Search results for "MUTATION"
showing 10 items of 2830 documents
A temperature-sensitive brain tumor suppressor mutation of Drosophila melanogaster: Developmental studies and molecular localization of the gene
1993
The recessive-lethal, temperature-sensitive (ts) mutation of the tumor suppressor gene lethal(3)malignant brain tumor (l(3)mbt) causes in a single step the malignant transformation of the adult optic neuroblasts and ganglion mother cells in the larval brain at the restrictive temperature of 29 degrees C. The transformed cells are differentiation-incompetent and grow autonomously in a lethal and invasive fashion in situ in the brain as well as after transplantation in vivo into wild-type adult hosts. The imaginal discs show epithelial overgrowth. At the permissive temperature of 22 degrees C development is completely normal. The ts-period of gene activity responsible for 100% brain tumor sup…
Identification of the essential protein domains for Mib2 function during the development of the Drosophila larval musculature and adult flight muscles
2016
The proper differentiation and maintenance of myofibers is fundamental to a functional musculature. Disruption of numerous mostly structural factors leads to perturbations of these processes. Among the limited number of known regulatory factors for these processes is Mind bomb2 (Mib2), a muscle-associated E3 ubiquitin ligase, which was previously established to be required for maintaining the integrity of larval muscles. In this study, we have examined the mechanistic aspects of Mib2 function by performing a detailed functional dissection of the Mib2 protein. We show that the ankyrin repeats, in its entirety, and the hitherto uncharacterized Mib-specific domains (MIB), are important for the…
Adverse events associated with encorafenib plus binimetinib in the COLUMBUS study: incidence, course and management.
2019
Abstract Background Dual inhibition of the mitogen-activated protein kinase pathway with BRAF/MEK inhibitor (BRAFi/MEKi) therapy is a standard treatment for BRAFV600-mutant metastatic melanoma and has historically been associated with grade III pyrexia or photosensitivity depending on the combination used. The objective of this study was to fully describe adverse events from the COLUMBUS study evaluating the most recent BRAF/MEK inhibitor combination encorafenib+binimetinib. Patients and methods Patients with locally advanced, unresectable or metastatic BRAFV600-mutant melanoma were randomised to receive encorafenib 450 mg once daily plus binimetinib 45 mg twice daily, encorafenib 300 mg on…
A membrane-destabilizing peptide in capsid protein L2 is required for egress of papillomavirus genomes from endosomes
2005
ABSTRACT Papillomaviruses are internalized via clathrin-dependent endocytosis. However, the mechanism by which viral genomes pass endosomal membranes has not been elucidated. In this report we show that the minor capsid protein L2 is required for egress of viral genomes from endosomes but not for initial uptake and uncoating and that a 23-amino-acid peptide at the C terminus of L2 is necessary for this function. Pseudogenomes encapsidated by L1 and L2 lacking this peptide accumulated in vesicular compartments similar to that observed with L1-only viral particles, and these mutant pseudoviruses were noninfectious. This L2 peptide displayed strong membrane-disrupting activity, induced cytolys…
Lipase maturation factor 1 is required for endothelial lipase activity
2011
Lipase maturation factor 1 (Lmf1) is an endoplasmic reticulum (ER) membrane protein involved in the posttranslational folding and/or assembly of lipoprotein lipase (LPL) and hepatic lipase (HL) into active enzymes. Mutations in Lmf1 are associated with diminished LPL and HL activities ("combined lipase deficiency") and result in severe hypertriglyceridemia in mice as well as in human subjects. Here, we investigate whether endothelial lipase (EL) also requires Lmf1 to attain enzymatic activity. We demonstrate that cells harboring a (cld) loss-of-function mutation in the Lmf1 gene are unable to generate active EL, but they regain this capacity after reconstitution with the Lmf1 wild type. Fur…
Simulation of a single-phase five-level cascaded H-Bridge inverter with multicarrier SPWM B-Spline based modulation techniques
2017
Multilevel Power Inverters are now often used to convert DC to AC voltage waveform. This kind of converter allows high power quality with low output harmonics and lower commutation losses with respect to the traditional ones in order to optimize this aspect. This paper presents a novel simulation analysis of the Multicarrier Sinusoidal Pulse Width Modulation (MC SPWM) techniques B-Spline functions based to control the switches of five-level single-phase cascaded H-bridge inverter. In order to verify the performance of the converter, the harmonic content of the voltage due to modulation techniques has been taken into account. Results highlight the comparison between different B-Spline functi…
Decay Heat Removal and Transient Analysis in Accidental Conditions in the EFIT Reactor
2008
The development of a conceptual design of an industrial-scale transmutation facility (EFIT) of several 100 MW thermal power based on accelerator-driven system (ADS) is addressed in the frame of the European EUROTRANS Integral Project. In normal operation, the core power of EFIT reactor is removed through steam generators by four secondary loops fed by water. A safety-related decay heat removal (DHR) system provided with four independent inherently safe loops is installed in the primary vessel to remove the decay heat by natural convection circulation under accidental conditions which are caused by a loss-of-heat sink (LOHS). In order to confirm the adequacy of the adopted solution for decay…
The measurement programme at the neutron time-of-flight facility n_TOF at CERN
2016
Neutron-induced reaction cross sections are important for a wide variety of research fields ranging from the study of nuclear level densities, nucleosynthesis to applications of nuclear technology like design, and criticality and safety assessment of existing and future nuclear reactors, radiation dosimetry, medical applications, nuclear waste transmutation, accelerator-driven systems and fuel cycle investigations. Simulations and calculations of nuclear technology applications largely rely on evaluated nuclear data libraries. The evaluations in these libraries are based both on experimental data and theoretical models. CERN’s neutron time-of-flight facility n TOF has produced a considerabl…
Biological effects and photodegradation by TiO(2) of terpenes present in industrial wastewater.
2010
Abstract The aim of this work was to study the biological effects of four monoterpenes, i.e. α-pinene, β-pinene, 3-carene and d -limonene present in the wastewater of a citrus transformation factory. The study was carried out by exposing V79 Chinese hamster cells to single terpene or to the mixture of four terpenes at concentrations corresponding to those in the wastewater evaluated by head space solid phase micro extraction and gas chromatography (HS-SPME-GC) analyses. Treatments with single or combined terpenes similarly affected cell vitality, but only the combined treatments induced the 6-thioguanine resistant mutants. Moreover the photocatalytic degradation of the four terpenes was suc…
Further development of the β-lactamase MutaGen assay and evaluation by comparison with Ames fluctuation tests and theumu test
2005
A rapid, high-throughput bacterial mutagenicity test system has been developed (MutaGen test) that detects reversions of inactivating base-pair substitutions and frameshifts in a TEM-1 class A β-lactamase (ampicillinase) gene. To quickly and sensitively detect mutagens, the system utilises a series of plasmids that contain the mutated ampicillinase gene and the mucAB operon. Inactivating mutations in the ampicillinase gene include frameshifts integrated into repetitive GC-sequences and G-runs known to be mutagenic hot-spots, and base-pair substitutions inserted in or around the β-lactamase active site. Frameshift mutations completely inactivated the enzyme only when located downstream of th…