A mutation in codon 717 of the CHO-K1 elongation factor 2 gene prevents the first step in the biosynthesis of diphthamide

The histidine residue at position 715 of elongation factor 2 (EF-2) is posttranslationally modified in a series of enzymatic reactions to 2-[3-carboxyamido-3-(trimethylammonio)-propyl]histidine, which has been given the trivial name diphthamide. The diphthamide residue of EF-2 is the target site for ADP ribosylation by diphtheria toxin and Pseudomonas exotoxin A. ADP-ribosylated EF-2 does not function in protein synthesis. EF-2 that has not been posttranslationally modified at histidine 715 is resistant to ADP ribosylation by these toxins. In this report we show that a G-to-A transition in the first position of codon 717 of the EF-2 gene results in substitution of arginine for glycine and prevents addition of the side chain of diphthamide to histidine 715 of EF-2. EF-2 produced by the mutant gene is fully functional in protein synthesis.This work was supported by Public Health Service grant AI-09100 from the National Institute of Allergy and Infectious Diseases and by Biomedical Research Support Grant PHS07RR05429-27. Brian Foley is supported by a Cancer Biology Training Grant T32Ca-09286 from the National Cancer Institute.     

Visual function in Huntington's disease patients and presymptomatic gene carriers.

Disturbances of visual cognition, visuomotor performance, and visual memory have been described frequently in Huntington's disease (HD). Early stage visual abnormalities could contribute to these deficits. We evaluated visual processing in 20 control subjects who were non-gene carriers at risk for HD, nine presymptomatic gene-positive subjects, and eight subjects with a recent diagnosis of Huntington's disease. Visual perceptual tests of contrast sensitivity and motion discrimination were used to probe early stage visual processing. Extraocular movements were evaluated in a neurologic examination, and the Digit Symbol test was used to test visual motor performance. Contrast sensitivity did not differ among the three groups. Motion discrimination was impaired in HD subjects but not in the presymptomatic gene carriers when compared to gene noncarriers. Among gene carriers, impaired motion discrimination performance was associated with poorer Digit Symbol performance and extraocular abnormalities. These findings suggest that the early stages of HD are associated with disturbances of motion perception as well as disruptions of visual motor and ocular motor performance.     

Gender differences in young adults' beliefs about sunscreen use.

This study employs focus group methodology to explore gender differences in sunscreen use. Guided by the theory of reasoned action, males and females were found to differ on each of the following constructs: behavior, behavioral beliefs, and normative beliefs. Males and females differed in their sunscreen use, with females adopting a more preventive style of sunscreen use and males a more reactive style. Males and females differed in their salient beliefs that motivated their sunscreen use, many of which were related to traditional American gender roles. In addition, although males and females were aware of both positive and negative sources of normative beliefs regarding sunscreen use, females received more encouragement from their mothers and peers than males. Findings are discussed in terms of their implications for the design of future interventions.     

NMDA Receptor Activation Triggers Voltage Oscillations, Plateau Potentials and Burstinq in Neonatal Rat Lumbar Motoneurons ln Vitro

Whole-cell recordings of lumbar motoneurons in the intact neonatal rat spinal cord in vitro were undertaken to examine the effects of Kmethyl-D-aspartate (NMDA) receptor activation on membrane behaviour. Bath application of NMDA induced rhythmic voltage oscillations of 5.9 ± 2.1 mV (SD) at a frequency of 4.4 ± 1.5 Hz. Amplitude, but not frequency, of the voltage oscillations was membrane potential-dependent. Voltage oscillations could recruit action potentials and/or plateau potentials with or without superimposed bursting. Blockade of synaptic transmission with tetrodotoxin (TTX) sometimes resulted in a loss of oscillatory activity which could then be restored by increasing the NMDA concentration. After application of TTX, the trajectory of NMDA-induced oscillations was similar to the trajectory induced in the presence of intact synaptic networks, although the mean oscillation duration was longer and the oscillation frequency was slower (1.8 ± 1.1 Hz). Current ramps delivered after bath application of NMDA demonstrated bistable membrane properties which may underlie the plateau potentials. Injection of intracellular current pulses could initiate, entrain and terminate individual plateau potentials. The results suggest that membrane depolarization produced by oscillations may activate other intrinsic conductances which generate plateau potentials, thereby providing the neuron with enhanced voltage sensitivity, compared to that produced by NMDA receptor activation alone. These oscillatory events may have a role in the regulation of motor output in a variety of rhythmic behaviours including locomotion.