tRNA Maturation: RNA Polymerization without a Nucleic Acid Template

AbstractThe CCA-adding enzyme, which builds and repairs the 3′ terminal CCA sequence of tRNA, is the only RNA polymerase that can synthesize a defined nucleotide sequence without using a nucleic acid template. New cocrystal structures tell us how this remarkable enzyme works

L2L: a simple tool for discovering the hidden significance in microarray expression data

L2L is a database consisting of lists of differentially expressed genes compiled from published mammalian microarray studies, along with an easy-to-use application for mining the database with the user's own microarray data. As illustrated by re-analysis of a recent study of diabetic nephropathy, L2L identifies novel biological patterns in microarray data, providing insights into the underlying nature of biological processes and disease. L2L is available online at the authors' website []

Association of snRNA genes with coiled bodies is mediated by nascent snRNA transcripts

AbstractBackground: Coiled bodies are nuclear organelles that are highly enriched in small nuclear ribonucleoproteins (snRNPs) and certain basal transcription factors. Surprisingly, coiled bodies not only contain mature U snRNPs but also associate with specific chromosomal loci, including gene clusters that encode U snRNAs and histone messenger RNAs. The mechanism(s) by which coiled bodies associate with these genes is completely unknown.Results: Using stable cell lines, we show that artificial tandem arrays of human U1 and U2 snRNA genes colocalize with coiled bodies and that the frequency of the colocalization depends directly on the transcriptional activity of the array. Association of the genes with coiled bodies was abolished when the artificial U2 arrays contained promoter mutations that prevent transcription or when RNA polymerase II transcription was globally inhibited by α-amanitin. Remarkably, the association was also abolished when the U2 snRNA coding regions were replaced by heterologous sequences.Conclusions: The requirement for the U2 snRNA coding region indicates that association of snRNA genes with coiled bodies is mediated by the nascent U2 RNA itself, not by DNA or DNA-bound proteins. Our data provide the first evidence that association of genes with a nuclear organelle can be directed by an RNA and suggest an autogenous feedback regulation model

Electrochemical evidence that pyranopterin redox chemistry controls the catalysis of YedY, a mononuclear Mo enzyme

A long-standing contradiction in the field of mononuclear Mo enzyme research is that small-molecule chemistry on active-site mimic compounds predicts ligand participation in the electron transfer reactions, but biochemical measurements only suggest metal-centered catalytic electron transfer. With the simultaneous measurement of substrate turnover and reversible electron transfer that is provided by Fourier-transformed alternating-current voltammetry, we show that Escherichia coli YedY is a mononuclear Mo enzyme that reconciles this conflict. In YedY, addition of three protons and three electrons to the well-characterized "as-isolated" Mo(V) oxidation state is needed to initiate the catalytic reduction of either dimethyl sulfoxide or trimethylamine N-oxide. Based on comparison with earlier studies and our UV-vis redox titration data, we assign the reversible one-proton and one-electron reduction process centered around +174 mV vs. standard hydrogen electrode at pH 7 to a Mo(V)-to-Mo(IV) conversion but ascribe the two-proton and two-electron transition occurring at negative potential to the organic pyranopterin ligand system. We predict that a dihydro-to-tetrahydro transition is needed to generate the catalytically active state of the enzyme. This is a previously unidentified mechanism, suggested by the structural simplicity of YedY, a protein in which Mo is the only metal site

Reducing prescribing errors through creatinine clearance alert redesign

Background Literature has shown that computerized creatinine clearance alerts reduce errors during prescribing, and applying human factors principles may further reduce errors. Our objective was to apply human factors principles to creatinine clearance alert design and assess whether the redesigned alerts increase usability and reduce prescribing errors compared with the original alerts. Methods Twenty Veterans Affairs (VA) outpatient providers (14 physicians, 2 nurse practitioners, and 4 clinical pharmacists) completed 2 usability sessions in a counterbalanced study to evaluate original and redesigned alerts. Each session consisted of fictional patient scenarios with 3 medications that warranted prescribing changes because of renal impairment, each associated with creatinine clearance alerts. Quantitative and qualitative data were collected to assess alert usability and the occurrence of prescribing errors. Results There were 43% fewer prescribing errors with the redesigned alerts compared with the original alerts (P = .001). Compared with the original alerts, redesigned alerts significantly reduced prescribing errors for allopurinol and ibuprofen (85% vs 40% and 65% vs 25%, P = .012 and P = .008, respectively), but not for spironolactone (85% vs 65%). Nine providers (45%) voiced confusion about why the alert was appearing when they encountered the original alert design. When laboratory links were presented on the redesigned alert, laboratory information was accessed 3.5 times more frequently. Conclusions Although prescribing errors were high with both alert designs, the redesigned alerts significantly improved prescribing outcomes. This investigation provides some of the first evidence on how alerts may be designed to support safer prescribing for patients with renal impairment

Evolution of the Rate and Mode of Star Formation in Galaxies since z=0.7

We present the star formation rate (SFR) and starburst fraction (SBF) for a sample of field galaxies from the ICBS intermediate-redshift cluster survey. We use [O II] and Spitzer 24 micron fluxes to measure SFRs, and 24 micron fluxes and H-delta absorption to measure of SBFs, for both our sample and a present-epoch field sample from the Sloan Digital Sky Survey (SDSS) and Spitzer Wide-area Infrared Extragalactic (SWIRE) survey. We find a precipitous decline in the SFR since z=1, in agreement with other studies, as well as a corresponding rapid decline in the fraction of galaxies undergoing long-duration moderate-amplitude starbursts. We suggest that the change in both the rate and mode of star formation could result from the strong decrease since z=1 of gas available for star formation.Comment: ApJ Letters in pres

Evidence-based selection of theories for designing behaviour change interventions : using methods based on theoretical construct domains to understand clinicians' blood transfusion behaviour

Peer reviewedPostprin

Alerting Doctors About Patient Life Challenges: A Randomized Control Trial of a Previsit Inventory of Contextual Factors

Objective. Effective care attends to relevant patient life context. We tested whether a patient-completed inventory helps providers contextualize care and increases patients’ perception of patient-centered care (PCC). Method. The inventory listed six red flags (e.g., emergency room visits) and if the patient checked any, prompted for related contextual factors (e.g., transportation difficulties). Patients were randomized to complete the inventory or watch health videos prior to their visit. Patients presented their inventory results to providers during audio-recorded encounters. Audios were coded for physician probing and incorporating context in care plans. Patients completed the Consultation and Relational Empathy (CARE) instrument after the encounter. Results. A total of 272 Veterans were randomized. Adjusting for covariates and clustering within providers, inventory patients rated visits as more patient-centered (44.5; standard error = 1.1) than controls (42.7, standard error = 1.1, P = 0.04, CARE range = 10–50). Providers were more likely to probe red flags (odds ratio = 1.54; confidence interval = 1.07–2.22; P = 0.02) when receiving the inventory, but not incorporating context into care planning. Conclusion. A previsit inventory of life context increased perceptions of PCC and providers’ likelihood of exploring context but not contextualizing care. Information about patients’ life challenges is not sufficient to assure that context informs provider decision making even when provided at the point of care by patients themselves

Association of Cervical Effacement With the Rate of Cervical Change in Labor Among Nulliparous Women

OBJECTIVE: To assess the association of cervical effacement with the rate of intrapartum cervical change among nulliparous women. METHODS: We conducted a secondary analysis of a prospective trial of intrapartum fetal pulse oximetry. For women who had vaginal deliveries, interval-censored regression was used to estimate the time to dilate at 1-cm intervals. For each given centimeter of progressive cervical dilation, women were divided into those who had achieved 100% cervical effacement and those who had not. The analysis was performed separately for women in spontaneous labor and those who were given oxytocin. RESULTS: A total of 3,902 women were included in this analysis, 1,466 (38%) who underwent labor induction, 1,948 (50%) who underwent labor augmentation (combined for the analysis), and 488 (13%) who labored spontaneously. For women in spontaneous labor, the time to dilate 1 cm was shorter for those who were 100% effaced starting at 4 cm of cervical dilation (P=.01 to <.001). For women who received oxytocin, the time to dilate 1 cm was shorter for those who were 100% effaced throughout labor (P<.001). CONCLUSION: The rate of cervical dilation among nulliparous women is associated with not only the degree of cervical dilation, but also with cervical effacement. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00098709