Interactions of hadrons in the CALICE SiW ECAL prototype

This article presents results of test beams obtained for pions with energies between 2 and 10 GeV which interact in the volume of the highly granular CALICE Silicon-Tungsten electromagnetic calorimeter prototype (SiW ECAL). An algorithm optimised to find interactions in the SiW ECAL at small hadron energies is developed. This allows identifying the interaction point in the calorimeter at an efficiency between 62% and 83% depending on the energy of the primary particle. The unprecedented granularity of the SiW ECAL allows for the distinction between different interaction types. This in turn permits more detailed examinations of hadronic models than was possible with traditional calorimeters. So far, it is possible to disentangle minimum ionising particle (MIP) events, elastic π-nucleus scattering and spallation reactions which lead to the start of a internuclear cascade or which result in a small number of highly ionising particles. Various observables are compared with predictions from hadronic physics lists as contained in the simulation toolkit geant4

Hawking radiation in different coordinate settings: Complex paths approach

We apply the technique of complex paths to obtain Hawking radiation in different coordinate representations of the Schwarzschild space-time. The coordinate representations we consider do not possess a singularity at the horizon unlike the standard Schwarzschild coordinate. However, the event horizon manifests itself as a singularity in the expression for the semiclassical action. This singularity is regularized by using the method of complex paths and we find that Hawking radiation is recovered in these coordinates indicating the covariance of Hawking radiation as far as these coordinates are concerned.Comment: 18 pages, 2 figures, Uses IOP style file; final version; accepted in Class. Quant. Gra

In vitro evidences of different fibroblast morpho-functional responses to red, near-infrared and violet-blue photobiomodulation: Clues for addressingwound healing

Although photobiomodulation (PBM) has proven promising to treat wounds, the lack of univocal guidelines and of a thorough understanding of light–tissue interactions hampers its mainstream adoption for wound healing promotion. This study compared murine and human fibroblast responses to PBM by red (635 ± 5 nm), near-infrared (NIR, 808 ± 1 nm), and violet-blue (405 ± 5 nm) light (0.4 J/cm2 energy density, 13 mW/cm2 power density). Cell viability was not altered by PBM treatments. Light and confocal laser scanning microscopy and biochemical analyses showed, in red PBM irradiated cells: F-actin assembly reduction, up-regulated expression of Ki67 proliferation marker and of vinculin in focal adhesions, type-1 collagen down-regulation, matrix metalloproteinase-2 and metalloproteinase-9 expression/functionality increase concomitant to their inhibitors (TIMP-1 and TIMP-2) decrease. Violet-blue and even more NIR PBM stimulated collagen expression/deposition and, likely, cell differentiation towards (proto)myofibroblast phenotype. Indeed, these cells exhibited a higher polygonal surface area, stress fiber-like structures, increased vinculin- and phospho-focal adhesion kinase-rich clusters and α-smooth muscle actin. This study may provide the experimental groundwork to support red, NIR, and violet-blue PBM as potential options to promote proliferative and matrix remodeling/maturation phases of wound healing, targeting fibroblasts, and to suggest the use of combined PBM treatments in the wound management setting

Sisters in structure but different in character, some benzaldehyde and cinnamaldehyde derivatives differentially tune Aspergillus flavus secondary metabolism

Great are the expectations for a new generation of antimicrobials, and strenuous are the research efforts towards the exploration of diverse molecular scaffolds—possibly of natural origin – aimed at the synthesis of new compounds against the spread of hazardous fungi. Also high but winding are the paths leading to the definition of biological targets specifically fitting the drug’s structural characteristics. The present study is addressed to inspect differential biological behaviours of cinnamaldehyde and benzaldehyde thiosemicarbazone scaffolds, exploiting the secondary metabolism of the mycotoxigenic phytopathogen Aspergillus flavus. Interestingly, owing to modifications on the parent chemical scaffold, some thiosemicarbazones displayed an increased specificity against one or more developmental processes (conidia germination, aflatoxin biosynthesis, sclerotia production) of A. flavus biology. Through the comparative analysis of results, the ligand-based screening strategy here described has allowed us to delineate which modifications are more promising for distinct purposes: from the control of mycotoxins contamination in food and feed commodities, to the environmental management of microbial pathogens, to the investigation of specific structure–activity features for new generation drug discovery

A possible role of fzd10 delivering exosomes derived from colon cancers cell lines in inducing activation of epithelial–mesenchymal transition in normal colon epithelial cell line

Exosomes belong to the family of extracellular vesicles released by every type of cell both in normal and pathological conditions. Growing interest in studies indicates that extracellular vesicles, in particular, the fraction named exosomes containing lipids, proteins and nucleic acid, represent an efficient way to transfer functional cargoes between cells, thus combining all the other cell–cell interaction mechanisms known so far. Only a few decades ago, the involvement of exosomes in the carcinogenesis in different tissues was discovered, and very recently it was also observed how they carry and modulate the presence of Wnt pathway proteins, involved in the carcinogenesis of gastrointestinal tissues, such as Frizzled 10 protein (FZD10), a membrane receptor for Wnt. Here, we report the in vitro study on the capability of tumor-derived exosomes to induce neoplastic features in normal cells. Exosomes derived from two different colon cancer cell lines, namely the non-metastatic CaCo-2 and the metastatic SW620, were found to deliver, in both cases, FZD10, thus demonstrating the ability to reprogram normal colonic epithelial cell line (HCEC-1CT). Indeed, the acquisition of specific mesenchymal characteristics, such as migration capability and expression of FZD10 and markers of mesenchymal cells, was observed. The exosomes derived from the metastatic cell line, characterized by a level of FZD10 higher than the exosomes extracted from the non-metastatic cells, were also more efficient in stimulating EMT activation. The overall results suggest that FZD10, delivered by circulating tumor-derived exosomes, can play a relevant role in promoting the CRC carcinogenesis and propagation

Ticks infesting humans in Italy and associated pathogens

Background: Ticks may transmit a large variety of pathogens, which cause illnesses in animals and humans, commonly referred to as to tick-borne diseases (TBDs). The incidence of human TBDs in Italy is underestimated because of poor surveillance and the scant amount of studies available. Methods. Samples (n = 561) were collected from humans in four main geographical areas of Italy (i.e., northwestern, northeastern, southern Italy, and Sicily), which represent a variety of environments. After being morphologically identified, ticks were molecularly tested with selected protocols for the presence of pathogens of the genera Rickettsia, Babesia, Theileria, Candidatus Neoehrlichia mikurensis, Borrelia and Anaplasma. Results: Ticks belonged to 16 species of the genera Argas, Dermacentor, Haemaphysalis, Hyalomma, Ixodes and Rhipicephalus, with Ixodes ricinus (59.5%) being the species most frequently retrieved, followed by Rhipicephalus sanguineus sensu lato (21.4%). Nymphs were the life stage most frequently retrieved (41%), followed by adult females (34.6%). The overall positivity to any pathogen detected was 18%. Detected microorganisms were Rickettsia spp. (17.0%), Anaplasma phagocytophilum (0.8%), Borrelia afzelii (0.5%), Borrelia valaisiana (0.3%), C. N. mikurensis (0.5%) and Babesia venatorum (0.6%). Conclusions: Results indicate that people living in the Italian peninsula are at risk of being bitten by different tick species, which may transmit a plethora of TBD causing pathogens and that co-infections may also occur. © 2014 Otranto et al.; licensee BioMed Central Ltd

Exosomes for diagnosis and therapy in gastrointestinal cancers

Exosomes are membrane-bound extracellular vesicles (EVs) released by most cells, having a size ranging from 30 to 150 nm, and are involved in mechanisms of cell-cell communication in physiological and pathological tissues. Exosomes are engaged in the transport of biomolecules, such as lipids, proteins, messenger RNAs, and microRNA, and in signal transmission through the intercellular transfer of components. In the context of proteins and nucleic acids transported from exosomes, our interest is focused on the Frizzled proteins family and related messenger RNA. Exosomes can regenerate stem cell phenotypes and convert them into cancer stem cells by regulating the Wnt pathway receptor family, namely Frizzled proteins. In particular, for gastrointestinal cancers, the Frizzled protein involved in those mechanisms is Frizzled-10 (FZD-10). Currently, increasing attention is being devoted to the protein and lipid composition of exosomes interior and membranes, representing profound knowledge of specific exosomes composition fundamental for their application as new delivering drug tools for cancer therapy. This review intends to cover the most recent literature on the use of exosome vesicles for early diagnosis, follow-up, and the use of these physiological nanovectors as drug delivery systems for gastrointestinal cancer therapy

A family history of type 2 diabetes as a predictor of fatty liver disease in diabetes-free individuals with excessive body weight

Comprehensive screening for non-alcoholic fatty liver disease (NAFLD) may help prompt clinical management of fatty liver disease. A family history, especially of diabetes, has been little studied as a predictor for NAFLD. We characterized the cross-sectional relationship between a family history of type 2 diabetes (FHT2D) and NAFLD probability in 1185 diabetes-free Apulian (Southern-Italy) subjects aged > 20 years with overweight or obesity not receiving any drug or supplementation. Clinical data and routine biochemistry were analysed. NAFLD probability was defined using the fatty liver index (FLI). A first-degree FHT2D was assessed by interviewing subjects and assigning a score of 0, 1, or 2 if none, only one, or both parents were affected by type 2 diabetes mellitus (T2DM). Our study population featured most females (70.9%, N = 840), and 48.4% (N = 574) of the sample had first-degree FHT2D. After dividing the sample by a FHT2D, we found a higher BMI, Waist Circumference (WC), and diastolic blood pressure shared by FHT2D subjects; they also showed altered key markers of glucose homeostasis, higher triglyceride levels, and worse liver function. FLI scores were significantly lower in subjects without a first-degree FHT2D. After running logistic regression models, a FHT2D was significantly associated with the NAFLD probability, even adjusting for major confounders and stratifying by age (under and over 40 years of age). A FHT2D led to an almost twofold higher probability of NAFLD, regardless of confounding factors (OR 2.17, 95% CI 1.63 to 2.89). A first-degree FHT2D acts as an independent determinant of NAFLD in excess weight phenotypes, regardless of the age group (younger or older than 40 years). A NAFLD risk assessment within multidimensional screening might be useful in excess weight subjects reporting FHT2D even in the absence of diabetes

Brain structural damage in Friedreich's ataxia.

ABSTRACT Objective: Neuropathological descriptions of the brain in Friedreich’s ataxia (FRDA) were obtained before avail- ability of the current molecular genetic tests for this disease. Voxel-based morphometry (VBM) enables an unbiased whole-brain quantitative analysis of differences in gray matter (GM) and white matter (WM) volume. Methods: Using VBM, we assessed the brain structural damage in 22 patients with genetically confirmed FRDA and 25 healthy controls. The results were correlated with the disease duration and the severity of the patients’ clinical deficits—evaluated using the International Cerebellar Ataxia Rating Scale and Inherited Ataxia Clinical Rating Scale. Results: In patients with FRDA, VBM showed a symmetrical volume loss in dorsal medulla, infero-medial portions of the cerebellar hemispheres, the rostral vermis and in the dentate region. No volume loss in cerebral hemispheres was observed. The atrophy of the cerebel- lum and medulla correlated with the severity of the clinical deficit and disease duration. Conclusions: In patients with FRDA, significant GM and WM loss was observed only in the cerebellum and dorsal medulla. These structural changes correlate with the severity of the clinical deficit and disease duration

Non alcoholic fatty liver disease is positively associated with increased glycated haemoglobin levels in subjects without diabetes

Screening for non-alcoholic fatty liver disease (NAFLD) is key step for primary management of fatty liver in the clinical setting. Excess weight subjects carry a greater metabolic risk even before exhibiting pathological patterns, including diabetes. We characterized the cross-sectional relationship between routine circulating biomarkers and NAFLD in a large sample of diabetes-free subjects with overweight or obesity, to elucidate any independent relationship. A population sample of 1232 consecutive subjects with a body mass index of at least 25 kg/m2, not receiving any drug or supplemental therapy, was studied. Clinical data and routine biochemistry were analyzed. NAFLD was defined using the validated fatty liver index (FLI), classifying subjects with a score ≥ 60% as at high risk. Due to extreme skewing of variables of interest, resampling matching for age and sex was performed. Our study population was characterized by a majority of females (69.90%) and a prevalence of NAFLD in males (88.90%). As a first step, propensity score matching was explicitly performed to balance the two groups according to the FLI cut-off. Based on the resulting statistical trajectories, corroborated even after data matching, we built two logistic regression models on the matched population (N = 732) to verify any independent association. We found that each unit increase of FT3 implicated a 50% increased risk of NAFLD (OR 1.506, 95%CI 1.064 to 2.131). When including glycated haemoglobin (HbA1c) in the model, free-triiodothyronine (FT3) lost significance (OR 1.557, 95%CI 0.784 to 3.089) while each unit increase in HbA1c (%) indicated a significantly greater NAFLD risk, by almost two-fold (OR 2.32, 95%CI 1.193 to 4.512). Glucose metabolism dominates a key pathway along the hazard trajectories of NAFLD, turned out to be key biomarker in monitoring the risk of fatty liver in diabetes-free overweight subjects. Each unit increase in HbA1c (%) indicated a significantly greater NAFLD risk, by almost two-fold, in our study