Predicting groundwater salinity changes in the coastal aquifer of Arborea (Central Western Sardinia)

The area of Arborea, extending over roughly 70 km2, is located in the Northern Campidano plain (central-western Sardinia - Italy). The plain, that was formed in a tectonic trough of the Tertiary, is characterised by Quaternary deposits of fluvial, lacustrine, marine and eolian facies. The Quaternary formation is several hundred meters thick. The stratigraphic sequence, whose characteristics vary from one place to another, is generally represented by gravelly, sandy, silty and clayey deposits. The aquifer basin consists of two main units, a shallow phreatic aquifer (around ten meters thick) and a deeper semiconfined - confined unit, separated by a variable thickness aquitard. The system is recharged by rainfall, irrigation and by lateral inflow from the volcanic rock aquifers bordering the plain. Owing to inadequate water management policies, the Arborea coastal aquifer system has been contaminated by seawater intrusion as a result of overexploitation during the frequent droughts that affect Sardinia. Groundwater withdrawals have caused saltwater to encroach landward and upward toward the withdrawal points. Periodic monitoring, carried out for several years by the Department of Land Engineering at the University of Cagliari showed a varying degree of salt water intrusion along the coast. High electrical conductivity values were found mostly in the deeper aquifer, as it is locally overexploited, whereas lower values were recorded in the shallow phreatic aquifer. Nevertheless, in the shallow aquifer the extension of contaminated areas is larger than in the deep aquifer. In this work an extensive quality assessment of the data was performed to characterise the area overlying the Arborea aquifer system. In this context we set up a geographical information system and applied an environmental model to study the migration of the contaminants. A preliminary model, elaborated with the CODESA 3D code, was implemented to simulate the impact of land management (different groundwater abstraction schemes, artificial recharge etc.) on the salt dispersion process.243-25

Cognition across the lifespan: Investigating age, sex, and other sociodemographic influences

Maintaining cognitive health across the lifespan has been the focus of a multi-billion-dollar industry. In order to guide treatment and interventions, a clear understanding of the way that proficiency in different cognitive domains develops and declines in both sexes across the lifespan is necessary. Additionally, there are sex differences in a range of other factors, including psychiatric illnesses such as anxiety, depression, and substance use, that are also known to affect cognition, although the scale of this interaction is unknown. Our objective was to assess differences in cognitive function across the lifespan in men and women in a large, representative sample. Leveraging online cognitive testing, a sample of 9451 men and 9451 women ranging in age from 12 to 69 (M = 28.21) matched on socio-demographic factors were studied. Segmented regression was used to model three cognitive domains—working memory, verbal abilities, and reasoning. Sex differences in all three domains were minimal; however, after broadening the sample in terms of socio-demographic factors, sex differences appeared. These results suggest that cognition across the lifespan differs for men and women, but is greatly influenced by environmental factors. We discuss these findings within a framework that describes sex differences in cognition as likely guided by a complex interplay between biology and environment

hMENA11a contributes to HER3-mediated resistance to PI3K inhibitors in HER2-overexpressing breast cancer cells.

Human Mena (hMENA), an actin regulatory protein of the ENA/VASP family, cooperates with ErbB receptor family signaling in breast cancer. It is overexpressed in high-risk preneoplastic lesions and in primary breast tumors where it correlates with HER2 overexpression and an activated status of AKT and MAPK. The concomitant overexpression of hMENA and HER2 in breast cancer patients is indicative of a worse prognosis. hMENA is expressed along with alternatively expressed isoforms, hMENA11a and hMENAΔv6 with opposite functions. A novel role for the epithelial-associated hMENA11a isoform in sustaining HER3 activation and pro-survival pathways in HER2-overexpressing breast cancer cells has been identified by reverse phase protein array and validated in vivo in a series of breast cancer tissues. As HER3 activation is crucial in mechanisms of cell resistance to PI3K inhibitors, we explored whether hMENA11a is involved in these resistance mechanisms. The specific hMENA11a depletion switched off the HER3-related pathway activated by PI3K inhibitors and impaired the nuclear accumulation of HER3 transcription factor FOXO3a induced by PI3K inhibitors, whereas PI3K inhibitors activated hMENA11a phosphorylation and affected its localization. At the functional level, we found that hMENA11a sustains cell proliferation and survival in response to PI3K inhibitor treatment, whereas hMENA11a silencing increases molecules involved in cancer cell apoptosis. As shown in three-dimensional cultures, hMENA11a contributes to resistance to PI3K inhibition because its depletion drastically reduced cell viability upon treatment with PI3K inhibitor BEZ235. Altogether, these results indicate that hMENA11a in HER2-overexpressing breast cancer cells sustains HER3/AKT axis activation and contributes to HER3-mediated resistance mechanisms to PI3K inhibitors. Thus, hMENA11a expression can be proposed as a marker of HER3 activation and resistance to PI3K inhibition therapies, to select patients who may benefit from these combined targeted treatments. hMENA11a activity could represent a new target for antiproliferative therapies in breast cancer

IMP-3 expression in keratoacanthomas and squamous cell carcinomas of the skin: an immunohistochemical study

<p>The protein insulin-like growth factor II mRNA binding protein 3 (IMP3) is an important factor for cell migration and adhesion in malignancies. Recent studies have shown a remarkable overexpression of IMP3 in different human malignant neoplasms and also revealed it as an important prognostic marker in some tumor entities. The purpose of this study is to compare IMP3 immunostaining in squamous cellular skin tumor and determine whether IMP3 can aid in the differential diagnosis of these lesions. To our knowledge, IMP3 expression has not been investigated in skin squamous cell proliferations thus far. Immunohistochemical staining for IMP3 was performed on slides organized by samples from 67 patients, 34 with keratoacanthoma and 33 with primary squamous cell carcinoma (16 invasive and 17 <em>in</em><em> situ</em>). The majority of our KAs (25/34) were negative for IMP-3 staining. The majority of SCCs (19/33) are positive for IMP3 staining. The percentage of IMP3 positive cells increases significantly in group SCC (p=0.0111), and in particular in the SCC <em>in situ</em> group (p=0.0021) with respect to the KA group.  IMP3 intensity staining increases significantly in SCCs (p=0.0213), and particularly in SCCs (p=0.008) with respect to KA. Our data show that IMP3 expression is different in keratoacanthomas with respect to squamous cell carcinoma. IMP3 assessment and staining pattern, together with a careful histological study, can be useful in the differential diagnosis between KA e SCC.</p

Apoptosis induced by a HIPK2 full-length-specific siRNA is due to off-target effects rather than prevalence of HIPK2-Δe8 isoform.

Small interfering RNAs (siRNAs) are widely used to study gene function and extensively exploited for their potential therapeutic applications. HIPK2 is an evolutionary conserved kinase that binds and phosphorylates several proteins directly or indirectly related to apoptosis. Recently, an alternatively spliced isoform skipping 81 nucleotides of exon 8 (Hipk2-∆e8) has been described. Selective depletion of Hipk2 full-length (Hipk2-FL) with a speci c siRNA that spares the Hipk2-∆e8 isoform has been shown to strongly induce apoptosis, suggesting an unpredicted dominant- negative effect of Hipk2-FL over the ∆e8 isoform. From this observation, we sought to take advantage and assessed the therapeutic potential of generating Hipk2 isoform unbalance in tumor-initiating cells derived from colorectal cancer patients. Strong reduction of cell viability was induced in vitro and in vivo by the originally described exon 8-speci c siRNA, supporting a potential therapeutic application. However, validation analyses performed with additional exon8-speci c siRNAs with different stabilities showed that all exon8-targeting siRNAs can induce comparable Hipk2 isoform unbalance but only the originally reported e8-siRNA promotes cell death. These data show that loss of viability does not depend on the prevalence of Hipk2- ∆e8 isoform but it is rather due to microRNA-like off-target effects

Wt-p53 action in human leukaemia cell lines corresponding to different stages of differentiation.

Recent studies support the potential application of the wt-p53 gene in cancer therapy. Expression of exogenous wt-p53 suppresses a variety of leukaemia phenotypes by acting on cell survival, proliferation and/or differentiation. As for tumour gene therapy, the final fate of the neoplastic cells is one of the most relevant points. We examined the effects of exogenous wt-p53 gene expression in several leukaemia cell lines to identify p53-responsive leukaemia. The temperature-sensitive p53Val135 mutant or the human wt-p53 cDNA was transduced in leukaemia cell lines representative of different acute leukaemia FAB subtypes, including M1 (KG1), M2 (HL-60), M3 (NB4), M5 (U937) and M6 (HEL 92.1.7), as well as blast crisis of chronic myelogenous leukaemia (BC-CML: K562, BV173) showing diverse differentiation features. By morphological, molecular and biochemical analyses, we have shown that exogenous wt-p53 gene expression induces apoptosis only in cells corresponding to M1, M2 and M3 of the FAB classification and in BC-CML showing morphological and cytochemical features of undifferentiated blast cells. In contrast, it promotes differentiation in the others. Interestingly, cell responsiveness was independent of the vector used and the status of the endogenous p53 gene

Risk perception and ethnic background in construction workers: Results of a cross-sectional study in a group of trainees of a vocational school in italy

Risk perception can be influenced by cultural background. The study aims to evaluate risk perception, considering different ethnicities of construction workers from vocational schools in Italy. We administered a questionnaire investigating four different dimensions: Perceived behavioral control (PBC), Danger perception (DP), Safety climate (SC), and Attitude towards safe actions (ATSA). 562 workers answered: 72.4% from Italy, 14.2% from eastern Europe, 9.4% from Balkans, and 3.9% from North Africa. The participants indicated quite low control, attributable to the haste in performing the job. The workers perceived their specific job tasks as riskier compared to the tasks of their colleagues. They reported as fundamental the respecting of safety rules, but indicating that supervisors do not adequately promote safety behaviors. Finally, construction workers judged as \u201cbrave\u201d the colleagues working without protective equipment. When compared to Italians, North Africa workers showed a lower perception of the possibility to control their safe behaviors (p = 0.040), while both eastern Europeans and Balkan obtained higher scores at the ATSA dimension, indicating a kind of fatalistic acceptance of the risky situations at work. Eastern Europeans also showed a lower perception of the dangers (p = 0.002), while Balkan demonstrated a perception of SC even better than the Italian group (p = 0.005)