Solar system effects in Schwarzschild--de Sitter spacetime

The Schwarzschild--de Sitter space--time describes the gravitational field of a spherically symmetric mass in a universe with cosmological constant $\Lambda$. Based on this space--time we calculate Solar system effects like gravitational redshift, light deflection, gravitational time delay, Perihelion shift, geodetic or de Sitter precession, as well as the influence of $\Lambda$ on a Doppler measurement, used to determine the velocity of the Pioneer 10 and 11 spacecraft. For $\Lambda=\Lambda_0 \sim 10^{-52} {\rm m}^{-2}$ the cosmological constant plays no role for all of these effects, while a value of $\Lambda \sim - 10^{-37} {\rm m}^{-2}$, if hypothetically held responsible for the Pioneer anomaly, is not compatible with the Perihelion shift.Comment: Published versio

A Convergent Finite Volume Method for a Kinetic Model for Interacting Species

We propose an upwind finite volume method for a system of two kinetic equations in one dimension that are coupled through nonlocal interaction terms. These cross-interaction systems were recently obtained as the mean-field limit of a second-order system of ordinary differential equations for two interacting species. Models of this kind are encountered in a myriad of contexts, for instance, to describe large systems of indistinguishable agents such as cell colonies, flocks of birds, schools of fish, herds of sheep. The finite volume method we propose is constructed to conserve mass and preserve positivity. Moreover, convex functionals of the discrete solution are controlled, which we use to show the convergence of the scheme. Finally, we investigate the scheme numerically

The molecular analysis of BRCA1 and BRCA2: Next-generation sequencing supersedes conventional approaches

Abstract Background Accurate and sensitive detection of BRCA 1/2 germ-line mutations is crucial for the clinical management of women affected by breast cancer, for prevention and, notably, also for the identification of at-risk healthy relatives. The most widely used methods for BRCA1 / 2 molecular analysis are Sanger sequencing, and denaturing high performance liquid chromatography (dHPLC) followed by the Sanger method. However, recent findings suggest that next-generation sequencing (NGS)-based approaches may be an efficient tool for diagnostic purposes. In this context, we evaluated the effectiveness of NGS for BRCA gene analysis compared with dHPLC/Sanger sequencing. Methods Seventy women were screened for BRCA1/2 mutations by both dHPLC/Sanger sequencing and NGS, and the data were analyzed using a bioinformatic pipeline. Results Sequence data analysis showed that NGS is more sensitive in detecting BRCA 1/2 variants than the conventional procedure, namely, dHPLC/Sanger. Conclusion Next-generation sequencing is more sensitive, faster, easier to use and less expensive than the conventional Sanger method. Consequently, it is a reliable procedure for the routine molecular screening of the BRCA 1/2 genes

The future direction of imaging in prostate cancer: MRI with or without contrast injection

Background: Multiparametric MRI (mpMRI) is the "state of the art" management tool for patients with prostate cancer (PCa) suspicion. The role of non-contrast MRI is investigated to move toward a more personalized, less invasive, and highly cost-effective PCa diagnostic workup. Objective: To perform a non-systematic review of the existing literature to highlight strength and flaws of performing non-contrast MRI, and to provide a critical overview of the international scientific production on the topic. Materials and methods: Online databases (Medline, PubMed, and Web of Science) were searched for original articles, systematic review and meta-analysis, and expert opinion papers. Results: Several investigations have shown comparable diagnostic accuracy of biparametric (bpMRI) and mpMRI for the detection of PCa. The advantage of abandoning contrast-enhanced sequences improves operational logistics, lowering costs, acquisition time, and side effects. The main limitations of bpMRI are that most studies which compared the non-contrast and contrast MRI come from centers with high expertise that might not be reproducible in the general community setting; besides, reduced protocols might be insufficient for estimation of the intra- and extra-prostatic extension and regional disease. The mentioned observations suggest that low quality mpMRI for the general population, might represent the main shortage to overcome. Discussion: Non-contrast MRI future trends are likely represented by PCa screening and the application of artificial intelligence (AI) tools. PCa screening is still a controversial topic and bpMRI, and has become one of the most promising diagnostic applications, as it is a more sensitive test for PCa early detection, compared to serum PSA level test. Also, AI applications and radiomic have been the object of several studies investigating PCa detection using bpMRI, showing encouraging results. Conclusion: Today, the accessibility to MRI for early detection of PCa is a priority. Results from prospective, multicenter, multireader and paired validation studies are needed to provided evidence supporting its role in the clinical practice

Relationship between p53 and p27 expression following HER2 signaling

HER2, frequently associated with low p27 expression in breast tumors, when activated has been found to upmodulate p53 in tumor cells. The aim of this work was to investigate the role of p53 in the connection between HER2 and p27. Fifty-two breast tumor specimens, characterized for p53 mutations, were analyzed immunohistochemically (IHC) for HER2, p53 and p27 expression. p27, inversely associated with HER2, was found in 29% of tumors with IHC-negative mutated p53 versus 93% of tumors with accumulation of p53 protein and 59% with wild-type p53 (p=0.001), indicating a direct association between p53 and p27 expression. HER2-overexpressing cell lines carrying wild-type or null p53 protein, and treated with heregulin beta1 (HRG), were analyzed for expression and subcellular localization of p53 and p27. In HER2-overexpressing cells stimulated with HRG, p27 protein expression increased in parallel with p53 with no corresponding increase in p27 transcript. No p27 increase was observed in p53-null cells. Transfection with wild-type p53 restored p27 upmodulation in HRG-stimulated cells, indicating a crucial role of p53 in determining p27 upmodulation following HER2 activation. Together, our data demonstrate the crucial role of p53 in determining p27 upmodulation following HER2 activation. This could have implications in the response to Transtuzumab therapy

Molecular signaling mediating the protective effect of A1 adenosine and mGluR3 metabotropic glutamate receptor activation against apoptosis by oxygen/glucose deprivation in cultured astrocytes. Mol Pharmacol 71

ABSTRACT Astrocyte death may occur in neurodegenerative disorders and complicates the outcome of brain ischemia, a condition associated with high extracellular levels of adenosine and glutamate. We show that pharmacological activation of A 1 adenosine and mGlu3 metabotropic glutamate receptors with N 6 -chlorocyclopentyladenosine (CCPA) and (Ϫ)2-oxa-4-aminocyclo-[3.1.0]hexane-4,6-dicarboxylic acid (LY379268), respectively, protects cultured astrocytes against apoptosis induced by a 3-h exposure to oxygen/glucose deprivation (OGD). Protection by CCPA and LY379268 was less than additive and was abrogated by receptor blockade with selective competitive antagonists or pertussis toxin. Both in control astrocytes and in astrocytes exposed to OGD, CCPA and LY379268 induced a rapid activation of the phosphatidylinositol-3-kinase (PI3K) and extracellular signal-regulated kinases 1 and 2 (ERK1/2)/mitogen-activated protein kinase (MAPK) pathways, which are known to support cell survival. In cultures exposed to OGD, CCPA and LY379268 reduced the activation of c-Jun N-terminal kinase and p38/MAPK, reduced the levels of the proapoptotic protein Bad, increased the levels of the antiapoptotic protein Bcl-X L , and were highly protective against apoptotic death, as shown by nuclear 4Ј-6-diamidino-2-phenylindole staining and measurements of caspase-3 activity. All of these effects were attenuated by treatment with 1,4-diamino-2,3-dicyano-1,4-bis(methylthio)butadiene (U0126) and 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002), which inhibit the MAPK and the PI3K pathways, respectively. These data suggest that pharmacological activation of A 1 and mGlu3 receptors protects astrocytes against hypoxic/ischemic damage by stimulating the PI3K and ERK1/2 MAPK pathways. Astrocytes, the most abundant glial cell types in the brain, provide metabolic and trophic support to neurons by several mechanisms that include the clearance of ions and environmental toxins, the supply of energy substrates, and the production of trophic factors, and modulate synaptic activity Recent studies have shown that ischemic and inflammatory insults induce astrocyte apoptotic death, and this contributes to the pathophysiology of short-and long-term neurodegenerative disorder

Positive effects of physical activity in autism spectrum disorder: how influences behavior, metabolic disorder and gut microbiota

Autism spectrum disorder is a neurodevelopmental disorder characterized by social interactions and communication skills impairments that include intellectual disabilities, communication delays and self-injurious behaviors; often are present systemic comorbidities such as gastrointestinal disorders, obesity and cardiovascular disease. Moreover, in recent years has emerged a link between alterations in the intestinal microbiota and neurobehavioral symptoms in children with autism spectrum disorder. Recently, physical activity and exercise interventions are known to be beneficial for improving communication and social interaction and the composition of microbiota. In our review we intend to highlight how different types of sports can help to improve communication and social behaviors in children with autism and also show positive effects on gut microbiota composition

Identification and Pathway Analysis of microRNAs with No Previous Involvement in Breast Cancer

microRNA expression signatures can differentiate normal and breast cancer tissues and can define specific clinico-pathological phenotypes in breast tumors. In order to further evaluate the microRNA expression profile in breast cancer, we analyzed the expression of 667 microRNAs in 29 tumors and 21 adjacent normal tissues using TaqMan Low-density arrays. 130 miRNAs showed significant differential expression (adjusted P value = 0.05, Fold Change = 2) in breast tumors compared to the normal adjacent tissue. Importantly, the role of 43 of these microRNAs has not been previously reported in breast cancer, including several evolutionary conserved microRNA*, showing similar expression rates to that of their corresponding leading strand. The expression of 14 microRNAs was replicated in an independent set of 55 tumors. Bioinformatic analysis of mRNA targets of the altered miRNAs, identified oncogenes like ERBB2, YY1, several MAP kinases, and known tumor-suppressors like FOXA1 and SMAD4. Pathway analysis identified that some biological process which are important in breast carcinogenesis are affected by the altered microRNA expression, including signaling through MAP kinases and TP53 pathways, as well as biological processes like cell death and communication, focal adhesion and ERBB2-ERBB3 signaling. Our data identified the altered expression of several microRNAs whose aberrant expression might have an important impact on cancer-related cellular pathways and whose role in breast cancer has not been previously described

A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis < 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11 years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982