Pharmacological characterization of mutant huntingtin aggregate-directed PET imaging tracer candidates.

Huntington's disease (HD) is caused by a CAG trinucleotide repeat expansion in the first exon of the huntingtin (HTT) gene coding for the huntingtin (HTT) protein. The misfolding and consequential aggregation of CAG-expanded mutant HTT (mHTT) underpin HD pathology. Our interest in the life cycle of HTT led us to consider the development of high-affinity small-molecule binders of HTT oligomerized/amyloid-containing species that could serve as either cellular and in vivo imaging tools or potential therapeutic agents.

The phenotypic spectrum of SCN8A encephalopathy.

Objective: SCN8A encodes the sodium channel voltage-gated α8-subunit (Nav1.6). SCN8A mutations have recently been associated with epilepsy and neurodevelopmental disorders.

Pyridoxine responsiveness in novel mutations of the PNPO gene.

Objective: To determine whether patients with pyridoxine-responsive seizures but normal biomarkers for antiquitin deficiency and normal sequencing of the ALDH7A1 gene may have PNPO mutations.

Methods: We sequenced the PNPO gene in 31 patients who fulfilled the above-mentioned criteria.

Results: We were able to identify 11 patients carrying 3 novel mutations of the PNPO gene.

Development of an evidence-based application and rubric for evaluating applicants' qualifications for promotion to professor.

Objective: Every promotion committee is challenged by the need to make value judgments on the quantity and quality of peer work. Decisions based upon subjective assessments may not do justice to the applicant's or the institution's needs. The purpose of this article is to (1) describe the process a college promotion committee used to increase the objectivity brought to this activity, (2) present the tools developed that facilitated the collection and evaluation of faculty work, and (3) describe their usage in a promotion cycle.

Analysis of [14C]-saterinone and its metabolites in dog plasma, urine and bile by high-performance liquid chromatography with radioactivity and fluorescence detection and by mass spectrometry.

An HPLC method was developed for the direct on-line radioactivity determination of [14C]-saterinone and its metabolites in biological canine fluids after intravenous and intraduodenal administration. After direct injection of 200 microliters of sample, the metabolites were separated on a semi-preparative reverse-phase column. The metabolites were identified by HPLC reference standards, enzymatic hydrolysis and mass spectrometry.