Spi-1, Fli-1 and Fli-3 (miR-17-92) Oncogenes Contribute to a Single Oncogenic Network Controlling Cell Proliferation in Friend Erythroleukemia

Clonal erythroleukemia developing in susceptible mice infected by Friend virus complex are associated with highly recurrent proviral insertions at one of three loci called Spi-1, Fli-1 or Fli-3, leading to deregulated expression of oncogenic Spi-1 or Fli-1 transcription factors or miR-17-92 miRNA cluster, respectively. Deregulated expression of each of these three oncogenes has been independently shown to contribute to cell proliferation of erythroleukemic clones. Previous studies showed a close relationship between Spi-1 and Fli-1, which belong to the same ETS family, Spi-1 activating fli-1 gene, and both Spi-1 and Fli-1 activating multiple common target genes involved in ribosome biogenesis. In this study, we demonstrated that Spi-1 and Fli-1 are also involved in direct miR-17-92 transcriptional activation through their binding to a conserved ETS binding site in its promoter. Moreover, we demonstrated that physiological re-expression of exogenous miR-17 and miR-20a are able to partially rescue the proliferation loss induced by Fli-1 knock-down and identified HBP1 as a target of these miRNA in erythroleukemic cells. These results establish that three of the most recurrently activated oncogenes in Friend erythroleukemia are actually involved in a same oncogenic network controlling cell proliferation. The putative contribution of a similar ETS-miR-17-92 network module in other normal or pathological proliferative contexts is discussed

Colloidal stability of tannins: astringency, wine tasting and beyond

Tannin-tannin and tannin-protein interactions in water-ethanol solvent mixtures are studied in the context of red wine tasting. While tannin self-aggregation is relevant for visual aspect of wine tasting (limpidity and related colloidal phenomena), tannin affinities for salivary proline-rich proteins is fundamental for a wide spectrum of organoleptic properties related to astringency. Tannin-tannin interactions are analyzed in water-ethanol wine-like solvents and the precipitation map is constructed for a typical grape tannin. The interaction between tannins and human salivary proline-rich proteins (PRP) are investigated in the framework of the shell model for micellization, known for describing tannin-induced aggregation of beta-casein. Tannin-assisted micellization and compaction of proteins observed by SAXS are described quantitatively and discussed in the case of astringency

PERC rule to exclude the diagnosis of pulmonary embolism in emergency low-risk patients: study protocol for the PROPER randomized controlled study.

BACKGROUND: The diagnosis of Pulmonary Embolism (PE) in the emergency department (ED) is crucial. As emergency physicians fear missing this potential life-threatening condition, PE tends to be over-investigated, exposing patients to unnecessary risks and uncertain benefit in terms of outcome. The Pulmonary Embolism Rule-out Criteria (PERC) is an eight-item block of clinical criteria that can identify patients who can safely be discharged from the ED without further investigation for PE. The endorsement of this rule could markedly reduce the number of irradiative imaging studies, ED length of stay, and rate of adverse events resulting from both diagnostic and therapeutic interventions. Several retrospective and prospective studies have shown the safety and benefits of the PERC rule for PE diagnosis in low-risk patients, but the validity of this rule is still controversial. We hypothesize that in European patients with a low gestalt clinical probability and who are PERC-negative, PE can be safely ruled out and the patient discharged without further testing. METHODS/DESIGN: This is a controlled, cluster randomized trial, in 15 centers in France. Each center will be randomized for the sequence of intervention periods: a 6-month intervention period (PERC-based strategy) followed by a 6-month control period (usual care), or in reverse order, with 2 months of "wash-out" between the 2 periods. Adult patients presenting to the ED with a suspicion of PE and a low pre test probability estimated by clinical gestalt will be eligible. The primary outcome is the percentage of failure resulting from the diagnostic strategy, defined as diagnosed venous thromboembolic events at 3-month follow-up, among patients for whom PE has been initially ruled out. DISCUSSION: The PERC rule has the potential to decrease the number of irradiative imaging studies in the ED, and is reported to be safe. However, no randomized study has ever validated the safety of PERC. Furthermore, some studies have challenged the safety of a PERC-based strategy to rule-out PE, especially in Europe where the prevalence of PE diagnosed in the ED is high. The PROPER study should provide high-quality evidence to settle this issue. If it confirms the safety of the PERC rule, physicians will be able to reduce the number of investigations, associated subsequent adverse events, costs, and ED length of stay for patients with a low clinical probability of PE. TRIAL REGISTRATION: NCT02375919

Projected increases in the annual flood pulse of the Western Amazon

The impact of a changing climate on the Amazon basin is a subject of intensive research because of its rich biodiversity and the significant role of rainforests in carbon cycling. Climate change has also a direct hydrological impact, and increasing efforts have focused on understanding the hydrological dynamics at continental and subregional scales, such as the Western Amazon. New projections from the Coupled Model Inter-comparison Project Phase 5 ensemble indicate consistent climatic warming and increasing seasonality of precipitation in the Peruvian Amazon basin. Here we use a distributed land surface model to quantify the potential impact of this change in the climate on the hydrological regime of the upper Amazon river. Using extreme value analysis, historical and future projections of the annual minimum, mean, and maximum river flows are produced for a range of return periods between 1 and 100 yr. We show that the RCP 4.5 and 8.5 scenarios of climate change project an increased severity of the wet season flood pulse (7.5% and 12% increases respectively for the 100 yr return floods). These findings agree with previously projected increases in high extremes under the Special Report on Emissions Scenarios climate projections, and are important to highlight due to the potential consequences on reproductive processes of in-stream species, swamp forest ecology, and socio-economy in the floodplain, amidst a growing literature that more strongly emphasises future droughts and their impact on the viability of the rainforest system over greater Amazonia

Exploitation des matrices de Mueller en vue d'applications au génie biologique et médical

L'exploitation de la matrice de Mueller permet un système d'imagerie dont le contraste est entièrement basé sur les propriétés polarimétriques du milieu observé. L'exploitation des différents contrastes de cette matrice demeure la problématique du domaine dans le cas de milieux multi-diffusants tel que les tissus biologiques. Nous proposons dans cet article une nouvelle méthode d'extraction de données polarimétriques basée sur une modélisation multi-couche du milieu observé. L'extraction de nouveaux contrastes pourrait permettre, à terme, une meilleure visualisation des pathologies dermatologiques

The myofibroblast, multiple origins for major roles in normal and pathological tissue repair

Myofibroblasts differentiate, invade and repair injured tissues by secreting and organizing the extracellular matrix and by developing contractile forces. When tissues are damaged, tissue homeostasis must be re-established, and repair mechanisms have to rapidly provide harmonious mechanical tissue organization, a process essentially supported by (myo)fibroblasts. Under physiological conditions, the secretory and contractile activities of myofibroblasts are terminated when the repair is complete (scar formation) but the functionality of the tissue is only rarely perfectly restored. At the end of the normal repair process, myofibroblasts disappear by apoptosis but in pathological situations, myofibroblasts likely remain leading to excessive scarring. Myofibroblasts originate from different precursor cells, the major contribution being from local recruitment of connective tissue fibroblasts. However, local mesenchymal stem cells, bone marrow-derived mesenchymal stem cells and cells derived from an epithelial-mesenchymal transition process, may represent alternative sources of myofibroblasts when local fibroblasts are not able to satisfy the requirement for these cells during repair. These diverse cell types probably contribute to the appearance of myofibroblast subpopulations which show specific biological properties and which are important to understand in order to develop new therapeutic strategies for treatment of fibrotic and scarring diseases

Electron-Phonon Interacation in Quantum Dots: A Solvable Model

The relaxation of electrons in quantum dots via phonon emission is hindered by the discrete nature of the dot levels (phonon bottleneck). In order to clarify the issue theoretically we consider a system of $N$ discrete fermionic states (dot levels) coupled to an unlimited number of bosonic modes with the same energy (dispersionless phonons). In analogy to the Gram-Schmidt orthogonalization procedure, we perform a unitary transformation into new bosonic modes. Since only $N(N+1)/2$ of them couple to the fermions, a numerically exact treatment is possible. The formalism is applied to a GaAs quantum dot with only two electronic levels. If close to resonance with the phonon energy, the electronic transition shows a splitting due to quantum mechanical level repulsion. This is driven mainly by one bosonic mode, whereas the other two provide further polaronic renormalizations. The numerically exact results for the electron spectral function compare favourably with an analytic solution based on degenerate perturbation theory in the basis of shifted oscillator states. In contrast, the widely used selfconsistent first-order Born approximation proves insufficient in describing the rich spectral features.Comment: 8 pages, 4 figure

Expanding the scope of leaf symbiosis: Caballeronia endophytes in Empogona and Tricalysia (Coffeeae, Rubiaceae)

Leaf symbiosis is a remarkable phenomenon observed in Rubiaceae host plants, where they interact with bacterial endophytes residing within their leaves. Although approximately 650 species from 8 genera across 4 tribes exhibit this symbiosis, its fiill extent within Rubiaceae remains unknown. Our primary objective is to investígate the potential presence of leaf endophytes in the African plant genera Empogona and Tricalysia and, if confirmed, determine their identity. To accomplish this, we extracted total DNA from the leaves of four Coffeeae tribe species {Empogona congesta, Tricalysia hensii, T. lasiodelphys, and T. semidecidua) and sequenced it. Subsequently, we filtered out bacterial reads. Through phylogenetic analysis o f the endophytes, we were able to ascertain their identity and establish their relationship with known symbiotic organisms. Notably, all four species harboured non-nodulated leaf endophytes, specifically identified as Caballeronia. Although these endophytes are distinct from one another, they are related to other nodulated and non-nodulated endophytes. Interestingly, we did not observe any discemible phylogenetic or geographic pattems among the endophytes or their host plants. Our findings demónstrate the presence of Caballeronia endophytes in the leaves o f Empogona and Tricalysia, two genera previously not associated with leaf symbiosis. This interaction is likely to have a broader distribution, and further discoveries are inevitable in the future

STM induced hydrogen desorption via a hole resonance

We report STM-induced desorption of H from Si(100)-H(2$\times1$) at negative sample bias. The desorption rate exhibits a power-law dependence on current and a maximum desorption rate at -7 V. The desorption is explained by vibrational heating of H due to inelastic scattering of tunneling holes with the Si-H 5$\sigma$ hole resonance. The dependence of desorption rate on current and bias is analyzed using a novel approach for calculating inelastic scattering, which includes the effect of the electric field between tip and sample. We show that the maximum desorption rate at -7 V is due to a maximum fraction of inelastically scattered electrons at the onset of the field emission regime.Comment: 4 pages, 4 figures. To appear in Phys. Rev. Let

First principles theory of inelastic currents in a scanning tunneling microscope

A first principles theory of inelastic tunneling between a model probe tip and an atom adsorbed on a surface is presented, extending the elastic tunneling theory of Tersoff and Hamann. The inelastic current is proportional to the change in the local density of states at the center of the tip due to the addition of the adsorbate. We use the theory to investigate the vibrational heating of an adsorbate below an STM tip. We calculate the desorption rate of H from Si(100)-H(2$\times$1) as function of the sample bias and tunnel current, and find excellent agreement with recent experimental data.Comment: 5 pages, RevTeX, epsf file