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Genetic profiles distinguish different types of hereditary ovarian cancer.

Heredity represents the strongest risk factor for ovarian cancer with disease predisposing mutations identified in 15% of the tumors. With the aim to identify genetic classifiers for hereditary ovarian cancer, we profiled hereditary ovarian cancers linked to the hereditary breast and ovarian cancer (HBOC) syndrome and the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Genome-wide arr

Embryonic Stem Cell-Derived Neural Stem Cells Fuse with Microglia and Mature Neurons.

Transplantation of neural stem cells (NSCs) is a novel strategy to restore function in the diseased brain, acting through multiple mechanisms, e.g., neuronal replacement, neuroprotection and modulation of inflammation. Whether transplanted NSCs can operate by fusing with microglial cells or mature neurons is largely unknown. Here we have studied the interaction of a mouse embryonic stem cell-deriv

Tracking differentiating neural progenitors in pluripotent cultures using microRNA-regulated lentiviral vectors.

In this study, we have used a microRNA-regulated lentiviral reporter system to visualize and segregate differentiating neuronal cells in pluripotent cultures. Efficient suppression of transgene expression, specifically in undifferentiated pluripotent cells, was achieved by using a lentiviral vector expressing a fluorescent reporter gene regulated by microRNA-292. Using this strategy, it was possib

Interactions between oral contraceptive status and GSTM1 and GSTT1 deletions on insulin-like growth factor-1 (IGF-1) plasma levels in young healthy women.

OBJECTIVE: Insulin-like growth factor-1 (IGF-1) is essential for the pubertal growth spurt and for normal mammary gland development. IGF-1 increases premenopausal breast cancer risk. Oral contraceptives (OCs) decrease IGF-1 in most women. The endogenous estrogens and their metabolites also influence IGF-1 levels. Glutathione S-transferases (GSTs) are involved in estrogen metabolism. We aimed to st

Towards optimised information about clinical trials; identification and validation of key issues in collaboration with cancer patient advocates.

DELLSON P., NILBERT M., BENDAHL P-O., MALMSTROM P. & CARLSSON C. (2010) European Journal of Cancer Care Towards optimised information about clinical trials; identification and validation of key issues in collaboration with cancer patient advocates Clinical trials are crucial to improve cancer treatment but recruitment is difficult. Optimised patient information has been recognised as a key iss

Platelet transcriptional profile and protein expression in patients with systemic lupus erythematosus: up-regulation of the type I interferon system is strongly associated with vascular disease.

Patients with systemic lupus erythematosus (SLE) have a markedly increased risk to develop cardiovascular disease, and traditional cardiovascular risk factors fail to account for this increased risk. We used microarray to probe the platelet transcriptome in individuals with SLE and healthy controls, and the gene and protein expression of a subset of differentially expressed genes was further inves

Functional properties of the human ventral mesencephalic neural stem cell line hVM1.

The human fetal ventral mesencephalon-derived stem cell line, hVM1, yields high number of tyrosine hydroxylase-expressing presumed dopaminergic neurons upon in vitro differentiation. Here we report that cells generated from this line differentiate into a neuronal phenotype, express electrophysiological properties of functional neurons and respond to neurotransmitters in vitro. However, the electro

Tired of Diabetes Genetics? Circadian Rhythms and Diabetes: The MTNR1B Story?

Circadian rhythms are ubiquitous in biological systems and regulate metabolic processes throughout the body. Misalliance of these circadian rhythms and the systems they regulate has a profound impact on hormone levels and increases risk of developing metabolic diseases. Melatonin, a hormone secreted by the pineal gland, is one of the major signaling molecules used by the master circadian oscillato

Dietary L-leucine improves the anemia in a mouse model for Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia caused by a functional haploinsufficiency of genes encoding for ribosomal proteins. Recently, a case study reported a patient who became transfusion-independent in response to treatment with the amino acid L-leucine. Therefore, we have validated the therapeutic effect of L-leucine using our recently generated mouse model for RPS19-

Browning of freshwaters : Consequences to ecosystem services, underlying drivers, and potential mitigation measures

Browning of surface waters, as a result of increasing dissolved organic carbon and iron concentrations, is a widespread phenomenon with implications to the structure and function of aquatic ecosystems. In this article, we provide an overview of the consequences of browning in relation to ecosystem services, outline what the underlying drivers and mechanisms of browning are, and specifically focus

Risk prediction of future cardiac arrest by evaluation of a genetic risk score alone and in combination with traditional risk factors

Objectives: Coronary heart disease (CHD) is a leading cause of death globally, commonly through sudden cardiac death. Cardiac arrest of cardiac origin (CA) is associated with a poor prognosis and there is a great need for risk assessment and intensified preventive actions. In this study we aim to assess if a genetic risk score for CHD, composed of 50 common CHD susceptibility variants (GRS), predi

Discovery of Procognitive Antipsychotics by Combining Muscarinic M1 Receptor Structure-Activity Relationship with Systems Response Profiles in Zebrafish Larvae

Current antipsychotic drugs are notably ineffective at addressing the cognitive deficits associated with schizophrenia. N-Desmethylclozapine (NDMC), the major metabolite of clozapine, displays muscarinic M1 receptor (M1) agonism, an activity associated with improvement in cognitive functioning. Preclinical and clinical data support that M1 agonism may be a desired activity in antipsychotic drugs.

Optimal measuring point for ST deviation in chest pain patients with possible acute coronary syndrome

INTRODUCTION: In the ECG, significant ST elevation or depression according to specific amplitude criteria can be indicative of acute coronary syndrome (ACS). Guidelines state that the ST amplitude should be measured at the J point, but data to support that this is the optimal measuring point for ACS detection is lacking. We evaluated the impact of different measuring points for ST deviation on the

Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data

Dental caries and periodontitis account for a vast burden of morbidity and healthcare spending, yet their genetic basis remains largely uncharacterized. Here, we identify self-reported dental disease proxies which have similar underlying genetic contributions to clinical disease measures and then combine these in a genome-wide association study meta-analysis, identifying 47 novel and conditionally

Positive psychological well-being predicts lower severe pain in the general population : A 2-year follow-up study of the SwePain cohort

Background: Positive psychology indicators like well-being and life satisfaction may play a pivotal role in pain-related outcomes. In this study, we aimed to examine the prospective associations of positive well-being and life satisfaction with pain severity. Methods and Subjects: This longitudinal study, with a follow-up of 2 years, included 9361 participants (4266 males, 5095 females; mean age:

Assessment of moderate coffee consumption and risk of epithelial ovarian cancer : a Mendelian randomization study

Background: Coffee consumption has been shown to be associated with various health outcomes in observational studies. However, evidence for its association with epithelial ovarian cancer (EOC) is inconsistent and it is unclear whether these associations are causal.Methods: We used single nucleotide polymorphisms associated with (i) coffee and (ii) caffeine consumption to perform Mendelian randomiz