Plasma exchange appears to be efficacious in neuropathy associated with MGUS, especially of the IgG or IgA type.

Large-scale activity profiling of enzyme superfamilies provides information about cellular functions as well as the intrinsic binding capabilities of conserved folds. Herein, the functional space of the ubiquitous haloalkanoate dehalogenase superfamily (HADSF) was revealed by screening a customized substrate library against >200 enzymes from representative prokaryotic species, enabling inferred annotation of ∼35% of the HADSF. An extremely high level of substrate ambiguity was revealed, with the majority of HADSF enzymes using more than five substrates. Substrate profiling allowed assignment of function to previously unannotated enzymes with known structure, uncovered potential new pathways, and identified isofunctional orthologs from evolutionarily distant taxonomic groups. Intriguingly, the HADSF subfamily having the least structural elaboration of the Rossmann fold catalytic domain was the most specific, consistent with the concept that domain insertions drive the evolution of new functions and that the broad specificity observed in HADSF may be a relic of this process.evolution | specificity | phosphatase | substrate screen | promiscuity S ince the first genomes were sequenced, there has been an exponential increase in the number of protein sequences deposited into databases worldwide. At the time of this writing the UniProtKB/TrEMBL database contains over 32 million protein sequences. Although this increase in sequence data has dramatically enhanced our understanding of the genomic organization of organisms, as the number of protein sequences grows, the proportion of firm functional assignments diminishes. Traditionally, methods of functional annotation involve comparing sequence identity between experimentally characterized proteins and newly sequenced ones, typically via BLAST (1). In cases where significant sequence similarity cannot be ascertained, proteins are annotated as "hypothetical" or "putative." Moreover, the decrease in sequence identity leads to an increased uncertainty in functional assignment, especially as the phylogenetic distance between organisms grows, limiting iso-functional ortholog discovery.As the number of newly sequenced genomes grows larger, more protein sequences are likely to be misannotated, oftentimes resulting in the propagation of incorrect functional annotation across newly identified sequences. To tackle the problem of unannotated or misannotated proteins, newer methods for computational assignment have been created with varying degrees of success (2). Although these methods outperform historical methods, continued improvement is necessary to ensure accurate annotation of function (2). A greater swath of functional space can be covered by screening substrates in a high-throughput manner on multiple enzymes from a family (3, 4). Family-wide substrate profiling offers a data-rich resource. The use of sparse screening of sequence space and a diversified library permits the determination of substrate specificity profiles to provide a familywide view of the range of substrates...

Initial results indicate that Temodar may be active in the treatment of low-grade glioma, and thus, further evaluation of this agent in the treatment of these tumors is warranted.

Objectives: The objective was to evaluate the association between hospital census variables and emergency department (ED) length of stay (LOS). This may give insights into future strategies to relieve ED crowding.Methods: This multicenter cohort study captured ED LOS and disposition for all ED patients in five hospitals during five 1-week study periods. A stepwise multiple regression analysis was used to examine associations between ED LOS and various hospital census parameters.Results: Data were analyzed on 27,325 patients on 161 study days. A significant positive relationship was demonstrated between median ED LOS and intensive care unit (ICU) census, cardiac telemetry census, and the percentage of ED patients admitted each day. There was no relationship in this cohort between ED LOS and ED volume, total hospital occupancy rate, or the number of scheduled cardiac or surgical procedures. Conclusions:In multiple hospital settings, ED LOS is correlated with the number of admissions and census of the higher acuity nursing units, more so than the number of ED patients each day, particularly in larger hospitals with busier EDs. Streamlining ED admissions and improving availability of inpatient critical care beds may reduce ED LOS.ACADEMIC EMERGENCY MEDICINE 2009; 16:597-602 ª