Electroweak Corrections to Photon Scattering, Polarization and Lensing in a Gravitational Background and the Near Horizon Limit

We investigate the semiclassical approach to the lensing of photons in a spherically symmetric gravitational background, starting from Born level and include in our analysis the radiative corrections obtained from the electroweak theory for the graviton/photon/photon vertex. In this approach, the cross section is related to the angular variation of the impact parameter ($b$), which is then solved for $b$ as a function of the angle of deflection, and measured in horizon units ($b_h\equiv b/(2 G M)$). Exact numerical solutions for the angular deflection are presented. The numerical analysis shows that perturbation theory in a weak background agrees with the classical Einstein formula for the deflection already at distances of the order of $20$ horizon units ($\sim 20\, b_h$) and it is optimal in the description both of very strong and weak lensings. We show that the electroweak corrections to the cross section are sizeable, becoming very significant for high energy gamma rays. Our analysis covers in energy most of the photon spectrum, from the cosmic microwave background up to very high energy gamma rays, and scatterings with any value of the photon impact parameter. We also study the helicity-flip photon amplitude, which is of $O(\alpha^2)$ in the weak coupling $\alpha$, and its massless fermion limit, which involves the exchange of a conformal anomaly pole. The corresponding cross section is proportional to the Born level result and brings to a simple renormalization of Einsten's formula.Comment: 38 pages, 18 figures. Revised final version, accepted on JHE

Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiota

Objective The gut microbiota, which is considered a causal factor in metabolic diseases as shown best in animals, is under the dual influence of the host genome and nutritional environment. This study investigated whether the gut microbiota per se, aside from changes in genetic background and diet, could sign different metabolic phenotypes in mice. Methods The unique animal model of metabolic adaptation was used, whereby C57Bl/6 male mice fed a high-fat carbohydrate-free diet (HFD) became either diabetic (HFD diabetic, HFD-D) or resisted diabetes (HFD diabetes-resistant, HFD-DR). Pyrosequencing of the gut microbiota was carried out to profile the gut microbial community of different metabolic phenotypes. Inflammation, gut permeability, features of white adipose tissue, liver and skeletal muscle were studied. Furthermore, to modify the gut microbiota directly, an additional group of mice was given a glucooligosaccharide (GOS)-supplemented HFD (HFD+GOS). Results Despite the mice having the same genetic background and nutritional status, a gut microbial profile specific to each metabolic phenotype was identified. The HFD-D gut microbial profile was associated with increased gut permeability linked to increased endotoxaemia and to a dramatic increase in cell number in the stroma vascular fraction from visceral white adipose tissue. Most of the physiological characteristics of the HFD-fed mice were modulated when gut microbiota was intentionally modified by GOS dietary fibres. Conclusions The gut microbiota is a signature of the metabolic phenotypes independent of differences in host genetic background and diet

The Gut Microbiota Regulates Intestinal CD4 T Cells Expressing RORγt and Controls Metabolic Disease

SummaryA high-fat diet (HFD) induces metabolic disease and low-grade metabolic inflammation in response to changes in the intestinal microbiota through as-yet-unknown mechanisms. Here, we show that a HFD-derived ileum microbiota is responsible for a decrease in Th17 cells of the lamina propria in axenic colonized mice. The HFD also changed the expression profiles of intestinal antigen-presenting cells and their ability to generate Th17 cells in vitro. Consistent with these data, the metabolic phenotype was mimicked in RORγt-deficient mice, which lack IL17 and IL22 function, and in the adoptive transfer experiment of T cells from RORγt-deficient mice into Rag1-deficient mice. We conclude that the microbiota of the ileum regulates Th17 cell homeostasis in the small intestine and determines the outcome of metabolic disease

Resveratrol Increases Glucose Induced GLP-1 Secretion in Mice: A Mechanism which Contributes to the Glycemic Control

Resveratrol (RSV) is a potent anti-diabetic agent when used at high doses. However, the direct targets primarily responsible for the beneficial actions of RSV remain unclear. We used a formulation that increases oral bioavailability to assess the mechanisms involved in the glucoregulatory action of RSV in high-fat diet (HFD)-fed diabetic wild type mice. Administration of RSV for 5 weeks reduced the development of glucose intolerance, and increased portal vein concentrations of both Glucagon-like peptid-1 (GLP-1) and insulin, and intestinal content of active GLP-1. This was associated with increased levels of colonic proglucagon mRNA transcripts. RSV-mediated glucoregulation required a functional GLP-1 receptor (Glp1r) as neither glucose nor insulin levels were modulated in Glp1r-/- mice. Conversely, levels of active GLP-1 and control of glycemia were further improved when the Dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin was co-administered with RSV. In addition, RSV treatment modified gut microbiota and decreased the inflammatory status of mice. Our data suggest that RSV exerts its actions in part through modulation of the enteroendocrine axis in vivo

Lipid-Induced Peroxidation in the Intestine Is Involved in Glucose Homeostasis Imbalance in Mice

BACKGROUND: Daily variations in lipid concentrations in both gut lumen and blood are detected by specific sensors located in the gastrointestinal tract and in specialized central areas. Deregulation of the lipid sensors could be partly involved in the dysfunction of glucose homeostasis. The study aimed at comparing the effect of Medialipid (ML) overload on insulin secretion and sensitivity when administered either through the intestine or the carotid artery in mice. METHODOLOGY/PRINCIPAL FINDINGS: An indwelling intragastric or intracarotid catheter was installed in mice and ML or an isocaloric solution was infused over 24 hours. Glucose and insulin tolerance and vagus nerve activity were assessed. Some mice were treated daily for one week with the anti-lipid peroxidation agent aminoguanidine prior to the infusions and tests. The intestinal but not the intracarotid infusion of ML led to glucose and insulin intolerance when compared with controls. The intestinal ML overload induced lipid accumulation and increased lipid peroxidation as assessed by increased malondialdehyde production within both jejunum and duodenum. These effects were associated with the concomitant deregulation of vagus nerve. Administration of aminoguanidine protected against the effects of lipid overload and normalized glucose homeostasis and vagus nerve activity. CONCLUSIONS/SIGNIFICANCE: Lipid overload within the intestine led to deregulation of gastrointestinal lipid sensing that in turn impaired glucose homeostasis through changes in autonomic nervous system activity

APOLLO 11 Project, Consortium in Advanced Lung Cancer Patients Treated With Innovative Therapies: Integration of Real-World Data and Translational Research

Introduction: Despite several therapeutic efforts, lung cancer remains a highly lethal disease. Novel therapeutic approaches encompass immune-checkpoint inhibitors, targeted therapeutics and antibody-drug conjugates, with different results. Several studies have been aimed at identifying biomarkers able to predict benefit from these therapies and create a prediction model of response, despite this there is a lack of information to help clinicians in the choice of therapy for lung cancer patients with advanced disease. This is primarily due to the complexity of lung cancer biology, where a single or few biomarkers are not sufficient to provide enough predictive capability to explain biologic differences; other reasons include the paucity of data collected by single studies performed in heterogeneous unmatched cohorts and the methodology of analysis. In fact, classical statistical methods are unable to analyze and integrate the magnitude of information from multiple biological and clinical sources (eg, genomics, transcriptomics, and radiomics). Methods and objectives: APOLLO11 is an Italian multicentre, observational study involving patients with a diagnosis of advanced lung cancer (NSCLC and SCLC) treated with innovative therapies. Retrospective and prospective collection of multiomic data, such as tissue- (eg, for genomic, transcriptomic analysis) and blood-based biologic material (eg, ctDNA, PBMC), in addition to clinical and radiological data (eg, for radiomic analysis) will be collected. The overall aim of the project is to build a consortium integrating different datasets and a virtual biobank from participating Italian lung cancer centers. To face with the large amount of data provided, AI and ML techniques will be applied will be applied to manage this large dataset in an effort to build an R-Model, integrating retrospective and prospective population-based data. The ultimate goal is to create a tool able to help physicians and patients to make treatment decisions. Conclusion: APOLLO11 aims to propose a breakthrough approach in lung cancer research, replacing the old, monocentric viewpoint towards a multicomprehensive, multiomic, multicenter model. Multicenter cancer datasets incorporating common virtual biobank and new methodologic approaches including artificial intelligence, machine learning up to deep learning is the road to the future in oncology launched by this project

Gut microbiota and diabetes: from pathogenesis to therapeutic perspective

More than several hundreds of millions of people will be diabetic and obese over the next decades in front of which the actual therapeutic approaches aim at treating the consequences rather than causes of the impaired metabolism. This strategy is not efficient and new paradigms should be found. The wide analysis of the genome cannot predict or explain more than 10–20% of the disease, whereas changes in feeding and social behavior have certainly a major impact. However, the molecular mechanisms linking environmental factors and genetic susceptibility were so far not envisioned until the recent discovery of a hidden source of genomic diversity, i.e., the metagenome. More than 3 million genes from several hundreds of species constitute our intestinal microbiome. First key experiments have demonstrated that this biome can by itself transfer metabolic disease. The mechanisms are unknown but could be involved in the modulation of energy harvesting capacity by the host as well as the low-grade inflammation and the corresponding immune response on adipose tissue plasticity, hepatic steatosis, insulin resistance and even the secondary cardiovascular events. Secreted bacterial factors reach the circulating blood, and even full bacteria from intestinal microbiota can reach tissues where inflammation is triggered. The last 5 years have demonstrated that intestinal microbiota, at its molecular level, is a causal factor early in the development of the diseases. Nonetheless, much more need to be uncovered in order to identify first, new predictive biomarkers so that preventive strategies based on pre- and probiotics, and second, new therapeutic strategies against the cause rather than the consequence of hyperglycemia and body weight gain

Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands

Aploinsufficienza di TACE e omeostasi del glucosio: effetti protettivi su insulino-resistenza e obesità durante un regime di dieta grassa

E’ noto che il TNF (Tumor Necrosis Factor)-α altera la sensibilità insulinica e i metabolismi glucidico e lipidico attraverso meccanismi diversi e ridondanti, sia a livello traduzionale che post-traduzionale. Il TNF-α esercita i suoi effetti paracrini in seguito al taglio proteolitico della forma ancorata alla membrana plasmatica e al rilascio della forma solubile ad opera dell’enzima TACE (TNF-α Converting Enzyme), che regola la funzione di altre proteine di membrana come il recettore dell’interleuchina-6 e i ligandi del recettore EGFR (Epidermal Growth Factor Receptor). Per comprendere il ruolo ancora sconosciuto di TACE nell’obesità indotta da dieta grassa e nelle sue complicanze metaboliche, topi Tace+/- e topi WT (Wild Type) sono stati alimentati con una dieta standard (Standard Chow, SC) o grassa (High Fat Diet, HFD) per sedici settimane. E’ stato osservato che i topi Tace+/- risultano parzialmente protetti da obesità e insulino-resistenza rispetto ai topi WT. Infatti, quando sottoposti ad un regime di HFD, i topi WT mostrano obesità viscerale, aumentati livelli plasmatici di acidi grassi liberi, aumento dell’espressione genica per MCP-1 (Monocyte Chemoattractant Protein-1), ipoadiponectinemia, intolleranza al glucosio e insulino-resistenza, rispetto ai topi Tace+/-. Inoltre i topi Tace+/- hanno mostrato aumentati livelli di espressione genica per UCP-1 (UnCoupling Protein-1) e GLUT (GLUcose Transporter)-4 nel tessuto adiposo bianco. Questi risultati suggeriscono che lo sviluppo di molecole in grado di modulare l’attività di TACE può rappresentare un importante passo nella prevenzione dell’obesità e delle sue complicanze metaboliche.TNF (Tumor Necrosis Factor)-α is known to affect glucose and lipid metabolism through alternative and redundant mechanisms at different levels. TNF-α exerts its paracrine effects once the membrane-anchored form is shed and the soluble form is released from the cell membrane. TNF-α cleavage is regulated by TACE (TNF-α Converting Enzyme), which regulates the shedding and the function of several transmembrane proteins, such as IL-6R (Interleukin-6 Receptor) and EGFR (Epidermal Growth Factor Receptor) ligands. To shed light into the unknown role of TACE in high fat diet (HFD)-induced obesity and its metabolic complications we used Tace+/- mice fed with a standard or HFD for 16 weeks. We observed that Tace+/- mice are relatively protected from obesity and insulin resistance compared with WT littermates. When fed a HFD, WT mice exhibited visceral obesity, increased FFA (Free Fatty Acids) and MCP-1 (Monocyte Chemoattractant Protein-1) levels, hypoadiponectinemia, glucose intolerance and insulin resistance (all features of the metabolic syndrome) compared with Tace+/- mice. Interestingly, Tace+/- mice exhibited increased UCP-1 (UnCoupling Protein-1) and GLUT (GLUcose Transporter)-4 expression in white adipose tissue. These results suggest the development of pharmacological modulators of TACE activity as a novel way to treat obesity and its metabolic complications