Double photoionization of propylene oxide: a coincidence study of the ejection of a pair of valence-shell electrons

Propylene oxide, a favorite target of experimental and theoretical studies of circular dichroism, was recently discovered in interstellar space, further amplifying the attention to its role in the current debate on protobiological homochirality. In the present work, a photoelectron-photoion-photoion coincidence technique, using an ion-imaging detector and tunable synchrotron radiation in the 18.0-37.0 eV energy range, permits us (i) to observe six double ionization fragmentation channels, their relative yields being accounted for about two-thirds by the couple (C2H4+, CH2O+) and one-fifth by (C2H3+, CH3O+); (ii) to measure thresholds for their openings as a function of photon energy; and (iii) to unravel a pronounced bimodality for a kinetic-energy-released distribution, fingerprint of competitive non-adiabatic mechanisms

Lactobacillus rhamnosus lowers zebrafish lipid content by changing gut microbiota and host transcription of genes involved in lipid metabolism.

The microbiome plays an important role in lipid metabolism but how the introduction of probiotic communities affects host lipid metabolism is poorly understood. Using a multidisciplinary approach we addressed this knowledge gap using the zebrafish model by coupling high-throughput sequencing with biochemical, molecular and morphological analysis to evaluate the changes in the intestine. Analysis of bacterial 16S libraries revealed that Lactobacillus rhamnosus was able to modulate the gut microbiome of zebrafish larvae, elevating the abundance of Firmicutes sequences and reducing the abundance of Actinobacteria. The gut microbiome changes modulated host lipid processing by inducing transcriptional down-regulation of genes involved in cholesterol and triglycerides metabolism (fit2, agpat4, dgat2, mgll, hnf4α, scap, and cck) concomitantly decreasing total body cholesterol and triglyceride content and increasing fatty acid levels. L. rhamnosus treatment also increased microvilli and enterocyte lengths and decreased lipid droplet size in the intestinal epithelium. These changes resulted in elevated zebrafish larval growth. This integrated system investigation demonstrates probiotic modulation of the gut microbiome, highlights a novel gene network involved in lipid metabolism, provides an insight into how the microbiome regulates molecules involved in lipid metabolism, and reveals a new potential role for L. rhamnosus in the treatment of lipid disorders

Hyperglycemia-Induced Platelet Activation in Type 2 Diabetes Is Resistant to Aspirin but Not to a Nitric Oxide–Donating Agent

OBJECTIVE: Acute, short-term hyperglycemia enhances high shear stress-induced platelet activation in type 2 diabetes. Several observations suggest that platelets in type 2 diabetes are resistant to inhibition by aspirin. Our aim was to assess comparatively the effect of aspirin, a nitric oxide-donating agent (NCX 4016), their combination, or placebo on platelet activation induced by acute hyperglycemia in type 2 diabetes. RESEARCH DESIGN AND METHODS: In a double-blind, placebo-controlled, randomized trial, 40 type 2 diabetic patients were allocated to 100 mg aspirin once daily, 800 mg NCX 4016 b.i.d., both of them, or placebo for 15 days. On day 15, 1 h after the morning dose, a 4-h hyperglycemic clamp (plasma glucose 13.9 mmol/l) was performed, and blood samples were collected before and immediately after it for platelet activation and cyclooxygenase-1 (COX-1) inhibition studies. RESULTS Acute hyperglycemia enhanced shear stress-induced platelet activation in placebo-treated patients (basal closure time 63 +/- 7.1 s, after hyperglycemia 49.5 +/- 1.4 s, -13.5 +/- 6.3 s, P < 0.048). Pretreatment with aspirin, despite full inhibition of platelet COX-1, did not prevent it (-12.7 +/- 6.9 s, NS vs. placebo). On the contrary, pretreatment with the NO donor NCX 4016, alone or in combination with aspirin, suppressed platelet activation induced by acute hyperglycemia (NCX 4016 +10.5 +/- 8.3 s; NCX 4016 plus aspirin: +12.0 +/- 10.7 s, P < 0.05 vs. placebo for both). Other parameters of shear stress-dependent platelet activation were also more inhibited by NCX 4016 than by aspirin, despite lesser inhibition of COX-1. CONCLUSIONS: Acute hyperglycemia-induced enhancement of platelet activation is resistant to aspirin; a NO-donating agent suppresses it. Therapeutic approaches aiming at a wider platelet inhibitory action than that exerted by aspirin may prove useful in patients with type 2 diabetes

Maraviroc Intensification Modulates Atherosclerotic Progression in HIV-Suppressed Patients at High Cardiovascular Risk. A Randomized, Crossover Pilot Study

Background Experimental CCR5 antagonism with maraviroc in atherosclerosis-prone mice and preliminary data in humans suggest an anti-atherosclerotic effect of the drug. We assessed the impact of maraviroc treatment in persons living with HIV on subclinical indicators of atherosclerosis. Methods Persons living with HIV on effective antiretroviral therapy (ART) including only protease inhibitors were recruited if they had a Framingham risk score &gt;20% and brachial flow-mediated dilation (bFMD) &lt;4%, as indices of high cardiovascular risk. Maraviroc (300 mg per os for 24 weeks) was administered, in addition to ongoing ART, to all patients using a crossover design. Brachial FMD, carotid-femoral pulse wave velocity (cfPWV), and carotid intima-media thickness (cIMT) were measured as markers of atherosclerosis. Vascular competence—as expressed by the ratio of circulating endothelial microparticles (EMPs) to endothelial progenitor cells (EPCs)—and markers of systemic inflammation and monocyte and platelet activation were assessed. Results Maraviroc treatment significantly improved bFMD, cfPWV, and cIMT by 66%, 11%, and 13%, respectively (P = .002, P = .022, P = .038, respectively). We also found a beneficial effect of maraviroc on the EMP/EPC ratio (P &lt; .001) and platelet/leucocyte aggregates (P = .013). No significant changes in markers of systemic inflammation, monocyte activation, and microbial translocation were observed. Conclusions Maraviroc led to significant improvements in several markers for cardiovascular risk, endothelial dysfunction, arterial stiffness, and early carotid atherosclerosis, which was accompanied by an increase of vascular competence, without seeming to affect systemic inflammation. Our data support the need for larger studies to test for any effects of maraviroc on preventing atherosclerosis-driven pathologies

The future of Cybersecurity in Italy: Strategic focus area

This volume has been created as a continuation of the previous one, with the aim of outlining a set of focus areas and actions that the Italian Nation research community considers essential. The book touches many aspects of cyber security, ranging from the definition of the infrastructure and controls needed to organize cyberdefence to the actions and technologies to be developed to be better protected, from the identification of the main technologies to be defended to the proposal of a set of horizontal actions for training, awareness raising, and risk management

Propranolol reduces IFN-γ driven PD-L1 immunosuppression and improves anti-tumour immunity in ovarian cancer

The immune system plays an important role in controlling epithelial ovarian cancer (EOC). EOC is considered to be a "cold tumour," a tumour that has not triggered a strong response by the immune system. However, tumour infiltrating lymphocytes (TILs) and the expression of programmed cell death ligand (PD-L1) are used as prognostic indicators in EOC. Immunotherapy such as PD-(L)1 inhibitors have shown limited benefit in EOC. Since the immune system is affected by behavioural stress and the beta-adrenergic signalling pathway, this study aimed to explore the impact of propranolol (PRO), a beta-blocker, on anti-tumour immunity in both in vitro and in vivo EOC models. Noradrenaline (NA), an adrenergic agonist, did not directly regulate PD-L1 expression but PD-L1 was significantly upregulated by IFN-γ in EOC cell lines. IFN-γ also increased PD-L1 on extracellular vesicles (EVs) released by ID8 cells. PRO significantly decreased IFN-γ levels in primary immune cells activated ex vivo and showed increased viability of the CD8+ cell population in an EV-immune cell co-incubation. In addition, PRO reverted PD-L1 upregulation and significantly decreased IL-10 levels in an immune-cancer cell co-culture. Chronic behavioural stress increased metastasis in mice while PRO monotherapy and the combo of PRO and PD-(L)1 inhibitor significantly decreased stress-induced metastasis. The combined therapy also reduced tumour weight compared to the cancer control group and induced anti-tumour T-cell responses with significant CD8 expression in tumour tissues. In conclusion, PRO showed a modulation of the cancer immune response by decreasing IFN-γ production and, in turn, IFN-γ-mediated PD-L1 overexpression. The combined therapy of PRO and PD-(L)1 inhibitor decreased metastasis and improved anti-tumour immunity offering a promising new therapy

An integrated framework for quantifying immune-tumour interactions in a 3D co-culture model

Investigational in vitro models that reflect the complexity of the interaction between the immune system and tumours are limited and difficult to establish. Herein, we present a platform to study the tumour-immune interaction using a co-culture between cancer spheroids and activated immune cells. An algorithm was developed for analysis of confocal images of the co-culture to evaluate the following quantitatively; immune cell infiltration, spheroid roundness and spheroid growth. As a proof of concept, the effect of the glucocorticoid stress hormone, cortisol was tested on 66CL4 co-culture model. Results were comparable to 66CL4 syngeneic in vivo mouse model undergoing psychological stress. Furthermore, administration of glucocorticoid receptor antagonists demonstrated the use of this model to determine the effect of treatments on the immune-tumour interplay. In conclusion, we provide a method of quantifying the interaction between the immune system and cancer, which can become a screening tool in immunotherapy design

Notulae to the Italian native vascular flora: 3.

In this contribution new data concerning the distribution of native vascular flora in Italy are presented. It includes new records, exclusions, and confirmations to the Italian administrative regions for taxa in the genera Asplenium, Bolboschoenus, Botrychium, Chamaerops, Crocus, Galeopsis, Grafia, Helosciadium, Hieracium, Juniperus, Leucanthemum, Lolium, Medicago, Phalaris, Piptatherum, Potamogeton, Salicornia, Salvia, Seseli, Silene, Spiraea, Torilis and Vicia. Rhaponticoides calabrica is proposed as synonym novum of R. centaurium. Furthermore, new combinations in the genera Galatella and Lactuca are proposed