bluuebunny/crossref_metadata_2025_split huggingface dataset:
Packaging of the Virion Host Shutoff (Vhs) Protein of Herpes Simplex Virus: Two Forms of the Vhs Polypeptide Are Associated with Intranuclear B and C Capsids, but Only One Is Associated with Enveloped Virions
Authors: Read G. Sullivan , Patterson Mary 
Published: November 2006

ABSTRACT
The virion host shutoff (Vhs) protein (UL41) is a minor component of herpes
simplex virus virions which, following penetration, accelerates
turnover of host and viral mRNAs. Infected cells contain 58-kDa and
59.5-kDa forms of Vhs, which differ in the extent of phosphorylation,
yet only a 58-kDa polypeptide is incorporated into virions. In
pulse-chase experiments, the primary Vhs translation product comigrated
in sodium dodecyl sulfate-polyacrylamide gel electrophoresis with the
58-kDa virion polypeptide, and could be chased to 59.5 kDa. While both
59.5-kDa and 58-kDa forms were found in nuclear and cytoplasmic
fractions, the 59.5-kDa form was significantly enriched in the nucleus.
Both forms were associated with intranuclear B and C capsids, yet only
the 58-kDa polypeptide was found in enveloped cytoplasmic virions. A
58-kDa form, but not the 59.5-kDa form, was found in L particles,
noninfectious particles that contain an envelope and tegument but no
capsid. The data suggest that virions contain two populations of Vhs
that are packaged by different pathways. In the first pathway, the
primary translation product is processed to 59.5 kDa, is transported to
the nucleus, binds intranuclear capsids, and is converted to 58 kDa at
some stage prior to final envelopment. The second pathway
does not involve the 59.5-kDa form or interactions between Vhs and
capsids. Instead, the primary translation product is phosphorylated to
the 58-kDa virion form and packaged through interactions with other
tegument proteins in the cytoplasm or viral envelope proteins at the
site of final
envelopment.
PATH-BASED SYSTEMS TO GUIDE SCIENTISTS IN THE MAZE OF BIOLOGICAL DATA SOURCES
Authors: COHEN-BOULAKIA SARAH , DAVIDSON SUSAN , FROIDEVAUX CHRISTINE , LACROIX ZOÉ , VIDAL MARIA-ESTHER 
Published: November 2006

Fueled by novel technologies capable of producing massive amounts of data for a single experiment, scientists are faced with an explosion of information which must be rapidly analyzed and combined with other data to form hypotheses and create knowledge. Today, numerous biological questions can be answered without entering a wet lab. Scientific protocols designed to answer these questions can be run entirely on a computer. Biological resources are often complementary, focused on different objects and reflecting various experts' points of view. Exploiting the richness and diversity of these resources is crucial for scientists. However, with the increase of resources, scientists have to face the problem of selecting sources and tools when interpreting their data. In this paper, we analyze the way in which biologists express and implement scientific protocols, and we identify the requirements for a system which can guide scientists in constructing protocols to answer new biological questions. We present two such systems, BioNavigation and BioGuide dedicated to help scientists select resources by following suitable paths within the growing network of interconnected biological resources.
Review: Combination therapy with non-clozapine atypical antipsychotic medication: a review of current evidence
Authors: Chan Jenifer , Sweeting Melinda 
Published: November 2006

Use of combined antipsychotics for patients with treatmentresistant/refractory schizophrenia is common practice in psychiatry. The objective of this paper is to review the current literature on combining non-clozapine atypical antipsychotics as well as discussing the theoretical benefits and risks, and summarizing the implications for clinical practice. We found in cases of treatment-resistant schizophrenia, where clozapine is deemed inappropriate, combination therapy with non-clozapine atypical antipsychotics is a strategy worthy of consideration. Combinations using olanzapine with either amisulpride or risperidone — or quetiapine with risperidone — in theory act on different receptor profiles and in the limited data available have shown improvement in symptoms, been used most frequently, and on balance have more data on safety. Initial case reports suggest that aripiprazole combined with non-clozapine atypicals may worsen psychosis. The current literature, however, has significant limitations. For this reason, due to the lack of data on safety, caution is recommended. There needs to be further well-designed studies with the aim to specifically investigate the effects of combination therapy to allow the clinician to better balance the risks and benefits (both clinical and economical) of treatment.
Selective verbal and spatial memory impairment after 5-HT1A and 5-HT2A receptor blockade in healthy volunteers pre-treated with an SSRI
Authors: Wingen M. , Kuypers K.P.C. , Ramaekers J.G. 
Published: November 2006

Serotonergic neurotransmission has been implicated in memory impairment. It is uncLear however if memory performance is mediated through general 5-HT availability, through specific 5-HT receptors or both. The aim of the present study was to assess the contribution of 5-HT reuptake inhibition and specific blockade of 5-HT1A and 5-HT2A receptors to memory impairment. The study was conducted according to a randomized, double-blind, placebo-controlled, four-way cross-over design including 16 healthy volunteers. The treatment consisted of oral administration of escitalopram 20 mg + placebo, escitalopram 20 mg + ketanserin 50 mg, escitalopram 20 mg + pindolol 10 mg and placebo on 4 separate days with a washout period of minimum 7 days. Different memory tasks were performed including verbal memory, spatial working memory and reversal learning. Escitalopram showed an impairing effect on immediate verbal recall which nearly reached statistical significance. No effects of escitalopram were found on other types of memory. In combination with pindolol, immediate verbal recall was significantly impaired. Escitalopram in combination with ketanserin impaired spatial working memory significantly. No effects were found on reversal learning. Selective impairment of immediate verbal recall after a 5-HT1A partial agonist and selective impairment of spatial working memory performance after 5-HT2A receptor antagonist, both in combination with a selective serotonergic reuptake inhibitor (escitalopram), suggests that 5-HT1A and 5-HT2A receptors are distinctly involved in verbal and spatial memory.
Effects of Local Administration of Vascular Endothelial Growth Factor on Mechanical Characteristics of the Semitendinosus Tendon Graft after Anterior Cruciate Ligament Reconstruction in Sheep
Authors: Yoshikawa Toshikazu , Tohyama Harukazu , Katsura Taro , Kondo Eiji , Kotani Yoshihisa , Matsumoto Hideo , Toyama Yoshiaki , Yasuda Kazunori 
Published: November 2006

Background Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis. Hypothesis An application of VEGF may enhance angiogenesis in the grafted tendon in anterior cruciate ligament (ACL) reconstruction, and the application may affect mechanical characteristics of the ACL graft. Study Design Controlled laboratory study. Methods Eighteen sheep were divided into groups I and II. In group I, the harvested semitendinosus tendon was soaked in VEGF solution, and the right knee then underwent ACL reconstruction using this tendon. In group II, the right knee underwent identical procedures to those of group I except that the harvested tendon was soaked in phosphate-buffered saline. All animals were sacrificed 12 weeks after ACL reconstruction. Results Histologic findings showed that newly formed vessels and infiltrative fibroblasts were more abundant in group I than in group II. The anterior-posterior translation of the knee during an anterior-posterior force of ±100 N was significantly larger in group I than in group II by 2.58 mm (95% confidence interval, -1.76 mm to 1.76 mm) (P =. 002). The linear stiffness of the femur-graft-tibia complex in group I was significantly lower than that in group II by 41.5 N/mm (95% confidence interval, -32.2 N/mm to 32.2 N/mm) (P=. 017). Conclusion This study has revealed that VEGF as administered in this study promotes angiogenesis in the ACL graft and significantly reduces the stiffness of the ACL graft with increased knee laxity at 12 weeks after ACL reconstruction. Clinical Relevance Exogenous VEGF application for ACL reconstruction can induce an increase in knee laxity and a decrease in the stiffness of the grafted tendon at least temporarily after ACL reconstruction. These potentially negative mechanical effects need to be taken into account when considering clinical use of VEGF.
Circulating proteasome levels are an independent prognostic factor for survival in multiple myeloma
Authors: Jakob Christian , Egerer Karl , Liebisch Peter , Türkmen Seval , Zavrski Ivana , Kuckelkorn Ulrike , Heider Ulrike , Kaiser Martin , Fleissner Claudia , Sterz Jan , Kleeberg Lorenz , Feist Eugen , Burmester Gerd-R. , Kloetzel Peter-M. , Sezer Orhan 
Published: November 2006

Abstract
The proteasome is a proteolytic complex for intracellular degradation of ubiquitinated proteins which are involved in cell-cycle regulation and apoptosis. A constitutively increased proteasome activity has been found in myeloma cells. We studied circulating proteasome levels and their prognostic significance in sera of 50 control subjects, 20 persons with monoclonal gammopathies of undetermined significance (MGUS), and 141 previously untreated patients with multiple myeloma (MM) by an anti-20S proteasome enzyme-linked immunoabsorbent assay (ELISA). Serum proteasome concentrations were significantly elevated in MM compared with controls (P < .001), in MM versus MGUS (P = .03), and in active (n = 101) versus smoldering (n = 40) MM (P < .001). In patients with active MM, there was a significant (P < .001) decrease from pretreatment to post-treatment proteasome concentrations in responders to chemotherapy, but not in nonresponders. Circulating proteasome levels were identified as a prognostic factor for overall survival in the univariate (P < .001 log-rank test) and in the multivariate (hazard ratio, 4.38) survival analysis in patients with active MM. We demonstrate for the first time that increased serum proteasome concentrations correlate with advanced disease and are an independent prognostic factor in MM.
Prognosis of children with acute lymphoblastic leukemia (ALL) and intrachromosomal amplification of chromosome 21 (iAMP21)
Authors: Moorman Anthony V. , Richards Susan M. , Robinson Hazel M. , Strefford Jon C. , Gibson Brenda E. S. , Kinsey Sally E. , Eden Tim O. B. , Vora Ajay J. , Mitchell Christopher D. , Harrison Christine J. ,   on behalf of the UK Medical Research Council (MRC)/National Cancer Research Institute (NCRI) Childhood Leukaemia Working Party (CLWP)
Published: November 2006

Abstract
Patients with acute lymphoblastic leukemia (ALL) and an intrachromosomal amplification of chromosome 21 (iAMP21) comprise a novel and distinct biological subgroup. We prospectively screened 1630 (84%) patients treated on the UK MRC ALL97 protocol for iAMP21 and herein present demographic, clinical, and survival data on the 28 (2%) children found to harbor this abnormality. They had a common or pre-B ALL immunophenotype, were significantly older (median 9 years vs 5 years), and had a lower white cell count (median 3.9 vs 12.4) compared with children without this abnormality. Notably, patients with iAMP21 had a significantly inferior event-free and overall survival at 5 years compared with other patients: 29% (95% confidence interval [CI], 13%-48%) versus 78% (95% CI, 76%-80%) and 71% (95% CI, 51%-84%) versus 87% (95% CI, 85%-88%), respectively. As a result of this 3-fold increase in relapse risk, newly diagnosed patients with iAMP21 recruited to the current UK MRC ALL2003 trial are being treated on the high-risk arm and are considered for bone marrow transplantation in first remission.
DWARF – a data warehouse system for analyzing protein families
Authors: Fischer Markus , Thai Quan K , Grieb Melanie , Pleiss Jürgen 
Published: November 2006

Abstract

Background
The emerging field of integrative bioinformatics provides the tools to organize and systematically analyze vast amounts of highly diverse biological data and thus allows to gain a novel understanding of complex biological systems. The data warehouse DWARF applies integrative bioinformatics approaches to the analysis of large protein families.

Description
The data warehouse system DWARF integrates data on sequence, structure, and functional annotation for protein fold families. The underlying relational data model consists of three major sections representing entities related to the protein (biochemical function, source organism, classification to homologous families and superfamilies), the protein sequence (position-specific annotation, mutant information), and the protein structure (secondary structure information, superimposed tertiary structure). Tools for extracting, transforming and loading data from public available resources (ExPDB, GenBank, DSSP) are provided to populate the database. The data can be accessed by an interface for searching and browsing, and by analysis tools that operate on annotation, sequence, or structure. We applied DWARF to the family of α/β-hydrolases to host the Lipase Engineering database. Release 2.3 contains 6138 sequences and 167 experimentally determined protein structures, which are assigned to 37 superfamilies 103 homologous families.

Conclusion
DWARF has been designed for constructing databases of large structurally related protein families and for evaluating their sequence-structure-function relationships by a systematic analysis of sequence, structure and functional annotation. It has been applied to predict biochemical properties from sequence, and serves as a valuable tool for protein engineering.
methBLAST and methPrimerDB: web-tools for PCR based methylation analysis
Authors: Pattyn Filip , Hoebeeck Jasmien , Robbrecht Piet , Michels Evi , De Paepe Anne , Bottu Guy , Coornaert David , Herzog Robert , Speleman Frank , Vandesompele Jo 
Published: November 2006

Abstract

Background
DNA methylation plays an important role in development and tumorigenesis by epigenetic modification and silencing of critical genes. The development of PCR-based methylation assays on bisulphite modified DNA heralded a breakthrough in speed and sensitivity for gene methylation analysis. Despite this technological advancement, these approaches require a cumbersome gene by gene primer design and experimental validation. Bisulphite DNA modification results in sequence alterations (all unmethylated cytosines are converted into uracils) and a general sequence complexity reduction as cytosines become underrepresented. Consequently, standard BLAST sequence homology searches cannot be applied to search for specific methylation primers.

Results
To address this problem we developed methBLAST, a sequence similarity search program, based on the original BLAST algorithm but querying in silico bisulphite modified genome sequences to evaluate oligonucleotide sequence similarities. Apart from the primer specificity analysis tool, we have also developed a public database termed methPrimerDB for the storage and retrieval of validated PCR based methylation assays. The web interface allows free public access to perform methBLAST searches or database queries and to submit user based information. Database records can be searched by gene symbol, nucleotide sequence, analytical method used, Entrez Gene or methPrimerDB identifier, and submitter's name. Each record contains a link to Entrez Gene and PubMed to retrieve additional information on the gene, its genomic context and the article in which the methylation assay was described. To assure and maintain data integrity and accuracy, the database is linked to other reference databases. Currently, the database contains primer records for the most popular PCR-based methylation analysis methods to study human, mouse and rat epigenetic modifications. methPrimerDB and methBLAST are available at http://medgen.ugent.be/methprimerdb and http://medgen.ugent.be/methblast.

Conclusion
We have developed two integrated and freely available web-tools for PCR based methylation analysis. methBLAST allows in silico assessment of primer specificity in PCR based methylation assays that can be stored in the methPrimerDB database, which provides a search portal for validated methylation assays.
Rtt107/Esc4 binds silent chromatin and DNA repair proteins using different BRCT motifs
Authors: Zappulla David C , Maharaj Arindel SR , Connelly Jessica J , Jockusch Rebecca A , Sternglanz Rolf 
Published: November 2006

Abstract

Background
By screening a plasmid library for proteins that could cause silencing when targeted to the HMR locus in Saccharomyces cerevisiae, we previously reported the identification of Rtt107/Esc4 based on its ability to e stablish s ilent c hromatin. In this study we aimed to determine the mechanism of Rtt107/Esc4 targeted silencing and also learn more about its biological functions.

Results
Targeted silencing by Rtt107/Esc4 was dependent on the SIR genes, which encode obligatory structural and enzymatic components of yeast silent chromatin. Based on its sequence, Rtt107/Esc4 was predicted to contain six BRCT motifs. This motif, originally identified in the human breast tumor suppressor gene BRCA1, is a protein interaction domain. The targeted silencing activity of Rtt107/Esc4 resided within the C-terminal two BRCT motifs, and this region of the protein bound to Sir3 in two-hybrid tests. Deletion of RTT107/ESC4 caused sensitivity to the DNA damaging agent MMS as well as to hydroxyurea. A two-hybrid screen showed that the N-terminal BRCT motifs of Rtt107/Esc4 bound to Slx4, a protein previously shown to be involved in DNA repair and required for viability in a strain lacking the DNA helicase Sgs1. Like SLX genes, RTT107ESC4 interacted genetically with SGS1; esc4 Δ sgs1 Δ mutants were viable, but exhibited a slow-growth phenotype and also a synergistic DNA repair defect.

Conclusion
Rtt107/Esc4 binds to the silencing protein Sir3 and the DNA repair protein Slx4 via different BRCT motifs, thus providing a bridge linking silent chromatin to DNA repair enzymes.
Socio-economic status and types of childhood injury in Alberta: a population based study
Authors: Gilbride Susan J , Wild Cameron , Wilson Douglas R , Svenson Lawrence W , Spady Donald W 
Published: November 2006

Abstract

Background
Childhood injury is the leading cause of mortality, morbidity and permanent disability in children in the developed world. This research examines relationships between socio-economic status (SES), demographics, and types of childhood injury in the province of Alberta, Canada.

Methods
Secondary analysis was performed using administrative health care data provided by Alberta Health and Wellness on all children, aged 0 to 17 years, who had injuries treated by a physician, either in a physician's office, outpatient department, emergency room and/or as a hospital inpatient, between April 1st. 1995 to March 31st. 1996. Thirteen types of childhood injury were assessed with respect to age, gender and urban/rural location using ICD9 codes, and were related to SES as determined by an individual level SES indicator, the payment status of the Alberta provincial health insurance plan. The relationships between gender, SES, rural/urban status and injury type were determined using logistic regression.

Results
Twenty-four percent of Alberta children had an injury treated by physician during the one year period. Peak injury rates occurred about ages 2 and 13–17 years. All injury types except poisoning were more common in males. Injuries were more frequent in urban Alberta and in urban children with lower SES (receiving health care premium assistance). Among the four most common types of injury (78.6% of the total), superficial wounds and open wounds were more common among children with lower SES, while fractures and dislocations/sprains/strains were more common among children receiving no premium assistance.

Conclusion
These results show that childhood injury in Alberta is a major health concern especially among males, children living in urban centres, and those living on welfare or have Treaty status. Most types of injury were more frequent in children of lower SES. Analysis of the three types of the healthcare premium subsidy allowed a more comprehensive picture of childhood injury with children whose families are on welfare and those of Treaty status presenting more frequently for an injury-related physician's consultation than other children. This report also demonstrates that administrative health care data can be usefully employed to describe injury patterns in children.
Culture and assessment of manic symptoms
Authors: Mackin Paul , Targum Steven D. , Kalali Amir , Rom Dror , Young Allan H. 
Published: November 2006

SummaryCultural background may influence the perception of psychiatric symptoms. We examined the effects of cultural biases on the identification of manic symptoms using the Young Mania Rating Scale. Two video interviews, each with an American person with mania, were shown to psychiatrists from three countries (US, UK and India). Total scores on the scale differed significantly between the US and UK (P < 0.001) and between India and UK (P < 0.001) rater groups. Overall, differences between India and US rater groups were less marked (P=0.28). These differences suggest that cultural biases influence the interpretation of manic symptoms.
Costs and consequences of enhanced primary care for depression
Authors: Gilbody Simon , Bower Peter , Whitty Paula 
Published: November 2006

BackgroundA number of enhancement strategies have been proposed to improve the quality and outcome of care for depression in primary care settings. Decision-makers are likely to need to know whether these interventions are cost-effective in routine primary care settings.MethodWe conducted a systematic review of all full economicevaluations (cost-effectiveness and cost-utility analyses) accompanying randomised controlled trials of enhanced primary care for depression. Costs were standardised to UK pounds/US dollars and incremental cost-effectiveness ratios (ICERs) were visually summarised using a permutation matrix.ResultsWe identified 11 full economic evaluations (4757 patients). A near-uniform finding was that the interventions based upon collaborative care/case management resulted in improved outcomes but were also associated with greater costs. When considering primary care depression treatment costs alone, ICER estimates ranged from £7 ($13, no confidence interval given) to £13 ($24, 95% CI—105 to 148) per additional depression-free day. Educational interventions alone were associated with increased cost and no clinical benefit.ConclusionsImproved outcomes through depression management programmes using a collaborative care/case management approach can be expected, but are associated with increased cost and will require investment.