Spleen Tyrosine Kinase (Syk) Regulates Systemic Lupus Erythematosus (SLE) T Cell Signaling

Engagement of the CD3/T cell receptor complex in systemic lupus erythematosus (SLE) T cells involves Syk rather than the zeta-associated protein. Because Syk is being considered as a therapeutic target we asked whether Syk is central to the multiple aberrantly modulated molecules in SLE T cells. Using a gene expression array, we demonstrate that forced expression of Syk in normal T cells reproduces most of the aberrantly expressed molecules whereas silencing of Syk in SLE T cells normalizes the expression of most abnormally expressed molecules. Protein along with gene expression modulation for select molecules was confirmed. Specifically, levels of cytokine IL-21, cell surface receptor CD44, and intracellular molecules PP2A and OAS2 increased following Syk overexpression in normal T cells and decreased after Syk silencing in SLE T cells. Our results demonstrate that levels of Syk affect the expression of a number of enzymes, cytokines and receptors that play a key role in the development of disease pathogenesis in SLE and provide support for therapeutic targeting in SLE patients

A game prototype for understanding the safety issues of a lifeboat launch

© 2018 The Author(s) Novel, advanced game techniques provide us with new possibilities to mimic a complicated training process, with the added benefit of enhanced safety. In this paper, we design and implement a 3D game with the support of virtual reality equipment which imitates the process of a lifeboat launch, involving both tractor manoeuvres and boat operations. It is a complex but vital process which can save lives at sea but also has many potential hazards. The primary objective of the game is to allow novices to better understand the sequence of the operations and manage the potential risks which may occur during the launch process. Additionally, the game has been promoted to the general public for educational purposes and to raise awareness of the safety issues involved. The key modules of the game are designed based on physical simulations to give the players enhanced plausible cognition and enjoyable interaction. We conducted two case studies for the two purposes of the games: one for training with volunteers without launching experience and the other for public awareness of the potential hazards with young children. The game is proven to be very promising for future professional training, and it serves the educational purpose of awareness of the safety issues for general public while being entertaining

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Photoactivatable drugs for nicotinic optopharmacology

Photoactivatable pharmacological agents have revolutionized neuroscience, but the palette of available compounds is limited. We describe a general method for caging tertiary amines by using a stable quaternary ammonium linkage that elicits a red shift in the activation wavelength. We prepared a photoactivatable nicotine (PA-Nic), uncageable via one- or two-photon excitation, that is useful to study nicotinic acetylcholine receptors (nAChRs) in different experimental preparations and spatiotemporal scales

Dystroglycan versatility in cell adhesion: a tale of multiple motifs

Dystroglycan is a ubiquitously expressed heterodimeric adhesion receptor. The extracellular a-subunit makes connections with a number of laminin G domain ligands including laminins, agrin and perlecan in the extracellular matrix and the transmembrane b-subunit makes connections to the actin filament network via cytoskeletal linkers including dystrophin, utrophin, ezrin and plectin, depending on context. Originally discovered as part of the dystrophin glycoprotein complex of skeletal muscle, dystroglycan is an important adhesion molecule and signalling scaffold in a multitude of cell types and tissues and is involved in several diseases. Dystroglycan has emerged as a multifunctional adhesion platform with many interacting partners associating with its short unstructured cytoplasmic domain. Two particular hotspots are the cytoplasmic juxtamembrane region and at the very carboxy terminus of dystroglycan. Regions which between them have several overlapping functions: in the juxtamembrane region; a nuclear localisation signal, ezrin/radixin/moesin protein, rapsyn and ERK MAP Kinase binding function, and at the C terminus a regulatory tyrosine governing WW, SH2 and SH3 domain interactions. We will discuss the binding partners for these motifs and how their interactions and regulation can modulate the involvement of dystroglycan in a range of different adhesion structures and functions depending on context. Thus dystroglycan presents as a multifunctional scaffold involved in adhesion and adhesion-mediated signalling with its functions under exquisite spatiotemporal regulation

The role of protected areas in the avoidance of anthropogenic conversion in a high pressure region : a matching method analysis in the core region of the brazilian cerrado

Global efforts to avoid anthropogenic conversion of natural habitat rely heavily on the establishment of protected areas. Studies that evaluate the effectiveness of these areas with a focus on preserving the natural habitat define effectiveness as a measure of the influence of protected areas on total avoided conversion. Changes in the estimated effectiveness are related to local and regional differences, evaluation methods, restriction categories that include the protected areas, and other characteristics. The overall objective of this study was to evaluate the effectiveness of protected areas to prevent the advance of the conversion of natural areas in the core region of the Brazil’s Cerrado Biome, taking into account the influence of the restriction degree, governmental sphere, time since the establishment of the protected area units, and the size of the area on the performance of protected areas. The evaluation was conducted using matching methods and took into account the following two fundamental issues: control of statistical biases caused by the influence of covariates on the likelihood of anthropogenic conversion and the non-randomness of the allocation of protected areas throughout the territory (spatial correlation effect) and the control of statistical bias caused by the influence of auto-correlation and leakage effect. Using a sample design that is not based on ways to control these biases may result in outcomes that underestimate or overestimate the effectiveness of those units. The matching method accounted for a bias reduction in 94–99% of the estimation of the average effect of protected areas on anthropogenic conversion and allowed us to obtain results with a reduced influence of the auto-correlation and leakage effects. Most protected areas had a positive influence on the maintenance of natural habitats, although wide variation in this effectiveness was dependent on the type, restriction, governmental sphere, size and age group of the unit

The association between maternal and partner experienced racial discrimination and prenatal perceived stress, prenatal and postnatal depression: findings from the growing up in New Zealand cohort study

Background A growing number of studies document the association between maternal experiences of racial discrimination and adverse children’s outcomes, but our understanding of how experiences of racial discrimination are associated with pre- and post-natal maternal mental health, is limited. In addition, existent literature rarely takes into consideration racial discrimination experienced by the partner. Methods We analysed data from the Growing Up in New Zealand study to examine the burden of lifetime and past year experiences of racial discrimination on prenatal and postnatal mental health among Māori, Pacific, and Asian women in New Zealand (NZ), and to study the individual and joint contribution of mother’s and partner’s experiences of lifetime and past year racial discrimination to women’s prenatal and postnatal mental health. Results Our findings show strong associations between lifetime and past year experiences of ethnically-motivated interpersonal attacks and unfair treatment on mother’s mental health. Māori, Pacific, and Asian women who had experienced unfair treatment by a health professional in their lifetime were 66 % more likely to suffer from postnatal depression, compared to women who did not report these experiences. We found a cumulative effect of lifetime experiences of ethnically-motivated personal attacks on poor maternal mental health if both the mother and the partner had experienced a racist attack. Conclusions Experiences of racial discrimination have severe direct consequences for the mother’s mental health. Given the importance of mother’s mental health for the basic human needs of a healthy child, racism and racial discrimination should be addressed

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

Identification of genes required for soil survival in Burkholderia thailandensis by transposon-directed insertion site sequencing.

Transposon-directed insertion site sequencing was used to identify genes required by Burkholderia thailandensis to survive in plant/soil microcosms. A total of 1,153 genetic loci fulfilled the criteria as being likely to encode survival characteristics. Of these, 203 (17.6 %) were associated with uptake and transport systems; 463 loci (40.1 %) coded for enzymatic properties, 99 of these (21.4 %) had reduction/oxidation functions; 117 (10.1 %) were gene regulation or sensory loci; 61 (5.3 %) encoded structural proteins found in the cell envelope or with enzymatic activities related to it, distinct from these, 46 (4.0 %) were involved in chemotaxis and flagellum, or pilus synthesis; 39 (3.4 %) were transposase enzymes or were bacteriophage-derived; and 30 (2.6 %) were involved in the production of antibiotics or siderophores. Two hundred and twenty genes (19.1 %) encoded hypothetical proteins or those of unknown function. Given the importance of motility and pilus formation in microcosm persistence the nature of the colonization of the rhizosphere was examined by confocal microscopy. Wild type B. thailandensis expressing red fluorescent protein was inoculated into microcosms. Even though the roots had been washed, the bacteria were still present but they were motile with no attachment having taken place, perhaps being retained in a biofilm

Contextual and individual factors associated with dental services utilisation by Brazilian adults: A multilevel analysis

BACKGROUND: Inequalities in the utilisation of dental services in Brazil are remarkable. The aim of this study was to evaluate the association of contextual and individual factors with the utilisation of dental services by Brazilian adults using the Andersen's behavioural model. METHODS: Individual-level data from 27,017 adults residents in the State capitals who were interviewed in the 2013 Brazilian National Health Survey were pooled with contextual city-level data. The outcomes were non-utilisation of dental services and last dental visit over 12 months ago. Individual predisposing variables were age, sex, race/skin colour, schooling and social network. Individual enabling variables included income, health insurance and registration in primary health care. Individual need variables were self-perceived dental health and self-reported missing teeth. Multilevel logistic regression models were performed to estimate odds ratio (OR) and 95% confidence intervals (95% CIs) of the association of contextual and individual predisposing, enabling and need-related variables with dental services outcomes. RESULTS: Predisposing (OR = 0.89; 95% CI 0.81-0.97) and enabling (OR = 0.90; 95% CI 0.85-0.96) contextual factors were associated with non-utilisation of dental services. Individual predisposing (sex, race/skin colour, schooling), enabling (income, health insurance) and need (self-perceived oral health, missing teeth) were associated with non-utilisation of dental services and last dental visit over 12 months ago. The latter was also associated with other individual predisposing (age, social network) and need (eating difficulties due to oral problems) characteristics. CONCLUSIONS: Individual and contextual determinants influenced dental services utilisation in Brazilian adults. These factors should be on the policy agenda and considered in the organisation of health services aiming to reduce oral health inequalities related to access and utilisation of dental services