308 research outputs found

    Acoustic comfort in open-plan offices: The role of employee characteristics

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    Purpose – This paper aims to determine the extent to which employees’ experiences of acoustic comfort, well-being and productivity in open-plan offices are determined by specific characteristics (including demographic information, task characteristics, and personality traits). Design/methodology/approach – A questionnaire was distributed to the occupants of three open-plan office sites and was completed by 166 employees in total. Findings – The results indicated that acoustic comfort in open-plan offices is largely determined by noise sensitivity. Higher noise sensitivity was associated with more negative ratings of acoustical quality, more perceived disturbance by speech and more difficulties in concentration. More negative experiences were also reported by employees with lower interactivity with colleagues. Practical implications – There is significant inter-individual variability in experiences of acoustic comfort, well-being and productivity in open-plan offices. As such, workplace practitioners should consider acoustic and behavioural solutions for introducing a greater diversity of functional workspaces within the office, so that employees can choose the most suitable working area for their requirements. Originality/value – Whereas the majority of past acoustics research has been laboratory-based, this study is conducted in real office environments with a representative sample of knowledge workers

    Loss of histone macroH2A1 in hepatocellular carcinoma cells promotes paracrine-mediated chemoresistance and CD4+CD25+FoxP3+ regulatory T cells activation

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    Rationale: Loss of histone macroH2A1 induces appearance of cancer stem cells (CSCs)-like cells in hepatocellular carcinoma (HCC). How CSCs interact with the tumor microenvironment and the adaptive immune system is unclear. Methods: We screened aggressive human HCC for macroH2A1 and CD44 CSC marker expression. We also knocked down (KD) macroH2A1 in HCC cells, and performed integrated transcriptomic and secretomic analyses. Results: Human HCC showed low macroH2A1 and high CD44 expression compared to control tissues. MacroH2A1 KD CSC-like cells transferred paracrinally their chemoresistant properties to parental HCC cells. MacroH2A1 KD conditioned media transcriptionally reprogrammed parental HCC cells activated regulatory CD4+/CD25+/FoxP3+ T cells (Tregs). Conclusions: Loss of macroH2A1 in HCC cells drives cancer stem-cell propagation and evasion from immune surveillance

    The PDGFRα-laminin B1-keratin 19 cascade drives tumor progression at the invasive front of human hepatocellular carcinoma

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    Human hepatocellular carcinomas (HCCs) expressing the biliary/hepatic progenitor cell marker keratin 19 (K19) have been linked with a poor prognosis and exhibit an increase in platelet-derived growth factor receptor a (PDGFR alpha) and laminin beta 1 (LAMB1) expression. PDGFR alpha has been reported to induce de novo synthesis of LAMB1 protein in a Sjogren syndrome antigen B (La/SSB)-dependent manner in a murine metastasis model. However, the role of this cascade in human HCC remains unclear. This study focused on the functional role of the PDGFR alpha-La/SSB-LAMB1 pathway and its molecular link to K19 expression in human HCC. In surgical HCC specimens from a cohort of 136 patients, PDGFR alpha expression correlated with K19 expression, microvascular invasion and metastatic spread. In addition, PDGFR alpha expression in pre-operative needle biopsy specimens predicted poor overall survival during a 5-year follow-up period. Consecutive histological staining demonstrated that the signaling components of the PDGFR alpha-La/SSB-LAMB1 pathway were strongly expressed at the invasive front. K19-positive HCC cells displayed high levels of alpha 2 beta 1 integrin (ITG) receptor, both in vitro and in vivo. In vitro activation of PDGFR alpha signaling triggered the translocation of nuclear La/SSB into the cytoplasm, enhanced the protein synthesis of LAMB1 by activating its internal ribosome entry site, which in turn led to increased secretion of laminin-111. This effect was abrogated by the PDGFR alpha-specific inhibitor crenolanib. Importantly LAMB1 stimulated ITG-dependent focal adhesion kinase/Src proto-oncogene non-receptor tyrosine kinase signaling. It also promoted the ITG-specific downstream target Rho-associated coiled-coil containing protein kinase 2, induced K19 expression in an autocrine manner, invadopodia formation and cell invasion. Finally, we showed that the knockdown of LAMB1 or K19 in subcutaneous xenograft mouse models resulted in significant loss of cells invading the surrounding stromal tissue and reduced HepG2 colonization into lung and liver after tail vein injection. The PDGFR alpha-LAMB1 pathway supports tumor progression at the invasive front of human HCC through K19 expression

    Impact of pollen on throughfall biochemistry in European temperate and boreal forests

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    Pollen is known to affect forest throughfall biochemistry, but underlying mechanisms are not fully understood. We used generalized additive mixed modelling to study the relationship between long-term series of measured throughfall fluxes in spring (April–June) at forest plots and corresponding airborne pollen concentrations (Seasonal Pollen Integral, SPIn) from nearby aerobiological monitoring stations. The forest plots were part of the intensive long term monitoring (Level II) network of the UNECE International Co-operative Programme on Assessment and Monitoring of Air Pollution Effects on Forests (ICP Forests) with dominant tree genera Fagus, Quercus, Pinus and Picea, and were distributed all across Europe. We also conducted a 7-day laboratory dissolution experiment with bud scales and flower stalks of European beech (Fagus sylvatica L.), pollen of beech, common oak (Quercus robur L.), silver birch (Betula pendula L.), Scots pine (Pinus sylvestris L.), Corsican pine (Pinus nigra Arnold ssp. laricio (Poiret) Maire), Norway spruce (Picea abies (L.) Karst.) and sterilized pollen of silver birch in a nitrate (NO3--N) solution (11.3 mg N L-1). Throughfall fluxes of potassium (K+), ammonium (NH4+-N), dissolved organic carbon (DOC) and dissolved organic nitrogen (DON) showed a positive relationship with SPIn whereas NO3--N fluxes showed a negative relationship with SPIn. In years with massive seed production of beech and oak SPIn and throughfall fluxes of K+ and DOC were higher, but fluxes of NO3--N were lower. The experiment broadly confirmed the findings based on field data. Within two hours, pollen released large quantities of K+, phosphate, DOC and DON, and lesser amounts of sulphate, sodium and calcium. After 24-48 hours, NO3--N started to disappear, predominantly in the treatments with broadleaved pollen, while concentrations of nitrite and NH4+-N increased. At the end of the experiment, the inorganic nitrogen (DIN) was reduced, presumably because it was lost as gaseous nitric oxide (NO). There was no difference for sterilized pollen, indicating that the involvement of microbial activity was limited in above N transformations. Our results show that pollen dispersal might be an overlooked factor in forest nutrient cycling and might induce complex canopy N transformations, although the net-impact on N throughfall fluxes is rather lo

    Pathogenesis of non-alcoholic fatty liver disease

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    Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of disease ranging from hepatocellular steatosis through steatohepatitis to fibrosis and irreversible cirrhosis. The prevalence of NAFLD has risen rapidly in parallel with the dramatic rise in obesity and diabetes, and is rapidly becoming the most common cause of liver disease in Western countries. Indeed, NAFLD is now recognized to be the aetiology in many cases previously labelled as cryptogenic cirrhosis

    The bashful and the boastful : prestigious leaders and social change in Mesolithic Societies

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    The creation and maintenance of influential leaders and authorities is one of the key themes of archaeological and historical enquiry. However the social dynamics of authorities and leaders in the Mesolithic remains a largely unexplored area of study. The role and influence of authorities can be remarkably different in different situations yet they exist in all societies and in almost all social contexts from playgrounds to parliaments. Here we explore the literature on the dynamics of authority creation, maintenance and contestation in egalitarian societies, and discuss the implications for our interpretation and understanding of the formation of authorities and leaders and changing social relationships within the Mesolithic

    Evidence for a common progenitor of epithelial and mesenchymal components of the liver

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    Tissues of the adult organism maintain the homeostasis and respond to injury by means of progenitor/stem cell compartments capable to give rise to appropriate progeny. In organs composed by histotypes of different embryological origins (e.g. The liver), the tissue turnover may in theory involve different stem/precursor cells able to respond coordinately to physiological or pathological stimuli. In the liver, a progenitor cell compartment, giving rise to hepatocytes and cholangiocytes, can be activated by chronic injury inhibiting hepatocyte proliferation. The precursor compartment guaranteeing turnover of hepatic stellate cells (HSCs) (perisinusoidal cells implicated with the origin of the liver fibrosis) in adult organ is yet unveiled. We show here that epithelial and mesenchymal liver cells (hepatocytes and HSCs) may arise from a common progenitor. Sca+ murine progenitor cells were found to coexpress markers of epithelial and mesenchymal lineages and to give rise, within few generations, to cells that segregate the lineage-specific markers into two distinct subpopulations. Notably, these progenitor cells, clonally derived, when transplanted in healthy livers, were found to generate epithelial and mesenchymal liver-specific derivatives (i.e. hepatocytes and HSCs) properly integrated in the liver architecture. These evidences suggest the existence of a 'bona fide' organ-specific meso-endodermal precursor cell, thus profoundly modifying current models of adult progenitor commitment believed, so far, to be lineage-restricted. Heterotopic transplantations, which confirm the dual differentiation potentiality of those cells, indicates as tissue local cues are necessary to drive a full hepatic differentiation. These data provide first evidences for an adult stem/precursor cell capable to differentiate in both parenchymal and non-parenchymal organ-specific components and candidate the liver as the instructive site for the reservoir compartment of HSC precursors as yet non-localized in the adult. © 2013 Macmillan Publishers Limited All rights reserved
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