz M. A. and Goldmann W. 2017 Prion protein gene polymorphisms in Turkish native goat breeds. ... Anatolia and contribute to the livelihood of resource-poor.

  8. From Monomorphic to Polymorphic Well-Typings and Beyond

    DEFF Research Database (Denmark)

    Schrijvers, Tom; Bruynooghe, Maurice; Gallagher, John Patrick

    2009-01-01

    the automatic inference of a well-typing is worthwhile. Existing inferences are either cheap and inaccurate, or accurate and expensive. By giving up the requirement that all calls to a predicate have types that are instances of a unique polymorphic type but instead allowing multiple polymorphic typings...

  9. Angiotensin converting enzyme (ACE D/I) polymorphism and its ...

    African Journals Online (AJOL)

    Hepatitis C virus (HCV) infection is a global health problem in Egypt and causes different liver disease spectrum. Evidence indicates that angiotensin I converting enzyme (ACE) gene polymorphism may play a role in determining disease progression. We aimed to determine the association of ACE gene I/D polymorphism ...

  10. Methylation sensitive-sequence related amplified polymorphism (MS ...

    African Journals Online (AJOL)

    Methylation sensitive-sequence related amplified polymorphism (MS-SRAP) marker system and its application to de novo methylation detection in Brassica napus. ... Combined methylation sensitive restriction enzyme digested genomic DNA with SRAP and methylation sensitive-sequence related amplified polymorphism ...

  11. Effects of β2-adrenergic receptor polymorphisms on asthma severity ...

    African Journals Online (AJOL)

    Background: Several polymorphisms of the β2-adrenergic receptor (ADRB2) gene have been identified. There is mounting evidence that these polymorphisms are associated with significant variability in response to bronchodilator therapy and thus in severity and duration of asthmatic symptoms. Objectives: to assess the ...

  12. Lack of association of insertion/deletion polymorphism in ...

    African Journals Online (AJOL)

    In the present preliminary study the insertion/deletion polymorphism within angiotensin converting enzyme gene is not likely to be associated with nephropathy in type 2 diabetic patients of Punjabi population of Pakistan. Key words: Angiotensin converting enzymes, insertion/deletion polymorphism, albuminuria and type 2 ...

  13. Association of genetic polymorphism in GH gene with milk ...

    Indian Academy of Sciences (India)

    Associations were analysed between polymorphisms of the growth hormone gene (GH-MspI) (localized in intron 3) and milk production traits of Beijing Holstein cows (a total of 543 cows). Polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method was used for identification of various ...

  14. Detection of new single nucleotide polymorphisms by means of real ...

    Indian Academy of Sciences (India)

    Unknown

    Real time polymerase chain reaction (RT-PCR) is a new technique in molecular genetics which allows quantifica- tion of polymorphic DNA regions and genotyping of sin- gle nucleotide polymorphisms (SNPs) in one run. A by- product of real time PCR is the opportunity to identify new SNPs in the proximity of gene loci of ...

  15. cDNA cloning and polymorphic domains of the major ...

    African Journals Online (AJOL)

    Major histocompatibility complex (MHC) is a highly polymorphic gene and plays an important role in immune system for vertebrate. To understand the polymorphism character of domestic, we cloned 32 cDNAs of MHC class I α genes of two local chicken breeds in different areas of China. There were 112 variable amino ...

  16. Contrasting genetic influence of PON 1 coding gene polymorphisms ...

    African Journals Online (AJOL)

    Background: Paraoxonase (PON1) is an A-esterase capable of hydrolyzing the active metabolites (oxons) of many organophosphorus (OP) insecticides. Human PON1 displays two polymorphisms in the coding region (Q192R and L55M) and several polymorphisms in the promoter and the 30-UTR regions. Animal studies ...

  17. Analysis of three polymorphisms in Bidayuh ethnic of Sarawak ...

    African Journals Online (AJOL)

    Insertion/deletion polymorphism of YAP (DYS287), M96 and M120 polymorphisms in Bidayuh ethnic populations of Sarawak, Malaysia were analyzed in this study. Genomic DNA was extracted from 180 buccal samples and amplified by Hot-Start PCR method. The amplified PCR products were separated by using 2% ...

  18. Association between GH encoding gene polymorphism and semen ...

    African Journals Online (AJOL)

    The objective of this present study was to investigate relationships between the growth hormone gene restriction fragment length polymorphism (RFLP) and bull sperm characteristics. A total of 89 bulls from two semen evaluation stations were genotyped for the bovine growth hormone (bGH)-AluI polymorphism by ...

  19. Contribution of genes polymorphism to susceptibility and outcome of ...

    African Journals Online (AJOL)

    Harapan Tumangger

    HMGB1, TLR, PAI-1, DEFB1, HSP and MMP-9 has contribution to susceptibility and outcome of sepsis in some research. .... inflammatory cytokine gene polymorphism to susceptibility and outcome of patients with systemic inflammation and sepsis. 2. Genes polymorphism and sepsis. 2.1. Tumor necrosis factor (TNF) a.

  20. Impact of genetic polymorphisms of four cytokine genes on treatment ...

    African Journals Online (AJOL)

    Background: Many factors contribute for viral clearance and response to antiviral therapy. Genetic polymorphisms of cytokines, chemokines, and their receptors can alter the immune response against Hepatitis C virus (HCV). Aim of the study: The aim of the current study is to assess single nucleotide polymorphism (SNP) in ...

  1. Do prion protein gene polymorphisms induce apoptosis in non

    Indian Academy of Sciences (India)

    To elucidate the relationship between the SNPs and apoptosis, TUNEL assays and active caspase-3 immunodetection techniques in brain sections of the polymorphic samples were performed. The results revealed that TUNEL-positive cells and active caspase-3-positive cells in the turtles with four polymorphisms were ...

  2. Microsatellite markers and polymorphism in cheatgrass (Bromus tectorum L.)

    Science.gov (United States)

    Alisa P. Ramakrishnan; Craig E. Coleman; Susan E. Meyer; Daniel J. Fairbanks

    2001-01-01

    Cheatgrass (Bromus tectorum) individuals were genetically characterized using polymorphic microsatellite markers. Through analysis of alleles of five polymorphic loci, genotypes were constructed of individuals from four populations in Utah and Nevada. There were 15 different genotypes: Whiterocks, UT, had nine genotypes, Hobble Creek, UT, had seven genotypes,...

  3. Effects of human SAMHD1 polymorphisms on HIV-1 susceptibility

    Energy Technology Data Exchange (ETDEWEB)

    White, Tommy E.; Brandariz-Nuñez, Alberto; Valle-Casuso, Jose Carlos [Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, 1301 Morris Park – Price Center 501, New York, NY 10461 (United States); Knowlton, Caitlin; Kim, Baek [Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642 (United States); Sawyer, Sara L. [Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712 (United States); Diaz-Griffero, Felipe, E-mail: Felipe.Diaz-Griffero@einstein.yu.edu [Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, 1301 Morris Park – Price Center 501, New York, NY 10461 (United States)

    2014-07-15

    SAMHD1 is a human restriction factor that prevents efficient infection of macrophages, dendritic cells and resting CD4+ T cells by HIV-1. Here we explored the antiviral activity and biochemical properties of human SAMHD1 polymorphisms. Our studies focused on human SAMHD1 polymorphisms that were previously identified as evolving under positive selection for rapid amino acid replacement during primate speciation. The different human SAMHD1 polymorphisms were tested for their ability to block HIV-1, HIV-2 and equine infectious anemia virus (EIAV). All studied SAMHD1 variants block HIV-1, HIV-2 and EIAV infection when compared to wild type. We found that these variants did not lose their ability to oligomerize or to bind RNA. Furthermore, all tested variants were susceptible to degradation by Vpx, and localized to the nuclear compartment. We tested the ability of human SAMHD1 polymorphisms to decrease the dNTP cellular levels. In agreement, none of the different SAMHD1 variants lost their ability to reduce cellular levels of dNTPs. Finally, we found that none of the tested human SAMHD1 polymorphisms affected the ability of the protein to block LINE-1 retrotransposition. - Highlights: • Human SAMHD1 single-nucleotide polymorphisms block HIV-1 and HIV-2 infection. • SAMHD1 polymorphisms do not affect its ability to block LINE-1 retrotransposition. • SAMHD1 polymorphisms decrease the cellular levels of dNTPs.

  4. Detection of MspI polymorphism and the single nucleotide ...

    African Journals Online (AJOL)

    The aim of this study was to detect the genetic polymorphism of GH gene in five camel breeds reared in Egypt which are Sudany, Somali, Mowaled, Maghrabi and Falahy, using polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) technique. Also, this work aimed to identify the single nucleotide ...

  5. Polymorphism of growth hormone gene and its association with ...

    African Journals Online (AJOL)

    sunny t

    2016-04-06

    Apr 6, 2016 ... recorded to be more frequent (83.3, 92.86 and 90%) than pattern II (16.7, 7.14 and 10%) in Barki,. Rahmani ... Key words: Sheep, wool, growth hormone (GH) gene, polymorphism, single strand conformation polymorphism. (SSCP). ... electrophoresis and chemical and ribonuclease cleavage,. SSCP has ...

  6. Mapping of randomly amplified polymorphic DNA primer (RAPD) on ...

    African Journals Online (AJOL)

    Genet & Botany only

    2012-08-14

    Aug 14, 2012 ... (Islam and Shepherd, 1992). But these markers were not considered suitable for large scale mapping. With the recent introduction of molecular biology, DNA based markers including polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), single nucleotide polymorphisms ...

  7. Association of transforming growth factor-ß3 gene polymorphism ...

    African Journals Online (AJOL)

    Genotyping for the TGF-β3 gene using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and BslI restriction endonuclease showed a mutation in 294-bp fragment located on the fourth intron of chromosome 5. Polymorphism in TGF-β3 gene was significantly (P < 0.1) associated with ...

  8. DNA Characterization and Polymorphism of KISS1 Gene in Egyptian ...

    African Journals Online (AJOL)

    The objective of this study was the detection of the restriction fragment length polymorphism (RFLP) and single nucleotide polymorphisms (SNPs) of KISS1 gene in six major Egyptian small ruminant breeds. The primers used in this study flanked a 377 bp fragment from intron 1 of KISS1 gene in sheep and goat. These PCR ...

  9. Male accessory gland secretory protein polymorphism in natural ...

    Indian Academy of Sciences (India)

    Male accessory gland secretory protein polymorphism was analysed in natural populations of Drosophila nasuta nasuta and. D. sulfurigaster neonasuta for the first time, using SDS-PAGE to score polymorphism of these proteins in 2788 individuals of D. n. nasuta and 2232 individuals of D. s. neonasuta from 12 different ...

  10. Identification of possible genetic polymorphisms involved in cancer ...

    Indian Academy of Sciences (India)

    Research Collaborative. J. Genet. 90, 165–177. Table 1. Summary of polymorphisms involving innate immune receptors and mediators of the immune response. Minor allele. Systemic. BMI/fat Lean mass/ Cancer. Repeat. Gene. Polymorphism frequency. Functional significance inflammation mass strength survival studies.

  11. Allelic polymorphism of Makoei sheep leptin gene identified by ...

    African Journals Online (AJOL)

    use

    2011-12-05

    Dec 5, 2011 ... intake, energy expenditure and whole-body energy balance in animals. In the present study, the polymorphism of the leptin gene (LEP) of Makoei sheep was investigated by polymerase chain reaction and single strand conformation polymorphism technique (PCR–SSCP). Genomic DNA was extracted.

  12. Fc receptor gamma subunit polymorphisms and systemic lupus erythematosus

    International Nuclear Information System (INIS)

    Al-Ansari, Aliya; Ollier, W.E.; Gonzalez-Gay, Miguel A.; Gul, Ahmet; Inanac, Murat; Ordi, Jose; Teh, Lee-Suan; Hajeer, Ali H.

    2004-01-01

    To investigate the possible association between Fc receptor gamma polymorphisms and systemic lupus erythematosus (SLE). We have investigated the full FcR gamma gene for polymorphisms using polymerase chain reaction (PCR)-single strand confirmational polymorphisms and DNA sequencing .The polymorphisms identified were genotype using PCR-restriction fragment length polymorphism. Systemic lupus erythematosus cases and controls were available from 3 ethnic groups: Turkish, Spanish and Caucasian. The study was conducted in the year 2001 at the Arthritis Research Campaign, Epidemiology Unit, Manchester University Medical School, Manchester, United Kingdom. Five single nucleotide polymorphisms were identified, 2 in the promoter, one in intron 4 and, 2 in the 3'UTR. Four of the 5 single nucleotide polymorphisms (SNPs) were relatively common and investigated in the 3 populations. Allele and genotype frequencies of all 4 investigated SNPs were not statistically different cases and controls. fc receptor gamma gene does not appear to contribute to SLE susceptibility. The identified polymorphisms may be useful in investigating other diseases where receptors containing the FcR gamma subunit contribute to the pathology. (author)

  13. cDNA cloning and polymorphic domains of the major ...

    African Journals Online (AJOL)

    Jane

    2011-10-24

    Oct 24, 2011 ... Major histocompatibility complex (MHC) is a highly polymorphic gene and plays an important role in immune system for vertebrate. To understand the polymorphism character of domestic, we cloned 32. cDNAs of MHC class I α genes of two local chicken breeds in different areas of China. There were 112.

  14. Prion protein gene polymorphisms in Turkish native goat breeds

    Indian Academy of Sciences (India)

    HASAN MEYDAN

    Susceptibility to 'scrapie' disease in goats is influenced by polymorphisms of the prion protein (PRNP) gene. The aim of ... [Meydan H., Pehlivan E., Özkan M. M., Yildiz M. A. and Goldmann W. 2017 Prion protein gene polymorphisms in Turkish native goat breeds. .... C. PCR products were resolved by electrophoresis on 2%.

  15. Fetal MTHFR C677T polymorphism confers no susceptibility to ...

    African Journals Online (AJOL)

    Vandana Rai

    for Down syndrome (DS) pregnancy but fetal MTHFR C677T polymorphism was not well studied as risk factor for DS. ... In conclusion, present meta-analysis suggests that MTHFR C677T polymorphism of fetus is not risk factor for DS. ..... IQ and etiology of DS. In the brain, epigenetic programming appears to be most sensi-.

  16. Apelin rs2235306 polymorphism is not related to metabolic ...

    African Journals Online (AJOL)

    Background: Apelin is an adipokine that was identified to play a role in the control of glucose homeostasis. Apelin rs2235306 gene polymorphism was linked to insulin resistance and poor glycemic control. Aim of the study: To assess the relation of apelin rs2235306 polymorphism with metabolic syndrome and its ...

  17. Amplified fragment length polymorphism (AFLP) studies on Indian ...

    African Journals Online (AJOL)

    Jane

    2011-07-11

    Jul 11, 2011 ... Amplified fragment length polymorphism (AFLP) technology was used to reveal the genetic variation in six species of Cycas collected from eleven natural populations. Two sets of primer with 4-selective nucleotides were used in this study and 78% polymorphism was found. The results correlated with.

  18. Plasminogen activator inhibitor-1 4G/5G polymorphism is associated with type 2 diabetes risk

    Science.gov (United States)

    Zhao, Luqian; Huang, Ping

    2013-01-01

    A number of studies were performed to assess the association between plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism and susceptibility to type 2 diabetes (T2DM). However, the results were inconsistent and inconclusive. In the present study, the possible association was investigated by a meta-analysis. Eligible articles were identified for the period up to June 2013. Pooled odds ratios (OR) with 95% confidence intervals (CI) were appropriately derived from random-effects models or fixed-effects models. Fourteen case-control studies with a total of 2487 cases and 3538 controls were eligible. In recessive model, PAI-1 4G/5G polymorphism was associated with T2DM risk (OR = 1.23; 95% CI 1.07-1.41; P = 0.004). In the subgroup analysis by ethnicity, a significant association was found among Asians (OR = 1.27; 95% CI 1.08-1.51; P = 0.005). This meta-analysis suggested that PAI-1 4G/5G polymorphism may be associated with T2DM development. PMID:24040470

  19. BIM Gene Polymorphism Lowers the Efficacy of EGFR-TKIs in Advanced Nonsmall Cell Lung Cancer With Sensitive EGFR Mutations: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Huang, Wu Feng; Liu, Ai Hua; Zhao, Hai Jin; Dong, Hang Ming; Liu, Lai Yu; Cai, Shao Xi

    2015-08-01

    The strong association between bcl-2-like 11 (BIM) triggered apoptosis and the presence of epidermal growth factor receptor (EGFR) mutations has been proven in nonsmall cell lung cancer (NSCLC). However, the relationship between EGFR-tyrosine kinase inhibitor's (TKI's) efficacy and BIM polymorphism in NSCLC EGFR is still unclear.Electronic databases were searched for eligible literatures. Data on objective response rates (ORRs), disease control rates (DCRs), and progression-free survival (PFS) stratified by BIM polymorphism status were extracted and synthesized based on random-effect model. Subgroup and sensitivity analyses were conducted.A total of 6 studies that involved a total of 773 EGFR mutant advanced NSCLC patients after EGFR-TKI treatment were included. In overall, non-BIM polymorphism patients were associated with significant prolonged PFS (hazard ratio 0.63, 0.47-0.83, P = 0.001) compared to patients with BIM polymorphism. However, only marginal improvements without statistical significance in ORR (odds ratio [OR] 1.71, 0.91-3.24, P = 0.097) and DCR (OR 1.56, 0.85-2.89, P = 0.153) were observed. Subgroup analyses showed that the benefits of PFS in non-BIM polymorphism group were predominantly presented in pooled results of studies involving chemotherapy-naive and the others, and retrospective studies. Additionally, we failed to observe any significant benefit from patients without BIM polymorphism in every subgroup for ORR and DCR.For advanced NSCLC EGFR mutant patients, non-BIM polymorphism ones are associated with longer PFS than those with BIM polymorphism after EGFR-TKIs treatment. BIM polymorphism status should be considered an essential factor in studies regarding EGFR-targeted agents toward EGFR mutant patients.

  20. Association between a serotonin transporter promoter polymorphism (5-HTTLPR) and personality disorder traits in a community sample

    Science.gov (United States)

    Blom, Rianne M.; Samuels, Jack F.; Riddle, Mark A.; Bienvenu, O. Joseph; Grados, Marco A.; Reti, Irving M.; Eaton, William W.; Liang, Kung-Yee; Nestadt, Gerald

    2011-01-01

    Background The serotonin transporter (SERT) polymorphism (5HTTLPR) has been reported to be associated with several psychiatric conditions. Specific personality disorders could be intermediate factors in the known relationship between 5HTTLPR and psychiatric disorders. This is the first study to test the association between this polymorphism and dimensions of all DSM-IV personality disorders in a community sample. Methods 374 white participants were assessed by clinical psychologists using the International Personality Disorder Examination (IPDE). Associations between dimensions of each DSM-IV personality disorder and the long (l) and short (s) alleles of the 5HTTLPR were evaluated using nonparametric tests and regression models. Results The s allele of the 5HTTLPR polymorphism was significantly associated with higher avoidant personality trait scores in the whole sample. Males with the s allele had a significantly lower likelihood of higher obsessive-compulsive personality disorder (OCPD) trait scores, whereas females with the s allele were likely to have higher OCPD personality trait scores. Conclusion This paper provides preliminary data on the relationship between personality disorders and the 5HTTLPR polymorphism. The relationship of the s allele and avoidant PD is consistent with findings of a nonspecific relationship of this polymorphism to anxiety and depressive disorders. Concerning the unusual sexual dimorphic result with OCPD, several hypotheses are presented. These findings need further replication, including a more detailed study of additional variants in SERT. PMID:21450307

  1. Association between interleukin 1 receptor antagonist gene 86-bp VNTR polymorphism and sepsis: a meta-analysis.

    Science.gov (United States)

    Fang, Fang; Pan, Jian; Li, Yiping; Xu, Lixiao; Su, Guanghao; Li, Gang; Wang, Jian

    2015-01-01

    Many studies have focused on the relationship between interleukin 1 receptor antagonist (IL1RN) gene 86-bp VNTR polymorphism and sepsis, but the results remain inconsistent. Thus, a meta-analysis was carried out to derive a more precise estimation of the association between IL1RN 86-bp VNTR polymorphism and risk of sepsis and sepsis-related mortality. Relevant publications were searched in several widely used databases and six eligible studies were included in the meta-analysis. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between IL1RN 86-bp VNTR polymorphism and risk of sepsis and sepsis-related mortality. Significant associations between IL1RN 86-bp VNTR polymorphism and sepsis risk were observed in both overall meta-analysis for L2 versus 22 (OR=0.75, 95% CI=0.59-0.94) and severe sepsis subgroup for LL+L2 versus 22 (OR=0.67, 95% CI=0.47-0.93). L stands for long alleles containing three to six repeats; 2 stands for short allele containing two repeats. However, no significant sepsis mortality variation was detected for all genetic models. According to the results of our meta-analysis, the IL1RN 86-bp VNTR polymorphism probably associates with sepsis risk but not with sepsis-related mortality. Copyright © 2014. Published by Elsevier Inc.

  2. Interleukin 4 (IL-4) gene promoter polymorphisms in Rhombomys opimus, the main reservoir of zoonotic cutaneous leishmaniasis.

    Science.gov (United States)

    Bakhshi, H; Borhani, N; Mohebali, M; Khamesipour, A; Abai, M R; Hajjaran, H; Tajedin, L; Rassi, Y; Akhavan, A A; Mohtarami, F; Oshaghi, M A

    2014-01-01

    Great gerbils (Rhombomys opimus) are the most common gerbils in center to northeast of Iran as well as central Asia and serve as reservoirs for the zoonotic agents, including Leishmania major, the principal etiologic agent of zoonotic cutaneous leishmaniasis (ZCL). The outcome of L. major infection in gerbils is not uniform. Among several immune-related factors including cytokine genes, the polymorphism in interleukin 4 (IL-4) promoter gene showed a great impact on outcome and pathological symptoms of L. major infection at least in mouse model. In this study gerbils' IL-4 promoter gene polymorphism is assessed. Specific primers were designed to develop a PCR-based assay to amplify IL-4 promoter gene to possibly define IL-4 promoter gene polymorphism in great gerbil populations with a range of Leishmania infection and symptoms collected from different foci of the central, north and northeast regions of Iran. The results showed that the designed primers amplify 689bp of the promoter gene. Sequence analysis of the promoter gene revealed five polymorphic sites assembly six haplotypes among the gerbil populations. Further studies are needed to assess whether or not the five polymorphisms cause different outcome phenotypes following infection with L. major in great gerbils. The data might be used to characterize the immune responses of R. opimus against L. major infection. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. The tumor necrosis factor-α-238 polymorphism and digestive system cancer risk: a meta-analysis.

    Science.gov (United States)

    Hui, Ming; Yan, Xiaojuan; Jiang, Ying

    2016-08-01

    Many studies have reported the association between tumor necrosis factor-α (TNF-α)-238 polymorphism and digestive system cancer susceptibility, but the results were inconclusive. We performed a meta-analysis to derive a more precise estimation of the relationship between TNF-α-238 G/A polymorphism and digestive system cancer risk. Pooled analysis for the TNF-α-238 G/A polymorphism contained 26 studies with a total of 4849 cases and 8567 controls. The meta-analysis observed a significant association between TNF-α-238 G/A polymorphism and digestive system cancer risk in the overall population (GA vs GG: OR 1.19, 95 % CI 1.00-1.40, P heterpgeneity = 0.016; A vs G: OR 1.19, 95 % CI 1.03-1.39, P heterpgeneity = 0.015; dominant model: OR 1.20, 95 % CI 1.02-1.41, P heterpgeneity = 0.012). In the analysis of the ethnic subgroups, however, similar results were observed only in the Asian population, but not in the Caucasian population. Therefore, this meta-analysis suggests that TNF-α-238 G/A polymorphism is associated with a significantly increased risk of digestive system cancer. Further large and well-designed studies are needed to confirm these findings.

  4. Association between Vascular Endothelial Growth Factor Polymorphisms and Age-Related Macular Degeneration: An Updated Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Martina Barchitta

    2016-01-01

    Full Text Available Age-related macular degeneration (AMD is the most common cause of blindness in elderly people worldwide and the major degenerative disease of the retina that leads to progressive impairment of central vision. Several polymorphisms in different genes have been proposed as factors that increase the disease susceptibility. The aim of the present study is to carry out a systematic review and an updated meta-analysis in order to summarize the current published studies and to evaluate the associations between four common vascular endothelial growth factor (VEGF polymorphisms (rs833061, rs1413711, rs3025039, and rs2010963 and AMD risk, also stratifying for AMD subtypes and ethnicity. A systematic literature search in the Medline database, using PubMed, was carried out for epidemiological studies, published before June 2016. Associations of VEGF polymorphisms with AMD were estimated by calculating pooled odds ratios (ORs and 95% confidence intervals (95% CIs based on different models. Twelve articles were included in the analysis. The present meta-analysis constitutes a useful guide for readers to study AMD and adds new evidence to the growing literature on the role of VEGF polymorphisms in the risk of AMD. Significant associations with AMD risk were showed for rs833061, rs1413711, and rs3025039 polymorphisms but not for rs2010963.

  5. Is colour polymorphism advantageous to populations and species?

    Science.gov (United States)

    Forsman, Anders

    2016-06-01

    I am writing in response to an article by Bolton, Rollins and Griffith (2015) entitled 'The danger within: the role of genetic, behavioural and ecological factors in population persistence of colour polymorphic species' that was recently published as an Opinion under the NEWS AND VIEWS section in Molecular Ecology. Bolton et al. (Molecular Ecology, 2015, 24, 2907) argue that colour polymorphism may reduce population fitness and increase extinction risk and emphasize that this is contrary to predictions put forward by Forsman et al. (Ecology, 89, 2008, 34) and Wennersten & Forsman (Biological Reviews 87, 2012, 756) that the existence of multiple colour morphs with co-adapted gene complexes and associated trait values may increase the ecological and evolutionary success of polymorphic populations and species. Bolton et al. (Molecular Ecology, 2015, 24, 2907) further state that there is no clear evidence from studies of 'true polymorphic species' that polymorphism promotes population persistence. In response, I (i) challenge their classifications of polymorphisms and revisit the traditional definitions recognizing the dynamic nature of polymorphisms, (ii) review empirical studies that have examined whether and how polymorphism is associated with extinction risk, (iii) discuss the roles of trait correlations between colour pattern and other phenotypic dimensions for population fitness and (iv) highlight that the causes and mechanisms that influence the composition and maintenance of polymorphisms are different from the consequences of the polymorphic condition and how it may impact on aspects of ecological success and long-term persistence of populations and species. © 2016 John Wiley & Sons Ltd.

  6. Effect of antibloom fat migration from a nut oil filling on the polymorphic transformation of cocoa butter.

    Science.gov (United States)

    Smith, Kevin W; Zand, Imro't; Talbot, Geoff

    2008-03-12

    In confectionery products, loss in texture contrast between chocolate and filling and the appearance of fat bloom on the surface of the chocolate can be caused by fat migration. Bloom is often linked to the transformation of the cocoa butter betaV polymorph into betaVI. A previous study showed that small additions (1%) of nut oil can have a significant impact on the rate of transformation and that migration of nut oil from a filling would increase polymorphic transformation of cocoa butter. In the present study, antibloom fat was added to the filling in a model system. The antibloom fat migrated with the nut oil and inhibited the transformation of cocoa butter from the betaV polymorph into betaVI. Despite experiencing migration of greater amounts of nut oil, cocoa butter closest to the filling transformed more slowly than that farther away (i.e., the reverse of the situation in the absence of antibloom fat).

  7. A Genetic Polymorphism in RBP4 Is Associated with Coronary Artery Disease

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    Ke Wan

    2014-12-01

    Full Text Available Insulin resistance and obesity is influenced by the retinol binding protein 4 (RBP4 adipokine. This study aims to determine if genetic polymorphisms in RBP4 are associated with the risk of coronary artery disease (CAD in Chinese patients. RBP4 polymorphisms were analyzed by high resolution melting (HRM analysis in a case-control study of 392 unrelated CAD patients and 368 controls from China. The Gensini score was used to determine the severity of CAD. The genotypic and allelic frequencies of RBP4 single-nucleotide polymorphisms were evaluated for associations with CAD and severity of disease. The A allele frequency was significantly higher in CAD case groups compared to control groups (16.7% vs. 8.8% at the RBP4 rs7094671 locus. Compared to the G allele, this allele was associated with a higher risk of CAD (OR = 2.07 (1.50–2.84. Polymorphisms at rs7094671 were found to associate with CAD using either a dominant or recessive model (OR, 95% CI: 1.97, 1.38–2.81; 3.81, 1.53–9.51, respectively. Adjusting for sex, history of smoking, serum TC, TG, LDL-c, and HDL-c, the risk of CAD for carriers remained significantly higher in both dominant and recessive models (OR, 95% CI: 1.68, 1.12–2.51; 2.74, 1.00–7.52, respectively. However, this SNP was not significantly associated with severity of CAD using angiographic scores in multivariable linear regression models (p = 0.373. The RBP4 rs7094671 SNP is associated with CAD; however, our results do not indicate that this locus is associated with clinical severity of CAD or the extent of coronary lesions.

  8. The association between brain-derived neurotrophic factor gene polymorphism and migraine: a meta-analysis.

    Science.gov (United States)

    Cai, Xiaoying; Shi, Xiaolei; Zhang, Ximeng; Zhang, Aiwu; Zheng, Minying; Fang, Yannan

    2017-12-01

    Migraine is a recurrent headache disease related to genetic variants. The brain-derived neurotrophic factor (BDNF) gene rs6265 (Val66Met) and rs2049046 polymorphism has been found to be associated with migraine. However, their roles in this disorder are not well established. Then we conduct this meta-analysis to address this issue. PubMed, Web of Science and Cochrane databases were systematically searched to identify all relevant studies. Odds ratio (OR) with corresponding 95% confidence interval (CI) was used to estimate the strength of association between BDNF gene rs6265 and rs2049046 polymorphism and migraine. Four studies with 1598 cases and 1585 controls, fulfilling the inclusion criteria were included in our meta-analysis. Overall data showed significant association between rs6265 polymorphism and migraine in allele model (OR = 0.86, 95%CI: 0.76-0.99, p = 0.03), recessive model (OR = 0.84, 95%CI: 0.72-0.98, p = 0.03) and additive model (GG vs GA: OR = 0.85, 95%CI: 0.72-1.00, p = 0.04), respectively. We also found significant association between rs2049046(A/T) polymorphism and migraine in allele model (OR = 0.88, 95%CI: 0.79-0.98, p = 0.02), recessive model (OR = 0.80, 95%CI: 0.67-0.96, p = 0.02) and additive model (AA vs TT: OR = 0.72, 95%CI: 0.57-0.92, p = 0.008; AA vs AT: OR = 0.81, 95%CI: 0.67-0.99, p = 0.03), respectively. Our meta-analysis suggested that BDNF rs6265 and rs2049046 polymorphism were associated with common migraine in Caucasian population. Further studies are awaited to update this finding in Asian population and other types of migraine.

  9. MDM2 promoter del1518 polymorphism and cancer risk: evidence from 22,931 subjects

    Directory of Open Access Journals (Sweden)

    Hua WF

    2017-07-01

    Full Text Available Wenfeng Hua,1,* Anqi Zhang,2,* Ping Duan,2,* Jinhong Zhu,3 Yuan Zhao,2 Jing He,4 Zhi Zhang1 1Department of Laboratory Medicine and Central Laboratories, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, 2Department of Obstetrics and Gynecology, The Second Affiliated Hospital & Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 3Molecular Epidemiology Laboratory and Department of Laboratory Medicine, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 4Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China *These authors contributed equally to this work Abstract: Studies have shown that single-nucleotide polymorphisms in MDM2 gene may play important roles in the development of malignant tumor. The association of del1518 polymorphism (rs3730485 in the MDM2 promoter with cancer susceptibility has been extensively studied; however, the results are contradictory. To quantify the association between this polymorphism and overall cancer risk, we conducted a meta-analysis with 12,905 cases and 10,026 controls from 16 eligible studies retrieved from PubMed, Embase, and Chinese Biomedical (CBM databases. We assessed the strength of the connection using odds ratios (ORs and 95% confidence intervals (CIs. In summary, no significant associations were discovered between the del1518 polymorphism and overall cancer risk (Del/Del vs Ins/Ins: OR =1.01, 95% CI =0.90–1.14; Ins/Del vs Ins/Ins: OR =1.03, 95% CI =0.96–1.12; recessive model: OR =0.98, 95% CI =0.90–1.07; dominant model: OR =1.03, 95% CI =0.94–1.12; and Del vs Ins: OR =1.01, 95% CI =0.94–1.07. In the stratified analysis by source of control, quality score, cancer type, and ethnicity, no significant associations were found. Despite some limitations, the current meta-analysis provides solid

  10. Relationships between TCF7L2 genetic polymorphisms and polycystic ovary syndrome risk: a meta-analysis.

    Science.gov (United States)

    Shen, Wen-Jing; Li, Tian-Ren; Hu, Yan-Jie; Liu, Hong-Bo; Song, Min

    2014-05-01

    This meta-analysis was performed to evaluate the relationships between genetic polymorphisms in the TCF7L2 gene and polycystic ovary syndrome (PCOS) risk. The PubMed, Centralised Information Service for Complementary Medicine (CISCOM), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, Google Scholar, EBSCO, Cochrane Library, and Common Biorepository Model (CBM) databases were searched for relevant articles published before November 1st, 2013, without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. The relationships were evaluated by calculating the pooled odds ratios (ORs) and their 95% confidence intervals (CIs). Seven case-control studies with a total 2458 PCOS patients and 5109 healthy subjects' met our inclusion criteria for qualitative data analysis. Two common polymorphisms (rs7903146 C→T and rs12255372 G→T) in the TCF7L2 gene were assessed. The results of our meta-analysis suggested that TCF7L2 genetic polymorphisms might be strongly correlated with an increased risk of PCOS (allele model, OR=1.33, 95% CI=1.15-1.54, P<0.001; dominant model, OR=1.40, 95% CI=1.12-1.75, P=0.003), especially for the rs7903146 C→T polymorphism. A subgroup analysis was done to investigate the effect of ethnicity on an individual's risk of PCOS. Our results revealed positive significant correlations between TCF7L2 genetic polymorphisms and an increased risk of PCOS among Caucasians (allele model, OR=1.26, 95% CI=1.08-1.47, P=0.004; dominant model, OR=1.33, 95% CI=1.00-1.76, P=0.046) and Asians (allele model, OR=2.02, 95% CI=1.42-2.89, P<0.001; dominant model, OR=2.02, 95% CI=1.40-2.92, P<0.001), but not among Africans (all P<0.05). Our findings provide convincing evidence that TCF7L2 genetic polymorphisms may contribute to susceptibility to PCOS, especially for the rs7903146 C→T polymorphism among Caucasians and Asians.

  11. Association of lactase 13910 C/T polymorphism with bone mineral density and fracture risk: a meta-analysis.

    Science.gov (United States)

    Wu, Yougen; Li, Yinghua; Cui, Yunqing; Zhou, Yunjiao; Qian, Qingqing; Hong, Yang

    2017-12-01

    A number of studies have investigated the association of lactase (LCT,C/T-13910) gene polymorphismwith bonemineral density (BMD) and fracture risk, but previous results were inconclusive. In this study, a meta-analysis was performed to quantify the association of LCT (C/T-13910) polymorphism with BMD and fracture risk. Eligible publications were searched in the PubMed, Web of Science, Embase databases, Google Scholar, Yahoo and Baidu. Pooled weighed mean difference (WMD) or odds ratio (OR) with their 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model. A total of nine articles with 8871 subjects were investigated in the presentmeta-analysis. Overall, the TT/TC genotypes of LCT 13910 C/T polymorphism showed significantly higher BMD than those with the CC genotype at femur neck (FN) (WMD = 0.011 g/cm 2 , 95% CI = 0.004-0.018, P = 0.003). Besides, LCT 13910 C/T polymorphism may decrease the risk of any site fractures (for TT versus TC+CC, OR = 0.813, 95% CI = 0.704-0.938, P = 0.005; for T allele versus C allele, OR = 0.885, 95% CI = 0.792-0.989, P = 0.032). However, there was no significant association of LCT 13910 C/T polymorphism with BMD at lumbar spine and risk of vertebral fractures under all genetic contrast models (all P values were >0.05). The meta-analysis suggests that there are significant effects of LCT 13910 C/T polymorphism on BMD and fracture risk. Large-scale studies with different ethnic populations will be needed to further investigate the possible race-specific effect of LCT 13910 C/T polymorphism on BMD and fracture risk.

  12. Interleukin-10 -1082A/G polymorphism is associated with the development of acute pancreatitis in a Chinese population.

    Science.gov (United States)

    Cai, Feng; Cui, Ning; Ma, Hongyan; Wang, Xueli; Qiao, Guihong; Liu, Danping

    2015-01-01

    We conducted a case-control study to investigate the association between IL-10 gene polymorphism (-1082A/G, -819T/C, and -592A/C) and risk of acute pancreatitis in a Chinese population. A total of 240 patients with proven acute pancreatitis and 240 control subjects were collected between May 2012 and January 2015. Genotyping of the IL-10-1082A/G, -819T/C, and -592A/C gene polymorphisms was conducted by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. By univariate logistic regression analysis, patients with acute pancreatitis were more likely to have higher BMI (OR=2.12, 95% CI=1.45-3.12; Pacute pancreatitis and control subjects (χ(2)=9.97, P=0.007). By multiple logistic regression analysis, we found that individuals with the GG genotype of IL-10-1082A/G were associated with an increased risk of acute pancreatitis when compared with the AA genotype (OR=2.32, 95% CI=1.20-4.59; P=0.007). In dominant and recessive models, the IL-10-1082A/G gene polymorphism was significantly correlated with an elevated risk of acute pancreatitis, and the adjusted Ors (95% CI) were 1.50 (1.03-2.20) and 1.99 (1.06-3.79), respectively. However, no significant different was found between IL-10-819T/C and -592A/C gene polymorphisms and susceptibility to acute pancreatitis. In conclusion, we suggest that IL-10-1082A/G gene polymorphisms contribute to the development of acute pancreatitis in codominant, dominant and recessive models.

  13. Polymorphism and Elastic Response of Molecular Materials from First Principles: How Hard Can it Be?

    Science.gov (United States)

    Reilly, Anthony; Tkatchenko, Alexandre

    2014-03-01

    Molecular materials are of great fundamental and applied importance in science and industry, with numerous applications in pharmaceuticals, electronics, sensing, and catalysis. A key challenge for theory has been the prediction of their stability, polymorphism and response to perturbations. While pairwise models of van der Waals (vdW) interactions have improved the ability of density functional theory (DFT) to model these systems, substantial quantitative and even qualitative failures remain. In this contribution we show how a many-body description of vdW interactions can dramatically improve the accuracy of DFT for molecular materials, yielding quantitative description of stabilities and polymorphism for these challenging systems. Moreover, the role of many-body vdW interactions goes beyond stabilities to response properties. In particular, we have studied the elastic properties of a series of molecular crystals, finding that many-body vdW interactions can account for up to 30% of the elastic response, leading to quantitative and qualitative changes in elastic behavior. We will illustrate these crucial effects with the challenging case of the polymorphs of aspirin, leading to a better understanding of the conflicting experimental and theoretical studies of this system.

  14. Thermodynamic description of polymorphism in Q- and N-rich peptide aggregates revealed by atomistic simulation.

    Science.gov (United States)

    Berryman, Joshua T; Radford, Sheena E; Harris, Sarah A

    2009-07-08

    Amyloid fibrils are long, helically symmetric protein aggregates that can display substantial variation (polymorphism), including alterations in twist and structure at the beta-strand and protofilament levels, even when grown under the same experimental conditions. The structural and thermodynamic origins of this behavior are not yet understood. We performed molecular-dynamics simulations to determine the thermodynamic properties of different polymorphs of the peptide GNNQQNY, modeling fibrils containing different numbers of protofilaments based on the structure of amyloid-like cross-beta crystals of this peptide. We also modeled fibrils with new orientations of the side chains, as well as a de novo designed structure based on antiparallel beta-strands. The simulations show that these polymorphs are approximately isoenergetic under a range of conditions. Structural analysis reveals a dynamic reorganization of electrostatics and hydrogen bonding in the main and side chains of the Gln and Asn residues that characterize this peptide sequence. Q/N-rich stretches are found in several amyloidogenic proteins and peptides, including the yeast prions Sup35-N and Ure2p, as well as in the human poly-Q disease proteins, including the ataxins and huntingtin. Based on our results, we propose that these residues imbue a unique structural plasticity to the amyloid fibrils that they comprise, rationalizing the ability of proteins enriched in these amino acids to form prion strains with heritable and different phenotypic traits.

  15. Oxytocin receptor gene polymorphisms are associated with human directed social behavior in dogs (Canis familiaris).

    Science.gov (United States)

    Kis, Anna; Bence, Melinda; Lakatos, Gabriella; Pergel, Enikő; Turcsán, Borbála; Pluijmakers, Jolanda; Vas, Judit; Elek, Zsuzsanna; Brúder, Ildikó; Földi, Levente; Sasvári-Székely, Mária; Miklósi, Adám; Rónai, Zsolt; Kubinyi, Enikő

    2014-01-01

    The oxytocin system has a crucial role in human sociality; several results prove that polymorphisms of the oxytocin receptor gene are related to complex social behaviors in humans. Dogs' parallel evolution with humans and their adaptation to the human environment has made them a useful species to model human social interactions. Previous research indicates that dogs are eligible models for behavioral genetic research, as well. Based on these previous findings, our research investigated associations between human directed social behaviors and two newly described (-212AG, 19131AG) and one known (rs8679684) single nucleotide polymorphisms (SNPs) in the regulatory regions (5' and 3' UTR) of the oxytocin receptor gene in German Shepherd (N = 104) and Border Collie (N = 103) dogs. Dogs' behavior traits have been estimated in a newly developed test series consisting of five episodes: Greeting by a stranger, Separation from the owner, Problem solving, Threatening approach, Hiding of the owner. Buccal samples were collected and DNA was isolated using standard protocols. SNPs in the 3' and 5' UTR regions were analyzed by polymerase chain reaction based techniques followed by subsequent electrophoresis analysis. The gene-behavior association analysis suggests that oxytocin receptor gene polymorphisms have an impact in both breeds on (i) proximity seeking towards an unfamiliar person, as well as their owner, and on (ii) how friendly dogs behave towards strangers, although the mediating molecular regulatory mechanisms are yet unknown. Based on these results, we conclude that similarly to humans, the social behavior of dogs towards humans is influenced by the oxytocin system.

  16. Seasonally fluctuating selection can maintain polymorphism at many loci via segregation lift.

    Science.gov (United States)

    Wittmann, Meike J; Bergland, Alan O; Feldman, Marcus W; Schmidt, Paul S; Petrov, Dmitri A

    2017-11-14

    Most natural populations are affected by seasonal changes in temperature, rainfall, or resource availability. Seasonally fluctuating selection could potentially make a large contribution to maintaining genetic polymorphism in populations. However, previous theory suggests that the conditions for multilocus polymorphism are restrictive. Here, we explore a more general class of models with multilocus seasonally fluctuating selection in diploids. In these models, the multilocus genotype is mapped to fitness in two steps. The first mapping is additive across loci and accounts for the relative contributions of heterozygous and homozygous loci-that is, dominance. The second step uses a nonlinear fitness function to account for the strength of selection and epistasis. Using mathematical analysis and individual-based simulations, we show that stable polymorphism at many loci is possible if currently favored alleles are sufficiently dominant. This general mechanism, which we call "segregation lift," requires seasonal changes in dominance, a phenomenon that may arise naturally in situations with antagonistic pleiotropy and seasonal changes in the relative importance of traits for fitness. Segregation lift works best under diminishing-returns epistasis, is not affected by problems of genetic load, and is robust to differences in parameters across loci and seasons. Under segregation lift, loci can exhibit conspicuous seasonal allele-frequency fluctuations, but often fluctuations may be small and hard to detect. An important direction for future work is to formally test for segregation lift in empirical data and to quantify its contribution to maintaining genetic variation in natural populations.

  17. Female sexual polymorphism and fecundity consequences of male mating harassment in the wild.

    Directory of Open Access Journals (Sweden)

    Thomas P Gosden

    2007-06-01

    Full Text Available Genetic and phenotypic variation in female response towards male mating attempts has been found in several laboratory studies, demonstrating sexually antagonistic co-evolution driven by mating costs on female fitness. Theoretical models suggest that the type and degree of genetic variation in female resistance could affect the evolutionary outcome of sexually antagonistic mating interactions, resulting in either rapid development of reproductive isolation and speciation or genetic clustering and female sexual polymorphisms. However, evidence for genetic variation of this kind in natural populations of non-model organisms is very limited. Likewise, we lack knowledge on female fecundity-consequences of matings and the degree of male mating harassment in natural settings. Here we present such data from natural populations of a colour polymorphic damselfly. Using a novel experimental technique of colour dusting males in the field, we show that heritable female colour morphs differ in their propensity to accept male mating attempts. These morphs also differ in their degree of resistance towards male mating attempts, the number of realized matings and in their fecundity-tolerance to matings and mating attempts. These results show that there may be genetic variation in both resistance and tolerance to male mating attempts (fitness consequences of matings in natural populations, similar to the situation in plant-pathogen resistance systems. Male mating harassment could promote the maintenance of a sexual mating polymorphism in females, one of few empirical examples of sympatric genetic clusters maintained by sexual conflict.

  18. Association between Mitofusin 2 Gene Polymorphisms and Late-Onset Alzheimer's Disease in the Korean Population

    Science.gov (United States)

    Kim, Young Jong; Park, Jin Kyung; Kang, Won Sub; Kim, Su Kang; Han, Changsu; Na, Hae Ri; Park, Hae Jeong; Kim, Jong Woo; Kim, Young Youl; Park, Moon Ho

    2017-01-01

    Objective Mitochondrial dysfunction is a prominent and early feature of Alzheimer's disease (AD). The morphologic changes observed in the AD brain could be caused by a failure of mitochondrial fusion mechanisms. The aim of this study was to investigate whether genetic polymorphisms of two genes involved in mitochondrial fusion mechanisms, optic atrophy 1 (OPA1) and mitofusin 2 (MFN2), were associated with AD in the Korean population by analyzing genotypes and allele frequencies. Methods One coding single nucleotide polymorphism (SNP) in the MFN2, rs1042837, and two coding SNPs in the OPA1, rs7624750 and rs9851685, were compared between 165 patients with AD (83 men and 82 women, mean age 72.3±4.41) and 186 healthy control subjects (82 men and 104 women, mean age 76.5±5.98). Results Among these three SNPs, rs1042837 showed statistically significant differences in allele frequency, and genotype frequency in the co-dominant 1 model and in the dominant model. Conclusion These results suggest that the rs1042837 polymorphism in MFN2 may be involved in the pathogenesis of AD. PMID:28096879

  19. [Lawrence Moon Biedl Bardet, a polymorphic syndrome].

    Science.gov (United States)

    Faraci, C; Galmozzi, A; Sesini, E; Ianniello, A; Milesi, S; Saija, A

    1984-01-01

    The Laurence Moon Biedl Bardet syndrome is a polymorphous disease whose pathogenesis is still obscure. It is characterize by obesity, oligophrenia, polidactylia, retinitis pigmentosa, hipogonadism, but often there are various others symptoms. AA describe two cases. After a short explanation of de main features of this disease, they dwell upon the study of clinical objective symtomatology and upon instrumental and laboratory parameters regarding hormonal, metabolic and functional order of various organs and apparatuses. Both cases present all classic symptoms of this disease. In the first case we have noticed a deficit in LH and FSH, besides we have also noticed an asymmetry of the lateral ventricles of the brain prevalently on the right and a small increase in 17-KS and 17-OH-KS urinary. On the contrary in the second case we have noticed an EEG of epileptic type.

  20. AMPD1 polymorphism and response to regadenoson.

    Science.gov (United States)

    Saab, Rayan; Zouk, Aline N; Mastouri, Ronald; Skaar, Todd C; Philips, Santosh; Kreutz, Rolf P

    2015-11-01

     AMPD1 c.34C > T (rs17602729) polymorphism results in AMPD1 deficiency. We examined the association of AMPD1 deficiency and variability of hemodynamic response to regadenoson. Genotyping for c.34C>T was performed in 267 patients undergoing regadenoson cardiac stress testing. Carriers of c.34C >T variant exhibited higher relative changes in systolic blood pressure (SBP) compared with wild-type subjects ([%] SBP change to peak: 12 ± 25 vs 5 ± 13%; p = 0.01) ([%] SBP change to nadir: -3 ± 15 vs -7 ± 11%; p = 0.04). Change in heart rate was similar between groups, but side effects were more common in carriers of the variant (+LR = 4.2; p = 0.04). AMPD1 deficiency may be involved in the modulation of regadenoson's systemic effects.

  1. Association of type 2 diabetes candidate polymorphisms in KCNQ1 with incretin and insulin secretion

    DEFF Research Database (Denmark)

    Müssig, Karsten; Staiger, Harald; Machicao, Fausto

    2009-01-01

    OBJECTIVE: KCNQ1 gene polymorphisms are associated with type 2 diabetes. This linkage appears to be mediated by altered beta-cell function. In an attempt to study underlying mechanisms, we examined the effect of four KCNQ1 single nucleotide polymorphisms (SNPs) on insulin secretion upon different...... C-peptide levels during OGTT, first-phase insulin secretion, and insulinogenic index after adjustment in the dominant model (all P insulin secretion indexes (all P ... and basal or stimulated incretin levels (all P > or = 0.05). CONCLUSIONS: Common genetic variation in KCNQ1 is associated with insulin secretion upon oral glucose load in a German population at increased risk of type 2 diabetes. The discrepancy between orally and intravenously administered glucose seems...

  2. Associations of myostatin gene polymorphisms with performance and mortality traits in broiler chickens

    Directory of Open Access Journals (Sweden)

    Lamont Susan J

    2007-01-01

    Full Text Available Abstract Myostatin is a negative regulator of skeletal muscle growth. We evaluated effects of myostatin polymorphisms in three elite commercial broiler chicken lines on mortality, growth, feed conversion efficiency, ultrasound breast depth, breast percentage, eviscerated carcass weight, leg defects, blood oxygen level, and hen antibody titer to infectious bursal disease virus vaccine. Progeny mean data adjusted for fixed and mate effects and DNA from 100 sires per line were used. Single nucleotide polymorphisms (SNPs of the myostatin gene segregating in these lines were identified by designing specific primers, amplifying individual DNA in each line by polymerase chain reaction, cloning, sequencing and aligning the corresponding products. Individual sires were genotyped for five identified SNPs which contributed to eight haplotypes. Frequencies of SNP alleles and haplotypes differed between lines. Using the allele substitution effect model, the myostatin SNPs were found to have significant (P

  3. Identification and quantitative determination of atorvastatin calcium polymorph in tablets using FT-Raman spectroscopy.

    Science.gov (United States)

    Skorda, Dimitra; Kontoyannis, Christos G

    2008-01-15

    Atorvastatin calcium (ATC) is the active pharmaceutical ingredient (API) of the best selling lipid-lowering formulation Lipitor. Twelve ATC crystal forms are known and several pharmaceutical companies are developing or have developed generic drug formulations based on different ATC polymorphs. The strong overlap of the X-ray diffraction patterns (XRD) of the polymorphs with the respective patterns of the excipients, the presence of small API quantities in the tablet and the similarity of the crystal phase VIII XRD pattern used in the tablet examined in this work to that of phases IV and IX made identification difficult. Quantitative determination of ATC was attempted using Raman spectroscopy (RS), IR spectroscopy and X-ray powder diffraction. It was found that RS exhibited lower detection limit and a calibration model was constructed. Its application on commercial ATC tablets with 40mg strength yielded an error of 1.25%.

  4. Goat acetyl-coenzyme A carboxylase alpha: molecular characterization, polymorphism, and association with milk traits.

    Science.gov (United States)

    Badaoui, B; Serradilla, J M; Tomàs, A; Urrutia, B; Ares, J L; Carrizosa, J; Sànchez, A; Jordana, J; Amills, M

    2007-02-01

    Acetyl-coenzyme A carboxylase alpha (ACACA), the major regulatory enzyme of fatty acid biosynthesis, catalyzes the conversion of acetyl-CoA to malonyl-CoA. We have sequenced 5.5 kb of the goat ACACA cDNA in 18 individuals. The translated cDNA sequence encodes 1,832 AA and shares a high AA identity (99%) with the ovine and bovine ACACA orthologous sequences. One silent single nucleotide polymorphism was identified at exon 45 (C5493T). The genotyping of this polymorphism in 4 goat breeds, Murciano-Granadina, Teramana, Majorera, and Malagueña, showed that it was segregating in all 4 breeds at variable frequencies. In addition, a mixed animal model was used to evaluate the association of C5493T genotypes with milk traits. Results from this study show that the C5493T mutation was suggestively associated with fat yield, lactose content, and somatic cell count.

  5. Class I mhc genes of cichlid fishes: identification, expression, and polymorphism.

    Science.gov (United States)

    Sato, A; Klein, D; Sültmann, H; Figueroa, F; O'hUigin, C; Klein, J

    1997-01-01

    Cichlid fishes of the East African Rift Valley lakes constitute an important model of adaptive radiation. Explosive speciation in the Great Lakes, in some cases as recently as 12 400 years ago, generated large species flocks that have been the focus of evolutionary studies for some time. The studies have, however, been hampered by the paucity of biochemical markers for phylogenetic reconstruction. Here, we describe a set of markers which should help to alleviate this problem. They are the class I genes of the major histocompatibility complex. We provide evidence for the existence of at least 17 class I loci in cichlid fishes, and for extensive polymorphism of three of these loci. Since the polymorphism has a trans-species character, it will be possible to use it in investigating the founding events of the individual species. The sequences of the cichlid class I fishes support the monophyly of actinopterygian fish on the one hand, and of tetrapods on the other.

  6. Associations of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms with genetic susceptibility to rheumatoid arthritis: a meta-analysis.

    Science.gov (United States)

    Cen, Han; Huang, Hua; Zhang, Li-Na; Liu, Li-Ya; Zhou, Li; Xin, Xia-Fei; Zhuo, Ren-Jie

    2017-02-01

    The aim of our study was to conduct a meta-analysis to assess whether combined evidence shows associations between C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and genetic susceptibility to rheumatoid arthritis (RA). A total of 11 articles involving 20 comparisons were included, containing 12 comparisons for the MTHFR C677T polymorphism and 8 comparisons for the MTHFR A1298C polymorphism. Significant evidence was detected for the association of RA susceptibility with the MTHFR C677T polymorphism T allele under allelic contrast and dominant model in Asians (T versus C, OR = 1.300, 95 % CI = 1.104-1.531, p = 0.002; TT + CT versus CC, OR = 1.495, 95 % CI = 1.187-1.882, p = 0.001). Significant association between RA susceptibility and the MTHFR A1298C polymorphism A allele under recessive model was found in the overall meta-analysis (AA versus AC + CC, OR = 1.281, 95 % CI = 1.048-1.565, p = 0.016). Our meta-analysis results demonstrate that the MTHFR C677T polymorphism is involved in the genetic susceptibility of RA in Asians, and the MTHFR A1298C polymorphism is associated with genetic susceptibility to RA in the overall population. Given the paucity of studies, especially in non-Asian populations, further studies with larger sample sizes are required to elucidate the role of MTHFR polymorphisms in the genetic basis of RA in different ethnic populations.

  7. Lack of Association Between the IL1B (-511 and +3954), IL1RN VNTR Polymorphisms and Tuberculosis Risk: A Meta-analysis.

    Science.gov (United States)

    Huang, Qiu-Pin; Liao, Ning; Zhao, Hua; Chen, Min-Li; Xie, Zheng-Fu

    2015-12-01

    Several recent studies have provided evidence that polymorphisms in the interleukin-1 (IL1) gene are implicated in tuberculosis (TB). However, results of different studies are inconsistent. The aim of this study was to perform a meta-analysis investigating the association of the IL1B (-511 and +3954) and IL1RN VNTR polymorphisms with TB risk. A systematic review of the English literature was conducted by searching Pubmed, Scopus, and ISI Web of Knowledge databases for relevant studies. Pooled odds ratios (OR) with 95 % confidence intervals (CI) were calculated using fixed effects models. Between-study heterogeneity and publication bias were also evaluated. Nine case-control studies including 3327 participants were reviewed and analyzed. Our results did not indicate any association of the IL1B (-511 and +3954) and IL1RN VNTR polymorphisms with TB risk in the overall populations. The pooled OR of the IL1B -511 polymorphism was 1.09 (95 % CI 0.87-1.36) for the dominant model, 1.11 (0.89-1.38) for the recessive model, 1.15 (0.87-1.50) for the homozygote model, and 1.07 (0.94-1.23) for the allelic comparison model. ORs for the IL1B +3954 and IL1RN VNTR polymorphisms were similar. In subgroup analysis stratified by ethnicity, the results revealed no association between these polymorphisms and TB risk in black people, Asians, and Caucasians, respectively. We did not identify significant between-study heterogeneity across all studies, and there was no evidence of publication bias. Our results indicate there is a lack of association between the IL1B (-511 and +3954), IL1RN VNTR polymorphisms and TB risk.

  8. Investigation of haemoglobin polymorphism in Ogaden cattle

    Directory of Open Access Journals (Sweden)

    Sanjoy Kumar Pal

    2014-04-01

    Full Text Available Background and Aim: The Ogaden cattle is one among the tropical cattle breeds (Bos indicus widely distributed in eastern and south eastern part of Ethiopia. The breed has been evolved in arid and semi arid agro-ecological setup, but later on distributed and adapted to the wide agro-ecological zones. Because of its multi-purpose role, the Ogaden cattle have been used for milk, beef, and income generation. Information on the inherent genetic diversity is important in the design of breeding improvement programmes, making rational decisions on sustainable utilization and conservation of Animal Genetic Resources. Limited information is available about genetic variation of Ogaden breed at molecular level. The present investigation was aimed to study the biochemical polymorphism at the Hemoglobin (Hb locus. Materials and Methods: Blood samples collected from 105 Ogaden cattle maintained at Haramaya beef farm by jugular vein puncture were subjected to agarose gel electrophoresis [pH range 8.4-8.5] to study the polymorphic activities of haemoglobin. Results: Three types of phenotypes were detected i.e. a slow moving (AA band, fast moving (BB band and a combination of slow + fast moving bands (AB. The frequency of the fast moving band was less [13 (12.3%] than the slow moving band [57 (54.2%]. Both slow & fast moving phenotype was observed in 35 (33.3% animals. The gene frequency of HBA allele was 0.709 and that of HBB allele 0.291. Conclusion: The distribution of phenotypes was in agreement with codominant single gene inheritance. The Chi-square (χ2 test revealed that the population is under Hardy-Weinberg equilibrium.

  9. HLA polymorphism in Sudanese renal donors

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    Ameer M Dafalla

    2011-01-01

    Full Text Available The main objective of this study is to provide a database for renal transplantation in Sudan and to determine the HLA antigens and haplotype frequencies (HFs in the study subjects. HLA typing was performed using the complement-dependant lymphocytotoxicity test in 250 unrelated healthy individuals selected as donors in the Sudanese Renal Transplantation Program. Considerable polymorphism was observed at each locus; A2 (0.28, A30 (0.12, A3 (0.09, A24 (0.09, A1 (0.09, and A68 (0.06 were the most frequent antigens in the A locus, while B51 (0.092, B41 (0.081, B39 (0.078, B57 (0.060, B35 (0.068, B 50 (0.053 and B 52 (0.051 were the most common B locus antigens. DR13 (0.444 and DR15 (0.160 showed the highest antigen frequencies (AFs in the DR locus. In the DQ locus, DQ1 showed the highest gene frequency (0.498, while DQ2 and DQ3 AFs were (0.185 and (0.238, respectively. The most common HLA-A and -B haplotypes in positive linkage disequilibrium were A24, B38; A1, B7; and A3, B52. The common HLA-A and -B HFs in positive linkage disequilibrium in the main three tribe-stocks of the study subjects (Gaalia, Nile Nubian and Johyna were A24, B38 for Gaalia; A24, B38 and A2, B7 for Johyna; and A2, B64 and A3, B53 for Nile Nubian. These results suggest that both class I and class II polymorphisms of the study subjects depict considerable heterogeneity, which reflects recent admixture of this group with neighboring Arabs and African populations.

  10. APOE gene polymorphism analysis in Barranquilla, Colombia.

    Science.gov (United States)

    Ruiz, Martha; Arias, Isis; Rolón, Gloria; Hernández, Enio; Garavito, Pilar; Silvera-Redondo, Carlos

    2016-03-03

    The genetic variability present in the APOE gene polymorphism is considered an important factor associated with predisposition to diseases affecting lipid metabolism, as well as heart diseases and Alzheimer's disease, among others. Understanding it as a risk factor in different populations and ethnic groups is a useful tool.  To analyze the APOE gene polymorphism and determine allelic and genotypic frequencies of a representative sample of population from Barranquilla, Colombia.  We performed a descriptive and comparative study. The sample size was 227 unrelated individuals from Barranquilla, Colombia.  The most frequent allele was the ε3, with 85%, followed by the ε4 allele (13%) and ε2 (1.8%). The genotypes found were: ε3/ε3: 71.8%, ε3/ε4: 24.2%, ε2/ε3: 2.2%, ε2/ε4: 1.3% and ε4/ε4: 0.4%. The ε2/ε2 genotype was not found in this study. The sample exhibited the Hardy-Weinberg equilibrium.  The frequency of the ε3 allele and the ε3/ε3 genotype was similar to that reported in the literature in countries like Brazil, Mexico, Colombia, and in some Colombian Amerindian ethnic groups. The ε2/ε2 genotype was absent. This result is consistent with those found in other population groups worldwide. The frequency of the ε4 allele and the genotypes associated in this population could be related to the presence of diseases such as hypercholesterolemia, myocardial infarction and Alzheimer.

  11. Back to basics: using colour polymorphisms to study evolutionary processes.

    Science.gov (United States)

    Svensson, Erik I

    2017-04-01

    Here, I suggest that colour polymorphic study systems have been underutilized to answer general questions about evolutionary processes, such as morph frequency dynamics between generations and population divergence in morph frequencies. Colour polymorphisms can be used to study fundamental evolutionary processes like frequency-dependent selection, gene flow, recombination and correlational selection for adaptive character combinations. However, many previous studies of colour polymorphism often suffer from weak connections to population genetic theory. I argue that too much focus has been directed towards noticeable visual traits (colour) at the expense of understanding the evolutionary processes shaping genetic variation and covariation associated with polymorphisms in general. There is thus no need for a specific evolutionary theory for colour polymorphisms beyond the general theory of the maintenance of polymorphisms in spatially or temporally variable environments or through positive or negative frequency-dependent selection. I outline an integrative research programme incorporating these processes and suggest some fruitful avenues in future investigations of colour polymorphisms. © 2017 John Wiley & Sons Ltd.

  12. Does colour polymorphism enhance survival of prey populations?

    Science.gov (United States)

    Wennersten, Lena; Forsman, Anders

    2009-01-01

    That colour polymorphism may protect prey populations from predation is an old but rarely tested hypothesis. We examine whether colour polymorphic populations of prey exposed to avian predators in an ecologically valid visual context were exposed to increased extinction risk compared with monomorphic populations. We made 2976 artificial pastry prey, resembling Lepidoptera larvae, in four different colours and presented them in 124 monomorphic and 124 tetramorphic populations on tree trunks and branches such that they would be exposed to predation by free-living birds, and monitored their ‘survival’. Among monomorphic populations, there was a significant effect of prey coloration on survival, confirming that coloration influenced susceptibility to visually oriented predators. Survival of polymorphic populations was inferior to that of monomorphic green populations, but did not differ significantly from monomorphic brown, yellow or red populations. Differences in survival within polymorphic populations paralleled those seen among monomorphic populations; the red morph most frequently went extinct first and the green morph most frequently survived the longest. Our findings do not support the traditional protective polymorphism hypothesis and are in conflict with those of earlier studies. As a possible explanation to our findings, we offer a competing ‘giveaway cue’ hypothesis: that polymorphic populations may include one morph that attracts the attention of predators and that polymorphic populations therefore may suffer increased predation compared with some monomorphic populations. PMID:19324729

  13. Association of Parkinson disease age of onset with DRD2, DRD3 and GRIN2B polymorphisms.

    Science.gov (United States)

    Hassan, Anhar; Heckman, Michael G; Ahlskog, J E; Wszolek, Zbigniew K; Serie, Daniel J; Uitti, Ryan J; van Gerpen, Jay A; Okun, Michael S; Rayaprolu, Sruti; Ross, Owen A

    2016-01-01

    Dopamine and glutamate are crucial neurotransmitters in Parkinson disease (PD). While recent large meta-analyses reported that genetic variation of dopamine (DRD2, DRD3) and glutamine (NMDA, GRIN2B) neurotransmitter receptors was not associated with PD risk, they could conceivably influence PD phenotype. We studied the association of these receptor polymorphisms relating to PD age of onset. There were 664 PD patients and 718 controls, all Caucasian, with stored DNA at Mayo Clinic, Jacksonville, Florida. Genotyping was performed for DRD2 (Taq 1A, rs1800497), DRD3 (rs6280), and NMDA (GRIN2B, rs7301328) polymorphisms with ABI Taqman assays. Single nucleotide polymorphism associations with age of onset were evaluated using dominant, recessive, and additive genotypic models. DRD3 variant carriers had an approximate 4.4-year decrease in mean age of onset when both copies of the minor allele were present (P = 0.0034) and an approximate 1.5-year decrease in mean age at onset for every additional minor allele (P = 0.023) (recessive and additive models, respectively). There was no association with age of onset for DRD2 or GRIN2B under any statistical model (all P ≥ 0.22). The DRD3 (rs6280) polymorphism, but not DRD2 (Taq1A) or GRIN2B, influences younger PD age of onset in the US Caucasian population. Validation of these findings in larger studies with other ethnic groups is indicated. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Association between Toll-like receptor 9 gene polymorphisms and risk of bacterial meningitis in a Chinese population.

    Science.gov (United States)

    Wang, X H; Shi, H P; Li, F J

    2016-07-25

    We determined whether two common single nucleotide polymorphisms (SNPs) in the Toll-like receptor 9 gene (TLR9) (TLR9+2848 rs352140 and TLR9-1237 rs5743836) influenced susceptibility to bacterial meningitis in a Chinese population. The study comprised 126 patients with bacterial meningitis and 252 control subjects, all of whom were recruited from the Tuberculosis Hospital of Shanxi Province. Genotyping of TLR9+2848 rs352140 and TLR9-1237 rs5743836 was performed by polymerase chain reaction coupled with restriction fragment length polymorphism. Using logistic regression analysis, we found that individuals with the AA genotype were associated with an increased risk of bacterial meningitis compared with those with the GG genotype (OR = 0.43, 95%CI = 0.19-0.95; P = 0.03). In a recessive model, the AA genotype was correlated with an elevated risk of bacterial meningitis compared with the GG+GA genotype (OR = 0.49, 95%CI = 0.22-0.99; P = 0.04). However, no significant differences were observed in the association between the TLR9-1237 rs5743836 polymorphism and the risk of bacterial meningitis in the codominant, dominant, or recessive models. In conclusion, the results of our study suggest an association between the TLR9+2848 polymorphism and a reduced risk of bacterial meningitis in the codominant and recessive models.

  15. Two functional serotonin polymorphisms moderate the effect of food reinforcement on BMI.

    Science.gov (United States)

    Carr, Katelyn A; Lin, Henry; Fletcher, Kelly D; Sucheston, Lara; Singh, Prashant K; Salis, Robbert J; Erbe, Richard W; Faith, Myles S; Allison, David B; Stice, Eric; Epstein, Leonard H

    2013-06-01

    Food reinforcement, or the motivation to eat, has been associated with increased energy intake, greater body weight, and prospective weight gain. Much of the previous research on the reinforcing value of food has focused on the role of dopamine, but it may be worthwhile to examine genetic polymorphisms in the serotonin and opioid systems as these neurotransmitters have been shown to be related to reinforcement processes and to influence energy intake. We examined the relationship among 44 candidate genetic polymorphisms in the dopamine, serotonin, and opioid systems, as well as food reinforcement and body mass index (BMI) in a sample of 245 individuals. Polymorphisms in the monoamine oxidase A (MAOA-LPR) and serotonin receptor 2A genes (rs6314) moderated the effect of food reinforcement on BMI, accounting for an additional 5-10% variance and revealed a potential role of the single nucleotide polymorphism, rs6314, in the serotonin 2A receptor as a differential susceptibility factor for obesity. Differential susceptibility describes a factor that can confer either risk or protection depending on a second variable, such that rs6314 is predictive of both high and low BMI based on the level of food reinforcement, while the diathesis stress or dual-gain model only influences one end of the outcome measure. The interaction with MAOA-LPR better fits the diathesis stress model, with the 3.5R/4R allele conferring protection for individuals low in food reinforcement. These results provide new insight into genes theoretically involved in obesity, and support the hypothesis that genetics moderate the association between food reinforcement and BMI. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  16. Melatonin receptor 1 B polymorphisms associated with the risk of gestational diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Yang Jae-Hyug

    2011-06-01

    Full Text Available Abstract Backgrounds Two SNPs in melatonin receptor 1B gene, rs10830963 and rs1387153 showed significant associations with fasting plasma glucose levels and the risk of Type 2 Diabetes Mellitus (T2DM in previous studies. Since T2DM and gestational diabetes mellitus (GDM share similar characteristics, we suspected that the two genetic polymorphisms in MTNR1B may be associated with GDM, and conducted association studies between the polymorphisms and the disease. Furthermore, we also examined genetic effects of the two polymorphisms with various diabetes-related phenotypes. Methods A total of 1,918 subjects (928 GDM patients and 990 controls were used for the study. Two MTNR1B polymorphisms were genotyped using TaqMan assay. The allele distributions of SNPs were evaluated by x2 models calculating odds ratios (ORs, 95% confidence intervals (CIs, and corresponding P values. Multiple regressions were used for association analyses of GDM-related traits. Finally, conditional analyses were also performed. Results We found significant associations between the two genetic variants and GDM, rs10830963, with a corrected P value of 0.0001, and rs1387153, with the corrected P value of 0.0008. In addition, we also found that the two SNPs were associated with various phenotypes such as homeostasis model assessment of beta-cell function and fasting glucose levels. Further conditional analyses results suggested that rs10830963 might be more likely functional in case/control analysis, although not clear in GDM-related phenotype analyses. Conclusion There have been studies that found associations between genetic variants of other genes and GDM, this is the first study that found significant associations between SNPs of MTNR1B and GDM. The genetic effects of two SNPs identified in this study would be helpful in understanding the insight of GDM and other diabetes-related disorders.

  17. Methylenetetrahydrofolate Reductase gene polymorphism in children with allergic rhinitis.

    Science.gov (United States)

    Dogru, M; Aydin, H; Aktas, A; Cırık, A A

    2015-01-01

    Methylenetetrahydrofolate Reductase (MTHFR) polymorphisms by impairing folate metabolism may influence the development of allergic diseases. The results of studies evaluating the relationship between MTHFR polymorphisms and atopic disease are controversial. The aim of this study was to investigate the association between the polymorphisms of C677T and A1298C for MTHFR gene and allergic rhinitis (AR) in children. Ninety patients followed up with diagnosis of allergic rhinitis in our clinic and 30 children with no allergic diseases were included in the study. All participants were genotyped for the MTHFR (C677T) and (A1298C) polymorphisms. Vitamin b12, folate and homocysteine levels were measured. The mean age of patients was 9.2±2.9 years; 66.7% of the patients were male. There was no significant difference between patient and control groups regarding gender, age and atopy history of the family (p>0.05). The frequency of homozygotes for MTHFR C677T polymorphism in the patient and control groups was 3.3% and 10%, respectively. The frequency of homozygotes for MTHFR A1298C polymorphism among groups was 26.7% and 16.7%, respectively. The association between allergic rhinitis and polymorphisms of C677T and A1298C for MTHFR gene was not statistically significant in patients compared with controls (p>0.05). There were no statistically significant differences between the patients and the control group in terms of serum vitamin b12, folate and homocysteine levels (p>0.05). We found no evidence for an association between allergic rhinitis and polymorphisms of C677T and A1298C for MTHFR gene in children. Further studies investigating the relationship between MTHFR polymorphism and AR are required. Copyright © 2014 SEICAP. Published by Elsevier Espana. All rights reserved.

  18. The HLA-G 14-bp polymorphism and recurrent implantation failure: a meta-analysis.

    Science.gov (United States)

    Fan, Wei; Huang, Zhongying; Li, Shangwei; Xiao, Zhun

    2017-11-01

    The human leucocyte antigen-G (HLA-G) 14-bp insertion/deletion polymorphism was implicated in recurrent implantation failure (RIF), but individual published studies showed inconclusive results. Thus, a meta-analysis was performed to clarify the effect of HLA-G 14-bp polymorphism on RIF risk. A comprehensive search for relevant articles was conducted. The odds ratios (ORs) and 95% confidence intervals (CIs) for HLA-G 14-bp polymorphism and RIF were calculated. A total of five studies were included. In studies conducted in RIF patients and controls who had at least one spontaneous pregnancy, meta-analysis revealed no statistically significant association between the HLA-G 14-bp polymorphism and RIF in allele contrast and all genetic models in the overall population, but significant association was found in the population of Caucasian origin under allele contrast (OR = 1.73, 95% CI, 1.20, 2.50) and genetic models of +14 bp/+14 bp vs. -14 bp/-14 bp (OR = 3.09, 95% CI, 1.43, 6.65). In studies conducted in RIF patients and controls who had successful pregnancy following IVF-ET, the meta-analysis showed that there was statistically significant association between the HLA-G 14 bp polymorphism and RIF in allele contrast (OR = 1.74, 95% CI, 1.13, 2.67) and genetic models of +14 bp/+14 bp vs. -14 bp/-14 bp (OR = 10.20, 95% CI, 2.47, 42.14) and dominant model (OR = 4.34, 95% CI, 1.72, 10.92). No publication bias was found in the present studies. This meta-analysis suggested that the HLA-G 14-bp insertion allele may increase the risk of RIF in Caucasians. Further studies with large sample size of different ethnic populations are necessary.

  19. Synthetic analysis of associations between IL-10 polymorphisms and skin cancer risk.

    Science.gov (United States)

    Zhao, Hongbo; Yang, Jiaoli; Yu, Zhenzhen; Shen, Hui; Huang, Xinlin; Zhang, Mi; Long, Teng; Cailing, A; Wang, Wenhui

    2018-01-23

    The current study was designed to quantitatively summarize the evidence for the strength of the associations between common IL-10 functional polymorphisms and skin cancer risk. Relevant publications concerning the associations between common IL-10 functional polymorphisms(-1082G>A, -819C>T and -592C>A) and skin cancer were retrieved by a comprehensive electronic literature search in PubMed, Web of Science, EBSCO, Embase, China National Knowledge Infrastructure, Wanfang, Chinese Biomedical Database (CBM). The odds ratio (OR) and 95% confidence interval (CI) were utilized to assess the strength of the relationship. A total of 26 studies including 4090 cases and 4133 controls (-1082G>A, 10 studies with 1809 cases and 1830 controls; -819C>T, 7 studies with 862 cases and 957 controls; -592C>A, 9 studies with 1419 cases and 1346 controls) were enrolled in the meta-analysis. Overall, the results revealed a borderline decreased risk of skin cancer in heterozygote model (OR = 0.82, 95CI = 0.67-1.00, p = 0.05). The subgroup analysis also presented similar association for non-melanoma skin cancer in heterozygote model (OR = 0.67, 95CI = 0.50-0.91, p = 0.01). Moreover, the further analysis based on the histological type of non-melanoma skin cancer indicated a significantly decreased risk of BCC in allele model (OR = 0.67, 95% CI = 0.50-0.91, p = 0.02) and dominant model (OR = 0.68, 95% CI = 0.48-0.98, p = 0.04). However, neither overall analysis nor subgroup analysis based on cancer subtype revealed a significant association of -1082G>A or -592C>A polymorphisms with skin cancer. The present study suggested a potential association between IL-10 -819C>T polymorphism and decreased risk of skin cancer, but a lack of association for -1082G>A and -592C>A polymorphisms. Further invalidation is urgently needed.

  20. Association between an interleukin-13 promoter polymorphism and atopy

    DEFF Research Database (Denmark)

    Hummelshoj, T; Bodtger, U; Datta, P

    2003-01-01

    polymorphism in the IL-13 gene (C to T exchange) at position -1055 and allergic asthma in a population study in the Netherlands. This observation was apparently confirmed in a case-control study using probands and spouses from a Dutch asthma family study, but the polymorphism in that study was reported...... to occur at position -1111. In the present study, we established that this polymorphism is located at position -1024 relative to the ATG translation initiation codon, and investigated whether it confers a genetic predisposition to atopic conditions and the Th1 condition multiple sclerosis (MS) in Caucasian...