The reported point centromeres of Scheffersomyces stipitis are retrotransposon long terminal repeats

Point centromeres, found in some ascomycete yeasts such Saccharomyces cerevisiae, are very different in structure from the centromeres of other eukaryotes. They are tiny and nonrepetitive and contain only two short conserved sequence motifs. Until recently, point centromeres were thought to have a single evolutionary origin, in the budding yeast family Saccharomycetaceae. Most yeasts outside this family have centromeres that are many kilobases in size. Some have centromeres consisting of a large inverted repeat sequence, others have centromeric clusters of retrotransposons, and a third group including Candida albicans has centromeres with no conserved sequence features. It was recently reported that Scheffersomyces stipitis has point centromeres with a strongly conserved 125-bp core sequence, which is unexpected because S. stipitis is only distantly related to the known point-centromere species. We show here that the 125-bp core sequence is actually part of the long terminal repeat (LTR) of the Ty5-like retrotransposon Tps5, which forms a cluster in the centromeric region of each S. stipitis chromosome. Thus, the LTR of a centromere-associated retrotransposon confers centromere-like mitotic stability when cloned into a plasmid. The centromeric regions of S. stipitis contain three types of Tps5 element (Tps5a, Tps5b, and Tps5c) and a noncoding nonautonomous large retrotransposon derivative.     

Sucralfate attenuates gastric mucosal lesions and increased vascular permeability induced by ischaemia and reperfusion in rats

Recent evidence suggests that oxygen-derived free radicals are involved in mediating gastric microvascular and parenchymal cell injuries induced by ischaemia and reperfusion. Therefore, the effect of the locally acting anti-ulcer drug, sucralfate, was studied on ischaemia and reperfusion (e.g. induced gastric lesions, intraluminal bleeding, changes in vascular permeability and non-protein sulfhydryl levels in the rat stomach). Allopurinol was used as a known standard antioxidant drug. Rats were subjected to 30 min of gastric ischaemia in the presence of 100 mmol/L hydrochloric acid and reperfusion periods of 15, 30 or 60 min duration. The gastric lesions were assessed microscopically under an inverted microscope. The vascular permeability was quantified by measuring the extravasated Evans blue in the stomach. There were significantly greater numbers of gastric lesions, intraluminal bleeding and leakage of Evans blue during all reperfusion periods as compared with those of ischaemia, with maximum effects occurring at 60 min following reperfusion. Pretreatment with sucralfate (31.25-250 mg/kg, p.o.) or allopurinol (12.5-50 mg/kg, i.p.) 30 min before the procedure, dose-dependently reduced the gastric lesions, intraluminal bleeding, and decreased the vascular permeability induced by ischaemia and reperfusion. Furthermore, sucralfate dose-dependently reverses the ischaemia and reperfusion-induced depletion of mucosal non-protein sulfhydryl levels and inhibited the superoxide radical production in both cell-free xanthine-xanthine oxidase and in the stimulated polymorphonuclear cellular systems. These results suggest that the protection produced by sucralfate against gastric injury may be due to its antioxidant effects.     

Intralesional radiolabeled human monoclonal IgM in human tumor xenografts

Sensory-perceptual abnormalities in people with autism are discussed from two perspectives: published firsthand accounts and existing psychological research evidence. A range of abnormalities, including hyper- and hyposensitivity, sensory distortion and overload, and multichannel receptivity and processing difficulties, are described in firsthand accounts and frequently portrayed as central to the autistic experience. A number of dangers are inherent in uncritically accepting these accounts at face value and in any wider generalization to the autistic population as a whole. Evidence from clinical studies suggests that unusual sensory responses are present in a majority of autistic children, that they are manifested very early in development, and that they may be linked with other aspects of autistic behavior. In addition, experimental studies using a range of indices have found evidence of unusual responses to sensory stimuli in autistic subjects. However the clinical and experimental research to date suffers from serious methodological limitations and more systematic investigation is warranted. Key issues for future psychological research in the area are identified.     

Differential divalent cation requirements uncouple the assembly and catalytic reactions of human immunodeficiency virus type 1 integrase

Previous in vitro analyses have shown that the human immunodeficiency virus type 1 (HIV-1) integrase uses either manganese or magnesium to assemble as a stable complex on the donor substrate and to catalyze strand transfer. We now demonstrate that subsequent to assembly, catalysis of both 3' end processing and strand transfer requires a divalent cation cofactor and that the divalent cation requirements for assembly and catalysis can be functionally distinguished based on the ability to utilize calcium and cobalt, respectively. The different divalent cation requirements manifest by these processes are exploited to uncouple assembly and catalysis, thus staging the reaction. Staged 3' end processing and strand transfer assays are then used in conjunction with exonuclease III protection analysis to investigate the effects of integrase inhibitors on each step in the reaction. Analysis of a series of related inhibitors demonstrates that these types of compounds affect assembly and not either catalytic process, therefore reconciling the apparent disparate results obtained for such inhibitors in assays using isolated preintegration complexes. These studies provide evidence for a distinct role of the divalent cation cofactor in assembly and catalysis and have implications for both the identification and characterization of integrase inhibitors.     

Long-term follow-up of a randomized post-induction therapy trial in acute myelogenous leukemia (a Southeastern Cancer Study Group trial)

A phase III clinical trial was designed to determine if more intensive induction and consolidation therapy for acute myeloblastic leukemia increases the remission rate and prolongs survival. A minor objective was to determine if the use of non-cross resistant drugs was more effective than the same drugs used for induction. Patients with untreated leukemia between the ages of 15 and 50 were given daunorubicin 45 mg/m2 for the first 3 days of a 10-day continuous infusion of cytosine arabinoside, initially at a dose of 2000 mg/m2 but reduced to 100 mg/m2 because of toxicity. Those under 36 achieving a complete remission and with an histocompatible donor were assigned to a transplant arm. The rest were randomized to receive one of three consolidation arms: A, cytosine arabinoside, 200 mg/m2 daily for 7 days and daunorubicin 45 mg/m2 daily for 3 days for three courses; B, one course as in Arm A followed by amsacrine, 120 mg/m2 daily for 5 days followed by a 5-day continuous infusion of azacytidine, 150 mg/m2/day; C, thioguanine and cytosine arabinoside, 100 mg/m2 every 12 h and daunorubicin 10 mg/m2 daily for 5 days for three courses followed by four maintenance courses of cytosine arabinoside, 100 mg/m2 daily for 5 days and daunorubicin, 45 mg/m2 for 2 days every 13 weeks. From 1981 to 1986, 398 eligible patients were enrolled and 219 achieved a complete remission. The initial induction dose of cytosine arabinoside was reduced after five of 29 patients exhibited fatal gastrointestinal toxicity. Only 11 patients were assigned to the transplant arm. There were no significant differences in the consolidation arms. The 5 year disease-free survivals were 38, 31 and 27% in arms A, B, and C respectively. Intensive consolidation therapy with the same or different drugs used in induction was as effective as lower dose consolidation followed by maintenance therapy.     

The effect of the length of a malarial epitope on its antigenicity and immunogenicity in an epitope presentation system using the Pseudomonas aeruginosa outer membrane protein OprF as the carrier

The phenotypic characteristics of three Serpulina pilosicoli strains isolated from humans with diarrhoea (WesB, Kar, Hrm7) and two porcine S. pilosicoli strains isolated from pigs with intestinal spirochaetosis (1648, 3295), were compared with the type strain of the species P43/6/78T (T = type strain) and other intestinal spirochaetes within the genus Serpulina. All S. pilosicoli strains had a characteristic ultrastructural appearance, displayed similar growth rates, hydrolysed hippurate, lacked beta-glucosidase activity, utilised D-ribose as a growth substrate, and had similar sensitivities to rifampicin and spiramycin. The only consistent phenotypic characteristic that differentiated human strains from porcine strains of S. pilosicoli was that the human strains all utilised the pentose sugar D-xylose. These distinguishing phenotypic traits appear useful for identifying S. pilosicoli.     

K-winner networks.

A special class of mutually inhibitory networks is analyzed, and parameters for reliable K-winner performance are presented. The network dynamics are modeled using interactive activation, and results are compared with the sigmoid model. For equal external inputs, network parameters that select the units with the larger initial activations (the network converges to the nearest stable state) are derived. Conversely, for equal initial activations, networks that select the units with larger external inputs (the network converges to the lowest energy stable state) are derived. When initial activations are mixed with external inputs, anomalous behavior results. These discrepancies are analyzed with several examples. Restrictions on initial states are derived which ensure accurate K-winner performance when unequal external inputs are used.