56 research outputs found
Investigations of ternary Cu3SbS3 thin films as absorber in photovoltaic devices
Magnetron sputtered Cu-Sb metallic precursors were sulphidised on glass and molybdenum/glass substrates at 6 different temperatures. Two techniques were adopted for the elemental sulphidisation process. Precursors sulphidised using evaporated elemental sulphur were successfully converted into Cu3SbS3 solar absorber layers on molybdenum substrates. The as-sulphidised films exhibited p-type conductivity were produced in the limited response when analysed using a Eu+ electrolyte arrangement to measure the photocurrent. The films exhibited an energy bandgap value of 1.84eV
GLUT10 deficiency leads to oxidative stress and non-canonical αvβ3 integrin-mediated TGFβ signalling associated with extracellular matrix disarray in arterial tortuosity syndrome skin fibroblasts
Arterial tortuosity syndrome (ATS) is an autosomal recessive connective tissue disorder caused by loss-of-function mutations in SLC2A10, which encodes facilitative glucose transporter 10 (GLUT10). The role of GLUT10 in ATS pathogenesis remains an enigma, and the transported metabolite(s), i.e. glucose and/or dehydroascorbic acid, have not been clearly elucidated. To discern the molecular mechanisms underlying the ATS aetiology, we performed gene expression profiling and biochemical studies on skin fibroblasts. Transcriptome analyses revealed the dysregulation of several genes involved in TGFβ signalling and extracellular matrix (ECM) homeostasis as well as the perturbation of specific pathways that control both the cell energy balance and the oxidative stress response. Biochemical and functional studies showed a marked increase in ROS-induced lipid peroxidation sustained by altered PPARγ function, which contributes to the redox imbalance and the compensatory antioxidant activity of ALDH1A1. ATS fibroblasts also showed activation of a non-canonical TGFβ signalling due to TGFBRI disorganization, the upregulation of TGFBRII and connective tissue growth factor, and the activation of the αvβ3 integrin transduction pathway, which involves p125FAK, p60Src and p38 MAPK. Stable GLUT10 expression in patients' fibroblasts normalized redox homeostasis and PPARγ activity, rescued canonical TGFβ signalling and induced partial ECM re-organization. These data add new insights into the ATS dysregulated biological pathways and definition of the pathomechanisms involved in this disorder
Application of thoracic ultrasonography for the diagnosis of Bovine Respiratory Disease in Piedmontese calves
Transcriptome-wide expression profiling in skin fibroblasts of patients with joint hypermobility syndrome/ehlers-danlos syndrome hypermobility type
Joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT), is likely the most common systemic heritable connective tissue disorder, and is mostly recognized by generalized joint hypermobility, joint instability complications, minor skin changes and a wide range of satellite features. JHS/EDS-HT is considered an autosomal dominant trait but is still without a defined molecular basis. The absence of (a) causative gene(s) for JHS/EDS-HT is likely attributable to marked genetic heterogeneity and/or interaction of multiple loci. In order to help in deciphering such a complex molecular background, we carried out a comprehensive immunofluorescence analysis and gene expression profiling in cultured skin fibroblasts from five women affected with JHS/EDS-HT. Protein study revealed disarray of several matrix structural components such as fibrillins, tenascins, elastin, collagens, fibronectin, and their integrin receptors. Transcriptome analysis indicated perturbation of different signaling cascades that are required for homeostatic regulation either during development or in adult tissues as well as altered expression of several genes involved in maintenance of extracellular matrix architecture and homeostasis (e.g., SPON2, TGM2, MMP16, GPC4, SULF1), cell-cell adhesion (e.g., CDH2, CHD10, PCDH9, CLDN11, FLG, DSP), immune/inflammatory/pain responses (e.g., CFD, AQP9, COLEC12, KCNQ5, PRLR), and essential for redox balance (e.g., ADH1C, AKR1C2, AKR1C3, MAOB, GSTM5). Our findings provide a picture of the gene expression profile and dysregulated pathways in JHS/EDS-HT skin fibroblasts that correlate well with the systemic phenotype of the patients
Clinical and molecular characterization of 40 patients with classic Ehlers–Danlos syndrome: identification of 18 COL5A1 and 2 COL5A2 novel mutations
GLUT10-Lacking in Arterial Tortuosity Syndrome-Is Localized to the Endoplasmic Reticulum of Human Fibroblasts.
GLUT10 belongs to a family of transporters that catalyze the uptake of sugars/polyols by facilitated diffusion. Loss-of-function mutations in the SLC2A10 gene encoding GLUT10 are responsible for arterial tortuosity syndrome (ATS). Since subcellular distribution of the transporter is dubious, we aimed to clarify the localization of GLUT10. In silico GLUT10 localization prediction suggested its presence in the endoplasmic reticulum (ER). Immunoblotting showed the presence of GLUT10 protein in the microsomal, but not in mitochondrial fractions of human fibroblasts and liver tissue. An even cytosolic distribution with an intense perinuclear decoration of GLUT10 was demonstrated by immunofluorescence in human fibroblasts, whilst mitochondrial markers revealed a fully different decoration pattern. GLUT10 decoration was fully absent in fibroblasts from three ATS patients. Expression of exogenous, tagged GLUT10 in fibroblasts from an ATS patient revealed a strict co-localization with the ER marker protein disulfide isomerase (PDI). The results demonstrate that GLUT10 is present in the ER
Glucose transporter type 10—lacking in arterial tortuosity syndrome—facilitates dehydroascorbic acid transport
Loss-of-function mutations in the gene encoding GLUT10 are responsible for arterial tortuosity syndrome (ATS), a rare connective tissue disorder. In this study GLUT10-mediated dehydroascorbic acid (DAA) transport was investigated, supposing its involvement in the pathomechanism. GLUT10 protein produced by in vitro translation and incorporated into liposomes efficiently transported DAA. Silencing of GLUT10 decreased DAA transport in immortalized human fibroblasts whose plasma membrane was selectively permeabilized. Similarly, the transport of DAA through endomembranes was markedly reduced in fibroblasts from ATS patients. Re-expression of GLUT10 in patients’ fibroblasts restored DAA transport activity. The present results demonstrate that GLUT10 is a DAA transporter and DAA transport is diminished in the endomembranes of fibroblasts from ATS patients
Sintomi comportamentali e psicologici della demenza (BPSD) nella Malattia di Alzheimer: correlazione con i biomarcatori liquorali.
Oltre ai tipici sintomi cognitivi, i pazienti affetti da demenza di Alzheimer (AD) presentano spesso un corteo sintomatologico caratterizzato da sintomi neuropsichiatrici - come è in uso definirli negli Stati uniti - ovvero sintomi comportamentali e psicologici (behavioral and psychological symptoms, BPSD) – come sono stati definiti nel 1996 dall’Associazione Internazionale di Psicogeriatria. Si tratta di disturbi molto eterogenei, che minano in maniera variabile i domini emotivi, percettivi e comportamentali del paziente. Nel presente studio sono stati reclutati 52 pazienti con diagnosi di AD probabile (in accordo con i criteri NIA-AA-2011) nei quali viene indagata la correlazione fra biomarcatori liquorali della AD e sintomi comportamentali e psicologici della demenza (BPSD)
Multifaced Roles of the αvβ3 Integrin in Ehlers–Danlos and Arterial Tortuosity Syndromes’ Dermal Fibroblasts
The αvβ3 integrin, an endothelial cells’ receptor-binding fibronectin (FN) in the extracellular matrix (ECM) of blood vessels, regulates ECM remodeling during migration, invasion, angiogenesis, wound healing and inflammation, and is also involved in the epithelial mesenchymal transition. In vitro-grown human control fibroblasts organize a fibrillar network of FN, which is preferentially bound on the entire cell surface to its canonical α5β1 integrin receptor, whereas the αvβ3 integrin is present only in rare patches in focal contacts. We report on the preferential recruitment of the αvβ3 integrin, due to the lack of FN–ECM and its canonical integrin receptor, in dermal fibroblasts from Ehlers–Danlos syndromes (EDS) and arterial tortuosity syndrome (ATS), which are rare multisystem connective tissue disorders. We review our previous findings that unraveled different biological mechanisms elicited by the αvβ3 integrin in fibroblasts derived from patients affected with classical (cEDS), vascular (vEDS), hypermobile EDS (hEDS), hypermobility spectrum disorders (HSD), and ATS. In cEDS and vEDS, respectively, due to defective type V and type III collagens, αvβ3 rescues patients’ fibroblasts from anoikis through a paxillin-p60Src-mediated cross-talk with the EGF receptor. In hEDS and HSD, without a defined molecular basis, the αvβ3 integrin transduces to the ILK-Snail1-axis inducing a fibroblast-to-myofibroblast-transition. In ATS cells, the deficiency of the dehydroascorbic acid transporter GLUT10 leads to redox imbalance, ECM disarray together with the activation of a non-canonical αvβ3 integrin-TGFBRII signaling, involving p125FAK/p60Src/p38MAPK. The characterization of these different biological functions triggered by αvβ3 provides insights into the multifaced nature of this integrin, at least in cultured dermal fibroblasts, offering future perspectives for research in this field
Chalcogenisation of Cu-Sb metallic precursors into Cu3Sb(SexS1-x)3
Cu3SbS3 is a novel chalcogenide semiconductor with p-type conductivity and an energy bandgap of 1.84 eV. By incorporating selenium into this material to form Cu3Sb(SexS1−x)3 where x=Se/(Se+S), the energy bandgap can be altered to be in the range 1.38–1.84 eV for 0<x<0.49. The energy bandgap can hence be adjusted to be near the optimum for making the absorber layer for use in single and multi-junction photovoltaic solar cell devices. In this paper these materials were prepared using a two-stage process that involved magnetron sputtering of the Cu–Sb precursor layers followed by conversion to Cu3SbS3 by annealing in the presence of elemental sulphur and to Cu3Sb(SxSe1−x)3 by annealing in the presence of a mixture of sulphur and selenium. The films synthesised were characterised using scanning electron microscopy, energy dispersive x-ray analysis, x-ray diffraction, secondary ion mass spectroscopy and photo-electrochemical measurements. When the Cu3SbS3 was formed on glass substrates it had a cubic crystal structure whereas when it was formed on Mo-coated glass it had the monoclinic crystal structure. Likewise the layers of Cu3Sb(S,Se)3 formed on Mo-coated glass also had the monoclinic crystal structure. Spectral response curves were recorded over the spectral range 400–1400 nm for semiconductor—electrolyte junctions. Photovoltaic solar cell devices were made using p-type Cu3Sb(SxSe1−x)3 as the absorber layer and n-type CdS as the buffer layer. The photovoltaic effect was observed in these devices
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