ABSTRACT
FtsJ RNA 2'-O-methyltransferase 1 (FTSJ1) gene has been implicated in X-linked intellectual disability (XLID), but the molecular pathogenesis is unknown. We show that Ftsj1 is responsible for 2'-O-methylation of 11 species of cytosolic transfer RNAs (tRNAs) at the anticodon region, and these modifications are abolished in Ftsj1 knockout (KO) mice and XLID patient-derived cells. Loss of 2'-O-methylation in Ftsj1 KO mouse selectively reduced the steady-state level of tRNAPhe in the brain, resulting in a slow decoding at Phe codons. Ribosome profiling showed that translation efficiency is significantly reduced in a subset of genes that need to be efficiently translated to support synaptic organization and functions. Ftsj1 KO mice display immature synaptic morphology and aberrant synaptic plasticity, which are associated with anxiety-like and memory deficits. The data illuminate a fundamental role of tRNA modification in the brain through regulation of translation efficiency and provide mechanistic insights into FTSJ1-related XLID.
Subject(s)
Dentists/economics , General Practice, Dental/economics , Pensions , State Dentistry/economics , HumansSubject(s)
Anti-Bacterial Agents/administration & dosage , Apicoectomy , Metronidazole/administration & dosage , Surgical Wound Infection/prevention & control , Tooth Extraction , Apicoectomy/adverse effects , Humans , Postoperative Care , Surgical Wound Infection/etiology , Tooth Extraction/adverse effectsSubject(s)
Referral and Consultation/economics , Reimbursement Mechanisms/organization & administration , State Dentistry/organization & administration , Humans , Referral and Consultation/organization & administration , State Dentistry/economics , Surgery, Oral/economics , Surgery, Oral/organization & administration , United KingdomABSTRACT
A thin, large area transparent transmission chamber mounted below the accessory tray is described and its suitability for daily treatment delivery consistency is investigated. The sensitivity of the detector to changes in monitor unit setting, field size, wedge size, missing blocks, and wedges is presented. Some of the other potential applications are also discussed.
Subject(s)
Particle Accelerators , Radiotherapy Dosage , Radiotherapy/instrumentation , Humans , Radiotherapy/methods , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
An insert for a well ionization chamber is described for quality assurance tests for high dose rate remote afterloaders. The use of this insert over time has shown its applicability for efficient QA tests for the high dose rate afterloader. The measurement results are six times greater than the uncertainties involved for the measurements. Checks on position can be made better than 1 mm and dwell times better than 1 s. The overall measurements can be done to better than 1.5%. QA checks can be accomplished in a shorter time period with as great or better accuracy than prior film techniques.
Subject(s)
Brachytherapy/standards , Models, Structural , Radiotherapy Dosage/standards , Humans , Lead , Mathematics , Quality Assurance, Health Care , Quality Control , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
3-[18F]Fluoro-alpha-fluoromethyl-p-tyrosine (3-F-FMPT) was evaluated as a tracer for CNS tyrosine hydroxylase (TH) activity in rodents and in a rhesus monkey. Results of in vitro experiments using rat striatal homogenates showed that the introduction of fluorine into the 3-phenyl position did not significantly alter the ability of FMPT to act as a TH-activated L-aromatic amino acid decarboxylase (L-AAAD) inhibitor. These studies further showed that 3-F-FMPT-induced L-AAAD inhibition was dose-dependent. Furthermore, striatal homogenates prepared from rats pretreated with the potent TH inhibitor alpha-methyl-p-tyrosine was found to have diminished 3-F-FMPT-induced L-AAAD inhibition. However, despite these promising in vitro results, the biodistribution of this compound in mice showed low brain uptake and fast clearance through the kidneys. A PET study using a Rhesus monkey injected with 3-[18F]F-FMPT confirmed the results obtained in mice, i.e. negligible brain uptake but high localization in the bladder. We conclude that 3-[18F]F-FMPT would not be useful as a tracer for cerebral TH activity.