Neuromyelitis optica MOG-IgG causes reversible lesions in mouse brain.

INTRODUCTION: Antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) are present in some neuromyelitis optica patients who lack antibodies against aquaporin-4 (AQP4-IgG). The effects of neuromyelitis optica MOG-IgG in the central nervous system have not been investigated in vivo. We microinjected MOG-IgG, obtained from patients with neuromyelitis optica, into mouse brains and compared the results with AQP4-IgG. RESULTS: MOG-IgG caused myelin changes and altered the expression of axonal proteins that are essential for action potential firing, but did not produce inflammation, axonal loss, neuronal or astrocyte death. These changes were independent of complement and recovered within two weeks. By contrast, AQP4-IgG produced complement-mediated myelin loss, neuronal and astrocyte death with limited recovery at two weeks. CONCLUSIONS: These differences mirror the better outcomes for MOG-IgG compared with AQP4-IgG patients and raise the possibility that MOG-IgG contributes to pathology in some neuromyelitis optica patients

Neuromyelitis optica MOG-IgG causes reversible lesions in mouse brain.

INTRODUCTION: Antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) are present in some neuromyelitis optica patients who lack antibodies against aquaporin-4 (AQP4-IgG). The effects of neuromyelitis optica MOG-IgG in the central nervous system have not been investigated in vivo. We microinjected MOG-IgG, obtained from patients with neuromyelitis optica, into mouse brains and compared the results with AQP4-IgG. RESULTS: MOG-IgG caused myelin changes and altered the expression of axonal proteins that are essential for action potential firing, but did not produce inflammation, axonal loss, neuronal or astrocyte death. These changes were independent of complement and recovered within two weeks. By contrast, AQP4-IgG produced complement-mediated myelin loss, neuronal and astrocyte death with limited recovery at two weeks. CONCLUSIONS: These differences mirror the better outcomes for MOG-IgG compared with AQP4-IgG patients and raise the possibility that MOG-IgG contributes to pathology in some neuromyelitis optica patients

Interpretation of ambiguous situations: evidence for a dissociation between social and physical threat in Williams syndrome

There is increasing evidence that Williams syndrome (WS) is associated with elevated anxiety that is non-social in nature, including generalised anxiety and fears. To date very little research has examined the cognitive processes associated with this anxiety. In the present research, attentional bias for non-social threatening images in WS was examined using a dot-probe paradigm. Participants were 16 individuals with WS aged between 13 and 34 years and two groups of typically developing controls matched to the WS group on chronological age and attentional control ability respectively. The WS group exhibited a significant attention bias towards threatening images. In contrast, no bias was found for group matched on attentional control and a slight bias away from threat was found in the chronological age matched group. The results are contrasted with recent findings suggesting that individuals with WS do not show an attention bias for threatening faces and discussed in relation to neuroimaging research showing elevated amygdala activation in response to threatening non-social scenes in WS

Transition of plasmodium sporozoites into liver stage-like forms is regulated by the RNA binding protein pumilio

Many eukaryotic developmental and cell fate decisions that are effected post-transcriptionally involve RNA binding proteins as regulators of translation of key mRNAs. In malaria parasites (Plasmodium spp.), the development of round, non-motile and replicating exo-erythrocytic liver stage forms from slender, motile and cell-cycle arrested sporozoites is believed to depend on environmental changes experienced during the transmission of the parasite from the mosquito vector to the vertebrate host. Here we identify a Plasmodium member of the RNA binding protein family PUF as a key regulator of this transformation. In the absence of Pumilio-2 (Puf2) sporozoites initiate EEF development inside mosquito salivary glands independently of the normal transmission-associated environmental cues. Puf2- sporozoites exhibit genome-wide transcriptional changes that result in loss of gliding motility, cell traversal ability and reduction in infectivity, and, moreover, trigger metamorphosis typical of early Plasmodium intra-hepatic development. These data demonstrate that Puf2 is a key player in regulating sporozoite developmental control, and imply that transformation of salivary gland-resident sporozoites into liver stage-like parasites is regulated by a post-transcriptional mechanism

The efficacy of surgical decompression before 24 hours versus 24 to 72 hours in patients with spinal cord injury from T1 to L1 – with specific consideration on ethics: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>There is no clear evidence that early decompression following spinal cord injury (SCI) improves neurologic outcome. Such information must be obtained from randomized controlled trials (RCTs). To date no large scale RCT has been performed evaluating the timing of surgical decompression in the setting of thoracolumbar spinal cord injury. A concern for many is the ethical dilemma that a delay in surgery may adversely effect neurologic recovery although this has never been conclusively proven. The purpose of this study is to compare the efficacy of early (before 24 hours) verse late (24–72 hours) surgical decompression in terms of neurological improvement in the setting of traumatic thoracolumbar spinal cord injury in a randomized format by independent, trained and blinded examiners.</p> <p>Methods</p> <p>In this prospective, randomized clinical trial, 328 selected spinal cord injury patients with traumatic thoracolumbar spinal cord injury are to be randomly assigned to: 1) early surgery (before 24 hours); or 2) late surgery (24–72 hours). A rapid response team and set up is prepared to assist the early treatment for the early decompressive group. Supportive care, i.e. pressure support, immobilization, will be provided on admission to the late decompression group. Patients will be followed for at least 12 months posttrauma.</p> <p>Discussion</p> <p>This study will hopefully assist in contributing to the question of the efficacy of the timing of surgery in traumatic thoracolumbar SCI.</p> <p>Trial Registration</p> <p><b>RCT registration number: ISRCTN61263382</b></p

Self-Reported Functional Status as Predictor of Observed Functional Capacity in Subjects with Early Osteoarthritis of the Hip and Knee: A Diagnostic Study in the CHECK Cohort

Objectives Patients with hip or knee osteoarthritis (OA) may experience functional limitations in work settings. In the Cohort Hip and Cohort Knee study (CHECK) physical function was both self-reported and measured performance-based, using Functional Capacity Evaluation (FCE). Relations between self-reported scores on SF-36 and WOMAC (Western Ontario and McMaster Arthritis Index, function scales) and FCE performance were studied, and their diagnostic value for clinicians in predicting observed physical work limitations was assessed. Methods Ninety-two subjects scored physical function on SF-36 (scale 0–100, 100 indicating the best health level) and WOMAC (scale 0–68, 68 indicates maximum restriction) and performed the FCE. Correlations were calculated between all scores. Cross-tables were constructed using both questionnaires as diagnostic tests to identify work limitations. Subjects lifting <22.5 kg on the FCE-test ‘lifting-low’ were labeled as having physical work limitations. Diagnostic aspects at different cut-off scores for both questionnaires were analysed. Results Statistically significant correlations (Spearman’s ρ 0.34–0.49) were found between questionnaire scores and lifting and carrying tests. Results of a diagnostic cross-table with cut-off point <60 on SF-36 ‘physical functioning’ were: sensitivity 0.34, specificity 0.97 and positive predictive value (PV+) 0.95. Cut-off point ≥21 on WOMAC ‘function’ resulted in sensitivity 0.51, specificity 0.88 and PV+ 0.88. Conclusion Low self-reported function scores on SF-36 and WOMAC diagnosed subjects with limitations on the FCE. However, high scores did not guarantee performance without physical work limitations. These results are specific to the tested persons with early OA, in populations with a different prevalence of limitations, different diagnostic values will be found. FCE may be indicated to help clinicians to assess actual work capacity

Has classical gene position been practically reduced?

One of the defining features of the classical gene was its position (a band in the chromosome). In molecular genetics, positions are defined instead as nucleotide numbers and there is no clear correspondence with its classical counterpart. However, the classical gene position did not simply disappear with the development of the molecular approach, but survived in the lab associated to different genetic practices. The survival of classical gene position would illustrate Waters’ view about the practical persistence of the genetic approach beyond reductionism and anti-reductionist claims. We show instead that at the level of laboratory practices there are also reductive processes, operating through the rise and fall of different techniques. Molecular markers made the concept of classical gene position practically dispensable, leading us to rethink whether it had any causal role or was just a mere heuristi

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

AHR2 Mutant Reveals Functional Diversity of Aryl Hydrocarbon Receptors in Zebrafish

The aryl hydrocarbon receptor (AHR) is well known for mediating the toxic effects of TCDD and has been a subject of intense research for over 30 years. Current investigations continue to uncover its endogenous and regulatory roles in a wide variety of cellular and molecular signaling processes. A zebrafish line with a mutation in ahr2 (ahr2hu3335), encoding the AHR paralogue responsible for mediating TCDD toxicity in zebrafish, was developed via Targeting Induced Local Lesions IN Genomes (TILLING) and predicted to express a non-functional AHR2 protein. We characterized AHR activity in the mutant line using TCDD and leflunomide as toxicological probes to investigate function, ligand binding and CYP1A induction patterns of paralogues AHR2, AHR1A and AHR1B. By evaluating TCDD-induced developmental toxicity, mRNA expression changes and CYP1A protein in the AHR2 mutant line, we determined that ahr2hu3335 zebrafish are functionally null. In silico modeling predicted differential binding of TCDD and leflunomide to the AHR paralogues. AHR1A is considered a non-functional pseudogene as it does not bind TCCD or mediate in vivo TCDD toxicity. Homology modeling, however, predicted a ligand binding conformation of AHR1A with leflunomide. AHR1A-dependent CYP1A immunohistochemical expression in the liver provided in vivo confirmation of the in silico docking studies. The ahr2hu3335 functional knockout line expands the experimental power of zebrafish to unravel the role of the AHR during development, as well as highlights potential activity of the other AHR paralogues in ligand-specific toxicological responses

Über eine Klasse polynomialer Scharen selbstadjungierter Operatoren im Hilbertraum

HEK293A cells expressing either mouse MOG (mMOG) or rat MOG (rMOG) C terminally tagged with EGFP. (DOCX 2792 kb