Search results for "ddc:61"
showing 10 items of 588 documents
Comparison of Different Hypotheses Regarding the Spread of Alzheimer’s Disease Using Markov Random Fields and Multimodal Imaging
2018
Alzheimer’s disease (AD) is characterized by a cascade of pathological processes that can be assessed in vivo using different neuroimaging methods. Recent research suggests a systematic sequence of pathogenic events on a global biomarker level, but little is known about the associations and dependencies of distinct lesion patterns on a regional level. Markov random fields are a probabilistic graphical modeling approach that represent the interaction between individual random variables by an undirected graph. We propose the novel application of this approach to study the interregional associations and dependencies between multimodal imaging markers of AD pathology and to compare different hy…
Physiological relevance of the neuronal isoform of inositol-1,4,5-trisphosphate 3-kinases in mice
2020
Inositol-1,4,5-trisphosphate 3-kinase-A (ITPKA) is the neuronal isoform of ITPKs and exhibits both actin bundling and InsP3kinase activity. In addition to neurons, ITPKA is ectopically expressed in tumor cells, where its oncogenic activity increases tumor cell malignancy. In order to analyze the physiological relevance of ITPKA, here we performed a broad phenotypic screening of itpka deficient mice. Our data show that among the neurobehavioral tests analyzed, itpka deficient mice reacted faster to a hotplate, prepulse inhibition was impaired and the accelerating rotarod test showed decreased latency of itpka deficient mice to fall. These data indicate that ITPKA is involved in the regulatio…
Adherence to a Mediterranean diet is associated with lower incidence of frailty: A longitudinal cohort study
2018
Background & aims There is a paucity of data investigating the relationship between the Mediterranean diet and frailty, with no data among North American people. We aimed to investigate if adherence to a Mediterranean diet is associated with a lower incidence of frailty in a large cohort of North American people. Methods This study included subjects at higher risk or having knee osteoarthritis. Adherence to the Mediterranean diet was evaluated using a validated Mediterranean diet score (aMED) as proposed by Panagiotakos and classified into five categories. Frailty was defined using the Study of Osteoporotic Fracture (SOF) index as the presence of ≥2 out of: (i) weight loss ≥5% between b…
Association of Common Polymorphisms in the Nicotinic Acetylcholine Receptor Alpha4 Subunit Gene with an Electrophysiological Endophenotype in a Large…
2016
PLoS one 11(4), e0152984 (2016). doi:10.1371/journal.pone.0152984
Shared genetic etiology between alcohol dependence and major depressive disorder
2018
Supplemental Digital Content is available in the text.
Molecular properties underlying regional vulnerability to Alzheimer’s disease pathology
2018
Amyloid deposition and neurofibrillary degeneration in Alzheimer's disease specifically affect discrete neuronal systems, but the underlying mechanisms that render some brain regions more vulnerable to Alzheimer's disease pathology than others remain largely unknown. Here we studied molecular properties underlying these distinct regional vulnerabilities by analysing Alzheimer's disease-typical neuroimaging patterns of amyloid deposition and neurodegeneration in relation to regional gene expression profiles of the human brain. Graded patterns of brain-wide vulnerability to amyloid deposition and neurodegeneration in Alzheimer's disease were estimated by contrasting multimodal amyloid-sensiti…
Inhibition of histone deacetylation rescues phenotype in a mouse model of Birk-Barel intellectual disability syndrome
2020
Mutations in the actively expressed, maternal allele of the imprinted KCNK9 gene cause Birk-Barel intellectual disability syndrome (BBIDS). Using a BBIDS mouse model, we identify here a partial rescue of the BBIDS-like behavioral and neuronal phenotypes mediated via residual expression from the paternal Kcnk9 (Kcnk9pat) allele. We further demonstrate that the second-generation HDAC inhibitor CI-994 induces enhanced expression from the paternally silenced Kcnk9 allele and leads to a full rescue of the behavioral phenotype suggesting CI-994 as a promising molecule for BBIDS therapy. Thus, these findings suggest a potential approach to improve cognitive dysfunction in a mouse model of an impri…
The landscape of epilepsy-related GATOR1 variants
2019
Purpose:\ud \ud To define the phenotypic and mutational spectrum of epilepsies related to DEPDC5, NPRL2 and NPRL3 genes encoding the GATOR1 complex, a negative regulator of the mTORC1 pathway.\ud \ud Methods:\ud \ud We analyzed clinical and genetic data of 73 novel probands (familial and sporadic) with epilepsy-related variants in GATOR1-encoding genes and proposed new guidelines for clinical interpretation of GATOR1 variants.\ud \ud Results:\ud \ud The GATOR1 seizure phenotype consisted mostly in focal seizures (e.g., hypermotor or frontal lobe seizures in 50%), with a mean age at onset of 4.4 years, often sleep-related and drug-resistant (54%), and associated with focal cortical dysplasia…
Genome-wide Association Studies Identify Genetic Loci Associated with Albuminuria in Diabetes
2016
Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10−10). Gene-by-diabetes interactions were…
The relationship between the dietary inflammatory index and prevalence of radiographic symptomatic osteoarthritis: data from the Osteoarthritis Initi…
2017
Purpose: To investigate whether higher dietary inflammatory index (DII ® ) scores were associated with higher prevalence of radiographic symptomatic knee osteoarthritis in a large cohort of North American people from the Osteoarthritis Initiative database. Methods: A total of 4358 community-dwelling participants (2527 females; mean age 61.2 years) from the Osteoarthritis Initiative were identified. DII ® scores were calculated using the validated Block Brief 2000 Food-Frequency Questionnaire and scores were categorized into quartiles. Knee radiographic symptomatic osteoarthritis was diagnosed clinically and radiologically. The strength of association between divided into quartiles (DII ® ) …