Late proliferation of retinal Müller cell progenitors facilitates preferential targeting with retroviral vectors in vitro

During vertebrate neural retina development, the relationship between mitotic activity in progenitor cells and the acquisition of a mature cell phenotype remains an area of controversy. The Müller glial cell has long been recognized as one of the last cell types of the retina to mature, which occurs under the influence of cell-cell interactions. In this report we examine the acquisition of the Müller cell phenotype in relation to mitotic activity. Using immunohistochemical markers, we demonstrate that a gene product characteristic of mature Müller cells, the 2M6 antigen, is expressed in mitotically active cells, even after all the major retina architectural features have been laid down. Furthermore, we show that retroviral infection, a process that requires mitotically active cells, preferentially targets Müller cell progenitors when late embryonic retina is infected in vitro. The two lines of evidence are consistent with a model for Müller cell differentiation that includes a mitotically active progenitor that has already begun to express specific differentiation gene products.     

Folding of omega-conotoxins. 2. Influence of precursor sequences and protein disulfide isomerase

The peptide Ca2+ channel antagonists found in the venoms of Conus snails, omega-conotoxins, are synthesized as precursors that include a leader peptide, presumed to direct the polypeptide to the endoplasmic reticulum, and a propeptide of unknown function. In addition, the precursors are synthesized with a C-terminal Gly residue that is posttranslationally converted to a terminal amide group. In order to determine whether the precursor sequences contain information that helps direct folding of the mature sequences, the disulfide-coupled folding of mature omega-conotoxin MVIIA was compared with that of two putative precursor forms: pro-omega-MVIIA-Gly, which contains the propeptide and the C-terminal Gly residue, and omega-MVIIA-Gly, which differs from the mature form only at the C-terminus. The three forms folded with similar kinetics, but the folding efficiency of omega-MVIIA-Gly was greater than 80%, versus approximately 50% for both mature omega-MVIIA and the form containing the propeptide. The enzyme protein disulfide isomerase was found to catalyze disulfide formation and folding of all three forms similarly. The affinity of omega-MVIIA-Gly for receptors in chick brain synaptosomes was approximately 10-fold lower than that of the mature peptide, and the N-terminal propeptide of pro-omega-MVIIA-Gly was found to decrease binding further, by approximately 100-fold. These results suggest that the omega-conotoxins do not rely on the propeptide region of their precursors to facilitate folding. Rather, the mature sequence contains most of the information required to specify the native disulfide pairings and three-dimensional conformation. The C-terminal Gly may enhance the folding efficiency by forming interactions that stabilize the native conformation with respect to other disulfide-bonded forms.     

Neuronal generators of visual evoked potentials in humans: visual processing in the human cortex

PURPOSE: We wished to define the localization of cortical generators of visual (pattern) evoked potentials (VEP) and the temporal sequence of activation in the occipital region. METHODS: In 4 candidates for epilepsy surgery, a large array of subdural electrodes was placed over occipital areas. Checkerboard pattern reversal stimuli were generated and the epileptogenic focus was localized and functionally mapped. Magnetic resonance imaging did not show any occipital lesions in any of the 4 patients. RESULTS: The area first activated was the lingual gyrus in the mesial occipital lobe (negative potential peaks at approximately 70 ms), followed by an area superior to the calcarine fissure (negative peaks at approximately 80 ms). Later (starting at approximately 90 ms), there were positive potentials over the occipital pole and lingual gyrus, followed by potentials at the lateral occipital lobe. CONCLUSIONS: These data support the idea that VEP are generated in the mesial and lateral occipital cortex by different circumscribed neuronal generators with different latencies of activation. The scalp-recorded N1 and P1 potential peaks most likely derive from the progressive activation of neuronal masses in different regions of the occipital lobe.     

Liver function tests in adults with Plasmodium falciparum infection

This study examines the levels of serum bilirubin, aspartate transaminase and alkaline phosphatase in adults with Plasmodium falciparum malaria. One hundred and six sets of liver function tests were obtained, and 63 (59.4%) patients had one of the above indices elevated outside the local reference range. Serum bilirubin and aspartate transaminase were relatively higher than alkaline phosphatase. Neither duration of illness nor severity of infection showed any significant correlation with any of the indices measured.     

Relevance of abattoir hygiene assessment to microbial contamination of British beef carcases

Eleven beef abattoirs were visited, each on five separate occasions. On each occasion, an audit was carried out according to the official Hygiene Assessment System (HAS) and 10 carcases were sampled at four different sites to assess total viable counts and counts of presumptive coliform bacteria. The HAS scores ranged from 11 to 84 (maximum 100), and the logarithmic mean total viable counts for all sampling sites on each batch of carcases varied between 1.98 and 4.14 colony forming units/cm2. The mean prevalence of coliform contamination ranged from 0 to 85 per cent. There was a significant negative correlation (P < 0.001) between the mean HAS scores and the mean total viable count for each abattoir, but not between the HAS scores and the numbers of coliforms. Within the HAS, the mean scores for all five categories, before weighting, showed a significant correlation with the mean total viable count (P < 0.001); however, the categories concerned with slaughter and dressing, and personnel and practices were of most value in determining trends in carcase contamination. A new advisory classification is proposed for levels of microbial contamination on beef carcases.