Are there right hemisphere contributions to visually-guided movement? Manipulating left hand reaction time advantages in dextrals

This is the final version of the article. It first appeared from Frontiers Media via http://dx.doi.org/10.3389/fpsyg.2015.01203Many studies have argued for distinct but complementary contributions from each hemisphere in the control of movements to visual targets. Investigators have attempted to extend observations from patients with unilateral left- and right-hemisphere damage, to those using neurologically-intact participants, by assuming that each hand has privileged access to the contralateral hemisphere. Previous attempts to illustrate right hemispheric contributions to the control of aiming have focussed on increasing the spatial demands of an aiming task, to attenuate the typical right hand advantages, to try to enhance a left hand reaction time advantage in right-handed participants. These early attempts have not been successful. The present study circumnavigates some of the theoretical and methodological difficulties of some of the earlier experiments, by using three different tasks linked directly to specialized functions of the right hemisphere: bisecting, the gap effect, and visuospatial localization. None of these tasks were effective in reducing the magnitude of left hand reaction time advantages in right handers. Results are discussed in terms of alternatives to right hemispheric functional explanations of the effect, the one-dimensional nature of our target arrays, power and precision given the size of the left hand RT effect, and the utility of examining the proportions of participants who show these effects, rather than exclusive reliance on measures of central tendency and their associated null hypothesis significance tests.We are grateful to Lorna Jakobson, A. David Milner, Irene Logan, John Orphan, Phil Surette, and Jim Urqhuart for expert technical assistance. Leah T. Johnstone and two anonymous referees provided detailed comments on this manuscript. This research was supported by Medical Research Council of Canada Grant MA-7269 to MG and a Wellcome Trust Travel Grant to DC

Are there right hemisphere contributions to visually-guided movement? Manipulating left hand reaction time advantages in dextrals.

Many studies have argued for distinct but complementary contributions from each hemisphere in the control of movements to visual targets. Investigators have attempted to extend observations from patients with unilateral left- and right-hemisphere damage, to those using neurologically-intact participants, by assuming that each hand has privileged access to the contralateral hemisphere. Previous attempts to illustrate right hemispheric contributions to the control of aiming have focussed on increasing the spatial demands of an aiming task, to attenuate the typical right hand advantages, to try to enhance a left hand reaction time advantage in right-handed participants. These early attempts have not been successful. The present study circumnavigates some of the theoretical and methodological difficulties of some of the earlier experiments, by using three different tasks linked directly to specialized functions of the right hemisphere: bisecting, the gap effect, and visuospatial localization. None of these tasks were effective in reducing the magnitude of left hand reaction time advantages in right handers. Results are discussed in terms of alternatives to right hemispheric functional explanations of the effect, the one-dimensional nature of our target arrays, power and precision given the size of the left hand RT effect, and the utility of examining the proportions of participants who show these effects, rather than exclusive reliance on measures of central tendency and their associated null hypothesis significance tests

Efam: an expanded, metaproteome-supported HMM profile database of viral protein families

Motivation: Viruses infect, reprogram and kill microbes, leading to profound ecosystem consequences, from elemental cycling in oceans and soils to microbiome-modulated diseases in plants and animals. Although metagenomic datasets are increasingly available, identifying viruses in them is challenging due to poor representation and annotation of viral sequences in databases. Results: Here, we establish efam, an expanded collection of Hidden Markov Model (HMM) profiles that represent viral protein families conservatively identified from the Global Ocean Virome 2.0 dataset. This resulted in 240 311 HMM profiles, each with at least 2 protein sequences, making efam >7-fold larger than the next largest, pan-ecosystem viral HMM profile database. Adjusting the criteria for viral contig confidence from 'conservative' to 'eXtremely Conservative' resulted in 37 841 HMM profiles in our efam-XC database. To assess the value of this resource, we integrated efam-XC into VirSorter viral discovery software to discover viruses from less-studied, ecologically distinct oxygen minimum zone (OMZ) marine habitats. This expanded database led to an increase in viruses recovered from every tested OMZ virome by ∼24% on average (up to ∼42%) and especially improved the recovery of often-missed shorter contigs (<5 kb). Additionally, to help elucidate lesser-known viral protein functions, we annotated the profiles using multiple databases from the DRAM pipeline and virion-associated metaproteomic data, which doubled the number of annotations obtainable by standard, single-database annotation approaches. Together, these marine resources (efam and efam-XC) are provided as searchable, compressed HMM databases that will be updated bi-annually to help maximize viral sequence discovery and study from any ecosystem

The Emergence and Development of Association Football: Influential Sociocultural Factors in Victorian Birmingham

This article explores the interdependent, complex sociocultural factors that facilitated the emergence and diffusion of football in Birmingham. The focus is the development of football in the city, against the backdrop of the numerous social changes in Victorian Birmingham. The aim is to fill a gap in the existing literature which seemingly overlooked Birmingham as a significant footballing centre, and the ‘ordinary and everyday’ aspects of the game’s early progression. Among other aspects, particular heed is paid to the working classes’ involvement in football, as previous literature has often focused on the middle classes and their influence on and participation in organized sport. As the agency of the working classes along with their mass participation and central role in the game’s development is unfolded, it is argued that far from being passive cultural beings, the working classes, from the beginnings, actively negotiated the development of their own emergent football culture

Repressive LTR Nucleosome Positioning by the BAF Complex Is Required for HIV Latency

The SWI/SNF BAF chromatin remodeling complex generates a repressive nucleosome structure at the HIV LTR conducive to establishment and maintenance of HIV latency, while PBAF augments HIV transcription

Dissection of the Role of PfEMP1 and ICAM-1 in the Sensing of Plasmodium falciparum-Infected Erythrocytes by Natural Killer Cells

BACKGROUND: Host innate immunity contributes to malaria clinical outcome by providing protective inflammatory cytokines such as interferon-γ, and by shaping the adaptive immune response. Plasmodium falciparum (Pf) is the etiologic agent of the most severe forms of human malaria. Natural Killer (NK) cells are lymphocytes of the innate immune system that are the first effectors to produce interferon-γ in response to Pf. However, the molecular bases of Pf-NK cell recognition events are unknown. Our study focuses on the role of Pf erythrocyte membrane protein 1 (PfEMP1), a major Pf virulence factor. PfEMP1 is expressed on parasitized-erythrocytes and participates to vascular obstruction through the binding to several host receptors. PfEMP1 is also a pivotal target for host antibody response to Pf infection. METHODOLOGY/PRINCIPAL FINDINGS: Using genetically-engineered parasite mutant strains, a human genetic deficiency, and blocking antibodies, we identified two receptor-ligand pairs involved in two uncoupled events occurring during the sensing of Pf infection by NK cells. First, PfEMP1 interaction with one of its host receptor, chondroitin sulfate A, mediates the cytoadhesion of Pf-infected erythrocytes to human NK cell lines, but is not required for primary NK cell activation. Second, intercellular adhesion molecule-1 (ICAM-1), another host receptor for PfEMP1, is mandatory for NK cell interferon-γ response. In this case, ICAM-1 acts via its engagement with its host ligand, LFA-1, and not with PfEMP1, consistent with the obligatory cross-talk of NK cells with macrophages for their production of interferon-γ. CONCLUSION/SIGNIFICANCE: PfEMP1-independent but ICAM-1/LFA-1-dependent events occurring during NK cell activation by Pf highlight the fundamental role of cellular cooperation during innate immune response to malaria

Strengthening screening for infectious diseases and vaccination among migrants in Europe: What is needed to close the implementation gaps?

Migration to the European Union (EU)/European Economic Area (EEA) affects the epidemiology of infectious diseases, including tuberculosis (TB), HIV, hepatitis B/C, and parasitic diseases. Some sub-populations of migrants are also considered to be an under-immunised group and thus at risk of vaccine-preventable diseases. Providing high-risk migrants access to timely and efficacious screening and vaccination, and understanding how best to implement more integrated screening and vaccination programmes into European health systems ensuring linkage to care and treatment, is key to improving the health of migrants and their communities, alongside meeting national and regional targets for infection surveillance, control, and elimination. The European Centre for Disease Prevention and Control (ECDC) has responded to calls to action to improve migrant health and strengthen universal health coverage by developing evidence-based guidance for policy makers, public health experts, and front-line healthcare professionals on how to approach screening and vaccination in newly arrived migrants within the EU/EEA. In this Commentary, we provide a perspective towards developing efficacious screening and vaccination of newly arrived migrants, with a focus on defining implementation challenges and evidence gaps in high-migrant receiving EU/EEA countries. There is a need now to leverage the increasing momentum around migrant health to both strengthen the evidence-base and to advocate for universal access to health care for all migrants in the EU/EEA, including undocumented migrants. This should include voluntary, confidential, and non-stigmatising screening and vaccination that should be free of charge and facilitate linkage to appropriate care and treatment

Normalization of the Lymph Node T Cell Stromal Microenvironment in lpr/lpr Mice Is Associated with SU5416-Induced Reduction in Autoantibodies

The vascular-stromal elements of lymph nodes can play important roles in regulating the activities of the lymphocytes within. During model immune responses, the vascular-stromal compartment has been shown to undergo proliferative expansion and functional alterations. The state of the vascular-stromal compartment and the potential importance of this compartment in a spontaneous, chronic model of autoimmunity have not been well studied. Here, we characterize the vascular expansion in MRL-lpr/lpr lymph nodes and attempt to ask whether inhibiting this expansion can interfere with autoantibody generation. We show that characteristics of vascular expansion in enlarging MRL-lpr/lpr lymph nodes resemble that of the VEGF-dependent expansion that occurs in wild-type mice after model immunization. Surprisingly, treatment with SU5416, an inhibitor of VEGF and other receptor tyrosine kinases, did not have sustained effects in inhibiting vascular growth, but attenuated the anti-dsDNA response and altered the phenotype of the double negative T cells that are expanded in these mice. In examining for anatomic correlates of these immunologic changes, we found that the double negative T cells are localized within ectopic follicles around a central B cell patch and that these T cell-rich areas lack the T zone stromal protein ER-TR7 as well as other elements of a normal T zone microenvironment. SU5416 treatment disrupted these follicles and normalized the association between T zone microenvironmental elements and T cell-rich areas. Recent studies have shown a regulatory role for T zone stromal elements. Thus, our findings of the association of anti-dsDNA responses, double negative T cell phenotype, and altered lymphocyte microenvironment suggest the possibility that lymphocyte localization in ectopic follicles protects them from regulation by T zone stromal elements and functions to maintain autoimmune responses. Potentially, altering the lymphocyte microenvironment that is set up by the vascular-stromal compartment can be a means by which to control undesired autoimmune responses

Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. Findings In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. Funding UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology