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GWAS risk factors in Parkinson's disease : LRRK2 coding variation and genetic interaction with PARK16

Parkinson's disease (PD) is a multifactorial movement disorder characterized by progressive neurodegeneration. Genome-wide association studies (GWAS) have nominated over fifteen distinct loci associated with risk of PD, however the biological mechanisms by which these loci influence disease risk are mostly unknown. GWAS are only the first step in the identification of disease genes: the specific c

Independent evolution of neurotoxin and flagellar genetic loci in proteolytic Clostridium botulinum

Background: Proteolytic Clostridium botulinum is the causative agent of botulism, a severe neuroparalytic illness. Given the severity of botulism, surprisingly little is known of the population structure, biology, phylogeny or evolution of C. botulinum. The recent determination of the genome sequence of C. botulinum has allowed comparative genomic indexing using a DNA microarray. Results: Whole ge

Epigenetics in Prostate Cancer: Biologic and Clinical Relevance

Context: Prostate cancer (PCa) is one of the most common human malignancies and arises through genetic and epigenetic alterations. Epigenetic modifications include DNA methylation, histone modifications, and microRNAs (miRNA) and produce heritable changes in gene expression without altering the DNA coding sequence. Objective: To review progress in the understanding of PCa epigenetics and to focus

Autism spectrum disorders and coexisting disorders in a nationwide Swedish twin study

Background: Evidence from twin and molecular genetic studies is accumulating that Autism Spectrum Disorder (ASD) shares substantial etiological factors with other disorders. This is mirrored in clinical practice where ASD without coexisting disorders is rare. The present study aims to examine the range of coexisting disorders in ASD in a genetically informative cohort. Methods: Parents of all Swed

Interdialytic weight gain and ultrafiltration rate in hemodialysis: Lessons about fluid adherence from a national registry of clinical practice

Excessive interdialytic weight gain (IWG) and ultrafiltration rates (UFR) above 10 mL/h/kg body weight imply higher morbidity and mortality. This study aimed to estimate the prevalence of high fluid consumers, describe UFR patterns, and describe patient characteristics associated with IWG and UFR. The Swedish Dialysis DataBase and The Swedish Renal Registry of Active Treatment of Uremia were used

A negative trend of biomedical research in Libya: a bibliometric study

Background: It is well established that Libya is lagging behind its peers in biomedical research. The aim of this study is to analyse all the original biomedical publications affiliated with Libya from 1973 to 2007. Methods: PubMed and the Science Citation Index Expanded were searched for 'original research' biomedical studies affiliated with Libya. The generated data were hand searched and 329 'o

Monitored versus experience-based perceptions of environmental change: evidence from coastal Tanzania

The impacts of climate change are likely to exacerbate many problems that coastal areas already face. In this study, we used multinomial logistic regression to examine human perception of climate change based on a cross-sectional survey of 1253 individuals in coastal regions of Tanzania. This was complemented with time series analysis of 50-year meteorological data. The results indicate that self-

Prevalence of Doctor-Diagnosed Thumb Carpometacarpal Joint Osteoarthritis: An Analysis of Swedish Health Care

Objective. While the prevalence of radiographic thumb carpometacarpal (CMC1) osteoarthritis (OA) is well-described, little is known about clinically symptomatic disease presenting to physicians for care. We sought to determine the prevalence of doctor-diagnosed CMC1 OA. Methods. Using health care data from Skane in southern Sweden (population 1.24 million), we identified all adults ages >= 20 year

Crop rotations including ley and manure can promote ecosystem services in conventional farming systems

Agricultural intensification has contributed substantially to the increase in food production, but has come at the expense of soil degradation and environmental problems. Management of soil based ecosystem services need to be considered in agricultural management since intensive management implies not only costs to the farmer but also to society. In this study we used data from four long-term (55

Identification and Characterization of New Mechanisms in Vascular Estrogen Signalling.

Estrogen exerts vasculoprotective effects in different experimental settings through inhibition of vascular smooth muscle cell proliferation, stimulation of nitric oxide production and attenuation of inflammation. Although these estrogen-evoked beneficial effects have been attributed to estrogen receptor α (ERα), also ERβ and the novel ER GPR30/GPER1 probably play significant roles in vascular est

Immune tolerance induction in patients with hemophilia A

Replacement therapy with factor VIII (FVIII) concentrates has become the mainstay of treatment for hemophilia, but about 30% of patients with a severe disease develop neutralizing antibodies against FVIII, which can lead to treatment resistance and an increased risk of bleeding. Immune tolerance induction (ITI) overcomes the immune response to FVIII concentrates in the majority of patients. Severa

BCL2A1 is a lineage-specific antiapoptotic melanoma oncogene that confers resistance to BRAF inhibition

Although targeting oncogenic mutations in the BRAF serine/threonine kinase with small molecule inhibitors can lead to significant clinical responses in melanoma, it fails to eradicate tumors in nearly all patients. Successful therapy will be aided by identification of intrinsic mechanisms that protect tumor cells from death. Here, we used a bioinformatics approach to identify drug-able, "driver" o

Hip Fracture Incidence and Prevalence of Osteoporosis in Sweden in Recent Decades

An increase in hip fracture incidence during the recent half-century has been reported worldwide and has been predicted to continue. Recent publications, however, have reported stable or even decreasing hip fracture incidence. No reports evaluate whether these changes in hip fracture incidence are associated with changes in bone mineral density (BMD), if they apply in both urban and rural settings

Polymorphisms in Arsenic(+III)methyltransferase (AS3MT) Predict Gene Expression of AS3MT as well as Arsenic Metabolism.

Background: Arsenic is mono- (MMA) and dimethylated (DMA) in humans and the methylation pattern demonstrates large inter-individual differences. The fraction of urinary MMA is a marker for susceptibility to arsenic-related diseases. Objectives: The impact of polymorphisms in five methyltransferase genes on arsenic metabolism was evaluated in two populations, one in South America, one in southeast

Inverse modeling of European CH4 emissions 2001-2006

European CH4 emissions are estimated for the period 2001-2006 using a four-dimensional variational (4DVAR) inverse modeling system, based on the atmospheric zoom model TM5. Continuous observations are used from various European monitoring stations, complemented by European and global flask samples from the NOAA/ESRL network. The available observations mainly provide information on the emissions fr

Factor H autoantibodies and deletion of Complement Factor H-Related protein-1 in rheumatic diseases in comparison to atypical hemolytic uremic syndrome

Introduction: Complement activation is involved in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and atypical hemolytic uremic syndrome (aHUS). Autoantibodies to complement inhibitor factor H (FH), particularly in association with deletions of the gene coding for FH-related protein 1 (CFHR1), are associated with aHUS. Methods: Autoantibodies against FH, factor I (FI) and C4b-bindin

Predominance of CIN versus MSI in the development of rectal cancer at young age.

BACKGROUND: Development of proximal and distal colorectal cancers involve partly different mechanisms associated with the microsatellite instability (MSI) and the chromosomal instability (CIN) pathways. Colorectal cancers in patients under 50 years of age represent about 5% of the total number of tumors and have been associated with an increased frequency of MSI tumors. However, MSI and CIN may pl

Investigation of turbulence models applied to premixed combustion using a level-set flamelet library approach

Most of the common modeling approaches to premixed combustion in engineering applications are either based on the assumption of infinitely fast chemistry or the flamelet assumption with simple chemistry. The level-set flamelet library approach (FLA) has shown great potential in predicting major species and heat release, as well as intermediate and minor species, where more simple models often fail