158 research outputs found
Intracranial haemorrhage in a dobermann puppy with von Willebrand's disease
Neurological examination of a lethargic, ataxic 12-week-old dobermann revealed decreased conscious proprioception in all its limbs. Haematological examination revealed a low platelet count. Cytological examination of a sample of cerebrospinal fluid revealed evidence of haemorrhage and chronic inflammation. The levels of von Willebrand's factor antigen were extremely low. Skull radiographs were consistent with mild hydrocephalus. Treatment resulted in little clinical improvement and the animal was euthanased. Post mortem examination of the brain revealed an internal hydrocephalus with haemorrhage into the ventricles. It was considered that the animal had suffered severe intracranial haemorrhage as a result of its low level of von Willebrand's factor antigen and that the bleeding may have been potentiated by the low platelet count
Comparison of structural transformations and superconductivity in compressed Sulfur and Selenium
Density-functional calculations are presented for high-pressure structural
phases of S and Se. The structural phase diagrams, phonon spectra,
electron-phonon coupling, and superconducting properties of the isovalent
elements are compared. We find that with increasing pressure, Se adopts a
sequence of ever more closely packed structures (beta-Po, bcc, fcc), while S
favors more open structures (beta-Po, simple cubic, bcc). These differences are
shown to be attributable to differences in the S and Se core states. All the
compressed phases of S and Se considered are calculated to have weak to
moderate electron-phonon coupling strengths consistent with superconducting
transition temperatures in the range of 1 to 20 K. Our results compare well
with experimental data on the beta-Po --> bcc transition pressure in Se and on
the superconducting transition temperature in beta-Po S. Further experiments
are suggested to search for the other structural phases predicted at higher
pressures and to test theoretical results on the electron-phonon interaction
and superconducting properties
The speed of corneal epithelial wound healing
We propose a reaction-diffusion model of the mechanisms involved in the healing of corneal surface wounds. The model focuses on the stimulus for increased mitotic and migratory activity, specifically the role of epidermal growth factor. We determine an analytic approximation for the speed of travelling wave solutions of the model and verify the result numerically. The predicted speed compares very well with experimentally measured healing rates
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Genome-Wide Association Scan for Diabetic Nephropathy Susceptibility Genes in Type 1 Diabetes
OBJECTIVE—Despite extensive evidence for genetic susceptibility
to diabetic nephropathy, the identification of susceptibility
genes and their variants has had limited success. To search for
genes that contribute to diabetic nephropathy, a genome-wide
association scan was implemented on the Genetics of Kidneys in
Diabetes collection.
RESEARCH DESIGN AND METHODS—We genotyped
360,000 single nucleotide polymorphisms (SNPs) in 820 case
subjects (284 with proteinuria and 536 with end-stage renal
disease) and 885 control subjects with type 1 diabetes. Confirmation
of implicated SNPs was sought in 1,304 participants of the
Diabetes Control and Complications Trial (DCCT)/Epidemiology
of Diabetes Interventions and Complications (EDIC) study, a
long-term, prospective investigation of the development of diabetes-
associated complications.
RESULTS—A total of 13 SNPs located in four genomic loci were
associated with diabetic nephropathy with P1105. The
strongest association was at the FRMD3 (4.1 protein ezrin,
radixin, moesin [FERM] domain containing 3) locus (odds ratio
[OR]1.45, P5.0107). A strong association was also
identified at the CARS (cysteinyl-tRNA synthetase) locus (OR
1.36, P3.1106). Associations between both loci and time to
onset of diabetic nephropathy were supported in the DCCT/EDIC
study (hazard ratio [HR]1.33, P0.02, and HR1.32, P
0.01, respectively). We demonstrated expression of both FRMD3
and CARS in human kidney.
CONCLUSIONS—We identified genetic associations for susceptibility
to diabetic nephropathy at two novel candidate loci near
the FRMD3 and CARS genes. Their identification implicates
previously unsuspected pathways in the pathogenesis of this
important late complication of type 1 diabetes
Genome-Wide Association Scan for Diabetic Nephropathy Susceptibility Genes in Type 1 Diabetes
10.2337/db08-1514Diabetes5861403-1410DIAE
Molecular and translational advances in meningiomas.
Meningiomas are the most common primary intracranial neoplasm. The current World Health Organization (WHO) classification categorizes meningiomas based on histopathological features, but emerging molecular data demonstrate the importance of genomic and epigenomic factors in the clinical behavior of these tumors. Treatment options for symptomatic meningiomas are limited to surgical resection where possible and adjuvant radiation therapy for tumors with concerning histopathological features or recurrent disease. At present, alternative adjuvant treatment options are not available in part due to limited historical biological analysis and clinical trial investigation on meningiomas. With advances in molecular and genomic techniques in the last decade, we have witnessed a surge of interest in understanding the genomic and epigenomic landscape of meningiomas. The field is now at the stage to adopt this molecular knowledge to refine meningioma classification and introduce molecular algorithms that can guide prediction and therapeutics for this tumor type. Animal models that recapitulate meningiomas faithfully are in critical need to test new therapeutics to facilitate rapid-cycle translation to clinical trials. Here we review the most up-to-date knowledge of molecular alterations that provide insight into meningioma behavior and are ready for application to clinical trial investigation, and highlight the landscape of available preclinical models in meningiomas
Identification of common genetic risk variants for autism spectrum disorder
Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.Peer reviewe
Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies
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