Normality in terms of distances and contractions

The main purpose of this paper is to explore normality in terms of distances between points and sets. We prove some important consequences on realvalued contractions, i.e. functions not enlarging the distance, showing that as in the classical context of closures and continuous maps, normality in terms of distances based on an appropriate numerical notion of $\gamma$-separation of sets, has far reaching consequences on real valued contractive maps, where the real line is endowed with the Euclidean metric. We show that normality is equivalent to (1) separation of $\gamma$-separated sets by some Urysohn contractive map, (2) to Kat\v{e}tov-Tong's interpolation, stating that for bounded positive realvalued functions, between an upper and a larger lower regular function, there exists a contractive interpolating map and (3) to Tietze's extension theorem stating that certain contractions defined on a subspace can be contractively extended to the whole space. The appropriate setting for these investigations is the category of approach spaces, but the results have (quasi)-metric counterparts in terms of non-expansive maps. Moreover when restricted to topological spaces, classical normality and its equivalence to separation by a Urysohn continuous map, to Kat\v{e}tov-Tong's interpolation for semicontinuous maps and to Tietze's extension theorem for continuous maps are recovered

IL-10 regulates adult neurogenesis by modulating ERK and STAT3 activity

The adult subventricular zone (SVZ) contains Nestin+ progenitors that differentiate mainly into neuroblasts. Our previous data showed that interleukin-10 (IL-10) regulates SVZ adult neurogenesis by up-regulating the expression of pro-neural genes and modulating cell cycle exit. Here we addressed the specific mechanism through which IL-10 carries out its signaling on SVZ progenitors. We found that,in vitro andin vivo, IL-10 targets Nestin+ progenitors and activates the phosphorylation of ERK and STAT3. The action of IL-10 on Nestin+ progenitors is reversed by treatment with a MEK/ERK inhibitor, thus restoring neurogenesis to normal levels. Silencing STAT3 expression by lentiviral vectors also impaired neurogenesis by blocking the effects of IL-10. Our findings unveil ERK and STAT3 as effectors of IL-10 in adult SVZ neurogenesis. © 2015, Frontiers Research Foundation. All rights reservedThis work was supported by Marató TV3, and Mapfre foundation to EP. EP was a researcher of the Ramón y Cajal program (MICINN Spain).Peer Reviewe

Intramontane lacustrine basins in the Siberian Altai: recorders of Cenozoic intracontinental tectonic and climatic events

The Altai Mountains are part of the vast intracontinental Central Asian orogenic system that formed during the Cenozoic as a distal effect of continued indentation of the Indian plate into the Eurasian continent. In the Siberian part of the Altai Mountains there is ample evidence to suggest that the pre-Cenozoic structural fabric of its basement is a controlling factor in the Cenozoic deformation and development of this intracontinental orogen. We give evidence that important Paleozoic fault zones were reactivated during the Cenozoic, particularly the Late Cenozoic and play a key role in the formation, evolution and current morphology of the Siberian Altai Mountains. Some of these faults are still active and recent and historic movements along them have triggered large seismic events. Late Cenozoic reactivation was expressed as pure thrust, oblique thrust to pure strike-slip faulting, resulting in an overall transpressive tectonic regime. In some cases, as for the graben basin of Lake Teletskoye, local, pure extensional stresses are responsible for its formation as we show in this contribution. Various other intramontane, tectonic basins developed. Some of these are very recent structures (the Teletskoye Basin) and are Pleistocene in age or younger, others have a prolonged history and contain a relatively complete Cenozoic sedimentary section, with evidence of Late Mesozoic precursor basins (Chuya Basin, Dzhulukul Basin). Some of these exhibit indications of marine incursions, but the basins are predominantly continental. The development of these basins is clearly associated with the location and Cenozoic reactivation of aforementioned long-lived fault zones in the Altai tectonic assemblage. Many of these basins accommodated fresh water lakes during their evolution and some are still the site of contemporary mountain lakes. Their stratigraphy, as well as the sedimentary architecture and basin morphology is manifestly influenced by and progresses with the stages of (Late) Cenozoic intracontinental mountain building and erosive denudation of the growing mountain ranges. Together with the clastic sedimentary input and the provenance characteristics, the intramontane Altai basin deposits are affected by evolving climatic conditions. These conditions dictate the main mode of erosion and transport, influence the sedimentary facies and supply rate and create the framework for a specific biocoenosis signature found in the fossil record. Our contribution reviews the data obtained over the last years from a selection of intramontane lacustrine basins in the Siberian Altai Mountains. We direct our attention in particular to the Teletskoye basin, the Chuya-Kurai Basin and the Dzhulukul Basin. We combine sedimentologic-stratigraphic data with basin architecture and morphology, and with basement geochronologic-thermochronologic constraints (apatite fission-track, U/Pb and Ar-dating) in order to show the potential of these basins as recorders of Cenozoic tectonic and climatic events in relation with basement features. While for example the data obtained from the Chuya Basin yields a continuous Cenozoic picture of deformation and climatic evolution of the Altai area, data from the Teletskoye Basin zooms in with higher resolution on the Pleistocene to Recent history. In general, all data point towards intensifying tectonic reactivation and mountain building of the Siberian Altai Mountains since the Middle Cenozoic, with clear peak activity in the Pliocene to Recent. This is demonstrated by the molassetype deposits in these basins, and by thermochronologic constraints. This activity is ongoing and structural, (paleo)seismic, geomorphologic and sedimentologic data corroborates this. The lacustrine Altai basins provide a record for a more or less continuous progressive cooling and aridification of the Altai area during the Cenozoic as manifested in the pollen fossil assemblages found in the Altai sediments

Hoge prevalentie van mentale stoornissen in de eerste lijn. Resultaten van een cross-sectioneel onderzoek.

Objective: To deternine the prevalence of common mental disorders in an adult primary care population. Design: Cross-sectional survey in randomly selected subjects, using the PRIME-MD questionnaire. Setting: Eighty-six general practices in Belgium. Subjects: A total of 2316 randomly selected patients, aged 18 years or older and consulting their general practitioner for other than administrative reasons alone, with slightly more women (58.1%) than men (41.3%). Main outcome result: Prevalence rates of mental disorders most commonly seen in primary care practice (mood, anxiety, somatoform, eating and alcohol disorders). Methods: To facilitate data collection and processing, the entire PRIME-MD questionnaire was programmed on a handheld computer. Patient answers and physician assessments were immediately electronically recorded during the interview. All investigators were trained on the use of the PRIME-MD. The recruitment period lasted 6 weeks: from 15 February to 25 March 1999, and patients were randomly selected for the interview based on a computerized procedure. Results: Although onky 5.4% of all patients consulted for a psychiatric reason, a threshold/subthreshold psychiatric disorder was detected in 42.5% of all patients. Most commonly detected disorders were mood disorders in 31.0% (major depressive disorder, 13.9% and dysthymia, 12.6%), anxiety disorders in 19.0% (generalized anxiety disorder, 10.3%), somatoform disorders in 18.0% and probable alcohol abuse/dependence in 10.1%. The results also showed the important rate of comorbidity between these disorders. Conclusion: The present study confirms the high prevalence of mental disorders in a general practice setting, and their frequent association. Prevalence rates of our study are even higher than those obtained in previously conducted trials. Our study also demonstrates the utility of the PRIME-MD as a screening tool for mental disorders in primary care. Inaddition the use of the handheld computer software version of the PRIME-MD allowed us to screen for ental disorders inpatients who are unable to attend the GP office and are seen during ‘hotne’ visits

Een 18de-eeuwse wraksite op de Buiten Ratel-zandbank (Belgische territoriale wateren): 1. Multidisciplinair onderzoek van het vondstenmateriaal

In 1996 werd op de Buiten Ratel-zandbank, op 9 mijl van de kust, ter hoogte van Koksijde, een houten scheepswrak gelokaliseerd. Het werd onderzocht door een groep sportduikers, met de naam NATA. Jarenlange verkenning van de wraksite leverde talrijke vondsten op. In 2003 zochten de duikers steun bij het toenmalige IAP (Instituut voor het Archeologisch Patrimonium), nu Vlaams Instituut voor het Onroerend Erfgoed (VIOE), om het onderzoek en de conservatie op wetenschappelijke basis verder te zetten. Het VIOE ontfermde zich over het onderzoek van de tot nu toe geborgen materiële resten van de wraksite. Het eerste hoofdstuk van het artikel geeft een overzicht van de observaties van de wraksite via duikonderzoek en via gespecialiseerde technieken vanop een onderzoeksschip. In hoofdstuk 2 worden de objecten beschreven, hun betekenis aan boord van het schip besproken, evenals hun datering en herkomst. Hoofdstuk 3 brengt alle informatie samen en geeft aan wat er in de toekomst nog aan onderzoek kan gebeuren

Efficient delivery of RNA Interference to peripheral neurons in vivo using herpes simplex virus

Considerable interest has been focused on inducing RNA interference (RNAi) in neurons to study gene function and identify new targets for disease intervention. Although small interfering RNAs (siRNAs) have been used to silence genes in neurons, in vivo delivery of RNAi remains a major challenge limiting its applications. We have developed a highly efficient method for in vivo gene silencing in dorsal root ganglia (DRG) using replication-defective herpes simplex viral (HSV-1) vectors. HSV-mediated delivery of short-hairpin RNA (shRNA) targeting reporter genes resulted in highly effective and specific silencing in neuronal and non-neuronal cells in culture and in the DRG of mice in vivo including in a transgenic mouse model. We further establish proof of concept by demonstrating in vivo silencing of the endogenous trpv1 gene. These data are the first to show silencing in DRG neurons in vivo by vector-mediated delivery of shRNA. Our results support the utility of HSV vectors for gene silencing in peripheral neurons and the potential application of this technology to the study of nociceptive processes and in pain gene target validation studies

Tomato: a crop species amenable to improvement by cellular and molecular methods

Tomato is a crop plant with a relatively small DNA content per haploid genome and a well developed genetics. Plant regeneration from explants and protoplasts is feasable which led to the development of efficient transformation procedures. In view of the current data, the isolation of useful mutants at the cellular level probably will be of limited value in the genetic improvement of tomato. Protoplast fusion may lead to novel combinations of organelle and nuclear DNA (cybrids), whereas this technique also provides a means of introducing genetic information from alien species into tomato. Important developments have come from molecular approaches. Following the construction of an RFLP map, these RFLP markers can be used in tomato to tag quantitative traits bred in from related species. Both RFLP's and transposons are in the process of being used to clone desired genes for which no gene products are known. Cloned genes can be introduced and potentially improve specific properties of tomato especially those controlled by single genes. Recent results suggest that, in principle, phenotypic mutants can be created for cloned and characterized genes and will prove their value in further improving the cultivated tomato.

HIV-1 RT-dependent DNAzyme expression inhibits HIV-1 replication without the emergence of escape viruses

DNAzymes are easier to prepare and less sensitive to chemical and enzymatic degradation than ribozymes; however, a DNA enzyme expression system has not yet been developed. In this study, we exploited the mechanism of HIV-1 reverse transcription (RT) in a DNA enzyme expression system. We constructed HIV-1 RT-dependent lentiviral DNAzyme expression vectors including the HIV-1 primer binding site, the DNA enzyme, and either a native tRNA (Lys-3), tRMDtRL, or one of two truncated tRNAs (Lys-3), tRMDΔARMtRL or tRMD3′-endtRL. Lentiviral vector-mediated DNAzyme expression showed high levels of inhibition of HIV-1 replication in SupT1 cells. We also demonstrated the usefulness of this approach in a long-term assay, in which we found that the DNAzymes prevented escape from inhibition of HIV. These results suggest that HIV-1 RT-dependent lentiviral vector-derived DNAzymes prevent the emergence of escape mutations

A systematic analysis of the effect of target RNA structure on RNA interference

RNAi efficiency is influenced by local RNA structure of the target sequence. We studied this structure-based resistance in detail by targeting a perfect RNA hairpin and subsequently destabilized its tight structure by mutation, thereby gradually exposing the target sequence. Although the tightest RNA hairpins were completely resistant to RNAi, we observed an inverse correlation between the overall target hairpin stability and RNAi efficiency within a specific thermodynamic stability (ΔG) range. Increased RNAi efficiency was shown to be caused by improved binding of the siRNA to the destabilized target RNA hairpins. The mutational effects vary for different target regions. We find an accessible target 3′ end to be most important for RNAi-mediated inhibition. However, these 3′ end effects cannot be reproduced in siRNA-target RNA-binding studies in vitro, indicating the important role of RISC components in the in vivo RNAi reaction. The results provide a more detailed insight into the impact of target RNA structure on RNAi and we discuss several possible implications. With respect to lentiviral-mediated delivery of shRNA expression cassettes, we present a ΔG window to destabilize the shRNA insert for vector improvement, while avoiding RNAi-mediated self-targeting during lentiviral vector production