Search results for "Local"

2017

Several studies have demonstrated that the expression of odorant receptors (ORs) occurs in various tissues. These findings have served as a basis for functional studies that demonstrate the potential of ORs as drug targets for a clinical application. To the best of our knowledge, this report describes the first evaluation of the mRNA expression of ORs and the localization of OR proteins in the human retina that set a stage for subsequent functional analyses. RNA-Sequencing datasets of three individual neural retinae were generated using Next-generation sequencing and were compared to previously published but reanalyzed datasets of the peripheral and the macular human retina and to reference…

Chimeric proteins tagged with specific 3xHA cassettes may present instability and functional problems

2017

Epitope-tagging of proteins has become a widespread technique for the analysis of protein function, protein interactions and protein localization among others. Tagging of genes by chromosomal integration of PCR amplified cassettes is a widely used and fast method to label proteins in vivo. Different systems have been developed during years in the yeast Saccharomyces cerevisiae. In the present study, we analysed systematically a set of yeast proteins that were fused to different tags. Analysis of the tagged proteins revealed an unexpected general effect on protein level when some specific tagging module was used. This was due in all cases to a destabilization of the proteins and caused a red…

Deviance sensitivity in the auditory cortex of freely moving rats.

2018

Deviance sensitivity is the specific response to a surprising stimulus, one that violates expectations set by the past stimulation stream. In audition, deviance sensitivity is often conflated with stimulus-specific adaptation (SSA), the decrease in responses to a common stimulus that only partially generalizes to other, rare stimuli. SSA is usually measured using oddball sequences, where a common (standard) tone and a rare (deviant) tone are randomly intermixed. However, the larger responses to a tone when deviant does not necessarily represent deviance sensitivity. Deviance sensitivity is commonly tested using a control sequence in which many different tones serve as the standard, eliminat…

Spike-wave discharges in absence epilepsy: segregation of electrographic components reveals distinct pathways of seizure activity.

2020

Key points The major electrophysiological hallmarks of absence seizures are spike and wave discharges (SWDs), consisting of a sharp spike component and a slow wave component. In a widely accepted scheme, these components are functionally coupled and reflect an iterative progression of neuronal excitation during the spike and post-excitatory silence during the wave. In a genetic rat model of absence epilepsy, local pharmacological inhibition of the centromedian thalamus (CM) selectively suppressed the spike component, leaving self-contained waves in epidural recordings. Thalamic inputs induced activity in cortical microcircuits underlying the spike component, while intracortical oscillations…

E2F1 interacts with BCL-xL and regulates its subcellular localization dynamics to trigger cell death

2018

International audience; E2F1 is the main pro-apoptotic effector of the pRB-regulated tumor suppressor pathway by promoting the transcription of various pro-apoptotic proteins. We report here that E2F1 partly localizes to mitochondria, where it favors mitochondrial outer membrane permeabilization. E2F1 interacts with BCL-xL independently from its BH3 binding interface and induces a stabilization of BCL-xL at mitochondrial membranes. This prevents efficient control of BCL-xL over its binding partners, in particular over BAK resulting in the induction of cell death. We thus identify a new, non-BH3-binding regulator of BCL-xL localization dynamics that influences its anti-apoptotic activity.

Mcl-1 and Bok transmembrane domains : Unexpected players in the modulation of apoptosis

2020

The Bcl-2 protein family comprises both proand antiapoptotic members that control the permeabilization of the mitochondrial outer membrane, a crucial step in the modulation of apoptosis. Recent research has demonstrated that the carboxyl-terminal transmembrane domain (TMD) of some Bcl-2 protein family mem-bers can modulate apoptosis; however, the transmembrane interactome of the antiapoptotic protein Mcl-1 remains largely unexplored. Here, we demonstrate that the Mcl-1 TMD forms homooligomers in the mitochondrial membrane, competes with full-length Mcl-1 protein with regards to its antiapoptotic function, and induces cell death in a Bok-dependent manner. While the Bok TMD oligomers locate p…

Diversity in AMPA receptor complexes in the brain.

2017

AMPA receptor (AMPAR) complexes comprise four of the AMPAR subunits GluA1-4 and several additional interacting proteins. Subunit composition determines AMPAR function. However, AMPAR function depends to a large extent also on interacting proteins, which influence trafficking to the cell surface, activity-dependent subcellular localization and gating of AMPARs. In this review we report about recent findings on the diversity of AMPAR complexes that allow us to better understand functional properties of native receptors in the brain.

Durvalumab after definitive chemoradiotherapy in locally advanced unresectable non-small cell lung cancer (NSCLC): Real-world data on survival and sa…

2020

Abstract Background Following the PACIFIC trial, durvalumab has been approved by the European Medicines Agency (EMA) for consolidation of locally advanced PD-L1-positive NSCLC after chemoradiotherapy (CRT). Patients were treated with durvalumab in the EAP from 22.11.2017 to 15.10.2018 allowing analysis of its efficacy and safety. Methods Data from 56 centres were analysed for adverse events (AE), progression-free survival (PFS), overall survival (OS). Results 126 patients actually received at least 1 cycle durvalumab. Compared to the PACIFIC trial, the EAP population had more advanced stage and included “oligometastatic” stage IV patients and patients with autoimmune disease. PFS (20.1 mont…

Genome-Wide DNA Methylation Profiling in Early Stage I Lung Adenocarcinoma Reveals Predictive Aberrant Methylation in the Promoter Region of the Long…

2020

Introduction: Surgical procedure is the treatment of choice in early stage I lung adenocarcinoma. However, a considerable number of patients experience recurrence within the first 2 years after complete resection. Suitable prognostic biomarkers that identify patients at high risk of recurrence (who may probably benefit from adjuvant treatment) are still not available. This study aimed at identifying methylation markers for early recurrence that may become important tools for the development of new treatment modalities. Methods: Genome-wide DNA methylation profiling was performed on 30 stage I lung adenocarcinomas, comparing 14 patients with early metastatic recurrence with 16 patients with …

The SCOPE of definitive chemoradiotherapy in locally advanced esophageal cancer: what direction for the future?

2016

Exclusive chemoradiotherapy (CRT) delivering 50 Gy over 5 weeks with cisplatin and fluorouracil-based chemotherapy is a cornerstone in locally advanced esophageal cancer or non-operable patients since the results of the pivotal study of US Intergroup RTOG-8501 (1). This trial has successfully demonstrated that some patients with esophageal carcinoma may be long-term survivors so that this treatment is now definitely accepted as curative (2). Nevertheless the prognosis is still very disappointing with a 5-year overall survival rate of approximately 25%. Attempts to improve overall survival by escalating the dose of radiotherapy with concurrent cisplatin and fluorouracil has been assessed in …