A mutant allele of the SUP45 (SAL4) gene of Saccharomyces cerevisiae shows temperature-dependent allosuppressor and omnipotent suppressor phenotypes

Using a plasmid-based termination-read-through assay, the sal4-2 conditional-lethal (temperature-sensitive) allele of the SUP45 (SAL4) gene was shown to enhance the efficiency of the weak ochre suppressor tRNA SUQ5 some 10-fold at 30°C. Additionally, this allele increased the suppressor efficiency of SRM2-2, a weak tRNA^Gln ochre suppressor, indicating that the allosuppressor phenotype is not SUQ5-specific. A sup ⁺ sal4-2 strain also showed a temperature-dependent omnipotent suppressor phenotype, enhancing readthrough of all three termination codons. Combining the sal4-2 allele with an efficient tRNA nonsense suppressor (SUP4) increased the temperature-sensitivity of that strain, indicating that enhanced nonsense suppressor levels contribute to the conditional-lethality conferred by the sal4-2 allele. However, UGA suppression levels in a sup ⁺ sal4-2 strain following a shift to the non-permissive temperature reached a maximum significantly below that exhibited by a non-temperature sensitive SUP4 suppressor strain. Enhanced nonsense suppression may not therefore be the primary cause of the conditional-lethality of this allele. These data indicate a role for Sup45p in translation termination, and possibly in an additional, as yet unidentified, cellular process.     

Polypeptide chain termination in Saccharomyces cerevisiae

Summary The study of translational termination in yeast has been approached largely through the identification of a range of mutations which either increase or decrease the efficiency of stop-codon recognition. Subsequent cloning of the genes encoding these factors has identified a number of proteins important for maintaining the fidelity of termination, including at least three ribosomal proteins (S5, S13, S28). Other non-ribosomal proteins have been identified by mutations which produce gross termination-accuracy defects, namely the SUP35 and SUP45 gene products which have closely-related higher eukaryote homologues (GST1-h and SUP45-h respectively) and which can complement the corresponding defective yeast proteins, implying that the yeast ribosome may be a good model for the termination apparatus existing in higher translation systems.While the yeast mitochondrial release factor has been cloned (Pel et al. 1992), the corresponding cytosolic RF has not yet been identified. It seems likely, however, that the identification of the gene encoding eRF could be achieved using a multicopy antisuppressor screen such as that employed to clone the E. coli prfA gene (Weiss et al. 1984). Identification of the yeast eRF and an investigation of its interaction with other components of the yeast translational machinery will no doubt further the definition of the translational termination process.While a large number of mutations have been isolated in which the efficiency of termination-codon recognition is impaired, it seems probable that a proportion of mutations within this class will comprise those where the accuracy of A site codon-anticodon interaction is compromised: such defects would also have an effect on termination-codon suppression, allowing mis- or non-cognate tRNAs to bind stop-condons, causing nonsense suppression. The remainder of mutatoons affecting termination fidelity should represent mutations in genes coding for components of the termination apparatus, including the eRF: these mutations reduce the efficiency of termination, allowing nonsense suppression by low-efficiency natural suppressor tRNAs. Elucidation of the mechanism of termination in yeast will require discrimination between these two classes of mutations, thus allowing definition of termination-specific gene products.     

16PF items discriminating recidivists and long-term recovered polyaddicts

Responses to 65 of the 187 items on Cattell's 16PF test were skewed by 83 members of Alcoholics Anonymous. Seventeen of those items had significantly different distributions when the 18 recidivists were compared to the 8 who had remained clean of all addictive substances and compulsive behaviors during the 2-year period studied. Another 14 items had significantly different distributions when the recidivists were compared to all the others. Comparisons with non-drug-disadvantaged groups and non-AA recovering addicts are suggested in order to isolate empirical predictor items for "addictive" versus "cured" scales.     

Gaze-shift strategies during functional activity in progressive supranuclear palsy

The relative sparing of visual fixation in parallel with disruption of saccade function in progressive supranuclear palsy (PSP) creates a unique human model for the study of gaze-shift strategies which are adopted when vertical gaze palsy impairs primarily the eye-movement component of gaze control. It was hypothesized that people with PSP would rely on head pitch as a primary component of gaze shift during a platform stepping task and that there would be a predominance of fixation behavior (counter rotation of the eyes during head pitch) while attempting a down-gaze shift. Fourteen subjects with probable and 5 subjects with possible PSP participated in two experiments to measure visual fixation and gaze shift on the same continuum (using a derived vertical gaze fixation score, vGFS). Experiment #1 required gaze fixation during passive head pitch at 0.1–0.2 Hz, whereas experiment #2 required gaze shifts during a continuous platform step on, over, and off task. The primary gaze-shift strategy involved pitching the head downward to compensate for a loss in vertical saccade function. This strategy produced head pitch velocity that leads vertical eye velocity on the order of 200–500 ms. Gaze shifts during platform stepping showed greater fixation suppression (e.g., lower vGFS) in both groups of PSP compared to the visual stabilization task, but some subjects showed “fixation intrusion” during attempted gaze shift. The amount of eye movement was relatively constant when corrected for orbit height, whereas the extent of head pitch varied in proportion to the task demands. The mechanism controlling gaze in PSP, therefore appears to modulate head pitch independently of eye movement, but the gaze strategy seems dependent upon the extent of gaze dysfunction. These findings support the view that the desired gaze signal is parsed into separate eye and head pathways upstream from the burst neurons.     

Paraneoplastic chorea associated with CRMP-5 neuronal antibody and lung carcinoma

Paraneoplastic chorea is described in 16 patients: 11 with limited small-cell carcinoma, 2 with lung cancer revealed by imaging, 1 with renal cell carcinoma, and 1 with lymphoma. All had CRMP-5-IgG; 6 also had ANNA-1 (anti-Hu), including 1 without evident cancer. Chorea was the initial and most prominent symptom in 11 patients, asymmetric or unilateral in 5 patients, and part of a multifocal syndrome in 14 patients. Basal ganglia abnormalities were revealed by magnetic resonance imaging and at autopsy (as perivascular inflammation and microglial activation). Four patients improved with chemotherapy, and 2 improved with intravenous methylprednisolone.     

MR imaging of the postoperative meniscus of the knee

Surgery for tears of the menisci of the knee has evolved greatly over the last century and is now an extremely common procedure. Meniscal repair and conservative therapy are the preferred methods of treatment, but most symptomatic torn menisci do not meet the requirements for these options and necessitate partial meniscectomy. After surgery, patients often have recurrent pain and need additional diagnosis. Conventional magnetic resonance imaging (MRI) in the postoperative patient is very helpful at diagnosing extrameniscal pathology. It has lower sensitivity for detecting retears after partial meniscectomy, however, as it relies primarily on demonstration of fluid entering the meniscal retear on T2-weighted images. Similarly, conventional MRI is less accurate after meniscal repair, in which the repair site usually maintains altered signal for years. MR arthrography has higher sensitivity for detecting retears in menisci and is the procedure of choice in many situations.     

Superior labrum anterior-posterior (SLAP) tears: evaluation of three MR signs on T2-weighted images

PURPOSE: To compare the sensitivity and specificity of three magnetic resonance (MR) imaging signs for the diagnosis of superior labrum anterior-posterior (SLAP) tears. MATERIALS AND METHODS: The study involved 23 consecutive patients with a type 2, 3, or 4 SLAP tear at arthroscopy and 31 age-matched control patients with an arthroscopically normal or type 1 SLAP lesion. The superior labrum was evaluated on MR images for high signal intensity extending to the articular surface in the posterior third of the labrum, an irregular or laterally curved area of high signal intensity, or two high-signal-intensity lines. RESULTS: The sensitivity, specificity, and accuracy of posterior high signal intensity for a type 2, 3, or 4 SLAP tear were 48%, 94%, and 74%, respectively, for observer 1 and 61%, 81%, and 72%, respectively, for observer 2. For laterally curved area of high signal intensity, these values were 65%, 84%, and 76%, respectively, and 56%, 84%, and 72%, respectively. For two high-signal-intensity lines, these values were 17%, 94%, and 61%, respectively, and 13%, 94%, and 59%, respectively. For the presence of either posterior or laterally curved high signal intensity, the sensitivity was 65% for both observers, whereas the specificity was 84% for observer 1 and 74% for observer 2. The kappa values for interobserver agreement were 0.60 for posterior high signal intensity and 0.58 for laterally curved high signal intensity. CONCLUSION: Laterally curved and posterior high signal intensities are specific signs for distinguishing a SLAP tear from a normal-variant superior sublabral recess.