Stable interaction between α5β1 integrin and Tie2 tyrosine kinase receptor regulates endothelial cell response to Ang-1

During angiogenic remodeling, Ang-1, the ligand of Tie2 tyrosine kinase, is involved in vessel sprouting and stabilization through unclear effects on nascent capillaries and mural cells. In our study, we hypothesized that the Ang-1/Tie2 system could crosstalk with integrins, and be influenced by the dynamic interactions between extracellular matrix and endothelial cells (ECs). Here, we show that α5β1 specifically sensitizes and modulates Tie2 receptor activation and signaling, allowing EC survival at low concentrations of Ang-1 and inducing persistent EC motility. Tie2 and α5β1 interact constitutively; α5β1 binding to fibronectin increases this association, whereas Ang-1 stimulation recruits p85 and FAK to this complex. Furthermore, we demonstrate that Ang-1 is able to mediate selectively α5β1 outside-in FAK phosphorylation. Thus, Ang-1 triggers signaling pathways through Tie2 and α5β1 receptors that could crosstalk when Tie2/α5β1 interaction occurs in ECs plated on fibronectin. By using blocking antibodies, we consistently found that α5β1, but not αvβ3 activation, is essential to Ang-1-dependent angiogenesis in vivo. © The Rockefeller University Press

Conservation actions for restoring the coastal lagoon habitats: Strategy and multidisciplinary approach of LIFE Lagoon Refresh

The Habitat Directive of European Union lists Costal Lagoons (habitat code 1150*) among priority habitats because they are in danger of disappearance. Natural ecosystems may recover from anthropogenic perturbations; however, the recovery can follow natural restoration or it can be redirected through ecological restoration by anthropogenic intervention. Accordingly, by collecting the available theoretical indications for restoration of estuarine and coastal areas, a methodological approach was detailed andit can be summarised into five issues: (i) Environmental context from which it began; (ii) Desired state to be achieved; (iii) Policies and socio-economic context; (iv) Typology of recovery and/or improvement of habitats and ecosystems; and (v) Methods for monitoring the impact of the project. The project strategy, management and measures of LIFE Lagoon Refresh were also presented and discussed, as a case study for the implementation of the multidisciplinary approach for restoration ecology in transitional waters. The project takes place in the northern Venice Lagoon (Italy), started in 2017 and it lasts 5 years. In the Venice Lagoon, since the 20th century, strong reductions of the typical salinity gradient of buffer areas between lagoon and mainland, and of reedbed extensions have occurred due to historic human interventions, with negative consequences on coastal lagoon habitats. To improve the conservation status of habitats and biodiversity of the area, the LIFE Lagoon Refresh project included several conservative actions, which are (i) the diversion of a freshwater flow from the Sile River into the lagoon; (ii) the restoration of intertidal morphology, through biodegradable structures; (iii) the reed and aquatic angiosperm transplantations with the involvement of local fishermen and hunters, and (iv) the reduction of hunting and fishing pressures in the intervention area. To achieve the restoration of the lagoon environment, the strategy of the project covered a combination of different aspects and tools, such as planning activities, through the involvement of local Institutions and communities; stakeholder's involvement to increase awareness of environment conservation and socioeconomic value improvement; an ecological engineering approach; numerical models as supporting tool for planning and managing of conservation actions; environmental monitoring performed before and after the conservation actions

Conservation actions for restoring the coastal lagoon habitats: Strategy and multidisciplinary approach of LIFE Lagoon Refresh

The Habitat Directive of European Union lists Costal Lagoons (habitat code 1150*) among priority habitats because they are in danger of disappearance. Natural ecosystems may recover from anthropogenic perturbations; however, the recovery can follow natural restoration or it can be redirected through ecological restoration by anthropogenic intervention. Accordingly, by collecting the available theoretical indications for restoration of estuarine and coastal areas, a methodological approach was detailed andit can be summarised into five issues: (i) Environmental context from which it began; (ii) Desired state to be achieved; (iii) Policies and socio-economic context; (iv) Typology of recovery and/or improvement of habitats and ecosystems; and (v) Methods for monitoring the impact of the project. The project strategy, management and measures of LIFE Lagoon Refresh were also presented and discussed, as a case study for the implementation of the multidisciplinary approach for restoration ecology in transitional waters. The project takes place in the northern Venice Lagoon (Italy), started in 2017 and it lasts 5 years. In the Venice Lagoon, since the 20th century, strong reductions of the typical salinity gradient of buffer areas between lagoon and mainland, and of reedbed extensions have occurred due to historic human interventions, with negative consequences on coastal lagoon habitats. To improve the conservation status of habitats and biodiversity of the area, the LIFE Lagoon Refresh project included several conservative actions, which are (i) the diversion of a freshwater flow from the Sile River into the lagoon; (ii) the restoration of intertidal morphology, through biodegradable structures; (iii) the reed and aquatic angiosperm transplantations with the involvement of local fishermen and hunters, and (iv) the reduction of hunting and fishing pressures in the intervention area. To achieve the restoration of the lagoon environment, the strategy of the project covered a combination of different aspects and tools, such as planning activities, through the involvement of local Institutions and communities; stakeholder’s involvement to increase awareness of environment conservation and socioeconomic value improvement; an ecological engineering approach; numerical models as supporting tool for planning and managing of conservation actions; environmental monitoring performed before and after the conservation actions

Continuous pulse advances in the negative ion source NIO1

Consorzio RFX and INFN-LNL have designed, built and operated the compact radiofrequency negative ion source NIO1 (Negative Ion Optimization phase 1) with the aim of studying the production and acceleration of H- ions. In particular, NIO1 was designed to keep plasma generation and beam extraction continuously active for several hours. Since 2020 the production of negative ions at the plasma grid (the first grid of the acceleration system) has been enhanced by a Cs layer, deposited though active Cs evaporation in the source volume. For the negative ion sources applied to fusion neutral beam injectors, it is essential to keep the beam current and the fraction of co-extracted electrons stable for at least 1 h, against the consequences of Cs sputtering and redistribution operated by the plasma. The paper presents the latest results of the NIO1 source, in terms of caesiation process and beam performances during continuous (6{\div}7 h) plasma pulses. Due to the small dimensions of the NIO1 source (20 x (diam.)10 cm), the Cs density in the volume is high (10^15 \div 10^16 m^-3) and dominated by plasma-wall interaction. The maximum beam current density and minimum fraction of co-extracted electrons were respectively about 30 A/m^2 and 2. Similarly to what done in other negative ion sources, the plasma grid temperature in NIO1 was raised for the first time, up to 80 {\deg}C, although this led to a minimal improvement of the beam current and to an increase of the co-extracted electron current.Comment: 11 pages, 7 figures. Contributed paper for the 8th International symposium on Negative Ions, Beams and Sources - NIBS'22. Revision 1 of the preprint under evaluation at Journal of Instrumentation (JINST

Evidence for directional selection at a novel major histocompatibility class I marker in wild common frogs (Rana temporaria) exposed to a viral pathogen (Ranavirus).

(c) 2009 Teacher et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Whilst the Major Histocompatibility Complex (MHC) is well characterized in the anuran Xenopus, this region has not previously been studied in another popular model species, the common frog (Rana temporaria). Nor, to date, have there been any studies of MHC in wild amphibian host-pathogen systems. We characterise an MHC class I locus in the common frog, and present primers to amplify both the whole region, and specifically the antigen binding region. As no more than two expressed haplotypes were found in over 400 clones from 66 individuals, it is likely that there is a single class I locus in this species. This finding is consistent with the single class I locus in Xenopus, but contrasts with the multiple loci identified in axolotls, providing evidence that the diversification of MHC class I into multiple loci likely occurred after the Caudata/Anura divergence (approximately 350 million years ago) but before the Ranidae/Pipidae divergence (approximately 230 mya). We use this locus to compare wild populations of common frogs that have been infected with a viral pathogen (Ranavirus) with those that have no history of infection. We demonstrate that certain MHC supertypes are associated with infection status (even after accounting for shared ancestry), and that the diseased populations have more similar supertype frequencies (lower F(ST)) than the uninfected. These patterns were not seen in a suite of putatively neutral microsatellite loci. We interpret this pattern at the MHC locus to indicate that the disease has imposed selection for particular haplotypes, and hence that common frogs may be adapting to the presence of Ranavirus, which currently kills tens of thousands of amphibians in the UK each year

Effects of Paramagnetic Ferrocenium Cations on the Magnetic Properties of the Anionic Single-Molecule Magnet [Mn12O12(O2CC6F5)16(H2O)4]-

The preparation and physical characterization are reported for several single-molecule magnet salts to investigate the effects of paramagnetic cations on the magnetization relaxation behavior of [Mn12]- anionic single-molecule magnets.Comment: 30 pages, 5 tables, 15 figure

Genome-Wide Transcriptional Response of Silurana (Xenopus) tropicalis to Infection with the Deadly Chytrid Fungus

Emerging infectious diseases are of great concern for both wildlife and humans. Several highly virulent fungal pathogens have recently been discovered in natural populations, highlighting the need for a better understanding of fungal-vertebrate host-pathogen interactions. Because most fungal pathogens are not fatal in the absence of other predisposing conditions, host-pathogen dynamics for deadly fungal pathogens are of particular interest. The chytrid fungus Batrachochytrium dendrobatidis (hereafter Bd) infects hundreds of species of frogs in the wild. It is found worldwide and is a significant contributor to the current global amphibian decline. However, the mechanism by which Bd causes death in amphibians, and the response of the host to Bd infection, remain largely unknown. Here we use whole-genome microarrays to monitor the transcriptional responses to Bd infection in the model frog species, Silurana (Xenopus) tropicalis, which is susceptible to chytridiomycosis. To elucidate the immune response to Bd and evaluate the physiological effects of chytridiomycosis, we measured gene expression changes in several tissues (liver, skin, spleen) following exposure to Bd. We detected a strong transcriptional response for genes involved in physiological processes that can help explain some clinical symptoms of chytridiomycosis at the organismal level. However, we detected surprisingly little evidence of an immune response to Bd exposure, suggesting that this susceptible species may not be mounting efficient innate and adaptive immune responses against Bd. The weak immune response may be partially explained by the thermal conditions of the experiment, which were optimal for Bd growth. However, many immune genes exhibited decreased expression in Bd-exposed frogs compared to control frogs, suggesting a more complex effect of Bd on the immune system than simple temperature-mediated immune suppression. This study generates important baseline data for ongoing efforts to understand differences in response to Bd between susceptible and resistant frog species and the effects of chytridiomycosis in natural populations

Combination Therapy Is Superior to Sequential Monotherapy for the Initial Treatment of Hypertension:A Double-Blind Randomized Controlled Trial

Background: Guidelines for hypertension vary in their preference for initial combination therapy or initial monotherapy, stratified by patient profile; therefore, we compared the efficacy and tolerability of these approaches. Methods and Results: We performed a 1‐year, double‐blind, randomized controlled trial in 605 untreated patients aged 18 to 79 years with systolic blood pressure (BP) ≥150 mm Hg or diastolic BP ≥95 mm Hg. In phase 1 (weeks 0–16), patients were randomly assigned to initial monotherapy (losartan 50–100 mg or hydrochlorothiazide 12.5–25 mg crossing over at 8 weeks), or initial combination (losartan 50–100 mg plus hydrochlorothiazide 12.5–25 mg). In phase 2 (weeks 17–32), all patients received losartan 100 mg and hydrochlorothiazide 12.5 to 25 mg. In phase 3 (weeks 33–52), amlodipine with or without doxazosin could be added to achieve target BP. Hierarchical primary outcomes were the difference from baseline in home systolic BP, averaged over phases 1 and 2 and, if significant, at 32 weeks. Secondary outcomes included adverse events, and difference in home systolic BP responses between tertiles of plasma renin. Home systolic BP after initial monotherapy fell 4.9 mm Hg (range: 3.7–6.0 mm Hg) less over 32 weeks (P<0.001) than after initial combination but caught up at 32 weeks (difference 1.2 mm Hg [range: −0.4 to 2.8 mm Hg], P=0.13). In phase 1, home systolic BP response to each monotherapy differed substantially between renin tertiles, whereas response to combination therapy was uniform and at least 5 mm Hg more than to monotherapy. There were no differences in withdrawals due to adverse events. Conclusions: Initial combination therapy can be recommended for patients with BP >150/95 mm Hg. Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00994617

Effect of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism: a randomized, double-blind, placebo-controlled trial

<p>Abstract</p> <p>Background</p> <p>Increasing evidence suggests the bidirectional interplay between parathyroid hormone and aldosterone as an important mechanism behind the increased risk of cardiovascular damage and bone disease observed in primary hyperparathyroidism. Our primary object is to assess the efficacy of the mineralocorticoid receptor-blocker eplerenone to reduce parathyroid hormone secretion in patients with parathyroid hormone excess.</p> <p>Methods/design</p> <p>Overall, 110 adult male and female patients with primary hyperparathyroidism will be randomly assigned to eplerenone (25 mg once daily for 4 weeks and 4 weeks with 50 mg once daily after dose titration] or placebo, over eight weeks. Each participant will undergo detailed clinical assessment, including anthropometric evaluation, 24-h ambulatory arterial blood pressure monitoring, echocardiography, kidney function and detailed laboratory determination of biomarkers of bone metabolism and cardiovascular disease.</p> <p>The study comprises the following exploratory endpoints: mean change from baseline to week eight in (1) parathyroid hormone(1–84) as the primary endpoint and (2) 24-h systolic and diastolic ambulatory blood pressure levels, NT-pro-BNP, biomarkers of bone metabolism, 24-h urinary protein/albumin excretion and echocardiographic parameters reflecting systolic and diastolic function as well as cardiac dimensions, as secondary endpoints.</p> <p>Discussion</p> <p>In view of the reciprocal interaction between aldosterone and parathyroid hormone and the potentially ensuing target organ damage, the EPATH trial is designed to determine whether eplerenone, compared to placebo, will effectively impact on parathyroid hormone secretion and improve cardiovascular, renal and bone health in patients with primary hyperparathyroidism.</p> <p>Trial registration</p> <p>ISRCTN33941607</p