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Chemical and organoleptic properties of dairy products largely depend on the action of microorganisms that tend to be selected in cheese during ripening in response to the availability of specific substrates. The aim of this work was to evaluate the effects of a diet enriched with hemp seeds on the microbiota composition of fresh and ripened cheese produced from milk of lactating ewes. Thirty-two half-bred ewes were involved in the study, in which half (control group) received a standard diet, and the other half (experimental group) took a diet enriched with 5% hemp seeds (on a DM basis) for 35 d. The dietary supplementation significantly increased the lactose in milk, but no variations in total fat, proteins, caseins, and urea were observed. Likewise, no changes in total fat, proteins, or ash were detected in the derived cheeses. The metagenomic approach was used to characterize the microbiota of raw milk and cheese. The phyla Proteobacteria and Firmicutes were in equally high abundance in both control and experimental raw milk samples, whereas Bacteroidetes was less abundant. The scenario changed when considering the dairy products. In all cheese samples, Firmicutes was clearly predominant, with Streptococcaceae being the most abundant family in the experimental group. The reduction of taxa observed during ripening was in accordance with the increment (relative abundance) of the starter culture Lactococcus lactis and Streptococcus thermophilus, which together dominate the microbial community. The analysis of the volatile profile in ripened cheeses led to the identification of 3 major classes of compounds: free fatty acids, ketones, and aldehydes, which indicate a prevalence of lipolysis compared with the other biochemical mechanisms that characterize the cheese ripening.

The Mediterranean recluse spider Loxosceles rufescens (Dufour, 1820) is a public health concern due to its ability to inject venom that can cause skin lesions, referred to as loxoscelism. The spreading alarmism about recluse spiders which recently arose in Italy made it advisable to deepen knowledge about L. rufescens habitat preferences in human housing. Here, we report 14 confirmed cases of its occurrence in synanthropic habitats, and describe the housing characteristics. Our results pinpoint that traditional Italian houses of central Italy, in medieval towns and countryside, can be suitable for recluse spider colonization. The main features include the presence of walls of stone (with cracks and crevices), cellars, false ceilings, crawl spaces, wood materials (woodshed or wooden beams), and the occurrence of prey. Further characteristics which make conditions even more suitable are: large size, complex structure, and unoccupied premises. Due to its cryptic habits, even where L. rufescens is abundant, only the deployment of traps, following the recovery of a single or few individuals, revealed severe infestations. Our results confirm an unjustified negative notoriety of recluse spiders, considering that none of the inhabitants concerned, even if living in heavily infested housing, suffered from confirmed loxoscelism.

Biodiesel is an alternative fuel and can be obtained by the transesterification of vegetable oils. Spectrophotometric methods can be used for the quantification of mixtures, associated with chemometric tools, enabling the analysis of overlapping signals. The aim of this work is to apply the multivariate calibration with PLS (partial least squares) and artificial neural network (ANN), to estimate the concentration of esters in the transesterification of soybean oil using molecular absorption spectrophotometry as analytical technique. Absorbance measurements were performed in a spectrophotometer UV/VIS. Synthetic solutions were prepared with standards of the five major compounds of soybean biodiesel and real samples were obtained by the reaction of transesterification of soybean oil with NaOH and enzymatic method was used Lipozyme® IM (Novozymes), as catalysts. Results shows that all components of this reaction medium absorb in the wavelength range of 190-280 nm. Reactions of basic catalysis reached conversions close to 100%, while enzymatic reactions reached lower conversions. For both methods, calibration and validation groups were composed, respectively, by synthetic and real samples. Results showed that the concentrations of esters estimated by ANN model in the real samples are more accurate (R2-0.93), showing the good ability to estimation of ANN.

We propose a theoretical model to study heat transfer at the nanoscale by means of high-order thermodynamic fluxes. The model is fully compatible with the model of heat transfer of extended irreversible thermodynamics, represents a generalization of the Guyer–Krumhansl proposal (Guyer & Krumhansl 1966 Phys. Rev. 148 ) and is able to deal with relaxational and non-local effects. It also accounts for the role played by the different heat carriers (electrons and/or lattice vibrations) and captures different heat-carrier temperatures. The proposed model is hyperbolic and is used to investigate the propagation of thermal waves.

The correct analysis of heat transport at nanoscale is one of the main reasons of new developments in physics and nonequilibrium thermodynamic theories beyond the classical Fourier law. In this paper, we provide a two-temperature model which allows to describe the different regimes which electrons and phonons can undergo in the heat transfer phenomenon. The physical admissibility of that model is showed in view of second law of thermodynamics. The above model is applied to study the propagation of heat waves in order to point out the special role played by nonlocal and nonlinear effects.

Background and purpose Sacubitril/valsartan (sac/val), an angiotensin receptor neprilysin inhibitor, reduces the risk for cardiovascular (CV) death or hospitalization for heart failure (HF) in HF with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are approved in patients with type 2 diabetes (T2D) and have shown to reduce the CV risk in T2D patients with established CV or at risk of CV disease. The SGLT2i dapagliflozin has shown to improve outcomes in patients with chronic HFrEF, with or without T2D, when used in addition to standard of care including sac/val. As the use of SGLT2i in HF evolves, and given the large overlap of HF and T2D populations, it is of interest to understand the population with concomitant use of sac/val and SGLT2i. This study describes the clinical characteristics of patients treated concomitantly with sac/val and SGLT2i or concomitantly with sac/val and dipeptidyl peptidase-4 inhibitors (DPP4i) or glucagon-like peptide-1 receptor agonists (GLP1), two comparable second line anti-diabetic drug classes. Methods This retrospective non-interventional study describes two mutually exclusive adult patient cohorts diagnosed with HF and T2D concomitantly prescribed sac/val and SGLT2i (cohort 1), or concomitantly prescribed sac/val and DDP4i/GLP1 (cohort 2). The index date was defined as the first date of concomitant use with prescriptions overlapping a minimum of 21 days. Patients were identified any time between 1/1/2015 and 30/6/2019 in the Optum® de-identified electronic health record (EHR) data from providers across the continuum of care. Results 2.3 million HF patients were identified, and 41.6% had a T2D diagnosis. 560 patients were concomitantly prescribed sac/val and SGLT2i (cohort 1) and 1,566 concomitantly sac/val and DDP4/GLP1 (cohort 2). There was a higher proportion of females in cohort 2 (35.0% vs 27.9%). Mean age was higher in cohort 2 (66.4 vs 61.4 years). The mean estimated glomerular filtration rate was 85.93 (SD 23.43) ml/min/1.73m2 (cohort 1) and 72.10 (Std. 27.11) ml/min/1.73m2 (cohort 2). The proportion of stage 3 CKD (30 ml/min/1.73m2) was 11.8% (cohort 1) and 24.4% (cohort 2). Mean systolic blood pressure was similar, 120 mmHg (cohort 1) and 122 mmHg (cohort 2). Mean hemoglobin was 13.60 g/dl (cohort 1) and 12.43 g/dl (cohort 2). Median (IQR) NT-proBNP differed between the two cohorts, 914 (2154) pg/ml (cohort 1) and 2,290 (5,301) pg/ml (cohort 2) but with complete values available in only 17.7 and 19.0% of each cohort. Conclusions This descriptive analysis of concomitant prescription of sac/val and SGLT2i or DPP4/GLP1 highlights differences in the clinical characteristics between the two cohorts. The patients treated with sac/val and SGLT2i start with a more favorable clinical profile compared to the patients treated with sac/val and DPP4/GLP1. Further analyses are needed to determine if these differences are driven by age, gender or other factors. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Novartis Pharma AG

Background Food is the main source of Listeria monocytogenes (Lm) infection. Lm is a highly heterogeneous species composed of hypervirulent and hypovirulent clones. Understanding the distribution of Lm clonal complexes (CCs) in different food categories has strong implications for risk assessment. The aim of this work was to analyse collection of Lm strains of National Reference Laboratory (NRL Lm) in order to assess link between genetic profile and matrices and the level of pathogenicity of circulating strains based on CCs. Methods NRL Lm database actually consists of 906 sequenced strains isolated in 10 years from 5 food compartments (meat, fish, dairy, vegetables and composite dishes). Epidata were analysed to remove redundant strains based on the same epidemiological description. After that, WGS data from 465 Lm strains were investigated. In silico MLST was defined and Roary 3.12.0 was used to obtain a pan-genome profile. Genes were later uploaded to Pasteur Institute platform for characterization. Results In silico MLST identified 36 CCs and 6 singleton. CC9 (23.0%), CC8 (15.3%) and CC121 (13.3%) were the prevalent CCs. In particular, CC9 was present in 35.2% of meat samples and CC8 in 25.8% of fish samples. Pan genome profile revealed high prevalence (>98%) of genes related to biofilm formation and resistance to environmental stress in CC9 strains and genes involved in tolerance to quaternary ammonium compounds in CC121 strains. Conclusions Results, in particular for meat products, confirmed in Italy, the prevalence of hypovirulent Lm strains previously observed at European Union level. The high presence of stress resistance and disinfectant tolerance genes in these strains could make them able to persist in food-production environment and should be taken into account evaluating the health hazards. In fish product is also relevant the prevalence of CC8 strains which are potentially highly pathogenic and have been responsible of recent European multi country outbreak. Key messages Pangenome of Listeria monocytogenes isolated from Italian food revealed high presence of disinfectant tolerance and stress resistance genes in meat products and virulence genes in fish products. Listeria monocytogenes CC9 and CC121 prevalence in Italian meat product confirms occurrence of hypovirulent strains detected at European Union level.

Background Bisphosphonates (BPs) contrast the bone fragility and improve bone density in some metastatic cancers and bone diseases, such as Osteogenesis Imperfecta (OI). BPs use has been associated with osteonecrosis of the jaws (BRONJs) in adults needing for invasive dental procedures. Aim To conduct a systematic review on BRONJ occurrence after dental surgery in paediatric population under BPs therapy for OI, so as to identify the pre-surgical protocols adopted. Design According to PRISMA guidelines, Pubmed, Web of Science (WoS) and Cochrane were investigated on September 2018, and re-checked on July 2019. Inclusion criteria were English-language papers on children/young adults (until 24 years old) reporting dental/oral surgery procedures. Results Totally, 60 articles were found. After title/abstract reviews and duplicates exclusion, 22 eligible titles underwent full-text evaluation. Finally, 10 studies were included. Conclusions The lack of BRONJ occurrence in paediatric population suffering OI and treated with BPs, was confirmed, but the reasons are still debated, being the BPs therapies and the surgical strategies various and not standardized. Longitudinal studies should evaluate what happens to those former children once adult, to evaluate the delayed BRONJs onset associated with the occurrence of comorbidities during the adulthood.

This paper reports on a collaborative activity developed as part of the DPC-ReLUIS Research Project, year 2017. It aims at comparing the results obtained by considering alternative options in the definition of the nonlinear FEM model employed in pushover analyses for seismic assessment of existing RC frames. Specifically, the RC frame structure of the De Gasperi-Battaglia school building located in Norcia, Italy, is considered as a relevant case-study. This structure has been designed in the ‘60s of the past century according to the seismic code of the time and, hence, without taking into account the principles of Capacity Design. Although the building was actually retrofitted before the 2016 Central Italian earthquake, in this paper its original configuration has been considered. The nonlinear behaviour of the frame structure has been modelled by both following alternative approaches and employing different analysis codes. Therefore, this paper proposes an overview about how different the simulation output can be as a result of different modelling and analysis choices. In doing that, the work can be relevant to practitioners, as they may be warned about the consequences of those choices in terms of seismic vulnerability evaluation.

Meiofauna includes an astonishing diversity of organisms, whose census is far from being complete. Most classic ecological studies have focused on hard-bodied Ecdysozoan taxa (notably Copepoda and Nematoda), whose cuticle allows determination at species-level after fixation, rather than soft-bodied, Spiralian taxa, which most often lose any diagnostic feature in fixed samples. Yet, metabarcoding studies have recently revealed a species-richness of soft-bodied taxa comparable, and in cases superior, to that of Copepoda and Nematoda together. However, given objective difficulties inherent to their study, which necessarily has to be performed on living individuals, and their limited utilisation for ecological and applicative research, taxonomic expertise on soft-bodied organisms has declined over the years, and diversity of these phyla in most areas of the world is presently completely unknown. Here we present an expert-based survey of current knowledge on the composition and distribution of soft-bodied meiofaunal taxa in Italy, with special references to the predominantly or exclusively meiobenthic phyla Gastrotricha, Gnathostomulida, Platyhelminthes, Rotifera, Xenacoelomorpha, and macrofaunal taxa with conspicuous meiofaunal representatives (Annelida, Mollusca and Nemertea). A total of 638 described species have been reported from Italian coasts; furthermore, the existence of a large number of undescribed species is mentioned. Knowledge of Annelida, Gastrotricha, and Rotifera appears particularly detailed, placing Italy among the best-known country worldwide. In contrast, knowledge of Platyhelminthes and Xenacoelomorpha appears patchy, and limited to few areas. Sampling effort has been uneven, with most species recorded from the Tyrrhenian Sea, while large sections of the Adriatic and Ionian seas have been poorly explored. Results highlight the role that Marine Biological Stations, notably the Zoological Station "Anton Dohrn" in Naples, have had in promoting the study of soft-bodied taxa in Italy. The authors thank Directors and Staff of the National Parks 'Arcipelago di La Maddalena' and 'Isola dell'Asinara' for allowing research, and offering financial and logistic support during the organisation of workshops on meiofauna. Regione Autonoma Sardegna is thanked for giving permissions to sample beach sediments, otherwise strictly forbidden regionally. The research has been partially funded by a FSC 2014-2020 grant "Patto per lo Sviluppo della Regione Sardegna" and LR7-2016 "The Contribution of interstitial flatworms in monitoring the effects of climate change". Curini-Galletti, M (corresponding author), Univ Sassari, Dipartimento Med Vet, Sassari, Italy. curini@uniss.it

This study investigated how a high school literacy coach provided coaching to support teachers’ understanding and implementation of disciplinary literacy instruction. With a focus on collaborations between the literacy coach and teachers in the disciplines of social studies, math, and English, this article presents three case studies that illustrate how the coach and teachers designed instruction within and beyond the district’s curricular frameworks. Findings suggest when the coach situated herself as a collaborator, rather than an expert, and positioned the teacher as the disciplinary expert, the coach and teacher were able to foreground the discipline and plan meaningful disciplinary literacy instruction. The use of open-ended questions, think-alouds, and an examination of instructional tasks from students’ perspectives enabled the teachers to strengthen their disciplinary literacy instruction.

Mycoplasma mycoides subsp. mycoides is the etiological agent of contagious bovine pleuropneumonia (CBPP). While several findings on CBPP prevalence in Nigeria were documented, no data were reported about the genomic characterization of Nigerian M. mycoides subsp. mycoides strains. Here, we present the draft genome sequences of two novel M. mycoides subsp. mycoides strains isolated in Nigeria.

Mycoplasma mycoides subsp. mycoides is the etiological agent of contagious bovine pleuropneumonia (CBPP). While several findings on CBPP prevalence in Nigeria were documented, no data were reported about the genomic characterization of Nigerian M. mycoides subsp. mycoides strains. Here, we present the draft genome sequences of two novel M. mycoides subsp. mycoides strains isolated in Nigeria.

We study the consequences of a nonlinear generalization of the Maxwell–Cattaneo equation on the speed of propagation of nonlinear thermal waves. It turns out that such speed depends on the amplitude of the waves and it is smaller than the speed of linear (small-amplitude) waves. This is analogous to the optical Kerr effect of nonlinear optics. In analogy with the electro-optical Kerr effect, an imposed external heat flux could be used to control the speed of thermal waves in a material layer. As a particular illustration, we consider an externally tunable lens for heat waves propagating in the layer.

Drug release from inorganic supports is a challenge for the scientific community for various reasons, related to the low costs of the systems and the possibility of easily regulating the drug release. In the present work, surface-modified zeolite particles are used as carriers for non steroidal antiflammatory drugs (NSAIDs). The release of the drug has been studied in a solution that simulates the intestinal fluid as well as in a gel-like system, based on a surfactant and a binding salt. In the solution case, the quantity of drug released has been tracked via spectrophotometric assay. Release in the gel has been monitored by rheological methods. The molecular conformation of the NSAIDs is fundamental for the interaction with the zeolite surface, whose modified surface has a strong binding energy. It has been proven that the main mechanism for the drug release is anion exchange. It has been found that the NSAIDs, used in their sodic form, can act as binding salts by themselves in the gel-like system, thus changing the viscoelastic response of the overall solution. Drug release kinetics in the solution compare quantitatively well with the released drug in the gel-like fluid, as measured by rheometry.

The linear theory of heat waves is generalized to nonlinear situations in a conservation-dissipation formalism in the context of extended thermodynamics. An analogy with the theory of nonlinear electromagnetic waves is pointed out. This analogy emphasizes several physical aspects of the nonlinear theory and allows a parallelism with nonlinear optics, which may be of interest in nonlinear phononics. The proposed nonlinear equation for heat waves is compared with nonlinear transport equations in other fields of non-equilibrium thermodynamics, and it is applied to second-harmonic generation of heat waves in graded materials.

Equine infectious anaemia (EIA) is a disease with an almost worldwide distribution, with several outbreaks having been reported recently in European countries. In Italy, two regions, Lazio and Abruzzo, are considered as endemic areas for this disease. In nature, the EIA virus is mechanically transmitted by biting flies such as tabanids (Diptera: Tabanidae), although few studies have investigated the epidemiological implications. In the present study, several sites characterized by different levels of EIA prevalence were sampled. In sites with high tabanid populations, a seasonal succession of tabanid species with a dual-peak corresponding to early active species (i.e. in June to July) and late active species (i.e. in August to September) was clearly observed. Moreover, a positive correlation was found between EIA prevalence and tabanid abundance and species richness, suggesting that tabanid diversity might extend the duration of the seasonal transmission period of EIA. Further observations are required to better assess how vector diversity influence EIA transmission.

Background As the epidemiology of human Q Fever generally reflects the spread of Coxiella burnetii in ruminant livestock, molecular characterization of strains is essential to prevent human outbreaks. In this study we report the genetic diversity of C. burnetii in central Italy accomplished by MST and MLVA-6 on biological samples from 20 goat, sheep and cow farms. Results Five MST and ten MLVA profiles emerged from the analysis establishing a part of C. burnetii strain world atlas. In particular, ST32 occurred on 12 farms (60%), prevalently in goat specimens, while ST12 (25%) was detected on 4 sheep and 1 goat samples. ST8 and a variant of this genotype were described on 2 different sheep farms, whereas ST55 was observed on a goat farm. Five complete MLVA profiles different from any other published genotypes were described in this study in addition to 15 MLVA incomplete panels. Despite this, polymorphic markers Ms23, Ms24 and Ms33 enabled the identification of samples sharing the same MST profile. Conclusions Integration of such data in international databases can be of further help in the attempt of building a global phylogeny and epidemiology of Q fever in animals, with a “One Health” perspective.

L’invenzione è frutto di uno studio durato anni in cui è stato dimostrato il coinvolgimento di determinate proteine nella progressione tumorale . Lo scopo è chiarire meccanismi molecolari che sottendono allo sviluppo del carcinoma del cavo orale, per individuare dei marcatori specifici in modo da evitare la progressione della patologia. La nostra attenzione si è concentrata su un recettore di membrana di natura proteica ,il recettore del fattore di crescita epiteliale (EGF-R) e l‘espressione di recettori steroidei universalmente riconosciuti come recettori nucleari.L’originalità del prodotto sta nella determinazione della co- espressione delle suddette proteine recettoriali che hanno una valenza predittiva per il tumore del cavo orale. Diversi sono i tessuti che possono essere interessati da tumori maligni del cavo orale : mucose orali, epitelio ghiandolare, mucosa linguale, faringea, laringea e palatina, rientrando così manifestazioni tumorali del distretto testa-collo . Il carcinoma del cavo orale è tra le 10 forme più diffuse al mondo e nel mondo vengono diagnosticati, ogni anno più di 500.000 nuovi casi. La ricerca si propone di diagnosticare precocemente patologia come il cancro che registrano un continuo aumento di mortalità.

Saccocirrids are tiny, slender annelids inhabiting the interstices among coarse sand sediments in shallow waters. The 22 nominal species can be grouped into two morphological groups “papillocercus” and “krusadensis”, based on the absence/presence of a pharyngeal bulbus muscle, absence/presence of ventral ciliary patterns, bilateral/unilateral gonad arrangement and chaetal differences. We present herein the first phylogenetic analyses of Saccocirridae based on four molecular markers and 34 morphological characters, employing maximum likelihood and Bayesian methods. All analyses confirmed the monophyly of each morphological group with high nodal support. As a consequence and based on several apomorphic characters, a new genus, Pharyngocirrus gen. nov., is erected for the “krusadensis” clade. Remarkably, the habitat preferences and trophic guilds are also shown to differ between the two genera, yet show strong consistency within each group. Geographic distribution analyses underscore the family preference for subtropical areas, but reject the previously proposed restriction of Pharyngocirrus gen. nov. to the Indo-Pacific. The finding of two morphologically diverging, cosmopolitan sister clades with different habitat preferences suggest an early ecological diversification of the family, conserved during the later evolution, speciation processes and dispersal of the family.

Meniere's disease (MD) is a common disorder of the inner ear whose hallmarks are vertigo, tinnitus, aural fullness, and progressive hearing loss. The degree of severity of the disease is quite heterogeneous, and so is its pathogenesis. A multifactorial inheritance of intrinsic and extrinsic factors has been described, but there is not a common agreement on the molecular basis of MD. In a recent article, we have demonstrated that patients suffering from MD share a common plasma proteomic signature, characterized by the presence of several up- and down-regulated proteins. In this study, we have further extended our analysis and show that the differential expression of plasma proteins can identify specific subsets of MD-affected individuals, depending on their stage. Our findings confirm our plasma proteomics-driven approach as a powerful tool for early diagnosis of MD and uncover a potentially starring role for some proteins in the development and fate of this frustrating disease, whose pathogenesis still remains unclear.

Interstitial annelids in the family Saccocirridae live in the extremely turbulent and dynamic swash zone of exposed sandy beaches. We examine herein the relationship between distribution patterns of Saccocirrus pussicus du Bois-Reymond Marcus 1948 and morphodynamics, hydrodynamic zones, and environmental variables at beaches sampled along the Brazilian Atlantic coast. The occurrence and the abundance of S. pussicus at regional scale were positively correlated with the presence of a steep slope, large waves and coarse sand, which are characteristic of reflective beaches. On a local scale, S. pussicus occurred at the swash zone and breaking surf zone of reflective beaches. On a microscale, it preferred the upper 20 cm of the swash zone sediment. Saccocirrus pussicus prefers hydrodynamic zones, which change temporally, suggesting dependence with the dynamics of the surging and plunging waves. The coupling of morphological and behavioral adaptations of S. pussicus to beach morphodynamics is crucial for understanding its surfing life strategies within turbulent environments.

Recent studies have shown that hyperinsulinemia may increase the cancer risk. Moreover, many tumors demonstrate an increased activation of IR signaling pathways. Phosphatidylinositol 3-kinase (PI3K) is necessary for insulin action. In epithelial cells, which do not express GLUT4 and gluconeogenic enzymes, insulin-mediated PI3K activation regulates cell survival, growth, and motility. Although the involvement of the regulatory subunit of PI3K (p85αPI3K) in insulin signal transduction has been extensively studied, the function of its N-terminus remains elusive. It has been identified as a serine (S83) in thep85αPI3Kthat is phosphorylated by protein kinase A (PKA). To determine the molecular mechanism linking PKA to insulin-mediated PI3K activation, we usedp85αPI3Kmutated forms to prevent phosphorylation (p85A) or to mimic the phosphorylated residue (p85D). We demonstrated that phosphorylation ofp85αPI3KS83 modulates the formation of thep85αPI3K/IRS-1complex and its subcellular localization influencing the kinetics of the insulin signaling both on MAPK-ERK and AKT pathways. Furthermore, thep85αPI3KS83 phosphorylation plays a central role in the control of insulin-mediated cell proliferation, cell migration, and adhesion. This study highlights thep85αPI3KS83 role as a key regulator of cell proliferation and motility induced by insulin in MCF-7 cells breast cancer model.

On June 2016, a major bloom of Dinophysis acuminata complex was noticed over the coast of Parana State (PR), southern Brazil, an area unprotected by any official monitoring program. Here we report the results of an extensive sampling effort that ultimately led PR authorities to issue the first State shellfish-harvesting ban due to multi-species okadaic acid (OA) contamination. During its peak, the bloom covered an area of 201 km2 (∼2.0–3.5 × 54.0 km), attaining unprecedentedly high cell densities along the shallow (

A theoretical model to describe heat transport in functionally graded nanomaterials is developed in the framework of extended thermodynamics. The heat-transport equation used in our theoretical model is of the Maxwell–Cattaneo type. We study the propagation of acceleration waves in functionally graded materials (FGMs). In the special case of functionally graded Si 1− c Ge c thin layers, we point out the influence of the composition gradient on the propagation of heat pulses. A possible use of heat pulses as exploring tool to infer the inner composition of FGMs is suggested.

The term ‘big data’ has recently emerged to describe a range of technological and commercial trends enabling the storage and analysis of huge amounts of customer data, such as that generated by social networks and mobile devices. Much of the commercial promise of big data is in the ability to generate valuable insights from collecting new types and volumes of data in ways that were not previously economically viable. At the same time a number of questions have been raised about the implications for individual privacy. This paper explores key perspectives underlying the emergence of big data, and considers both the opportunities andethical challenges raised for market research.

Serotonergic neurotransmission is mediated by at least 14 subtypes of 5-HT receptors. Among these, the CNS serotonin receptor 7 (5-HTR7) is involved in diverse physiological processes. Here we show that treatment of murine striatal and cortical neuronal cultures with 5-HTR7 agonists (8-OH-DPAT and LP-211) significantly enhances neurite outgrowth. This effect is abolished by the selective 5-HTR7 antagonist SB-269970, by the ERK inhibitor U0126, by the cyclin-dependent kinase 5 (Cdk5) inhibitor roscovitine, as well as by cycloheximide, an inhibitor of protein synthesis. These data indicate that 5-HTR7 activation stimulates extensive neurite elongation in CNS primary cultures, subserved by ERK and Cdk5 activation, and de novo protein synthesis. Two-dimensional (2D) gel electrophoresis coupled to Western blot analyses reveals both qualitative and quantitative expression changes in selected cytoskeletal proteins, following treatment of striatal primary cultures with LP-211. In particular, the 34 kDa isoform of MAP1B is selectively expressed in stimulated cultures, consistent with a role of this protein in tubulin polymerization and neurite elongation. In summary, our results show that agonist-dependent activation of the endogenous 5-HTR7 in CNS neuronal primary cultures stimulates ERK- and Cdk5-dependent neurite outgrowth, sustained by modifications of cytoskeletal proteins. These data support the hypothesis that the 5-HTR7 might play a crucial role in shaping neuronal morphology and behaviorally relevant neuronal networks, paving the way to new approaches able to modulate CNS connectivity. © 2012 Elsevier Ltd. All rights reserved.

Fast real-time PCR TaqMan assays were developed and validated for species identification in dairy products. Based on the amplification of 12S rRNA and cytB partial genes of mitochondrial DNA, the methods were demonstrated to be sensitive, fast, and species-specific for Bos taurus, Ovis aries, Bubalus bubalis, and Capra hircus. The limit of detection calculated was lower than 1%, and the efficiency was reported to be higher than 96% in every assay. An internal amplification control was used to detect possible false negatives. The method was validated by means of laboratory-prepared samples mixing different species. Moreover, 18 commercial dairy samples were analyzed by both real-time PCR and isoelectric focusing, the official European Union reference method. The 4 TaqMan assays were confirmed to be a useful tool for milk and dairy product authentication.

STUDY QUESTION Is the methylation status of the methylenetetrahydrofolate reductase (MTHFR) promoter region in semen samples associated with 'recurrent spontaneous abortion' (RSA)? SUMMARY ANSWER MTHFR promoter hypermethylation is more frequent in semen samples from RSA couples than in semen samples from infertile couples with no history of RSA (NRSA) and affects the whole sperm population significantly more often. WHAT IS KNOWN ALREADY Modifications to the MTHFR gene such as polymorphisms and promoter methylations are associated with male infertility. STUDY DESIGN, SIZE AND DURATION Retrospective cohort study of semen samples from 20 RSA couples, 147 NRSA couples and 20 fertile men between 2011 and 2012. MATERIALS, SETTING AND METHODS DNA from the semen samples of RSA, NRSA and fertile men were analyzed by methylation-specific PCR amplification using primers which anneal to the methylated or unmethylated cytosine-phosphodiester bond guanine (CpG) islands within the promoter region of MTHFR. The specificity of the PCR products was assessed by DNA sequencing. MAIN RESULTS AND THE ROLE OF CHANCE The methylated MTHFR epigenotype (including samples where it co-existed with unmethylated MTHFR epigenotypes) was detected in 75% of RSA men, 54% of NRSA men and 15% of fertile men. MTHFR methylation was observed in the whole sperm population in semen samples from 55% of RSA men compared with 8% in NRSA men (P < 0.05) and 0% in fertile men (P < 0.05). DNA sequencing analysis was fully concordant with the PCR results and revealed that when MTHFR methylation occurred, CpG islands within the promoter region were 100% methylated (hypermethylation of MTHFR promoter). LIMITATIONS, REASONS FOR CAUTION The relatively small sample size of RSA infertile couples. WIDER IMPLICATIONS OF THE FINDINGS The hypermethylation of the MTHFR gene promoter should be taken into consideration as a novel putative risk factor in RSA etiology. STUDY FUNDING/COMPETING INTEREST(S) Our institution has received an FAR research grant from the University of Ferrara, Ferrara, Italy. No competing interests declared.

Human granulocytic anaplasmosis (HGA) is an emerging tick-borne zoonosis worldwide. As is the case for many tick-borne diseases, the epidemiological cycle is associated to the environmental conditions, including the presence of wild vertebrate reservoir hosts, vectors, climate and vegetation. In this study a total number of 87 spleen samples of wild ruminants carcasses from Central Italy, and 77 Ixodes ricinus collected from the same dead animals were screened for Anaplasma phagocytophilum by using Real Time PCR. A. phagocytophilum DNA was detected in 75%, 66.7% and 54.2% of the spleen samples from red deer (Cervus elaphus), Apennine chamois (Rupicapra pyrenaica ornata) and roe deer (Capreolus capreolus) respectively, whereas it was detected in the 31.2% of I. ricinus. A total of 27 positive samples were characterized by sequencing a portion of the groEL gene. Two A. phagocytophilum lineages could clearly be delineated from the phylogenetic tree. Four sequences from red deer, 2 from I. ricinus and 1 from Apennine chamois clustered into lineage I together with those previously described as virulent genotypes related to HGA. The presence of A. phagocytophilum DNA in the Apennine chamois represents the first report for this Italian endemic subspecies.

Il presente articolo si pone l'obiettivo di analizzare la Proposta della Commissione europea e l'attuale contesto normativo e operativo. La proposta sul nuovo regolamento per lo sviluppo rurale 2014-2020 conferma l'orientamento della Commissione, chiaramente emerso durante i lavori preparatori, di prevedere nel II Pilastro della Politica Agricola Comunitaria (PAC) risorse dedicate alla gestione dei rischi in agricoltura, incluso quello di reddito. In particolare, la Comunicazione della Commissione del 18 novembre 2010 (1) ha evidenziato, in diversi passaggi, l'esigenza di irrobustire la strumentazione disponibile agli agricoltori europei per fronteggiare un'esposizione ai rischi istituzionali, naturali e di mercato, che nel corso di questi ultimi anni si è progressivamente ampliata.

We observed that sex steroid hormones, like growth factors, stimulate the Src/Ras/erk pathway of cell lines derived from human mammary or prostate cancers. In addition, hormone-dependent pathway activation can be induced in Cos cells, upon transfection of classic steroid receptors. Cross-talks between sex steroid receptors regulate their association with Src and consequent pathway activation. Oestradiol treatment of MCF-7 cells triggers simultaneous association of ER with Src and p85, the regulatory subunit of phosphatidylinositol-3-kinase (PI3-kinase) and activation of Src- and PI3-K-dependent pathways. Activation of the latter pathway triggers cyclin D1 transcription, that is unaffected by Mek-1 activation. This suggests that simultaneous activation of different signalling effectors is required to target different cell cycle components. Thus, a novel reciprocal cross-talk between the two pathways appears to be mediated by the ER. In all tested cells, activation of the signalling pathways has a proliferative role. Transcriptionally inactive ER expressed in NIH 3T3 cells responds to hormone causing Src/Ras/Erk pathway activation and DNA synthesis. This suggests that in these cells genomic activity is required for later events of cell growth.

To investigate the factor structure of psychotic symptoms, we compared the clinical characteristics of manic patients with those of schizophrenic patients evaluated with positive and negative syndrome scale (PANSS). The clinical symptoms of 148 bipolar patients and 86 schizophrenic patients hospitalized for an index psychotic episode were assessed. Schizophrenic patients showed more positive and cognitive symptoms than bipolars. The factor analysis of the two PANSS scores showed a three-factor solution with 'positive', 'negative' and 'mixed' depressive-activated factors for bipolars and 'positive', 'negative' and 'depressive' factors for schizophrenics. In both groups, the 'cognitive cluster' loaded on the first 'positive' factor while the 'lack of insight' (LOI) has a different meaning in the two groups, more related to the positive symptoms in the bipolar patients and more related to the negative symptoms in the schizophrenic patients. This finding suggests that LOI could be a non-unitary phenomenon in psychoses and it should be further explored to better elucidate differences in symptom structures between schizophrenic and bipolar disorders.

Background: The prognosis of the oral squamous cell carcinoma (OSCC) patients remains very poor, mainly due to their high propensity to invade and metastasize. E-cadherin reduced expression occurs in the primary step of oral tumour progression and gene methylation is a mode by which the expression of this protein is regulated in cancers. In this perspective, we investigated E-cadherin gene (CDH1) promoter methylation status in OSCC and its correlation with Ecadherin protein expression, clinicopathological characteristics and patient outcome. Methods: Histologically proven OSCC and paired normal mucosa were analyzed for CDH1 promoter methylation status and E-cadherin protein expression by methylation-specific polymerase chain reaction and immunohistochemistry. Colocalization of E-cadherin with epidermal growth factor (EGF) receptor (EGFR) was evidenced by confocal microscopy and by immunoprecipitation analyses. Results: This study indicated E-cadherin protein down-regulation in OSCC associated with protein delocalization from membrane to cytoplasm. Low E-cadherin expression correlated to aggressive, poorly differentiated, high grade carcinomas and low patient survival. Moreover, protein down-regulation appeared to be due to E-cadherin mRNA downregulation and CDH1 promoter hypermethylation. In an in vitro model of OSCC the treatment with EGF caused internalization and co-localization of E-cadherin with EGFR and the addition of demethylating agents increased E-cadherin expression. Conclusion: Low E-Cadherin expression is a negative prognostic factor of OSCC and is likely due to the hypermethylation of CDH1 promoter. The delocalization of E-cadherin from membrane to cytoplasm could be also due to the increased expression of EGFR in OSCC and the consequent increase of E-cadherin co-internalization with EGFR. © 2014 Bentham Science Publishers.

Cyclic adenosine 3'5' monophosphate (cAMP) and protein kinase A (PKA) cooperate with phosphatidylinositol 3' kinase (PI3K) signals in the control of growth and survival. To determine the molecular mechanism(s) involved, we identified and mutagenized a specific serine (residue 83) in p85alpha(PI3K), which is phosphorylated in vivo and in vitro by PKA. Expression of p85alpha(PI3K) mutants (alanine or aspartic substitutions) significantly altered the biological responses of the cells to cAMP. cAMP protection from anoikis was reduced in cells expressing the alanine version p85alpha(PI3K). These cells did not arrest in G1 in the presence of cAMP, whereas cells expressing the aspartic mutant p85D accumulated in G1 even in the absence of cAMP. S phase was still efficiently inhibited by cAMP in cells expressing both mutants. The binding of PI3K to Ras p21 was greatly reduced in cells expressing p85A in the presence or absence of cAMP. Conversely, expression of the aspartic mutant stimulated robustly the binding of PI3K to p21 Ras in the presence of cAMP. Mutation in the Ser 83 inhibited cAMP, but not PDGF stimulation of PI3K. Conversely, the p85D aspartic mutant amplified cAMP stimulation of PI3K activity. Phosphorylation of Ser 83 by cAMP-PKA in p85alpha(PI3K) was also necessary for estrogen signaling as expression of p85A or p85D mutants inhibited or amplified, respectively, the binding of estrogen receptor to p85alpha and AKT phosphorylation induced by estrogens. The data presented indicate that: (1) phosphorylation of Ser 83 in p85alpha(PI3K) is critical for cAMP-PKA induced G1 arrest and survival in mouse 3T3 fibroblasts; (2) this site is necessary for amplification of estrogen signals by cAMP-PKA and related receptors. Finally, these data suggest a general mechanism of PI3K regulation by cAMP, operating in various cell types and under different conditions.

This paper contains a numerical examination concerning the ignition behavior of a spray nozzle mounted in a rectangular channel under atmospheric conditions which is run with Jet A-1. On the basis of a comprehensive data set of experimental results, the numerical approach is verified primarily by means of a comparison of the flame growth and position after ignition. In the following several distinct igniter positions and boundary condition settings are simulated. The conditions which prevail at the location of the ignition are investigated with respect to how they influence the ignition process. Due to changes in the fuel placement and flow field characteristics which follow from alternating the boundary conditions such as air and fuel mass flow, ignition is either promoted or impeded. The underlying causes which can lead to a success or failure of the ignition are analyzed. The ignition in the experiment is achieved through a laser-induced breakdown, which is modelled through a Turbulent Flame Speed Closure combustion model with an additional spark ignition extension. A comparison with the ignition statistics from the experiment shows that numerical tools can be used to determine preferential boundary conditions and igniter locations to accomplish a successful ignition in multiphase flow configurations.Copyright © 2012 by ASME

Brugada Syndrome (BS) is a polygenic inherited cardiac disease characterized by life-threatening arrhythmias and high incidence of sudden death. In this study, two-dimensional gel electrophoresis (2D-PAGE) coupled to mass spectrometry (LC-MS/MS) was used to investigate specific changes in the plasma proteome of BS patients and family members sharing the same gene mutation (SCN5AQ1118X), with the aim to identify novel disease biomarkers. Our data demonstrate that the levels of several proteins were significantly altered in BS patients compared with controls. In particular, apolipoprotein E, prothrombin, vitronectin, complement-factor H, vitamin-D-binding protein, voltage-dependent anion-selective channel protein 3 and clusterin were considerably increased in plasma sample of BS patients, whereas alpha-1-antitrypsin, fibrinogen and angiotensinogen were considerably decreased; moreover, post-translational modifications of antithrombin-III were detected in all affected individuals. On the light of these results, we hypothesize that these proteins might be considered as potential markers for the identification of disease status in BS.

Some species of Candida are opportunistic pathogens that can cause disease in a host immunocompromised by underlying local or systemic pathological processes. C. albicans is the species most often associated with oral lesions, but other species of Candida, including C. glabrata, C. tropicalis and C. parapsilosis, have also been isolated in the saliva of subjects with and without candidiasis. In the present study we evaluated the host defence mechanisms induced by Candida albicans and other Candida species in monocytes and oral epithelial cells in order to establish the existence of a species-specific cellular response. Our results indicated that, during Candida species infection, the epithelial cells actively participate in the host defence by producing antimicrobial peptides and proinflammatory cytokines. Moreover, in infections caused by Candida tropicalis and Candida glabrata, the host defence may be strengthened by the release of perforin and granzyme by polymorphonuclear leukocytes recruited at the site of infection. Copyright © by BIOLIFE, s.a.s.

Orthodontics is a branch of dentistry that aims at the resolution of dental malocclusions. The specialist carries out the treatment using intraoral or extraoral orthodontic appliances that require forces of a given load level to obtain a tooth movement in a certain direction in dental arches. Orthodontic tooth movement is dependent on efficient remodeling of periodontal ligament and alveolar bone, correlated with several biological and mechanical responses of the tissues surrounding the teeth. A periodontal ligament placed under pressure will result in bone resorption whereas a periodontal ligament under tension results in bone formation. In the primary stage of the application of orthodontic forces, an acute inflammation occurs in periodontium. Several proinflammatory cytokines are produced by immune-competent cells migrating by means of dilated capillaries. In this paper we summarize, also through the utilization of animal models, the role of some of these molecules, namely, interleukin-1βand vascular endothelial growth factor, that are some proliferation markers of osteoclasts and osteoblasts, and the macrophage colony stimulating factor.

A swirled can combustor is the object of the numerical study presented in this paper. Simulation parameters are chosen to realize a lean premixed combustion process, as it is nowadays typical for industrial low NOx burners. The fuel considered is gaseous methane. Accurate numerical experiments, performed with reliable hybrid LES-RANS methods, create the database to address and analyze dierent unstable processes in the system. Particular attention is given to the cooling eect of walls on the flame root next to the combustion chamber dump plane, since this interaction may lead to thermo-kinetic instabilities, as it is observed in our study. The dynamics of the structures typical of confined swirled flows are also investigated. A link between the tornado-like vortical structure at the outlet of the combustion chamber and a high frequency instability is suggested.

Steroid hormones are expressed at low levels in mesenchymal cells and are highly expressed in soft tissue sarcoma. In human soft tissue fibrosarcoma cell line (HT-1080), the epidermal growth factor (EGF) stimulates the express of matrix metal (MMPs) expression through a Src-dependent mechanism. In human fibrosarcomas, increased expression of MMPs correlates with the metastatic progression. Our recent data in human breast cancer cell line MCF-7, demonstrates that EGF stimulates estradiol receptor (ER) phosphorylation on tyrosine at position 537 thereby promoting the association of a complex among EGF receptor (EGFR), androgen receptor (AR), ER, and Src that activates EGF-dependent signaling pathway. In the present study, we demonstrate that, in HT-1080 cells, the Src kinase activity is involved in EGFR phosphorylation and this activity is regulated by an interplay between Src, steroid receptors, and EGFR. In these cells, estradiol (E(2))/ER and synthetic androgen (R1881)/AR trans-activate EGFR leading to the downstream signaling and to ERK activation. Indeed, the association between ER/AR and EGFR enhances metastatic progression of fibrosarcoma tumors. A population pilot study performed on 16 patients with soft tissue neoplasias highlights that MMPs expression correlates with progression of anaplastic sarcoma as well as overexpression of EGFR. These findings suggest that there is a crosstalk among AR, ER, and EGFR that lead to src activation also in fibrosarcoma cells. J. Cell. Physiol. 226: 2997-3003, 2011. (C) 2011 Wiley-Liss, Inc.