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Commonly used estimates of the genetic contribution to disease are subject to the same fallacies as bad luck estimates

The scientific debate following the initial formulation of the “bad luck” hypothesis in cancer development highlighted how measures based on analysis of variance are inappropriately used for risk communication. The notion of “explained” variance is not only used to quantify randomness, but also to quantify genetic and environmental contribution to disease in heritability coefficients. In this pape

Cerebro-spinal fluid biomarker levels : phosphorylated tau (T) and total tau (N) as markers for rate of progression in Alzheimer's disease

BACKGROUND: We investigated the potential associations between cerebro-spinal fluid (CSF) levels of phosphorylated tau (P-tau) and total tau (T-tau) with short-term response to cholinesterase inhibitor (ChEI) treatment, longitudinal outcome and progression rates in Alzheimer's disease (AD). METHODS: This prospective, observational study included 129 participants clinically diagnosed with mild-to-m

Excited State Dynamics of Bistridentate and Trisbidentate RuII Complexes of Quinoline-Pyrazole Ligands

Three homoleptic ruthenium(II) complexes, [Ru(Q3PzH)3]2+, [Ru(Q1Pz)3]2+, and [Ru(DQPz)2]2+, based on the quinoline–pyrazole ligands, Q3PzH (8-(3-pyrazole)-quinoline), Q1Pz (8-(1-pyrazole)-quinoline), and DQPz (bis(quinolinyl)-1,3-pyrazole), have been spectroscopically and theoretically investigated. Spectral component analysis, transient absorption spectroscopy, density functional theory calculati

Reelin Immunoreactivity in the Adult Spinal Cord : A Comparative Study in Rodents, Carnivores, and Non-human Primates

Reelin is a large extracellular matrix (ECM) glycoprotein secreted by several neuronal populations in a specific manner in both the developing and the adult central nervous system. The extent of Reelin protein distribution and its functional role in the adult neocortex is well documented in different mammal models. However, its role in the adult spinal cord has not been well characterized and its

Second primary cancers in melanoma patients critically shorten survival

Background: Survival in malignant cutaneous melanoma has improved but increasing survival will result in an increased likelihood of the occurrence of second primary cancers (SPCs). SPCs may adversely interfere with survival. We quantified survival in patients with different types of SPCs, in comparison to known poor prognostic indicators of metastatic disease. Methods: Data for melanoma and any SP

The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes : an IMI DIRECT study

Aims/hypothesis: It is well established that physical activity, abdominal ectopic fat and glycaemic regulation are related but the underlying structure of these relationships is unclear. The previously proposed twin-cycle hypothesis (TC) provides a mechanistic basis for impairment in glycaemic control through the interactions of substrate availability, substrate metabolism and abdominal ectopic fa

Heritability of Caries Scores, Trajectories, and Disease Subtypes

Previous studies report that dental caries is partially heritable, but there is uncertainty in the magnitude of genetic effects and little understanding of how genetic factors might influence caries progression or caries subtypes. This study aimed to estimate the relative importance of genetic and environmental factors in the etiology of different caries outcomes using a twin-based design. Analysi

Enhancing Hematopoiesis from Murine Embryonic Stem Cells through MLL1-Induced Activation of a Rac/Rho/Integrin Signaling Axis

The Mixed Lineage Leukemia (MLL1, KMT2A) gene is critical for development and maintenance of hematopoietic stem cells (HSCs), however, whether this protein is limiting for HSC development is unknown due to lack of physiologic model systems. Here, we develop an MLL1-inducible embryonic stem cell (ESC) system and show that induction of wild-type MLL1 during ESC differentiation selectively increases

The catalytic nature of protein aggregation

The formation of amyloid fibrils from soluble peptide is a hallmark of many neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Characterization of the microscopic reaction processes that underlie these phenomena have yielded insights into the progression of such diseases and may inform rational approaches for the design of drugs to halt them. Experimental evidence suggests th

Epilepsy in immigrants and Swedish-born : A cohort study of all adults 18 years of age and older in Sweden

Purpose: We aimed to study the association between country of birth and incident epilepsy in several immigrant groups using Swedish-born individuals as referents. Method: The study population included all adults aged 18 years and older in Sweden, living and deceased, 6,690,598 in the first-generation and 6,683,125 in the second-generation sub-study. Epilepsy was defined as having at least one regi

Occupational load as a risk factor for clinically relevant base of thumb osteoarthritis

Objective: It is postulated that increased load from pinch and grasp in occupational tasks increases the risk of thumb carpometacarpal (CMC1) osteoarthritis (OA). We sought to characterise the relationship between doctor-diagnosed CMC1 OA and occupation in a large working population. Methods: We performed a matched case-control study using a Swedish healthcare register. We identified residents age

Pearls randomized lifestyle trial in pregnant hispanic women with overweight/obesity : Gestational weight gain and offspring birthweight

Background: Inappropriate gestational weight gain (GWG) has been associated with adverse perinatal events. High rates of GWG have been reported among Hispanic women. Observational studies indicate that dietary and physical activity interventions during the prenatal period may improve maternal and infant health, but very few randomized trials have been conducted among high-risk overweight/obese His

Myt1l safeguards neuronal identity by actively repressing many non-neuronal fates

Normal differentiation and induced reprogramming require the activation of target cell programs and silencing of donor cell programs. In reprogramming, the same factors are often used to reprogram many different donor cell types. As most developmental repressors, such as RE1-silencing transcription factor (REST) and Groucho (also known as TLE), are considered lineage-specific repressors, it remain