Characterization of human platelet binding of recombinant T cell receptor ligand

<p>Abstract</p> <p>Background</p> <p>Recombinant T cell receptor ligands (RTLs) are bio-engineered molecules that may serve as novel therapeutic agents for the treatment of neuroinflammatory conditions such as multiple sclerosis (MS). RTLs contain membrane distal α1 plus β1 domains of class II major histocompatibility complex linked covalently to specific peptides that can be used to regulate T cell responses and inhibit experimental autoimmune encephalomyelitis (EAE). The mechanisms by which RTLs impede local recruitment and retention of inflammatory cells in the CNS, however, are not completely understood.</p> <p>Methods</p> <p>We have recently shown that RTLs bind strongly to B cells, macrophages, and dendritic cells, but not to T cells, in an antigenic-independent manner, raising the question whether peripheral blood cells express a distinct RTL-receptor. Our study was designed to characterize the molecular mechanisms by which RTLs bind human blood platelets, and the ability of RTL to modulate platelet function.</p> <p>Results</p> <p>Our data demonstrate that human blood platelets support binding of RTL. Immobilized RTL initiated platelet intracellular calcium mobilization and lamellipodia formation through a pathway dependent upon Src and PI3 kinases signaling. The presence of RTL in solution reduced platelet aggregation by collagen, while treatment of whole blood with RTL prolonged occlusive thrombus formation on collagen.</p> <p>Conclusions</p> <p>Platelets, well-known regulators of hemostasis and thrombosis, have been implicated in playing a major role in inflammation and immunity. This study provides the first evidence that blood platelets express a functional RTL-receptor with a putative role in modulating pathways of neuroinflammation.</p

Strong Ultraviolet Pulse From a Newborn Type Ia Supernova

Type Ia supernovae are destructive explosions of carbon oxygen white dwarfs. Although they are used empirically to measure cosmological distances, the nature of their progenitors remains mysterious, One of the leading progenitor models, called the single degenerate channel, hypothesizes that a white dwarf accretes matter from a companion star and the resulting increase in its central pressure and temperature ignites thermonuclear explosion. Here we report observations of strong but declining ultraviolet emission from a Type Ia supernova within four days of its explosion. This emission is consistent with theoretical expectations of collision between material ejected by the supernova and a companion star, and therefore provides evidence that some Type Ia supernovae arise from the single degenerate channel.Comment: Accepted for publication on the 21 May 2015 issue of Natur

Resistance to Wheat streak mosaic virus identified in synthetic wheat lines

Citation: Shoup Rupp, J. L., Simon, Z. G., Gillett-Walker, B., & Fellers, J. P. (2014). Resistance to Wheat streak mosaic virus identified in synthetic wheat lines. Retrieved from http://krex.ksu.eduWheat streak mosaic virus (WSMV) is an important pathogen in wheat that causes significant yield losses each year. WSMV is typically controlled using cultural practices such as the removal of volunteer wheat. Genetic resistance is limited. Until recently, no varieties have been available with major resistance genes to WSMV. Two resistance genes have been derived from Thinopyrum intermedium through chromosome engineering, while a third gene was transferred from bread wheat through classical breeding. New sources of resistance are needed and synthetic wheat lines provide a means of accessing genetic variability in wheat progenitors. A collection of wheat synthetic lines was screened for WSMV resistance. Four lines, 07-SYN-27, -106, -164, and -383 had significant levels of resistance. Resistance was effective at 18 °C and virus accumulation was similar to the resistant control, WGGRC50 containing Wsm1. At 25 °C, resistance was no longer effective and virus accumulation was similar to the susceptible control, Tomahawk

Planetary population synthesis

In stellar astrophysics, the technique of population synthesis has been successfully used for several decades. For planets, it is in contrast still a young method which only became important in recent years because of the rapid increase of the number of known extrasolar planets, and the associated growth of statistical observational constraints. With planetary population synthesis, the theory of planet formation and evolution can be put to the test against these constraints. In this review of planetary population synthesis, we first briefly list key observational constraints. Then, the work flow in the method and its two main components are presented, namely global end-to-end models that predict planetary system properties directly from protoplanetary disk properties and probability distributions for these initial conditions. An overview of various population synthesis models in the literature is given. The sub-models for the physical processes considered in global models are described: the evolution of the protoplanetary disk, the planets' accretion of solids and gas, orbital migration, and N-body interactions among concurrently growing protoplanets. Next, typical population synthesis results are illustrated in the form of new syntheses obtained with the latest generation of the Bern model. Planetary formation tracks, the distribution of planets in the mass-distance and radius-distance plane, the planetary mass function, and the distributions of planetary radii, semimajor axes, and luminosities are shown, linked to underlying physical processes, and compared with their observational counterparts. We finish by highlighting the most important predictions made by population synthesis models and discuss the lessons learned from these predictions - both those later observationally confirmed and those rejected.Comment: 47 pages, 12 figures. Invited review accepted for publication in the 'Handbook of Exoplanets', planet formation section, section editor: Ralph Pudritz, Springer reference works, Juan Antonio Belmonte and Hans Deeg, Ed

Modulation of endogenous antioxidant defense and the progression of kidney disease in multi-heritage groups of patients with type 2 diabetes: PRospective EValuation of Early Nephropathy and its Treatment (PREVENT).

BACKGROUND: Diabetes is the western world's leading cause of end-stage renal disease. Glucose-dependent, oxidative stress is linked to the development of renal inflammation and sclerosis, which, in animal models of diabetes, can be prevented by anti-oxidative treatment. Patients of non-Caucasian heritage have low activity of the selenoprotein, antioxidant enzyme, glutathione peroxidase (GPx) and its co-factor vitamin E, which may be linked to their increased propensity to developing end-stage renal disease. RESEARCH DESIGN AND METHODS: We have designed a double-blind, randomized, placebo controlled study with selenium and/or vitamin E versus placebo as the interventions for patients with type 2 diabetes and chronic kidney disease (CKD) stages 1-3. A 2 × 2 factorial design will allow a balanced representation of the heritage groups exposed to each intervention. The primary biochemical outcome is change in GPx activity, and clinical outcome measure is the actual, rate of-and/or percentage change in estimated glomerular filtration rate (eGFR) from baseline. Analysis will be with a marginal model for longitudinal data using Generalized Estimating Equations corrected for measures of baseline serum antioxidant enzyme activities (GPx, superoxide dismutase and catalase), micronutrient levels (vitamins E and C), measures of inflammation (interleukin 6, c-reactive protein and monocyte chemoattractant protein-1) and markers of oxidative damage (plasma 8-isoprostaglandin F2α and urinary 8-hydroxydeoxyguanosine). EXPECTED RESULTS: The study will assess the relationship between GPx activity, oxidative stress, inflammation and eGFR. It will test the null hypothesis that antioxidant therapy does not influence the activity of GPx or other antioxidant enzymes and/or alter the rate of change in eGFR in these patient groups. CONCLUSIONS: Outcome data on the effect of antioxidants in human diabetic renal disease is limited. Previous post hoc analyses have not shown a beneficial effect of vitamin E on renal function. A recent trial of a pharmaceutical antioxidant agent, improved eGFR, but in patients with advanced diabetes-related chronic kidney disease its use was associated with an increased incidence of cardiovascular events. We will explore whether the nutritional antioxidants, vitamin E and selenium alone, or in combination in patients at high risk of renal disease progression, forestalls a reduction in eGFR. The study will describe whether endogenous antioxidant enzyme defenses can be safely modified by this intervention and how this is associated with changes in markers of oxidative stress. Trial registration ISRCTN 97358113. Registered 21st September 2009

Prevalence of inappropriate medication using Beers criteria in Japanese long-term care facilities

BACKGROUND: The prevalence and risk factors of potentially inappropriate medication use among the elderly patients have been studied in various countries, but because of the difficulty of obtaining data on patient characteristics and medications they have not been studied in Japan. METHODS: We conducted a retrospective cross-sectional study in 17 Japanese long-term care (LTC) facilities by collecting data from the comprehensive MDS assessment forms for 1669 patients aged 65 years and over who were assessed between January and July of 2002. Potentially inappropriate medications were identified on the basis of the 2003 Beers criteria. RESULTS: The patients in the sample were similar in terms of demographic characteristics to those in the national survey. Our study revealed that 356 (21.1%) of the patients were treated with potentially inappropriate medication independent of disease or condition. The most commonly inappropriately prescribed medication was ticlopidine, which had been prescribed for 107 patients (6.3%). There were 300 (18.0%) patients treated with at least 1 inappropriate medication dependent on the disease or condition. The highest prevalence of inappropriate medication use dependent on the disease or condition was found in patients with chronic constipation. Multiple logistic regression analysis revealed psychotropic drug use (OR = 1.511), medication cost of per day (OR = 1.173), number of medications (OR = 1.140), and age (OR = 0.981) as factors related to inappropriate medication use independent of disease or condition. Neither patient characteristics nor facility characteristics emerged as predictors of inappropriate prescription. CONCLUSION: The prevalence and predictors of inappropriate medication use in Japanese LTC facilities were similar to those in other countries

Evolutionary potential and adaptation of Banksia attenuata (Proteaceae) to climate and fire regime in southwestern Australia, a global biodiversity hotspot

Substantial climate changes are evident across Australia, with declining rainfall and rising temperature in conjunction with frequent fires. Considerable species loss and range contractions have been predicted; however, our understanding of how genetic variation may promote adaptation in response to climate change remains uncertain. Here we characterized candidate genes associated with rainfall gradients, temperatures, and fire intervals through environmental association analysis. We found that overall population adaptive genetic variation was significantly affected by shortened fire intervals, whereas declining rainfall and rising temperature did not have a detectable influence. Candidate SNPs associated with rainfall and high temperature were diverse, whereas SNPs associated with specific fire intervals were mainly fixed in one allele. Gene annotation further revealed four genes with functions in stress tolerance, the regulation of stomatal opening and closure, energy use, and morphogenesis with adaptation to climate and fire intervals. B. attenuata may tolerate further changes in rainfall and temperature through evolutionary adaptations based on their adaptive genetic variation. However, the capacity to survive future climate change may be compromised by changes in the fire regime

The implementation of the serial trial intervention for pain and challenging behaviour in advanced dementia patients (STA OP!): a clustered randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Pain (physical discomfort) and challenging behaviour are highly prevalent in nursing home residents with dementia: at any given time 45-80% of nursing home residents are in pain and up to 80% have challenging behaviour. In the USA Christine Kovach developed the serial trial intervention (STI) and established that this protocol leads to less discomfort and fewer behavioural symptoms in moderate to severe dementia patients. The present study will provide insight into the effects of implementation of the Dutch version of the STI-protocol (STA OP!) in comparison with a control intervention, not only on behavioural symptoms, but also on pain, depression, and quality of life. This article outlines the study protocol.</p> <p>Methods/Design</p> <p>The study is a cluster randomized controlled trial in 168 older people (aged >65 years) with mild or moderate dementia living in nursing homes. The clusters, Dutch nursing homes, are randomly assigned to either the intervention condition (training and implementation of the STA OP!-protocol) or the control condition (general training focusing on challenging behaviour and pain, but without the step-wise approach). Measurements take place at baseline, after 3 months (end of the STA OP! training period) and after 6 months.</p> <p>Primary outcome measures are symptoms of challenging behaviour (measured with the Cohen-Mansfield Agitation Inventory (CMAI) and the Neuropsychiatric Inventory-Nursing Home version (NPI-NH)), and pain (measure with the Dutch version of the Pain Assessment Checklist for Seniors (PACSLAC-D) and the Minimum Data Set of the Resident Assessment Instrument (MDS-RAI) pain scale). Secondary outcome measures include symptoms of depression (Cornell and MDS-RAI depression scale), Quality of Live (Qualidem), changes in prescriptions of analgesics and psychotropic drugs, and the use of non-pharmacological comfort interventions (e.g. snoezelen, reminiscence therapy).</p> <p>Discussion</p> <p>The transfer from the American design to the Dutch design involved several changes due to the different organisation of healthcare systems. Specific strengths and limitations of the study are discussed.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1967">NTR1967</a></p