The Language of Adolescents in Depicting Migrants

This study (N = 161 Italian adolescents attending 11th and 12th grade of secondary school) investigated how adolescents linguistically portray migrants. Over a year and a half, the study considered whether positive factors known to reduce social discrimination – i.e., multiple categorization of migrants and/or the degree of identification with the human group – are associated with relatively unbiased linguistic descriptions of migrants. The coding system had three categories of terms referring to the outgroup: generalized/categorical definitions, individuating piecemeal information or membership in the human group. We found that adolescents who used multiple categorizations to describe migrants and self-identified with the human group (at T1) also linguistically described migrants in human and individuating terms (at T2). The findings are discussed underlying the implications of defying the self and outgroups in multiple complex ways through language, as an ecological means used by adolescents to communicate their views of others

When Just One Phosphate Is One Too Many: The Multifaceted Interplay between Myc and Kinases

Myc transcription factors are key regulators of many cellular processes, with Myc target genes crucially implicated in the management of cell proliferation and stem pluripotency, energy metabolism, protein synthesis, angiogenesis, DNA damage response, and apoptosis. Given the wide involvement of Myc in cellular dynamics, it is not surprising that its overexpression is frequently associated with cancer. Noteworthy, in cancer cells where high Myc levels are maintained, the overexpression of Myc-associated kinases is often observed and required to foster tumour cells' proliferation. A mutual interplay exists between Myc and kinases: the latter, which are Myc transcriptional targets, phosphorylate Myc, allowing its transcriptional activity, highlighting a clear regulatory loop. At the protein level, Myc activity and turnover is also tightly regulated by kinases, with a finely tuned balance between translation and rapid protein degradation. In this perspective, we focus on the cross-regulation of Myc and its associated protein kinases underlying similar and redundant mechanisms of regulation at different levels, from transcriptional to post-translational events. Furthermore, a review of the indirect effects of known kinase inhibitors on Myc provides an opportunity to identify alternative and combined therapeutic approaches for cancer treatment

Modulation of STAT3 signaling, cell redox defenses and cell cycle checkpoints by β-caryophyllene in cholangiocarcinoma cells: possible mechanisms accounting for doxorubicin chemosensitization and chemoprevention

Cholangiocarcinoma (CCA) is an aggressive group of biliary tract cancers, characterized by late diagnosis, low effective chemotherapies, multidrug resistance, and poor outcomes. In the attempt to identify new therapeutic strategies for CCA, we studied the antiproliferative activity of a combination between doxorubicin and the natural sesquiterpene β-caryophyllene in cholangiocarcinoma Mz-ChA-1 cells and nonmalignant H69 cholangiocytes, under both long-term and metronomic schedules. The modulation of STAT3 signaling, oxidative stress, DNA damage response, cell cycle progression and apoptosis was investigated as possible mechanisms of action. β-caryophyllene was able to synergize the cytotoxicity of low dose doxorubicin in Mz-ChA-1 cells, while producing cytoprotective effects in H69 cholangiocytes, mainly after a long-term exposure of 24 h. The mechanistic analysis highlighted that the sesquiterpene induced a cell cycle arrest in G2/M phase along with the doxorubicin-induced accumulation in S phase, reduced the γH2AX and GSH levels without affecting GSSG. ROS amount was partly lowered by the combination in Mz-ChA-1 cells, while increased in H69 cells. A lowered expression of doxorubicin-induced STAT3 activation was found in the presence of β-caryophyllene in both cancer and normal cholangiocytes. These networking effects resulted in an increased apoptosis rate in Mz-ChA-1 cells, despite a lowering in H69 cholangiocytes. This evidence highlighted a possible role of STAT3 as a final effector of a complex network regulated by β-caryophyllene, which leads to an enhanced doxorubicin-sensitivity of cholangiocarcinoma cells and a lowered chemotherapy toxicity in nonmalignant cholangiocytes, thus strengthening the interest for this natural sesquiterpene as a dual-acting chemosensitizing and chemopreventive agent

Microimaging FT-IR of Head and Neck Tumours. The case of salivary glands

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From the Amelioration of a NADP+-dependent Formate Dehydrogenase to the Discovery of a New Enzyme: Round Trip from Theory to Practice

NADP+-dependent formate dehydrogenases (FDHs) are biotechnologically relevant enzymes for cofactors regeneration in industrial processes employing redox biocatalysts. Their effective applicability is however hampered by the low cofactor and substrate affinities of the few enzymes described so far. After different efforts to ameliorate the previously studied GraFDH from the acidobacterium Granulicella mallensis MP5ACTX8, an enzyme having double (NAD+ and NADP+) cofactor specificity, we started over our search with the advantage of hindsight. We identified and characterized GraFDH2, a novel highly active FDH, which proved to be a good NAD+-dependent catalyst. A rational engineering approach permitted to switch its cofactor specificity, producing an enzyme variant that displays a 10-fold activity improvement over the wild-type enzyme with NADP+. Such variant resulted to be one of the best performing enzyme among the NADP+-dependent FDHs reported so far in terms of catalytic performance

Shmt2: a stat3 signaling new player in prostate cancer energy metabolism

Prostate cancer (PCa) is a multifactorial disease characterized by the aberrant activity of different regulatory pathways. STAT3 protein mediates some of these pathways and its activation is implicated in the modulation of several metabolic enzymes. A bioinformatic analysis indicated a STAT3 binding site in the upstream region of SHMT2 gene. We demonstrated that in LNCaP, PCa cells' SHMT2 expression is upregulated by the JAK2/STAT3 canonical pathway upon IL-6 stimulation. Activation of SHTM2 leads to a decrease in serine levels, pushing PKM2 towards the nuclear compartment where it can activate STAT3 in a non-canonical fashion that in turn promotes a transient shift toward anaerobic metabolism. These results were also confirmed on FFPE prostate tissue sections at different Gleason scores. STAT3/SHMT2/PKM2 loop in LNCaP cells can modulate a metabolic shift in response to inflammation at early stages of cancer progression, whereas a non-canonical STAT3 activation involving the STAT3/HIF-1α/PKM2 loop is responsible for the maintenance of Warburg effect distinctive of more aggressive PCa cells. Chronic inflammation might thus prime the transition of PCa cells towards more advanced stages, and SHMT2 could represent a missing factor to further understand the molecular mechanisms responsible for the transition of prostate cancer towards a more aggressive phenotyp

Evaluation and validation of an alternative method to detect Campylobacter spp. in dairy products

Foods implicated in human campylobacteriosis include raw or undercooked poultry and raw dairy products. Because Campylobacter spp. are the most frequently reported cause of bacterial infection in the European Union and because conventional methods are cumbersome, rapid methods for Campylobacter detection and quantification in food are needed. With this study we sought to validate, according to the standard procedure (UNI EN ISO 16140:2003), an alternative to the reference analytical method (UNI EN ISO 10272- 1:2006) for official controls of Campylobacter spp. in raw milk and dairy products. Milk samples collected from 16 milk vending machines located throughout the Genoa metropolitan area were analyzed using two different methods, an enzymelinked fluorescent assay (ELFA) and a real-time PCR assay, and evaluated in parallel against the reference method. In addition, a total of 460 samples of raw milk collected from milk vending machines were analyzed by ELFA. Results obtained with ELFA showed it was compliant with UNI EN ISO 10272-1:2006 criteria and that the immunoassay had 100% sensitivity, specificity, and accuracy. Regarding samples of milk vending machines, 5.0% (23/460) tested positive at ELFA screening and were subsequently confirmed as C. jejuni. Validation according to UNI EN ISO 16140:2003 of the ELFA method suggests it may be a useful alternative to conventional methods for detecting Campylobacter spp. in official controls

The Imaging X-ray Polarimetry Explorer (IXPE): Technical Overview

The Imaging X-ray Polarimetry Explorer (IXPE) will expand the information space for study of cosmic sources, by adding linear polarization to the properties (time, energy, and position) observed in x-ray astronomy. Selected in 2017 January as a NASA Astrophysics Small Explorer (SMEX) mission, IXPE will be launched into an equatorial orbit in 2021. The IXPE mission will provide scientifically meaningful measurements of the x-ray polarization of a few dozen sources in the 2-8 keV band, including polarization maps of several x-ray-bright extended sources and phase-resolved polarimetry of many bright pulsating x-ray sources

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Impact of β-hexachlorocyclohexane on human cellular biochemistry and environmental remediation strategies.

Environmental pollution represents one of the most pressing problems in developed countries and in recent years has raised concern and doubts also from the scientific perspective. In fact, an ever-growing number of epidemiologic-observational studies, carried out on population at risk, correlated the exposure to environmental chemicals with the incidence of several pathological conditions, ranging from metabolic to cardiological and reproductive diseases, until the development of cancers. These evidences have made more urgent the need for further investigations on the biological mechanism at the basis of pollutants toxicity. In particular, significant attention has been paid to evaluating the impact of organochlorine pesticides (OCPs) on human health. OCPs belong to a large class of organic compounds that the Stockholm Convention catalogued as “POPs” (Persistent Organic Pollutants). The list of banned chemicals includes dioxins and their derivatives, hexachlorocyclohexane, polychlorinated biphenyls and aldrin, whereas many other similar substances are subjected to restrictions. OCPs are widely distributed in the biosphere and their hazardousness is mostly related to physicochemical properties such as lipophilia and energetic stability, that allow these molecules to be resistant to biodegradation and to bio-accumulate into the adipose tissue. Information about the molecular mechanisms of the most popular OCPs (i.e. dioxins, DDT) is already present in scientific literature and several studies indicated them as endocrine disrupting chemicals as well as oncogenes. On the other hand, not much is known about a dangerous and widely diffused compound: the hexachlorocyclohexane. Hexachlorocyclohexane (HCH) is a chlorinated cyclic saturated hydrocarbon that exists in four isomers: α, β, γ and δ hexachlorocyclohexane. The g-isomer of HCH, also known as lindane, is a broad-spectrum insecticide that has been extensively used for the control of agricultural pests and for health purposes. Among HCH isomers, which are by-products of lindane industrial synthesis, β-HCH is the most recalcitrant because of its higher energetic stability due to the equatorial position of all six chlorine atoms in the chair cyclohexane conformation; in addition, few reports are available about its metabolic breakdown. For this characteristic, it is usually the predominant isomer remaining in soils and in animal tissue and can still be detected at low background environmental levels. The improper disposal of huge amounts of β-HCH led to the generation of contaminated sites in several parts of the world (Italy, Turkey, Spain, Kazakhstan, Canada, India, China, Russia, Poland, Germany, Argentine): this classifies “lindane’s contamination” as one of the environmental catastrophe of global proportions on the planetary scale. A detailed epidemiological study, ongoing since 2006, has found correlation between high blood levels of β-HCH and the occurrence of a wide range of diseases in a sample of 660 exposed patients living close the Valle del Sacco, south of Rome. The Valle del Sacco, in fact, is characterized by the presence of a large industrial conglomerate in which lindane production has been stopped in 70’s. Although the biomonitoring study highlighted a link between β-HCH contamination and the incidence of several pathological conditions, few data are currently available in the scientific literature regarding the molecular mechanism of β-HCH. For this reason, our laboratory is investigating since 2015 the intracellular effects of β-HCH with a particular focus on its impact on cancer cells. In a first published study, experiments were carried out on a panel of cells representing different human tumor types (i.e. liver, lungs, prostate, breast) associated with the expression and activation of specific receptors or kinases that are related to STAT3 activity. The experimental concentration of 10 µM for β-HCH was chosen averaging across all the plasma concentration values detected in patients under the biomonitoring study carried out in the Valle del Sacco, in order to reproduce the real exposure conditions. After evaluating the effects of β-HCH on cellular viability, different types of analysis were performed to identify the transduction cascades involved in the molecular responses to β-HCH. Obtained results established that β-HCH can activate cell-line specific pathways that all converge in STAT3 activation. Then, a special focus was placed on investigating the putative role of β-HCH in prostate cancer progression; in fact, literature data, together with our previous findings, suggest that β-HCH could have an endocrine disrupting activity by interfering with Androgen Receptor (AR) signaling. To confirm this hypothesis, LNCaP cells (hormone-sensitive prostate cancer cell line) were treated with β-HCH or testosterone in the presence or absence of the chemotherapeutic agent bicalutamide. The outcomes show that AR nuclear translocation occurs upon both β-HCH and testosterone treatment, whereas is inhibited in the presence of bicalutamide, as evidenced by immunoblotting analysis on nuclear extracts and immunofluorescence experiments. Subsequently, was verified whether β-HCH could affect the activity of AhR (Aryl Hydrocarbon Receptor), the xenobiotic sensor par excellence, in both hormone-dependent and independent tumor types. Immunofluorescence analysis evidenced the capability of β-HCH to induce AhR nuclear translocation. In addition, immunoblotting analysis were performed on cells treated with β-HCH in the presence or not of MG-132 (proteasome inhibitor) and CH223191 (AhR inhibitor) and obtained results clearly highlighted the influence of β-HCH on AhR signaling. Then, experiments were performed to investigate whether β-HCH, on par with other organochlorine pesticides, can induce oxidative stress. For this purpose, ROS production and GSSG/GSH ratio were measured, evidencing the impact of β-HCH on cellular redox homeostasis. In parallel, variations in cellular bioenergetic profile were monitored, demonstrating that β-HCH promote a metabolic shift toward aerobic glycolysis. In this altered context, β-HCH can also induce DNA damage through H2AX phosphorylation. Subsequently, the potential role of β-HCH as a contributor in tumor initiation was inspected. Experiments were carried out on a continuous normal bronchial epithelium cell line to investigate whether β-HCH could trigger cellular malignant transformation toward cancer development. For this reason, β-HCH impact was evaluated on cells viability and morphology and some markers for tumorigenesis, as Ki67 positive-cells and EGF secretion, were studied along with β-HCH activation pathways. Experimental outcomes strongly support the oncogenic potential of this molecule. Considering the capability of β-HCH to promote cell growth and tumor progression, the next question to answer is whether the exposure to β-HCH may lead to a loss of response to chemotherapeutic agents such as tyrosine kinases inhibitors. Experiments carried out on a HER2-positive lung cancer cell line revealed that β-HCH can counteract the inhibitory activity of lapatinib, leading to a higher cell proliferation rate via STAT3 activation. Further investigations were conducted using other chemotherapeutic agents (cisplatin, camptothecin and paclitaxel) and preliminar results seem to confirm the loss of sensitivity to drugs in the presence of β-HCH. From an environmental point of view, the persistence of β-HCH still represents an open question for the presence of massive illegal repositories all around the world. For this reason, β-HCH degradation through a copper-based Fenton-like method was explored by setting up a HPLC protocol under different experimental conditions. The process focused on the quantitative degradation of the parental β-HCH, since the detection of its breakdown products or transformed molecules would need a mass-spectrometry for their qualitative characterization. In parallel with the β-HCH research topic, the role of the protein STAT3 in prostate cancer was further deepened. STAT3 (Signal Transducer and Activator of Transcription 3) is a converging point for many signaling cascades and has been reported constitutively activated in a wide range of solid tumors and hematological malignancies. STAT3 is a latent cytosolic transcription factor and upregulates the expression of genes involved in cell survival and proliferation upon a wide variety of stimuli, including cytokines, oncogenes, growth factors or cytosolic kinases. The dynamic biological behavior of STAT3 can explain the higher proliferation rate triggered by β-HCH through the activation of STAT3-mediated pathways. STAT3 fulfils its multifaceted molecular functions through two different intracellular mechanisms, generally referred as canonical and non-canonical pathways. The canonical activation of STAT3 is strictly dependent on its phosphorylation at the tyrosine residue 705; upon phosphorylation at Y705, induced by the binding of a ligand to its receptor, STAT3 undergoes homodimerization to form an active dimer that can translocate to nucleus and mediates its transcriptional activity. Besides its well-described canonical signaling, STAT3 can be subjected to alternative post-translational modifications. In addition, recent studies assessed the involvement of STAT3, by means of both its canonical and non-canonical pathway, in the metabolic shift toward aerobic glycolysis known as Warburg Effect, which is typical of the more aggressive tumor phenotypes. On the basis of these premises, the existence of a link between PTMs and specific STAT3-mediated pathways was investigated in LNCaP (less aggressive PCa form) and DU-145 (more aggressive) cells performing experiments that simulated inflammatory and oxidative-stress conditions. Cells were treated with IL-6 to induce an inflammatory response, whereas tert-butyl hydroperoxide (t-BHP) was used to simulate oxidative stress. Obtained results on cellular models confirmed the relationship between STAT3 PTMs and cellular conditions, thereby reinforcing the hypothesis that PTMs can drive intracellular responses through STAT3-mediated signaling pathways. Thus, it is possible to identify STAT3 PTMs and STAT3 modulators as suitable markers or targets for PCa prevention, diagnosis and therapy. Then the role of STAT3 in prostate cancer energy metabolism was further investigated, with particular focus on the protein SHMT2 (Serine-Hydroxymethyltransferase). Results indicate that SHMT2 is an active player in STAT3 signaling and that its expression is upregulated by the JAK2/STAT3 canonical pathway upon IL-6 stimulation. Experiments were carried out on two different prostate cancer cell lines, LNCaP (less aggressive) and DU145 (more aggressive). The observation was extended to PCa formalin-fixed paraffin-embedded (FFPE) tissue sections obtained from total prostatectomies: collected specimens are characterized by a different Gleason score, ranging from 6 (less aggressive) to 9 (more aggressive). In both cell lines, STAT3 activation mode, the amount and distribution of PKM2, SHMT2, and HIF-1a proteins, as well as the cellular metabolic conditions, were evaluated in the presence or absence of IL-6-induced inflammation. Expression levels of PKM2, SHMT2, and HIF-1a, together with interleukin-6, were also analyzed utilizing normal and tumor FFPE tissues.Doctorat en Sciences agronomiques et ingénierie biologiqueinfo:eu-repo/semantics/nonPublishe