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The North Makran Domain in the Makran Accretionary Prism consists of an imbricate stack of Mesozoic Neo Tethyan ophiolitic and metaophiolitic units. The Deyader Complex is an important metamorphic unit of this Domain and includes tectonic slices of HP-LT blueschists derived from upper oceanic crust protoliths. The volcanic protoliths consist of basalts with Mg#=75.1-62.7, SiO2 = 41.59-48.02 wt%, and TiO2 = 0.79-1.53 wt%. Based on incompatible and REE contents and ratios, three geochemical types can be distinguished. Group 1 basalts show trace element compositions, and LaN/YbN and LaN/SmN ratios

Phthalates and bisphenol A (BPA), plasticizers used in several products of daily life, are considered as endocrine disrupters, therefore children exposure is particularly relevant. The LIFE PERSUADED project aims to define the following: (a) the evaluation of internal levels of DEHP's metabolites and BPA in Italian children and their mothers, (b) the association of the exposure with puberty development and obesity diseases, and (c) the effects of exposure in juvenile in vivo model. The cross-sectional study has involved 2160 mother-child pairs, including males and females, children and adolescents, from urban and rural areas of North, Center, and South Italy. A structured questionnaire and a food diary are designed to evaluate the association between lifestyle variables potentially related to DEHP/BPA exposure and internal levels, through univariate and multivariate analyses. Two pilot case-control studies are carried out on idiopathic premature thelarche and precocious puberty (30 girls each group, aged 2-7 years) and idiopathic obesity (30 boys and 30 girls, aged 6-10 years), matched to healthy controls. BPA and DEHP's metabolites are analyzed in urine samples from all recruited subjects. Clinical and toxicological biomarkers are evaluated in serum of case-control subjects. Moreover, the toxicity study is carried out in a juvenile rodent model exposed to mixtures of BPA and DEHP at dose levels recorded in children population. The scientific results of LIFE PERSUADED will contribute to risk assessment of BPA and DEHP.

Although the Po river is the most important fluvial system of Northern Italy, the systematic geochemical and isotopic investigations of its water are rare and were never reported for the whole basin. The present contribution aims to fill this knowledge gap, reporting a comprehensive data set including oxygen and hydrogen stable isotopes as well as major and trace element concentration of dissolved species for 54 Po river water samples, mainly collected in different hydrological conditions (peak discharge in April, drought in August) at increasing distance from the source, i.e., from the upper part of the catchment to the terminal (deltaic) part of the river at the confluence with the Adriatic Sea. The isotopic compositions demonstrate that the predominant part of the runoff derives from the Alpine sector of the catchment through important tributaries such as the Dora Baltea, Ticino, Adda, and Tanaro rivers, whereas the contribution from the Apennines tributaries is less important. The geochemical and isotopic compositions show that the Po river water attains a homogeneous composition at ca. 100 km from the source. The average composition is characterized by δ(18)O -9.8‰, δD -66.2‰, total dissolved solid (TDS) 268 mg/L, and chloride 17 mg/L and by a general Ca-HCO3 hydrochemical facies, which is maintained for most of the river stream, only varying in the terminal part where the river is diverted in a complex deltaic system affected by more significant evaporation and mixing with saline water evidenced by higher TDS and chloride content (up to 8198 and 4197 mg/L, respectively). Geochemical and isotopic maps have been drawn to visualize spatial gradients, which reflect the evolution of the river water composition at progressive distance from the source; more detailed maps were focused on the deltaic part in order to visualize the processes occurring in the transitional zone toward the Adriatic Sea. The data also highlight anthropogenic contributions, mainly represented by significant concentrations of nitrate (average 8 mg/L) and possibly arsenic (average 12 μg/L). These data allow the calculation of geochemical fluxes transferred from the river to the sea, and generally, they contribute to the definition of a "hydro-archive" which is useful to highlight ongoing variations in the related ecosystems.

Objectives. Chlamydia trachomatis genital infections can cause long-term complications in female reproductive tract, even in absence of acute symptoms. The most common complication is pelvic inflammatory disease (PID), that can lead to tubal infertility and extra-uterine pregnancies. Although the pathologic consequences of Chlamydia genital infection are well-established, the mechanisms leading to tissue damage are not completely understood. In this study we analyzed gene expression of metalloproteinases (MMP-2 and MMP-9) in genital organs obtained from female mice infected by C. muridarum, closely mimicking human infections in the mouse model. Methods. All the experiments were approved by the Ethical Committee of the University of Bologna. Animals used were 30 female Balb/c mice, 6-8 weeks old. All the animals received medroxyprogesterone acetate 9 and 2 days prior the infection. Twelve mice were infected by placing 15 μl of sucrose-phosphate-glutamic acid (SPG) buffer containing 106 inclusion forming units (IFUs) of C. muridarum into the vaginal vault. Twelve animals were treated with 15 μl of SPG containing heat-inactivated 106 IFUs of C. muridarum. As controls of inflammation, 6 animals were challenged with 15 μl of SPG. At 3, 10, and 20 days post-infection 4 infected animals, 4 animals inoculated with heat-inactivated bacteria and 2 controls were sacrificed. Genital tracts were divided into the cervical-vaginal region, uterine horns, and oviducts. A part of uterine horns, oviducts and vagina were stored in formalin and later processed for histological examinations. The remaining parts of the organs were used for RNA extraction, by using Trizol Reagent (Invitrogen), in combination with RNeasy Mini Kit (Qiagen). cDNA was synthesized with 500 ng of total RNA and SuperScript III RT (Invitrogen). Real-time RT-PCR was performed with SYBR Green Fast start kit (Roche Diagnostics). Primers used in Real-time RT-PCR to assess GAPDH, MMP-2, and MMP-9 levels were from SuperArray (SABiosciences Corporation). Results. At histological examination no controls showed inflammation. On the contrary, scores of inflammation in all the organs from infected animals peaked at day 10, whereas only a single animal inoculated with inactivated bacteria showed a very mild inflammation at day 10 in its right uterine horn. At day 10, organs from infected animals showed significantly higher gene expression of MMP-2 and MMP-9 than the respective organs obtained from non-infected mice. Conclusions. Our study showed statistically significant higher MMPs gene expression in infected animals compared to both controls and animals injected with inactivated chlamydiae. These results confirm the pivotal role of MMPs in the development of tissue damage observed during Chlamydia genital infection.

The prevalence of asthma increased worldwide until the 1990s, but since then there has been no clear temporal pattern. The present study aimed to assess time trends in the prevalence of current asthma, asthma-like symptoms and allergic rhinitis in Italian adults from 1990 to 2010. The same screening questionnaire was administered by mail or phone to random samples of the general population (age 20-44 yrs) in Italy, in the frame of three multicentre studies: the European Community Respiratory Health Survey (ECRHS) (1991-1993; n=6,031); the Italian Study on Asthma in Young Adults (ISAYA) (1998-2000; n=18,873); and the Gene Environment Interactions in Respiratory Diseases (GEIRD) study (2007-2010; n=10,494). Time trends in prevalence were estimated using Poisson regression models in the centres that repeated the survey at different points in time. From 1991 to 2010, the median prevalence of current asthma, wheezing and allergic rhinitis increased from 4.1% to 6.6%, from 10.1% to 13.9% and from 16.8% to 25.8%, respectively. The prevalence of current asthma was stable during the 1990s and increased (relative risk 1.38, 95% CI 1.19-1.59) from 1998-2000 to 2007-2010, mainly in subjects who did not report allergic rhinitis. The prevalence of allergic rhinitis has increased continuously since 1991. The asthma epidemic is not over in Italy. During the past 20 yrs, asthma prevalence has increased by 38%, in parallel with a similar increase in asthma-like symptoms and allergic rhinitis. Copyright©ERS 2012.

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Among perinatal stem cells of the umbilical cord, human Wharton’s jelly mesenchymal stem cells (hWJ-MSCs) are of great interest for cell-based therapy approaches in regenerative medicine, showing some advantages over other MSCs. In fact, hWJ-MSCs, placed between embryonic and adult MSCs, are not tumorigenic and are harvested with few ethical concerns. Furthermore, these cells can be easily cultured in vitro, maintaining both stem properties and a high proliferative rate for several passages, as well as trilineage capacity of differentiation. Recently, it has been demonstrated that cytoskeletal organization influences stem cell biology. Among molecules able to modulate its dynamics, Cytochalasin B (CB), a cyto-permeable mycotoxin, influences actin microfilament polymerization, thus affecting several cell properties, such as the ability of MSCs to differentiate towards a specific commitment. Here, we investigated for the first time the effects of a 24 h-treatment with CB at different concentrations (0.1–3 μM) on hWJ-MSCs. CB influenced the cytoskeletal organization in a dose-dependent manner, inducing changes in cell number, proliferation, shape, and nanomechanical properties, thus promoting the osteogenic commitment of hWJ-MSCs, as confirmed by the expression analysis of osteogenic/autophagy markers.

ERBB3, also known as HER3, is a tyrosine kinase transmembrane receptor of the ERBB family. Upon binding to neuregulin 1 (NRG1), ERBB3 preferentially dimerizes with HER2 (ERBB2), in turn inducing aggressive features in several cancer types. The analysis of a dataset of breast cancer patients unveiled that higher ERBB3 mRNA expression correlates with shorter relapse-free survival in basal-like breast cancers, despite low ERBB3 expression in this breast cancer subtype. Administration of neuregulin 1 beta (NRG1β) significantly affected neither cellular proliferation nor the basal migratory ability of basal-like/triple-negative quasi-normal MCF10A breast cells, cultured in mono-layer conditions. Furthermore, no significant regulation in cell morphology or in the expression of basal/myoepithelial and luminal markers was observed upon stimulation with NRG1β. In non-adherent conditions, NRG1β administration to MCF10A cells did not significantly influence cell survival; however, it robustly induced cell growth as spheroids (3D growth). Intriguingly, a remarkable upregulation of ERBB3 and ERBB2 protein abundance was observed in 3D compared to 2D cell cultures, and NRG1β-induced 3D cell growth was efficiently prevented by the anti-HER2 monoclonal antibody pertuzumab. Similar results were obtained by the analysis of basal-like/triple-negative breast cancer cellular models, MDA-MB-468 and MDA-MB-231 cells, in which NRG1β induced anchorage-independent cell growth that in turn was prevented or reduced by the simultaneous administration of anti-HER2 neutralizing antibodies. Finally, the ability of pertuzumab in suppressing NRG1β-induced 3D growth was also evaluated and confirmed in MCF10A engineered with HER2-overexpression. We suggest that the NRG1/ERBB3/ERBB2 pathway promotes the anchorage-independent growth of basal-like breast cancer cells. Importantly, we provide evidence that ERBB2 neutralization, in particular by pertuzumab, robustly inhibits this process. Our results pave the way towards the development of novel anticancer strategies for basal-like breast cancer patients based on the interception of the NRG1/ERBB3/ERBB2 signaling axis.

We discuss emerging views on the complexity of signals controlling the onset of biological shapes and functions, from the nanoarchitectonics arising from supramolecular interactions, to the cellular/multicellular tissue level, and up to the unfolding of complex anatomy. We highlight the fundamental role of physical forces in cellular decisions, stressing the intriguing similarities in early morphogenesis, tissue regeneration, and oncogenic drift. Compelling evidence is presented, showing that biological patterns are strongly embedded in the vibrational nature of the physical energies that permeate the entire universe. We describe biological dynamics as informational processes at which physics and chemistry converge, with nanomechanical motions, and electromagnetic waves, including light, forming an ensemble of vibrations, acting as a sort of control software for molecular patterning. Biomolecular recognition is approached within the establishment of coherent synchronizations among signaling players, whose physical nature can be equated to oscillators tending to the coherent synchronization of their vibrational modes. Cytoskeletal elements are now emerging as senders and receivers of physical signals, “shaping” biological identity from the cellular to the tissue/organ levels. We finally discuss the perspective of exploiting the diffusive features of physical energies to afford in situ stem/somatic cell reprogramming, and tissue regeneration, without stem cell transplantation.