Stress-Induced Premature Senescence or Stress-Induced Senescence-Like Phenotype: One In Vivo

No consensus exists so far on the definition of cellular senescence. The narrowest definition of senescence is irreversible growth arrest triggered by telomere shortening counting cell generations (definition 1). Other authors gave an enlarged functional definition encompassing any kind of irreversible arrest of proliferative cell types induced by damaging agents or cell cycle deregulations after overexpression of proto-oncogenes (definition 2). As stress increases, the proportion of cells in “stress-induced premature senescence-like phenotype” according to definition 1 or “stress-induced premature senescence,” according to definition 2, should increase when a culture reaches growth arrest, and the proportion of cells that reached telomere-dependent replicative senescence due to the end-replication problem should decrease. Stress-induced premature senescence-like phenotype and telomere-dependent replicatively senescent cells share basic similarities such as irreversible growth arrest and resistance to apoptosis, which may appear through different pathways. Irreversible growth arrest after exposure to oxidative stress and generation of DNA damage could be as efficient in avoiding immortalisation as “telomere-dependent” replicative senescence. Probabilities are higher that the senescent cells (according to definition 2) appearing in vivo are in stress-induced premature senescence rather than in telomere-dependent replicative senescence. Examples are given suggesting these cells affect in vivo tissue (patho)physiology and aging

Modeling the growth of stylolites in sedimentary rocks

[1] Stylolites are ubiquitous pressure solution seams found in sedimentary rocks. Their morphology is shown to follow two self-affine regimes. Analyzing the scaling properties of their height over their average direction shows that (1) at small scale, they are self-affine surfaces with a Hurst exponent around 1, and (2) at large scale, they follow another self-affine scaling with Hurst exponent around 0.5. In the present paper, we show theoretically the influence of the main principal stress and the local geometry of the stylolitic interface on the dissolution reaction rate. We compute how it is affected by the deviation between the principal stress axis and the local interface between the rock and the soft material in the stylolite. The free energy entering in the dissolution reaction kinetics is expressed from the surface energy term and via integration from the stress perturbations due to these local misalignments. The resulting model shows the interface evolution at different stress conditions. In the stylolitic case, i.e., when the main principal stress is normal to the interface, two different stabilizing terms dominate at small and large scales which are linked respectively to the surface energy and to the elastic interactions. Integrating the presence of small-scale heterogeneities related to the rock properties of the grains in the model leads to the formulation of a Langevin equation predicting the dynamic evolution of the surface. This equation leads to saturated surfaces obeying the two observed scaling laws. Analytical and numerical analysis of this surface evolution model shows that the crossover length separating both scaling regimes depends directly on the applied far-field stress magnitude. This method gives the basis for the development of a paleostress magnitude marker. We apply the computation of this marker, i.e., the morphological analysis, on a stylolite found in the Dogger limestone layer located in the neighborhood of the ANDRA Underground Research Laboratory at Bure (eastern France). The results are consistent with the two scaling regimes expected, and the practical determination of the major principal paleostress, from the estimation of a crossover length, is illustrated on this example

Reduced CSF turnover and decreased ventricular Aβ42 levels are related

International audienceBACKGROUND: The appearance of Aβ42 peptide deposits is admitted to be a key event in the pathogenesis of Alzheimer's disease, although amyloid deposits also occur in aged non-demented subjects. Aβ42 is a degradation product of the amyloid protein precursor (APP). It can be catabolized by several enzymes, reabsorbed by capillaries or cleared into cerebrospinal fluid (CSF). The possible involvement of a decrease in CSF turnover in A4β2 deposit formation is up to now poorly known. We therefore investigated a possible relationship between a reduced CSF turnover and the CSF levels of the A4β2 peptide.To this aim, CSF of 31 patients with decreased CSF turnover were studied. These patients presented chronic hydrocephalus communicating or obstructive, which required surgery (ventriculostomy or ventriculo-peritoneal shunt). Nine subjects had idiopathic normal pressure hydrocephalus (iNPH), and the other 22 chronic hydrocephalus from other origins (oCH).The Aβ42 peptide concentration was measured by an ELISA test in 31 ventricular CSF samples and in 5 lumbar CSF samples from patients with communicating hydrocephalus. RESULTS: The 5 patients with lumbar CSF analysis had similar levels of lumbar and ventricular Aβ42. A significant reduction in Aβ42 ventricular levels was observed in 24 / 31 patients with hydrocephalus. The values were lower than 300 pg/ml in 5 out of 9 subjects with iNPH, and in 15 out of 22 subjects with oCH. CONCLUSION: The decrease of CSF Aβ42 seems to occur independently of the surgical hydrocephalus aetiology. This suggests that a CSF reduced turnover may play an important role in the decrease of CSF Aβ42 concentration

Generation of Priority Research Questions to Inform Conservation Policy and Management at a National Level

Integrating knowledge from across the natural and social sciences is necessary to effectively address societal tradeoffs between human use of biological diversity and its preservation. Collaborative processes can change the ways decision makers think about scientific evidence, enhance levels of mutual trust and credibility, and advance the conservation policy discourse. Canada has responsibility for a large fraction of some major ecosystems, such as boreal forests, Arctic tundra, wetlands, and temperate and Arctic oceans. Stressors to biological diversity within these ecosystems arise from activities of the country's resource-based economy, as well as external drivers of environmental change. Effective management is complicated by incongruence between ecological and political boundaries and conflicting perspectives on social and economic goals. Many knowledge gaps about stressors and their management might be reduced through targeted, timely research. We identify 40 questions that, if addressed or answered, would advance research that has a high probability of supporting development of effective policies and management strategies for species, ecosystems, and ecological processes in Canada. A total of 396 candidate questions drawn from natural and social science disciplines were contributed by individuals with diverse organizational affiliations. These were collaboratively winnowed to 40 by our team of collaborators. The questions emphasize understanding ecosystems, the effects and mitigation of climate change, coordinating governance and management efforts across multiple jurisdictions, and examining relations between conservation policy and the social and economic well-being of Aboriginal peoples. The questions we identified provide potential links between evidence from the conservation sciences and formulation of policies for conservation and resource management. Our collaborative process of communication and engagement between scientists and decision makers for generating and prioritizing research questions at a national level could be a model for similar efforts beyond Canada

Apprendre à innover dans un monde incertain

L’agriculture est aujourd’hui interpellée par la société, qui exige bien plus qu’une simple production alimentaire : aliments de qualité, services environnementaux, insertion de populations marginalisées, revitalisation des territoires ruraux, habitabilité des milieux urbains, développement de productions énergétiques… Cette ouverture des futurs agricoles incite les acteurs ruraux à expérimenter de nouveaux systèmes de production et valorisation, faisant ainsi preuve de créativité et d’obstination pour exister face aux modèles de développement dominants. Parallèlement, ces modèles dominants fondés sur la production de masse à moindre coût continuent à s’étendre, avec les promesses d’un futur basé sur les technologies vertes. Ces évolutions posent des questions. Quel type de développement durable les sociétés veulent-elles ? Comment choisir les innovations qui leur permettront d’y parvenir ? Quels rôles peuvent jouer la recherche et les politiques publiques pour favoriser l’émergence de ces innovations ? Au-delà de l’analyse des options techniques, cet ouvrage s’intéresse aux innovations sociales et institutionnelles. Il démontre que l’innovation est le résultat d’une confrontation entre des visions portées par des acteurs aux intérêts parfois divergents. Il n’y a pas de chemin unique vers un développement durable, il faut à la fois encourager l’émergence et la coexistence de différents modes d’agriculture et de systèmes alimentaires. Le succès ne dépendra pas uniquement de notre capacité à repenser les modèles existants mais également de notre volonté à nous engager dans un processus d’apprentissage dont nous sortirons forcément transformés

Innovation et développement dans les systèmes agricoles et alimentaires

L’innovation est souvent présentée comme l’un des principaux leviers pour promouvoir un développement plus durable et plus inclusif. Dans les domaines de l’agriculture et de l’alimentation, l’innovation est marquée par des spécificités liées à sa relation à la nature, mais aussi à la grande diversité d’acteurs concernés, depuis les agriculteurs jusqu’aux consommateurs, en passant par les services de recherche et de développement. L’innovation émerge des interactions entre ces acteurs, qui mobilisent des ressources et produisent des connaissances dans des dispositifs collaboratifs, afin de générer des changements. Elle recouvre des domaines aussi variés que les pratiques de production, l’organisation des marchés, ou les pratiques alimentaires. L’innovation est reliée aux grands enjeux de développement : innovation agro-écologique, innovation sociale, innovation territoriale, etc. Cet ouvrage porte un regard sur l’innovation dans les systèmes agricoles et alimentaires. Il met un accent particulier sur l’accompagnement de l’innovation, en interrogeant les méthodes et les organisations, et sur l’évaluation de l’innovation au regard de différents critères. Il s’appuie sur des réflexions portées par différentes disciplines scientifiques, sur des travaux de terrain conduits tant en France que dans de nombreux pays du Sud, et enfin sur les expériences acquises en accompagnant des acteurs qui innovent. Il combine des synthèses sur l’innovation et des études de cas emblématiques pour illustrer les propos. L’ouvrage est destiné aux enseignants, professionnels, étudiants et chercheurs

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema

The effect of the arbuscular mycorrhizal symbiosis on the production of phytochemicals in basil.

The overall objective of this thesis was to investigate how the arbuscular mycorrhizal (AM) symbiosis can affect the production of phytochemicals (antioxidants; rosmarinic and caffeic acid, RA & CA) in the shoots of basil (Ocimum basilicum L.). As a result of an increasing interest in natural/herbal medicines, more effort is now needed to produce herbal products of better quality, i.e. higher and standardised phytochemical concentrations. Thus, it was hypothesised that the naturally occurring AM fungi (AMF) could play an important role in improving the growth and phytochemical concentrations in medicinal herbs such as basil, as organic methods of cultivation are increasingly sought after to grow such plants. Despite a reasonable amount of information available in the literature on the changes of phytochemical concentrations in the roots of host plants following AM colonisation, very little is known about such processes in the aerial part of such plants. Furthermore, basil has hardly been studied as a host plant in AM research, and very little is known of its responsiveness to AM colonisation. As AMF are well known to improve phosphorus (P) uptake in their host plant, the first objective of this work was to obtain AM and non-mycorrhizal (NM) plants matched for tissue P concentrations and growth rates. Only under such conditions would it then be possible to separate benefits derived from improved plant P uptake from non-nutritional benefits. It was found that basil is highly responsive to P, and that under low or little P supply it is quite dependent on the AM symbiosis in order to grow. However, growth depressions were observed when growing basil in winter with Glomus intraradices, suggesting that the fungal symbiont can act as a strong sink of carbon (C) under such conditions. Thus, in order to obtain AM and NM plants with matched growth rates and tissue P concentrations, it was found that basil needed to be cultivated in summer in a soil/sand mixture with a ratio of 1:3 (w/w), along with 0.2 g/kg CaHPO4 and 25% of AM inoculum (AM plants). Under these conditions, AM plants grew as well as NM plants and G. caledonium and G. mosseae were shown to increase the concentrations of RA and CA in the shoots of basil, but not in roots. Such results were not an indirect effect of improved P uptake. In order to understand the mechanisms by which AMF increased RA and CA concentrations in basil, further experiments were set up to investigate the effect of 1) AM developmental stages, 2) nitrogen (N) supply and 3) phytohormone changes on the production of RA and CA in the shoots. None of these factors was found to contribute to increases in antioxidants in basil under AM symbiosis. Therefore, the mechanisms by which AMF affect RA and CA concentrations in basil still remain unknown. A final experiment was carried out to investigate the potential of an AM fungus to improve the growth of basil when challenged with a specific pathogen Fusarium oxysporum f.sp. basilici (Fob), which causes significant production losses. The results showed that inoculation of basil with G. mosseae not only improved plant growth compared to NM plants, but also conferred a protective effect against Fob. However, shoot antioxidant concentrations (RA, CA, total phenolics and essential oils) were not increased in AM plants compared to NM plants, and the mechanism of protection against Fob could not be elucidated. Due to the high variability of RA and CA concentrations obtained in AM plants in different experiments, it cannot be concluded that AMF confer an absolute advantage over uninoculated plants if the main concern is to obtain standardised concentrations of phytochemical in basil. On the other hand, the key results presented in this thesis do indicate that inoculating basil with AMF can be beneficial to improve its growth as well as antioxidant concentrations, compared to NM plants grown under similar conditions. Such results could be of potential interest to basil growers who wish to cultivate this medicinal herb organically (i.e. low P supply and no chemical fertilisers added).Thesis (Ph.D) -- University of Adelaide, School of Earth and Environmental Sciences, 200