bluuebunny/crossref_metadata_2025 huggingface dataset:
Original Paper: Does evidence-based information about screening for prostate cancer enhance consumer decision-making? A randomised controlled trial
Authors: Gattellari M , Ward J E
Published: January 2004

Objectives: Efforts to educate men about the controversy surrounding prostate cancer screening are well intended but rarely evaluated rigorously. We evaluated an evidence-based (EB) booklet for men designed to promote informed decision-making. We also determined whether men's preference for involvement in decision-making ("passive", "collaborative" or "active") modified its impact.

Setting and methods: Men aged 40-70 years were recruited from the practices of 13 local general practitioners (GPs) in Sydney, Australia. They completed a self-administered questionnaire before seeing their GP, who, according to pre-randomised codes, distributed either our EB booklet or conventional information. Post-test questionnaires were mailed to men three days later. Of the 248 eligible men recruited, 214 (86% response rate) returned post-test questionnaires. Knowledge of evidence and of risk of developing and dying from prostate cancer, attitudes, interest in screening for prostate-specific antigen (PSA), worry and decisional conflict were the main outcome measures.

Results: Compared with those receiving conventional information, men receiving the EB booklet had significantly improved knowledge (50% of items correct, 95% CI 46-53%; vs 45% correct, 95% CI 42-48%) (p=0.048) and lower levels of decisional conflict (mean 21.6, 95% CI 20.7-22.5; vs mean 24.3, 95% CI 23.4-25.2) (p<0.001). Interest in PSA screening was significantly reduced in both groups at post-test (p<0.001). Men preferring a "passive" approach to decision-making gained as much from our EB booklet as those with "active" or "collaborative" preferences.

Conclusions: Our findings show the benefits of providing evidence-based information to men about PSA screening. Our EB booklet facilitated informed choice, even among "passive" decision-makers.
Review: Screening for vulnerability to psychological disorders in the military: an historical survey
Authors: Jones E , Hyams K C , Wessely S
Published: January 2004

Objectives: To evaluate attempts in the military to screen for vulnerability to psychological disorders from World War I to the present.

Methods: An extensive literature review was conducted by hand-searching leading medical and psychological journals relating to World Wars I and II. Recent publications were surveyed electronically and UK archives investigated for British applications.

Results: Despite the optimism shown in World War I and the concerted efforts of World War II, followup studies showed that screening programmes did not succeed in reducing the incidence of psychological casualties. Furthermore, they had a counter-productive effect on manpower, often rejecting men who would have made good soldiers. Continued experimentation with screening methods for psychiatric vulnerability failed to yield convincing results during the post-war period.

Conclusions: Although well-measured variables, such as intelligence, have been shown to predict success in training and aptitude, no instrument has yet been identified which can accurately assess psychological vulnerability. Previous attempts have failed because of false-positives, false-negatives and reluctance in the target population because of stigma. Early findings suggest that psychological surveillance, if not screening, may yield valuable results when applied to military populations exposed to stress.
Is there a case for hepatitis C infection screening in the antenatal period?
Authors: Pembrey Lucy , Newell Marie-Louise , Peckham Catherine
Published: January 2004

Based on research evidence the UK National Screening Committee recently recommended that routine antenatal screening for hepatitis C virus (HCV) infection should not be introduced into the UK antenatal screening programme. In this paper we review the evidence on which this decision was based, addressing the criteria that need to be considered before the introduction of a new screening programme.
The quality of routine examinations of the newborn performed by midwives and SHOs; an evaluation using video recordings
Authors: Bloomfield L , Rogers C , Townsend J , Wolke D , Quist-Therson E
Published: January 2004

Objective: To evaluate the quality of the routine examination of the newborn as carried out by senior house officers (SHOs) and midwives.

Design: Randomised controlled trial set in a district general hospital in Southeast England. Eligible babies were randomised to a midwife (11) or an SHO (8) who were then video recorded undertaking the routine newborn examination.

Main outcome measures: Quality of 62 observed technical and communication components of the newborn examination, as agreed between independent consultant paediatrician and senior midwife raters.

Results: Major differences were found in the rated quality of examinations between midwives and SHOs for the examinations of the heart and lungs, for the overall quality of the examination, and in areas of communication skills. Quality of examination of the hips was assessed as poor for both professional groups. Where there were significant differences between examiners, the quality of the midwives' examinations was higher. Inter-rater agreement between the consultant paediatricians and senior midwives ranged from excellent to poor for different items of the examination with a mean kappa value of 0.42 across all items indicating moderate agreement.

Conclusions: The quality of midwife examinations exceeded that of SHOs. All midwives who examine receive formalised training in the examination of the newborn; SHOs may benefit from similar specific training. Training for both professional groups may need to be reviewed, particularly in relation to agreement on 'gold standards' for the screening of developmental dysplasia of the hip.
Health authority cervical screening recall policies and time since last smear: a retrospective cohort analysis in the north west of England
Authors: Howe A , Owen-Smith V , Richardson J
Published: January 2004

Objectives: To evaluate the impact of health authority cervical screening programmes upon the actual screening interval for women attending as a result of routine recall and to assess the impact of general practice recall policies on attendance for smears.

Setting: Nine health authorities constituting the Lancashire and Greater Manchester zones of the North West region of the National Health Service.

Methods: Information was obtained on the invitation and recall policies of each health authority. A retrospective analysis of information held on cervical screening databases ("Exeter" computer systems) was performed. The proportions of smears, classified by a screening interval of "unscheduled", "on-time", or "overdue", in the different health authority recall programmes were compared. General practices in one health authority (operating five-yearly recall) were contacted to determine their current practice screening policy.

Results: Women who were invited as part of a three-yearly recall programme were more likely to attend for smears at intervals of 3-5 years than those on a five-yearly recall programme (68% vs 47%). Those health authorities operating three-yearly recall that issued recall invitations to women more than four weeks before the date the smear was due had higher rates of "unscheduled" smears. In the one health authority (operating a five-yearly recall programme) in which we determined general practice screening policy, 62% of the general practitioners (GPs) were operating their own three-yearly recall policy; these GPs had a higher proportion of the women who attended for smears "on-time" (51%) than did those who relied on the heath authority five-yearly recall procedure (44%).

Conclusions: Despite the cervical screening programme being a national programme, there is scope at a local level for considerable variation in the interpretation of national guidance. This variation effects the extent to which programmes comply with the requirement to screen all women at an interval of 3-5 years.
Risk of invasive cervical cancer after three consecutive negative Pap smears
Authors: Coldman A , Phillips N , Kan L , Matisic J , Benedet L , Towers L
Published: January 2004

Objectives: To determine the factors that influence risk of cervical cancer after three consecutive negative Pap smears.

Methods: A cohort study was conducted using data from the British Columbia Cervical Cancer Screening Program and British Columbia Cancer Registry. Analysis was based on a one percent sample of women aged 20-69 years with Pap smears enriched with all invasive cervical cancer cases diagnosed between 1994-99. Screening intervals, after three negative screens, were created with the following variables: age at beginning of interval, interval length, previous cytologic abnormality and previous cervical procedure. The risk of cervical cancer by histologic type was calculated using survival analysis methods.

Results: The sample consisted of 10,509 women, who contributed 28,309 intervals, and 371 cervical cancer cases. The incidence rate of invasive squamous cervical cancer increased with time since last screen up to six years. Women with a history of dysplasia remained at elevated risk for squamous cancer, hazard ratio=2.6 (95% confidence interval [CI]=1.9, 3.4) but age or previous procedure were not related to risk. No relationship between time since last screen and non-squamous cancer risk was found although history of a previous procedure was significant. The marginal effectiveness of Pap smears declined with increasing frequency of use.

Conclusions: This study confirmed the preventive effect of Pap smear screening and its dependency on frequency of use. Women with a history of dysplasia, prior to three consecutive negatives, were at increased risk of developing invasive squamous cervical cancer compared with women with no such history.
An assessment of smear taker training in the Northern & Yorkshire cervical screening programme
Authors: Faulkner Keith , Greenwood Lesley , Stamp Elaine
Published: January 2004

Objective: To assess the impact of a regional smear taker training scheme within the Northern and Yorkshire Cervical Screening Programme.

Design: An analysis of cervical screening KC activity returns to the Department of Health before and after the introduction of a structured training programme for smear takers.

Setting: Northern and Yorkshire Region of England.

Subjects: Women participating in cervical screening.

Results: The introduction of a region-wide smear taker training programme has resulted in fewer inadequate cervical smears, fewer opportunistic smears and fewer women aged below 20 having cervical smears. The training programme is cost effective.

Conclusions: It is recommended that all cervical screening programmes consider the introduction of smear taker training. It is a cost-effective approach to running the cervical screening programme.
Screening for liver cancer: results of a randomised controlled trial in Qidong, China
Authors: Chen J-G , Parkin D M , Chen Q-G , Lu J-H , Shen Q-J , Zhang B-C , Zhu Y-R
Published: January 2004

Objectives: To investigate the effectiveness of screening for liver cancer in reducing mortality from the disease in a high-risk population in China.

Setting: A randomised controlled trial was carried out among men aged 30-69 who were chronic carriers of hepatitis-B virus (HBsAg positive) during the period 1989-1995 in Qidong county, Jiangsu Province, China.

Methods: 5581 HBsAg carriers were identified by population screening and randomly assigned to a screening group (group A, 3712 men), and controls (group B, 1869 men). Screening was planned to be six monthly alpha-fetoprotein (AFP) assays, with follow-up of subjects having an abnormal (≥20 μg/l) test. All subjects were followed up for liver cancer and/or death until 31 December 1995.

Results: The overall sensitivity and specificity of the programme was 55.3% and 86.5%, respectively; in subjects who complied with all scheduled screening tests, the values were 80.0% and 80.9%. Three hundred and seventy-four primary liver cancer (PLC) cases were diagnosed. The percentage of cases in stage I was significantly higher in group A (29.6%) than in group B (6.0%). The one-, three-, and five-year relative survival rates were 23.7%, 7.0%, and 4.0% in group A, and 9.7%, 4.0%, and 4.1% in group B respectively, with no difference in five-year survival between the groups. The mortality rate in the screened group (1138 per 100,000 person-years) was not significantly different from that in the controls (1114 per 100,000). A Poisson regression model showed that the probability of death (rate ratio) in the screening group was 0.83 (95% CI 0.68-1.03) relative to the control group.

Conclusions: Screening with AFP resulted in earlier diagnosis of liver cancer, but the gain in lead time did not result in any overall reduction in mortality, because therapy for the patients found by screening was ineffective. Further studies using improved methods of screening, diagnosis and treatment are indicated.
Packaging and reverse transcription of snRNAs by retroviruses may generate pseudogenes
Authors: GILES KEITH E. , CAPUTI MASSIMO , BEEMON KAREN L.
Published: January 2004

Retroviruses specifically package two copies of their RNA genome in each viral particle, along with some small cellular RNAs, including tRNAs and 7S L RNA. We show here that Rous sarcoma virus (RSV) also packages U6 snRNA at approximately one copy per virion. In addition, trace amounts of U1 and U2 snRNAs were detected in purified virus by Northern blotting. U6 snRNA comigrated with the RSV 70S genomic RNA dimer on sucrose gradients. We observed reverse transcription of U6 snRNA in an endogenous reaction in which RSV particles were the source of both reverse transcriptase and RNA substrates. This finding led us to examine mammalian genomic sequences for the presence of snRNA pseudogenes. A survey of the human, mouse, and rat genomes revealed a high number of spliceosomal snRNA pseudogenes. U6 pseudogenes were the most abundant, with approximately 200 copies in each genome. In the human genome, 67% of U6 snRNA pseudogenes, and a significant number of the other snRNA pseudogenes, were associated with LINE, SINE, or retroviral LTR repeat sequences. We propose that the packaging of snRNAs in retroviral particles leads to their reverse transcription in an infected cell and the integration of snRNA/viral recombinants into the host genome.
Not all pseudouridine synthases are potently inhibited by RNA containing 5-fluorouridine
Authors: SPEDALIERE CHRISTOPHER J. , MUELLER EUGENE G.
Published: January 2004

RNA containing 5-fluorouridine has been assumed to inhibit strongly or irreversibly the pseudouridine synthases that act on the RNA. RNA transcripts containing 5-fluorouridine in place of uridine have, therefore, been added to reconstituted systems in order to investigate the importance of particular pseudouridine residues in a given RNA by inactivating the pseudouridine synthase responsible for their generation. In sharp contradiction to the assumption of universal inhibition of pseudouridine synthases by RNA containing 5-fluorouridine, the Escherichia coli pseudouridine synthase TruB, which has physiologically critical eukaryotic homologs, is not inhibited by such RNA. Instead, the RNA containing 5-fluorouridine was handled as a substrate by TruB. The E. coli pseudouridine synthase RluA, on the other hand, forms a covalent complex and is inhibited stoichiometrically by RNA containing 5-fluorouridine. We offer a hypothesis for this disparate behavior and urge caution in interpreting results from reconstitution experiments in which RNA containing 5-fluorouridine is assumed to inhibit a pseudouridine synthase, as normal function may result from a failure to inactivate the targeted enzyme rather than from the absence of nonessential pseudouridine residues.
P-site tRNA is a crucial initiator of ribosomal frameshifting
Authors: BARANOV PAVEL V. , GESTELAND RAYMOND F. , ATKINS JOHN F.
Published: January 2004

The expression of some genes requires a high proportion of ribosomes to shift at a specific site into one of the two alternative frames. This utilized frameshifting provides a unique tool for studying reading frame control. Peptidyl-tRNA slippage has been invoked to explain many cases of programmed frameshifting. The present work extends this to other cases. When the A-site is unoccupied, the P-site tRNA can be repositioned forward with respect to mRNA (although repositioning in the minus direction is also possible). A kinetic model is presented for the influence of both, the cognate tRNAs competing for overlapping codons in A-site, and the stabilities of P-site tRNA:mRNA complexes in the initial and new frames. When the A-site is occupied, the P-site tRNA can be repositioned backward. Whether frameshifting will happen depends on the ability of the A-site tRNA to subsequently be repositioned to maintain physical proximity of the tRNAs. This model offers an alternative explanation to previously published mechanisms of programmed frameshifting, such as out-of-frame tRNA binding, and a different perspective on simultaneous tandem tRNA slippage.
Two-step affinity purification of the hepatitis C virus ribonucleoprotein complex
Authors: WARIS GULAM , SARKER SHAMEEMA , SIDDIQUI ALEEM
Published: January 2004

Positive-strand RNA viruses replicate their RNA genome within a ribonucleoprotein (RNP) complex that is associated with cellular membranes. We used a two-step method of purification to isolate hepatitis C virus (HCV) RNP complexes from human hepatoma cell line Huh7, which stably expresses HCV subgenomic replicons. The procedure involved hybridization of replicon-expressing cellular lysates with oligonucleotides tagged with biotin and digoxigenin at their respective termini complementary to subgenomic replicon RNA followed by avidin-agarose enrichment of the mixture and subsequent immunoprecipitation of biotin-eluted material with anti-digoxigenin antibody. The immunoprecipitates were immunoblotted with antisera against HCV nonstructural (NS) proteins. The analysis revealed the association of all the HCV NS proteins (NS3, NS4a, NS4b, NS5a, and NS5b) that are encoded by the subgenomic replicon RNA. The HCV RNP complex migrated in a native polyacrylamide gel with an approximate molecular mass of 450 kD. The association of these viral proteins in the RNP complex reinforces the widely acknowledged notion that RNA viruses accomplish replication within a membranous RNP complex.
L-Myc protein synthesis is initiated by internal ribosome entry
Authors: JOPLING CATHERINE L. , SPRIGGS KEITH A. , MITCHELL SALLY A. , STONELEY MARK , WILLIS ANNE E.
Published: January 2004

An internal ribosome entry segment (IRES) has been identified in the 5′ untranslated region (5′ UTR) of two members of the myc family of proto-oncogenes, c-myc and N-myc. Hence, the synthesis of c-Myc and N-Myc polypeptides can involve the alternative mechanism of internal initiation. Here, we show that the 5′ UTR of L-myc, another myc family member, also contains an IRES. Previous studies have shown that the translation of mRNAs containing the c-myc and N-myc IRESs can involve both cap-dependent initiation and internal initiation. In contrast, the data presented here suggest that internal initiation can account for all of the translation initiation that occurs on an mRNA with the L-myc IRES in its 5′ UTR. Like many other cellular IRESs, the L-myc IRES appears to be modular in nature and the entire 5′ UTR is required for maximum IRES efficiency. The ribosome entry window within the L-myc IRES is located some distance upstream of the initiation codon, and thus, this IRES uses a “land and scan” mechanism to initiate translation. Finally, we have derived a secondary structural model for the IRES. The model confirms that the L-myc IRES is highly structured and predicts that a pseudoknot may form near the 5′ end of the mRNA.
The conserved RNA recognition motif 3 of U2 snRNA auxiliary factor (U2AF65) is essential in vivo but dispensable for activity in vitro
Authors: BANERJEE HIREN , RAHN ANDREW , GAWANDE BHARAT , GUTH SABINE , VALCÁRCEL JUAN , SINGH RAVINDER
Published: January 2004

The general splicing factor U2AF65 recognizes the polypyrimidine tract (Py tract) that precedes 3′ splice sites and has three RNA recognition motifs (RRMs). The C-terminal RRM (RRM3), which is highly conserved, has been proposed to contribute to Py-tract binding and establish protein–protein contacts with splicing factors mBBP/SF1 and SAP155. Unexpectedly, we find that the human RRM3 domain is dispensable for U2AF65 activity in vitro. However, it has an essential function in Schizosaccharomyces pombe distinct from binding to the Py tract or to mBBP/SF1 and SAP155. First, deletion of RRM3 from the human protein has no effect on Py-tract binding. Second, RRM123 and RRM12 select similar sequences from a random pool of RNA. Third, deletion of RRM3 has no effect on the splicing activity of U2AF65 in vitro. However, deletion of the RRM3 domain of S. pombe U2AF59 abolishes U2AF function in vivo. In addition, certain amino acid substitutions on the four-stranded β-sheet surface of RRM3 compromise U2AF function in vivo without affecting binding to mBBP/SF1 or SAP155 in vitro. We propose that RRM3 has an unrecognized function that is possibly relevant for the splicing of only a subset of cellular introns. We discuss the implications of these observations on previous models of U2AF function.
Preferential translation of cold-shock mRNAs during cold adaptation
Authors: GIULIODORI ANNA MARIA , BRANDI ANNA , GUALERZI CLAUDIO O. , PON CYNTHIA L.
Published: January 2004

Upon temperature downshift below the lower threshold of balanced growth (~20°C), the Escherichia coli translational apparatus undergoes modifications allowing the selective translation of the transcripts of cold shock-induced genes, while bulk protein synthesis is drastically reduced. Here we were able to reproduce this translational bias in E. coli cell-free extracts prepared at various times during cold adaptation which were found to display different capacities to translate different types of mRNAs as a function of temperature. Several causes were found to contribute to the cold-shock translational bias: Cold-shock mRNAs contain cis-elements, making them intrinsically more prone to being translated in the cold, and they are selective targets for trans-acting factors present in increased amounts in the translational apparatus of cold-shocked cells. CspA was found to be among these trans-acting factors. In addition to inducing a higher level of CspA, cold shock was found to cause a strong (two- to threefold) stoichiometric imbalance of the ratio between initiation factors (IF1, IF2, IF3) and ribosomes without altering the stoichiometric ratio between the factors themselves. The most important sources of cold-shock translational bias is IF3, which strongly and selectively favors translation of cold-shock mRNAs in the cold. IF1 and the RNA chaperone CspA, which stimulate translation preferentially in the cold without mRNA selectivity, can also contribute to the translational bias. Finally, in contrast to a previous claim, translation of cold-shock cspA mRNA in the cold was found to be as sensitive as that of a non-cold-shock mRNA to both chloramphenicol and kanamycin inhibition.
Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs
Authors: BOHNSACK MARKUS T. , CZAPLINSKI KEVIN , GÖRLICH DIRK
Published: January 2004

microRNAs (miRNAs) are widespread among eukaryotes, and studies in several systems have revealed that miRNAs can regulate expression of specific genes. Primary miRNA transcripts are initially processed to ≈70-nucleotide (nt) stem–loop structures (pre-miRNAs), exported to the cytoplasm, further processed to yield ≈22-nt dsRNAs, and finally incorporated into ribonucleoprotein particles, which are thought to be the active species. Here we study nuclear export of pre-miRNAs and show that the process is saturable and thus carrier-mediated. Export is sensitive to depletion of nuclear RanGTP and, according to this criterion, mediated by a RanGTP-dependent exportin. An unbiased affinity chromatography approach with immobilized pre-miRNAs identified exportin 5 as the pre-miRNA-specific export carrier. We have cloned exportin 5 from Xenopus and demonstrate that antibodies raised against the Xenopus receptor specifically block pre-miRNA export from nuclei of Xenopus oocytes. We further show that exportin 5 interacts with double-stranded RNA in a sequence-independent manner.
Mitochondrial proteins and complexes in Leishmania and Trypanosoma involved in U-insertion/deletion RNA editing
Authors: SIMPSON LARRY , APHASIZHEV RUSLAN , GAO GUANGHAN , KANG XUEDONG
Published: January 2004

A number of mitochondrial proteins have been identified in Leishmania sp. and Trypanosoma brucei that may be involved in U-insertion/deletion RNA editing. Only a few of these have yet been characterized sufficiently to be able to assign functional names for the proteins in both species, and most have been denoted by a variety of species-specific and laboratory-specific operational names, leading to a terminology confusion both within and outside of this field. In this review, we summarize the present status of our knowledge of the orthologous and unique putative editing proteins in both species and the functional motifs identified by sequence analysis and by experimentation. An online Supplemental sequence database (http://164.67.60.200/proteins/protsmini1.asp) is also provided as a research resource.
The kink-turn motif in RNA is dimorphic, and metal ion-dependent
Authors: GOODY TERRY A. , MELCHER SONYA E. , NORMAN DAVID G. , LILLEY DAVID M.J.
Published: January 2004

The kink-turn (K-turn) is a new motif in RNA structure that was identified by examination of the crystal structures of the ribosome. We examined the structural and dynamic properties of this element in free solution. The K-turn RNA exists in a dynamic equilibrium between a tightly kinked conformation and a more open structure similar to a simple bulge bend. The highly kinked form is stabilized by the noncooperative binding of metal ions, but a significant population of the less-kinked form is present even in the presence of relatively high concentrations of divalent metal ions. The conformation of the tightly kinked population is in excellent agreement with that of the K-turn structures observed in the ribosome by crystallography. The end-to-end FRET efficiency of this species agrees closely with that of the ribosomal K-turn, and the direction of the bend measured by comparative gel electrophoresis also corresponds very well. These results show that the tightly kinked conformation of the K-turn requires stabilization by other factors, possibly by protein binding, for example. The K-turn is therefore unlikely to be of itself a primary organizing feature in RNA.
The three-dimensional architecture of the class I ligase ribozyme
Authors: BERGMAN NICHOLAS H. , LAU NELSON C. , LEHNERT VALERIE , WESTHOF ERIC , BARTEL DAVID P.
Published: January 2004

The class I ligase ribozyme catalyzes a Mg++-dependent RNA-ligation reaction that is chemically analogous to a single step of RNA polymerization. Indeed, this ribozyme constitutes the catalytic domain of an accurate and general RNA polymerase ribozyme. The ligation reaction is also very rapid in both single- and multiple-turnover contexts and thus is informative for the study of RNA catalysis as well as RNA self-replication. Here we report the initial characterization of the three-dimensional architecture of the ligase. When the ligase folds, several segments become protected from hydroxyl-radical cleavage, indicating that the RNA adopts a compact tertiary structure. Ribozyme folding was largely, though not completely, Mg++ dependent, with a K1/2[Mg] < 1 mM, and was observed over a broad temperature range (20°C –50°C). The hydroxyl-radical mapping, together with comparative sequence analyses and analogy to a region within 23S ribosomal RNA, were used to generate a three-dimensional model of the ribozyme. The predictive value of the model was tested and supported by a photo-cross-linking experiment.
Crystal structure of the catalytic domain of RluD, the only rRNA pseudouridine synthase required for normal growth of Escherichia coli
Authors: DEL CAMPO MARK , OFENGAND JAMES , MALHOTRA ARUN
Published: January 2004

Escherichia coli pseudouridine synthase RluD makes pseudouridines 1911, 1915, and 1917 in the loop of helix 69 in 23S RNA. These are the most highly conserved ribosomal pseudouridines known. Of 11 pseudouridine synthases in E. coli, only cells lacking RluD have severe growth defects and abnormal ribosomes. We have determined the 2.0 Å structure of the catalytic domain of RluD (residues 77–326), the first structure of an RluA family member. The catalytic domain folds into a mainly antiparallel β-sheet flanked by several loops and helices. A positively charged cleft that presumably binds RNA leads to the conserved Asp 139. The RluD N-terminal S4 domain, connected by a flexible linker, is disordered in our structure. RluD is very similar in both catalytic domain structure and active site arrangement to the pseudouridine synthases RsuA, TruB, and TruA. We identify five sequence motifs, two of which are novel, in the RluA, RsuA, TruB, and TruA families, uniting them as one superfamily. These results strongly suggest that four of the five families of pseudouridine synthases arose by divergent evolution. The RluD structure also provides insight into its multisite specificity.
Complementary miRNA pairs suggest a regulatory role for miRNA:miRNA duplexes: FIGURE 1.
Authors: LAI ERIC C. , WIEL COLIN , RUBIN GERALD M.
Published: January 2004

microRNAs (miRNAs) are 21–22-nucleotide noncoding RNAs that are widely believed to regulate complementary mRNA targets. However, due to the modest amount of pairing involved, only a few out of the hundreds of known animal miRNAs have thus far been connected to mRNA targets. Here, we considered the possibility that miRNAs might regulate non-mRNA targets, namely other miRNAs. To do so, we conducted a systematic assessment of the nearly complete catalogs of animal miRNAs for potential miRNA:miRNA complements. Our analysis uncovered several compelling examples that strongly suggest a function for miRNA duplexes, thus adding a potential layer of regulatory sophistication to the small RNA world. Interestingly, the most striking examples involve miRNAs complementary to members of the K-box family and Brd-box family, two classes of miRNAs previously implicated in regulation of Notch target genes. We emphasize that patterns of nucleotide constraint indicate that miRNA complementarity is not a simple consequence of miRNA:miRNA* complementarity; however, our findings do suggest that the potential regulatory consequences of the latter also deserve investigation.
The Varkud satellite ribozyme
Authors: LILLEY DAVID M.J.
Published: January 2004

The VS ribozyme is the largest nucleolytic ribozyme, for which there is no crystal structure to date. The ribozyme consists of five helical sections, organized by two three-way junctions. The global structure has been determined by solution methods, particularly FRET. The substrate stem–loop binds into a cleft formed between two helices, while making a loop–loop contact with another section of the ribozyme. The scissile phosphate makes a close contact with an internal loop (the A730 loop), the probable active site of the ribozyme. This loop contains a particularly critical nucleotide A756. Most changes to this nucleotide lead to three-orders of magnitude slower cleavage, and the Watson-Crick edge is especially important. NAIM experiments indicate that a protonated base is required at this position for the ligation reaction. A756 is thus a strong candidate for nucleobase participation in the catalytic chemistry.
eIF4A3 is a novel component of the exon junction complex
Authors: CHAN CHIA C. , DOSTIE JOSÉE , DIEM MICHAEL D. , FENG WENQIN , MANN MATTHIAS , RAPPSILBER JURI , DREYFUSS GIDEON
Published: January 2004

The exon junction complex (EJC) is a protein complex that assembles near exon–exon junctions of mRNAs as a result of splicing. EJC proteins play important roles in postsplicing events including mRNA export, cytoplasmic localization, and nonsense-mediated decay. Recent evidence suggests that mRNA translation is also influenced by the splicing history of the transcript. Here we identify eIF4A3, a DEAD-box RNA helicase and a member of the eIF4A family of translation initiation factors, as a novel component of the EJC. We show that eIF4A3 associates preferentially with nuclear complexes containing the EJC proteins magoh and Y14. Furthermore, eIF4A3, but not the highly related eIF4A1 or eIF4A2, preferentially associates with spliced mRNA. In vitro splicing and mapping experiments demonstrate that eIF4A3 binds mRNAs at the position of the EJC. Using monoclonal antibodies, we show that eIF4A3 is found in the nucleus whereas eIF4A1 and eIF4A2 are found in the cytoplasm. Thus, eIF4A3 likely provides a splicing-dependent influence on the translation of mRNAs.
Localization of a promoter in the putative internal ribosome entry site of the Saccharomyces cerevisiae TIF4631 gene
Authors: VERGÉ VALÉRIE , VONLANTHEN MARTIN , MASSON JEAN-MICHEL , TRACHSEL HANS , ALTMANN MICHAEL
Published: January 2004

The 5′-region of the TIF4631 gene of Saccharomyces cerevisiae (encoding the translation initiation factor eIF4G1) was reported earlier to harbor a very active internal ribosome entry site (IRES) allowing for internal initiation of translation of TIF4631 mRNA. Here, we report the presence of a promoter in the region −112 to −36 relative to the translation initiation codon of the TIF4631 gene. This promoter stimulates transcription from a start site at position −36 and generates an mRNA that is actively translated in vitro and able to sustain growth of yeast cells in vivo as the only source of eIF4G. The data show that the IRES activity reported earlier is due to this promoter. On the contrary, the presumed IRES represents a strongly inhibitory element for translation in vitro.
Analysis of Snu13p mutations reveals differential interactions with the U4 snRNA and U3 snoRNA
Authors: DOBBYN HELEN C. , O’KEEFE RAYMOND T.
Published: January 2004

Pre-mRNA splicing is executed by the spliceosome, a complex of small nuclear RNAs (snRNAs) and numerous proteins. One such protein, 15.5K/Snu13p, is associated with the spliceosomal U4/U6.U5 tri-snRNP and box C/D small nucleolar ribonucleoprotein particles (snoRNPs), which act during preribosomal RNA (rRNA) processing. As such, it is the first splicing factor to be identified in two functionally distinct particles. 15.5K binds to an internal helix–bulge–helix (K-turn) structure in the U4 snRNA and two such structures in the U3 snoRNA. Previous work has concentrated on the structural basis of the interaction of 15.5K with the RNAs and has been carried out in vitro. Here we present a functional analysis of Snu13p in vivo, using a galactose inducible SNU13 strain to investigate the basis of three lethal mutations in Saccharomyces cerevisiae. Two are point mutations that map to the RNA-binding domain, and the third is a C-terminal deletion. These mutations result in accumulation of unspliced pre-mRNA, confirming a role for Snu13p in pre-mRNA splicing. In addition, these mutants also display rRNA processing defects that are variable in nature. Analysis of one mutant in the RNA-binding domain reveals a reduction in the levels of the U4 snRNA, U6 snRNA, and box C/D snoRNAs, but not H/ACA snoRNAs, supporting a role for Snu13p in accumulation and/or maintenance of specific RNAs. The mutations in the RNA-binding domain exhibit differential binding to the U4 snRNA and U3 snoRNA in vitro, suggesting that there are differences in the mode of interaction of Snu13p with these two RNAs.
Book Reviews
Authors: Lev Benjamin
Published: January 2004

The range of books reviewed is wide, covering theory and applications in operations research, statistics, management science, econometrics, mathematics, computers, and information systems (no software is reviewed). In addition, we include books in other fields that emphasize technical applications. Publishers who wish to have their books reviewed should send them to Professor Benjamin Lev. We list the books received; not all books received can be reviewed because space is limited. Those who would like to review books are urged to send me their names, addresses, and specific areas of expertise. We commission all reviews and do not accept unsolicited book reviews. Readers are encouraged to suggest books that might be reviewed or to ask publishers to send me copies of such books.

The authors or editors of the books reviewed in this issue are Louis Anthony Cox, Jr., George S. Fishman, Paolo Toth, and Daniele Vigo.
The Challenge of Closed-Loop Supply Chains
Authors: Guide V. Daniel R. , Harrison Terry P. , Van Wassenhove Luk N.
Published: January 2004

Closed-loop supply chains differ significantly from forward supply chains in many aspects. These differences are not well understood in many contexts, and the situation is complicated by many types of product returns. Progress is slow since closed-loop supply chains are rarely considered as value-creating systems, and much of the focus is on the operational aspects, rather than the larger strategic issues. Interest is growing in the US because of the potential profitability and in the European Union because of legislation. New business models need to be developed by joint cooperation between industry and academia that take a life-cycle approach to products.
Closed-Loop Supply Chains for Spent Batteries
Authors: Schultmann Frank , Engels Bernd , Rentz Otto
Published: January 2004

In Germany, a battery decree prescribes measures for collecting and recycling spent batteries. We developed a hybrid approach to establishing a closed-loop supply chain for spent batteries that combines an optimization model for planning a reverse-supply network and a flow-sheeting process model that enables a simulation tailored to potential recycling options for spent batteries in the steelmaking industry. Our results show that almost complete recycling of spent batteries can be achieved by transforming the current structure into a modified recovery network.
Strategic Management of Spare Parts in Closed-Loop Supply Chains—A System Dynamics Approach
Authors: Spengler Thomas , Schröter Marcus
Published: January 2004

We developed tools for information management and spare-parts management in closed-loop supply chains. Our Internet-based information and communication platform provides data relevant to recycling based on Agfa-Gevaert's concept of a “recycling passport.” We defined what data is relevant based on the product-recovery strategy. Using system dynamics, we modeled an integrated production and recovery system for supplying spare parts to evaluate possible strategies for meeting spare-parts demand for electronic equipment in the end-of-life service period. We will implement these instruments and methods in a pilot study within our partner companies, Agfa-Gevaert AG and Electrocycling GmbH. Decision makers at Agfa-Gevaert will then be able to determine whether and how recovering components could reduce costs in spare-parts management in the end-of-life service period.
Ancient Greeks' Practices and Contributions in Public and Entrepreneurship Decision Making
Authors: Zanakis Stelios H. , Theofanides Stavros , Kontaratos Anthony N. , Tassios Theodosios P.
Published: January 2004

In addition to the arts and philosophy, the ancients Greeks contributed greatly to the ideas and practices of economic and social decision making. In the fourth century BC, in his manuals on public administration, Xenophon offered pioneering ideas on leadership, management, stimulating economic growth, and fund raising. In Athens during the fifth to third centuries BC, random-drawing devices were used regularly to foster the democratic selection of public officials and jurors. The Delphic oracle of the ninth to the third centuries BC was the first central intelligence database of the ancient world, an interdisciplinary think tank of approximately 90 priests, deemed the best educated experts of antiquity. They collected and evaluated information and advised ordinary people and leaders, among them Alexander the Great. Major project management in the fourth century BC included the following two cases: In Samos island, a one-kilometer water-supply tunnel was built, connecting two tunnels originating at opposite ends of a mountain and meeting in the middle only 0.6 meters apart. A preserved contract for the draining of a lake in the Eretria region near Athens shows the project to be the first build-operate-and-transfer project in history.
A Specialism of Primary Dental Care?
Authors: Toy Andy , Richards Wayne
Published: January 2004

This opinion paper contends that a wide gap exists between the theory and practice of preventive dentistry. The reasons for this lie partly in the lack of recognition given to the potential for general dental practitioners (GDPs) to deliver health-focused care to their community of patients. This lack of recognition begins at undergraduate level and is also found among GDPs themselves. The creation of a specialism of primary dental care would help to bridge the gap between theory and practice, and help practitioners to create significantly improved levels of oral health within their respective communities.
Does the Community Dental Service Provide Primary Dental Care for Dentally Disadvantaged Children?
Authors: Dugmore Christopher R , Nunn June H
Published: January 2004

Objective

To compare the caries prevalence of Community Dental Service (CDS) patients in Leicestershire with the same age groups in the population, and to assess the effectiveness of the CDS in reaching dentally disadvantaged children.

Method

The caries prevalence of five- and 12-year-old children attending CDS clinics in Leicestershire was recorded in parallel with population data obtained from the British Association of Community Dentistry (BASCD) survey of these age groups in the county. BASCD criteria and conventions were used in both studies.

Participants

A total of 354 five-year-old and 383 12-year-old CDS clinic patients, and the respective BASCD population samples of 1815 for five-year-olds and 1753 for 12-year-olds.

Results

In both age groups CDS clinic patients had a significantly (P<0.01) higher caries experience. The provision of treatment for five-year-old CDS clinic patients was greater than that for the five-year-old BASCD population sample. This was also the case for the 12-year-old CDS clinic patients, who, in addition, had twice as many fissure sealants per patient than those in the BASCD sample. The mean DMFT of 12-year-old clinic attenders and the proportion of these children with caries experience were found to be higher than those for children with the poorest scores on the Townsend Deprivation Index.

Conclusion

The CDS appeared to be effective in reaching, and providing treatment for, dentally disadvantaged children in Leicestershire, and as such in providing a complementary service to the GDS.
Angioedema of the Lips and Tongue Induced by Angiotensin-Converting Enzyme Inhibitor. A Report of Two Cases
Authors: Stevenson Helen A , Steele John C , Field E Anne , Darroch Campbell J
Published: January 2004

The following case reports describe the clinical presentation, diagnosis and management of two patients who attended Liverpool University Dental Hospital with rapidly increasing swelling of the lips and tongue. Both patients were suffering from angioedema and were taking an angiotensin-converting enzyme (ACE) inhibitor (ACEI). A provisional diagnosis of ACEI-induced angioedema was made. An intramuscular injection of chlorpheniramine maleate was given to both patients and they were immediately transferred to the local accident and emergency department.

These cases illustrate the potential role of the general dental practitioner in the early recognition and management of this potentially life-threatening condition.
Do Referrals from Primary Dental Care for Treatment Using General Anaesthesia Comply with General Dental Council Guidelines?
Authors: Thomas David , Royle Ian , John Jeyanthi H , Bainton Peter
Published: January 2004

Objectives

To investigate the quality of information in referrals for patients aged under 16 years referred for dental extraction under general anaesthesia (GA), to ascertain the knowledge and expectations of the parents of these patients, and to determine whether the number of teeth extracted in secondary care coincides with that of the referring dentist.

Design

Retrospective study of referrals of all patients aged under 16 years referred to community dental clinics in Berkshire, Buckinghamshire, Northamptonshire and Oxfordshire over a 26-day period.

Results

The majority (62.2%) of the 251 referrals examined were for extractions under GA. Of these, 125 were by letter and 117 using a pro forma. Significantly more pro formas (33) than letters (8) contained a full medical history (P<0.001). A treatment plan was included in significantly more pro formas (76) than letters (49) (P<0.01). Few referrals contained a note about the discussion of alternatives to a GA procedure and only 37% (58/156) of parents reported that the referring general dental practitioner had discussed alternative treatments with them. A total of 551 primary teeth were indicated for removal but 846 teeth were eventually removed.

Conclusions

Our findings indicate a need for parents of patients referred for GA procedures to be better informed about alternatives. Improvement in the quality of referrals, perhaps with the aid of standard pro formas, would also facilitate more effective management of referred patients.
Geological and Mineralogical Characterization of Zeolites in Lacustrine Tuffs, Ngakuru, Taupo Volcanic Zone, New Zealand
Authors: Brathwaite R. L.
Published: January 2004

Mordenite and clinoptilolite have replaced glass shards and pumice in vitric tuffs that are the products of ash fall-out into lake basins of late Quaternary age in the Taupo Volcanic Zone. The vitric tuffs are intercalated with siltstone and diatomite and overlie pumice-rich, rhyolitic ignimbrite. A Zr/TiO2-Nb/Y immobile element ratio plot indicates that the vitric tuffs, like the ignimbrite, are of rhyolitic composition. X-ray diffraction and scanning electron microscopy studies indicate that the mordenite and clinoptilolite are accompanied by authigenic K-feldspar and Opal-CT. The zeolites and other authigenic minerals are very fine grained (<10 µm), with open meshes of acicular mordenite crystals that result in low densities (0.7–1.0 g cm−3) in mordenite-rich tuffs. From Pearce element ratio analysis of whole-rock chemical analyses, only Na and K appear to have been mobilized during alteration. The zeolite deposits are associated with sinter, hydrothermal eruption breccias and silicified fault breccias that represent surface or near-surface manifestations of geothermal activity. Plant material extracted from a sinter overlying one of the deposits has a 14C age of 8498±60 BP, which is interpreted to be the age of zeolite deposition for this deposit. Mordenite and clinoptilolite occur in the lower-T (60–110°C) parts of some active or recently active geothermal systems elsewhere in the Taupo Volcanic Zone. The main fluid in these systems is weakly saline (alkali-chloride) water heated by geothermal activity. The Ngakuru zeolite deposits are interpreted as the products of the reaction of vitric tuffs with this type of water in the near-surface part of recently active geothermal systems.