A neuraminidase from Trypanosoma cruzi removes sialic acid from the surface of mammalian myocardial and endothelial cells

Trypanosoma cruzi causes Chagasic heart disease, a major public health problem in Latin America. The mechanism of interaction of this protozooan parasite with host cells is poorly understood. We recently found that the infective trypomastigote form a T. cruzi exhibits neuraminidase activity and can desialylate mammalian erythrocytes. However, it is not known if T. cruzi can also modify the surfaces of cardiovascular cells that are directly involved in the most important clinical manifestations of this disease. Accordingly, this study determined whether T. cruzi can remove sialic acid from cultured rat myocardial or human vascular endothelial cells. Sialic acid was labeled metabolically with the precursor 3H-N-acetyl-D-mannosamine. Soluble neuraminidase, isolated from intact T. cruzi trypomastigotes, caused significant release of labeled material from myocardial cells (e.g., 2,174 +/- 27 dpm/h vs. spontaneous release of 306 +/- 30 dpm/h, n = 4, P less than 0.001). Chromatographic analysis showed that the bulk of the radioactivity released by T. cruzi neuraminidase was sialic acid. Intact T. cruzi trypomastigotes also released sialic acid from metabolically labeled myocardial cells in a concentration-dependent manner. In contrast, a noninfective form of T. cruzi, the amastigote, did not desialylate these cells. Galactose oxidase labeling demonstrated newly desialylated glycoproteins on the surface of myocardial cells treated with T. cruzi neuraminidase. Desialylation of myocardial cells was confirmed histochemically by the appearance of binding sites for peanut agglutinin, a lectin that binds to complex oligosaccharide moieties after removal of the terminal sialyl residue. T. cruzi neuraminidase also removed sialic acid from adult human saphenous vein endothelial cells, as determined by both histochemical and metabolic labeling studies. Thus, infective forms of T. cruzi can chemically modify the surfaces of myocardial and vascular endothelial cells by desialylation. This alteration may play a role in the initial interaction of this parasite with these important target cells of the host cardiovascular system

Routine Outcome Monitoring in CAMHS: How Can We Enable Implementation in Practice?

Background: Many CAMHS teams across the United Kingdom are now required to use Routine Outcome Monitoring (ROM). However, some clinicians hold negative attitudes towards ROM and various practical implementation issues have been identified. Method: The aim of this study was to explore clinician experiences of using ROM in the context of an ‘enforced’ initial implementation initiative. Twenty clinicians were surveyed at the beginning (T1) and end (T2) of the six-month period in a large UK CAMHS network adopting CYP-IAPT practice. Changes in the use of and attitudes towards ROM were investigated, as well as barriers to implementation. Results: Overall, a small but significant increase in clinician use of ROM was observed from T1 to T2, but attitudes towards ROM did not change significantly. On the whole, clinicians were more positive than negative about ROM during the implementation period, but key implementation challenges included clinician concerns about the value and (mis)use of ROM data, poor technological support and additional workload demands. Conclusions: CAMHS clinicians will not necessarily become more receptive to ROM simply as a by-product of being asked to use it more. Seeking clinician feedback at the early stages of implementation can help provide a focus for improvement efforts. Ideas for future research and important limitations of the study are discussed.</p

Rights or containment? The politics of Aboriginal cultural heritage in Victoria

Aboriginal cultural heritage protection, and the legislative regimes that underpin it, constitute important mechanisms for Aboriginal people to assert their rights and responsibilities. This is especially so in Victoria, where legislation vests wide-ranging powers and control of cultural heritage with Aboriginal communities. However, the politics of cultural heritage, including its institutionalisation as a scientific body of knowledge within the state, can also result in a powerful limiting of Aboriginal rights and responsibilities. This paper examines the politics of cultural heritage through a case study of a small forest in north-west Victoria. Here, a dispute about logging has pivoted around differing conceptualisations of Aboriginal cultural heritage values and their management. Cultural heritage, in this case, is both a powerful tool for the assertion of Aboriginal rights and interests, but simultaneously a set of boundaries within which the state operates to limit and manage the challenge those assertions pose. The paper will argue that Aboriginal cultural heritage is a politically contested and shifting domain structured around Aboriginal law and politics, Australian statute and the legacy of colonial history

Reduction of Experimental Myocardial Infarct Size by Corticosteroid Administration

The influence of the administration of pharmacologic doses of hydrocortisone on the extent and severity of acute myocardial ischemic injury and on subsequent necrosis after acute coronary occlusion was investigated in 28 dogs. In order to study acute myocardial injury, repeated epicardial electrocardiograms were recorded from 10 to 15 sites on the anterior surface of the left ventricle. Average ST segment elevation (ST) and the number of sites in which ST segment elevation exceeded 2 mV (NST), indices of the magnitude and extent of myocardial injury, respectively, were analyzed at 30 and 60 min after coronary occlusion. In the control group ST and NST did not change significantly in this time interval while in the treated group, which received 50 mg/kg hydrocortisone just after the 30 min recording, ST fell from 3.5+/-0.8 to 1.1+/-0.4 mV (P 2 mV) in the control group showed histologic changes compatible with early myocardial infarction in 96% of specimens, while this occurred only in 61% and 63% of specimens, respectively, in the treated groups, showing that over one third of the sites were protected from undergoing necrosis due to the intervening hydrocortisone treatment. Thus pharmacological doses of hydrocortisone prevent myocardial cells from progressing to ischemic necrosis even when administration is initiated 6 h after coronary occlusion

skelesim : an extensible, general framework for population genetic simulation in R

Simulations are a key tool in molecular ecology for inference and forecasting, as well as for evaluating new methods. Due to growing computational power and a diversity of software with different capabilities, simulations are becoming increasingly powerful and useful. However, the widespread use of simulations by geneticists and ecologists is hindered by difficulties in understanding these softwares’ complex capabilities, composing code and input files, a daunting bioinformatics barrier, and a steep conceptual learning curve. skeleSim (an R package) guides users in choosing appropriate simulations, setting parameters, calculating genetic summary statistics, and organizing data output, in a reproducible pipeline within the R environment. skeleSim is designed to be an extensible framework that can ‘wrap’ around any simulation software (inside or outside the R environment) and be extended to calculate and graph any genetic summary statistics. Currently, skeleSim implements coalescent and forward-time models available in the fastsimcoal2 and rmetasim simulation engines to produce null distributions for multiple population genetic statistics and marker types, under a variety of demographic conditions. skeleSim is intended to make simulations easier while still allowing full model complexity to ensure that simulations play a fundamental role in molecular ecology investigations. skeleSim can also serve as a teaching tool: demonstrating the outcomes of stochastic population genetic processes; teaching general concepts of simulations; and providing an introduction to the R environment with a user-friendly graphical user interface (using shiny)

Comparative Design, Scaling, and Control of Appendages for Inertial Reorientation

This paper develops a comparative framework for the design of an actuated inertial appendage for planar reorientation. We define the Inertial Reorientation template, the simplest model of this behavior, and leverage its linear dynamics to reveal the design constraints linking a task with the body designs capable of completing it. As practicable inertial appendage designs lead to physical bodies that are generally more complex, we advance a notion of “anchoring” whereby a judicious choice of physical design in concert with an appropriate control policy yields a system whose closed loop dynamics are sufficiently captured by the template as to permit all further design to take place in its far simpler parameter space. This approach is effective and accurate over the diverse design spaces afforded by existing platforms, enabling performance comparison through the shared task space. We analyze examples from the literature and find advantages to each body type, but conclude that tails provide the highest potential performance for reasonable designs. Thus motivated, we build a physical example by retrofitting a tail to a RHex robot and present empirical evidence of its efficacy. For more information: Kod*la

Pre- and Postnatal Exposures to Tobacco Smoking and Survival of Childhood Acute Lymphoblastic and Myeloid Leukemias in California, United States.

BackgroundTobacco smoke adversely affects the prognosis of adult cancers including myeloid leukemia, but less is known in children.MethodsWe evaluated whether pre- and postnatal exposures to tobacco smoke decrease 5-year survival of 1,235 childhood acute lymphoblastic leukemia (ALL) and 188 childhood acute myeloid leukemia (AML) cases derived from a population-based case-control study in California. Cases were diagnosed between 1995 and 2015 (median follow-up time of 13.2 years overall). We obtained data on tobacco smoking (before conception, during pregnancy, after birth), parental education and income, clinical features, and vital status through 2020. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for mortality associated with smoking, adjusting for sociodemographic characteristics and risk group (ALL only).ResultsAbout 23% of mothers and 39% of fathers reported smoking and 130 children with ALL and 52 with AML died within 5 years. For AML, increased risks of death were observed among children whose fathers smoked before conception compared with nonsmoking fathers [HR = 1.41; 95% confidence interval (CI), 0.95-3.44 and 3.47; 95% CI, 1.37-8.81, respectively for &lt;20 vs. ≥20 cigarettes per day; Ptrend = 0.01]. HR for child's passive smoking was 1.74, 95% CI, 0.81-3.73. Paternal preconception smoking may also reduce 5-year survival among ALL with favorable prognostic molecular subtypes (high hyperdiploidy and absence of IKZF1 gene deletion), although the associations did not reach statistical significance (Pheterogeneity = 0.07).ConclusionsPaternal preconception smoking decreased 5-year survival of childhood AML.ImpactKnowledge of exposure to tobacco smoking should be integrated in the treatment plan of childhood leukemias

Egg Cannibalism in a Gull Colony Increases with Sea Surface Temperature

Cannibalism occurs regularly across a broad range of taxa with a variety of ecological and evolutionary consequences. Rises in sea surface temperature (SST) have been linked to increased cannibalism in some species, including polar bears (Ursus maritimus), Peruvian anchovy (Engraulis ringens), and Peruvian hake (Merluccius gayi peruanus), and might be expected in birds that depend on marine food webs for sustenance. Increased SSTs are associated with lowered ocean thermoclines and weakened upwellings. These changes, in turn, lead to decreased productivity in surface water and movement of surviving forage fish to deeper water, thereby food-stressing surface feeders such as gulls, diminishing energy intake and lengthening foraging bouts. While controlling for a suite of other environmental factors, we tested whether egg cannibalism and hatching success were independent of rises in local SST at a colony of Glaucous-winged Gulls (Larus glaucescens) and Glaucous-winged3Western Gull (L. glaucescens3occidentalis) hybrids during 2006–2011 on Protection Island, Washington, USA. Cannibalism increased and hatching success decreased with rises in SST. It is unclear if rises in SST impact overall population trends. Gulls are multiyear breeders; if they experience reproductive failure during one or several El Ni ˜ no-Southern Oscillation–related events, they typically have other opportunities to breed. With rising SSTs associated with climate change, however, increasing levels of cannibalism could lead to declining populations in the absence of compensatory adaptive modifications or range shifts

Coronary Artery Reperfusion

The effects of coronary artery reperfusion 3 hr after coronary occlusion on contractile function and the development of myocardial damage at 24 hr was studied experimentally. In 14 control and 6 reperfused dogs, relationships between epicardial ST segment elevation 15 min after coronary occlusion and myocardial creatine phosphokinase activity (CPK) and histologic appearance 24 hr later were examined. The electrocardiograms were recorded from 10 to 15 sites on the left ventricular epicardium and transmural samples for CPK and histology were obtained from the same sites where epicardial electrocardiograms had been recorded. An inverse relation existed between ST segment elevation (mv) 15 min after occlusion and log CPK activity (IU/ mg of protein) 24 hr later, log CPK = - 0.06ST + 1.26. In dogs subjected to coronary artery reperfusion, there was significantly less CPK depression (log CPK = - 0.01ST + 1.31, [P < 0.01]) than that expected from the control group. In the control group 97% of specimens showing ST segment elevations over 2 mv at 15 min showed abnormal histology 24 hr later. In contrast, in the reperfused group 43% of sites exhibiting elevated ST segment at 15 min showed abnormal histology 24 hr later. In six additional dogs it was shown that the paradoxical movement of the left ventricular wall could be reversed within 1 hr of perfusion. Therefore, by enzymatic and histologic criteria, as well as by functional assessment, coronary artery reperfusion 3 hr after occlusion resulted in salvage of myocardial tissue

Coefficient Functions and Open Charm Production in Deep Inelastic Scattering

It is shown that the problem of double counting in open charm production in DIS can be solved by using the expression for DIS coefficient functions in terms of 2PI diagramsComment: 11 pages, REVTeX, no figure