Zinc-finger proteins of the classical Cys2His2 type are the most frequently used class of transcription factor and account for about 3% of genes in the human genome. The zinc-finger motif was ...discovered during biochemical studies on the transcription factor TFIIIA, which regulates the 5S ribosomal RNA genes of Xenopus laevis. Zinc-fingers mostly interact with DNA, but TFIIIA binds not only specifically to the promoter DNA, but also to 5S RNA itself. Increasing evidence indicates that zinc-fingers are more widely used to recognize RNA. There have been numerous structural studies on DNA binding, but none on RNA binding by zinc-finger proteins. Here we report the crystal structure of a three-finger complex with 61 bases of RNA, derived from the central regions of the complete nine-finger TFIIIA-5S RNA complex. The structure reveals two modes of zinc-finger binding, both of which differ from that in common use for DNA: first, the zinc-fingers interact with the backbone of a double helix; and second, the zinc-fingers specifically recognize individual bases positioned for access in otherwise intricately folded 'loop' regions of the RNA.
Depression is highly prevalent yet often poorly detected and treated among cancer patients. In light of the move towards evidence-based healthcare policy, we have developed a simple tool that can ...assist policy makers, organisations and researchers to logically think through the steps involved in improving patient outcomes, and to help guide decisions about where to allocate resources.
The model assumes that a series of filters operate to determine outcomes and cost-effectiveness associated with depression care for cancer patients, including: detection of depression, provider response to detection, patient acceptance of treatment, and effectiveness of treatment provided. To illustrate the utility of the model, hypothetical data for baseline and four scenarios in which filter outcomes were improved by 15% were entered into the model.
The model provides outcomes including: number of people successfully treated, total costs per scenario, and the incremental cost-effectiveness ratio per scenario compared to baseline. The hypothetical data entered into the model illustrate the relative effectiveness (in terms of the number of additional incremental successes) and relative cost-effectiveness (in terms of cost per successful outcome and total cost) of making changes at each step or filter.
The model provides a readily accessible tool to assist decision makers to think through the steps involved in improving depression outcomes for cancer patents. It provides transparent guidance about how to best allocate resources, and highlights areas where more reliable data are needed. The filter model presents an opportunity to improve on current practice by ensuring that a logical approach, which takes into account the available evidence, is applied to decision making.
In the nine-zinc finger Xenopus transcription factor TFIIIA the central group of fingers, fingers 4 to 7, have been shown to bind to 5 S RNA. In this study, we have attempted to assess the role of ...this region of the TFIIIA molecule in more detail than hitherto. High-resolution footprinting by RNases A and CV1 has been used to probe the binding to 5 S RNA of three TFIIIA peptides Tf(1-6), Tf(4-6) and Tf(4-7), consisting of fingers 1 to 6, 4 to 6, and 4 to 7, respectively, and of full-length TFIIIA. The results pinpoint the outer margins of binding of the central fingers within helices IV and II of TFIIIA. A comparison of the footprints reveals that the presence of finger 7 affords protection at positions C19 and U55, the distal portion of helix II and the proximal portion of loop B. In addition, our footprints suggest that the central fingers bind in the same manner, whether in an isolated group or in the intact TFIIIA molecule. In a companion study, we have determined the binding affinities of Tf(4-6) and Tf(4-7) for full-length and three truncated 5 S RNA molecules, the latter selected on the basis of the regions of the 5 S RNA molecule known to be important in the binding of TFIIIA. The analysis uses only fully active protein involved in the binding and the results are consistent with the corresponding footprinting results. This is the first time that a detailed study of the binding site of one particular zinc finger to RNA has been reported; the results should be of use in the design of 5 S RNA molecules and TFIIIA peptides for structural studies of the interaction between zinc fingers and RNA.
Food and beverage products stored in polyethylene (PE) containers may absorb some of PE's volatile minor components and become tainted by its characteristic “plastic” odor. High-density PE containers ...that had imparted “plastic” odor to an experimental corn chip product were analyzed by simultaneous distillation/extraction to remove the volatile components, by gas chromatography/olfactometry (GC/O) to locate the offending components and by 2-D GC/mass spectrometry (MS) to identify the major “plastic” odor contributor (8-nonenal). The identification was made using high-resolution electron ionization and chemical ionization MS data to narrow the possibilities to two isomers of nonenal, followed by retrieval of reference spectra and confirmatory synthesis. By monitoring 8-nonenal in HDPE containers and corn chips it was demonstrated that 8-nonenal tracks with “plastic” aroma observed in containers and with “plastic” flavor observed in corn chips stored in the containers. Keywords: Polyethylene volatiles; HDPE; 8-nonenal; plastic off-odor; plastic off-flavor; packaging off-odor
Highlights • Hospital costs over an eight and a half year period were 41% higher for women in the Australian Longitudinal Study on Women’s Health (ALSWH) who self-reported diabetes mellitus than for ...those who did not self-report diabetes mellitus. • On average, women who self-reported diabetes mellitus had 5.3 hospital admissions compared with 3.4 admissions for women with no self-reported diabetes mellitus. • Self-reported diabetes mellitus is a predictor of higher hospital costs and is a practical indicator for targeting health promotion. • Mean length of hospital stay was not statistically significantly different between the two groups of women.
Interstellar naphthalene cations (C10H+ 8) have been proposed by a study to be the carriers of a small number of diffuse interstellar bands (DIBs). Using an archive of high signal-to-noise spectra ...obtained at the Apache Point Observatory, we used two methods to test the hypothesis. Both methods failed to detect significant absorption at lab wavelengths of interstellar spectra with laboratory spectra. We thereby conclude that C10H+ 8 is not a DIB carrier in typical reddened sight lines.
This Letter reports one of the most precise measurements to date of the antineutrino spectrum from a purely 235U-fueled reactor, made with the final dataset from the PROSPECT-I detector at the High ...Flux Isotope Reactor. By extracting information from previously unused detector segments, this analysis effectively doubles the statistics of the previous PROSPECT measurement. Further, the reconstructed energy spectrum is unfolded into antineutrino energy and compared with both the Huber-Mueller model and a spectrum from a commercial reactor burning multiple fuel isotopes. A local excess over the model is observed in the 5–7 MeV energy region. Comparison of the PROSPECT results with those from commercial reactors provides new constraints on the origin of this excess, disfavoring at 2.0 and 3.7 standard deviations the hypotheses that antineutrinos from 235U are solely responsible and noncontributors to the excess observed at commercial reactors, respectively.
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OBJECTIVES
To evaluate the efficacy of dilatation of the stenotic urethral meatus in boys at home.
PATIENTS AND METHODS
Eighteen boys aged 3–15 years, or their parents, were taught to dilate the ...urethral meatus at home. The cause of the stricture was balanitis xerotica obliterans (BXO) in five and consequent upon hypospadias surgery in 12, of whom two were complicated by BXO, and one after circumcision for cultural reasons. One boy was re‐referred after an interval of 3 years because of apparent deterioration of the stream of urine. Meatal dilatation was taught in the home by one of the authors (J.M.S.)
RESULTS
Nine patients were cured by the first course of dilatation, four relapsed early after initial success but responded to further treatment, and three proceeded to meatoplasty because they had no response. Two relapsed late and one responded to further dilatation but the other required surgery.
CONCLUSION
Dilatation of the urethral meatus can be taught successfully to boys or their families at home, thus avoiding repeated hospital attendance and often general anaesthesia.
To estimate the cost of resources required to deliver a program to assess international medical graduates (IMGs) in Newcastle, Australia, known as the Workplace Based Assessment (WBA) Program.
A ...costing study to identify and evaluate the resources required and the overheads of delivering the program for a cohort of 15 IMGs, based on costs in 2012.
Labour-related costs.
The total cost in 2012 for delivering the program to a typical cohort of 15 candidates was $243,384. This equated to an average of $16,226 per IMG. After allowing for the fees paid by IMGs, the WBA Program had a deficit of $153,384, or $10,226 per candidate, which represents the contribution made by the health system.
The cost per candidate to the health system of this intensive WBA program for IMGs is small.
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