Research on interpersonal convergence and synchrony characterizes the way in which interacting individuals come to have more similar affect, behaviour, and cognition over time. Although its dynamics have been explored in many settings, convergence during conflict has been almost entirely overlooked. We present a simple but ecologically valid study comparing how different situational contexts that highlight affiliation and argument impact interpersonal convergence of body movement and to what degree emotional states affect convergence in both conversational settings.
View Article and Find Full Text PDFOver the recent years, antibodies against surface and conformational proteins involved in neurotransmission have been detected in autoimmune CNS diseases in children and adults. These antibodies have been used to guide diagnosis and treatment. Cell-based assays have improved the detection of antibodies in patient serum.
View Article and Find Full Text PDFFor many years, zebrafish have been the prototypical model for studies in developmental biology. In recent years, zebrafish has emerged as a powerful model system to study infectious diseases, including viral infections. Experiments conducted with herpes simplex virus type-1 in adult zebrafish or in embryo models are encouraging as they establish proof of concept with viral-host tropism and possible screening of antiviral compounds.
View Article and Find Full Text PDFBackground: We recently observed mutations in ADAR1 to cause a phenotype of bilateral striatal necrosis (BSN) in a child with the type I interferonopathy Aicardi-Goutières syndrome (AGS). We therefore decided to screen patients with apparently non-syndromic BSN for ADAR1 mutations, and for an upregulation of interferon-stimulated genes (ISGs).
Methods: We performed Sanger sequencing of ADAR1 in a series of patients with BSN presenting to us during our routine clinical practice.
The knowledge of immune dysregulation and autoimmunity in neurological disorders has expanded considerably in recent times. Recognition of clinical syndromes, reliable methods of diagnosis, and early targeted immunotherapy can lead to a favourable outcome in acute and subacute neurological disorders that may be associated with significant morbidity and mortality if left untreated. This review focuses on the rapidly expanding field of autoimmune encephalitis.
View Article and Find Full Text PDFAutoantibodies to the extracellular domain of neuronal proteins cause different neurological conditions with movement disorders as a prominent feature. We reviewed the literature of autoantibody-mediated and autoantibody-associated diseases focusing on anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, autoimmune basal ganglia encephalitis, Sydenham chorea, and the rare syndrome of progressive encephalomyelitis with rigidity and myoclonus. NMDAR encephalitis is a diffuse encephalitis with psychiatric and cognitive features associated with autoantibodies against the NR1 subunit of the NMDAR.
View Article and Find Full Text PDFBackground: Aicardi-Goutières syndrome (AGS) is an inflammatory disorder caused by mutations in any of six genes (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR). The disease is severe and effective treatments are urgently needed. We investigated the status of interferon-related biomarkers in patients with AGS with a view to future use in diagnosis and clinical trials.
View Article and Find Full Text PDFPurpose: Potentially pathogenic autoantibodies are found increasingly in adults with seizure disorders, including focal seizures and those of unknown cause. In this study, we investigated a cohort of children with new-onset seizures to see whether there were autoantibodies and the relationship to any specific seizure or epilepsy type.
Methods: We prospectively recruited 114 children (2 months to 16 years) with new-onset seizures presenting between September 2009 and November 2011, as well as 65 controls.
Background: Movement disorder relapses after herpes simplex virus 1 (HSV1) encephalitis have been hypothesized to be secondary to postviral autoimmunity. Recently, a proportion of patients with HSV1 encephalitis (HSE) were shown to produce autoantibodies against N-methyl-D-aspartate receptor (NMDAR).
Methods: We measured autoantibodies against NMDAR and dopamine-2 receptor (D2R) expressed at the cell surface in the stored acute serum of 9 children with HSE, 3 of whom had a relapsing course with chorea.
The pathophysiology of psychosis is poorly understood, with both the cognitive and cellular changes of the disease process remaining mysterious. There is a growing body of evidence that points to dysfunction of the immune system in a subgroup of patients with psychosis. Recently, autoantibodies directed against neuronal cell surface targets have been identified in a range of syndromes that feature psychosis.
View Article and Find Full Text PDFAutoantibodies targeting conformationally intact myelin oligodendrocyte glycoprotein (MOG) are found in different inflammatory diseases of the CNS, but their antigenic epitopes have not been mapped. We expressed mutants of MOG on human HeLa cells and analyzed sera from 111 patients (104 children, 7 adults) who recognized cell-bound human MOG, but had different diseases, including acute disseminated encephalomyelitis (ADEM), one episode of transverse myelitis or optic neuritis, multiple sclerosis (MS), anti-aquaporin-4 (AQP4)-negative neuromyelitis optica (NMO), and chronic relapsing inflammatory optic neuritis (CRION). We obtained insight into the recognition of epitopes in 98 patients.
View Article and Find Full Text PDFThe purpose of this study was to review the magnitude of contribution of chemotherapy (CT) in the local control of muscle invasive bladder carcinoma in the studies where a combined radio-chemotherapy (RCT) was used (how much higher local control rates are obtained with RCT compared to RT alone). Studies on radiotherapy (RT) and combined RCT, neo-adjuvant, concurrent, adjuvant or combinations, reported after 1990 were reviewed. The mean complete response (CR) rates were significantly higher for the RCT studies compared to RT-alone studies: 75.
View Article and Find Full Text PDFBackground: Knowledge of the mechanisms of herbicide resistance is important for designing long term sustainable weed management strategies. Here, we have used an integrated biology and molecular approach to investigate the mechanisms of resistance to acetyl-CoA carboxylase inhibiting herbicides in a UK black-grass population (BG2).
Methodology/principal Findings: Comparison between BG2 phenotypes using single discriminant rates of herbicides and genotypes based on ACCase gene sequencing showed that the I1781L, a novel I1781T, but not the W2027C mutations, were associated with resistance to cycloxydim.
Chromatin insulators are DNA protein complexes situated throughout the genome capable of demarcating independent transcriptional domains. Previous studies point to an important role for RNA in gypsy chromatin insulator function in Drosophila; however, the identity of these putative insulator-associated RNAs is not currently known. Here we utilize RNA-immunoprecipitation and high throughput sequencing (RIP-seq) to isolate RNAs stably associated with gypsy insulator complexes.
View Article and Find Full Text PDFEur J Med Genet
September 2013
Benign hereditary chorea caused by mutations in the NK2 homeobox 1 gene (NKX2-1), shares clinical features with ataxic and dyskinetic cerebral palsy (CP), resulting in the possibility of misdiagnosis. A father and his two children were considered to have ataxic CP until a possible diagnosis of benign familial chorea was made in the children in early teenage. The father's neurological condition had not been appreciated prior to examination of the affected son.
View Article and Find Full Text PDFIntroduction: This study aims to quantify the radiobiology of the MammoSite applicator and examine whether there is a relationship between equivalent uniform dose (EUD) and radiotherapy-associated toxicity.
Methods And Materials: A previously-published version of the linear quadratic (LQ) model, designed to address the impact of dose-gradients in brachytherapy applications, was used to determine the biological effective dose (BED), equivalent dose in 2 Gray per fraction (EQD2) and EUD for the most common fractionation scheme for the MammoSite catheter (34 Gy in 10 fractions prescribed to 1cm from the balloon surface), using a range of balloon sizes in a series of patients treated with single or multiple dwell positions. Toxicity from the MammoSite catheter was assessed and statistical associations with the calculated EUDs were investigated.
Within decisions, perceived alternatives compete until one is preferred. Across decisions, the playing field on which these alternatives compete evolves to favor certain alternatives. Mouse cursor trajectories provide rich continuous information related to such cognitive processes during decision making.
View Article and Find Full Text PDFRNA-binding proteins are key regulators of gene expression, yet only a small fraction have been functionally characterized. Here we report a systematic analysis of the RNA motifs recognized by RNA-binding proteins, encompassing 205 distinct genes from 24 diverse eukaryotes. The sequence specificities of RNA-binding proteins display deep evolutionary conservation, and the recognition preferences for a large fraction of metazoan RNA-binding proteins can thus be inferred from their RNA-binding domain sequence.
View Article and Find Full Text PDFIntroduction: Functional impairment associated with mood disorders may be related to a characteristic "profile" of normative personality dimensions.
Methods: Individuals (age ≥ 18 years) with MDD (n = 400) or BD (n = 317), as defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR), were enrolled in the IMDCP. Personality was evaluated with the Neuroticism-Extraversion-Openness Five-Factor Inventory (NEO-FFI), and functionality with the Sheehan Disability Scale and Endicott Work Productivity Scale.
We report a female with infantile onset of systemic lupus erythematosus secondary to C1q deficiency, in whom we identified a novel homozygous mutation in C1qB. The patient developed a progressive encephalopathy associated with spasticity, and suffered several arterial ischaemic strokes. Cerebral imaging demonstrated acquired intracranial calcification and a cerebral vasculopathy reminiscent of moyamoya.
View Article and Find Full Text PDFHandb Clin Neurol
March 2014
Immune-mediated extrapyramidal movement disorders typically occur in previously healthy children. Immune-mediated movement disorders may occur as a postinfectious, paraneoplastic, or idiopathic process. Sydenham chorea (SC) is the classical poststreptococcal movement and psychiatric disorder, and may be associated with other features of rheumatic fever.
View Article and Find Full Text PDFBackground And Objective: Acute disseminated encephalomyelitis (ADEM) and relapsing-remitting multiple sclerosis (RRMS) share overlapping clinical, radiologic and laboratory features at onset. Because autoantibodies may contribute to the pathogenesis of both diseases, we sought to identify autoantibody biomarkers that are capable of distinguishing them.
Methods: We used custom antigen arrays to profile anti-myelin-peptide autoantibodies in sera derived from individuals with pediatric ADEM (n = 15), pediatric multiple sclerosis (Ped MS; n = 11) and adult MS (n = 15).
Erythropoiesis is dependent on the lineage-specific transcription factors Gata1, Tal1, and Klf1. Several erythroid genes have been shown to require all 3 factors for their expression, suggesting that they function synergistically; however, there is little direct evidence for widespread cooperation. Gata1 and Tal1 can assemble within higher-order protein complexes (Ldb1 complexes) that include the adapter molecules Lmo2 and Ldb1.
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