ABSTRACT
Muonic helium atom hyperfine structure (HFS) measurements are a sensitive tool to test the three-body atomic system and bound-state quantum electrodynamics theory, and determine fundamental constants of the negative muon magnetic moment and mass. The world's most intense pulsed negative muon beam at the Muon Science Facility of the Japan Proton Accelerator Research Complex allows improvement of previous measurements and testing further CPT invariance by comparing the magnetic moments and masses of positive and negative muons (second-generation leptons). We report new ground-state HFS measurements of muonic helium-4 atoms at a near-zero magnetic field, performed for the first time using a small admixture of CH_{4} as an electron donor to form neutral muonic helium atoms efficiently. Our analysis gives Δν=4464.980(20) MHz (4.5 ppm), which is more precise than both previous measurements at weak and high fields. The muonium ground-state HFS was also measured under the same conditions to investigate the isotopic effect on the frequency shift due to the gas density dependence in He with CH_{4} admixture and compared with previous studies. Muonium and muonic helium can be regarded as light and heavy hydrogen isotopes with an isotopic mass ratio of 36. No isotopic effect was observed within the current experimental precision.
ABSTRACT
BACKGROUND AND PURPOSE: The microrchidia family CW-type zinc finger 2 gene (MORC2) was newly identified as a causative gene of Charcot-Marie-Tooth disease (CMT) type 2Z in 2016. We aimed to describe the clinical and mutational spectrum of patients with CMT harboring MORC2 mutations in Japan. METHODS: We analyzed samples from 781 unrelated patients clinically diagnosed with CMT using deoxyribonucleic acid microarray or targeted resequencing by next-generation sequencing, and samples from 434 mutation-negative patients were subjected to whole-exome sequencing. We extracted MORC2 variants from these whole-exome sequencing data and classified them according to American College of Medical Genetics standards and guidelines. RESULTS: We identified MORC2 variants in 13 patients. As the second most common causative gene of CMT type 2 after MFN2, MORC2 variants were detected in 2.7% of patients with CMT type 2. The mean age of onset was 10.3 ± 8.7 years, and the inheritance pattern was mostly sporadic (11/13 patients, 84.6%). The clinical phenotype was typically length-dependent polyneuropathy, and electrophysiological studies revealed sensory-dominant axonal neuropathy. Mental retardation was identified in 4/13 patients (30.8%). p.Arg190Trp, as a mutational hotspot, was observed in eight unrelated families. We also identified two novel probably pathogenic variants, p.Cys345Tyr and p.Ala369Val, and one novel uncertain significance variant, p.Tyr332Cys. CONCLUSIONS: Our study is the largest report of patients harboring MORC2 variants. We revealed a clinical and mutational spectrum of Japanese patients with MORC2 variants. More attention should be paid to cognitive impairment, and the responsible mechanism requires further research for elucidation.
Subject(s)
Charcot-Marie-Tooth Disease/genetics , Mutation , Transcription Factors/genetics , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Japan , Male , Middle Aged , Phenotype , Young AdultSubject(s)
Face/abnormalities , Hyperventilation , Psychomotor Disorders , Adult , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors , Basic Helix-Loop-Helix Transcription Factors , DNA-Binding Proteins/genetics , Humans , Hyperventilation/diagnosis , Hyperventilation/genetics , Male , Mutation , Psychomotor Disorders/diagnosis , Psychomotor Disorders/genetics , Syndrome , Transcription Factor 4 , Transcription Factors/geneticsABSTRACT
PURPOSE: Biliary organic anion excretion is mediated by an ATP-dependent primary active transporter, a so-called canalicular multispecific organic anion transporter (cMOAT). As there appear to be many canalicular organic anion transports, we examined the effects of various organic anions and bile acid conjugates on the biliary excretion of pravastatin in rats. METHODS: [14C]pravastatin was intravenously injected into rats with bile drainage in the presence and absence of the continuous infusion of organic anions and bile acids, and radioactivity of its biliary excretion was studied. RESULTS: Biliary excretion of [14C]pravastatin was markedly inhibited by sulfobromophthalein-glutathione, taurolithocholate-3-sulfate, ursodeoxycholate-3, 7-sulfate, and ursodeoxycholate-3-O-glucuronide. In contrast, dibromosulfophthalein only slightly inhibited biliary pravastatin excretion, and cefpiramide did not affect biliary pravastatin excretion. CONCLUSIONS: These findings further support the multiplicity of canalicular organic anion transport, and pravastatin is considered to be excreted through a canalicular transporter which is absent in EHBR in addition to through cMOAT.
