Transglutaminase 2 in cartilage homoeostasis: novel links with inflammatory osteoarthritis.

Transglutaminase 2 (TG2) is highly expressed during chondrocyte maturation and contributes to the formation of a mineralised scaffold by introducing crosslinks between extracellular matrix (ECM) proteins. In healthy cartilage, TG2 stabilises integrity of ECM and likely influences cartilage stiffness and mechanistic properties. At the same time, the abnormal accumulation of TG2 in the ECM promotes chondrocyte hypertrophy and cartilage calcification, which might be an important aspect of osteoarthritis (OA) initiation. Although excessive joint loading and injuries are one of the main causes leading to OA development, it is now being recognised that the presence of inflammatory mediators accelerates OA progression. Inflammatory signalling is known to stimulate the extracellular TG2 activity in cartilage and promote TG2-catalysed crosslinking of molecules that promote chondrocyte osteoarthritic differentiation. It is, however, unclear whether TG2 activity aims to resolve or aggravate damages within the arthritic joint. Better understanding of the complex signalling pathways linking inflammation with TG2 activities is needed to identify the role of TG2 in OA and to define possible avenues for therapeutic interventions

Interplay between transglutaminases and heparan sulphate in progressive renal scarring

Transglutaminase-2 (TG2) is a new anti-fibrotic target for chronic kidney disease, for its role in altering the extracellular homeostatic balance leading to excessive build-up of matrix in kidney. However, there is no confirmation that TG2 is the only transglutaminase involved, neither there are strategies to control its action specifically over that of the conserved family-members. In this study, we have profiled transglutaminase isozymes in the rat subtotal nephrectomy (SNx) model of progressive renal scarring. All transglutaminases increased post-SNx peaking at loss of renal function but TG2 was the predominant enzyme. Upon SNx, extracellular TG2 deposited in the tubulointerstitium and peri-glomerulus via binding to heparan sulphate (HS) chains of proteoglycans and co-associated with syndecan-4. Extracellular TG2 was sufficient to activate transforming growth factor-β1 in tubular epithelial cells, and this process occurred in a HS-dependent way, in keeping with TG2-affinity for HS. Analysis of heparin binding of the main transglutaminases revealed that although the interaction between TG1 and HS is strong, the conformational heparin binding site of TG2 is not conserved, suggesting that TG2 has a unique interaction with HS within the family. Our data provides a rationale for a novel anti-fibrotic strategy specifically targeting the conformation-dependent TG2-epitope interacting with HS

Characteristics and applications of small, portable gaseous air pollution monitors

BackgroundTraditional approaches for measuring air quality based on fixed measurements are inadequate for personal exposure monitoring. To combat this issue, the use of small, portable gas-sensing air pollution monitoring technologies is increasing, with researchers and individuals employing portable and mobile methods to obtain more spatially and temporally representative air pollution data. However, many commercially available options are built for various applications and based on different technologies, assumptions, and limitations. A review of the monitor characteristics of small, gaseous monitors is missing from current scientific literature.PurposeA state-of-the-art review of small, portable monitors that measure ambient gaseous outdoor pollutants was developed to address broad trends during the last 5-10 years, and to help future experimenters interested in studying gaseous air pollutants choose monitors appropriate for their application and sampling needs.MethodsTrends in small, portable gaseous air pollution monitor uses and technologies were first identified and discussed in a review of literature. Next, searches of online databases were performed for articles containing specific information related to performance, characteristics, and use of such monitors that measure one or more of three criteria gaseous air pollutants: ozone, nitrogen dioxide, and carbon monoxide. All data were summarized into reference tables for comparison between applications, physical features, sensing capabilities, and costs of the devices.ResultsRecent portable monitoring trends are strongly related to associated applications and audiences. Fundamental research requires monitors with the best individual performance, and thus the highest cost technology. Monitor networking favors real-time capabilities and moderate cost for greater reproduction. Citizen science and crowdsourcing applications allow for lower-cost components; however important strengths and limitations for each application must be addressed or acknowledged for the given use

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Enabling technologies for distributed picosatellite missions in LEO

Picosatellites are very small satellites with a mass of less than 1 kg. A number of picosatellite projects have been undertaken by University and government research teams. Constellations of picosatellites could prove to be a low-cost and efficient solution to remote sensing in LEO. Reconfiguration and adaptation are capabilities, which are of critical importance to such constellations.A conceptual model of a constellation consisting of heterogeneous picosatellite nodes with a payload function distributed among the nodes will be outlined. Enabling technologies for picosatellite constellations such as wireless intersatellite links, reconfigurable on-board computing and distributed processing will be discussed. A proposal for a test-bed to demonstrate a reconfigurable distributed computing platform will be outlined