Biosynthetic Gene Cluster for the Cladoniamides, Bis-Indoles with a Rearranged Scaffold

The cladoniamides are bis-indole alkaloids isolated from Streptomyces uncialis, a lichen-associated actinomycete strain. The cladoniamides have an unusual, indenotryptoline structure rarely observed among bis-indole alkaloids. I report here the isolation, sequencing, and annotation of the cladoniamide biosynthetic gene cluster and compare it to the recently published gene cluster for BE-54017, a closely related indenotryptoline natural product. The cladoniamide gene cluster differs from the BE-54017 gene cluster in gene organization and in the absence of one N-methyltransferase gene but otherwise contains close homologs to all genes in the BE-54017 cluster. Both gene clusters encode enzymes needed for the construction of an indolocarbazole core, as well as flavin-dependent enzymes putatively involved in generating the indenotryptoline scaffold from an indolocarbazole. These two bis-indolic gene clusters exemplify the diversity of biosynthetic routes that begin from the oxidative dimerization of two molecules of l-tryptophan, highlight enzymes for further study, and provide new opportunities for combinatorial engineering

Predictors of Death in Trauma Patients who are Alive on Arrival at Hospital

Objective: To determine which factors predict death occurring in trauma patients who are alive on arrival at hospital Design Prospective cohort study Method Data were collected from 507 trauma patients with multiple injuries, with a Hospital Trauma Index–Injury Severity Score of 16 or more, who were initially delivered by the Emergency Medical Services to the Emergency Department of the University Medical Centre Utrecht (UMCU) during the period 1999–2000. Results: Univariate analysis showed that every year of age increase resulted in a 2% greater risk of death. If the patient had been intubated at the scene of the accident, this risk was increased 4.3-fold. Every point of increase in the Triage Revised Trauma Score (T-RTS) reduced the risk of death by 30%. A similar (but inverse) tendency was found for the HTI–ISS score, with every point of increase resulting in a 5% greater risk of death. There was a clear relationship between the base excess (BE) and hemoglobin (Hb) levels and the risk of death, the latter being increased by 8% for each mmol/l drop in BE, and reduced by 22% for each mmol/l increase in Hb. The risk of death occurring was 2.6 times higher in cases with isolated neurotrauma. These associations hardly changed in the multivariate analysis; only the relation with having been intubated at the scene disappeared. Conclusion: The risk of severely injured accident patients dying after arriving in hospital is mainly determined by the T-RTS, age, presence of isolated neurological damage, BE and Hb level. Skull/brain damage and hemorrhage appear to be the most important causes of death in the first 24 h after the accident. The time interval between the accident and arrival at the hospital does not appear to affect the risk of death. Includes erratu