Cytotoxins, mycotoxins and drugs from a new deuteromycete, Acremonium neo-caledoniae, from the southwestern lagoon of New Caledonia

A new cytotoxic trichothecene sesquiterpene, verrol 4-acetate, was isolated, along with known macrocyclic trichothene mycotoxins and medicinal styrylpyrones, from cultures of a new deuteromycete Acremonium neo-caledoniae Roquebert et Dupont n. sp., taken from drifting wood in the southwestern lagoon of New Caledonia.     

Direct hybridization of sorted human chromosomes: localization of the Y chromosome on the flow karyotype.

A method is described for directly hybridizing a small number of sorted chromosomes with specific DNA probes. The chromosomes are analyzed by flow cytometry and sorted by deflecting the droplets containing the desired chromosomes onto a nitrocellulose filter. By using probes specific for the human Y chromosome, it has been possible to unambiguously identify the peak corresponding to the Y chromosome in the flow karyotypes of a variety of male cell lines. The position of this peak was found to vary significantly from individual to individual, correlating with the heterochromatin chromosomal polymorphism of the human Y chromosome. The sensitivity of the hybridization was such that, with a probe for a male-specific repetitive sequence, only 2,500 sorted chromosomes were enough to obtain a clear, positive signal; 10,000 were needed with a probe specific for a weakly repeated (maximum, 3-fold) sequence of Y chromosome. With this new method, chromosome sorting may be a rapid and efficient way to assign DNA sequences to chromosomes.     

Effect of tegaserod in chronic constipation: a randomized, double-blind, controlled trial.

BACKGROUND AND AIMS: Chronic constipation is a common gastrointestinal disorder. The aim of this study was to evaluate the efficacy, safety, and tolerability of tegaserod, a serotonin subtype 4 receptor partial agonist in patients with chronic constipation. METHODS: This was a randomized, double-blind, placebo-controlled study. After a 2-week baseline, patients received tegaserod 2 mg twice daily (n = 450), tegaserod 6 mg twice daily (n = 451), or placebo (n = 447) for 12 weeks, followed by a 4-week withdrawal period. Responders were those patients having been treated for at least 7 days with an increase of > or =1 complete spontaneous bowel movement/week vs. baseline during weeks 1-4 (primary variable) and weeks 1-12 (secondary variable). Other secondary variables included patient assessment of constipation symptoms (number of bowel movements, stool form, abdominal bloating/distention, straining, and abdominal pain/discomfort), and global assessment of constipation and bowel habits. RESULTS: Responder rates for complete spontaneous bowel movement during weeks 1-4 were significantly greater ( P < 0.0001) in the tegaserod 2 mg twice daily (41.4%) and 6 mg twice daily groups (43.2%) vs. placebo (25.1%). This effect was maintained over 12 weeks. Statistically significant improvements over placebo were observed across the majority of secondary variables for both tegaserod doses. No rebound effect was observed after treatment withdrawal. Tegaserod was well tolerated; headache and nasopharyngitis, the most frequent adverse events, were more common in the placebo group than in either tegaserod group. CONCLUSIONS: Over 12 weeks, tegaserod treatment produced significant improvements in chronic constipation symptoms and was also safe and well tolerated.     

c-mip down-regulates NF-κB activity and promotes apoptosis in podocytes

The mechanisms of podocyte disorders in cases of idiopathic nephrotic syndrome (INS) are complex and remain incompletely elucidated. The abnormal regulation of NF-κB may play a key role in the pathophysiology of these podocyte diseases, but at present, NF-κB has not been thoroughly investigated. In this study, we report that induction of c-mip in podocytes of patients with INS is associated with a down-regulation of RelA, a potent antiapoptotic factor that belongs to the NF-κB family. Overexpression of c-mip in differentiated podocytes promotes apoptosis by inducing caspase-3 activity and up-regulating the proapoptotic protein Bax, whereas the overall levels of the antiapoptotic protein Bcl-2 was concomitantly decreased. The associated overexpression of RelA prevented the proapoptotic effects of c-mip. In addition, the targeted induction of c-mip in podocytes in vivo inhibited the expression of the RelA protein and increased the Bax/Bcl-2 ratio. The expression of both c-mip and active caspase-3 increased in focal and segmental glomerulosclerosis biopsies, and both proteins displayed a close spatial relationship. These results suggest that alterations in NF-κB activity might result from the up-regulation of c-mip and are likely to contribute to podocyte disorders in cases of INS.     

Synthesis of marine natural products with antimalarial activity

The role played by synthetic organic chemistry of marine metabolites as potential leads for drug discovery of antimalarial agents is discussed. Syntheses of the most promising molecules are summarized, with emphasis on structure-activity relationship (SAR) studies and their mechanism of action.     

Genomic metrics made easy: what to do and where to go in the new era of bacterial taxonomy

With the advent of high-throughput DNA sequencing technologies, traditional methodologies for taxonomic classification of bacteria as DNA–DNA hybridization and 16S rRNA identity analyses are being challenged by the development of a fast-growing number of genomic metrics. The large amount of portable and digitized genome sequences available in public repositories constitutes an invaluable data for bacterial classification. Consequently, several genomic metrics and tools were developed to aid the interpretation of these massive data. Genomic metrics are based on the assumption that higher genome similarities would reflect closer phylogenetic relationships. Different metrics would vary in their methodology of analysis, resolution power, limitations and easiness of use. The aim of this review is to highlight the differences among available genome-based methods and tools to provide a guide for in silico bacterial identification and classification.     

EBV-induced lymphoproliferative disorders in rheumatic patients: A systematic review of the literature

Objectives

Epstein-Barr virus (EBV) is involved in the pathogenesis of approximately 40% of lymphoproliferative disorders (LPDs) arising in patients receiving immunosuppressive treatment (IST) for rheumatic diseases, but data from large cohorts are still not available. We aimed to identify clinicopathological features, management and outcome of this condition.