Impaired nutrient signaling and body weight control in a Na⁺ neutral amino acid cotransporter (Slc6a19)-deficient mouse

Amino acid uptake in the intestine and kidney is mediated by a variety of amino acid transporters. To understand the role of epithelial neutral amino acid uptake in whole body homeostasis, we analyzed mice lacking the apical broad-spectrum neutral (0) amino acid transporter BᴼAT1 (Slc6a19). A general neutral aminoaciduria was observed similar to human Hartnup disorder which is caused by mutations in SLC6A19. Na⁺ -dependent uptake of neutral amino acids into the intestine and renal brush-border membrane vesicles was abolished. No compensatory increase of peptide transport or other neutral amino acid transporters was detected. Mice lacking BᴼAT1 showed a reduced body weight. When adapted to a standard 20% protein diet, BᴼAT1-deficient mice lost body weight rapidly on diets containing 6 or 40% protein. Secretion of insulin in response to food ingestion after fasting was blunted. In the intestine, amino acid signaling to the mammalian target of rapamycin (mTOR) pathway was reduced, whereas the GCN2/ATF4 stress response pathway was activated, indicating amino acid deprivation in epithelial cells. The results demonstrate that epithelial amino acid uptake is essential for optimal growth and body weight regulation.This work was supported by National Health and Medical Research Council Grant 525415, Australian Research Council Grant DP0877897, University of Sydney Bridging Grant RIMS2009-02579), and by an anonymous foundatio

Self-organisation after embryonic kidney dissociation is driven via selective adhesion of ureteric epithelial cells

Human pluripotent stem cells, after directed differentiation in vitro, can spontaneously generate complex tissues via self-organisation of the component cells. Self-organisation can also reform embryonic organ structure after tissue disruption. It has previously been demonstrated that dissociated embryonic kidneys can recreate component epithelial and mesenchymal relationships sufficient to allow continued kidney morphogenesis. Here, we investigate the timing and underlying mechanisms driving self-organisation after dissociation of the embryonic kidney using time-lapse imaging, high-resolution confocal analyses and mathematical modelling. Organotypic self-organisation sufficient for nephron initiation was observed within a 24 h period. This involved cell movement, with structure emerging after the clustering of ureteric epithelial cells, a process consistent with models of random cell movement with preferential cell adhesion. Ureteric epithelialisation rapidly followed the formation of ureteric cell clusters with the reformation of nephron-forming niches representing a later event. Disruption of P-cadherin interactions was seen to impair this ureteric epithelial cell clustering without affecting epithelial maturation. This understanding could facilitate improved regulation of patterning within organoids and facilitate kidney engineering approaches guided by cell-cell self-organisation

Organic rankine cycle as efficient alternative to steam cycle for small scale power generation

Paper presented at the 8th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Mauritius, 11-13 July, 2011.To generate electricity from biomass combustion heat, geothermal wells, recovered waste heat from internal combustion engines, gas turbines or industrial processes, both the steam cycle and the organic Rankine cycle are widely in use. Both technologies are well established and can be found on comparable industrial applications. This paper presents a thermodynamic analysis and a comparative study of the cycle efficiency for a simplified steam cycle versus an ORC cycle. The most commonly used organic fluids have been considered : R245fa, Toluene, (cyclo)-pentane, Solkatherm and 2 siliconeoils (MM and MDM). Working fluid selection and its application area is being discussed based on fluid properties. The thermal efficiency is mainly determined by the temperature level of the heat source and the condenser conditions. The influence of several process parameters such as turbine inlet and condenser temperature, turbine isentropic efficiency, vapour quality and pressure, use of a regenerator (ORC), is derived from numerous computer simulations. The temperature profile of the heat source is the main restricting factor for the evaporation temperature and pressure. Finally, some general and economic considerations related to the choice between a steam cycle and ORC are discussed.mp201

Melorheostosis of the foot

A 48-year old male patient of Arabic origin presented to the orthopedic consultation with a history of slow progressive pain, joint stiffness and swelling of the left foot. Local tenderness was present and a painful, hard mass was clearly palpable. Conventional radiography (Fig. A) revealed undulating and sclerotic enlarged areas (candle wax-appearance) in the lateral cuneiform bone, the third metatarsal bone and the proximal, intermediate and distal phalanx bone of the third row. Cortical hyperostosis was also apparent in the middle phalanx and metatarsal bone of the second row. Areas of extraosseous bone formation could be seen, most clearly adjacent to the metatarsal head and the middle phalanx of the third row. A diagnosis of melorheostosis was made. A CT-scan, which is not strictly required to make the diagnosis, confirmed the radiographic findings (Fig. B). The patient was treated conservatively

Prihodnost na obrobju: nacionalno in internacionalno v ruski izseljenski poeziji z Daljnega vzhoda

Članek proučuje medsebojno delovanje nacionalizma in internacionalizma pri treh rodovih ruskih izseljenskih pesnikov z Daljnega vzhoda: Nikolaju Matvejevu, Venediktu Martu in Ivanu Elaginu. Slednji v nasprotju s svetovljanstvom svojih prednikov poudarja domotožje po Rusiji, vidi v ruskem jeziku očetno dediščino in izbriše svoj judovski izvor.This paper investigates the interplay of nationalism and internationalism in three generations of Russian émigré poets from the Far East: Nikolai Matveev, Venedikt Mart, and Ivan Elagin who, in contrast to the cosmopolitanism of his forefathers, emphasises nostalgia for Russia, considering the Russian languageas paternal heritage and deleting his Jewish descent

Loss of solute carriers in T cell mediated rejection in mouse and human kidneys: An active epithelial injury-repair response

T cell-mediated rejection of kidney allografts causes epithelial deterioration, manifested by tubulitis, but the mechanism remains unclear. We hypothesized that interstitial inflammation triggers a stereotyped epithelial response similar to that triggered by other types of injury such as ischemia-reperfusion. We identified solute carrier transcripts with decreased expression in mouse allografts, and compared their behavior in T cell-mediated rejection to native kidneys with ischemic acute tubular necrosis (ATN). Average loss of solute carrier expression was similar in ATN (77%) and T cell-mediated rejection (75%) with high correlation of individual transcripts. Immunostaining of SLC6A19 confirmed loss of proteins. Analysis of human kidney transplant biopsies confirmed that T cell-mediated rejection and ATN showed similar loss of solute carrier mRNAs. The loss of solute carrier expression was weakly correlated with interstitial inflammation, but kidneys with ATN showed decreased solute carriers despite minimal inflammation. Loss of renal function correlated better with decreased solute carrier expression than with histologic lesions (r = 0.396, p < 0.001). Thus the loss of epithelial transcripts in rejection is not a unique consequence of T cell-mediated rejection but an active injury-repair response of epithelium, triggered by rejection but also by other injury mechanisms. © 2010 The American Society of Transplantation and the American Society of Transplant Surgeons

Exploring the Affordance of Distance Learning Platform (DLP) in COVID19 Remote Learning Environment

2020, Springer Nature Switzerland AG. Higher Education has been facing the dilemma of the preferred delivery method for over two decades. COVID19 pandemic in 2020 made the need for further exploration of the same even more imperative. Although the urgency of events did not leave much time for policymakers and educators to decide, it did inspire the authors of this article to analyse the affordances of Distance Learning Platform (DLP), and the ways students perceived the online learning due to current uncertain circumstances. Students as critical stakeholders in the learning process were on the receiving end of the decisions taken to facilitate distance learning. The focus of this study was to understand students\u27 experience of using the Distance Learning Platform (DLP) in a crises-induced environment at a university in the United Arab Emirates. A sample size of 60 undergraduate students who took academic study skills classes was used to collect data. Students were asked to reflect on their experience of distance learning, and the data were analysed to understand the students\u27 preferences of their study method while enabling them to recognise their cognitive skillset. The data indicated reasons behind students\u27 preferences of the preferred delivery method