A natural kinase-deficient variant of fibroblast growth factor receptor 1

A fibroblast growth factor receptor 1 variant missing 37 amino acids from the carboxy-terminal tyrosine kinase catalytic domain was discovered in human lung fibroblasts and several other human cell lines. The receptor variant binds specifically to acidic fibroblast growth factor but has no tyrosine kinase activity. It was found that cellular transfectants expressing the fibroblast growth factor receptor 1 variant are mitogenically inactive and ligand binding to the receptor causes neither receptor autophosphorylation nor phospholipase C-gamma transphosphorylation. The fibroblast growth factor receptor 1 variant therefore represents an inactive receptor for acidic fibroblast growth factor. Since both kinase and kinase-deficient receptor forms are expressed in cells, it is conceivable that the kinase-deficient receptor plays an important role in regulating cellular responses elicited by acidic fibroblast growth factor stimulation.     

Managing the uncertainties of low-level radioactive waste disposal

A special program developed by the authors, called Pombe, identifies protein coding regions in the Schizosaccharomyces pombe genome. Linear discriminant analysis was applied to predict 5'-terminal, internal, 3'-terminal exons (coding-exon) and introns. The accuracy of the prediction was tested by cross verifications. The sensitivity, specificity and correlation coefficient for the internal exon prediction were 98.5%, 99.9% and 98.3% respectively at the nucleotide level. Open reading frames were studied and used to predict intron-less genes: 99.0% of such genes were identified with correct stopping sites. The gene structure was determined by dynamic programming and the prediction achieved 97.0% correlation coefficient at the nucleotide level. The program is available at http:(/)/clio.cshl.org/genefinder.     

Assessment of the biodegradation potential of psychrotrophic microorganisms

These experiments were designed to establish an animal model of acute carbon monoxide (CO) poisoning in awake habituated rats. On the day before exposure, under a brief anesthesia, a Levine preparation (unilateral common carotid artery occlusion) was performed on group 1 (n = 8) and 2 (n = 28), but not on group 3 rats (n = 8). Group 1 rats were exposed to air as control. Groups 2 and 3 rats were exposed to 0.27% CO in air for 60 min [carboxyhemoglobin (HbCO) = 70%] followed by a 2-day recovery in air. The Levine preparation per se did not induce any detectable physiologic effects on group 1 rats. Identical cardiovascular and metabolic responses to CO occurred in groups 2 and 3. After the CO exposure, all group 3 rats lived for 2 days with normal neurologic index (NI). In group 2 (n = 25 post-CO), 84% of the rats showed increased NI and edema of the ipsilateral cerebral hemisphere, and 76% of the rats died 8.7 +/- 1.7 h after the CO exposure. NI correlated with the brain edema (rs = 0.748, P < 0.001) and inversely correlated with the survival time after the CO exposure (rs = -0.777, P < 0.001). We therefore may conclude that exposure of the Levine-prepared rats to 0.27% CO in air for 60 min will provide a valuable model for testing of different treatments for CO poisoning.     

Prevalence of Cyclospora species and other enteric pathogens among children less than 5 years of age in Nepal

Stools from 124 Nepalese children aged 6 to 60 months with diarrhea were examined for organisms of the coccidian genus Cyclospora and for other enteric pathogens. Enterotoxigenic Escherichia coli, Giardia Lamblia, Campylobacter species, Cyclospora species, and Cryptosporidium species were the most common pathogens identified. Cyclospora species were detected in none of 74 children < 18 months of age compared with 6 (12%) of 50 children > or = 18 months of age (P = 0.004).     

Carcinoma of the male breast: a review and recommendations for management

OBJECTIVES: To investigate whether occupational exposure to organic solvents increases the risk of dementia. METHODS: Cases of dementia were identified from the computed tomography records of eight neuroradiology centres in England and Wales, and were compared with two sets of controls investigated at the same centres. The first set of controls were patients with brain cancer and the second set were patients with other disorders that were not chronically disabling. Lifetime occupational histories were obtained through a postal questionnaire completed by the subjects or their next of kin. Associations between dementia and occupation were examined by logistic regression. RESULTS: Usable questionnaires were returned for 204 (61%) of the cases, 225 (51%) of the controls with brain cancer, and 441 (61%) of the other controls. The findings with each of the two sets of controls were similar. In comparison with all controls combined, cases had less often worked ever as a painter or printer (odds ratio (OR) 0.6, 95% confidence interval (95% CI) 0.3 to 1.2), and were less likely to have worked for > 1 year as a printer, painter, or launderer or dry cleaner (OR 0.6, 95% CI 0.3 to 1.4). CONCLUSIONS: These findings provide no support for the hypothesis that occupational exposure to solvents is a cause of dementia. An excess risk in subsets of workers with extremes of exposure cannot be discounted, but the data indicate that any influence of exposure to solvents on the overall incidence of severe dementia in the general population of England and Wales is small.     

The yeast spindle pole body is assembled around a central crystal of Spc42p

The spindle pole body (SPB) is the microtubule organizing center (MTOC) in the yeast Saccharomyces that plays a pivotal role in such diverse processes as mitosis, budding, and mating. We have used cryoelectron microscopy and image processing to study the structure of isolated diploid SPBs. We show that SPBs are present in two lateral-size classes, sharing a similar vertical architecture comprised of six major layers. Tomographic reconstructions of heparin-stripped SPBs reveal a central hexagonally packed layer. Overexpression of Spc42p results in the growth of a similar layer, forming a crystal that encircles the SPB. Hence, the SPB is an MTOC that utilizes crystallographic packing of subunits in its construction.     

Circular dichroism and electron microscopy of a core Y61F mutant of the F1 gene 5 single-stranded DNA-binding protein and theoretical analysis of CD spectra of four Tyr --> Phe substitutions

A core Y61F mutant of the gene 5 single-stranded DNA-binding protein (g5p) of f1 bacterial virus aggregated when expressed from a plasmid, but, after refolding in vitro, it behaved much like wild-type and may be a stability or folding mutant. Circular dichroism (CD) titrations showed the same cooperative polynucleotide binding modes for Y61F and wild-type g5p. There are n = 4 and n congruent with 2.5 modes for binding to poly[d(A)] at low ionic strengths, but n = 4, n = 3, and n congruent with 2-2.5 modes for binding to fd single-stranded viral DNA (fd ssDNA), where n is the number of nucleotides occluded by each bound g5p monomer in a given mode. Y61F g5p has slightly reduced affinity in the n = 4 mode. Electron microscopy showed that Y61F g5p forms left-handed nucleoprotein superhelices indistinguishable from wild-type. Progression from binding to fd ssDNA in the n = 4 to n = 3 to n congruent with 2-2.5 mode is accompanied by an increase in the number of helical turns, an increase from (7.7 +/- 0.3) to (9.5 +/- 0.3) to ( approximately 10-13) g5p dimers per turn, and a decrease in the number of DNA nucleotides per turn. From CD spectra for four of five possible Y --> F g5p mutants, we infer that the fifth tyrosine, Tyr 56, contributes strongly to the CD. Retention of a strong 229 nm CD band in all mutants indicates that all retain elements of the native structure. Spectra of Y26F, Y34F, and Y61F g5p imply limited mobility of the replacement Phe. Comparison of measured with calculated CD spectra also suggests limited mobility for Tyr 26 and Tyr 34 in g5p in solution, and provides new information that the g5p structure in solution may be dominated by Tyr 41 rotamers differing from that stabilized in the crystal.