The Caenorhabditis elegans unc-45 locus has been proposed to encode a protein machine for myosin assembly. The UNC-45 protein is predicted to contain an NH2-terminal domain with three tetratricopeptide repeat motifs, a unique central region, and a COOH-terminal domain homologous to CRO1 and She4p. CRO1 and She4p are fungal proteins required for the segregation of other molecules in budding, endocytosis, and septation. Three mutations that lead to temperature-sensitive (ts) alleles have been localized to conserved residues within the CRO1/She4p-like domain, and two lethal alleles were found to result from stop codon mutations in the central region that would prevent translation of the COOH-terminal domain. Electron microscopy shows that thick filament accumulation in vivo is decreased by ∼50% in the CB286 ts mutant grown at the restrictive temperature. The thick filaments that assemble have abnormal structure. Immunofluorescence and immunoelectron microscopy show that myosins A and B are scrambled, in contrast to their assembly into distinct regions at the permissive temperature and in wild type. This abnormal structure correlates with the high degree of instability of the filaments in vitro as reflected by their extremely low yields and shortened lengths upon isolation. These results implicate the UNC-45 CRO1/She4p-like region in the assembly of myosin isoforms in C. elegans and suggest a possible common mechanism for the function of this UCS (UNC-45/CRO1/She4p) protein family.

We recently identified a frame-shift mutation in the PAX9 gene as the underlying cause for hypodontia involving permanent molar teeth segregating in an autosomal dominant pattern in a single large family (Stockton et al. 2000). Here we report a small nuclear family in which a father and his daughter are affected with severe hypodontia, involving agenesis of all primary and permanent molars, evidently caused by deletion of the entire PAX9 gene. Hemizygosity at the PAX9 locus in the two affected individuals was initially discovered when an informative single nucleotide polymorphism, identified while sequencing the gene for mutations, appeared to demonstrate non-Mendelian inheritance. Fluorescence in situ hybridization (FISH) analysis with a cosmid containing the PAX9 gene yielded a signal on only one chromosome 14 homologue and confirmed the presence of a deletion encompassing the PAX9 locus. Analysis of microsatellite loci in the vicinity of PAX9 delineated one breakpoint of the deletion. These data, in concert with FISH analysis with cosmids encompassing a 199 kb region, indicated that the deletion is between approximately 44 kb and 100 kb. PAX9 is one of two genes, and the only odontogenic gene within the deletion interval, thus supporting the model of haploinsufficiency for PAX9 as the underlying basis for hypodontia.

Introduction Comprehensive Behavioral Intervention for Tics (CBIT) has been shown to be efficacious for Chronic Tic Disorders (CTDs), but utilization is limited by a lack of treatment providers and perceived financial and time burden of commuting to treatment. A promising alternative to in-person delivery is Voice over Internet Protocol (VoIP), allowing for remote, real-time treatment delivery to patients’ homes. However, little is known about the effectiveness of VoIP for CTDs. Therefore, the present study examined the preliminary efficacy, feasibility, and acceptability of VoIP-delivered CBIT (CBIT-VoIP). Methods Twenty youth (8–17) with CTDs participated in a randomized, waitlist-controlled pilot trial of CBIT-VoIP. The main outcome was pre- to post-treatment change in clinician-rated tic severity (Yale Global Tic Severity Scale). The secondary outcome was clinical responder rate (Clinical Global Impressions – Improvement Scale), assessed using ratings of ‘very much improved’ or ‘much improved’ indicating positive treatment response. Results Intention-to-treat analyses with the last observation carried forward were performed. At post-treatment (10-weeks), significantly greater reductions in clinician-rated, [F (1, 18) = 3.05, p < 0.05, partial η2 = 0.15], and parent-reported tic severity, [F (1, 18) = 6.37, p < 0.05, partial η2 = .26] were found in CBIT-VoIP relative to waitlist. One-third (N = 4) of those in CBIT-VoIP were considered treatment responders. Treatment satisfaction and therapeutic alliance were high. Discussion: CBIT can be delivered via VoIP with high patient satisfaction, using accessible, low-cost equipment. CBIT-VoIP was generally feasible to implement, with some audio and visual challenges. Modifications to enhance treatment delivery are suggested.

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The nifJ gene of KkebsieUa pneumoniae encodes an oxidoreductase required for the transfer of electrons from pyruvate to flavodoxin, which reduces nitrogenase. The