Penetration depth study of superconducting gap structure of 2H-NbSe2

International audienceWe report measurements of the temperature dependence of both in-plane and out-of-plane penetration depths (lambda(a) and lambda(c) respectively) in 2H-NbSe2. Measurements were made with a radio-frequency tunnel diode oscillator circuit at temperatures down to 100 mK. Analysis of the anisotropic superfluid density shows that a reduced energy gap is located on one or more of the quasi-two-dimensional Nb Fermi surface sheets rather than on the Se sheet, in contrast with some previous reports. This result suggests that the gap structure is not simply related to the weak electron-phonon coupling on the Se sheet and is therefore important for microscopic models of anisotropic superconductivity in this compound

Uterine B cells exhibit regulatory properties during the peri-implantation stage of murine pregnancy

A successful outcome to pregnancy is dependent on the ability of the maternal uterine microenvironment to regulate inflammation processes and establish maternal tolerance. Recently, B cells have been shown to influence pregnancy outcomes as aberrations in their numbers and functions are associated with obstetric complications. In this study, we aimed to comprehensively examine the population frequency and phenotypic profile of B cells over the course of murine pregnancy. Our results demonstrated a significant expansion in B cells within the uterus during the peri-implantation period, accompanied by alterations in B cell phenotype. Functional evaluation of uterine B cells purified from pregnant mice at day 5.5 post-coitus established their regulatory capacity as evidenced by effective suppression of proliferation and activation of syngeneic CD4+ T cells. Flow cytometric analysis revealed that the uterine B cell population has an expanded pool of IL-10-producing B cells bearing upregulated expression of co-stimulatory molecules CD80 and CD86 and activation marker CD27. Our investigations herein demonstrate that during the critical stages surrounding implantation, uterine B cells are amplified and phenotypically modified to act in a regulatory manner that potentially contributes toward the establishment of maternal immunological tolerance in early pregnancy.Ruth Marian Guzman-Genuino, Preethi Eldi, Pablo Garcia-Valtanen, John D. Hayball and Kerrilyn R. Diene

Improved constraints on the expansion rate of the Universe up to z~1.1 from the spectroscopic evolution of cosmic chronometers

We present new improved constraints on the Hubble parameter H(z) in the redshift range 0.15 < z < 1.1, obtained from the differential spectroscopic evolution of early-type galaxies as a function of redshift. We extract a large sample of early-type galaxies (\sim11000) from several spectroscopic surveys, spanning almost 8 billion years of cosmic lookback time (0.15 < z < 1.42). We select the most massive, red elliptical galaxies, passively evolving and without signature of ongoing star formation. Those galaxies can be used as standard cosmic chronometers, as firstly proposed by Jimenez & Loeb (2002), whose differential age evolution as a function of cosmic time directly probes H(z). We analyze the 4000 {\AA} break (D4000) as a function of redshift, use stellar population synthesis models to theoretically calibrate the dependence of the differential age evolution on the differential D4000, and estimate the Hubble parameter taking into account both statistical and systematical errors. We provide 8 new measurements of H(z) (see Tab. 4), and determine its change in H(z) to a precision of 5-12% mapping homogeneously the redshift range up to z \sim 1.1; for the first time, we place a constraint on H(z) at z \neq 0 with a precision comparable with the one achieved for the Hubble constant (about 5-6% at z \sim 0.2), and covered a redshift range (0.5 < z < 0.8) which is crucial to distinguish many different quintessence cosmologies. These measurements have been tested to best match a \Lambda CDM model, clearly providing a statistically robust indication that the Universe is undergoing an accelerated expansion. This method shows the potentiality to open a new avenue in constrain a variety of alternative cosmologies, especially when future surveys (e.g. Euclid) will open the possibility to extend it up to z \sim 2.Comment: 34 pages, 15 figures, 6 tables, published in JCAP. It is a companion to Moresco et al. (2012b, http://arxiv.org/abs/1201.6658) and Jimenez et al. (2012, http://arxiv.org/abs/1201.3608). The H(z) data can be downloaded at http://www.physics-astronomy.unibo.it/en/research/areas/astrophysics/cosmology-with-cosmic-chronometer

Regulatory B cells: dark horse in pregnancy immunotherapy?

There are many unanswered questions surrounding the function of immune cells and how they interact with the reproductive system to support successful pregnancy or contribute to pregnancy pathologies. Whilst the role of immune cells such as uterine natural killer and dendritic cells, and more recently regulatory T cells have been established, the role of another major immune cell population, the B cell, and particularly the regulatory B cells, is relatively poorly understood. This review outlines what is known about B cell subsets in the context of pregnancy, what constitutes a regulatory B cell and what role they may play, particularly during early pregnancy. Lastly, we discuss why immunotherapies for the treatment of pregnancy disorders are not widely progressed clinically and speculate on the potential of functional regulatory B cells as the basis of novel immunotherapeutic approaches for the treatment of immune-based pregnancy pathologies.Ruth Marian Guzman-Genuino, John D. Hayball and Kerrilyn R. Diene

Non-vitamin-K oral anticoagulants (NOACs) for the prevention of secondary stroke

Introduction: In patients with atrial fibrillation (AF), oral anticoagulation with vitamin K antagonists (VKA) (warfarin, phenprocoumon) is effective both for primary and secondary stroke prevention with a 60–70% relative reduction in stroke risk compared with placebo. Mortality is reduced by 26%. VKA have a number of well-documented shortcomings which were overcome by non-vitamin-K oral anticoagulants (NOACs). Areas covered: Results of randomized trials for four NOACs (apixaban, dabigatran, edoxaban, rivaroxaban) have been published (ARISTOTLE, RE-LY, ENGAGE, ROCKET-AF). In this review, the authors discuss the results in subgroups of patients with prior transient ischemic attacks or ischemic stroke. In aggregate, the NOACs are superior to warfarin for secondary prevention and result in a 50% reduction in intracerebral hemorrhage. Apixaban was superior to aspirin in the AVERROES trial and had a similar rate of major bleeding complications. Expert opinion: NOACs add to the therapeutic options for secondary stroke prevention in patients with AF and offer advantages over warfarin including a favorable bleeding profile and convenience of use. Aspirin should no longer be used for secondary stroke prevention in patients with AF. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group

Review and update of the concept of embolic stroke of undetermined source

Ischaemic strokes have traditionally been classified according to the TOAST criteria, in which strokes with unclear aetiology are classified as cryptogenic strokes. However, the definition of cryptogenic stroke did not meet the operational criteria necessary to define patient populations for randomized treatment trials. To address this problem, the concept of embolic stroke of undetermined source (ESUS) was developed and published in 2014. A hypothesis that underpinned this concept was that most strokes in patients with ESUS are caused by embolic events, perhaps many cardioembolic, and that anticoagulation would prevent secondary ischaemic events. On this basis, two large randomized trials were conducted to compare the non-vitamin K antagonist oral anticoagulants (NOACs) dabigatran and rivaroxaban with aspirin. Neither NOAC was superior to aspirin in these trials, although subgroups of patients with ESUS seemed to benefit specifically from anticoagulation or antiplatelet therapy. The neutral results of the trials of anticoagulation and insights into ESUS from research conducted since the concept was introduced warrant reassessment of the ESUS construct as a research concept and a treatment target. In this Review, we discuss the evidence produced since the concept of ESUS was introduced, and propose updates to the criteria and diagnostic algorithm in light of the latest knowledge. © 2022, Springer Nature Limited

Trophoblasts promote induction of a regulatory phenotype in B cells that can protect against detrimental T cell-mediated inflammation

PROBLEM:A successful outcome to pregnancy is critically dependent on the initiation of maternal immune tolerance before embryo implantation. Cells of embryonic origin that come in contact with the uterine microenvironment can exert influence over the phenotype and function of immune cells to facilitate robust implantation, however what influence they may have on B cells remains unknown. In this study, we investigate the effect of human trophoblast cells on B cell phenotype and the subsequent effect on peri-implantation events. METHOD OF STUDY:We cultured purified human B cells with the first trimester human trophoblast cell line Swan-71 to investigate trophoblast-B cell interactions and utilized trophoblast spheroids in an in vitro implantation model of migration and invasion. RESULTS:Trophoblast-educated B cells or TE-B cells were found to consist of B cells in committed lineages such as plasmablasts and memory B cells, as well as increased proportions in subsets of CD24hi CD27+ regulatory B cells and CD19+ IL-10+ B cells. Conditioned media from the TE-B cells showed reduced production of pro-inflammatory cytokines that influenced the T cell proliferation and cytokine production. Using trophoblast spheroids, we assessed the role of TE-B cells in trophoblast invasion and migration. Our results demonstrate a protective effect of TE-B conditioned media against deleterious inflammation as evidenced by survival of the trophoblast spheroid in the presence of an immune assault and promotion of a migratory phenotype. CONCLUSION:We posit that trophoblast-mediated education of B cells leads to their acquisition of properties capable of modulating inflammation in the uterine environment during the peri-implantation period. This article is protected by copyright. All rights reserved.Ruth Marian Guzman‐Genuino, Tanya Dimova, Yuan You, Paulomi Aldo, John D. Hayball, Gil Mor, Kerrilyn R. Diene

Maternal host responses to poly(I:C) during pregnancy leads to both dysfunctional immune profiles and altered behaviour in the offspring

Problem: Autism spectrum disorder (ASD)-like phenotypes in murine models are linked to elevated proinflammatory cytokine profiles caused by maternal immune activation (MIA) but whether MIA alters the immune response in the offspring remains unclear. Method of Study: Polyinosinic:polycytidylic acid (poly:[IC]) was used to induce MIA in immunocompetent and control TLR3-deficient pregnant mice and cytokine levels were measured in maternal and fetal organs. Furthermore, cytokines and behaviour responses were tested after challenge with lipopolysaccharide in 7-day-old and adult mice. Results: MIA induced on E12 resulted in changes in the cytokine expression profile in maternal and fetal organs and correlated with TNFα and IL-18 dysregulation in immune organs and brains from neonatal mice born to MIA-induced dams. Such changes further correlated with altered behavioural responses in adulthood. Conclusion: MIA induced by pathogens during pregnancy can interfere with the development of the fetal immune and nervous systems leading to dysfunctional immune responses and behaviour in offspring.Pablo Garcia-Valtanen, Bianca A. van Diermen, Nerissa Lakhan, Erin L. Lousberg, Sarah A. Robertson, John D. Hayball, Kerrilyn R. Diene

High mobility group box protein 1 neutralization therapy in ovine bacteremia: lessons learned from an ovine septic shock model incorporating intensive care support

Sepsis is a highly complex and often fatal syndrome which varies widely in its clinical manifestations, and therapies that target the underlying uncontrolled immune status in sepsis are needed. The failure of preclinical approaches to provide significant sepsis survival benefit in the clinic is often attributed to inappropriate animal disease models. It has been demonstrated that high mobility group box protein 1 (HMGB1) blockade can reduce inflammation, mortality and morbidity in experimental sepsis without promoting immunosuppression. Within this study, we explored the use of ovine anti-HMGB1 antibodies in a model of ovine septic shock incorporating intensive care supports (OSSICS). Results: Septic sheep exhibited elevated levels of HMGB1 within 12 h after the induction of sepsis. In this study, sepsis was induced in six anaesthetized adult Border Leicester × Merino ewes via intravenous instillation of E. coli and sheep monitored according to intensive care unit standard protocols for 26 h, with the requirement for noradrenaline as the primary endpoint. Septic sheep exhibited a hyperdynamic circulation, renal dysfunction, deranged coagulation profile and severe metabolic acidosis. Sheep were assigned a severity of illness score, which increased over time. While a therapeutic effect of intravenous anti-HMGB1 antibody could not be observed in this model due to limited animal numbers, a reduced bacterial dose induced a septic syndrome of much lower severity. With modifications including a reduced bacterial dose, a longer timeframe and broad spectrum antibiotics, the OSSICS model may become a robust tool for preclinical assessment of sepsis therapeutics.Natalie E. Stevens, Coralie H. Nash, Cara K. Fraser, Tim R. Kuchel, Matthew J. Maiden, Marianne J. Chapman, Kerrilyn R. Diener, and John D. Haybal