In Situ Fe and S isotope analyses in pyrite from the 3.2 Ga Mendon Formation (Barberton Greenstone Belt, South Africa): Evidence for early microbial iron reduction

International audienceOn the basis of phylogenetic studies and laboratory cultures, it has been proposed that the ability of microbes to metabolize iron has emerged prior to the Archaea/ Bacteria split. However, no unambiguous geochemical data supporting this claim have been put forward in rocks older than 2.7-2.5 giga years (Gyr). In the present work, we report in situ Fe and S isotope composition of pyrite from 3.28-to 3.26-Gyr-old cherts from the upper Mendon Formation, South Africa. We identified three populations of microscopic pyrites showing a wide range of Fe isotope compositions, which cluster around two δ 56 Fe values of −1.8‰ and +1‰. These three pyrite groups can also be distinguished based on the pyrite crystallinity and the S isotope mass-independent signatures. One pyrite group displays poorly crystallized pyrite minerals with positive Δ 33 S values > +3‰, while the other groups display more variable and closer to 0‰ Δ 33 S values with recrystallized pyrite rims. It is worth to note that all the pyrite groups display positive Δ 33 S values in the pyrite core and similar trace element compositions

Lung transplantation after allogeneic stem cell transplantation : a pan-European experience

Late-onset noninfectious pulmonary complications (LONIPCs) affect 6% of allogeneic stem cell transplantation (SCT) recipients within 5 years, conferring subsequent 5-year survival of 50%. Lung transplantation is rarely performed in this setting due to concomitant extrapulmonary morbidity, excessive immunosuppression and concerns about recurring malignancy being considered contraindications. This study assesses survival in highly selected patients undergoing lung transplantation for LONIPCs after SCT. SCT patients undergoing lung transplantation at 20 European centres between 1996 and 2014 were included. Clinical data pre- and post-lung transplantation were reviewed. Propensity score-matched controls were generated from the Eurotransplant and Scandiatransplant registries. Kaplan-Meier survival analysis and Cox proportional hazard regression models evaluating predictors of graft loss were performed. Graft survival at 1, 3 and 5 years of 84%, 72% and 67%, respectively, among the 105 SCT patients proved comparable to controls (p=0.75). Sepsis accounted for 15 out of 37 deaths (41%), with prior mechanical ventilation (HR 6.9, 95% CI 1.0-46.7; p Lung transplantation outcomes following SCT were comparable to other end-stage diseases. Lung transplantation should be considered feasible in selected candidates. No SCT-specific factors influencing outcome were identified within this carefully selected patient cohort.Peer reviewe

Liposomal antagomiR-155-5p restores anti-inflammatory macrophages and improves arthritis in preclinical models of rheumatoid arthritis

Objective: We previously reported an increased expression of microRNA‐155 (miR‐155) in the blood monocytes of patients with rheumatoid arthritis (RA) that could be responsible for impaired monocyte polarization to anti‐inflammatory M2‐like macrophages. In this study, we employed two preclinical models of RA, collagen‐induced arthritis and K/BxN serum transfer arthritis, to examine the therapeutic potential of antagomiR‐155‐5p entrapped within PEGylated (polyethylene glycol [PEG]) liposomes in resolution of arthritis and repolarization of monocytes towards the anti‐inflammatory M2 phenotype. Methods: AntagomiR‐155‐5p or antagomiR‐control were encapsulated in PEG liposomes of 100 nm in size and −10 mV in zeta potential with high antagomiR loading efficiency (above 80%). Mice were injected intravenously with 1.5 nmol/100 μL PEG liposomes containing antagomiR‐155‐5p or control after the induction of arthritis. Results: We demonstrated the biodistribution of fluorescently tagged PEG liposomes to inflamed joints one hour after the injection of fluorescently tagged PEG liposomes, as well as the liver's subsequent accumulation after 48 hours, indicative of hepatic clearance, in mice with arthritis. The injection of PEG liposomes containing antagomiR‐155‐5p decreased arthritis score and paw swelling compared with PEG liposomes containing antagomiR‐control or the systemic delivery of free antagomiR‐155‐5p. Moreover, treatment with PEG liposomes containing antagomiR‐155‐5p led to the restoration of bone marrow monocyte defects in anti‐inflammatory macrophage differentiation without any significant functional change in other immune cells, including splenic B and T cells. Conclusion: The injection of antagomiR‐155‐5p encapsulated in PEG liposomes allows the delivery of small RNA to monocytes and macrophages and reduces joint inflammation in murine models of RA, providing a promising strategy in human disease.imag

Community-Level Responses to Iron Availability in Open Ocean Plankton Ecosystems

Predicting responses of plankton to variations in essential nutrients is hampered by limited in situ measurements, a poor understanding of community composition, and the lack of reference gene catalogs for key taxa. Iron is a key driver of plankton dynamics and, therefore, of global biogeochemical cycles and climate. To assess the impact of iron availability on plankton communities, we explored the comprehensive bio-oceanographic and bio-omics data sets from Tara Oceans in the context of the iron products from two state-of-the-art global scale biogeochemical models. We obtained novel information about adaptation and acclimation toward iron in a range of phytoplankton, including picocyanobacteria and diatoms, and identified whole subcommunities covarying with iron. Many of the observed global patterns were recapitulated in the Marquesas archipelago, where frequent plankton blooms are believed to be caused by natural iron fertilization, although they are not captured in large-scale biogeochemical models. This work provides a proof of concept that integrative analyses, spanning from genes to ecosystems and viruses to zooplankton, can disentangle the complexity of plankton communities and can lead to more accurate formulations of resource bioavailability in biogeochemical models, thus improving our understanding of plankton resilience in a changing environment

Helios Is Associated with CD4 T Cells Differentiating to T Helper 2 and Follicular Helper T Cells In Vivo Independently of Foxp3 Expression

Although in vitro IL-4 directs CD4 T cells to produce T helper 2 (Th2)-cytokines, these cytokines can be induced in vivo in the absence of IL-4-signalling. Thus, mechanism(s), different from the in vitro pathway for Th2-induction, contribute to in vivo Th2-differentiation. The pathway for in vivo IL-4-independent Th2-differentiation has yet to be characterized. - upregulate Th1 features - T-bet and IFN-γ - but not Helios. In addition, CD4 T cells induced to produce Th2 cytokines in vitro do not express Helios. The kinetics of Helios mRNA and protein induction mirrors that of GATA-3. The induction of IL-4, IL-13 and CXCR5 by alumOVA requires NF-κB1 and this is also needed for Helios upregulation. Importantly, Helios is induced in Th2 and TFh cells without parallel upregulation of Foxp3. These findings suggested a key role for Helios in Th2 and TFh development in response to alum-protein vaccines. We tested this possibility using Helios-deficient OTII cells and found this deficiency had no discernable impact on Th2 and TFh differentiation in response to alumOVA.Helios is selectively upregulated in CD4 T cells during Th2 and TFh responses to alum-protein vaccines in vivo, but the functional significance of this upregulation remains uncertain

Regulation of cortical stability by RhoGEF3 in mitotic Sensory Organ Precursor cells in Drosophila

International audienceIn epithelia, mitotic cells round up and push against their neighbors to divide. Mitotic rounding results from increased assembly of F-actin and cortical recruitment of Myosin II, leading to increased cortical stability. Whether this process is developmentally regulated is not well known. Here, we examined the regulation of cortical stability in Sensory Organ Precursor cells (SOPs) in the Drosophila pupal notum. SOPs differed in apical shape and actomyosin dynamics from their epidermal neighbors prior to division, and appeared to have a more rigid cortex at mitosis. We identified RhoGEF3 as an actin regulator expressed at higher levels in SOPs, and showed that RhoGEF3 had in vitro GTPase Exchange Factor (GEF) activity for Cdc42. Additionally, RhoGEF3 genetically interacted with both Cdc42 and Rac1 when overexpressed in the fly eye. Using a null RhoGEF3 mutation generated by CRISPR-mediated homologous recombination, we showed using live imaging that the RhoGEF3 gene, despite being dispensable for normal development, contributed to cortical stability in dividing SOPs. We therefore suggest that cortical stability is developmentally regulated in dividing SOPs of the fly notum

0548: Heart failure with preserved ejection fraction: an echocardiographic based approach to assess the prognosis. A report from the large prospective KaRen study

BackgroundKaRen is a prospective study designed to characterize and follow a cohort of heart failure with preserved ejection fraction (HFpEF) patients. HFpEF remains a challenging syndrome. Patients have clinical signs linked to congestion but left ventricular (LV) EF is > 45%. We sought to test the relevance of echocardiographic parameters as predictors of death or hospitalization for cardiovascular reasons.Methods and resultsFollowing an acute HF accompanied with NT-proBNP >300pg/ml (BNP >100pg/ml) and LVEF >45%, patients were included (n=349). The patients were reassessed by echo-Doppler after 4-8 weeks. Echocardiographies were standardized and the analysis centralized. LVEF was 62±13%, LV global longitudinal strain: – 15±3%, E/e’:12.9±6.2, Left atrial volume: 49±18ml/m², Tricuspid regurgitation: 2.9±0.9m/s. Two parameters are correlated with the survival without any death or hospitalisation for cardiovascular reason and could be combined in a score: 2 x (E / e’) + RA area. This score has a theoretical range between 0 and 14. Based on tertiles of the score, censoring (frequencies of death or hospitalization for heart failure) were 48 (37.80), 67 (57.76) and 85 (75.22) in the 1st tertile – poor prognosis (N = 127), the 2nd tertile – intermediate (N = 116) and the 3rd tertile – good prognosis (N = 113), respectively.ConclusionCombination of simple echocardiographic criteria (right atrial area and E/e’ ratio) was found relevant to predict the long term prognosis in a large cohort of patients diagnosed for heart failure with preserved ejection fraction

Value of exercise echocardiography in heart failure with preserved ejection fraction: a substudy from the KaRen study

International audienceBackground KaRen is a multicentre study designed to characterize and follow patients with heart failure and preserved ejection fraction (HFpEF). In a subgroup of patients with clinical signs of congestion but left ventricular ejection fraction (LVEF) \textgreater45%, we sought to describe and analyse the potential prognostic value of echocardiographic parameters recorded not only at rest but also during a submaximal exercise stress echocardiography. Exercise-induced changes in echo parameters might improve our ability to characterize HFpEF patients.Method and results Patients were prospectively recruited in a single tertiary centre following an acute HF episode with NT-pro-BNP \textgreater300 pg/mL (BNP \textgreater 100 pg/mL) and LVEF \textgreater 45% and reassessed by exercise echo-Doppler after 4–8 weeks of dedicated treatment. Image acquisitions were standardized, and analysis made at end of follow-up blinded to patients' clinical status and outcome. In total, 60 patients having standardized echocardiographic acquisitions were included in the analysis. Twenty-six patients (43%) died or were hospitalized for HF (primary outcome). The mean ± SD workload was 45 ± 14 watts (W). Mean ± SD resting LVEF and LV global longitudinal strain was 57.6 ± 9.5% and −14.5 ± 4.2%, respectively. Mean ± SD resting E/e′ was 11.3 ± 4.7 and 13.1 ± 5.3 in those patients who did not and those who did experience the primary outcome, respectively (P = 0.03). Tricuspid regurgitation (TR) peak velocity during exercise were 3.3 ± 0.5 and 3.7 ± 0.5 m/s (P = 0.01). Exercise TR was independently associated with HF-hospitalization or death after adjustment on baseline clinical and biological characteristics.Conclusion Exercise echocardiography may contribute to identify HFpEF patients and especially high-risk ones. Our study suggested a prognostic value of TR recorded during an exercise. That was demonstrated independently of the value of resting E/e

Importance of combined left atrial size and estimated pulmonary pressure for clinical outcome in patients presenting with heart failure with preserved ejection fraction

International audienceAims: Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome with various phenotypes and outcomes. The prognostic relevance of echocardiography and the E/e' ratio has previously been reported. We sought to study in addition, the value of estimated pulmonary pressure and left atrial size for diagnosing and determining a prognosis for HFpEF-patients in a prospective multi-centric cohort. Methods and results: Patients with an acute-HF event accompanied with NT-proBNP >300 pg/mL (BNP >100 pg/mL) and LVEF >45% were included (n = 237) and clinically reassessed using echo-Doppler after 4-8 weeks of HF treatment as part of the prospective KaRen HFpEF study. A core-centre performed the echocardiographic analyses. A combined primary endpoint of either HF hospitalizations and mortality over a span of 18-month, or simply mortality (secondary endpoint) were used. The mean LVEF was 62 ± 7%, E/e':12.9 ± 6.0, left atrial volume index (LAVI): 48.1 ± 15.9 ml/m2, TR: 2.9 ± 0.9 m/s. Patients with both LAVI > 40 ml/m2 and TR > 3.1 m/s had a significantly greater risk of death or heart failure related hospitalization than others (P = 0.014 after adjustment). Conclusion: The combination of enlarged LA and elevated estimated pulmonary pressure has a strong prognostic impact in patients suffering from HFpEF. Our results indicate that such patients constitute a risk group in HFpEF which requires dedicated medical attention. ClinicalTrials.gov: NCT00774709

Heart failure with a preserved ejection fraction additive value of an exercise stress echocardiography.

International audienceBACKGROUND: Heart failure (HF) with a preserved (P) left ventricular (LV) ejection fraction (EF) is common, though its diagnosis and physiopathology remains unclear. We sought to analyse the myocardial characteristics at rest and during a sub-maximal exercise test in patients with HFPEF. METHODS AND RESULTS: Standardized sub-maximal exercise stress echocardiography was performed in (i) 21 patients from the Karolinska Rennes Prospective Study of Heart Failure with Preserved Left Ventricular Ejection Fraction HFPEF registry, whose LVEF was ≥45% and (ii) 15 control patients free of any manifestations of HF. During a sub-maximal exercise test, LV systolic function measured as a global four-chamber longitudinal strain was -17±5% in patients with HFPEF vs. -22±4% in controls (P<0.001), LV longitudinal diastolic relaxation, expressed as e' (septal and lateral walls averaged) was 9±2 cm/s in patients vs. 15±4 cm/s in controls (P<0.001), and RV longitudinal systolic function, expressed as RV s', was 14±3 cm/s in patients vs. 18±1 cm/s in controls (P=0.03). LV afterload (arterial elastance) was 2.7±1 mmHg/mL and was correlated with a decrease in LV longitudinal strain (R=0.51, P<0.01) during exercise. CONCLUSION: The assessment of longitudinal systolic and diastolic LV and RV functions is valuable during a sub-maximal exercise stress echocardiography to confirm the heart dysfunction related to the HFPEF symptoms. It might be used as a diagnostic test for difficult clinical situations. ClinicalTrials.gov identifier: NCT01091467