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Among 283 cryptogenic stroke patients, 136 (48.1%) were tested for aPLs and 56 (41.2%) were positive. aPL tests were performed predominantly in patients aged <50years rather than in older patients, even among cryptogenic stroke patients. The two age groups had similar positivity rates of >40% (<50years 43.2%; ≥50years 40.4%; p=0.92) and their antibody profiles were similar.
A significant number of patients with cryptogenic stroke had positive aPL results regardless of age. aPL testing may offer additional diagnostic opportunities in cryptogenic stroke patients, and thus may reduce the incidence of cryptogenic stroke.
A significant number of patients with cryptogenic stroke had positive aPL results regardless of age. aPL testing may offer additional diagnostic opportunities in cryptogenic stroke patients, and thus may reduce the incidence of cryptogenic stroke.The initial clinical trials of pig solid organ xenotransplantation (XTx) are drawing closer and could begin in the coming years. The first clinical trials may aim to transplant genetically-modified pig kidneys into adult humans. The impetus for beginning these first-in-human trials is the severe lack of deceased donor kidneys for transplantation and the number of patients with end-stage renal disease currently on transplant waitlists, which in the USA approaches 100 000. The majority of patients on the kidney transplant waitlist receive continuous renal replacement therapy. In the United States, for patients on the kidney waitlist, the median wait-time to receive a deceased human donor organ is approximately 4.5 years for patients aged 45-74, with a 5-year mortality (or removal from the waitlist because of deteriorating health) of approximately 40%. XTx has the potential to reduce the kidney waitlist morbidity and mortality while improving quality of life. By focusing on scientific and psychosocial criteria, we present ethical considerations of certain inclusion and exclusion criteria for these first-in-human clinical trials that we suggest have not yet been fully explored.The unfolded states of fibronectin (FN) subsequently induce the formation of an extracellular matrix (ECM) fibrillar network, which is necessary to generate new substitutive tissues. Here, the authors demonstrate that negatively charged small unilamellar vesicles (SUVs) qualify as candidates for FN delivery due to their remarkable effects on the autonomous binding and unfolding of FN, which leads to increased tissue regeneration. In vitro experiments revealed that the FN-SUV complex remarkably increased the attachment, differentiation, and migration of fibroblasts. The potential utilization of this complex in vivo to treat inflammatory colon diseases is also described based on results obtained for ameliorated conditions in rats with ulcerative colitis (UC) that had been treated with the FN-SUV complex. Their findings provide a new ECM-delivery platform for ECM-based therapeutic applications and suggest that properly designed SUVs may be an unprecedented FN-delivery system that is highly effective in treating UC and inflammatory bowel diseases.The pathogenic fungus Cryptococcus neoformans must overcome iron limitation to cause disease in mammalian hosts. Previously, we reported a screen for insertion mutants with poor growth on haem as the sole iron source. In this study, we characterised one such mutant and found that the defective gene encoded a Vam6/Vps39/TRAP1 domain-containing protein required for robust growth on haem, an important iron source in host tissue. We designated this protein Vps3 based on reciprocal best matches with the corresponding protein in Saccharomyces cerevisiae. Compactin C. neoformans encodes a second Vam6/Vps39/TRAP1 domain-containing protein designated Vam6/Vlp1, and we found that this protein is also required for robust growth on haem as well as on inorganic iron sources. link2 This protein is predicted to be a component of the homotypic fusion and vacuole protein sorting complex involved in endocytosis. Further characterisation of the vam6Δ and vps3Δ mutants revealed perturbed trafficking of iron acquisition functions (e.g., the high affinity iron permease Cft1) and impaired processing of the transcription factor Rim101, a regulator of haem and iron acquisition. The vps3Δ and vam6Δ mutants also had pleiotropic phenotypes including loss of virulence in a mouse model of cryptococcosis, reduced virulence factor elaboration and increased susceptibility to stress, indicating pleiotropic roles for Vps3 and Vam6 beyond haem use in C. neoformans. TAKE AWAYS Two Vam6/Vps39/TRAP1-domain proteins, Vps3 and Vam6, support the growth of Cryptococcus neoformans on haem. Loss of Vps3 and Vam6 influences the trafficking and expression of iron uptake proteins. Loss of Vps3 or Vam6 eliminates the ability of C. neoformans to cause disease in a mouse model of cryptococcosis.Wheat (Triticum aestivum L.) cultivation differs considerably in respect of soil type, temperature, pH, organic matter, moisture regime, etc. Among these, rising atmospheric temperature due to global warming is most important as it affects grain yield drastically. Studies have shown that for every 1°C rise in temperature above wheat's optimal growing temperature range of 20-25°C, there is a decrease in 2.8 days and 1.5 mg in the grain filling period and kernel weight, respectively, resulting in wheat yield reduction by 4-6 quintal per hectare. Growing demand for food and multidimensional issues of global warming may further push wheat crop to heat stress environments that can substantially affect heading duration, percent grain setting, maturity duration, grain growth rate and ultimately total grain yield. Considerable genetic variation exists in wheat gene pool with respect to various attributes associated with high temperature and stress tolerance; however, only about 15% of the genetic variability could be incorporated into cultivated wheat so far. Thus, alternative strategies have to be explored and implemented for sustainable, more productive and environment friendly agriculture. One of the feasible and environment friendly option is to look at micro-organisms that reside inside the plant without adversely affecting its growth, known as 'endophytes', and these colonize virtually all plant organs such as roots, stems, leaves, flowers and grains. The relationship between plant and endophytes is vital to the plant health, productivity and overall survival under abiotic stress conditions. Thus, it becomes imperative to enlist the endophytes (bacterial and fungal) isolated till date from wheat cultivars, their mechanism of ingression and establishment inside plant organs, genes involved in ingression, the survival advantages they confer to the plant under abiotic stress conditions and the potential benefits of their use in sustainable wheat cultivation.We test whether vegetation community composition from a 10-year climate manipulation experiment on a Welsh peat bog resembles vegetation communities during periods of climate change inferred from a peat core. Experimentally warmed and combined warmed and droughted treatments drove significant increases in ericaceous shrubs but Sphagnum was unaffected. Similarly, Calluna vulgaris seeds increase during inferred warmer periods in the palaeoecological record. Experimental short-term episodic drought (four 4-week drought treatments) did not affect vegetation. Plant community composition has undergone several abrupt changes throughout the past c. 1500 years, often in response to human disturbance. Only slight changes occurred during the Medieval Climate Anomaly (c. 950-1250 Common Era [CE]) in vegetation and hydrology, while abrupt changes occurred during the Little Ice Age (c. 1300-1850 CE) when water tables were highest, suggesting that these shifts were driven by changes in water table, modulated by climate. A pdifferently to future climate change.Hexosaminidase A (HexA), a heterodimer consisting of HEXA and HEXB, converts the ganglioside sphingolipid GM2 to GM3 by removing a terminal N-acetyl-d-galactosamine. HexA enzyme deficiency in humans leads to GM2 accumulation in cells, particularly in neurons, and is associated with neurodegeneration. link3 While HexA and sphingolipid metabolism have been extensively investigated in the context of neuronal lipid metabolism, little is known about the metabolic impact of HexA and ganglioside degradation in other tissues. Here, we focussed on the role of HexA in the liver, which is a major regulator of systemic lipid metabolism. We find that hepatic Hexa expression is induced by lipid availability and increased in the presence of hepatic steatosis, which is associated with increased hepatic GM3 content. To assess the impact of HEXA on hepatic lipid metabolism, we used an adeno-associated virus to overexpress HEXA in the livers of high-fat diet fed mice. HEXA overexpression was associated with increased hepatic GM3 content and increased expression of enzymes involved in the degradation of glycated sphingolipids, ultimately driving sphingomyelin accumulation in the liver. In addition, HEXA overexpression led to substantial proteome remodeling in cell surface lipid rafts, which was associated with increased VLDL processing and secretion, hypertriglyceridemia and ectopic lipid accumulation in peripheral tissues. This study established an important role of HEXA in modulating hepatic sphingolipid and lipoprotein metabolism.The responses of forests to nitrogen (N) deposition largely depend on the fates of deposited N within the ecosystem. Nitrogen-fixing legume trees widely occur in terrestrial forests, but the fates of deposited N in legume-dominated forests remain unclear, which limit a global evaluation of N deposition impacts and feedbacks on carbon sequestration. Here, we performed the first ecosystem-scale 15 N labeling experiment in a typical legume-dominated forest as well as in a nearby non-legume forest to determine the fates of N deposition between two different forest types and to explore their underlying mechanisms. The 15 N was sprayed bimonthly for 1 year to the forest floor in control and N addition (50 kg N ha-1 year-1 for 10 years) plots in both forests. We unexpectedly found a strong capacity of the legume forest to retain deposited N, with 75 ± 5% labeled N recovered in plants and soils, which was higher than that in the non-legume forest (56 ± 4%). The higher 15 N recovery in legume forest was mainly driven by uptake by the legume trees, in which 15 N recovery was approximately 15% more than that in the nearby non-legume trees. This indicates higher N-demand by the legume than non-legume trees. Mineral soil was the major sink for deposited N, with 39 ± 4% and 34 ± 3% labeled N retained in the legume and non-legume forests, respectively. Moreover, N addition did not significantly change the 15 N recovery patterns of both forests. Overall, these findings indicate that legume-dominated forests act as a strong sink for deposited N regardless of high soil N availability under long-term atmospheric N deposition, which suggest a necessity to incorporate legume-dominated forests into N-cycling models of Earth systems to improve the understanding and prediction of terrestrial N budgets and the global N deposition effects.