Search results for "Replication"

Enhanced oxidative stress and increased mitochondrial mass during Efavirenz-induced apoptosis in human hepatic cells

2010

BACKGROUND AND PURPOSE Efavirenz (EFV) is widely used in the treatment of HIV-1 infection. Though highly efficient, there is growing concern about EFV-related side effects, the molecular basis of which remains elusive. EXPERIMENTAL APPROACH In vitro studies were performed to address the effect of clinically relevant concentrations of EFV (10, 25 and 50 µM) on human hepatic cells. KEY RESULTS Cellular proliferation and viability were reduced in a concentration-dependent manner. Analyses of the cell cycle and several cell death parameters (chromatin condensation, phosphatidylserine exteriorization, mitochondrial proapoptotic protein translocation and caspase activation) revealed that EFV trig…

2015

ABSTRACT Dengue fever is a severe, widespread, and neglected disease with more than 2 million diagnosed infections per year. The dengue virus NS2B/NS3 protease (PR) represents a prime target for rational drug design. At the moment, there are no clinical PR inhibitors (PIs) available. We have identified diaryl (thio)ethers as candidates for a novel class of PIs. Here, we report the selective and noncompetitive inhibition of the serotype 2 and 3 dengue virus PR in vitro and in cells by benzothiazole derivatives exhibiting 50% inhibitory concentrations (IC 50 s) in the low-micromolar range. Inhibition of replication of DENV serotypes 1 to 3 was specific, since all substances influenced neither…

Spatial recurrence strategies reveal different routes to Turing pattern formation in chemical systems

2009

We analyze the temporal evolution of hexagonal Turing patterns in two Belousov–Zhabotinsky reactions performed in water-in-oil reverse micro-emulsions under different experimental conditions. The two reactions show different routes to pattern formation through localized spots and through a self replication mechanism. The Generalized Recurrence Plot (GRP) and the Generalized Recurrence Quantification Analysis (GRQA) are used for the investigation of spatial patterns and clearly reveal the different routes leading to the formation of stationary Turing structures.

Transmission of ultra-cold neutrons through guides coated with materials of high optical potential

2014

Abstract We have measured the transmission of ultra-cold neutrons (UCN) through tubes coated on the inside with materials of high optical potentials. The best transmission value, T, normalised to 1 m long UCN guides was obtained with a beryllium coated quartz guide, T=(99.0±1.0)%. Furthermore, excellent transmission coefficients were found for (i) a glass tube coated with NiMo(88/12), T=(97.3 ±0.6)%, (ii) a NiMo(85/15) guide made by the replication technique, T=(97.1 ±0.8)% and (iii) a glass guide coated with NiMo(82/18), T=(96.3 ±2.1)%. The results demonstrate that UCN guides made from coated glass tubes have the same excellent transmission properties as those produced with the replication…

To make innovations such as replication mainstream, publish them in mainstream journals.

2019

AbstractIt was a pleasure to read Zwaan et al.'s wise and balanced target article. Here, I use it as a shining example for bolstering the argument that to make innovations such as replication mainstream, it seems advisable to move the debates from social media to respected “mainstream” psychology journals. Only then will mainstream psychologists be reached and, we hope, convinced.

Entry of Human Parechovirus 1

2001

ABSTRACT Human parechovirus 1 (HPEV-1) is a prototype member of parechoviruses, a recently established picornavirus genus. Although there is preliminary evidence that HPEV-1 recognizes α V integrins as cellular receptors, our understanding of early events during HPEV-1 infection is still very limited. The aim of this study was to clarify the entry mechanisms of HPEV-1, including the attachment of the virus onto the host cell surface and subsequent internalization. In blocking experiments with monoclonal antibodies against different receptor candidates, antibodies against α V and β 3 integrin subunits, in particular in combination, appeared to be the most efficient ones in preventing the HPE…

Genetic Analysis of Sequences in the 3′ Nontranslated Region of Hepatitis C Virus That Are Important for RNA Replication

2002

ABSTRACT The genome of the hepatitis C virus (HCV) is a plus-strand RNA molecule that carries a single long open reading frame. It is flanked at either end by highly conserved nontranslated regions (NTRs) that mediate crucial steps in the viral life cycle. The 3′ NTR of HCV has a tripartite structure composed of an about 40-nucleotide variable region, a poly(U/UC) tract that has a heterogeneous length, and a highly conserved 98-nucleotide 3′-terminal sequence designated the X tail or 3′X. Conflicting data as to the role the sequences in the 3′ NTR play in RNA replication have been reported. By using the HCV replicon system, which is based on the self-replication of subgenomic HCV RNAs in hu…

Cost of host radiation in an RNA virus.

2000

Abstract Although host radiation allows a parasite to expand its ecological niche, traits governing the infection of multiple host types can decrease fitness in the original or alternate host environments. Reasons for this reduction in fitness include slower replication due to added genetic material or modifications, fitness trade-offs across host environments, and weaker selection resulting from simultaneous adaptation to multiple habitats. We examined the consequences of host radiation using vesicular stomatitis virus (VSV) and mammalian host cells in tissue culture. Replicate populations of VSV were allowed to evolve for 100 generations on the original host (BHK cells), on either of two …

Mutagenesis scanning uncovers evolutionary constraints on tobacco etch Potyvirus membrane-associated 6K2 protein

2019

RNA virus high mutation rate is a double-edged sword. At the one side, most mutations jeopardize proteins functions; at the other side, mutations are needed to fuel adaptation. The relevant question then is the ratio between beneficial and deleterious mutations. To evaluate this ratio, we created a mutant library of the 6K2 gene of tobacco etch potyvirus that contains every possible single-nucleotide substitution. 6K2 protein anchors the virus replication complex to the network of endoplasmic reticulum membranes. The library was inoculated into the natural host Nicotiana tabacum, allowing competition among all these mutants and selection of those that are potentially viable. We identified 1…

DNA damage-induced cell death by apoptosis

2006

Following the induction of DNA damage, a prominent route of cell inactivation is apoptosis. During the last ten years, specific DNA lesions that trigger apoptosis have been identified. These include O6-methylguanine, base N-alkylations, bulky DNA adducts, DNA cross-links and DNA double-strand breaks (DSBs). Repair of these lesions are important in preventing apoptosis. An exception is O6-methylguanine-thymine lesions, which require mismatch repair for triggering apoptosis. Apoptosis induced by many chemical genotoxins is the consequence of blockage of DNA replication, which leads to collapse of replication forks and DSB formation. These DSBs are thought to be crucial downstream apoptosis-tr…