Anomalous cellular proliferation in vitro associated with Huntington's disease

Summary Detailed growth analyses of cultured skin fibroblasts from two patients with Huntington's Disease (HD) were compared with those from controls matched for age and sex. In contrast to control cells, HD fibroblasts plated more efficiently at the low seeding densities used. Subsequent exponential growth of HD cultures was more stable towards routine trypsinisation than that of controls. However, the most striking feature of HD cultures was their ability to grow to significantly higher cell saturation densities. Experiments with trypsinised and untrypsinised cultures imply an inherent alteration in the HD cell membrane.     

Nucleotide sequences of HS-α satellite DNA from kangaroo rat dipodomys ordii and characterization of similar sequences in other rodents

The most common repeated nucleotide sequences of the highly repetitive satellite HS-α fraction from kangaroo rat Dipodomys ordii was determined using ribosubstitution methods. This sequence was α nucleotides long and represented about 25% of the total HS-α satellite DNA, while the remaining DNA was composed of sequence variants related to the most common sequence. The sequences of the commonest of these variants are reported. Furthermore, the most common repeated sequence was identical to that reported for the α satellite of guinea pig Cavia porcellus. The α satellites of guinea pig, Cavia porcellus, pocket gopher, Thomomys bottae and antelope ground squirrel, Ammospermophilus leucurus, are shown to have sequences in common with the kangaroo rat. This implies that the simplest repeated sequences of mammalian satellite DNAs may persist over much longer evolutionary times than previously thought.Attempts to explain the very rapid quantitative changes in satellites whose sequence is strongly conserved have led us to consider that they might have a role in sympatric speciation. Among the novel features of the model presented is that fluctuations in satellites could be due to “speciation genes.” Such genes would confer a strong selective advantage in certain situations, and could explain the many puzzling instances in which large numbers of new related species have appeared over a short evolutionary span.     

Carrier-mediated Uptake of Arginine and Urea by Volvox carteri f. nagariensis

Volvox carteri f. nagariensis takes up arginine via a high affinity, highly specific carrier, whereas carriers for neutral and acidic amino acids cannot be detected (even in nitrogen-starved cultures). Exogenous arginine is accumulated against a steep concentration gradient and is incorporated into protein with high efficiency, but it is not catabolized to any significant extent and will not serve as a nitrogen source adequate to support growth. Urea is also taken up by a saturable carrier, but several lines of evidence indicate that the arginine and urea carriers are distinct and different. Preexposure to arginine suppresses arginine uptake while stimulating urea uptake. The K_i values observed for reciprocal, competitive inhibition of uptake by arginine and urea are orders of magnitude different from the respective K_m values for uptake. The two uptake systems show entirely different patterns of sensitivity to inhibition by structural analogs. Finally, the V_max values for arginine and urea uptake fluctuate independently (but in a regular pattern) during the asexual life cycle. The fluctuations of urea uptake activity are of considerable magnitude and appear to be linked to key phases of the developmental program.     

Retinal illumination produces synaptic inhibition of a neurosecretory organ in the crayfish,pacifastacus leniusculus (Dana)

We have identified a cluster of neurosecretory cells in the crayfish eyestalk that possess dendrites in the second optic neuropil (Medulla) and project axons to the first optic neuropil (Lamina). Illumination of the ipsilateral retina produces a synaptic inhibition of these cells that is mimicked by iontophoresis of gamma-aminobutyric acid within the medullary neuropil. The neurosecretory nature of the cells, the efferent projection of their axons, and the strong inhibition of their spiking activity upon retinal illumination suggest that they may be involved in the feedback control of dark adaptation and/or circadian changes in visual sensitivity.     

Innervation and motor patterns of the abdominal superficial flexor muscles in larval lobsters

The pattern of innervation and motor program of the abdominal superficial flexor muscle was investigated electrophysiologically in larval lobsters (Homarus americanus). The muscle receives both excitatory and inhibitory innervation in the larval as well as in the embryonic stages. Individual muscle fibers receive a single inhibitory neuron (f5) and a maximum of three excitors. Based on spike heights these axons belong to either the small (f1 or f2) or large (f3, f4) motoneurons. While the small axons preferentially innervate the medial muscle fibers the large axons innervate medial as well as lateral fibers. This larval pattern of innervation resembles the pattern in the adult lobster. The resemblance extends to the firing patterns as well with both large and small excitors firing spontaneously. Furthermore, evoked activity in the larvae produces reciprocal (and occasionally cyclical) bursts of excitor and inhibitor neurons denoting abdominal extension and flexion and resembling the firing patterns in adults. Consequently motor programs employed in steering the pelagic larvae are reminiscent of the programs for maintaining posture in the benthic adult lobsters.     

Dissecting the molecular mechanism of ion-solute cotransport: Substrate specificity mutations in theputP gene affect the kinetics of proline transport

Summary Rare mutations that alter the substrate specificity of proline permease cluster in discrete regions of theputP gene, suggesting that they may replace amino acids at the active site of the enzyme. IfputP substrate specificity mutations directly alter the active site of proline permease, the mutants should show specific defects in the kinetics of proline transport. In order to test this prediction, we examined the kinetics of threeputP substrate specificity mutants. One class of mutation increases theK _m over 120-fold but only decreases theV _max fourfold. SuchK _m mutants may be specifically defective in substrate recognition, thus identifying an amino acid critical for substrate binding. Another class of mutation decreases theV _max 80-fold without changing theK _m .V _max mutants appear to alter the rate of substrate translocation without affecting the substrate binding site. The last class of mutation alters both theK _m andV _max of proline transport. These results indicate that substrate specificity mutations alter amino acids critical for Na⁺/proline symport.