Distinct promoter elements mediate the co-operative effect of Brn-3a and p53 on the p21 promoter and their antagonism on the Bax promoter

Although the promoters of both the Bax and p21 genes are activated by p53, they differ in the effect on this activation of the POU family transcription factor Brn-3a. Thus, Brn-3a inhibits activation of the Bax promoter by p53 but enhances the ability of p53 to activate the p21 promoter. We demonstrate that repression of p53-mediated activation of the Bax promoter involves a complex upstream sequence in which two Brn-3a response elements flank the p53 response element. In contrast, a minimal p21 promoter is activated by Brn-3a and such activation cannot be abolished without abolishing basal promoter activity. Moreover, synergistic activation by Brn-3a and p53 continues to be observed when the p53-binding sites in the p21 promoter are substituted by the Bax p53 site or by the region of the Bax promoter essential for Brn-3a-mediated repression, indicating that the p21 core promoter plays a central role in this response. The significance of these effects is discussed in terms of the different responses of the Bax and p21 promoters and the overlapping but distinct roles of Brn-3a and p53 in neuronal growth arrest and apoptosis

Artificial Micro-Swimmers in Simulated Natural Environments

open11107sciescopu

Crystal growth and quantum oscillations in the topological chiral semimetal CoSi

We survey the electrical transport properties of the single-crystalline, topological chiral semimetal CoSi which was grown via different methods. High-quality CoSi single crystals were found in the growth from tellurium solution. The sample's high carrier mobility enables us to observe, for the first time, quantum oscillations (QOs) in its thermoelectrical signals. Our analysis of QOs reveals two spherical Fermi surfaces around the R point in the Brillouin zone corner. The extracted Berry phases of these electron orbits are consistent with the -2 chiral charge as reported in DFT calculations. Detailed analysis on the QOs reveals that the spin-orbit coupling induced band-splitting is less than 2 meV near the Fermi level, one order of magnitude smaller than our DFT calculation result. We also report the phonon-drag induced large Nernst effect in CoSi at intermediate temperatures

Fluoxetine: a case history of its discovery and preclinical development

Introduction: Depression is a multifactorial mood disorder with a high prevalence worldwide. Until now, treatments for depression have focused on the inhibition of monoaminergic reuptake sites, which augment the bioavailability of monoamines in the CNS. Advances in drug discovery have widened the therapeutic options with the synthesis of so-called selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine. Areas covered: The aim of this case history is to describe and discuss the pharmacokinetic and pharmacodynamic profiles of fluoxetine, including its acute effects and the adaptive changes induced after long-term treatment. Furthermore, the authors review the effect of fluoxetine on neuroplasticity and adult neurogenesis. In addition, the article summarises the preclinical behavioural data available on fluoxetine’s effects on depressive-like behaviour, anxiety and cognition as well as its effects on other diseases. Finally, the article describes the seminal studies validating the antidepressant effects of fluoxetine. Expert opinion: Fluoxetine is the first selective SSRI that has a recognised clinical efficacy and safety profile. Since its discovery, other molecules that mimic its mechanism of action have been developed, commencing a new age in the treatment of depression. Fluoxetine has also demonstrated utility in the treatment of other disorders for which its prescription has now been approved

Three-dimensional localization of ultracold atoms in an optical disordered potential

We report a study of three-dimensional (3D) localization of ultracold atoms suspended against gravity, and released in a 3D optical disordered potential with short correlation lengths in all directions. We observe density profiles composed of a steady localized part and a diffusive part. Our observations are compatible with the self-consistent theory of Anderson localization, taking into account the specific features of the experiment, and in particular the broad energy distribution of the atoms placed in the disordered potential. The localization we observe cannot be interpreted as trapping of particles with energy below the classical percolation threshold.Comment: published in Nature Physics; The present version is the initial manuscript (unchanged compared to version 1); The published version is available online at http://www.nature.com/nphys/journal/vaop/ncurrent/full/nphys2256.htm

Effect of peri-implant mucosal thickness on esthetic outcomes and the efficacy of soft tissue augmentation procedures: Consensus report of group 2 of the SEPA/DGI/OF workshop

OBJECTIVES: The aim of this study was to comprehensively assess the literature in terms of the effect of peri‐implant mucosal thickness on esthetic outcomes and the efficacy of soft tissue augmentation procedures to increase the mucosal thickness with autogenous grafts or soft tissue substitutes. MATERIAL AND METHODS: Two systematic reviews (SR) were performed prior to the consensus meeting to assess the following questions. Review 1, focused question: In systemically healthy patients with an implant‐supported fixed prosthesis, what is the influence of thin as compared to thick peri‐implant mucosa on esthetic outcomes? Review 2, focused question 1: In systemically healthy humans with at least one dental implant (immediate or staged implant), what is the efficacy of connective tissue graft (CTG), as compared to absence of a soft tissue grafting procedure, in terms of gain in peri‐implant soft tissue thickness (STT) reported by randomized controlled clinical trials (RCTs) or controlled clinical trials (CCTs)? Review 2, focused question 2: In systemically healthy humans with at least one dental implant (immediate or staged implant), what is the efficacy of CTG, as compared to soft tissue substitutes, in terms of gain in peri‐implant STT reported by RCTs or CCTs? The outcomes of the two SRs, the consensus statements, the clinical implications, and the research recommendations were discussed and subsequently approved at the consensus meeting during the group and plenary sessions. CONCLUSIONS: There was a tendency of superior esthetic outcomes in the presence of a thick mucosa. The connective tissue graft remains the standard of care in terms of increasing mucosa thickness

Modeling the Impact of Tuberculosis Control Strategies in Highly Endemic Overcrowded Prisons

International audienceBACKGROUND: Tuberculosis (TB) in prisons is a major health problem in countries of high and intermediate TB endemicity such as Brazil. For operational reasons, TB control strategies in prisons cannot be compared through population based intervention studies. METHODOLOGY/PRINCIPAL FINDINGS: A mathematical model is proposed to simulate the TB dynamics in prison and evaluate the potential impact on active TB prevalence of several intervention strategies. The TB dynamics with the ongoing program was simulated over a 10 year period in a Rio de Janeiro prison (TB prevalence 4.6 %). Then, a simulation of the DOTS strategy reaching the objective of 70 % of bacteriologically-positive cases detected and 85 % of detected cases cured was performed; this strategy reduced only to 2.8% the average predicted TB prevalence after 5 years. Adding TB detection at entry point to DOTS strategy had no major effect on the predicted active TB prevalence. But, adding further a yearly X-ray mass screening of inmates reduced the predicted active TB prevalence below 1%. Furthermore, according to this model, after applying this strategy during 2 years (three annual screenings), the TB burden would be reduced and the active TB prevalence could be kept at a low level by associating X-ray screening at entry point and DOTS. CONCLUSIONS/SIGNIFICANCE: We have shown that X-ray mass screenings should be considered to control TB in highly endemic prison. Prisons with different levels of TB prevalence could be examined thanks to this model which provides a rational tool for public health deciders

Morphological and molecular characterization of Curvularia and related species associated with leaf spot disease of rice in Peninsular Malaysia

Curvularia species are important phytopathogens reported worldwide. They are closely related; consist of major destructive pathogens mainly for grasses and cereal plants including rice (Oryza sativa). A leaf spot symptom of rice is one of the common symptoms found in the rice field and caused reduction of rice yield. However, there are no reports on Curvularia species associated with rice leaves showing spot symptoms. The objectives are to isolate and characterize Curvularia and related species from leaf spot of rice by using morphological and molecular characterization and to determine the phylogenetic relationship between the isolated fungi. Fungal isolation was done from diseased rice leaves showing leaf spot symptoms collected throughout Peninsular Malaysia. Thirty-three isolates were recovered and identified based on their morphological characteristics such as conidia morphology, colony appearance, pigmentation and growth rate for species delimitation. Internal transcribed spacer (ITS) region was amplified to confirm the species identification. The 33 isolates were identified as Bipolaris sorokiniana (10 isolates), Curvularia hawaiiensis (8 isolates), C. geniculata (6 isolates), C. eragrostidis (6 isolates), C. aeria (2 isolates) and C. lunata (1 isolate). A phylogenetic tree was constructed based on ITS sequences using neighbour-joining method. The tree grouped members of Curvularia and Bipolaris into different clades. The phylogenetic tree indicated that the presence of two groups of fungi species; highly virulent and mild pathogens. In conclusion, Curvularia species and Bipolaris sorokiniana were present in rice field in Malaysia and associated with leaf spot of rice