Syndecan-4 knockout leads to reduced extracellular transglutaminase-2 and protects against tubulointerstitial fibrosis

Transglutaminase type 2 (TG2) is an extracellular matrix crosslinking enzyme with a pivotal role in kidney fibrosis. The interaction of TG2 with the heparan sulfate proteoglycan syndecan-4 (Sdc4) regulates the cell surface trafficking, localization, and activity of TG2 in vitro but remains unstudied in vivo. We tested the hypothesis that Sdc4 is required for cell surface targeting of TG2 and the development of kidney fibrosis in CKD. Wild-type and Sdc4-null mice were subjected to unilateral ureteric obstruction and aristolochic acid nephropathy (AAN) as experimental models of kidney fibrosis. Analysis of renal scarring by Masson trichrome staining, kidney hydroxyproline levels, and collagen immunofluorescence demonstrated progressive fibrosis associated with increases in extracellular TG2 and TG activity in the tubulointerstitium in both models. Knockout of Sdc-4 reduced these effects and prevented AAN-induced increases in total and active TGF-b1. In wild-type mice subjected to AAN, extracellular TG2 colocalized with Sdc4 in the tubular interstitium and basement membrane, where TG2 also colocalized with heparan sulfate chains. Heparitinase I, which selectively cleaves heparan sulfate, completely abolished extracellular TG2 in normal and diseased kidney sections. In conclusion, the lack of Sdc4 heparan sulfate chains in the kidneys of Sdc4-null mice abrogates injury-induced externalization of TG2, thereby preventing profibrotic crosslinking of extracellular matrix and recruitment of large latent TGF-b1. This finding suggests that targeting the TG2- Sdc4 interaction may provide a specific interventional strategy for the treatment of CKD

An extracellular transglutaminase is required for apple pollen tube growth

An extracellular form of the calcium-dependent protein-crosslinking enzyme TGase (transglutaminase) was demonstrated to be involved in the apical growth of Malus domestica pollen tube. Apple pollen TGase and its substrates were co-localized within aggregates on the pollen tube surface, as determined by indirect immunofluorescence staining and the in situ cross-linking of fluorescently labelled substrates. TGase-specific inhibitors and an anti-TGase monoclonal antibody blocked pollen tube growth, whereas incorporation of a recombinant fluorescent mammalian TGase substrate (histidine-tagged green fluorescent protein:His6– Xpr–GFP) into the growing tube wall enhanced tube length and germination, consistent with a role of TGase as a modulator of cell wall building and strengthening. The secreted pollen TGase catalysed the cross-linking of both PAs (polyamines) into proteins (released by the pollen tube) and His6-Xpr-GFP into endogenous or exogenously added substrates. A similar distribution of TGase activitywas observed in planta on pollen tubes germinating inside the style, consistent with a possible additional role for TGase in the interaction between the pollen tube and the style during fertilization

Evaluation and Action: Sustaining Excellence in Collegiate Aviation Distance Education

This study assesses the role of the evaluation process in sustaining and developing quality distance education programs in collegiate aviation. Distance education encompasses distance learning and distributive learning as well as e-learning and multiple method crossover delivery that includes some form of electronic delivery. The research explores the sanctioned position of evaluation procedures and their practical application in the outcomes assessment process within collegiate aviation distance education programs as compared to traditional delivery methods. Additionally, the study investigates the criteria for determining outcomes assessment based on establishing methods for interpolating contact hours, applied testing, and gauging learning. The methodological approach includes a literature review and a survey instrument implemented by semi-structured phone interviews. The gathered data are based on a review of accredited graduate and undergraduate collegiate aviation distance programs. The findings demonstrate that evaluation is an underutilized method for sustaining and ensuring a high-level academic product is delivered via distance education. The lack of consistent terminology for classifying and measuring distance education, and more specifically, the meaning of quality, further complicate this. Further research is recommended in order to reach a consensus on defining vocabulary of distance education elements and the role and application of evaluation. Additionally, the recommendations provide guidance in modifying the curriculum for achieving consistent results commensurate with accreditation standards

How the other half lives: CRISPR-Cas's influence on bacteriophages

CRISPR-Cas is a genetic adaptive immune system unique to prokaryotic cells used to combat phage and plasmid threats. The host cell adapts by incorporating DNA sequences from invading phages or plasmids into its CRISPR locus as spacers. These spacers are expressed as mobile surveillance RNAs that direct CRISPR-associated (Cas) proteins to protect against subsequent attack by the same phages or plasmids. The threat from mobile genetic elements inevitably shapes the CRISPR loci of archaea and bacteria, and simultaneously the CRISPR-Cas immune system drives evolution of these invaders. Here we highlight our recent work, as well as that of others, that seeks to understand phage mechanisms of CRISPR-Cas evasion and conditions for population coexistence of phages with CRISPR-protected prokaryotes.Comment: 24 pages, 8 figure

ADVANCED MATERIALS: PREPARATION, STUDY AND OPTIMIZATION OF THIN FILM FOR OPTO-ELECTRONIC DEVICE

The term “optoelectronic devices” is by now used for devices in which both electrons and photons are essential for their operation, as a natural evolution from the definitions of electronic devices that involved only electrons and holes in their operation and of photonic devices that involved only photons in their operation. One of the new lighting technologies which emerged within the past two decades and has the potential of becoming more energy-efficient then the existing light sources, is the Solid State Lighting technology of Organic Light Emitting Diodes (OLEDs). In general, the basic OLED structure consists of a stack of fluorescent organic layers sandwiched between a transparent conducting anode and metallic cathode. When an appropriate current is applied to the device, holes are injected from the anode and electrons from the cathode; some of the recombination events between the holes and electrons result in electroluminescence (EL). The first part of this PhD Thesis surveyed different aspect in OLED technology that are currently under debate. In particular chapter 2 is devoted to the study, preparation and optimization of thin films between the organic hole transport layer and the anode surface while chapter 3 deals with the synthesis of trifluorene compound, with methoxy substituents, as possible UV-blue emitter. The second part of this PhD work is dedicated to the synthesis and study of new materials with interesting emissive and second order NLO properties. In particular pyrene based chromophores are investigated in chapter 4, while chapter 5 deals with the synthesis of organic-inorganic perylene-POSS hybrids with enhanced emissive properties

Novel interactions of transglutaminase-2 with heparan sulphate proteoglycans: reflection on physiological implications

This mini-review brings together information from publications and recent conference proceedings that have shed light on the biological interaction between transglutaminase-2 and heparan sulphate proteoglycans. We subsequently draw hypothesis of possible implications in the wound healing process. There is a substantial overlap in the action of transglutaminase-2 and the heparan sulphate proteoglycan syndecan-4 in normal and abnormal wound repair. Our latest findings have identified syndecan-4 as a possible binding and signalling partner of fibronectinbound TG2 and support the idea that transglutaminase-2 and syndecan-4 acts in synergy

Environmental disclosure and Eco-innovation interrelation. The case of Spanish firms

The actual drivers of companies' environmental disclosure have been widely studied and yet with no conclusive results. Most literature looks for the link between environmental performance and environmental disclosure, as reflection of the company instrumental or normative approach to sustainability. However, over the last decade, a growing number of companies are joining the ranks of eco-innovation, focusing their strategy on environmental innovation, and paving the way for new approaches to environmental disclosure. The main objective of this paper is to assess if eco-innovation in companies can be acting as a non-intended driver to disclosure of environmental reporting, in connection to the Resources Based View theory, and the search for competitive advantage. An extensive research has been undertaken with Spanish eco-innovative companies, evaluating their environmental disclosure standards from a two-fold perspective: managers' perception and public available environmental reporting. The findings bring in interesting implications about the mismatch between managers' perception of their environmental disclosure and accounting standards, and the actual disclosure of environmental reporting made available to their stakeholders. Within the studied sample, eco-innovation appears to be a driver for environmental disclosure from an inside-out approach encompassed in the RBV theory, where environmental information is primarily meant for managerial purposes and only secondarily to inform stakeholders. Los impulsores reales de la divulgación ambiental de las empresas han sido ampliamente estudiados y, sin embargo, sin resultados concluyentes. La mayoría de la literatura busca el vínculo entre el desempeño ambiental y la divulgación ambiental, como reflejo del enfoque instrumental o normativo de la compañía hacia la sostenibilidad. Sin embargo, durante la última década, un número creciente de compañías se están uniendo a las filas de la ecoinnovación, enfocando su estrategia en la innovación ambiental y allanando el camino para nuevos enfoques para la divulgación ambiental. El objetivo principal de este documento es evaluar si la ecoinnovación en las empresas puede actuar como un impulsor no intencionado de la divulgación de informes ambientales, en relación con la teoría de la Vista basada en los recursos y la búsqueda de una ventaja competitiva. Se ha llevado a cabo una extensa investigación con empresas ecoinnovadoras españolas, evaluando sus estándares de divulgación ambiental desde una doble perspectiva: la percepción de los administradores y la información ambiental disponible al público. Los hallazgos traen implicaciones interesantes sobre el desajuste entre la percepción de los gerentes sobre su divulgación ambiental y sus normas contables, y la divulgación real de los informes ambientales puestos a disposición de sus partes interesadas. Dentro de la muestra estudiada, la ecoinnovación parece ser un impulsor para la divulgación ambiental desde un enfoque integral incluido en la teoría de la RBV, donde la información ambiental se destina principalmente a fines administrativos y solo de manera secundaria a informar a los interesados

Biabduction (and related problems) in array separation logic

We investigate array separation logic (\mathsf {ASL}), a variant of symbolic-heap separation logic in which the data structures are either pointers or arrays, i.e., contiguous blocks of memory. This logic provides a language for compositional memory safety proofs of array programs. We focus on the biabduction problem for this logic, which has been established as the key to automatic specification inference at the industrial scale. We present an \mathsf {NP} decision procedure for biabduction in \mathsf {ASL}, and we also show that the problem of finding a consistent solution is \mathsf {NP}-hard. Along the way, we study satisfiability and entailment in \mathsf {ASL}, giving decision procedures and complexity bounds for both problems. We show satisfiability to be \mathsf {NP}-complete, and entailment to be decidable with high complexity. The surprising fact that biabduction is simpler than entailment is due to the fact that, as we show, the element of choice over biabduction solutions enables us to dramatically reduce the search space

Environmental management capabilities for a “circular eco-innovation”

At a micro level, eco-innovation marks a transition towards a circular economy (CE), and standardised routines and controls are being implemented by businesses to introduce eco-innovative processes and thus a circular business model. Eco-innovation applied to a circular model implies changes to companies'' environmental management and accounting practices used to manage natural resources. In this context, this study analyses and measures formal and informal environmental management systems, such as certification standards and other management and environmental accounting procedures used in eco-innovation and the CE within the dynamic capabilities theoretical framework. The study also investigates the cause-and-effect relationship between firms'' “circular eco-innovation” and environmental capabilities using partial least squares structural equation modelling and tests it using a sample of Spanish companies. This study offers new knowledge about the interposition of business eco-innovation and CE-related activities introduced by firms from the dynamic capabilities perspective. © 2020 John Wiley & Sons, Ltd and ERP Environmen