Behavioral profiling of SLC38A10 knockout mice using the multivariate concentric square field™ test

Introduction: SLC38A10 is a gene that encodes the SLC38A10 protein, also known as SNAT10. The SLC38 family is evolutionary old, and SLC38A10 is one of the oldest members of the family. It is ubiquitously expressed, and its substrates are glutamine, glutamate, alanine, aspartate, and serine. However, little is known about its biological importance.Methods: In the current study, an SLC38A10 knockout mouse was run in the multivariate concentric square fieldTM (MCSF) test. The MCSF test gives the mouse a choice of areas to explore; sheltered areas, elevated and illuminated areas, or open spaces, and a behavioral profile is obtained. The multivariate data obtained were analyzed (i) for each parameter, (ii) parameters grouped into functional categories, and (iii) with a principal component analysis.Results: In the trend analysis, knockout mice had a decreased exploratory behavior compared to controls but did not show a distinct grouping in the principal component analysis.Discussion: There was not a pronounced difference in the behavioral profile in SLC38A10 knockout mice compared to their wild-type controls, although subtle alterations in zones associated with exploratory behavior and risk assessment in female and male knockout mice, respectively, could be observed. These results imply that a loss of function of the SLC38A10 protein in mice does not drastically alter behavior in the MSCF test

Deflection Analysis of the Space Shuttle External Tank Door Drive Mechanism

Upon observing an abnormal closure of the Space Shuttle s External Tank Doors (ETD), a dynamic model was created in MSC/ADAMS to conduct deflection analyses for assessing whether the Door Drive Mechanism (DDM) was subjected to excessive additional stress, and more importantly, to evaluate the magnitude of the induced step or gap with respect to shuttle s body tiles. To model the flexibility of the DDM, a lumped parameter approximation was used to capture the compliance of individual parts within the drive linkage. These stiffness approximations were then validated using FEA and iteratively updated in the model to converge on the actual distributed parameter equivalent stiffnesses. The goal of the analyses is to determine the deflections in the mechanism and whether or not the deflections are in the region of elastic or plastic deformation. Plastic deformation may affect proper closure of the ETD and would impact aero-heating during re-entry

Endothelial cell-surface tissue transglutaminase inhibits neutrophil adhesion by binding and releasing nitric oxide

Nitric oxide (NO) produced by endothelial cells in response to cytokines displays anti-inflammatory activity by preventing the adherence, migration and activation of neutrophils. The molecular mechanism by which NO operates at the blood-endothelium interface to exert anti-inflammatory properties is largely unknown. Here we show that on endothelial surfaces, NO is associated with the sulfhydryl-rich protein tissue transglutaminase (TG2), thereby endowing the membrane surfaces with anti-inflammatory properties. We find that tumor necrosis factor-α-stimulated neutrophil adherence is opposed by TG2 molecules that are bound to the endothelial surface. Alkylation of cysteine residues in TG2 or inhibition of endothelial NO synthesis renders the surface-bound TG2 inactive, whereas specific, high affinity binding of S-nitrosylated TG2 (SNO-TG2) to endothelial surfaces restores the anti-inflammatory properties of the endothelium, and reconstitutes the activity of endothelial-derived NO. We also show that SNO-TG2 is present in healthy tissues and that it forms on the membranes of shear-activated endothelial cells. Thus, the anti-inflammatory mechanism that prevents neutrophils from adhering to endothelial cells is identified with TG2 S-nitrosylation at the endothelial cell-blood interface

The effect of Staphylococcus aureus carriage in late pregnancy on antibody levels to staphylococcal toxins in cord blood and breast milk.

We investigated the effect of carriage of Staphylococcus aureus in the later stages of pregnancy on levels of antibody specific to the S. aureus toxins, staphylococcal enterotoxin B (SEB), staphylococcal enterotoxin C (SEC) and toxic shock syndrome toxin-1 (TSST-1), in cord blood and breast milk and also explored the relationship between levels of antibody in antenatal serum and cord blood. Nasopharyngeal swabs and stool samples were collected on two occasions, from 96 women, during the last 6 weeks of pregnancy. Samples were cultured and S. aureus isolates were identified. Antenatal and cord blood samples from the same women and their infants were analysed for IgG antibody to SEB, SEC and TSST-1 by enzyme-linked immunosorbent assay. Breast milk samples were analysed for IgA antibody to the same toxins. We found that S. aureus carriage in pregnancy is common and exposure to a toxin-producing isolate boosts immunity. Over 89% of women and infants have some protective antibody to the toxins, and antitoxin IgG levels are higher in cord blood samples compared with antenatal samples. Levels of cord blood IgG and breast milk IgA specific for the staphylococcal toxins vary. Some infants lack protection and could be at risk of toxin-induced disease

Diffusing an Innovation: Clinician Perceptions of Continuous Predictive Analytics Monitoring in Intensive Care

Background The purpose of this article is to describe neonatal intensive care unit clinician perceptions of a continuous predictive analytics technology and how those perceptions influenced clinician adoption. Adopting and integrating new technology into care is notoriously slow and difficult; realizing expected gains remain a challenge. Methods Semistructured interviews from a cross-section of neonatal physicians (n ¼ 14) and nurses (n ¼ 8) from a single U.S. medical center were collected 18 months following the conclusion of the predictive monitoring technology randomized control trial. Following qualitative descriptive analysis, innovation attributes from Diffusion of Innovation Theory-guided thematic development. Results Results suggest that the combination of physical location as well as lack of integration into work flow or methods of using data in care decisionmaking may have delayed clinicians from routinely paying attention to the data. Once data were routinely collected, documented, and reported during patient rounds and patient handoffs, clinicians came to view data as another vital sign. Through clinicians’ observation of senior physicians and nurses, and ongoing dialogue about data trends and patient status, clinicians learned how to integrate these data in care decision making (e.g., differential diagnosis) and came to value the technology as beneficial to care delivery. Discussion The use of newly created predictive technologies that provide early warning of illness may require implementation strategies that acknowledge the risk–benefit of treatment cliniciansmust balance and take advantage of existing clinician trainingmethods

Elections and Ethnic Civil War

Existing research on how democratization may influence the risk of civil war tends to consider only changes in the overall level of democracy and rarely examines explicitly the postulated mechanisms relating democratization to incentives for violence. The authors argue that typically highlighted key mechanisms imply that elections should be especially likely to affect ethnic groups’ inclination to resort to violence. Distinguishing between types of conflict and the order of competitive elections, the authors find that ethnic civil wars are more likely to erupt after competitive elections, especially after first and second elections following periods of no polling. When disaggregating to the level of individual ethnic groups and conflicts over territory or government, the authors find some support for the notion that ethno-nationalist mobilization and sore-loser effects provoke postelectoral violence. More specifically, although large groups in general are more likely to engage in governmental conflicts, they are especially likely to do so after noncompetitive elections. Competitive elections, however, strongly reduce the risk of conflict. </jats:p

Glyconanoparticles for colorimetric bioassays

Carbohydrate molecules are involved in many of the cellular processes that are important for life. By combining the specific analyte targeting of carbohydrates with the multivalent structure and change of solution colour as a consequence of plasmonic interactions with the aggregation of metal nanoparticles, glyconanoparticles have been used extensively for the development of bioanalytical assays. The noble metals used to create the nanocore, the methodologies used to assemble the carbohydrates on the nanoparticle surface, the carbohydrate chosen for each specific target, the length of the tether that separates the carbohydrate from the nanocore and the density of carbohydrates on the surface all impact on the structural formation of metal based glyconanoparticles. This tutorial review highlights these key components, which directly impact on the selectivity and sensitivity of the developed bioassay, for the colorimetric detection of lectins, toxins and viruses

Scientific Opportunities with an X-ray Free-Electron Laser Oscillator

An X-ray free-electron laser oscillator (XFELO) is a new type of hard X-ray source that would produce fully coherent pulses with meV bandwidth and stable intensity. The XFELO complements existing sources based on self-amplified spontaneous emission (SASE) from high-gain X-ray free-electron lasers (XFEL) that produce ultra-short pulses with broad-band chaotic spectra. This report is based on discussions of scientific opportunities enabled by an XFELO during a workshop held at SLAC on June 29 - July 1, 2016Comment: 21 pages, 12 figure

Metal-Free ALS Variants of Dimeric Human Cu,Zn-Superoxide Dismutase Have Enhanced Populations of Monomeric Species

Amino acid replacements at dozens of positions in the dimeric protein human, Cu,Zn superoxide dismutase (SOD1) can cause amyotrophic lateral sclerosis (ALS). Although it has long been hypothesized that these mutations might enhance the populations of marginally-stable aggregation-prone species responsible for cellular toxicity, there has been little quantitative evidence to support this notion. Perturbations of the folding free energy landscapes of metal-free versions of five ALS-inducing variants, A4V, L38V, G93A, L106V and S134N SOD1, were determined with a global analysis of kinetic and thermodynamic folding data for dimeric and stable monomeric versions of these variants. Utilizing this global analysis approach, the perturbations on the global stability in response to mutation can be partitioned between the monomer folding and association steps, and the effects of mutation on the populations of the folded and unfolded monomeric states can be determined. The 2- to 10-fold increase in the population of the folded monomeric state for A4V, L38V and L106V and the 80- to 480-fold increase in the population of the unfolded monomeric states for all but S134N would dramatically increase their propensity for aggregation through high-order nucleation reactions. The wild-type-like populations of these states for the metal-binding region S134N variant suggest that even wild-type SOD1 may also be prone to aggregation in the absence of metals