bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of SWI/SNF chromatin remodeling complex on HIV-1 Tat activated transcription
Authors: Agbottah Emmanuel , Deng Longwen , Dannenberg Luke O , Pumfery Anne , Kashanchi Fatah
Published: August 2006

Background

Human immunodeficiency virus type 1 (HIV-1) is the etiologic agent of acquired immunodeficiency virus (AIDS). Following entry into the host cell, the viral RNA is reverse transcribed into DNA and subsequently integrated into the host genome as a chromatin template. The integrated proviral DNA, along with the specific chromatinized environment in which integration takes place allows for the coordinated regulation of viral transcription and replication. While the specific roles of and interplay between viral and host proteins have not been fully elucidated, numerous reports indicate that HIV-1 retains the ability for self-regulation via the pleiotropic effects of its viral proteins. Though viral transcription is fully dependent upon host cellular factors and the state of host activation, recent findings indicate a complex interplay between viral proteins and host transcription regulatory machineries including histone deacetylases (HDACs), histone acetyltransferases (HATs), cyclin dependent kinases (CDKs), and histone methyltransferases (HMTs).

Results

Here, we describe the effect of Tat activated transcription at the G1/S border of the cell cycle and analyze the interaction of modified Tat with the chromatin remodeling complex, SWI/SNF. HIV-1 LTR DNA reconstituted into nucleosomes can be activated in vitro using various Tat expressing extracts. Optimally activated transcription was observed at the G1/S border of the cell cycle both in vitro and in vivo, where chromatin remodeling complex, SWI/SNF, was present on the immobilized LTR DNA. Using a number of in vitro binding as well as in vivo chromatin immunoprecipitation (ChIP) assays, we detected the presence of both BRG1 and acetylated Tat in the same complex. Finally, we demonstrate that activated transcription resulted in partial or complete removal of the nucleosome from the start site of the LTR as evidenced by a restriction enzyme accessibility assay.

Conclusion

We propose a model where unmodified Tat is involved in binding to the CBP/p300 and cdk9/cyclin T1 complexes facilitating transcription initiation. Acetylated Tat dissociates from the TAR RNA structure and recruits bromodomain-binding chromatin modifying complexes such as p/CAF and SWI/SNF to possibly facilitate transcription elongation.
Three options for citation tracking: Google Scholar, Scopus and Web of Science
Authors: Bakkalbasi Nisa , Bauer Kathleen , Glover Janis , Wang Lei
Published: August 2006

Background

Researchers turn to citation tracking to find the most influential articles for a particular topic and to see how often their own published papers are cited. For years researchers looking for this type of information had only one resource to consult: the Web of Science from Thomson Scientific. In 2004 two competitors emerged – Scopus from Elsevier and Google Scholar from Google. The research reported here uses citation analysis in an observational study examining these three databases; comparing citation counts for articles from two disciplines (oncology and condensed matter physics) and two years (1993 and 2003) to test the hypothesis that the different scholarly publication coverage provided by the three search tools will lead to different citation counts from each.

Methods

Eleven journal titles with varying impact factors were selected from each discipline (oncology and condensed matter physics) using the Journal Citation Reports (JCR). All articles published in the selected titles were retrieved for the years 1993 and 2003, and a stratified random sample of articles was chosen, resulting in four sets of articles. During the week of November 7–12, 2005, the citation counts for each research article were extracted from the three sources. The actual citing references for a subset of the articles published in 2003 were also gathered from each of the three sources.

Results

For oncology 1993 Web of Science returned the highest average number of citations, 45.3. Scopus returned the highest average number of citations (8.9) for oncology 2003. Web of Science returned the highest number of citations for condensed matter physics 1993 and 2003 (22.5 and 3.9 respectively). The data showed a significant difference in the mean citation rates between all pairs of resources except between Google Scholar and Scopus for condensed matter physics 2003. For articles published in 2003 Google Scholar returned the largest amount of unique citing material for oncology and Web of Science returned the most for condensed matter physics.

Conclusion

This study did not identify any one of these three resources as the answer to all citation tracking needs. Scopus showed strength in providing citing literature for current (2003) oncology articles, while Web of Science produced more citing material for 2003 and 1993 condensed matter physics, and 1993 oncology articles. All three tools returned some unique material. Our data indicate that the question of which tool provides the most complete set of citing literature may depend on the subject and publication year of a given article.
Stochastic modeling of empirical time series of childhood infectious diseases data before and after mass vaccination
Authors: Trottier Helen , Philippe Pierre , Roy Roch
Published: August 2006

The goal of this paper is to analyze the stochastic dynamics of childhood infectious disease time series. We present an univariate time series analysis of pertussis, mumps, measles and rubella based on Box-Jenkins or AutoRegressive Integrated Moving Average (ARIMA) modeling. The method, which enables the dependency structure embedded in time series data to be modeled, has potential research applications in studies of infectious disease dynamics. Canadian chronological series of pertussis, mumps, measles and rubella, before and after mass vaccination, are analyzed to characterize the statistical structure of these diseases. Despite the fact that these infectious diseases are biologically different, it is found that they are all represented by simple models with the same basic statistical structure. Aside from seasonal effects, the number of new cases is given by the incidence in the previous period and by periodically recurrent random factors. It is also shown that mass vaccination does not change this stochastic dependency. We conclude that the Box-Jenkins methodology does identify the collective pattern of the dynamics, but not the specifics of the diseases at the biological individual level.
Characterization of the IFN-γ T-cell responses to immediate early antigens in humans with genital herpes
Authors: Braun Ralph P , Payne Lendon G , Dong Lichun
Published: August 2006

Background

The IFN-γ ELISPOT assay has been used to examine the T-cell repertoire for many disease states in humans but, as yet, not genital herpes. Using overlapping synthetic peptide libraries, an IFN-γ ELISPOT assay was established that could measure CD4 and CD8 T-cell responses to HSV-2 antigens in patients with genital herpes.

Results

In unexpanded T-cells isolated from peripheral blood, CD4 responses were readily measured against four immediate early antigens (ICP0, ICP4, ICP22 and ICP27), VP22 and gD. The CD4 responses were characterized by a low number of positive cells which produced large ELISPOTs. CD4 responses had a broad specificity and within individual patients several of the test antigens were recognized. In contrast, CD8 responses were found only in approximately 50% of patients and were typically specific to a single antigen. When disease status and immune responses were compared, an enhanced CD4 response to ICP4 in patients with a low recurrence rate was found. The ICP4 response was striking in three HSV-1 single positive genital herpes patients.

Conclusion

The survey of T-cell responses is an important step to understand the host cellular immune response in individuals with genital herpes. The assay described here has the capability of measuring CD4 and CD8 T-cell responses that may be used to correlate disease status with specific immune responses. In an evaluation of 18 subjects a trend of positive responses to an immediate early protein, ICP4, was found in individuals that had a low rate of disease recurrence.
Nonassociative learning as gated neural integrator and differentiator in stimulus-response pathways
Authors: Poon Chi-Sang , Young Daniel L
Published: August 2006

Nonassociative learning is a basic neuroadaptive behavior exhibited across animal phyla and sensory modalities but its role in brain intelligence is unclear. Current literature on habituation and sensitization, the classic "dual process" of nonassociative learning, gives highly incongruous accounts between varying experimental paradigms. Here we propose a general theory of nonassociative learning featuring four base modes: habituation/primary sensitization in primary stimulus-response pathways, and desensitization/secondary sensitization in secondary stimulus-response pathways. Primary and secondary modes of nonassociative learning are distinguished by corresponding activity-dependent recall, or nonassociative gating, of neurotransmission memory. From the perspective of brain computation, nonassociative learning is a form of integral-differential calculus whereas nonassociative gating is a form of Boolean logic operator – both dynamically transforming the stimulus-response relationship. From the perspective of sensory integration, nonassociative gating provides temporal filtering whereas nonassociative learning affords low-pass, high-pass or band-pass/band-stop frequency filtering – effectively creating an intelligent sensory firewall that screens all stimuli for attention and resultant internal model adaptation and reaction. This unified framework ties together many salient characteristics of nonassociative learning and nonassociative gating and suggests a common kernel that correlates with a wide variety of sensorimotor integration behaviors such as central resetting and self-organization of sensory inputs, fail-safe sensorimotor compensation, integral-differential and gated modulation of sensorimotor feedbacks, alarm reaction, novelty detection and selective attention, as well as a variety of mental and neurological disorders such as sensorimotor instability, attention deficit hyperactivity, sensory defensiveness, autism, nonassociative fear and anxiety, schizophrenia, addiction and craving, pain sensitization and phantom sensations, etc.
Failure of catecholamines to shift T-cell cytokine responses toward a Th2 profile in patients with rheumatoid arthritis
Authors: Wahle Matthias , Hanefeld Gesine , Brunn Stephan , Straub Rainer H , Wagner Ulf , Krause Andreas , Häntzschel Holm , Baerwald Christoph GO
Published: August 2006

To further understand the role of neuro-immunological interactions in the pathogenesis of rheumatoid arthritis (RA), we studied the influence of sympathetic neurotransmitters on cytokine production of T cells in patients with RA. T cells were isolated from peripheral blood of RA patients or healthy donors (HDs), and stimulated via CD3 and CD28. Co-incubation was carried out with epinephrine or norepinephrine in concentrations ranging from 10-5 M to 10-11 M. Interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-4, and IL-10 were determined in the culture supernatant with enzyme-linked immunosorbent assay. In addition, IFN-γ and IL-10 were evaluated with intracellular cytokine staining. Furthermore, basal and agonist-induced cAMP levels and catecholamine-induced apoptosis of T cells were measured. Catecholamines inhibited the synthesis of IFN-γ, TNF-α, and IL-10 at a concentration of 10-5 M. In addition, IFN-γ release was suppressed by 10-7 M epinephrine. Lower catecholamine concentrations exerted no significant effect. A reduced IL-4 production upon co-incubation with 10-5 M epinephrine was observed in RA patients only. The inhibitory effect of catecholamines on IFN-γ production was lower in RA patients as compared with HDs. In RA patients, a catecholamine-induced shift toward a Th2 (type 2) polarised cytokine profile was abrogated. Evaluation of intracellular cytokines revealed that CD8-positive T cells were accountable for the impaired catecholaminergic control of IFN-γ production. The highly significant negative correlation between age and catecholamine effects in HDs was not found in RA patients. Basal and stimulated cAMP levels in T-cell subsets and catecholamine-induced apoptosis did not differ between RA patients and HDs. RA patients demonstrate an impaired inhibitory effect of catecholamines on IFN-γ production together with a failure to induce a shift of T-cell cytokine responses toward a Th2-like profile. Such an unfavorable situation is a perpetuating factor for inflammation.
Effects of prolonged endotoxemia on liver, skeletal muscle and kidney mitochondrial function
Authors: Porta Francesca , Takala Jukka , Weikert Christian , Bracht Hendrik , Kolarova Anna , Lauterburg Bernhard H , Borotto Erika , Jakob Stephan M
Published: August 2006

Introduction

Sepsis may impair mitochondrial utilization of oxygen. Since hepatic dysfunction is a hallmark of sepsis, we hypothesized that the liver is more susceptible to mitochondrial dysfunction than the peripheral tissues, such as the skeletal muscle. We studied the effect of prolonged endotoxin infusion on liver, muscle and kidney mitochondrial respiration and on hepatosplanchnic oxygen transport and microcirculation in pigs.

Methods

Twenty anesthetized pigs were randomized to receive either endotoxin or saline infusion for 24 hours. Muscle, liver and kidney mitochondrial respiration was assessed. The cardiac output (thermodilution) and the carotid, superior mesenteric and kidney arterial, portal venous (ultrasound Doppler) and microcirculatory blood flow (laser Doppler) were measured, and systemic and regional oxygen transport and lactate exchange were calculated.

Results

Endotoxin infusion induced hyperdynamic shock and impaired the glutamate-dependent and succinate-dependent mitochondrial respiratory control ratio in the liver (glutamate, median (range) endotoxemia 2.8 (2.3–3.8) vs controls 5.3 (3.8–7.0); P < 0.001; succinate, endotoxemia 2.9 (1.9–4.3) vs controls 3.9 (2.6–6.3), P = 0.003). While the ADP added/oxygen consumed ratio was reduced with both substrates, the maximal ATP production was impaired only in the succinate-dependent respiration. Hepatic oxygen consumption and extraction, and the liver surface laser Doppler blood flow remained unchanged. Glutamate-dependent respiration in the muscle and kidney was unaffected.

Conclusion

Endotoxemia reduces the efficiency of hepatic mitochondrial respiration but neither skeletal muscle nor kidney mitochondrial respiration, independent of regional and microcirculatory blood flow changes.
Automatic annotation of eukaryotic genes, pseudogenes and promoters
Authors: Solovyev Victor , Kosarev Peter , Seledsov Igor , Vorobyev Denis
Published: August 2006

Background

The ENCODE gene prediction workshop (EGASP) has been organized to evaluate how well state-of-the-art automatic gene finding methods are able to reproduce the manual and experimental gene annotation of the human genome. We have used Softberry gene finding software to predict genes, pseudogenes and promoters in 44 selected ENCODE sequences representing approximately 1% (30 Mb) of the human genome. Predictions of gene finding programs were evaluated in terms of their ability to reproduce the ENCODE-HAVANA annotation.

Results

The Fgenesh++ gene prediction pipeline can identify 91% of coding nucleotides with a specificity of 90%. Our automatic pseudogene finder (PSF program) found 90% of the manually annotated pseudogenes and some new ones. The Fprom promoter prediction program identifies 80% of TATA promoters sequences with one false positive prediction per 2,000 base-pairs (bp) and 50% of TATA-less promoters with one false positive prediction per 650 bp. It can be used to identify transcription start sites upstream of annotated coding parts of genes found by gene prediction software.

Conclusion

We review our software and underlying methods for identifying these three important structural and functional genome components and discuss the accuracy of predictions, recent advances and open problems in annotating genomic sequences. We have demonstrated that our methods can be effectively used for initial automatic annotation of the eukaryotic genome.
GENCODE: producing a reference annotation for ENCODE
Authors: Harrow Jennifer , Denoeud France , Frankish Adam , Reymond Alexandre , Chen Chao-Kung , Chrast Jacqueline , Lagarde Julien , Gilbert James GR , Storey Roy , Swarbreck David , Rossier Colette , Ucla Catherine , Hubbard Tim , Antonarakis Stylianos E , Guigo Roderic
Published: August 2006

Background

The GENCODE consortium was formed to identify and map all protein-coding genes within the ENCODE regions. This was achieved by a combination of initial manual annotation by the HAVANA team, experimental validation by the GENCODE consortium and a refinement of the annotation based on these experimental results.

Results

The GENCODE gene features are divided into eight different categories of which only the first two (known and novel coding sequence) are confidently predicted to be protein-coding genes. 5' rapid amplification of cDNA ends (RACE) and RT-PCR were used to experimentally verify the initial annotation. Of the 420 coding loci tested, 229 RACE products have been sequenced. They supported 5' extensions of 30 loci and new splice variants in 50 loci. In addition, 46 loci without evidence for a coding sequence were validated, consisting of 31 novel and 15 putative transcripts. We assessed the comprehensiveness of the GENCODE annotation by attempting to validate all the predicted exon boundaries outside the GENCODE annotation. Out of 1,215 tested in a subset of the ENCODE regions, 14 novel exon pairs were validated, only two of them in intergenic regions.

Conclusion

In total, 487 loci, of which 434 are coding, have been annotated as part of the GENCODE reference set available from the UCSC browser. Comparison of GENCODE annotation with RefSeq and ENSEMBL show only 40% of GENCODE exons are contained within the two sets, which is a reflection of the high number of alternative splice forms with unique exons annotated. Over 50% of coding loci have been experimentally verified by 5' RACE for EGASP and the GENCODE collaboration is continuing to refine its annotation of 1% human genome with the aid of experimental validation.
Pairagon+N-SCAN_EST: a model-based gene annotation pipeline
Authors: Arumugam Manimozhiyan , Wei Chaochun , Brown Randall H , Brent Michael R
Published: August 2006

Background

This paper describes Pairagon+N-SCAN_EST, a gene annotation pipeline that uses only native alignments. For each expressed sequence it chooses the best genomic alignment. Systems like ENSEMBL and ExoGean rely on trans alignments, in which expressed sequences are aligned to the genomic loci of putative homologs. Trans alignments contain a high proportion of mismatches, gaps, and/or apparently unspliceable introns, compared to alignments of cDNA sequences to their native loci. The Pairagon+N-SCAN_EST pipeline's first stage is Pairagon, a cDNA-to-genome alignment program based on a PairHMM probability model. This model relies on prior knowledge, such as the fact that introns must begin with GT, GC, or AT and end with AG or AC. It produces very precise alignments of high quality cDNA sequences. In the genomic regions between Pairagon's cDNA alignments, the pipeline combines EST alignments with de novo gene prediction by using N-SCAN_EST. N-SCAN_EST is based on a generalized HMM probability model augmented with a phylogenetic conservation model and EST alignments. It can predict complete transcripts by extending or merging EST alignments, but it can also predict genes in regions without EST alignments. Because they are based on probability models, both Pairagon and N-SCAN_EST can be trained automatically for new genomes and data sets.

Results

On the ENCODE regions of the human genome, Pairagon+N-SCAN_EST was as accurate as any other system tested in the EGASP assessment, including ENSEMBL and ExoGean.

Conclusion

With sufficient mRNA/EST evidence, genome annotation without trans alignments can compete successfully with systems like ENSEMBL and ExoGean, which use trans alignments.
Using several pair-wise informant sequences for de novo prediction of alternatively spliced transcripts
Authors: Flicek Paul , Brent Michael R
Published: August 2006

Background

As part of the ENCODE Genome Annotation Assessment Project (EGASP), we developed the MARS extension to the Twinscan algorithm. MARS is designed to find human alternatively spliced transcripts that are conserved in only one or a limited number of extant species. MARS is able to use an arbitrary number of informant sequences and predicts a number of alternative transcripts at each gene locus.

Results

MARS uses the mouse, rat, dog, opossum, chicken, and frog genome sequences as pairwise informant sources for Twinscan and combines the resulting transcript predictions into genes based on coding (CDS) region overlap. Based on the EGASP assessment, MARS is one of the more accurate dual-genome prediction programs. Compared to the GENCODE annotation, we find that predictive sensitivity increases, while specificity decreases, as more informant species are used. MARS correctly predicts alternatively spliced transcripts for 11 of the 236 multi-exon GENCODE genes that are alternatively spliced in the coding region of their transcripts. For these genes a total of 24 correct transcripts are predicted.

Conclusion

The MARS algorithm is able to predict alternatively spliced transcripts without the use of expressed sequence information, although the number of loci in which multiple predicted transcripts match multiple alternatively spliced transcripts in the GENCODE annotation is relatively small.
Delay in the Diagnosis of Acute Myocardial Infarction: Effect on Quality of Care and Its Assessment
Authors: Graff Louis G. , Wang Yun , Borkowski Brian , Tuozzo Kathy , Foody JoAnne M. , Krumholz Harlan M. , Radford Martha J.
Published: August 2006

Background:
Delay in diagnosis of acute myocardial infarction (AMI) may affect quality of care and its assessment.

Objectives:
To examine over time the frequency of delay in AMI diagnosis and the effect of this delay on the quality of patient care and its assessment.

Methods:
The authors examined the trend in coded admission diagnosis, age, comorbidities, procedures during hospitalization, and discharge status for 42,406 Connecticut Medicare cases with the principal discharge diagnosis of AMI for the time period 1992 through 2001. For 2,583 cases discharged in 1992 and 1993 and for 1,398 cases discharged in 1998 through 2001, the rates of administration of aspirin (ASA) and beta blocker (BB) on admission and discharge, by admission diagnosis, were ascertained.

Results:
For patients discharged with the principal diagnosis of AMI over the decade examined, the proportion with this diagnosis on admission fell (59% to 40%, p < 0.001), the proportion with a non–acute coronary syndrome (ACS) admission diagnosis rose (18% to 26%, p < 0.001), and the population aged (proportion older than 85 years of age increased from 16% to 28%, p < 0.001). Patients with ACS as the admission diagnosis more frequently received cardiac catheterization (during 2000–2001, 39% versus 17%, p < 0.001), percutaneous coronary intervention (19% versus 4%, p < 0.001), and evidence‐based therapy; during 1998–2001, opportunities to give ASA or BB on admission were fulfilled for 88% versus 73% (p < 0.001), and on discharge, for 87% versus 74% (p < 0.005).

Conclusions:
The diagnosis of AMI is delayed after admission for a significant proportion of cases who receive care that is measured to be of lower quality. There is a need to more effectively diagnose and treat these cases with delayed diagnosis and to develop new quality measures to address changes in the characteristics of patients who are hospitalized with AMI.
Emergency Department Sexually Transmitted Disease and Human Immunodeficiency Virus Screening: Findings from a National Survey
Authors: Gift Thomas L. , Hogben Matthew
Published: August 2006

Objectives:
To use a previously conducted national physician survey to determine the extent of human immunodeficiency virus (HIV) and sexually transmitted disease (STD) screening by emergency physicians compared with physicians practicing in other settings (primary care offices, hospital ambulatory care clinics, or other).

Methods:
From the survey responses, the authors determined the percentage of emergency physicians and physicians not practicing in EDs screening various patient groups for syphilis, gonorrhea, chlamydia, and HIV. Additional data from the survey (for practice location, physician gender, and patient demographics of race and gender) were used in multivariate logistic regressions to determine adjusted odds ratios (ORs).

Results:
Of 3,838 survey respondents providing answers to all questions analyzed for this study, 401 (10.5%) practiced in an emergency department. Of the remaining 3,437 physicians, 89% practiced in primary care offices or hospital ambulatory care clinics. Based on unadjusted ORs, emergency physicians were less likely than physicians not practicing in EDs to screen for all STDs and HIV in all patient groups (men, nonpregnant women, and pregnant women), although the differences in screening rates in male patients for chlamydia or gonorrhea were not significant. The adjusted ORs varied from 0.136 (for HIV screening of pregnant women) to 1.177 (for gonorrhea screening of pregnant women). All adjusted ORs that were significant at p < 0.05 were < 1.0.

Conclusions:
Although prior research has shown that STD and HIV rates are relatively high in emergency department patients compared with the population as a whole, screening rates are lower than in other settings. Addressing barriers may increase screening rates.
A Comparison of Five Simplified Scales to the Out‐of‐hospital Glasgow Coma Scale for the Prediction of Traumatic Brain Injury Outcomes
Authors: Gill Michelle , Steele Robert , Windemuth Ryan , Green Steven M.
Published: August 2006

Background:
The 15‐point Glasgow Coma Scale (GCS) frequently is used in the initial evaluation of traumatic brain injury (TBI) in out‐of‐hospital settings. We hypothesized that the GCS might be unnecessarily complex for out‐of‐hospital use.

Objectives:
To assess whether a simpler scoring system might demonstrate similar accuracy in the prediction of TBI outcomes.

Methods:
We performed a retrospective analysis of a trauma registry consisting of patients evaluated at our Level 1 trauma center from 1990 to 2002. The ability of out‐of‐hospital GCS scores to predict four clinically relevant TBI outcomes (emergency intubation, neurosurgical intervention, brain injury, and mortality) by using areas under receiver operating characteristic curves (AUROCs) was calculated. The same analyses for five simplified scales were performed, and compared with the predictive accuracies of the total GCS score.

Results:
In this evaluation of 7,233 trauma patients over a 12‐year period of time, the AUROCs for the total GCS score were 0.83 (95% confidence interval [CI] = 0.81 to 0.84) for emergency intubation, 0.86 (95% CI = 0.85 to 0.88) for neurosurgical intervention, 0.83 (95% CI = 0.82 to 0.84) for brain injury, and 0.89 (95% CI = 0.88 to 0.90) for mortality. The five simplified scales approached the performance of the total GCS score for all clinical outcomes.

Conclusions:
In the evaluation of injured patients, five simplified neurological scales approached the performance of the total GCS score for the prediction of four clinically relevant TBI outcomes.
A GCUA tetranucleotide loop found in the poliovirus oriL by in vivo SELEX (un)expectedly forms a YNMG-like structure: Extending the YNMG family with GYYA
Authors: Melchers Willem J.G. , Zoll Jan , Tessari Marco , Bakhmutov Denis V. , Gmyl Anatoly P. , Agol Vadim I. , Heus Hans A.
Published: August 2006

The cloverleaf structure in the 5′-untranslated region of enterovirus RNA that regulates viral RNA replication contains an evolutionarily conserved YNMG tetraloop closed by a Y-G base pair. This loop is believed to interact specifically with the viral protease 3C. To further characterize the specificity of this interaction, the tetraloop and two flanking base pairs of the poliovirus RNA were randomized, and viable viral clones were obtained using in vivo SELEX. Among many different mutants with the canonical YNMG sequences to be described elsewhere, a large-plaque-forming clone contained a deviating uGCUAg sequence. The NMR structure of a small hairpin capped with uGCUAg that we present here shows that the GCUA tetraloop adopts a novel fold, which is highly similar to that of the YNMG tetraloop with common stacking properties and hydrogen-bond interactions including an unusual syn conformation of the adenosine. Thermodynamic studies show moderate stabilities of hairpins with canonical YNMG and the novel GCUA loops, which, together with the similarity of spatial structures, illustrates that the tetraloop structure itself is crucial for the RNA–protein interaction required for the viral replication. A re-evaluation of the ribosomal secondary structure database reveals a hairpin containing a GCUA loop, which covaries with YNMG and is involved in a tertiary interaction, and in the 50S ribosomal subunit from Haloarcula marismortui the structurally comparable apex of stem–loop 35a is a recognition site for protein L2. These observations show a more general occurrence and importance of the so-far unrecognized GYYA hairpin loops.
Fluorescence and solution NMR study of the active site of a 160-kDa group II intron ribozyme
Authors: Gumbs Orlando H. , Padgett Richard A. , Dayie Kwaku T.
Published: August 2006

We have reconstructed the group II intron from Pylaiella littoralis (PL) into a hydrolytic ribozyme, comprising domains 1–3 (D123) connected in cis plus domain 5 (D5) supplied in trans that efficiently cleaves spliced exon substrates. Using a novel gel-based fluorescence assay and nuclear magnetic resonance (NMR) spectroscopy, we monitored the direct binding of D5 to D123, characterized the kinetics of the spliced exon hydrolysis reaction (which is mechanistically analogous to the reverse of the second catalytic step of splicing), and identified the binding surface of D123 on D5. This PL ribozyme acts as an RNA endonuclease even at low monovalent (100 mM KCl) and divalent ion concentrations (1–10 mM MgCl2). This is in contrast to other group II intron ribozyme systems that require high levels of salt, making NMR analysis problematic. D5 binds tightly to D123 with a Kd of 650 ± 250 nM, a Km of ∼300 nM, and a Kcat of 0.02 min−1 under single turnover conditions. Within the ∼160-kDa D123–D5 binary complex, site-specific binding to D123 leads to dramatic chemical shift perturbation of residues localized to the tetraloop and internal bulge within D5, suggesting a structural switch model for D5-assisted splicing. This minimal ribozyme thus recapitulates the essential features of the reverse of the second catalytic step and represents a well-behaved system for ongoing high-resolution structural work to complement folding and catalytic functional studies.
Thermodynamic Study of Complexation of (2-Mercapto-4-Methyl Phenyl)-2-Benzamido-3-Ethoxy Thiopropenate with Cu2+, Co2+, and Hg2+ in Binary Dimethylsulphoxide–Acetonitrile Solutions
Authors: Hosseini S. M. A. , Saeed. S V.
Published: August 2006

The complexation of a newly synthesized mercapto compound, (2-mercapto-4-methyl phenyl)-2-benzamido-3-ethoxy thiopropenate, with Co2+, Cu2+, and Hg2+ have been studied in binary dimethylsulphoxide–acetonitrile (DMSO-AN) mixtures at different temperatures by a conductometric technique. Stoichiometry and stability of the resulting complexes were evaluated by KINFIT program and from molar conductivity–mol ratio (ligand to metal) data were found to vary in the sequence Co2+ > Cu2+ > Hg2+. In all cases, evidence for the formation of both 1:1 and 2:1 (ligand to metal) complexes were obtained. The stability of these complexes increases with decreasing temperature. The enthalpy and entropy of complexation were determined from the temperature dependence of the formation constants. In all cases, the complexes were found to be enthalpy and entropy stabilized. Furthermore, in all of the complexes which were studied, not only an increase in the percentage of dimethylsulfoxide in DMSO-AN solvents mixtures would drastically decrease the stability of the resulting complexes, but also enthalpy and entropy would be more positive and negative respectively (decrease of stability).
Effect of Sodium Acetate and Magnesium Acetate on the Solution Behavior of Some Amino Acids in Water at 298.15 K: A Compressibility Approach
Authors: Banipal Tarlok Singh , Kaur Damanjit , Banipal Parampaul Kaur
Published: August 2006

Apparent molar adiabatic compressibility, K
2,φ,S, of glycine, DL-α-alanine, DL-α-amino-n-butyric acid, L-leucine and L-phenylalanine in water and in (0.5, 1.0, 2.0, 4.0, 5.5 mol kg−1) aqueous sodium acetate and in (0.5, 1.0, 1.5, 2.0 mol kg−1) aqueous magnesium acetate solutions has been determined from sound velocity, u, measurements at 298.15 K. The partial molar adiabatic compressibilities at infinite dilution, K
0
2,S, obtained from K
2,φ,S data have been used to calculate the corresponding partial molar adiabatic compressibilities of transfer at infinite dilution, Δt
K
0
2,S, from water to aqueous sodium acetate and magnesium acetate (cosolutes) solutions. The Δt
K
0
2,S values are positive for the studied amino acids in case of both the cosolutes and the values increase with the increase of the concentrations of both the cosolutes. The trends of Δt
K
0
2,S have been rationalized in terms of the hydration of hydrophilic and hydrophobic parts of the amino acids studied. The interaction coefficients and hydration number, n
H, have also been calculated and are discussed in terms of the dehydration effect of sodium acetate and magnesium acetate upon the amino acids in solutions. Attempt has been made to correlate these results with the earlier reported volumetric and viscometric studies for the same systems.
Studies on the Formation and Kinetics of Self-Decomposition of Ni(IV)-N3
− Complexes in Aqueous Media
Authors: Jurczakowski Rafał , Litwinienko Grzegorz , Orlik Marek
Published: August 2006

Both electrochemical (at Pt electrode) and homogeneous (with Cl2(aq)) oxidation of the aqueous solution of Ni(II)-N3
− yields the solution of a brown product that was found to be the azide complex of Ni(IV). Its UV/Vis spectrum, consisting of a single band of high intensity (ε = 26500 cm−1 dm3 mol−1 at λmax = 471 nm), has been ascribed to the ligand-to-metal charge-transfer mechanism (LMCT). The Ni(IV)-N3
− complex undergoes spontaneous decomposition in aqueous solution, with Ni(IV) reduced back to Ni(II) and N3
− oxidized to molecular nitrogen. The first-order kinetics of this process was studied spectrophotometrically and the following parameters were found: rate constant k = 1.96×10−2 s−1, Arrhenius activation energy E
a = 82±7 kJ mol−1, standard activation enthalpy ΔH
≠0 = 79±7 kJ mol−1, and small standard activation entropy ΔS
≠0 = 10±20 J mol−1 K−1. The outline mechanism for the intramolecular redox Ni(IV)-N3
− decomposition has been suggested. Nickel ions at various oxidation states were found to be powerful catalysts for the redox processes of azide ions.
Characterizations of univariate continuous distributions, III
Authors: Hamedani Gholamhoss G. , Hamedani Gholamhoss G.
Published: August 2006

This is a follow up to our previous works characterizing well-known univariate continuous distributions based on a simple relationship between two truncated moments. Three of the distributions considered here unify many distributions employed for size distribution of income (which were characterized in our previous works). Another three distributions characterized here, were first introduced in the context of minimum dynamic discrimination information approch to probability modeling.
Lethal congenital contracture syndrome (LCCS) and other lethal arthrogryposes in Finland—An epidemiological study
Authors: Pakkasjärvi Niklas , Ritvanen Annukka , Herva Riitta , Peltonen Leena , Kestilä Marjo , Ignatius Jaakko
Published: August 2006

Arthrogryposis multiplex congenita is a heterogeneous group of disorders characterized by multiple contractures with an estimated frequency of 1 in 3,000 births. With improving diagnostic methods, increasing numbers of fetuses with arthrogryposis are found. The pathogenetic mechanisms are relatively well known but the epidemiology and genetics of the prenatally lethal forms of arthrogryposis are less well known. In this study we collected all cases of a multiple contractures diagnosed in Finland during 1987–2002 including live born infants, stillbirths, and terminated pregnancies. Ninety‐two cases of 214 suffered intrauterine demise (68 selective pregnancy terminations and 24 stillbirths) and 58 died in infancy. In 141 out of these cases the diagnosis could be included within lethal arthrogryposes, with a prevalence of 1 in 6,985 (1.43/10,000) births. Of these, 59 had spinal cord pathology at autopsy and thus were of neurogenic origin. Thirty‐nine cases had lethal congenital contracture syndrome (LCCS) clinically characterized by total immobility of the fetus at all ultrasound examinations (12 weeks or later), multiple joint contractures in both upper and lower limbs, hydrops, and fetal death before the 32nd week of pregnancy. LCCS is noted as a unique Finnish disorder with a prevalence of 1 in 25,250 (0.40/10,000) births and is a major cause of lethal arthrogryposis in Finland. © 2006 Wiley‐Liss, Inc.
SALL1 mutations in sporadic Townes–Brocks syndrome are of predominantly paternal origin without obvious paternal age effect
Authors: Böhm Johann , Munk‐Schulenburg Susanne , Felscher Stephanie , Kohlhase Jürgen
Published: August 2006

Autosomal dominant Townes–Brocks syndrome (TBS) is characterized by imperforate anus, triphalangeal and supernumerary thumbs, dysplastic ears and sensorineural hearing loss, and may also involve other organ systems. Strong inter‐ and intrafamiliar variability is known. Approximately 50% of TBS cases are sporadic and due to de novo mutations in the SALL1 gene. SALL1 encodes a zinc finger protein operating as a transcriptional repressor and localizing to pericentromeric heterochromatin. We traced the parental origin of SALL1 mutations in sporadic TBS by analysis of linkage between SALL1 mutations and exonic or intronic polymorphisms in 16 families with 10 different mutations. Mutations were of paternal origin in 14 of 16 cases (87.5%). Paternal origin was independent of the mutation type. The mean paternal age at conception was 29.9 and the mean maternal age 26.5 years. We conclude that de novo mutations in SALL1 mostly occur on the paternally derived chromosome 16 without an obvious age effect. © 2006 Wiley‐Liss, Inc.
Clinical outcome of infants with confined placental mosaicism and intrauterine growth restriction of unknown cause
Authors: Miura Kiyonori , Yoshiura Koh‐ichiro , Miura Shoko , Kondoh Tatsuro , Harada Naoki , Yamasaki Kentaro , Fujimoto Yoko , Yamasaki Yoko , Tanigawa Terumi , Kitajima Yuriko , Shimada Takako , Yoshida Atsushi , Nakayama Daisuke , Tagawa Masato , Yoshimura Shuichiro , Wagstaff Joseph , Jinno Yoshihiro , Ishimaru Tadayuki , Niikawa Norio , Masuzaki Hideaki
Published: August 2006

The purpose of this study was to know a role of confined placental mosaicism (CPM) in perinatal outcome and postnatal growth and development of infants with intrauterine growth restriction (IUGR). We selected 50 infants with IUGR (<−2.0 SD) from 3,257 deliveries in a regional medical center during the past 10‐year period, and carried out cytogenetic and molecular analyses in their placenta and cord blood. Of the 50 infants, 8 had CPM (CPM group) and were composed of five single (CPM2, 7, 13, 22, and 22), one double (CPM7/13), and one quadruple trisomy (CPM2/7/15/20), and one partial monosomy [del(2)(p16)]. The origin of an extra chromosome of trisomy was maternal in six cases of CPM, paternal in one, and undetermined in one. Uniparental disomy in disomic cell lines was ruled out in all these mosaics. We also compared clinical parameters for perinatal outcome between CPM group and infants without evidence of CPM (non‐CPM group), such as maternal and gestational age, birth weight, Apgar score, cord blood pH, gender, and uterine artery patterns by Doppler ultrasonography, as well as weight, height, and developmental quotient (DQ) by Denver Developmental Screening Test at age 12 months. Phenotypic abnormalities were noted in two infants with CPM and three infants of non‐CPM group: One with CPM22 had ASD and hypospadias, one with CPM7/13 had Russell–Silver syndrome (RSS), and one without CPM had polydactyly, and two without CPM had RSS. All but one infant with CPM are alive at age 12 months. Among the clinical parameters, the detection rate of a notch waveform pattern of the uterine artery was significantly higher in the CPM group (P < 0.05). However, no significant difference was noted in perinatal outcome of pregnancy and in DQ at age 12 months between the two groups. Interestingly, short stature (<−2 SD) at age 12 months was more frequently seen in CPM group (7/8 infants with CPM vs. 8/15 infants without CPM), although no statistically significant difference was obtained. The information obtained will be useful for perinatal care and genetic counseling for infants with IUGR and CPM. © 2006 Wiley‐Liss, Inc.
Increased eNOS accounts for changes in connexin expression in renal arterioles during diabetes
Authors: Zhang Jian Hong , Kawashima Seinosuke , Yokoyama Mitsuhiro , Huang Paul , Hill Caryl E.
Published: August 2006

Previous studies have shown that connexin (Cx) expression is considerably higher in the preglomerular compared to postglomerular vasculature and that these differences are accentuated during diabetes. Since nitric oxide (NO) has been reported to alter Cx expression in endothelial cells and muscle cells and NO bioavailability is altered in diabetes, we hypothesized that NO may be responsible for the changes during diabetes. Cx expression was studied using immunohistochemistry in mice in which eNOS expression was either upregulated (eNOS transgenic) or downregulated (eNOS knockout). Diabetes was induced intraperitoneally with a single dose of alloxan or multiple low doses of streptozotocin. Expression of Cx40 in smooth muscle cells of afferent arterioles was increased, while expression of Cx43 in endothelial cells of efferent arterioles was absent in eNOS transgenic mice, similar to the changes occurring in wild‐type mice during diabetes. Expression of Cx40 and Cx43 in eNOS knockout mice was not different from control; however, induction of diabetes in eNOS knockout mice failed to produce any changes in Cx40 or Cx43 in either afferent or efferent arterioles. Immunohistochemistry showed that eNOS expression was increased in the endothelium of renal arterioles in wild‐type diabetic and eNOS transgenic mice, but absent from arterioles of eNOS knockout mice. We conclude that changes occurring in Cx expression in afferent and efferent arterioles during diabetes may result from increased eNOS. Anat Rec Part A, 288A:1000–1008, 2006. © 2006 Wiley‐Liss, Inc.
Plan to be Flexible: A Commentary on Adaptive Designs
Authors: Shih Weichung Joe
Published: August 2006

This is a discussion of the following three papers appearing in this special issue on adaptive designs: ‘Nested repeated confidence intervals and switching between noninferiority and superiority’ by Joachim Hartung and Guido Knapp; ‘Confirmatory Seamless Phase II/III Clinical trials with Hypotheses Selection at Interim: General Concepts’ by Frank Bretz, Heinz Schmidli, Franz König, Amy Racine and Willi Maurer; and ‘Confirmatory Seamless Phase II/III Clinical Trials with Hypotheses Selection at Interim: Applications and Practical Considerations’ by Heinz Schmidli, Frank Bretz, Amy Racine and Willi Maurer. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Discrimination of normal, benign, and malignant breast tissues by Raman spectroscopy
Authors: Chowdary M. V. P. , Kumar K. Kalyan , Kurien Jacob , Mathew Stanley , Krishna C. Murali
Published: August 2006

Breast cancers are the leading cancers among females. Diagnosis by fine needle aspiration cytology (FNAC) is the gold standard. The widely practiced screening method, mammography, suffers from high false positive results and repeated exposure to harmful ionizing radiation. As with all other cancers survival rates are shown to heavily depend on stage of the cancers (Stage 0, 95%; Stage IV, 75%). Hence development of more reliable screening and diagnosis methodology is of considerable interest in breast cancer management. Raman spectra of normal, benign, and malignant breast tissue show significant differences. Spectral differences between normal and diseased breast tissues are more pronounced than between the two pathological conditions, malignant and benign tissues. Based on spectral profiles, the presence of lipids (1078, 1267, 1301, 1440, 1654, 1746 cm−1) is indicated in normal tissue and proteins (stronger amide I, red shifted ΔCH2, broad and strong amide III, 1002, 1033, 1530, 1556 cm−1) are found in benign and malignant tissues. The major differences between benign and malignant tissue spectra are malignant tissues seem to have an excess of lipids (1082, 1301, 1440 cm−1) and presence of excess proteins (amide I, amide III, red shifted ΔCH2, 1033, 1002 cm−1) is indicated in benign spectra. The multivariate statistical tool, principal components analysis (PCA) is employed for developing discrimination methods. A score of factor 1 provided a reasonable classification of all three tissue types. The analysis is further finetuned by employing Mahalanobis distance and spectral residuals as discriminating parameters. This approach is tested both retrospectively and prospectively. The limit test, which provides the most unambiguous discrimination, is also considered and this approach clearly discriminated all three tissue types. These results further support the efficacy of Raman spectroscopic methods in discriminating normal and diseased breast tissues. © 2006 Wiley Periodicals, Inc. Biopolymers 83:556–569, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Percutaneous ex‐vivo femoral arterial bypass: A novel approach for treatment of acute limb ischemia as a complication of femoral arterial catheterization
Authors: Merhi William M. , Turi Zoltan G. , Dixon Simon , Safian Robert D.
Published: August 2006

This report describes the use of a percutaneous ex‐vivo femoral arterial bypass in three patients with acute lower extremity ischemia that occurred as a complication of femoral artery catheterization. Utilizing standard equipment and techniques, a percutaneous ex‐vivo femoral artery bypass can restore antegrade flow to the ischemic limb in patients with impaired aorto‐iliac inflow circulation, which may arise from iatrogenic dissection or the need for large in‐dwelling sheaths required for hemodynamic support. This technique is considered a temporizing measure when conventional therapies are not possible. Contrast angiography is recommended to localize and define the cause of limb ischemia, and to permit safe placement of vascular sheaths in the “donor and recipient” arteries. © 2006 Wiley‐Liss, Inc.