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Discovery of Small Molecules That Induce Lysosomal Cell Death in Cancer Cell Lines Using an Image-Based Screening Platform

The lysosomal cell death (LCD) pathway is a caspase 3-independent cell death pathway that has been suggested as a possible target for cancer therapy, making the development of sensitive and specific high-throughput (HT) assays to identify LCD inducers highly desirable. In this study, we report a two-step HT screening platform to reliably identify such molecules. First, using a robust HT primary sc

Too Young to Die: Regression Discontinuity of a Two-Part Minimum Legal Drinking Age Policy and the Causal Effect of Alcohol on Health

This study examines the impact of Sweden’s unique two-part Minimum Legal Drinking Age (MLDA) policy on alcohol consumption and health using regression discontinuity design. In Sweden on-licence purchasing of alcohol is legalised at 18 and off-licence purchasing is legalised later at 20 years of age. We find an immediate and significant 6% jump in participation and a larger increase in number of da

Sensitive detection of lysosomal membrane permeabilization by lysosomal galectin puncta assay

Lysosomal membrane permeabilization (LMP) contributes to tissue involution, degenerative diseases, and cancer therapy. Its investigation has, however, been hindered by the lack of sensitive methods. Here, we characterize and validate the detection of galectin puncta at leaky lysosomes as a highly sensitive and easily manageable assay for LMP. LGALS1/galectin-1 and LGALS3/ galectin-3 are best suite

Lysosomal cell death at a glance

Lysosomes serve as the cellular recycling centre and are filled with numerous hydrolases that can degrade most cellular macromolecules. Lysosomal membrane permeabilization and the consequent leakage of the lysosomal content into the cytosol leads to so-called "lysosomal cell death". This form of cell death is mainly carried out by the lysosomal cathepsin proteases and can have necrotic, apoptotic

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

The Effect of a Sibling's Gender on Earnings, Education and Family Formation

We examine how the gender of a sibling affects earnings, education and family formation. Identification is complicated by parental preferences: if parents prefer certain sex compositions over others, children's gender affects not only the outcomes of other children but also the existence of potential additional children. We employ two empirical strategies that both address this problem. First, we

Abstract P1-06-01: Putting multigene signatures to the test: Prognostic assessment in population-based contemporary clinical breast cancer

Abstract Background Gene expression signatures hold promise for a molecularly driven division of primary breast cancer with clinical implications. A gap still remains in the application/validation of such signatures in actual clinical treatment groups from unselected, population-based, primary breast cancer receiving current standard of care therapy. We analyzed classification proportions and ovBackground Gene expression signatures hold promise for a molecularly driven division of primary breast cancer with clinical implications. A gap still remains in the application/validation of such signatures in actual clinical treatment groups from unselected, population-based, primary breast cancer receiving current standard of care therapy. We analyzed classification proportions and overall surv

α Decay of High-K Isomers in 270Ds and 266Hs in a Superfluid Tunneling Model

We use the superfluid tunneling model (STM) to calculate the half-lives of ground-state α decays of even-even superheavy nuclei (SHN) with Z≥100. The experimental data are reproduced to accuracies comparable to other contemporary models of α decay of SHN. We apply the STM to the case of the α decaying high-K isomers identified in the decay chains of 270Ds. By accounting for the α-decay Q values, Q

Abstract P2-02-09: Breast cancer subtype distribution and circulating tumor DNA in response to neoadjuvant chemotherapy: Experiences from a preoperative cohort within SCAN-B

Introduction: Preoperative chemotherapy in early breast cancer increases the rate of breast preservation and provides prognostic information. In the case of residual disease, a change in subtypes may be observed. Sensitive and reproducible biomarkers predicting treatment response early during the treatment course are needed in order to better exploit the potential benefit of an individualized preo

The effect of individual enabling and support on empowerment and depression severity in persons with affective disorders : outcome of a randomized control trial

Purpose: To evaluate the effect of Individual Enabling and Support (IES) on empowerment and depression severity as compared to Traditional Vocational Rehabilitation (TVR) in people with affective disorders at 12 months follow-up. Additionally, longitudinal changes within the intervention groups and the correlation over time between empowerment and depression severity were evaluated. Method: A sing

Decreased global myocardial perfusion at adenosine stress as a potential new biomarker for microvascular disease in systemic sclerosis : A magnetic resonance study

Background: Patients with systemic sclerosis (SSc) have high cardiovascular mortality even though there is no or little increase in prevalence of epicardial coronary stenosis. First-pass perfusion on cardiovascular magnetic resonance (CMR) have detected perfusion defects indicative of microvascular disease, but the quantitative extent of hypoperfusion is not known. Therefore, we aimed to determine