Amyloid fibril structures link CHCHD10 and CHCHD2 to neurodegeneration.

CHCHD10 is mutated in rare cases of FTD and ALS and aggregates in mouse models of disease. Here we show that the disordered N-terminal domain of CHCHD10 forms amyloid fibrils and report their cryoEM structure. Disease-associated mutations cannot be accommodated by the WT fibril structure, while sequence differences between CHCHD10 and CHCHD2 are tolerated, explaining the co-aggregation of the two proteins and linking CHCHD10 and CHCHD2 amyloid fibrils to neurodegeneration.

Control of G protein-coupled receptor function via membrane-interacting intrinsically disordered C-terminal domains.

G protein-coupled receptors (GPCRs) control intracellular signaling cascades via agonist-dependent coupling to intracellular transducers including heterotrimeric G proteins, GPCR kinases (GRKs), and arrestins. In addition to their critical interactions with the transmembrane core of active GPCRs, all three classes of transducers have also been reported to interact with receptor C-terminal domains (CTDs). An underexplored aspect of GPCR CTDs is their possible role as lipid sensors given their proximity to the membrane.

Control of G protein-coupled receptor function via membrane-interacting intrinsically disordered C-terminal domains.

G protein-coupled receptors (GPCRs) control intracellular signaling cascades via agonist-dependent coupling to intracellular transducers including heterotrimeric G proteins, GPCR kinases (GRKs), and arrestins. In addition to their critical interactions with the transmembrane core of active GPCRs, all three classes of transducers have also been reported to interact with receptor C-terminal domains (CTDs). An underexplored aspect of GPCR CTDs is their possible role as lipid sensors given their proximity to the membrane.

SARS-CoV-2 antibodies in inflammatory neurological conditions: a multicentre retrospective comparative study.

It is well established that neurological and non-neurological autoimmune disorders can be triggered by viral infections. It remains unclear whether SARS-CoV-2 infection induces similar conditions and whether they show a distinctive phenotype. We retrospectively identified patients with acute inflammatory CNS conditions referred to our laboratory for antibody testing during the pandemic (March 1 to August 31, 2020).

Optical Nanosensor for Intracellular and Intracranial Detection of Amyloid-Beta.

Amyloid-beta (Aβ) deposition occurs in the early stages of Alzheimer's disease (AD), but the early detection of Aβ is a persistent challenge. Herein, we engineered a near-infrared optical nanosensor capable of detecting Aβ intracellularly in live cells and intracranially in vivo. The sensor is composed of single-walled carbon nanotubes functionalized with Aβ wherein Aβ-Aβ interactions drive the response.

Risk of disease relapse following COVID-19 vaccination in patients with AQP4-IgG-positive NMOSD and MOGAD.

Post-vaccination disease relapses have been reported in patients with MOGAD and AQP4-IgG+NMOSD. In this retrospective multicenter Italian study we assessed the frequency of relapses after SARS-CoV-2 vaccination. We included 56 cases: MOGAD, 30; AQP4-IgG+NMOSD, 26.

Post-translational modifications within tau paired helical filament nucleating motifs perturb microtubule interactions and oligomer formation.

Post-translationally modified tau is the primary component of tau neurofibrillary tangles, a pathological hallmark of Alzheimer's disease and other tauopathies. Post-translational modifications (PTMs) within the tau microtubule (MT)-binding domain (MBD), which encompasses two hexapeptide motifs that act as critical nucleating regions for tau aggregation, can potentially modulate tau aggregation as well as interactions with MTs and membranes. Here, we characterize the effects of a recently discovered tau PTM, lysine succinylation, on tau-tubulin interactions and compare these to the effects of two previously reported MBD modifications, lysine acetylation and tyrosine phosphorylation.

Ocrelizumab for the Treatment of Multiple Sclerosis: Safety, Efficacy, and Pharmacology.

The success of selective B-cells depleting therapies, as the anti-CD20 antibodies, in patients with multiple sclerosis (MS) has confirmed that B-cells are critical in the immune pathogenesis of the disease. Ocrelizumab, a humanized monoclonal antibody that selectively targets CD20+ B-cells, profoundly suppresses acute inflammatory disease activity, representing a highly effective therapy for relapsing-remitting multiple sclerosis (RRMS). It is also the first proven therapy able to slow disability progression in primary progressive multiple sclerosis (PPMS), particularly in patients with signs of acute radiological activity before being enrolled.

NfL levels predominantly increase at disease onset in MOG-Abs-associated disorders.

The unpredictable course and uncertain impact of relapses make treatment strategies of anti-myelin oligodendrocyte glycoprotein antibodies associated disorders (MOGAD) challenging. We analysed neurofilament light chain levels (NfL) in onset and follow-up sera of 18 patients with MOGAD to clarify the timing of axonal damage. In comparison with disease onset values (median 8.

Early use of low dose tocilizumab in patients with COVID-19: A retrospective cohort study with a complete follow-up.

Background: Pneumonia with severe respiratory failure represents the principal cause of death in COVID-19, where hyper-inflammation plays an important role in lung damage. An effective treatment aiming at reducing the inflammation without preventing virus clearance is thus urgently needed. Tocilizumab, an anti-soluble IL-6 receptor monoclonal antibody, has been proposed for treatment of patients with COVID-19.

Switching to ocrelizumab in RRMS patients at risk of PML previously treated with extended interval dosing of natalizumab.

Discontinuation of natalizumab in patients with relapsing-remitting multiple sclerosis (RRMS) at risk of progressive multifocal leukoencephalopathy (PML) is associated with disease reactivation. Forty-two RRMS patients, who switched from an extended interval dose (EID) of natalizumab to ocrelizumab, underwent magnetic resonance imaging (MRI) and clinical monitoring during washout and after ocrelizumab starting. During the first 3 months, disease reactivation was observed in five (12%) patients; 6 months after ocrelizumab starting, no further relapses were recorded, and Expanded Disability Status Scale (EDSS) remained stable in 38 (90%) patients.

Diagnostic features of initial demyelinating events associated with serum MOG-IgG.

Background: Myelin oligodendrocyte glycoprotein (MOG)-IgG associated disorders are increasingly recognized as a distinct disease entity. However, diagnostic sensitivity and specificity of serum MOG-IgG as well as recommendations for testing are still debated.

Materials And Methods: Between October 2015 and July 2017 we tested serum MOG-IgG in 91 adult patients (49 females) with a demyelinating event (DE) not fulfilling 2010 McDonald criteria for MS at sampling, negative for neuromyelitis optica (NMO)-IgG and followed-up for at least 12 months.

Induction Versus Escalation in Multiple Sclerosis: A 10-Year Real World Study.

In this independent, multicenter, post-marketing study, we directly compare induction immunosuppression versus escalation strategies on the risk of reaching the disability milestone of Expanded Disability Status Scale (EDSS) ≥ 6.0 over 10 years in previously untreated patients with relapsing-remitting multiple sclerosis. We collected data of patients who started interferon beta (escalation) versus mitoxantrone or cyclophosphamide (induction) as initial treatment.

Minimal evidence of disease activity (MEDA) in relapsing-remitting multiple sclerosis.

Objective: This study aimed to define the minimal evidence of disease activity (MEDA) during treatment that can be tolerated without exposing patients with relapsing-remitting multiple sclerosis at risk of long-term disability.

Methods: We retrospectively collected data of patients followed up to 10 years after starting interferon beta or glatiramer acetate. Survival analyses explored the association between the long-term risk of reaching an Expanded Disability Status Scale≥6.

Kartogenin-loaded coaxial PGS/PCL aligned nanofibers for cartilage tissue engineering.

Electrospinning is a valuable technology for cartilage tissue engineering (CTE) due to its ability to produce fibrous scaffolds mimicking the nanoscale and alignment of collagen fibers present within the superficial zone of articular cartilage. Coaxial electrospinning allows the fabrication of core-shell fibers able to incorporate and release bioactive molecules (e.g.

Distinct serum and cerebrospinal fluid cytokine and chemokine profiles in autoantibody-associated demyelinating diseases.

Background: Demyelinating diseases of the central nervous system associated with autoantibodies against aquaporin-4 and myelin-oligodendrocyte-glycoprotein are mediated by different immunopathological mechanisms compared to multiple sclerosis.

Objective: The purpose of this study was to evaluate serum and cerebrospinal fluid cytokine/chemokine profiles in patients with autoantibodies against aquaporin-4 or autoantibodies against myelin-oligodendrocyte-glycoprotein-associated demyelination compared to multiple sclerosis and autoimmune encephalitis.

Methods: Serum and cerebrospinal fluid cytokine/chemokine levels were analysed using Procartaplex Multiplex Immunoassays.

Novel Cellulose-Halloysite Hemostatic Nanocomposite Fibers with a Dramatic Reduction in Human Plasma Coagulation Time.

High-performance cellulose-halloysite hemostatic nanocomposite fibers (CHNFs) are fabricated using a one-step wet-wet electrospinning process and evaluated for human plasma coagulation by activated partial thromboplastin time. These novel biocompatible CHNFs exhibit 2.4 times faster plasma coagulation time compared with the industry gold standard QuikClot Combat Gauze (QCG).

Mycobacterium avium subspecies paratuberculosis and myelin basic protein specific epitopes are highly recognized by sera from patients with Neuromyelitis optica spectrum disorder.

Epstein-Barr virus (EBV) is the main environmental agent associated to neuromyelitis optica spectrum disorder (NMOSD). Following to studies reporting an increased prevalence of antibodies against peptides derived from Mycobacterium avium subsp. paratuberculosis (MAP) homologous to EBV and human epitopes (MBP, IRF5) in multiple sclerosis (MS), we investigated whether seroreactivity to these antigens display a NMOSD-specific pattern.

Antibody response against HERV-W env surface peptides differentiates multiple sclerosis and neuromyelitis optica spectrum disorder.

Background: A specific humoral immune response against HERV-W envelope surface (env-su) glycoprotein antigens has been reported in serum of patients with multiple sclerosis (MS). However, it has not been evaluated to date in patients with neuromyelitis optica spectrum disorder (NMOSD).

Objective: The objective of this paper is to investigate whether antibody (Ab) response against HERV-W env-su antigenic peptides differs between NMOSD and MS.