692 research outputs found

    Endoplasmic Reticulum Stress, Unfolded Protein Response and Altered T Cell Differentiation in Necrotizing Enterocolitis

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    Background:Endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) play important roles in chronic intestinal inflammation. Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm infants and is characterized by acute intestinal inflammation and necrosis. The objective of the study is to investigate the role of ER stress and the UPR in NEC patients.Methods:Ileal tissues from NEC and control patients were obtained during surgical resection and/or at stoma closure. Splicing of XBP1 was detected using PCR, and gene expression was quantified using qPCR and Western blot.Results:Splicing of XBP1 was only detected in a subset of acute NEC (A-NEC) patients, and not in NEC patients who had undergone reanastomosis (R-NEC). The other ER stress and the UPR pathways, PERK and ATF6, were not activated in NEC patients. A-NEC patients showing XBP1 splicing (A-NEC-XBP1s) had increased mucosal expression of GRP78, CHOP, IL6 and IL8. Similar results were obtained by inducing ER stress and the UPR in vitro. A-NEC-XBP1s patients showed altered T cell differentiation indicated by decreased mucosal expression of RORC, IL17A and FOXP3. A-NEC-XBP1s patients additionally showed more severe morphological damage and a worse surgical outcome. Compared with A-NEC patients, R-NEC patients showed lower mucosal IL6 and IL8 expression and higher mucosal FOXP3 expression.Conclusions:XBP1 splicing, ER stress and the UPR in NEC are associated with increased IL6 and IL8 expression levels, altered T cell differentiation and severe epithelial injury

    Photonic Characterisation of Indium Tin Oxide as a Function of Deposition Conditions

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    Indium tin oxide (ITO) has recently gained prominence as a photonic nanomaterial, for example, in modulators, tuneable metasurfaces and for epsilon-near-zero (ENZ) photonics. The optical properties of ITO are typically described by the Drude model and are strongly dependent on the deposition conditions. In the current literature, studies often make several assumptions to connect the optically measured material parameters to the electrical properties of ITO, which are not always clear, nor do they necessarily apply. Here, we present a comprehensive study of the structural, electrical, and optical properties of ITO and showed how they relate to the deposition conditions. We use guided mode resonances to determine the dispersion curves of the deposited material and relate these to structural and electrical measurements to extract all relevant material parameters. We demonstrate how the carrier density, mobility, plasma frequency, electron effective mass, and collision frequency vary as a function of deposition conditions, and that the high-frequency permittivity ((Formula presented.)) can vary significantly from the value of (Formula presented.) = 3.9 that many papers simply assume to be a constant. The depth of analysis we demonstrate allows the findings to be easily extrapolated to the photonic characterisation of other transparent conducting oxides (TCOs), whilst providing a much-needed reference for the research area

    Design management: changing roles of the professions

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    This paper sets out to explore how recent changes in procurement in construction have affected the roles that professions play in the design process. It discusses how professions that traditionally took the role of design manager now find themselves participating within previously unforeseen contexts, working in multidisciplinary teams led by contractors and with changed responsibilities at the design stage. Supply chain members who were not previously involved during the early project phases are being engaged at the earliest phases of the project life cycle and even taking leadership roles while designers sometimes work as supply chain partners. A study of design in construction and other sectors shows that in dealing with design management issues it is critical to deepen appreciation for the unique characteristics of design and the design process. The paper argues that contractors and designers taking on design management roles in a dynamic industry seeking to explore best practice and innovative approaches to procurement and in the delivery of projects need to acquire new skills, management education and develop the necessary qualities

    Transcriptional control of the multi-drug transporter ABCB1 by transcription factor Sp3 in different human tissues

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    The ATP-binding cassette (ABC) transporter ABCB1, encoded by the multidrug resistance gene MDR1, is expressed on brain microvascular endothelium and several types of epithelium, but not on endothelia outside the CNS. It is an essential component of the blood-brain barrier. The aim of this study was to identify cell-specific controls on the transcription of MDR1 in human brain endothelium. Reporter assays identified a region of 500bp around the transcription start site that was optimally active in brain endothelium. Chromatin immunoprecipitation identified Sp3 and TFIID associated with this region and EMSA (electrophoretic mobility shift assays) confirmed that Sp3 binds preferentially to an Sp-target site (GC-box) on the MDR1 promoter in brain endothelium. This result contrasts with findings in other cell types and with the colon carcinoma line Caco-2, in which Sp1 preferentially associates with the MDR1 promoter. Differences in MDR1 transcriptional control between brain endothelium and Caco-2 could not be explained by the relative abundance of Sp1:Sp3 nor by the ratio of Sp3 variants, because activating variants of Sp3 were present in both cell types. However differential binding of other transcription factors was also detected in two additional upstream regions of the MDR1 promoter. Identification of cell-specific controls on the transcription of MDR1 indicates that it may be possible to modulate multi-drug resistance on tumours, while leaving the blood brain barrier intact

    AGRONOMIC QUALITIES OF GENETIC PYRAMIDS OF COMMON BEAN DEVELOPED FOR MULTIPLE-DISEASE-RESISTANCE

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    Multiple co-infections by different pathogens on common bean ( Phaseolus vulgaris L.) affect its productivity and cause complete crop loss in susceptible varieties. Therefore, gene pyramiding using marker assisted selection (MAS) and backcrossing, provide alternative cost-effective control measures to bean diseases. However, in the process of developing pyramids, linkage drags were likely to affect the qualities of progeny lines, hence, special attention was paid to this situation. The objective of this study was thus to assess the agronomic qualities of advanced genetic pyramids developed from a four-way cross for multiple disease resistance. The disease resistance genes (R) pyramided from four parents were: Co42 and Co-5 from G2333; Phg-2 from MEX54; Pythium ultimum Dennis from MLB49-89A and I & bc3 from MCM5001. The progeny lines were planted in an incomplete block design, and replicated thrice for two seasons (2015A and 2015B) in fields at CIAT, Kawanda in Uganda. Agronomic traits were highly heritable (0.6), except number of pods per plant (< 0.3). Backcrossing generated high-yielding bean lines, with 270 - 290 seed per plant and early maturity (95-100 days). Nine superior lines with desirable qualities, such as earliness (95 days), high seed rate (290 seeds per plant), and climbing ability, were obtained. Pyramiding R genes did not affect yield traits, except time to flowering and number of flower buds per plant due to transgressive segregation.Les co-infections multiples par de diff\ue9rents pathog\ue8nes sur le haricot commun ( Phaseolus vulgaris L.) affectent sa productivit\ue9 et causent la perte totale des vari\ue9t\ue9s susceptibles de la culture. Par cons\ue9quent, la pyramide des g\ue8nes en utilisant la s\ue9lection assist\ue9e par des marqueurs (MAS) et le r\ue9trocroisement, fournissent des mesures alternatives de contr\uf4le moins ch\ue8res des maladies du haricot. N\ue9anmoins, dans le processus du d\ue9veloppement des pyramides, les poids des liaisons affectent probablement les qualit\ue9s des lign\ue9es de prog\ue9nitures, de ce fait, une attention particuli\ue8re \ue9tait port\ue9e \ue0 cette situation. L\u2019objectif de cette \ue9tude \ue9tait d\u2019\ue9valuer les qualit\ue9s agronomiques des pyramides g\ue9n\ue9tiques avanc\ue9es d\ue9velopp\ue9es d\u2019un croisement de quatre parents pour la r\ue9sistance aux maladies multiples. Les g\ue8nes pyramid\ue9s de r\ue9sistance (R) \ue0 la maladie de quatre parents \ue9taient\ua0: Co42 et Co-5 de G2333; Phg-2 de MEX54; Pythium ultimum Dennis de MLB49-89A et I & bc3 de MCM5001. Les lign\ue9es de prog\ue9nitures \ue9taient plant\ue9es en arrangement de block incomplet et r\ue9pliqu\ue9 trois fois pendant deux saisons (2015A et 2015B) dans les champs \ue0 CIAT, Kawanda en Ouganda. Les traits agronomiques \ue9taient hautement h\ue9ritables (0,6), \ue0 l\u2019exception du nombre de gousses par plant (<0.3). Le r\ue9trocroisement a g\ue9n\ue9r\ue9 des lign\ue9es d\u2019haricot \ue0 haut rendement, avec 270-290 graines par plant et \ue0 maturit\ue9 pr\ue9coce (95-100 jours). Neuf lign\ue9es sup\ue9rieures avec des qualit\ue9s d\ue9sirables, telles que la pr\ue9cocit\ue9 (95 jours), taux de graines \ue9lev\ue9s (290 graines par plant) et l\u2019habilit\ue9 grimpante, \ue9taient obtenues. La pyramide des g\ue8nes R n\u2019avait pas affect\ue9 les traits li\ue9s au rendement, \ue0 l\u2019exception de la p\ue9riode de floraison et le nombre de bougeons de fleurs par plant d\ufb \ue0 la s\ue9gr\ue9gation transgressive

    Phosphino-Triazole Ligands for Palladium-Catalyzed Cross-Coupling

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    Twelve 1,5-disubtituted and fourteen 5-substituted 1,2,3-triazole derivatives bearing diaryl or dialkyl phosphines at the 5-position were synthesized and used as ligands for palladium-catalyzed Suzuki–Miyaura cross-coupling reactions. Bulky substrates were tested, and lead-like product formation was demonstrated. The online tool SambVca2.0 was used to assess steric parameters of ligands and preliminary buried volume determination using XRD-obtained data in a small number of cases proved to be informative. Two modeling approaches were compared for the determination of the buried volume of ligands where XRD data was not available. An approach with imposed steric restrictions was found to be superior in leading to buried volume determinations that closely correlate with observed reaction conversions. The online tool LLAMA was used to determine lead-likeness of potential Suzuki–Miyaura cross-coupling products, from which 10 of the most lead-like were successfully synthesized. Thus, confirming these readily accessible triazole-containing phosphines as highly suitable ligands for reaction screening and optimization in drug discovery campaigns
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