On the development of Aurelia aurita and Cotylorhiza borboniea

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Inhibitors of the Hepatitis C Virus RNA-Dependent RNA Polymerase NS5B

More than 20 years after the identification of the hepatitis C virus (HCV) as a novel human pathogen, the only approved treatment remains a combination of pegylated interferon-α and ribavirin. This rather non-specific therapy is associated with severe side effects and by far not everyone benefits from treatment. Recently, progress has been made in the development of specifically targeted antiviral therapy for HCV (STAT-C). A major target for such direct acting antivirals (DAAs) is the HCV RNA-dependent RNA polymerase or non-structural protein 5B (NS5B), which is essential for viral replication. This review will examine the current state of development of inhibitors targeting the polymerase and issues such as the emergence of antiviral resistance during treatment, as well as strategies to address this problem

Negative effect of the M184V mutation in HIV-1 reverse transcriptase on initiation of viral DNA synthesis

AbstractThe M184V mutation in HIV reverse transcriptase (RT) is associated with high-level resistance against the nucleoside inhibitor lamivudine as well as diminished viral replication capacity. We have previously demonstrated that HIV variants containing the M184V mutation were relatively unable to successfully undergo compensatory mutagenesis following deletion of an A-rich loop located upstream of the primer binding site (PBS). To understand the mechanisms involved, we synthesized viral RNA templates containing different compensatory mutations that were emergent during the long-term culture of the A-rich loop-deleted viruses. These templates were then used in cell-free reverse transcription initiation assays and in tRNA primer placement assays performed with either recombinant wild-type RT or recombinant RT containing the M184V substitution. The results showed that the RNA template that contained the A-rich loop deletion was impaired in ability to initiate reverse transcription and that the presence of the M184V substitution in RT amplified this effect. Clearance from pausing at position +3 during synthesis of viral DNA was identified as a sensitive step in this reaction that could not be efficiently bypassed with the M184V mutant enzyme. Increased efficiency of initiation was seen with the deleted RNA templates that also contained mutations identified in the revertant viruses, provided that these mutations facilitated formation of a competent binary tRNA/RNA complex. These findings provide biochemical evidence that initiation of tRNALys3-primed DNA synthesis is an important rate-limiting step in reverse transcription that correlates with viral replication fitness

Event-Related Potentials during a Gambling Task in Young Adults with Attention-Deficit/Hyperactivity Disorder.

Attention-deficit hyperactivity disorder (ADHD) is characterized by deficits in executive functions and decision making during childhood and adolescence. Contradictory results exist whether altered event-related potentials (ERPs) in adults are associated with the tendency of ADHD patients toward risky behavior. Clinically diagnosed ADHD patients ( javax.xml.bind.JAXBElement@5fb8b0ff = 18) and healthy controls ( javax.xml.bind.JAXBElement@76b3b68b = 18), aged between 18 and 29 (median 22 Yo), were screened with the Conners' Adult ADHD Rating Scales and assessed by the Mini-International Neuropsychiatric Interview, adult ADHD Self-Report Scale, and by the 60-item HEXACO Personality Inventory. The characteristic personality traits of ADHD patients were the high level of impulsiveness associated with lower values of agreeableness. All participants performed a probability gambling task (PGT) with two frequencies of the feedback information of the outcome. For each trial, ERPs were triggered by the self-paced trial onset and by the gamble selection. After trial onset, N2-P3a ERP component associated with the attentional load peaked earlier in the ADHD group than in controls. An N500 component related to the feedback frequency condition after trial onset and an N400-like component after gamble selection suggest a large affective stake of the decision making and an emphasized post-decisional evaluation of the choice made by the ADHD participants. By combining ERPs, related to the emotions associated with the feedback frequency condition, and behavioral analyses during completion of PGT, this study provides new findings on the neural dynamics that differentiate controls and young ADHD adults. In the patients' group, we raise the hypothesis that the activity of frontocentral and centroparietal neural circuits drive the decision-making processes dictated by an impaired cognitive workload followed by the build-up of large emotional feelings generated by the conflict toward the outcome of the gambling choice. Our results can be used for new investigations aimed at studying the fine spatiotemporal distribution of cortical activity, and the neural circuits that underly the generation of that activity, associated with the behavioral deficits characteristic of ADHD

mRNA-Expression of ERα, ERβ, and PR in Clonal Stem Cell Cultures Obtained from Human Endometrial Biopsies

Background. Proliferation and differentiation of the endometrium are regulated by estrogen and progesterone. The enormous regenerative capacity of the endometrium is thought to be based on the activity of adult stem cells. However, information on endocrine regulatory mechanisms in human endometrial stem cells is scarce. In the present study, we investigated the expression of ERα, ERβ, and PR in clonal cultures of human endometrial stem cells derived from transcervical biopsies. Methods. Endometrial tissue of 11 patients was obtained by transcervical biopsy. Stromal cell suspensions were plated at clonal density and incubated for 15 days. Expression of ERα, ERβ and PR was determined by qPCR prior to and after one cloning round, and normalized to 18 S rRNA expression. Results. Expression of ERα and ERβ was downregulated by 64% and 89%, respectively (P = 0.002 and P < 0.001). In contrast, PR was not significantly downregulated, due to a more heterogenous expression pattern. Conclusions. Culture of human endometrial stroma cells results in a downregulation of ERα and ERβ, while expression of PR remained unchanged in our patient collective. These results support the hypothesis that stem cells may not be subject to direct stimulation by sex steroids, but rather by paracrine mechanisms within the stem cell niche

How effective is the European Union energy label? Evidence from a real-stakes experiment

Imperfect information and inattention can lead consumers to undervalue the energy efficiency of products, contributing to growing environmental problems and climate change. To nudge individuals towards energy efficiency, environmental certification schemes, such as the European Union (EU) energy label, present grade-like efficiency classes. In a real-stakes randomized controlled trial, we contrast this approach with a control condition that gives no energy-related information and an alternative treatment condition that provides detailed information on the lifetime cost of energy-using durables. Our results show that the EU energy label does not increase demand for energy-efficient products over a control condition. By contrast, lifetime-cost information increases the willingness-to-pay for energy efficiency considerably

Large-uncertainty intelligent states for angular momentum and angle

The equality in the uncertainty principle for linear momentum and position is obtained for states which also minimize the uncertainty product. However, in the uncertainty relation for angular momentum and angular position both sides of the inequality are state dependent and therefore the intelligent states, which satisfy the equality, do not necessarily give a minimum for the uncertainty product. In this paper, we highlight the difference between intelligent states and minimum uncertainty states by investigating a class of intelligent states which obey the equality in the angular uncertainty relation while having an arbitrarily large uncertainty product. To develop an understanding for the uncertainties of angle and angular momentum for the large-uncertainty intelligent states we compare exact solutions with analytical approximations in two limiting cases.Comment: 20 pages, 9 figures, submitted to J. Opt. B special issue in connection with ICSSUR 2005 conferenc

Topological approach of characterizing optical Skyrmions and Skyrmion lattices

The Skyrmion number of paraxial optical Skyrmions can be defined solely via their polarization singularities and associated winding numbers, using a mathematical derivation that exploits Stokes's theorem. It is demonstrated that this definition provides a robust way to extract the Skyrmion number from experimental data, as illustrated for a variety of optical (N\'eel-type) Skyrmions and bimerons, and their corresponding lattices. This method generates not only an increase in accuracy, but also provides an intuitive geometrical approach to understanding the topology of such quasi-particles of light, and their robustness against smooth transformations