BAFF and MyD88 signals promote a lupuslike disease independent of T cells

Systemic lupus erythernatosus (SLE) is a systemic autoimmune disease characterized by the production of autoantibodies. However, the underlying cause of disease appears to relate to defects in T cell tolerance or T cell help to 13 cells. Transgenic (Tg) mice over-expressing the cytokine 13 cell-activating factor of the tumor necrosis factor family (BAFF) develop an autoimmune disorder similar to SLE and show impaired B cell tolerance and altered T cell differentiation. We generated BAFF Tg mice that were completely deficient in T cells, and, surprisingly, these mice developed an SLE-like disease indistinguishable from that of BAFF Tg mice. Autoimmunity in BAFF Tg mice did, however, require 13 cell-intrinsic signals through the Toll-like receptor (TLR)-associated signaling adaptor MyD88, which controlled the production of proinflammatory autoantibody isotypes. TLR7/9 activation strongly up-regulated expression of transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), which is a receptor for BAFF involved in 13 cell responses to T cell-independent antigens. Moreover, BAFF enhanced TLR7/9 expression on 13 cells and TLR-mediated production of autoantibodies. Therefore, autoirnmunity in BAFF Tg mice results from altered 13 cell tolerance, but requires TLR signaling and is independent of T cell help. It is possible that SLE patients with elevated levels of BAFF show a similar basis for disease

Equal versus equivalent access to the scientific literature

<p>Abstract</p

Diode area melting single-layer parametric analysis of 316L stainless steel powder

Diode area melting (DAM) is a novel additive manufacturing process that utilises customised architectural arrays of low power laser diode emitters for high speed parallel processing of metallic powdered feedstock. The laser diodes operate at shorter laser wavelengths (808 nm) than conventional SLM fibre lasers (1064 nm) theoretically enabling more efficient energy absorption for specific materials. This investigation presents a parametric analysis of the DAM process, identifying the effect of powder characteristics, laser beam profile, laser power and scan speed on the porosity of a single-layer sample. Also presented is the effect of process energy density on melt pool depth (irradiated thermal energy penetration capable of achieving melting) on 316L stainless steel powder. An analysis of the density and the melt depth fraction of single layers is presented in order to identify the conditions that lead to the fabrication of fully dense DAM parts. Energy densities in excess of 86 J/mm3 were theorised as sufficient to enable processing of fully dense layers

Study of user-experience of an objective test (QbTest) to aid ADHD assessment and medication management: a multi-methods approach

Background The diagnosis and monitoring of Attention deficit hyperactivity disorder (ADHD) typically relies on subjective reports and observations. Objective continuous performance tests (CPTs) have been incorporated into some services to support clinical decision making. However, the feasibility and acceptability of adding such a test into routine practice is unknown. The study aimed to investigate the feasibility and acceptability of adding an objective computerised test to the routine assessment and monitoring of attention deficit hyperactivity disorder (ADHD). Methods Semi-structured interviews were conducted with clinicians (n = 10) and families (parents/young people, n = 20) who participated in a randomised controlled trial. Additionally, the same clinicians (n = 10) and families (n = 76) completed a survey assessing their experience of the QbTest. The study took place in child and adolescent mental health and community paediatric clinics across the UK. Interview transcripts were thematically analysed. Results Interviewed clinicians and families valued the QbTest for providing an objective, valid assessment of symptoms. The QbTest was noted to facilitate communication between clinicians, families and schools. However, whereas clinicians were more unanimous on the usefulness of the QbTest, survey findings showed that, although the majority of families found the test useful, less than half felt the QbTest helped them understand the clinician’s decision making around diagnosis and medication. The QbTest was seen as a potentially valuable tool to use early in the assessment process to streamline the care pathway. Although clinicians were conscious of the additional costs, these could be offset by reductions in time to diagnosis and the delivery of the test by a Healthcare Assistant. Conclusions The findings indicate the QbTest is an acceptable and feasible tool to implement in routine clinical settings. Clinicians should be mindful to discuss the QbTest results with families to enable their understanding and engagement with the process. Further findings from definitive trials are required to understand the cost/benefit; however, the findings from this study support the feasibility and acceptability of integrating QbTest in the ADHD care pathway

Matrin 3 and HIV Rev Regulation of mRNA

The nuclear matrix protein, MATR3, is a newly-described Rev cofactor whose mechanism of action is only starting to be revealed

A comparison of populations vaccinated in a public service and in a private hospital setting in the same area

<p>Abstract</p> <p>Background</p> <p>Improving immunisation rates in risk groups is one of the main objectives in vaccination strategies. However, achieving high vaccination rates in children with chronic conditions is difficult. Different types of vaccine providers may differently attract high risk children.</p> <p>Aim</p> <p>To describe the characteristics of two populations of children who attended a private and a public immunisation provider in the same area. Secondarily, to determine if prevalence of patients with underlying diseases by type of provider differs and to study if the choice of different providers influences timeliness in immunisation.</p> <p>Methods</p> <p>We performed a cross-sectional study on parents of children 2 – 36 months of age who attended a private hospital immunisation service or a public immunisation office serving the same metropolitan area of Rome, Italy. Data on personal characteristics and immunisation history were collected through a face to face interview with parents of vaccinees, and compared by type of provider. Prevalence of underlying conditions was compared in the two populations. Timeliness in immunisation and its determinants were analysed through a logistic regression model.</p> <p>Results</p> <p>A total of 202 parents of children 2–36 months of age were interviewed; 104 were in the public office, and 98 in the hospital practice. Children immunised in the hospital were more frequently firstborn female children, breast fed for a longer period, with a lower birthweight, and more frequently with a previous hospitalisation. The prevalence of high risk children immunised in the hospital was 9.2 vs 0% in the public service (P = 0.001). Immunisation delay for due vaccines was higher in the hospital practice than in the public service (DTP, polio, HBV, and Hib: 39.8% vs 22.1%; P = 0.005). Anyway multivariate analyses did not reveal differences in timeliness between the public and private hospital settings.</p> <p>Conclusion</p> <p>Children with underlying diseases or a low birthweight were more frequently immunised in the hospital. This finding suggests that offering immunisations in a hospital setting may facilitate vaccination uptake in high risk groups. An integration between public and hospital practices and an effort to improve communication on vaccines to parents, may significantly increase immunisation rates in high risk groups and in the general population, and prevent immunisation delays.</p

Neurological and psychiatric adverse effects of long-term methylphenidate treatment in ADHD: A map of the current evidence

Methylphenidate (MPH), the most common medication for children with Attention Deficit/Hyperactivity Disorder (ADHD) in many countries, is often prescribed for long periods of time. Any long-term psychotropic treatment in childhood raises concerns about possible adverse neurological and psychiatric outcomes. // We aimed to map current evidence regarding neurological and psychiatric outcomes, adverse or beneficial, of long-term MPH (> 1 year) treatment in ADHD. We coded studies using a “traffic light” system: Green: safe/favours MPH; Amber: warrants caution; Red: not safe/not well-tolerated. Un-categorisable study findings were coded as “Unclear”. // Although some evidence suggests an elevated risk of psychosis and tics, case reports describe remission on discontinuation. Several studies suggest that long-term MPH may reduce depression and suicide in ADHD. Evidence suggests caution in specific groups including pre-school children, those with tics, and adolescents at risk for substance misuse. // We identified a need for more studies that make use of large longitudinal databases, focus on specific neuropsychiatric outcomes, and compare outcomes from long-term MPH treatment with outcomes following shorter or no pharmacological intervention

Advancing integrated research on European river–sea systems: the DANUBIUS-RI project

Research at the interface between terrestrial, riverine, estuarine and marine environments is frequently constrained by significant disciplinary and geographical boundaries. This article outlines an international initiative, DANUBIUS-RI, which aims to address these problems by facilitating biogeochemical monitoring and interdisciplinary research on river–sea systems. The scope of the project spans the environmental, social and economic sciences and was accepted into the European Strategy Forum on Research Infrastructures roadmap in 2016. When operational, DANUBIUS-RI will offer researchers access to interdisciplinary expertise, facilities and European river–sea systems, providing a comprehensive platform for multidisciplinary research and training

Serologic and PCR testing of persons with chronic fatigue syndrome in the United States shows no association with xenotropic or polytropic murine leukemia virus-related viruses

In 2009, a newly discovered human retrovirus, xenotropic murine leukemia virus (MuLV)-related virus (XMRV), was reported by Lombardi et al. in 67% of persons from the US with chronic fatigue syndrome (CFS) by PCR detection of gag sequences. Although six subsequent studies have been negative for XMRV, CFS was defined more broadly using only the CDC or Oxford criteria and samples from the US were limited in geographic diversity, both potentially reducing the chances of identifying XMRV positive CFS cases. A seventh study recently found polytropic MuLV sequences, but not XMRV, in a high proportion of persons with CFS. Here we tested blood specimens from 45 CFS cases and 42 persons without CFS from over 20 states in the United States for both XMRV and MuLV. The CFS patients all had a minimum of 6 months of post-exertional malaise and a high degree of disability, the same key symptoms described in the Lombardi et al. study. Using highly sensitive and generic DNA and RNA PCR tests, and a new Western blot assay employing purified whole XMRV as antigen, we found no evidence of XMRV or MuLV in all 45 CFS cases and in the 42 persons without CFS. Our findings, together with previous negative reports, do not suggest an association of XMRV or MuLV in the majority of CFS cases

Strong interface-induced spin-orbit coupling in graphene on WS2

Interfacial interactions allow the electronic properties of graphene to be modified, as recently demonstrated by the appearance of satellite Dirac cones in the band structure of graphene on hexagonal boron nitride (hBN) substrates. Ongoing research strives to explore interfacial interactions in a broader class of materials in order to engineer targeted electronic properties. Here we show that at an interface with a tungsten disulfide (WS2) substrate, the strength of the spin-orbit interaction (SOI) in graphene is very strongly enhanced. The induced SOI leads to a pronounced low-temperature weak anti-localization (WAL) effect, from which we determine the spin-relaxation time. We find that spin-relaxation time in graphene is two-to-three orders of magnitude smaller on WS2 than on SiO2 or hBN, and that it is comparable to the intervalley scattering time. To interpret our findings we have performed first-principle electronic structure calculations, which both confirm that carriers in graphene-on-WS2 experience a strong SOI and allow us to extract a spin-dependent low-energy effective Hamiltonian. Our analysis further shows that the use of WS2 substrates opens a possible new route to access topological states of matter in graphene-based systems.Comment: Originally submitted version in compliance with editorial guidelines. Final version with expanded discussion of the relation between theory and experiments to be published in Nature Communication