BMP9 is a potent inducer of chondrogenesis, volumetric expansion and collagen type II accumulation in bovine auricular cartilage chondroprogenitors

Reconstruction of the outer ear currently requires harvesting of cartilage from the posterior of the auricle or ribs leading to pain and donor site morbidity. An alternative source for auricular reconstruction is in vitro tissue engineered cartilage using stem/progenitor cells. Several candidate cell-types have been studied with tissue-specific auricular cartilage progenitor cells (AuCPC) of particular interest. Whilst chondrogenic differentiation of competent stem cells using growth factor TGFβ1 produces cartilage this tissue is frequently fibrocartilaginous and lacks the morphological features of hyaline cartilage. Recent work has shown that growth factor BMP9 is a potent chondrogenic and morphogenetic factor for articular cartilage progenitor cells, and we hypothesised that this property extends to cartilage-derived progenitors from other tissues. In this study we show monoclonal populations of AuCPCs from immature and mature bovine cartilage cultured with BMP9 produced cartilage pellets have 3-5-fold greater surface area in sections than those grown with TGFβ1. Increased volumetric growth using BMP9 was due to greater sGAG deposition in immature pellets and significantly greater collagen accumulation in both immature and mature progenitor pellets. Polarised light microscopy and immunohistochemical analyses revealed that the organisation of collagen fibrils within pellets is an important factor in the growth of pellets. Additionally, chondrocytes in BMP9 stimulated cell pellets had larger lacunae and were more evenly dispersed throughout the extracellular matrix. Interestingly, BMP9 tended to normalise the response of immature AuCPC monoclonal cell lines to differentiation cues whereas cells exhibited more variation under TGFβ1. In conclusion, BMP9 appears to be a potent inducer of chondrogenesis and volumetric growth for AuCPCs a property that can be exploited for tissue engineering strategies for reconstructive surgery though with the caveat of negligible elastin production following 21-day treatment with either growth factor

De-pollution efficacy of photocatalytic roofing granules

Photocatalytic building surfaces can harness sunlight to reduce urban air pollution. The NOx abatement capacity of TiO2-coated granules used in roofing products was evaluated for commercial product development. A laboratory test chamber and ancillary setup were built following conditions prescribed by ISO Standard 22197-1. It was validated by exposing reference P25-coated aluminum plates to a 3 L min−1 air flow enriched in 1 ppm NO under UVA irradiation (360 nm, 11.5 W m−2). We characterized prototype granule-surfaced asphalt shingles and loose granules prepared with different TiO2 loadings and post-treatment formulations. Tests performed at surface temperatures of 25 and 60 °C showed that NOx abatement was more effective at the higher temperature. Preliminary tests explored the use of 1 ppm NO2 and of 1 ppm and 0.3 ppm NO/NO2 mixtures. Specimens were aged in a laboratory accelerated weathering apparatus, and by exposure to the outdoor environment over periods that included dry and rainy seasons. Laboratory aging led to higher NO removal and NO2 formation rates, and the same catalyst activation was observed after field exposure with frequent precipitation. However, exposure during the dry season reduced the performance. This inactivation was mitigated by cleaning the surface of field-exposed specimens. Doubling the TiO2 loading led to a 50–150% increase in NO removal and NOx deposition rates. Application of different post-treatment coatings decreased NO removal rates (21–35%) and NOx deposition rates (26–74%) with respect to untreated granules. The mass balance of nitrogenated species was assessed by extracting granules after UV exposure in a 1 ppm NO-enriched atmosphere

Association of Mineralocorticoid Receptor Antagonists With the Mortality and Cardiovascular Effects in Dialysis Patients: A Meta-analysis

Whether Mineralocorticoid receptor antagonists (MRA) reduce mortality and cardiovascular effects of dialysis patients remains unclear. A meta-analysis was designed to investigate whether MRA reduce mortality and cardiovascular effects of dialysis patients, with a registration in INPLASY (INPLASY2020120143). The meta-analysis revealed that MRA significantly reduced all-cause mortality (ACM) and cardiovascular mortality (CVM). Patients receiving MRA presented improved left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF), decreased systolic blood pressure (SBP) and diastolic blood pressure (DBP). There was no significant difference in the serum potassium level between the MRA group and the placebo group. MRA vs. control exerts definite survival and cardiovascular benefits in dialysis patients, including reducing all-cause mortality and cardiovascular mortality, LVMI, and arterial blood pressure, and improving LVEF. In terms of safety, MRA did not increase serum potassium levels for dialysis patients with safety. Systematic Review Registration: (https://inplasy.com/inplasy-protocol-1239-2/), identifier (INPLASY2020120143)

How plants cope with temperature stress

A cold night can follow a hot day, and because they cannot move, plants subjected to such temperature fluctuations must acclimate on the basis mainly of pre-existing proteins. Zhang et al. report in a paper in BMC Plant Biology, however, that heat-induced cell death results from transcriptional activation of a kinase related to disease resistance factors and leading to a localized hypersensitive response. This specialized response reflects the failure of adaptations that normally enable plants to survive over a remarkable temperature range, by mechanisms that are not fully understood

Full-field 3D shape measurement of discontinuous specular objects by direct phase measuring deflectometry

With the advent of intelligent manufacturing, phase measuring deflectometry (PMD) has been widely studied for the measurement of the three-dimensional (3D) shape of specular objects. However, existing PMDs cannot measure objects having discontinuous specular surfaces. This paper presents a new direct PMD (DPMD) method that measures the full-field 3D shape of complicated specular objects. A mathematical model is derived to directly relate an absolute phase map to depth data, instead of the gradient. Two relevant parameters are calibrated using a machine vision-based method. On the basis of the derived model, a full-field 3D measuring system was developed. The accuracy of the system was evaluated using a mirror with known positions along an accurate translating stage. The 3D shape of a monolithic multi-mirror array having multiple specular surfaces was measured. Experimental results show that the proposed DPMD method can obtain the full-field 3D shape of specular objects having isolated and/or discontinuous surfaces accurately and effectively

Smith-Waterman peak alignment for comprehensive two-dimensional gas chromatography-mass spectrometry

<p>Abstract</p> <p>Background</p> <p>Comprehensive two-dimensional gas chromatography coupled with mass spectrometry (GC × GC-MS) is a powerful technique which has gained increasing attention over the last two decades. The GC × GC-MS provides much increased separation capacity, chemical selectivity and sensitivity for complex sample analysis and brings more accurate information about compound retention times and mass spectra. Despite these advantages, the retention times of the resolved peaks on the two-dimensional gas chromatographic columns are always shifted due to experimental variations, introducing difficulty in the data processing for metabolomics analysis. Therefore, the retention time variation must be adjusted in order to compare multiple metabolic profiles obtained from different conditions.</p> <p>Results</p> <p>We developed novel peak alignment algorithms for both homogeneous (acquired under the identical experimental conditions) and heterogeneous (acquired under the different experimental conditions) GC × GC-MS data using modified Smith-Waterman local alignment algorithms along with mass spectral similarity. Compared with literature reported algorithms, the proposed algorithms eliminated the detection of landmark peaks and the usage of retention time transformation. Furthermore, an automated peak alignment software package was established by implementing a likelihood function for optimal peak alignment.</p> <p>Conclusions</p> <p>The proposed Smith-Waterman local alignment-based algorithms are capable of aligning both the homogeneous and heterogeneous data of multiple GC × GC-MS experiments without the transformation of retention times and the selection of landmark peaks. An optimal version of the SW-based algorithms was also established based on the associated likelihood function for the automatic peak alignment. The proposed alignment algorithms outperform the literature reported alignment method by analyzing the experiment data of a mixture of compound standards and a metabolite extract of mouse plasma with spiked-in compound standards.</p

Evidence for Anthropogenic Surface Loading as Trigger Mechanism of the 2008 Wenchuan Earthquake

Two and a half years prior to China's M7.9 Wenchuan earthquake of May 2008, at least 300 million metric tons of water accumulated with additional seasonal water level changes in the Minjiang River Valley at the eastern margin of the Longmen Shan. This article shows that static surface loading in the Zipingpu water reservoir induced Coulomb failure stresses on the nearby Beichuan thrust fault system at <17km depth. Triggering stresses exceeded levels of daily lunar and solar tides and perturbed a fault area measuring 416+/-96km^2. These stress perturbations, in turn, likely advanced the clock of the mainshock and directed the initial rupture propagation upward towards the reservoir on the "Coulomb-like" Beichuan fault with rate-and-state dependent frictional behavior. Static triggering perturbations produced up to 60 years (0.6%) of equivalent tectonic loading, and show strong correlations to the coseismic slip. Moreover, correlations between clock advancement and coseismic slip, observed during the mainshock beneath the reservoir, are strongest for a longer seismic cycle (10kyr) of M>7 earthquakes. Finally, the daily event rate of the micro-seismicity (M>0.5) correlates well with the static stress perturbations, indicating destabilization.Comment: 22 pages, 4 figures, 3 table

A metabolite-derived protein modification integrates glycolysis with KEAP1-NRF2 signalling.

Mechanisms that integrate the metabolic state of a cell with regulatory pathways are necessary to maintain cellular homeostasis. Endogenous, intrinsically reactive metabolites can form functional, covalent modifications on proteins without the aid of enzymes1,2, and regulate cellular functions such as metabolism3-5 and transcription6. An important 'sensor' protein that captures specific metabolic information and transforms it into an appropriate response is KEAP1, which contains reactive cysteine residues that collectively act as an electrophile sensor tuned to respond to reactive species resulting from endogenous and xenobiotic molecules. Covalent modification of KEAP1 results in reduced ubiquitination and the accumulation of NRF27,8, which then initiates the transcription of cytoprotective genes at antioxidant-response element loci. Here we identify a small-molecule inhibitor of the glycolytic enzyme PGK1, and reveal a direct link between glycolysis and NRF2 signalling. Inhibition of PGK1 results in accumulation of the reactive metabolite methylglyoxal, which selectively modifies KEAP1 to form a methylimidazole crosslink between proximal cysteine and arginine residues (MICA). This posttranslational modification results in the dimerization of KEAP1, the accumulation of NRF2 and activation of the NRF2 transcriptional program. These results demonstrate the existence of direct inter-pathway communication between glycolysis and the KEAP1-NRF2 transcriptional axis, provide insight into the metabolic regulation of the cellular stress response, and suggest a therapeutic strategy for controlling the cytoprotective antioxidant response in several human diseases

GLAST: Understanding the High Energy Gamma-Ray Sky

We discuss the ability of the GLAST Large Area Telescope (LAT) to identify, resolve, and study the high energy gamma-ray sky. Compared to previous instruments the telescope will have greatly improved sensitivity and ability to localize gamma-ray point sources. The ability to resolve the location and identity of EGRET unidentified sources is described. We summarize the current knowledge of the high energy gamma-ray sky and discuss the astrophysics of known and some prospective classes of gamma-ray emitters. In addition, we also describe the potential of GLAST to resolve old puzzles and to discover new classes of sources.Comment: To appear in Cosmic Gamma Ray Sources, Kluwer ASSL Series, Edited by K.S. Cheng and G.E. Romer

Cortical depth dependent functional responses in humans at 7T: improved specificity with 3D GRASE

Ultra high fields (7T and above) allow functional imaging with high contrast-to-noise ratios and improved spatial resolution. This, along with improved hardware and imaging techniques, allow investigating columnar and laminar functional responses. Using gradient-echo (GE) (T2* weighted) based sequences, layer specific responses have been recorded from human (and animal) primary visual areas. However, their increased sensitivity to large surface veins potentially clouds detecting and interpreting layer specific responses. Conversely, spin-echo (SE) (T2 weighted) sequences are less sensitive to large veins and have been used to map cortical columns in humans. T2 weighted 3D GRASE with inner volume selection provides high isotropic resolution over extended volumes, overcoming some of the many technical limitations of conventional 2D SE-EPI, whereby making layer specific investigations feasible. Further, the demonstration of columnar level specificity with 3D GRASE, despite contributions from both stimulated echoes and conventional T2 contrast, has made it an attractive alternative over 2D SE-EPI. Here, we assess the spatial specificity of cortical depth dependent 3D GRASE functional responses in human V1 and hMT by comparing it to GE responses. In doing so we demonstrate that 3D GRASE is less sensitive to contributions from large veins in superficial layers, while showing increased specificity (functional tuning) throughout the cortex compared to GE