Study of Structural, Compression, and Soft Magnetic Properties of Fe65Ni28Mn7 Alloy Prepared by Arc Melting, Mechanical Alloying, and Spark Plasma Sintering.

Soft magnetic Fe65Ni28Mn7 (at. %) alloy was successfully synthesized by mechanical alloying and spark plasma sintering (SPS) and, in parallel, the same composition was prepared by arc melting (AM) for comparison. Several SPS conditions were tested. X-ray diffraction and scanning electron microscopy were used to investigate the structure, phase composition, and morphology of the samples. It was found that mechanical alloying produced BCC and FCC supersaturated solid solution after 130 h of milling, with a fine microstructure (i.e., crystallite size of 10 nm). Spark plasma sintering performed at 750 °C and 1000 °C under two pressures of 50 MPa and 75 MPa revealed stable FCC phases. A single FCC phase was observed after the arc melting synthesis. The magnetic properties of milled powders and solids obtained by AM and SPS were investigated. The specimen consolidated by SPS at 1000 °C under the pressure of 50 MPa exhibits soft magnetic behavior (coercivity 0.07 Oe), whereas the mechanically alloyed sample revealed hard magnetic behavior. The specimen consolidated at 750 °C under a pressure of 75 MPa showed a higher compressive strength of 1700 MPa and a Vickers hardness of 425 ± 18 HV. As a result, sintering at 750 °C/75 MPa can be utilized to enhance the mechanical properties, while those sintered at 1000 °C/50 MPa increase magnetic softness.

24-hydroxycholesterol replacement rate measured in blood is a non-invasive biomarker of brain demyelination and remyelination in cuprizone-treated mice.

In mice, dietary cuprizone causes brain demyelination with subsequent spontaneous remyelination upon return to normal chow. Heavy water (2H2O) labeling with mass spectrometric analysis can be used to measure brain de novo synthesis of several myelin components including cholesterol, phospholipids, galactocereboside (GalC) and myelin-associated proteins. 24-hydroxycholesterol (24-OHC), the major metabolite of brain cholesterol, is detected in blood and is believed to be specifically derived from CNS cholesterol metabolism. We assessed changes in syntheses of myelin components in brain and of blood sterols during cuprizone-induced experimental demyelination and remyelination, with and without thyroid hormone (T3) treatment. Mice were fed cuprizone for 4 weeks, then returned to control diet and treated with either placebo or T3 (0.005 mg/day). 2H2O was administered for the last 14 days of cuprizone diet, and for either 6, 12 or 19 days of treatment during recovery from cuprizone, after which blood and corpus callosum (CC) samples were collected (n = 5/time point/treatment). 2H incorporation into cholesterol and 24-OHC in blood and CC, and incorporation into phospholipid (PL)-palmitate, GalC, myelin basic protein (MBP) and 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) in CC were measured. Cuprizone significantly (p < 0.05) decreased syntheses of cholesterol, 24-OHC, GalC, MBP, CNPase and PL-palmitate in the CC and these effects were all reversed during recovery. T3 treatment significantly (p < 0.05) increased syntheses of cholesterol, 24-OHC and palmitate compared to placebo. 24-OHC and cholesterol turnover rates in brain and blood were nearly identical and 24-OHC rates in blood paralleled rates in CC, indicating that blood 24-OHC derives primarily from the brain and reflects oligodendrocyte function. In summary, changes in synthesis of several lipid and protein components in brain during cuprizone-induced demyelination and remyelination are measurable through stable isotope labeling. Blood 24-OHC turnover rates closely reflect flux rates of brain cholesterol in response to cuprizone and T3, which alter oligodendrocyte function. Labeling of blood 24-OHC has potential as a non-invasive marker of brain de novo cholesterol synthesis and breakdown rates in demyelinating conditions.

Validation of a commercial version of a competitive enzyme linked immunosorbent assay for the detection of antibodies to Besnoitia besnoiti.

BACKGROUND: Several reports suggest a further spread of besnoitiosis to countries in which Besnoitia besnoiti-infected bovine herds have not been noticed yet. Cattle infected without clinical signs may represent reservoirs. Serological analyses in affected herds or animals from endemic regions are necessary to identify subclinical or inapparent infections and stop transmission to naïve animals or herds. The Monoscreen AbELISA Besnoitia besnoiti (BIO K 466) is based on a previously published in-house competitive ELISA, the Bb-cELISA1, but has a different test architecture. The present study aimed to use sera from a previous evaluation of Bb-cELISA1 to assess whether BIO K466 shows identical results. In addition, further well-characterized positive and negative samples were analysed to estimate diagnostic sensitivity and specificity. METHODS: A first set of sera consisted of a total of 305 bovine sera, collected from German herds infected by B. besnoiti, Neospora caninum or Sarcocystis spp. Sera had been characterized by reference serological tests (i.e. immunoblot, immunofluorescence antibody test and an in-house indirect ELISA). A second set consisted of 200 confirmed B. besnoiti-positive sera from French herds. Negative cattle sera (n = 624) originated from Norway and The Netherlands, countries in which bovine besnoitiosis has not been reported yet. RESULTS: Using the first set of sera, the BIO K466 showed an estimated diagnostic sensitivity of 97.9% (95% CI: 91.9%-99.6) and a diagnostic specificity of 99.5% (95% CI: 96.9%-100%) relative to reference serological tests. A direct comparison of the results revealed an almost perfect agreement between the results of the in-house Bb-cELISA1 and the commercialized version (kappa 0.98; 95% CI: 0.95-1). The validation using positive bovine sera from France and negative sera from other European countries revealed a diagnostic sensitivity of 97.5% (95% CI: 93.9%-99.1%) and specificity of 99.5% (95% CI: 98.5%-99.9%). CONCLUSION: In conclusion, BIO K 466 appears to be a suitable tool to diagnose bovine besnoitiosis, but needs further validation especially in cases of inconclusive, suspected false-positive or -negative results in other serological tests.

Elaboration and Characterization of WMoTaNb High Entropy Alloy Prepared by Powder Metallurgy Processes.

This work concerns the sintering of tungsten-based (i.e WMoTaNb) high entropy alloy (HEA) powders using the spark plasma sintering (SPS) technique and their mechanical properties. The synthesis was performed by a self-propagating high-temperature synthesis (SHS) type reaction in which the mixture of metallic oxides (WO3, MoO3 …) is reduced by magnesium. For this, a specific reactor has been developed. Different conditions including the addition of a moderator were tested. These powders are then densified by SPS technology which allows for keeping the initial microstructure of the powder. The optimization of sintering conditions was performed with the objective to control simultaneously the chemical composition, the grain growth and the densification stages.

The hippocampal region is necessary for text comprehension and memorization: a combined VBM/DTI study in neuropsychological patients.

According to the Construction-Integration model (Kintsch 1988; Kintsch 1998), two forms of representation are activated during the reading and the comprehension of a text: 1) the text base, which includes semantic propositions and 2) the situation model, corresponding to the integration of the information contained in the text to the memories and knowledge of the reader. Functional neuroimaging studies in healthy subjects have shown that the text base is underpinned by frontal regions and lateral temporal regions whereas the situation model would rather depend on the posterior cingulate cortex, the precuneus and other regions depending on the dimension studied. However, the brain regions highlighted so far were only involved in comprehension and not necessary for this cognitive ability. For the first time, we explored the brain structures necessary to understand texts using a combined VBM/DTI approach in neuropsychological patients with whom we obtained comprehension scores (text base and situation model) after the reading of narrative texts. To our great surprise and contrary to our hypotheses, which were based on the results of functional neuroimaging studies, our own results show that it is the hippocampal region that is necessary to activate and memorize/remember the text base and the situation model. The highlighting of a link between the integrity of a portion of the uncinate fasciculus which is well known to play a role in semantic processing and the performance scores of the text base suggests that the hippocampal region is necessary not only for the retrieval of the text base and of the situation model thanks to episodic memory, but also for the activation of the text base during the reading and the comprehension of a text.

Discovery of novel Cyclophilin D inhibitors starting from three dimensional fragments with millimolar potencies.

Fragment-based screening by SPR enabled the discovery of chemical diverse fragment hits with millimolar binding affinities to the peptidyl-prolyl isomerase Cyclophilin D (CypD). The CypD protein crystal structures of 6 fragment hits provided the basis for subsequent medicinal chemistry optimization by fragment merging and linking yielding three different chemical series with either urea, oxalyl or amide linkers connecting millimolar fragments in the S1' and S2 pockets. We successfully improved the in vitro CypD potencies in the biochemical FP and PPIase assays and in the biophysical SPR binding assay from millimolar towards the low micromolar and submicromolar range by >1000-fold for some fragment derivatives. The initial SAR together with the protein crystal structures of our novel CypD inhibitors provide a suitable basis for further hit-to-lead optimization.

Discrete multi-physics: A mesh-free model of blood flow in flexible biological valve including solid aggregate formation.

We propose a mesh-free and discrete (particle-based) multi-physics approach for modelling the hydrodynamics in flexible biological valves. In the first part of this study, the method is successfully validated against both traditional modelling techniques and experimental data. In the second part, it is further developed to account for the formation of solid aggregates in the flow and at the membrane surface. Simulations of various types of aggregates highlight the main benefits of discrete multi-physics and indicate the potential of this approach for coupling the hydrodynamics with phenomena such as clotting and calcification in biological valves.

Comparative study of false memory in dementia with Lewy bodies and Alzheimer's disease.

The production of false memories (FMs) is a normal phenomenon, which can be affected in neurodegenerative diseases such as Alzheimer's disease (AD). Only few studies investigated FMs in patients with dementia with Lewy bodies (DLB). The aim of our preliminary study was to assess FMs in patients with DLB and to identify the underlying cognitive deficits influencing the production of FMs in DLB and AD. Ten AD patients and nine DLB patients performed a memory task (free recall and recognition) coupling two paradigms, namely the DRM (Deese-Roediger-McDermott) paradigm, promoting the production of FMs and the "Remember/Know" (R/K) paradigm, allowing to investigate the phenomenological experience during the recollection of a memory. A standard cognitive evaluation of memory, executive and instrumental functions completed the assessment. No FM was found in the DLB group during free recall, while the number of FMs was substantially identical in both groups during recognition. However, FMs differed from the phenomenological experience, with more K responses in DLB patients and more R responses in AD patients. None of the tests of the standard neuropsychological evaluation did correlate with measures of interest of FMs. In AD patients, the R responses associated with FMs reflect an alteration of the source memory. In DLB patients, the critical item lead to a sense of familiarity, without recollection of the circumstances in which the item was encoded, hence the K responses. This indicates a preservation of their source memory. Contrary to expectations, the type of FMs in both groups was not correlated to their cognitive profile. Hence, cognitive processes underlying the FMs appear to be different in AD and the LBD, but FMs seem independent of memory and executive abilities in these diseases.

Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study.

An international phase 2 study combining cladribine and cytarabine (Ara-C) was initiated for patients with refractory, risk-organ-positive Langerhans cell histiocytosis (LCH) in 2005. The protocol, comprising at least two 5-day courses of Ara-C (1 g/m(2) per day) plus cladribine (9 mg/m(2) per day) followed by maintenance therapy, was administered to 27 patients (median age at diagnosis, 0.7 years; median follow-up, 5.3 years). At inclusion, all patients were refractory after at least 1 course of vinblastine (VBL) plus corticosteroid, all had liver and spleen involvement, and 25 patients had hematologic cytopenia. After 2 courses, disease status was nonactive (n = 2), better (n = 23), or stable (n = 2), with an overall response rate of 92%. Median disease activity scores decreased from 12 at the start of therapy to 3 after 2 courses (P < .0001). During maintenance therapy, 4 patients experienced reactivation in risk organs. There were 4 deaths; 2 were related to therapy toxicity and 2 were related to reactivation. All patients experienced severe toxicity, with World Health Organization grade 4 hematologic toxicity and 6 documented severe infections. The overall 5-year survival rate was 85% (95% confidence interval, 65.2%-94.2%). Thus, the combination of cladribine/Ara-C is effective therapy for refractory multisystem LCH but is associated with high toxicity.

The development of a foliar fungal pathogen does react to leaf temperature!

The thermal performance curve is an ecological concept relating the phenotype of organisms and temperature. It requires characterization of the leaf temperature for foliar fungal pathogens. Epidemiologists, however, use air temperature to assess the impacts of temperature on such pathogens. Leaf temperature can differ greatly from air temperature, either in controlled or field conditions. This leads to a misunderstanding of such impacts. Experiments were carried out in controlled conditions on adult wheat plants to characterize the response of Mycosphaerella graminicola to a wide range of leaf temperatures. Three fungal isolates were used. Lesion development was assessed twice a week, whereas the temperature of each leaf was monitored continuously. Leaf temperature had an impact on disease dynamics. The latent period of M. graminicola was related to leaf temperature by a quadratic relationship. The establishment of thermal performance curves demonstrated differences among isolates as well as among leaf layers. For the first time, the thermal performance curve of a foliar fungal pathogen has been established using leaf temperature. The experimental setup we propose is applicable, and efficient, for other foliar fungal pathogens. Results have shown the necessity of such an approach, when studying the acclimatization of foliar fungal pathogens.

Dissecting the mechanisms of Notch induced hyperplasia.

The outcome of the Notch pathway on proliferation depends on cellular context, being growth promotion in some, including several cancers, and growth inhibition in others. Such disparate outcomes are evident in Drosophila wing discs, where Notch overactivation causes hyperplasia despite having localized inhibitory effects on proliferation. To understand the underlying mechanisms, we have used genomic strategies to identify the Notch-CSL target genes directly activated during wing disc hyperplasia. Among them were genes involved in both autonomous and non-autonomous regulation of proliferation, growth and cell death, providing molecular explanations for many characteristics of Notch induced wing disc hyperplasia previously reported. The Notch targets exhibit different response patterns, which are shaped by both positive and negative feed-forward regulation between the Notch targets themselves. We propose, therefore, that both the characteristics of the direct Notch targets and their cross-regulatory relationships are important in coordinating the pattern of hyperplasia.

Role of transmembrane semaphorin Sema6A in oligodendrocyte differentiation and myelination.

Myelination is regulated by extracellular proteins, which control interactions between oligodendrocytes and axons. Semaphorins are repulsive axon guidance molecules, which control the migration of oligodendrocyte precursors during normal development and possibly in demyelinating diseases. We show here that the transmembrane semaphorin 6A (Sema6A) is highly expressed by myelinating oligodendrocytes in the postnatal mouse brain. In adult mice, Sema6A expression is upregulated in demyelinating lesions in cuprizone-treated mice. The analysis of the optic nerve and anterior commissure of Sema6A-deficient mice revealed a marked delay of oligodendrocyte differentiation. Accordingly, the development of the nodes of Ranvier is also transiently delayed. We also observed an arrest in the in vitro differentiation of purified oligodendrocytes lacking Sema6A, with a reduction of the expression level of Myelin Basic Protein. Their morphology is also abnormal, with less complex and ramified processes than wild-type oligodendrocytes. In myelinating co-cultures of dorsal root ganglion neurons and purified oligodendrocytes we found that myelination is perturbed in absence of Sema6A. These results suggest that Sema6A might have a role in myelination by controlling oligodendrocyte differentiation.

Functional parcellation of the lateral mesencephalus.

The mesencephalic locomotor region (MLR), which includes the pedunculopontine nucleus (PPN) and the cuneiform nucleus (CN), has been recently identified as a key structure for locomotion and gait control in mammals. However, the function and the precise anatomy of the MLR remain unclear in humans. To study the lateral mesencephalus, we used fMRI in 15 right-handed healthy volunteers performing two tasks: imagine walking in a hallway and imagine an object moving along the same hallway. Both tasks were performed at two different speeds: normal and 30% faster. We identified two distinct networks of cortical activation: one involving motor/premotor cortices and the cerebellum for the walking task and the other involving posterior parietal and dorsolateral prefrontal cortices for the object moving task. In the lateral mesencephalus, we found that two different but anatomically connected parts of the MLR were activated during the fast condition of each task. The CN and the dorsal part of the PPN were activated during the fast imaginary walking task, whereas the ventral part of the PPN and the ventral part of the reticular formation were activated while subjects were imagining the object moving fast. Our data suggest that the lateral mesencephalus participates in different aspects of gait in humans, with the CN and dorsal PPN controlling motor aspects of locomotion and the ventral PPN being involved in integrating sensory information.

When Higher Activations Reflect Lower Deactivations: A PET Study in Alzheimer's Disease during Encoding and Retrieval in Episodic Memory.

The aim of the present study was to explore the cerebral substrates of episodic memory disorders in Alzheimer's disease (AD) and investigate patients' hyperactivations frequently reported in the functional imaging literature. It remains unclear whether some of these hyperactivations reflect real increased activity or deactivation disturbances in the default mode network (DMN). Using positron emission tomography ((15)O-H(2)O), cerebral blood flow was measured in 11 AD patients and 12 healthy elderly controls at rest and during encoding and stem-cued recall of verbal items. Subtractions analyses between the target and control conditions were performed and compared between groups. The average signal was extracted in regions showing hyperactivation in AD patients versus controls in both contrasts. To determine whether hyperactivations occurred in regions that were activated or deactivated during the memory tasks, we compared signal intensities between the target conditions versus rest. Our results showed reduced activation in AD patients compared to controls in several core episodic memory regions, including the medial temporal structures, during both encoding and retrieval. Patients also showed hyperactivations compared to controls in a set of brain areas. Further analyses conducted on the signal extracted in these areas indicated that most of these hyperactivations actually reflected a failure of deactivation. Indeed, whereas almost all of these regions were significantly more activated at rest than during the target conditions in controls, only one region presented a similar pattern of deactivation in patients. Altogether, our findings suggest that hyperactivations in AD must be interpreted with caution and may not systematically reflect increased activity. Although there has been evidence supporting the existence of genuine compensatory mechanisms, dysfunction within the DMN may be responsible for part of the apparent hyperactivations reported in the literature on AD.

How cognitive performance-induced stress can influence right VLPFC activation: an fMRI study in healthy subjects and in patients with social phobia.

The neural bases of interactions between anxiety and cognitive control are not fully understood. We conducted an fMRI study in healthy participants and in patients with an anxiety disorder (social phobia) to determine the impact of stress on the brain network involved in cognitive control. Participants performed two working memory tasks that differed in their level of performance-induced stress. In both groups, the cognitive tasks activated a frontoparietal network, involved in working memory tasks. A supplementary activation was observed in the right ventrolateral prefrontal cortex (VLPFC) in patients during the more stressful cognitive task. Region of interest analyses showed that activation in the right VLPFC decreased in the more stressful condition as compared to the less stressful one in healthy subjects and remain at a similar level in the two cognitive tasks in patients. This pattern was specific to the right when compared to the left VLPFC activation. Anxiety was positively correlated with right VLPFC activation across groups. Finally, left dorsolateral prefrontal cortex (DLPFC) activation was higher in healthy subjects than in patients in the more stressful task. These findings demonstrate that in healthy subjects, stress induces an increased activation in left DLPFC, a critical region for cognitive control, and a decreased activation in the right VLPFC, an area associated with anxiety. In patients, the differential modulation between these dorsal and ventral PFC regions disappears. This absence of modulation may limit anxious patients' ability to adapt to demanding cognitive control tasks.

Tin-based mesoporous silica for the conversion of CO2 into dimethyl carbonate.

Sn-based SBA-15 was prepared by reacting di-n-butyldimethoxystannane with SBA-15 pretreated with trimethylchlorosilane (TMCS) to cap the external hydroxyl groups. Small-angle X-ray diffraction (SXRD), infrared spectroscopy (IR), nitrogen adsorption/desorption, transmission electron microscopy (TEM), thermogravimetric analysis (TGA), and inductively coupled plasma atomic emission (ICP-AES) measurements allow us to propose that the organotin species are located within the pore channels of the mesoporous host. This novel material catalyzes selectively the coupling of CO(2) with methanol to dimethyl carbonate (DMC). The reaction time-conversion dependence shows that a turnover number (TON) of 16 can be reached at 423 K under 20 MPa, which is among the highest reported so far in the absence of water traps. Moreover, as the catalytic activity is retained after recycling, even higher values can be obtained on a cumulative basis. A further TON increase is observed with the reaction temperature. Interestingly, the tin-based SBA-15 mesoporous material exhibits lower TONs if the TMCS pretreatment is left out. Therefore, the organotin species located outside the channels are far less active than those located within.

Imatinib is effective in children with previously untreated chronic myelogenous leukemia in early chronic phase: results of the French national phase IV trial.

PURPOSE: Imatinib is the standard of care in adults with chronic myeloid leukemia (CML) in chronic phase (CP). Only a few studies to assess efficacy in children have been performed. We report on the results of the French prospective trial (ClinicalTrials.gov identifier NCT00845221) conducted in children and adolescents with newly diagnosed CML in CP. PATIENTS AND METHODS: A total of 44 patients from age 10 months to 17 years with newly diagnosed CML in CP received daily imatinib 260 mg/m(2). Progression-free survival, responses, and tolerance were evaluated. RESULTS: With a median follow-up times of 31 months (range, 11 to 64 months), the estimated progression-free survival rate at 36 months was 98% (95% CI, 85% to 100%). A complete hematologic response was achieved in 98% of the patients. The rates of complete cytogenetic response (CCyR) and major molecular response (MMR) were 61% and 31% at 12 months, respectively. During follow-up, CCyR and MMR were achieved in 36 children (77%) and 25 children (57%), respectively. Overall, 30% of the patients discontinued imatinib, mainly because of unsatisfactory response. The most common adverse events were neutropenia and musculoskeletal events. CONCLUSION: Imatinib is effective in children with CML in CP with response rates similar to rates reported in adults. The adverse effects are acceptable, but longer follow-up studies are required to fully assess the long-term impact.

Cholinergic mesencephalic neurons are involved in gait and postural disorders in Parkinson disease.

Gait disorders and postural instability, which are commonly observed in elderly patients with Parkinson disease (PD), respond poorly to dopaminergic agents used to treat other parkinsonian symptoms. The brain structures underlying gait disorders and falls in PD and aging remain to be characterized. Using functional MRI in healthy human subjects, we have shown here that activity of the mesencephalic locomotor region (MLR), which is composed of the pedunculopontine nucleus (PPN) and the adjacent cuneiform nucleus, was modulated by the speed of imagined gait, with faster imagined gait activating a discrete cluster within the MLR. Furthermore, the presence of gait disorders in patients with PD and in aged monkeys rendered parkinsonian by MPTP intoxication correlated with loss of PPN cholinergic neurons. Bilateral lesioning of the cholinergic part of the PPN induced gait and postural deficits in nondopaminergic lesioned monkeys. Our data therefore reveal that the cholinergic neurons of the PPN play a central role in controlling gait and posture and represent a possible target for pharmacological treatment of gait disorders in PD.

Integration of differentiation signals during indirect flight muscle formation by a novel enhancer of Drosophila vestigial gene.

The gene vestigial (vg) plays a key role in indirect flight muscle (IFM) development. We show here that vg is controlled by the Notch anti-myogenic signaling pathway in myoblasts and is regulated by a novel 822 bp enhancer during IFM differentiation. Interestingly, this muscle enhancer is activated in developing fibers and in a small number of myoblasts before the fusion of myoblasts with the developing muscle fibers. Moreover, we show that this enhancer is activated by Drosophila Myocyte enhancing factor 2 (MEF2), Scalloped (SD) and VG but repressed by Twist, demonstrating a sensitivity to differentiation in vivo. In vitro experiments reveal that SD can directly bind this enhancer and MEF2 can physically interact with both SD and TWI. Cumulatively, our data reveal the interplay between different myogenic factors responsible for the expression of an enhancer activated during muscle differentiation.

Promotion of central nervous system remyelination by induced differentiation of oligodendrocyte precursor cells.

OBJECTIVE: Repair of demyelinated axons in diseases such as multiple sclerosis requires activation of the myelination program in existing or newly recruited oligodendrocyte precursor cells (OPCs). The control of OPC differentiation and initiation of myelination during repair is poorly understood. In this study, we test the ability of anti-LINGO-1 reagents to promote myelination in vitro and remyelination in the rodent adult central nervous system in vivo. METHODS: The effects of LINGO-1 antagonists on the differentiation of OPCs and the promotion of myelination has been assayed using a combination of coculture and slice culture preparations. Using three different animal models of demyelination and remyelination, we morphologically and functionally assessed the effects of LINGO-1 antagonists on OPC differentiation and myelin repair. RESULTS: The data indicate that in vitro treatment with antagonists of LINGO-1 promote OPC differentiation and myelination, whereas in vivo remyelination is accelerated in lysophosphatidylcholine- or cuprizone-induced demyelination. This remyelination is associated with enhanced OPC differentiation and functional recovery of conduction velocities in demyelinated axons. INTERPRETATION: Our studies demonstrate that LINGO-1 antagonism promotes OPC differentiation and remyelination, and suggest LINGO-1 functions as an inhibitor of OPC differentiation to retard central nervous system remyelination.