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Genome-wide association study identifies four novel loci associated with Alzheimer’s endophenotypes and disease modifiers

More than 20 genetic loci have been associated with risk for Alzheimer’s disease (AD), but reported genome-wide significant loci do not account for all the estimated heritability and provide little information about underlying biological mechanisms. Genetic studies using intermediate quantitative traits such as biomarkers, or endophenotypes, benefit from increased statistical power to identify var

Differences in glycemic control across world regions : A post-hoc analysis in patients with type 2 diabetes mellitus on dual antidiabetes drug therapy

Objective:This post-hoc analysis of the EDGE (Effectiveness of Diabetes control with vildaGliptin and vildagliptin/mEtformin) study assessed inter-regional differences in baseline characteristics and response to treatment intensification with dual oral antidiabetes drugs (OADs) in patients with type 2 diabetes mellitus (T2DM).Methods:Patients with T2DM inadequately controlled with first-line monot

N-Terminal Prosomatostatin and Risk of Vascular Dementia

BACKGROUND: Increased somatostatin plasma concentration has been found in patients with vascular dementia. However, it is unknown whether or not somatostatin levels may predict dementia development in the general population. To this end, we sought to assess the association of circulating N-terminal prosomatostatin (NT-proSST) with incident dementia among community-dwelling older adults.METHODS: In

Evaluation of original and modified APC-resistance tests in unselected outpatients with clinically suspected thrombosis and in healthy controls

APC-resistance is the most common hereditary condition associated with venous thrombosis. It is in a majority of cases due to a single point mutation in the factor V gene (FVR506Q). Currently used functional APC-resistance tests have 85-90% sensitivity and specificity for the FVR506Q mutation. A modified test which includes predilution of patient plasma in factor V depleted plasma has increased th

Defence versus defence : Are crucian carp trading off immune function against predator-induced morphology?

Numerous species adopt inducible defence strategies; that is, they have phenotypically plastic traits that decrease the risk of capture and consumption by potential predators. The benefits of expressing alternative phenotypes in high- vs. low-risk environments are well documented. However, inducible anti-predator traits are also expected to incur costs, as they are not expressed when predators are

Impact of a multifactorial treatment programme on clinical outcomes and cardiovascular risk estimates : A retrospective cohort study from a specialised diabetes centre in Denmark

Objectives To investigate the impact of a multifactorial treatment programme in a real-life setting on clinical outcomes and estimated cardiovascular disease (CVD) risk. Design A retrospective observational cohort study, using data from the electronic medical records and national registers. Setting Tertiary diabetes centre in Denmark. Participants Patients with type 2 diabetes (n=4299) referred to

Biogeochemistry in Subarctic birch forests : Perspectives on insect herbivory

Växtätare kan påverka ekosystemprocesser, dels genom långsiktiga förändringar av växtsamhällets sammansättning, men också på kortare sikt genom derasmatspjälkning av organiskt material som cyklas genom markens nedbryderorganismer och tillbaka till de primära producenterna. Särskilt störreväxtätare har studerats i stor utsträckning, men i vissa ekosystem som skogar kan de mindre ryggradslösa växtätHerbivory can influence ecosystem processes, partly through long-term changes of the plant community compositions, but also more rapidly through the herbivores’ digestive alteration of the organic matter that is cycled through the soil and back to the primary producers. In the Subarctic mountain birch (Betula pubescens ssp. czerepanovii) forest (SMBF) in Northern Fennoscandia, outbreaks by the geo

PBB3 Imaging in Parkinsonian disorders: Evidence for binding to abnormally aggregated proteins in addition to tau proteins

Objective: To study selective regional binding for tau pathology in vivo, using PET with [11C]PBB3 ([11C]methylamino pyridin-3-yl buta-1,3-dienyl benzo[d]thiazol-6-ol) in tauopathies, and in conditions not typically associated with tauopathy. Background: Tau imaging is a promising tool to study the link between tau and neurodegeneration. The specificity of tracers in vivo however remains uncertain

Occupational exposure to particles and mitochondrial DNA : Relevance for blood pressure

Background: Particle exposure is a risk factor for cardiovascular diseases. Mitochondrial DNA (mtDNA) is a primary target for oxidative stress generated by particle exposure. We aimed to elucidate the effects of occupational exposure to particle-containing welding fumes on different biomarkers of mtDNA function, and in turn, explore if they modify the association between particle exposure and card

Genome-Wide DNA Methylation Profiling of Chronic Lymphocytic Leukemia Subsets Carrying Stereotyped B Cell Receptors

In recent years, subsets of chronic lymphocytic leukemia (CLL) patients carrying quasi-identical or stereotyped B cell receptors (BcRs) have been identified that share clinicobiological features and disease outcome. While these stereotyped subsets show distinct gene expression and genomic profiles, the DNA methylation landscape remains largely unexplored. By applying high-resolution 450K methylati

HOXC8 regulates self-renewal, differentiation and transformation of breast cancer stem cells

Background: Homeobox genes are master regulators of cell fate during embryonic development and their expression is altered in cancer. By regulating the balance between cell proliferation and differentiation, they maintain homeostasis of normal tissues. Here, we screened the expression of homeobox genes in mammary stem cells to establish their role in stem cells transformation in breast cancer. Met

Mircostructure and rheological properties of concentrated tomato suspensions during processing

Food processing comprises operations such as dilution (changing the concentration), homogenisation (changing the particle size), and subsequent pumping (shearing), among others. It is thus of great interest to gain a better understanding of the mechanisms governing the creation and disruption of structures during these engineering operations, and the way in which they are related to the textural a

Law, the Domestic and Sovereignty in Interwar Women's Writing

My Ph.D. examines women’s writing in the interwar period through a questioning of the boundaries between the public and private sphere as traditional masculine forms of power based on a system of sovereignty and law enter the domestic realm. I also consider how power might be reimagined abroad. I juxtapose works of popular fiction from E.M. Hull, Agatha Christie and Marie Belloc Lowndes with the m

The pattern of deoxycytidine- and deoxyguanosine kinase activity in relation to messenger RNA expression in blood cells from untreated patients with B-cell chronic lymphocytic leukemia

Deoxycytidine kinase (dCK) and deoxyguanosine kinase (dGK) catalyze the first step in the intracellular cascade of fludarabine (2-fluoroadenine-beta-D-arabinofuranoside) and cladribine (2-chlorodeoxyadenosine) phosphorylation, which leads to activation of these prodrugs, commonly used for treatment of chronic lymphocytic leukemia (CLL). Thus, resistance to nucleoside analogues may primarily be due

Cloud condensation nuclei in pristine tropical rainforest air of Amazonia: size-resolved measurements and modeling of atmospheric aerosol composition and CCN activity

Atmospheric aerosol particles serving as cloud condensation nuclei (CCN) are key elements of the hydrological cycle and climate. We have measured and characterized CCN at water vapor supersaturations in the range of S=0.10-0.82% in pristine tropical rainforest air during the AMAZE-08 campaign in central Amazonia. The effective hygroscopicity parameters describing the influence of chemical composit

Amorphous silica pools in permafrost soils of the Central Canadian Arctic and the potential impact of climate change

We investigated the distribution, storage and landscape partitioning of soil amorphous silica (ASi) in a central Canadian region dominated by tundra and peatlands to provide a first estimate of the amount of ASi stored in Arctic permafrost ecosystems. We hypothesize that, similar to soil organic matter, Arctic soils store large amounts of ASi which may be affected by projected climate changes and

In vitro cytotoxicity evaluation of HDAC inhibitor Apicidin in pancreatic carcinoma cells subsequent time and dose dependent treatment.

Apicidin is a potent histone deacetylase inhibitor (HDACI) that selectively binds to histone deacetylases (HDACs) class I and interferes with the deacetylation process, which results in modification of acetylation level of cellular proteins. The aim of the study was to investigate the potential time and dose dependent cytotoxicity of the test compound, Apicidin, in pancreatic cancer cells Capan-1

Triparental Families: A New Genetic-Epidemiological Design Applied to Drug Abuse, Alcohol Use Disorders, and Criminal Behavior in a Swedish National Sample.

Objective: The authors sought to clarify the sources of parent-offspring resemblance for drug abuse, alcohol use disorders, and criminal behavior, using a novel genetic-epidemiological design. Method: Using national registries, the authors identified rates of drug abuse, alcohol use disorders, and criminal behavior in 41,360 Swedish individuals born between 1960 and 1990 and raised in triparental

Ovarian Cancer and Body Size: Individual Participant Meta-Analysis Including 25,157 Women with Ovarian Cancer from 47 Epidemiological Studies

Background: Only about half the studies that have collected information on the relevance of women's height and body mass index to their risk of developing ovarian cancer have published their results, and findings are inconsistent. Here, we bring together the worldwide evidence, published and unpublished, and describe these relationships. Methods and Findings: Individual data on 25,157 women with o

Mendelian randomization of blood lipids for coronary heart disease

Aims To investigate the causal role of high-density lipoprotein cholesterol (HDL-C) and triglycerides in coronary heart disease (CHD) using multiple instrumental variables for Mendelian randomization. Methods and results We developed weighted allele scores based on single nucleotide polymorphisms (SNPs) with established associations with HDL-C, triglycerides, and low-density lipoprotein cholestero