RESUMO
Single-molecule measurements of biomaterials bring novel insights into cellular events. For almost all of these events, post-translational modifications (PTMs), which alter the properties of proteins through their chemical modifications, constitute essential regulatory mechanisms. However, suitable single-molecule methodology to study PTMs is very limited. Here we show single-molecule detection of peptide phosphorylation, an archetypal PTM, based on electrical measurements. We found that the phosphate group stably bridges a nanogap between metal electrodes and exhibited high electrical conductance, which enables specific single-molecule detection of peptide phosphorylation. The present methodology paves the way to single-molecule studies of PTMs, such as single-molecule kinetics for enzymatic modification of proteins as shown here.
Assuntos
Peptídeos , Fosfatos , Materiais Biocompatíveis , Peptídeos/metabolismo , Fosfatos/metabolismo , Fosforilação , Processamento de Proteína Pós-Traducional , Proteínas/metabolismoRESUMO
OBJECTIVE: In 2012, a large number of myositis cases with anti-mitochondrial M2 (AMA-M2) antibody, which had well been known as the serological hallmark for primary biliary cholangitis (PBC), were reported in Japan. Recently, some case series from Japan, France, America, China and India have shown that approximately 2.5% to 19.5% of patients with myositis have AMA-M2 antibody. The objective of this study was to clarify the prevalence, clinical features, treatment outcome, and severity determinants of AMA-M2 positive myositis. METHODS: This study was a multicenter observational study. We enrolled patients who were diagnosed with myositis during a ten-year period between 2012 and 2021. RESULTS: Of the total of 185 patients with inflammatory myopathy, 17 patients were positive for AMA-M2 antibody. The typical symptoms were weakness mainly involving paravertebral muscles, weight loss, respiratory failure, and cardiac complications. Thirteen of the 17 patients had cardiac complications. A strong correlation was found between respiratory failure and modified Rankin Scale (mRS) score. A strong correlation was also found between respiratory failure and body weight, indicating that weight loss can be an indicator of potential progression of respiratory failure. Six of the 17 patients were complicated by malignancy. CONCLUSIONS: This study showed significant correlations between % vital capacity (VC), body mass index (BMI), and mRS score in patients with AMA-M2-positive myositis. Immunotherapy often improved CK level and respiratory dysfunction. We therefore propose that %VC and BMI should be monitored as disease indicators in treatment of AMA-M2-positive myositis.
Assuntos
Cirrose Hepática Biliar , Miosite , Insuficiência Respiratória , Humanos , Cirrose Hepática Biliar/diagnóstico , Autoanticorpos , Miosite/diagnóstico , Miosite/terapia , Redução de PesoRESUMO
Myasthenia gravis (MG) is an immune-related adverse event (irAE), and as an irAE, MG (irAE-MG) generally has a monophasic course, with only a few case reports of irAE-MG flare-ups during the course of the disease. We herein report a case of pembrolizumab-induced MG with relapsing symptoms. irAE-MG is a rare disease that has not yet been fully characterized, and our case shows that MG symptoms may relapse. Therefore, regular follow-up is necessary, even after the symptoms improve with immunosuppressive therapy.
Assuntos
Miastenia Gravis , Recidiva Local de Neoplasia , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Miastenia Gravis/induzido quimicamente , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/diagnóstico , Terapia de ImunossupressãoRESUMO
A 42-year-old man with a history of two previous coronary embolisms was referred to our hospital. He had been experiencing muscle weakness since he was around 40 years old. He had muscle atrophy of the scapula, upper arm, and lower extremities, and electromyography revealed myogenic changes in the limb muscles. Histopathological analysis of the muscle biopsy specimen revealed a complete deficiency of emerin protein, and genetic examination revealed a mutation in the emerin (EMD) gene, resulting in a diagnosis of Emery-Dreifuss muscular dystrophy (EDMD). EDMD is a muscular disorder with three symptoms: joint contracture at early onset, muscle weakness and atrophy, and cardiac dysfunction. Although this patient showed no obvious joint contracture, the course and clinical symptoms vary among patients. Therefore, in patients in whom clinical diagnosis is difficult, muscle biopsy and genetic testing should be performed for EDMD in order to prevent sudden death due to this disease.
Assuntos
Contratura , Articulações , Distrofia Muscular de Emery-Dreifuss/diagnóstico , Adulto , Contratura/patologia , Humanos , Articulações/patologia , Masculino , Proteínas de Membrana/genética , Debilidade Muscular/patologia , Músculo Esquelético/patologia , Atrofia Muscular/patologia , Distrofia Muscular de Emery-Dreifuss/genética , Distrofia Muscular de Emery-Dreifuss/patologia , Mutação , Proteínas Nucleares/genéticaRESUMO
Molecular isomerism has been discussed from the viewpoint of the tiniest switch and memory elements in electronics. Here, we report an overcrowded ethylene-based molecular conductance switch, which fulfills all the essential requirements for implementation into electronic devices, namely, electric-field-controllable reversible conductance change with a molecular-level spatial resolution, robust conformational bistability under ambient conditions, and ordered monolayer formation on electrode surfaces. The conformational state of this overcrowded ethylene, represented by a folded or twisted conformer, is susceptible to external environments. Nanoscopic measurements using scanning tunneling microscopy techniques, together with theoretical simulations, revealed the electronic properties of each conformer adsorbed on Au(111). While the twisted conformer prevails in the molecularly dispersed state, upon self-assembly into a monolayer, a two-dimensional network structure of the folded conformer is preferentially formed due to particular intermolecular interaction. In the monolayer state, folded-to-twisted and its reverse isomerization can be controlled by the modulation of electric fields.