12,395 research outputs found

    Brauer-Thrall for totally reflexive modules over local rings of higher dimension

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    Let RR be a commutative Noetherian local ring. Assume that RR has a pair {x,y}\{x,y\} of exact zerodivisors such that dimR/(x,y)2\dim R/(x,y)\ge2 and all totally reflexive R/(x)R/(x)-modules are free. We show that the first and second Brauer--Thrall type theorems hold for the category of totally reflexive RR-modules. More precisely, we prove that, for infinitely many integers nn, there exists an indecomposable totally reflexive RR-module of multiplicity nn. Moreover, if the residue field of RR is infinite, we prove that there exist infinitely many isomorphism classes of indecomposable totally reflexive RR-modules of multiplicity nn.Comment: to appear in Algebras and Representation Theor

    A study on the association of the chromosome 12p13 locus with sporadic late-onset alzheimer's disease in Chinese

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    Recent linkage and association studies have implicated the chromosome 12p13 locus as possibly harboring genetic variants predisposed to Alzheimer's disease (AD). We attempted to replicate this association in a Chinese data set comprised of 256 AD cases and 264 age-matched normal controls. A total of 14 single nucleotide polymorphisms (SNPs) were examined. Single marker association revealed the two SNPs in NCAPD2 (rs7311174 and rs2072374) as showing nominal significant p values (p = 0.0491 and 0.0116, respectively). Haplotype analysis found LD block one to be significantly associated with AD (global p = 0.0250). Haplotypes CGGATG and CAGTCG were also significantly associated with AD (p = 0.0498 and p = 0.0482, respectively). These genetic analyses provide evidence that the chromosome 12p13 locus is associated with AD in Chinese. © 2009 S. Karger AG, Basel.postprin

    A cautionary tale: the non-causal association between type 2 diabetes risk SNP, rs7756992, and levels of non-coding RNA, CDKAL1-v1

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    Journal ArticleCopyright © The Author(s) 2015. This article is published with open access at Springerlink.com.Aims/hypothesis: Intronic single nucleotide polymorphisms (SNPs) in the CDKAL1 gene are associated with risk of developing type 2 diabetes. A strong correlation between risk alleles and lower levels of the non-coding RNA, CDKAL1-v1, has recently been reported in whole blood extracted from Japanese individuals. We sought to replicate this association in two independent cohorts: one using whole blood from white UK-resident individuals, and one using a collection of human pancreatic islets, a more relevant tissue type to study with respect to the aetiology of diabetes. Methods: Levels of CDKAL1-v1 were measured by real-time PCR using RNA extracted from human whole blood (n = 70) and human pancreatic islets (n = 48). Expression with respect to genotype was then determined. Results: In a simple linear regression model, expression of CDKAL1-v1 was associated with the lead type 2 diabetes-associated SNP, rs7756992, in whole blood and islets. However, these associations were abolished or substantially reduced in multiple regression models taking into account rs9366357 genotype: a moderately linked SNP explaining a much larger amount of the variation in CDKAL1-v1 levels, but not strongly associated with risk of type 2 diabetes. Conclusions/interpretation: Contrary to previous findings, we provide evidence against a role for dysregulated expression of CDKAL1-v1 in mediating the association between intronic SNPs in CDKAL1 and susceptibility to type 2 diabetes. The results of this study illustrate how caution should be exercised when inferring causality from an association between disease-risk genotype and non-coding RNA expression.MRCNIH

    A cautionary tale: the non-causal association between type 2 diabetes risk SNP, rs7756992, and levels of non-coding RNA, CDKAL1-v1

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    This is the final version of the article. Available from Springer Verlag via the DOI in this record.AIMS/HYPOTHESIS: Intronic single nucleotide polymorphisms (SNPs) in the CDKAL1 gene are associated with risk of developing type 2 diabetes. A strong correlation between risk alleles and lower levels of the non-coding RNA, CDKAL1-v1, has recently been reported in whole blood extracted from Japanese individuals. We sought to replicate this association in two independent cohorts: one using whole blood from white UK-resident individuals, and one using a collection of human pancreatic islets, a more relevant tissue type to study with respect to the aetiology of diabetes. METHODS: Levels of CDKAL1-v1 were measured by real-time PCR using RNA extracted from human whole blood (n = 70) and human pancreatic islets (n = 48). Expression with respect to genotype was then determined. RESULTS: In a simple linear regression model, expression of CDKAL1-v1 was associated with the lead type 2 diabetes-associated SNP, rs7756992, in whole blood and islets. However, these associations were abolished or substantially reduced in multiple regression models taking into account rs9366357 genotype: a moderately linked SNP explaining a much larger amount of the variation in CDKAL1-v1 levels, but not strongly associated with risk of type 2 diabetes. CONCLUSIONS/INTERPRETATION: Contrary to previous findings, we provide evidence against a role for dysregulated expression of CDKAL1-v1 in mediating the association between intronic SNPs in CDKAL1 and susceptibility to type 2 diabetes. The results of this study illustrate how caution should be exercised when inferring causality from an association between disease-risk genotype and non-coding RNA expression.This paper presents independent research funded by the Medical Research Council (grant number MR/J006777/1) and supported by the National Institute for Health Research (NIHR) Exeter Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the Medical Research Council, UK National Health Service, NIHR or the UK Department of Health

    Purpura Fulminans with Disseminated Intravascular Coagulopathy and Symmetric Peripheral Gangrene Complicating Sepsis in an Infant: A Case Report

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    Purpura fulminans is a rare consequence of sepsis that could be complicated by DIC and gangrene. We report the case of a 2-months-old infant who developed gangrenous limbs. He presented with fever, diarrhoea, vomiting and irritability for 5 days and was dehydrated and unconscious with global hypertonia. With a clinical impression of sepsis antibiotics, IV fluids and supportive care were commenced. He developed purpuric rashes over the trunk and feet, the latter of which gradually ascended over the legs, with swellings and ischemic skin changes up to the knees. A diagnosis of purpura fulminans was made and further evaluation revealed deranged haematologic parameters, features of Disseminated Intravascular Coagulopathy (DIC), hypernatraemia, azotaemia and arterial occlusion. Despite blood transfusions and supportive care gangrene emerged and progressively ascended towards the knees. Parents however rejected offer for surgical amputation and left against medical advice. The coexistence of purpura fulminans with multiple triggers for DIC should alert clinicians of a potential risk of peripheral gangrene.Keywords: Infant, Sepsis, Purpura fulminans, DIC, Gangren

    Electrical stimulation alleviates depressive-like behaviors of rats: investigation of brain targets and potential mechanisms

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    Deep brain stimulation (DBS) is a promising therapy for patients with refractory depression. However, key questions remain with regard to which brain target(s) should be used for stimulation, and which mechanisms underlie the therapeutic effects. Here, we investigated the effect of DBS, with low- and high-frequency stimulation (LFS, HFS), in different brain regions (ventromedial prefrontal cortex, vmPFC; cingulate cortex, Cg; nucleus accumbens (NAc) core or shell; lateral habenula, LHb; and ventral tegmental area) on a variety of depressive-like behaviors using rat models. In the naive animal study, we found that HFS of the Cg, vmPFC, NAc core and LHb reduced anxiety levels and increased motivation for food. In the chronic unpredictable stress model, there was a robust depressive-like behavioral phenotype. Moreover, vmPFC HFS, in a comparison of all stimulated targets, produced the most profound antidepressant effects with enhanced hedonia, reduced anxiety and decreased forced-swim immobility. In the following set of electrophysiological and histochemical experiments designed to unravel some of the underlying mechanisms, we found that vmPFC HFS evoked a specific modulation of the serotonergic neurons in the dorsal raphe nucleus (DRN), which have long been linked to mood. Finally, using a neuronal mapping approach by means of c-Fos expression, we found that vmPFC HFS modulated a brain circuit linked to the DRN and known to be involved in affect. In conclusion, HFS of the vmPFC produced the most potent antidepressant effects in naive rats and rats subjected to stress by mechanisms also including the DRN.postprin
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