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Identification of Cytoskeleton-Associated Proteins Essential for Lysosomal Stability and Survival of Human Cancer Cells

Microtubule-disturbing drugs inhibit lysosomal trafficking and induce lysosomal membrane permeabilization followed by cathepsin-dependent cell death. To identify specific trafficking-related proteins that control cell survival and lysosomal stability, we screened a molecular motor siRNA library in human MCF7 breast cancer cells. SiRNAs targeting four kinesins (KIF11/Eg5, KIF20A, KIF21A, KIF25), my

Computationally-efficient modeling of inelastic single crystal responses via anisotropic yield surfaces : Applications to shape memory alloys

Phenomenological constitutive models of inelastic responses based on the methods of classical plasticity provide several advantages, especially in terms of computational efficiency. For this reason, they are attractive for the analysis of complex boundary value problems comprising large computational domains. However, for the analysis of problems dominated by single crystal behavior (e.g., inclusi

Effect of metformin on plasma metabolite profile in the Copenhagen Insulin and Metformin Therapy (CIMT) trial

Aim: Metformin is the first-line treatment for Type 2 diabetes. However, not all people benefit from this drug. Our aim was to investigate the effects of metformin on the plasma metabolome and whether the pretreatment metabolite profile can predict HbA1c outcome. Methods: Post hoc analysis of the Copenhagen Insulin and Metformin Therapy (CIMT) trial, a multicentre study from May 2008 to December 2

Depression in type 1 diabetes was associated with high levels of circulating galectin-3

Objective: Neuroinflammatory responses are implicated in depression. The aim was to explore whether depression in patients with type 1 diabetes (T1D) was associated with high circulating galectin-3, controlling for metabolic variables, s-creatinine, life style factors, medication, and cardiovascular complications.Design: Cross-sectional.Methods: Participants were T1D patients (n=283, 56% men, age

Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study

Objectives Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs). Methods The modified Rodnan skin score (mRSS)

Visualizing energy consumption activities as a tool for developing effective policy

Analysing and understanding energy consumption from the household activity perspective is vital for developing policy that promotes sustainable everyday life. Doing so entails learning how to connect policy with household activities and everyday life. We use a time-geographic visualization to analyse several dimensions of everyday life as a totality. From household members' time diaries, we can an

DNA Methylation of LRRC3B : A Biomarker for Survival of Early-Stage Non-Small Cell Lung Cancer Patients

Background: Previous studies support a tumor-suppressor role for LRRC3B across various types of cancers. We aimed to investigate the association between DNA methylation of LRRC3B and overall survival (OS) for patients with early-stage non-small cell lung cancer (NSCLC).Methods: This study included 1,230 patients with early-stage NSCLC. DNA was extracted from lung tumor tissues and DNA methylation

Cost-effectiveness of revascularization in patients with intermittent claudication

Background: Revascularization is a treatment option for patients with intermittent claudication. However, there is a lack of evidence to support its long-term benefits and cost-effectiveness. The aim of this study was to compare the cost-effectiveness of revascularization and best medical therapy (BMT) with that of BMT alone. Methods: Data were used from the IRONIC (Invasive Revascularization Or N

NMDA‐receptor blockers but not NBQX, an AMPA‐receptor antagonist, inhibit spreading depression in the rat brain

The effect of different glutamate‐receptor antagonists on the induction of cortical spreading depression of Leao and of cortical anoxic membrane depolarization were investigated in the anaesthetized rat. Spreading depression (SD), elicited by mechanical stimulation of the cortical surface, was inhibited by the non‐competitive N‐methyl‐d‐aspartate (NMDA)‐receptor blocker, (±)‐5‐methyl‐10,11‐dihydro

Activation of Hormone-sensitive Lipase Requires Two Steps, Protein Phosphorylation and Binding to the PAT-1 Domain of Lipid Droplet Coat Proteins

Lipolysis is an important metabolic pathway controlling energy homeostasis through degradation of triglycerides stored in lipid droplets and release of fatty acids. Lipid droplets of mammalian cells are coated with one or more members of the PAT protein family, which serve important functions in regulating lipolysis. In this study, we investigate the mechanisms by which PAT family members, perilip

Risk of plasma cell and lymphoproliferative disorders among 14 621 first-degree relatives of 4458 patients with monoclonal gammopathy of undetermined significance in Sweden

Familial clustering of the precursor condition, monoclonal gammopathy of undetermined significance (MGUS) has been observed in case reports and in smaller studies. Using population-based data from Sweden, we identified 4458 MGUS patients, 17 505 population-based controls, and first-degree relatives of patients (n = 14 621) and controls (n = 58 387) with the aim to assess risk of MGUS and lymphopro

Contractile endothelin-B (ETB) receptors in human small bronchi

Endothelins (ETs) are a family of novel regulatory peptides and various lines of evidence suggest an important role for ETs in regulating pulmonary function. Two receptors for endothelin, ETA and ETB, have been found in the human lung, and according to recent studies a non-ETA receptor seems to mediate the contraction of large sized human bronchi. Several studies have emphasized the importance of

Regulation of neuropeptide mRNA expression in the basal ganglia by intrastriatal and intranigral transplants in the rat Parkinson model.

Previous studies have shown that intrastriatal transplants of dopamine (DA)-rich fetal ventral mesencephalic (VM) tissue can correct denervation-induced changes in the cellular expression of neuropeptide and receptor mRNAs in the rat Parkinson model. However, with the standard transplantation approach normalization of all cellular parameters has not been obtained. This may be due either to the inc

Activation of cPLA2 is required for leukotriene D4-induced proliferation in colon cancer cells.

It is well documented that prolonged inflammatory conditions, particularly those relating to the colon, have been shown to induce cancer. We have previously demonstrated that the pro-inflammatory mediator leukotriene D-4 (LTD4) induces survival and proliferation in intestinal cells and that its receptor, CysLT(1), is upregulated in human colon cancer tissue. Here we demonstrate, for the first time

Body composition profiles derived from dual-energy X-ray absorptiometry, total body scan, and mortality

Little has been reported on the association of derived body composition data and cardiovascular mortality. The authors defined body composition profiles based on one- and two-variable measures from dual-energy x-ray absorptiometry (DXA) total body scans. Scan results are labeled "apple" if Z score for percent of total fat in trunk is >0 and "pear" if Z score for height-corrected limb fat is > or =

Estimating environmental effects on population dynamics: consequences of observation error

Within the paradigm of population dynamics a central task is to identify environmental factors affecting population change and to estimate the strength of these effects. We here investigate the impact of observation errors in measurements of population densities on estimates of environmental effects. Adding observation errors may change the autocorrelation of a population time series with potentia

Multiple rare variants in high-risk pancreatic cancer-related genes may increase risk for pancreatic cancer in a subset of patients with and without germline CDKN2A mutations

The risk of pancreatic cancer (PC) is increased in melanoma-prone families but the causal relationship between germline CDKN2A mutations and PC risk is uncertain, suggesting the existence of non-CDKN2A factors. One genetic possibility involves patients having mutations in multiple high-risk PC-related genes; however, no systematic examination has yet been conducted. We used next-generation sequenc

Preparedness for side effects and bother in symptomatic men after radical prostatectomy in a prospective, non-randomized trial, LAPPRO

Background: Many clinicians believe that preparedness before surgery for possible post-surgery side effects reduces the level of bother experienced from urinary incontinence and decreased sexual health after surgery. There are no published studies evaluating this belief. Therefore, we aimed to study the level of preparedness before radical prostatectomy and the level of bother experienced from uri

A twin study of anxiety-related behaviours in pre-school children

Background: From middle childhood onwards, substantial evidence points to phenotypic differentiation between anxiety diagnostic categories such as generalised anxiety, separation anxiety, specific phobia, and obsessive-compulsive disorders. However, little is known about the genetics of these categories and especially about the phenotypic and genetic structure of related behaviours in pre-school c