Recent advances on the mechanisms regulating cholangiocyte proliferation and the significance of the neuroendocrine regulation of cholangiocyte pathophysiology

Cholangiocytes are epithelial cells lining the biliary epithelium. Cholangiocytes play several key roles in the modification of ductal bile and are also the target cells in chronic cholestatic liver diseases (i.e., cholangiopathies) such as PSC, PBC, polycystic liver disease (PCLD) and cholangiocarcinoma (CCA). During these pathologies, cholangiocytes (which in normal condition are in a quiescent state) begin to proliferate acquiring phenotypes of neuroendocrine cells, and start secreting different cytokines, growth factors, neuropeptides, and hormones to modulate cholangiocytes proliferation and interaction with the surrounding environment, trying to reestablish the balance between proliferation/loss of cholangiocytes for the maintenance of biliary homeostasis. The purpose of this review is to summarize the recent findings on the mechanisms regulating cholangiocyte proliferation and the significance of the neuroendocrine regulation of cholangiocyte pathophysiology. To clarify the mechanisms of action of these factors we will provide new potential strategies for the management of chronic liver diseases

Improving flexibility of industrial microgrids through thermal storage and HVAC management strategies

Abstract The increasing share of non-programmable renewable energy sources in national energy portfolios requires a high flexibility to balance demand and offer in energy markets. Demand side management programs and microgrids will play a key role in achieving flexibility on the demand side. This paper aims at presenting the increase of flexibility that can be achieved by an industrial microgrid. On field tests were carried out in an Italian industrial microgrid, where a set of load management strategies were implemented. These strategies aim at leveraging the thermal inertia of a building using both thermal energy storage and the HVAC system. Results show that the thermal energy storage can contribute to limit the peak cooling load by up to 40 kWe for three hours, while implementing a load shifting strategy using the HVAC system can provide a temporary reduction in power consumption of 20 kWe. Results also prove that it is possible to identify the effect of a load shifting strategy using electricity consumption data sampled with a 15-minutes granularity

Embedding sustainability in risk management: The impact of environmental, social, and governance ratings on corporate financial risk

This study investigates the effect of corporate social and environmental evaluation on investors’ risk perception to explore the potential market risk for public companies that adopt a sustainable and responsible corporate strategy. We referred to the triple corporate assessment according to environmental, social, and governance (ESG) criteria to check whether ESG factors—meant to direct firms toward social and environmental needs—improve corporate market performance or trigger, among investors, a perception of “window dressing.” In doing so, we tested the impact of corporate social performance—proxied by an ESG assessment—on corporate financial risk using double risk measurement. We conducted a five-year longitudinal study (fiscal years 2014–2018) of 222 companies listed on the Standard & Poor’s index. The empirical findings show higher investor uncertainty regarding corporate sustainability performance, probably due to the misalignment of objectives between investors and investees. Indeed, an overall ESG assessment corresponds to higher systematic risk for firms, and a corporate environmental rating has an upward effect on the same risk dimension

Short-term physiological and biometrical responses of Lepidium sativum seedlings exposed to PET-made microplastics and acid rain.

Abstract Plastics enter in terrestrial natural system primarily by agricultural purposes, while acid rain is the result of anthropogenic activities. The synergistic effects of microplastics and acid rain on plant growth are not known. In this study, different sizes of polyethylene terephthalate (PET) and acid rain are tested on Lepidium sativum, in two separate experimental sets. In the first one we treated plants only with PET, in the second one we used PET and acid rain together. In both experimentations we analyzed: i) plant biometrical parameters (shoot height, leaf number, percentage inhibition of seed germination, fresh biomass), and ii) oxidative stress responses (hydrogen peroxide; ascorbic acid and glutathione). Results carried out from our experiments highlighted that different sizes of polyethylene terephthalate are able to affect plant growth and physiological responses, with or without acid rain supplied during acute toxicity (6 days). Short description This study showed that different sizes of PET microplastics affect physiological and biometrical responses of Lepidum sativum seedlings, with or without acid rain; roots and leaves responded differently

Skeletal muscle myopenia in mice model of bile duct ligation and carbon tetrachloride-induced liver cirrhosis

Skeletal muscle myopathy is universal in cirrhotic patients, however, little is known about the main mechanisms involved. The study aims to investigate skeletal muscle morphological, histological, and functional modifications in experimental models of cirrhosis and the principal molecular pathways responsible for skeletal muscle myopathy. Cirrhosis was induced by bile duct ligation (BDL) and carbon tetrachloride (CCl4) administration in mice. Control animals (CTR) underwent bile duct exposure or vehicle administration only. At sacrifice, peripheral muscles were dissected and weighed. Contractile properties of extensor digitorum longus (EDL) were studied in vitro. Muscle samples were used for histological and molecular analysis. Quadriceps muscle histology revealed a significant reduction in cross-sectional area of muscle and muscle fibers in cirrhotic mice with respect to CTR. Kinetic properties of EDL in both BDL and CCl4 were reduced with respect to CTR; BDL mice also showed a reduction in muscle force and a decrease in the resistance to fatigue. Increase in myostatin expression associated with a decrease in AKT-mTOR expressions was observed in BDL mice, together with an increase in LC3 protein levels. Upregulation of the proinflammatory citochines TNF-a and IL6 and an increased expression of NF-kB and MuRF-1 were observed in CCl4 mice. In conclusion, skeletal muscle myopenia was present in experimental models of BDL and CCl4-induced cirrhosis. Moreover, reduction in protein synthesis and activation of protein degradation were the main mechanisms responsible for myopenia in BDL mice, while activation of ubiquitin-pathway through inflammatory cytokines seems to be the main potential mechanism involved in CCl4 mice

Stem/Progenitor Cell Niches Involved in Hepatic and Biliary Regeneration

Niches containing stem/progenitor cells are present in different anatomical locations along the human biliary tree and within liver acini. The most primitive stem/progenitors, biliary tree stem/progenitor cells (BTSCs), reside within peribiliary glands located throughout large extrahepatic and intrahepatic bile ducts. BTSCs are multipotent and can differentiate towards hepatic and pancreatic cell fates. These niches’ matrix chemistry and other characteristics are undefined. Canals of Hering (bile ductules) are found periportally and contain hepatic stem/progenitor cells (HpSCs), participating in the renewal of small intrahepatic bile ducts and being precursors to hepatocytes and cholangiocytes. The niches also contain precursors to hepatic stellate cells and endothelia, macrophages, and have a matrix chemistry rich in hyaluronans, minimally sulfated proteoglycans, fetal collagens, and laminin. The microenvironment furnishes key signals driving HpSC activation and differentiation. Newly discovered third niches are pericentral within hepatic acini, contain Axin

Working in a tourism company: experience at Dixo´s Oporto Apartments

The present report is part of the curricular internship of the Master’s degree in Intercultural Studies for Business, from the Porto Accounting and Business School (Instituto Superior de Contabilidade e Administração do Porto). This internship took place at the tourism field related company, Dixo’s Oporto Apartments. Globalization has been increasing at unprecedented rates and with that, the limits and the borders between countries and nations have been reducing. As a result, there has been a marked increase in the need for intercultural communication as it becomes reality and people depend more on this type of communication. The tourism sector is no exception from the inevitable changes imposed by globalization, and it too depends on intercultural communication. Cities such as Porto with a great flux of tourism rely on the finest quality services delivered by leading professionals. High standards can only be achieved by those who are used to intercultural communication and are familiarized with concepts such as globalization and interculturality. The purpose of this report is to describe and understand, at the most precise level the activities carried out during the internship based on the concepts and knowledge learnt during the master’s degree.O presente relatório insere-se no âmbito do estágio curricular do Mestrado em Estudos Interculturais para Negócio, no Instituto Superior de Contabilidade e Administração do Porto (ISCAP). O estágio decorreu na empresa Dixo’s Oporto Apartments que se insere na área do Turismo. A globalização tem vindo a crescer a níveis nunca previstos e, com isso, os limites e as fronteiras entre países e nações vêm diminuindo. Com isso, a comunicação intercultural tem crescido assim como o crescimento da comunicação entre diferentes culturas, uma constante e as pessoas dependem cada vez mais desse tipo de comunicação sendo uma realidade óbvia atualmente. O turismo vive desse tipo de comunicação e da globalização. Cidades como o Porto, com grande fluxo turístico, contam com serviços de qualidade prestados por profissionais formados por excelência. Padrões elevados só podem ser alcançados por aqueles que estão acostumados a comunicação intercultural e familiarizados com conceitos como globalização e interculturalidade. O objetivo deste relatório é descrever e compreender da forma mais precisa as atividades desenvolvidas durante o estágio com base nos conceitos e conhecimentos aprendidos durante o mestrado

Histamine stimulates the proliferation of small and large cholangiocytes by activation of both IP3/Ca2+ and cAMP-dependent signaling mechanisms

Although large cholangiocytes exert their functions by activation of cyclic adenosine 3',5'-monophosphate (cAMP), Ca(2+)-dependent signaling regulates the function of small cholangiocytes. Histamine interacts with four receptors, H1-H4HRs. H1HR acts by Gαq activating IP(3)/Ca(2+), whereas H2HR activates Gα(s) stimulating cAMP. We hypothesize that histamine increases biliary growth by activating H1HR on small and H2HR on large cholangiocytes. The expression of H1-H4HRs was evaluated in liver sections, isolated and cultured (normal rat intrahepatic cholangiocyte culture (NRIC)) cholangiocytes. In vivo, normal rats were treated with histamine or H1-H4HR agonists for 1 week. We evaluated: (1) intrahepatic bile duct mass (IBDM); (2) the effects of histamine, H1HR or H2HR agonists on NRIC proliferation, IP(3) and cAMP levels and PKCα and protein kinase A (PKA) phosphorylation; and (3) PKCα silencing on H1HR-stimulated NRIC proliferation. Small and large cholangiocytes express H1-H4HRs. Histamine and the H1HR agonist increased small IBDM, whereas histamine and the H2HR agonist increased large IBDM. H1HR agonists stimulated IP(3) levels, as well as PKCα phosphorylation and NRIC proliferation, whereas H2HR agonists increased cAMP levels, as well as PKA phosphorylation and NRIC proliferation. The H1HR agonist did not increase proliferation in PKCα siRNA-transfected NRICs. The activation of differential signaling mechanisms targeting small and large cholangiocytes is important for repopulation of the biliary epithelium during pathologies affecting different-sized bile ducts

Evaluating the Surgeons' Perception of Difficulties of Two Techniques to Perform STARR for Obstructed Defecation Syndrome: A Multicenter Randomized Trial.

BACKGROUND After initial enthusiasm in the use of a dedicated curved stapler (CCS-30 Contour Transtar) to perform stapled transanal rectal resection (STARR) for obstructed defecation syndrome (ODS), difficulties have emerged in this surgical technique. OBJECTIVE First, to compare surgeons' perception of difficulties of STARR performed with only Transtar versus STARR performed with the combined use of linear staplers and Transtar to cure ODS associated with large internal prolapse and rectocele; second, to compare the postoperative incidence of the urge to defecate between the 2 STARR procedures. DESIGN AND SETTING An Italian multicenter randomized trial involving 25 centers of colorectal surgery. PATIENTS Patients with obstructed defecation syndrome and rectocele or rectal intussusception, treated between January and December 2012. INTERVENTIONS Participants were randomly assigned to undergo STARR with a curved alone stapler (CAS group) or with the combined use of linear and curved staplers (LCS group). MAIN OUTCOME MEASURES Primary end-points were the evaluation of surgeons' perception of difficulties score and the incidence of the "urge to defecate" at 3-month follow up. Secondary end-points included duration of hospital stay, rates of early and late complications, incidence of "urge to defecate" at 6 and 12 months, success of the procedures at 12 months of follow-up. RESULTS Of 771 patients evaluated, 270 patients (35%) satisfied the criteria. Follow-up data were available for 254 patients: 128 patients (114 women) in the CAS group (mean age, 52.1; range, 39-70 years) and 126 (116 women) in LCS group (mean age, 50.7 years; range, 41-75 years). The mean surgeons' perception score, was 15.36 (SD, 3.93) in the CAS group and 12.26 (SD, 4.22) in the LCS group (P < .0001; 2-sample t test). At 3-month follow-up, urge to defecate was observed in 18 (14.6%) CAS group patients and in 13 (10.7%) LCS group patients (P = .34; Fisher's exact test). These values drastically decrease at 6 months until no urge to defecate in all patients at 12 months was observed. At 12-month follow-up, a successful outcome was achieved in 100 (78.1%) CAS group patients and in 105 (83.3%) LCS group patients (P = .34; Fisher's exact test). No significant differences between groups were observed in the hospital stay and rates of early or late complications occurring after STARR. CONCLUSIONS STARR with Transtar associated with prior decomposition of prolapse, using linear staplers, seems to be less difficult than that without decomposition. Both procedures appear to be safe and effective in the treatment of obstructed defecation syndrome resulting in similar success rates and complications

Diversity of naturalized hairy vetch (Vicia villosa Roth) populations in central Argentina as a source of potential adaptive traits for breeding

Hairy vetch (Vicia villosa ssp. villosa Roth) is native of Europe and Western Asia and it is the second most cultivated vetch worldwide. Hairy vetch is used as forage species in semiarid environments and as a legume cover crop in sub-humid and humid regions. Being an incompletely domesticated species, hairy vetch can form spontaneous populations in a new environment. These populations might contain novel and adaptive traits valuable for breeding. Niche occupancy based on geographic occurrence and environmental data of naturalized populations in central Argentina showed that these populations were distributed mainly on disturbed areas with coarse soil texture and alkaline-type soils. Low rainfall and warm temperatures during pre- and post-seed dispersal explained the potential distribution under sub-humid and semiarid conditions from Pampa and Espinal ecoregions. Conversely, local adaptation along environmental gradients did not drive the divergence among recently established Argentinian (AR) populations. The highest genetic diversity revealed by microsatellite analysis was observed within accessions (72%) while no clear separation was detected between AR and European (EU) genotypes, although naturalized AR populations showed strong differentiation with the wild EU accessions. Common garden experiments were conducted in 2014-16 in order to evaluate populations? germination, flowering and biomass traits. European cultivars were characterized by low physical seed dormancy (PY), while naturalized AR accessions showed higher winter biomass production. Detected variation in the quantitative assessment of populations could be useful for selection in breeding for traits that convey favourable functions within specific contexts.Fil: Renzi, Juan Pablo. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Hilario Ascasubi; Argentina. Universidad Nacional del Sur. Departamento de Agronomía; ArgentinaFil: Chantre Balacca, Guillermo Ruben. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; Argentina. Universidad Nacional del Sur. Departamento de Agronomía; ArgentinaFil: Smýkal, Petr. Palacký University; República ChecaFil: Presotto, Alejandro Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; Argentina. Universidad Nacional del Sur. Departamento de Agronomía; ArgentinaFil: Zubiaga, Luciano. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Hilario Ascasubi; ArgentinaFil: Garayalde, Antonio Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; Argentina. Universidad Nacional del Sur. Departamento de Matemática; ArgentinaFil: Cantamutto, Miguel Ángel. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Hilario Ascasubi; Argentina. Universidad Nacional del Sur. Departamento de Agronomía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; Argentin