Search results for "dm1"

Constraining the spin-dependent WIMP-nucleon cross sections with XENON1T

2019

We report the first experimental results on spin-dependent elastic weakly interacting massive particle (WIMP) nucleon scattering from the XENON1T dark matter search experiment. The analysis uses the full ton year exposure of XENON1T to constrain the spin-dependent proton-only and neutron-only cases. No significant signal excess is observed, and a profile likelihood ratio analysis is used to set exclusion limits on the WIMP-nucleon interactions. This includes the most stringent constraint to date on the WIMP-neutron cross section, with a minimum of 6.3 × 10−42 cm2 at 30 GeV/c2 and 90% confidence level. The results are compared with those from collider searches and used to exclude new paramet…

Participating Laboratories. Diabetes Antibody Standardization Program: evaluation of assays for autoantibodies to glutamic acid decarboxylase and isl…

2008

PANHER study: a 20-year treatment outcome analysis from a multicentre observational study of HER2-positive advanced breast cancer patients from the r…

2021

Background: The evolution of therapeutic landscape of human epidermal growth factor receptor-2 (HER2)-positive breast cancer (BC) has led to an unprecedented outcome improvement, even if the optimal sequence strategy is still debated. To address this issue and to provide a picture of the advancement of anti-HER2 treatments, we performed a large, multicenter, retrospective study of HER2-positive BC patients. Methods: The observational PANHER study included 1,328 HER2-positive advanced BC patients treated with HER2 blocking agents since June 2000 throughout July 2020. Endpoints of efficacy were progression-free survival (PFS) and overall survival (OS). Results: Patients who received a first-l…

Protective effects of mirtazapine in mice lacking the Mbnl2 gene in forebrain glutamatergic neurons: Relevance for myotonic dystrophy 1

2019

Myotonic dystrophy type 1 (DM1) is a multisystemic disorder characterized by muscle weakness and wasting and by important central nervous system-related symptoms including impairments in executive functions, spatial abilities and increased anxiety and depression. The Mbnl2 gene has been implicated in several phenotypes consistent with DM1 neuropathology. In this study, we developed a tissue-specific knockout mouse model lacking the Mbnl2 gene in forebrain glutamatergic neurons to examine its specific contribution to the neurobiological perturbations related to DM1. We found that these mice exhibit long-term cognitive deficits and a depressive-like state associated with neuronal loss, increa…

Lysine-specific demethylase 1 (LSD1/KDM1A/AOF2/BHC110) is expressed and is an epigenetic drug target in chondrosarcoma, Ewing's sarcoma, osteosarcoma…

2011

Summary Lysine-specific demethylase 1 (GeneID 23028), a flavin-dependent monoamine oxidoreductase and a histone demethylase, serves as an epigenetic coregulator of transcription. Lysine-specific demethylase 1 is up-regulated in neuroblastoma and in bladder, breast, colorectal, gastric, lung, and neuroendocrine cancers, and its overexpression drives the cell cycle of otherwise nontransformed human cells, suggesting oncogenic properties. Lysine-specific demethylase 1 was recently reported to be also overexpressed in several different mesenchymal tumors. We investigated lysine-specific demethylase 1 expression in over 500 sarcomas by gene expression profiling and tissue microarray-coupled immu…

Therapeutic Potential of AntagomiR-23b for Treating Myotonic Dystrophy

2020

Myotonic dystrophy type 1 (DM1) is a chronically debilitating, rare genetic disease that originates from an expansion of a noncoding CTG repeat in the dystrophia myotonica protein kinase (DMPK) gene. The expansion becomes pathogenic when DMPK transcripts contain 50 or more repetitions due to the sequestration of the muscleblind-like (MBNL) family of proteins. Depletion of MBNLs causes alterations in splicing patterns in transcripts that contribute to clinical symptoms such as myotonia and muscle weakness and wasting. We previously found that microRNA (miR)-23b directly regulates MBNL1 in DM1 myoblasts and mice and that antisense technology (“antagomiRs”) blocking this microRNA (miRNA) boost…

Modelling hydrolysis: Simultaneous versus sequential biodegradation of the hydrolysable fractions

2018

Hydrolysis is considered the limiting step during solid waste anaerobic digestion (including co-digestion of sludge and biosolids). Mechanisms of hydrolysis are mechanistically not well understood with detrimental impact on model predictive capability. The common approach to multiple substrates is to consider simultaneous degradation of the substrates. This may not have the capacity to separate the different kinetics. Sequential degradation of substrates is theoretically supported by microbial capacity and the composite nature of substrates (bioaccessibility concept). However, this has not been experimentally assessed. Sequential chemical fractionation has been successfully used to define i…

Loss of HER2 and decreased T-DM1 efficacy in HER2 positive advanced breast cancer treated with dual HER2 blockade: the SePHER Study

2020

AbstractBackgroundHER2-targeting agents have dramatically changed the therapeutic landscape of HER2+ advanced breast cancer (ABC). Within a short time frame, the rapid introduction of new therapeutics has led to the approval of pertuzumab combined with trastuzumab and a taxane in first-line, and trastuzumab emtansine (T-DM1) in second-line. Thereby, evidence of T-DM1 efficacy following trastuzumab/pertuzumab combination is limited, with data from some retrospective reports suggesting lower activity. The purpose of the present study is to investigate T-DM1 efficacy in pertuzumab-pretreated and pertuzumab naïve HER2 positive ABC patients. We also aimed to provide evidence on the exposure to d…

Considering syntrophic acetate oxidation and ionic strength improves the performance of models for food waste anaerobic digestion.

2021

Current mechanistic anaerobic digestion (AD) models cannot accurately represent the underlying processes occurring during food waste (FW) AD. This work presents an update of the Anaerobic Digestion Model no. 1 (ADM1) to provide accurate estimations of free ammonia concentrations and related inhibition thresholds, and model syntrophic acetate oxidation as acetate-consuming pathway. A modified Davies equation predicted NH3 concentrations and pH more accurately, and better estimated associated inhibitory limits. Sensitivity analysis results showed the importance of accurate disintegration kinetics and volumetric mass transfer coefficients, as well as volatile fatty acids (VFAs) and hydrogen up…

Proof of Concept of Therapeutic Gene Modulation of MBNL1/2 in Myotonic Dystrophy

2022

La distrofia miotónica tipo 1 es una enfermedad genética rara multisistémica que afecta a 1 de cada 3000-8000 personas. La causa molecular de la enfermedad proviene de repeticiones tóxicas “CTG” en el gen DMPK (DM Protein Kinase). Tras la transcripción, estas repeticiones forman una estructura de horquilla que se une con alta afinidad a la familia de proteínas MBNL (Muscleblind-like) que agota su función de regulación de la poliadenilación y el splicing alternativo postranscripcional en numerosos transcritos. La pérdida de función de MBNL provoca una cascada de efectos posteriores, que eventualmente conducen a síntomas clínicos que incluyen miotonía, debilidad y atrofia muscular, cataratas,…