Search results for "ENSA"

The Emerging Therapeutic Landscape of ALK Inhibitors in Non-Small Cell Lung Cancer.

2020

The treatment of metastatic non-small cell lung cancer (NSCLC) has undergone a paradigm shift over the last decade. Better molecular characterization of the disease has led to the rapid improvement of personalized medicine and the prompt delivery of targeted therapies to patients with NSCLC. The discovery of the EML4-ALK fusion gene in a limited subset of patients affected by NSCLC and the subsequent clinical development of crizotinib in 2011 has been an impressive milestone in lung cancer research. Unfortunately, acquired resistances regularly develop, hence disease progression occurs. Afterward, modern tyrosine kinase inhibitors (TKIs), such as ceritinib, alectinib, brigatinib, and lorlat…

The quality of cortical network function recovery depends on localization and degree of axonal demyelination

2016

AbstractMyelin loss is a severe pathological hallmark common to a number of neurodegenerative diseases, including multiple sclerosis (MS). Demyelination in the central nervous system appears in the form of lesions affecting both white and gray matter structures. The functional consequences of demyelination on neuronal network and brain function are not well understood. Current therapeutic strategies for ameliorating the course of such diseases usually focus on promoting remyelination, but the effectiveness of these approaches strongly depends on the timing in relation to the disease state. In this study, we sought to characterize the time course of sensory and behavioral alterations induced…

Engineered Functional Redundancy Relaxes Selective Constraints upon Endogenous Genes in Viral RNA Genomes

2018

Functional redundancy, understood as the functional overlap of different genes, is a double-edge sword. At the one side, it is thought to serve as a robustness mechanism that buffers the deleterious effect of mutations hitting one of the redundant copies, thus resulting in pseudogenization. At the other side, it is considered as a source of genetic and functional innovation. In any case, genetically redundant genes are expected to show an acceleration in the rate of molecular evolution. Here, we tackle the role of functional redundancy in viral RNA genomes. To this end, we have evaluated the rates of compensatory evolution for deleterious mutations affecting an essential function, the suppr…

Expectation or Sensorial Reality? An Empirical Investigation of the Biodynamic Calendar for Wine Drinkers.

2017

International audience; The study's aim was to investigate a central tenet of biodynamic philosophy as applied to wine tasting, namely that wines taste different in systematic ways on days determined by the lunar cycle. Nineteen New Zealand wine professionals tasted blind 12 Pinot noir wines at times determined within the biodynamic calendar for wine drinkers as being favourable (Fruit day) and unfavourable (Root day) for wine tasting. Tasters rated each wine four times, twice on a Fruit day and twice on a Root day, using 20 experimenter-provided descriptors. Wine descriptors spanned a range of varietal-relevant aroma, taste, and mouthfeel characteristics, and were selected with the aim of …

Summertime observations of ultrafine particles and cloud condensation nuclei from the boundary layer to the free troposphere in the Arctic

2016

Abstract. The Arctic is extremely sensitive to climate change. Shrinking sea ice extent increases the area covered by open ocean during Arctic summer, which impacts the surface albedo and aerosol and cloud properties among many things. In this context extensive aerosol measurements (aerosol composition, particle number and size, cloud condensation nuclei, and trace gases) were made during 11 flights of the NETCARE July, 2014 airborne campaign conducted from Resolute Bay, Nunavut (74N, 94W). Flights routinely included vertical profiles from about 60 to 3000 m a.g.l. as well as several low-level horizontal transects over open ocean, fast ice, melt ponds, and polynyas. Here we discuss the vert…

Frequent Ultrafine Particle Formation and Growth in the Canadian Arctic Marine Environment

2017

Abstract. The source strength and capability of aerosol particles in the Arctic to act as cloud condensation nuclei have important implications for understanding the indirect aerosol-cloud effect within the polar climate system. It has been shown in several Arctic regions that ultrafine particle (UFP) formation and growth is a key contributor to aerosol number concentrations during the summer. This study uses aerosol number size distribution measurements from ship-board measurement expeditions aboard the research icebreaker CCGS Amundsen in the summers of 2014 and 2016 throughout the Canadian Arctic to gain a deeper understanding of the drivers of UFP formation and growth within this marine…

Commensal Bacterium Rothia aeria Degrades and Detoxifies Gluten via a Highly Effective Subtilisin Enzyme

2020

Celiac disease is characterized by a chronic immune-mediated inflammation of the small intestine, triggered by gluten contained in wheat, barley, and rye. Rothia aeria, a gram-positive natural colonizer of the oral cavity and the upper digestive tract is able to degrade and detoxify gluten in vitro. The objective of this study was to assess gluten-degrading activity of live and dead R. aeria bacteria in vitro, and to isolate the R. aeria gluten-degrading enzyme. Methods: After an overnight fast, Balb/c mouse were fed a 1 g pellet of standard chow containing 50% wheat (and 4% gliadin) with or without 1.6 &times

Minor environmental concentrations of antibiotics can modify bacterial virulence in co-infection with a non-targeted parasite.

2018

Leakage of medical residues into the environment can significantly impact natural communities. For example, antibiotic contamination from agriculture and aquaculture can directly influence targeted pathogens, but also other non-targeted taxa of commensals and parasites that regularly co-occur and co-infect the same host. Consequently, antibiotics could significantly alter interspecific interactions and epidemiology of the co-infecting parasite community. We studied how minor environmental concentrations of antibiotic affects the co-infection of two parasites, the bacterium Flavobacterium columnare and the fluke Diplostomum pseudospathaceum , in their fish host. We found that antibiotic in …

2019

The gut microbiota influence host vascular physiology locally in the intestine, but also evoke remote effects that impact distant organ functions. Amongst others, the microbiota affect intestinal vascular remodeling, lymphatic development, cardiac output and vascular function, myelopoiesis, prothrombotic platelet function, and immunovigilance of the host. Experimentally, host-microbiota interactions are investigated by working with animals devoid of symbiotic bacteria, i.e., by the decimation of gut commensals by antibiotic administration, or by taking advantage of germ-free mouse isolator technology. Remarkably, some of the vascular effects that were unraveled following antibiotic treatmen…

Hepatic benefits of HCV cure

2020

Direct-acting antiviral (DAA)-induced HCV clearance conceivably leads to improved outcomes at all stages of liver disease. However, available data suggest that the maximum measurable benefit is obtained by treating patients before they reach the stage of compensated advanced chronic liver disease (cACLD). Ideally, all patients with chronic hepatitis C should be treated before they develop advanced fibrosis or cirrhosis, since even if sustained virologic response (SVR) reduces the risk of hepatic events (e.g. decompensation and hepatocellular carcinoma [HCC]) and improves survival, further progression of liver disease and adverse outcomes, including hepatic deaths, cannot be entirely avoided…