Exon scrambling of MLL transcripts occur commonly and mimic partial genomic duplication of the gene

The aim of this study was to test the hypothesis that prolactin may up- and down-regulate prolactin receptor gene expression in the anterior pituitary gland and hypothalamus respectively. Experiments were carried out in bantams (Gallus domesticus). Comparisons were made of concentrations of PRLR mRNA in the anterior pituitary gland and basal and preoptic hypothalamus in adult males and females held on long days (low vs high plasma prolactin); in 3-week-old juvenile male and females on short days (high vs low plasma prolactin); in 8-week-old juvenile male and females on short days (both low plasma prolactin); in adult laying, incubating, and out-of-lay (high, very high, and low plasma prolactin, respectively); in adult cockerels exposed to long or short days (high vs low prolactin); and in adult hens exposed to long or short days (high vs low prolactin). There was a sex difference in anterior pituitary and basal hypothalamic PRLR mRNA, with lower values in both tissues in females than in males. Compared with laying and out-of-lay hens, anterior pituitary and basal hypothalamic PRLR mRNA concentrations in incubating hens were increased and decreased, respectively. In adult birds of either sex held on long or short days, there was no difference in pituitary PRLR mRNA, while basal hypothalamic PRLR mRNA was lower on short days. PRLR mRNA in the preoptic hypothalamus was not affected by sex, reproductive state, or photoperiod. It is concluded that there is no consistent relationship between plasma prolactin, in the physiological range, and the concentration of PRLR mRNA in the anterior pituitary gland, basal hypothalamus, and preoptic hypothalamus.     

Role of an inhibitory pyrimidine element and polypyrimidine tract binding protein in repression of a regulated alpha-tropomyosin exon

The lipogenic enzyme fatty acid synthase (FAS) is elevated in various human primary cancers and certain human cancer cell lines. FAS overexpression in human neoplasia has clinical relevance because of its association with tumor aggression and potential chemotherapeutic intervention. Here, we surveyed FAS in cell lines established from normal murine mammary epithelium (NMuMG) and from mammary tumors induced by either rodent polyoma (Py) virus or murine mammary tumor virus (MMTV). Western blotting revealed greater content of FAS in Py-transformed A1-1 and T1 than NMuMG or MMTV-transformed Mm5MT, RIIIMT and MMT060562. These data suggest that signaling events mediated by Py transformation may increase cellular amounts of FAS. Although FAS content was elevated to similar levels in A1-1 and T1, specific activities were significantly different as enzyme activity in T1 was 3-fold higher than A1-1. Likewise, FAS activity in NMuMG was about 0.5-fold higher than the MMTV-transformed lines, even though enzyme content was similar. Immunoprecipitation studies employing anti-phosphoamino acid antibodies followed by immunoblot analysis with anti-FAS antisera (and vice versa) were used to characterize the constitutive phosphorylation state of the enzyme. Phosphoserine and phosphothreonine residues were detected in the more active FAS from T1 and NMuMG, but not in the less active FAS from Mm5MT or A1-1. Discovery of phosphorylated FAS suggests that the enzyme may have more immediate control over lipogenesis than previously thought. High-dose (10-4 M) dexamethasone induced FAS content and activity in NMuMG and MMTV-transformed lines but not Py-transformed cells. Lower concentrations (10-8, 10-6 M) of dexamethasone also activated FAS but without concomitant elevation of its protein content, which was consistent with a phosphorylated form of FAS. Finally, cell lines were treated with the FAS inhibitor cerulenin: almost all breast cancer lines were growth inhibited at significantly lower amounts of drug than normal cell lineages, suggesting that FAS plays a greater role in viability of tumor cells than normal cells. Pretreatment with palmitate (a primary end-product of FAS) prior to cerulenin rescued A1-1 cells only slightly from growth inhibition, whereas pretreatment with oleate (a monounsaturated fatty acid synthesized from palmitate) synergized cerulenin's cytotoxic effects.     

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.