Evolutionary Chance Mutation: A Defense of the Modern Synthesis' Consensus View

[Disponible en ligne : http://hdl.handle.net/2027/spo.6959004.0002.003]International audienceOne central tenet of the Modern Evolutionary Synthesis (1930s-1950s), and the consensus view among biologists until now, is that all genetic mutations occur by "chance" or at "random" with respect to adaptation. However, the discovery of some molecular mechanisms enhancing mutation rate in response to environmental conditions has given rise to discussions among biologists, historians and philosophers of biology about the "chance" vs "directed" character of mutations (1980s-2000s). In fact, some argue that mutations due to a particular kind of mutator mechanisms challenge the Modern Synthesis because they are produced when and where needed by the organisms concerned. This paper provides a defense of the Modern Synthesis' consensus view about the chance nature of all genetic mutations by reacting to Jablonka and Lamb's analysis of genetic mutations (2005) and the explicit Lamarckian flavor of their arguments. I argue that biologists can continue to talk about chance mutations according to what I call and define as the notion of "evolutionary chance," which I claim is the Modern Synthesis' consensus view and a reformulation of Darwin's most influential idea of "chance" variation. Advances in molecular genetics are therefore significant but not revolutionary with respect to the Modern Synthesis' paradigm

Introduction - Actes du congrès de la SPS 2014

Introduction - Actes du congrès de la SPS 2014Introduction - Actes du congrès de la SPS 201

Sustainable milk-based postbiotics beverages fermented by Lactobacillus plantarum: allies in celiac disease inflammation

BackgroundCeliac disease (CeD) is an autoimmune disorder characterized by damage to the small intestine that occurs in genetically predisposed individuals after gluten consumption. Dietary exclusion is the only treatment. Gliadin is one of the main protein component of wheat gluten, and is poorly digested. Undigested peptide, p31-43, triggers several different processes, including inflammation. Intestinal organoids from CeD biopsies are good models for studying CeD inflammation. Postbiotics have been shown to modulate the effects of p31-43 in Caco-2 cells and inflammation in CeD organoids. The aims of this study was to study the anti-inflammatory activity of milk-based postbiotics from of L. plantarum.MethodsPostbiotics from L. plantarum CECT 749-fermented milk enriched with LA (linoleic acid), SCGs (Spent Coffee Grounds) and SCG oil were produced. Gliadin peptide p31-43 was used to induce inflammation on Caco2 cells. Organoids were derived from intestinal biopsies of 3 controls (CTRs) and 3 GCD (gluten containing diet)-CeD patients. NF-kB activation, a marker of inflammation, was evaluated by Western Blot analysis.ResultsThe results showed that pretreatment with all milk-based postbiotics of L. plantarum, except for SCG oil, inhibited the activation of NF-kB in the presence of the gliadin peptide in Caco-2 cells. The most efficient postbiotics, namely, milk-based postbiotics of L. plantarum with or without SCGs, could also reduce inflammation in intestinal organoids from CeD patients.ConclusionMilk-based postbiotics of L. plantarum, with or without SCGs, prevents the proinflammatory effects of gliadin on Caco-2 cells and constitutive inflammation in CeD intestinal organoids, independent of the CLA (Conjugated linoleic acid) concentration

Measurements of the pp → ZZ production cross section and the Z → 4ℓ branching fraction, and constraints on anomalous triple gauge couplings at √s = 13 TeV

Four-lepton production in proton-proton collisions, pp -> (Z/gamma*)(Z/gamma*) -> 4l, where l = e or mu, is studied at a center-of-mass energy of 13 TeV with the CMS detector at the LHC. The data sample corresponds to an integrated luminosity of 35.9 fb(-1). The ZZ production cross section, sigma(pp -> ZZ) = 17.2 +/- 0.5 (stat) +/- 0.7 (syst) +/- 0.4 (theo) +/- 0.4 (lumi) pb, measured using events with two opposite-sign, same-flavor lepton pairs produced in the mass region 60 4l) = 4.83(-0.22)(+0.23) (stat)(-0.29)(+0.32) (syst) +/- 0.08 (theo) +/- 0.12(lumi) x 10(-6) for events with a four-lepton invariant mass in the range 80 4GeV for all opposite-sign, same-flavor lepton pairs. The results agree with standard model predictions. The invariant mass distribution of the four-lepton system is used to set limits on anomalous ZZZ and ZZ. couplings at 95% confidence level: -0.0012 < f(4)(Z) < 0.0010, -0.0010 < f(5)(Z) < 0.0013, -0.0012 < f(4)(gamma) < 0.0013, -0.0012 < f(5)(gamma) < 0.0013

Liver gene therapy with intein-mediated F8 trans-splicing corrects mouse haemophilia A

: Liver gene therapy with adeno-associated viral (AAV) vectors is under clinical investigation for haemophilia A (HemA), the most common inherited X-linked bleeding disorder. Major limitations are the large size of the F8 transgene, which makes packaging in a single AAV vector a challenge, as well as the development of circulating anti-F8 antibodies which neutralise F8 activity. Taking advantage of split-intein-mediated protein trans-splicing, we divided the coding sequence of the large and highly secreted F8-N6 variant in two separate AAV-intein vectors whose co-administration to HemA mice results in the expression of therapeutic levels of F8 over time. This occurred without eliciting circulating anti-F8 antibodies unlike animals treated with the single oversized AAV-F8 vector under clinical development. Therefore, liver gene therapy with AAV-F8-N6 intein should be considered as a potential therapeutic strategy for HemA

Reconstruction of primary vertices at the ATLAS experiment in Run 1 proton–proton collisions at the LHC

This paper presents the method and performance of primary vertex reconstruction in proton–proton collision data recorded by the ATLAS experiment during Run 1 of the LHC. The studies presented focus on data taken during 2012 at a centre-of-mass energy of √s=8 TeV. The performance has been measured as a function of the number of interactions per bunch crossing over a wide range, from one to seventy. The measurement of the position and size of the luminous region and its use as a constraint to improve the primary vertex resolution are discussed. A longitudinal vertex position resolution of about 30μm is achieved for events with high multiplicity of reconstructed tracks. The transverse position resolution is better than 20μm and is dominated by the precision on the size of the luminous region. An analytical model is proposed to describe the primary vertex reconstruction efficiency as a function of the number of interactions per bunch crossing and of the longitudinal size of the luminous region. Agreement between the data and the predictions of this model is better than 3% up to seventy interactions per bunch crossing

Correction: Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential

[This corrects the article DOI: 10.1371/journal.pone.0137999.]

Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential

A major obstacle to an effective myocardium stem cell therapy has always been the delivery and survival of implanted stem cells in the heart. Better engraftment can be achieved if cells are administered as cell aggregates, which maintain their extra-cellular matrix (ECM). We have generated spheroid aggregates in less than 24 h by seeding human cardiac progenitor cells (hCPCs) onto methylcellulose hydrogel-coated microwells. Cells within spheroids maintained the expression of stemness/mesenchymal and ECM markers, growth factors and their cognate receptors, cardiac commitment factors, and metalloproteases, as detected by immunofluorescence, q-RT-PCR and immunoarray, and expressed a higher, but regulated, telomerase activity. Compared to cells in monolayers, 3D spheroids secreted also bFGF and showed MMP2 activity. When spheroids were seeded on culture plates, the cells quickly migrated, displaying an increased wound healing ability with or without pharmacological modulation, and reached confluence at a higher rate than cells from conventional monolayers. When spheroids were injected in the heart wall of healthy mice, some cells migrated from the spheroids, engrafted, and remained detectable for at least 1 week after transplantation, while, when the same amount of cells was injected as suspension, no cells were detectable three days after injection. Cells from spheroids displayed the same engraftment capability when they were injected in cardiotoxin-injured myocardium. Our study shows that spherical in vivo ready-to-implant scaffold-less aggregates of hCPCs able to engraft also in the hostile environment of an injured myocardium can be produced with an economic, easy and fast protocol

Community engagement in maternal and perinatal death surveillance and response (MPDSR): Realist review protocol

BACKGROUND: While there has been a decline in maternal and perinatal mortality, deaths remain high in sub-Saharan Africa and Asia. With the sustainable development goals (SDGs) targets to reduce maternal and perinatal mortality, more needs to be done to accelerate progress and improve survival. Maternal and perinatal death surveillance and response (MPDSR) is a strategy to identify the clinical and social circumstances that contribute to maternal and perinatal deaths. Through MPDSR, an active surveillance and response cycle is established by bringing together different stakeholders to review and address these social and clinical factors. Community engagement in MPDSR provides a strong basis for collective action to address social factors and quality of care issues that contribute to maternal and perinatal deaths. Studies have shown that community members can support identification and reporting of maternal and/or perinatal deaths. Skilled care at birth has been increasing globally, but there are still gaps in quality of care. Through MPDSR, community members can collaborate with health workers to improve quality of care. But we do not know how community engagement in MPDSR works in practice; for whom it works and what aspects work (or do not work) and why. This realist review answers the question: which strategies of community engagement in MPDSR produce which outcomes in which contexts? METHODS: For this realist review, we will identify published and grey literature by searching relevant databases for articles. We will include papers published from 2004 in all languages and from all countries. We have set up an advisory group drawn from academia, international organizations, and practitioners of both MPDSR and community engagement to guide the process. CONCLUSION: This protocol and the subsequent realist review will use theoretical approaches from the community engagement literature to generate theory on community engagement in MPDSR. Prospero registration number:  CRD4202234521