bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recognizing protein–protein interfaces with empirical potentials and reduced amino acid alphabets
Authors: Launay Guillaume , Mendez Raul , Wodak Shoshana , Simonson Thomas 
Published: August 2007

Abstract

Background
In structural genomics, an important goal is the detection and classification of protein–protein interactions, given the structures of the interacting partners. We have developed empirical energy functions to identify native structures of protein–protein complexes among sets of decoy structures. To understand the role of amino acid diversity, we parameterized a series of functions, using a hierarchy of amino acid alphabets of increasing complexity, with 2, 3, 4, 6, and 20 amino acid groups. Compared to previous work, we used the simplest possible functional form, with residue–residue interactions and a stepwise distance-dependence. We used increased computational ressources, however, constructing 290,000 decoys for 219 protein–protein complexes, with a realistic docking protocol where the protein partners are flexible and interact through a molecular mechanics energy function. The energy parameters were optimized to correctly assign as many native complexes as possible. To resolve the multiple minimum problem in parameter space, over 64000 starting parameter guesses were tried for each energy function. The optimized functions were tested by cross validation on subsets of our native and decoy structures, by blind tests on series of native and decoy structures available on the Web, and on models for 13 complexes submitted to the CAPRI structure prediction experiment.

Results
Performance is similar to several other statistical potentials of the same complexity. For example, the CAPRI target structure is correctly ranked ahead of 90% of its decoys in 6 cases out of 13. The hierarchy of amino acid alphabets leads to a coherent hierarchy of energy functions, with qualitatively similar parameters for similar amino acid types at all levels. Most remarkably, the performance with six amino acid classes is equivalent to that of the most detailed, 20-class energy function.

Conclusion
This suggests that six carefully chosen amino acid classes are sufficient to encode specificity in protein–protein interactions, and provide a starting point to develop more complicated energy functions.
3'-UTR SIRF: A database for identifying clusters of short interspersed repeats in 3' untranslated regions
Authors: Andken Benjamin B , Lim In , Benson Gary , Vincent John J , Ferenc Matthew T , Heinrich Bianca , Jarzylo Larissa A , Man Heng-Ye , Deshler James O 
Published: August 2007

AbstractBackgroundShort (~5 nucleotides) interspersed repeats regulate several aspects of post-transcriptional gene expression. Previously we developed an algorithm (REPFIND) that assigns P-values to all repeated motifs in a given nucleic acid sequence and reliably identifies clusters of short CAC-containing motifs required for mRNA localization inXenopusoocytes.DescriptionIn order to facilitate the identification of genes possessing clusters of repeats that regulate post-transcriptional aspects of gene expression in mammalian genes, we used REPFIND to create a database of all repeated motifs in the 3' untranslated regions (UTR) of genes from the Mammalian Gene Collection (MGC). The MGC database includes seven vertebrate species: human, cow, rat, mouse and three non-mammalian vertebrate species. A web-based application was developed to search this database of repeated motifs to generate species-specific lists of genes containing specific classes of repeats in their 3'-UTRs. This computational tool is called 3'-UTR SIRF (ShortInterspersedRepeatFinder), and it reveals that hundreds of human genes contain an abundance of short CAC-rich and CAG-rich repeats in their 3'-UTRs that are similar to those found in mRNAs localized to the neurites of neurons. We tested four candidate mRNAs for localization in rat hippocampal neurons byin situhybridization. Our results show that two candidate CAC-rich (Syntaxin 1BandTubulin β4) and two candidate CAG-rich (Sec61αandSyntaxin 1A) mRNAs are localized to distal neurites, whereas two control mRNAs lacking repeated motifs in their 3'-UTR remain primarily in the cell body.ConclusionComputational data generated with 3'-UTR SIRF indicate that hundreds of mammalian genes have an abundance of short CA-containing motifs that may direct mRNA localization in neurons.In situhybridization shows that four candidate mRNAs are localized to distal neurites of cultured hippocampal neurons. These data suggest that short CA-containing motifs may be part of a widely utilized genetic code that regulates mRNA localization in vertebrate cells. The use of 3'-UTR SIRF to search for new classes of motifs that regulate other aspects of gene expression should yield important information in future studies addressingcis-regulatory information located in 3'-UTRs.
Computer-aided identification of polymorphism sets diagnostic for groups of bacterial and viral genetic variants
Authors: Price Erin P , Inman-Bamber John , Thiruvenkataswamy Venugopal , Huygens Flavia , Giffard Philip M 
Published: August 2007

AbstractBackgroundSingle nucleotide polymorphisms (SNPs) and genes that exhibit presence/absence variation have provided informative marker sets for bacterial and viral genotyping. Identification of marker sets optimised for these purposes has been based on maximal generalized discriminatory power as measured by Simpson's Index of Diversity, or on the ability to identify specific variants. Here we describe the Not-N algorithm, which is designed to identify small sets of genetic markers diagnostic for user-specified subsets of known genetic variants. The algorithm does not treat the user-specified subset and the remaining genetic variants equally. Rather Not-N analysis is designed to underpin assays that provide 0% false negatives, which is very important for e.g. diagnostic procedures for clinically significant subgroups within microbial species.ResultsThe Not-N algorithm has been incorporated into the "Minimum SNPs" computer program and used to derive genetic markers diagnostic for multilocus sequence typing-defined clonal complexes, hepatitis C virus (HCV) subtypes, and phylogenetic clades defined by comparative genome hybridization (CGH) data forCampylobacter jejuni,Yersinia enterocoliticaandClostridium difficile.ConclusionNot-N analysis is effective for identifying small sets of genetic markers diagnostic for microbial sub-groups. The best results to date have been obtained with CGH data from several bacterial species, and HCV sequence data.
A systematic screen for genes expressed in definitive endoderm by Serial Analysis of Gene Expression (SAGE)
Authors: Hou Juan , Charters Anita M , Lee Sam C , Zhao Yongjun , Wu Mona K , Jones Steven JM , Marra Marco A , Hoodless Pamela A 
Published: August 2007

AbstractBackgroundThe embryonic definitive endoderm (DE) gives rise to organs of the gastrointestinal and respiratory tract including the liver, pancreas and epithelia of the lung and colon. Understanding how DE progenitor cells generate these tissues is critical to understanding the cause of visceral organ disorders and cancers, and will ultimately lead to novel therapies including tissue and organ regeneration. However, investigation into the molecular mechanisms of DE differentiation has been hindered by the lack of early DE-specific markers.ResultsWe describe the identification of novel as well as known genes that are expressed in DE using Serial Analysis of Gene Expression (SAGE). We generated and analyzed three longSAGE libraries from early DE of murine embryos: early whole definitive endoderm (0–6 somite stage), foregut (8–12 somite stage), and hindgut (8–12 somite stage). A list of candidate genes enriched for expression in endoderm was compiled through comparisons within these three endoderm libraries and against 133 mouse longSAGE libraries generated by the Mouse Atlas of Gene Expression Project encompassing multiple embryonic tissues and stages. Using whole mountin situhybridization, we confirmed that 22/32 (69%) genes showed previously uncharacterized expression in the DE. Importantly, two genes identified,Pyyand5730521E12Rik, showed exclusive DE expression at early stages of endoderm patterning.ConclusionThe high efficiency of this endoderm screen indicates that our approach can be successfully used to analyze and validate the vast amount of data obtained by the Mouse Atlas of Gene Expression Project. Importantly, these novel early endoderm-expressing genes will be valuable for further investigation into the molecular mechanisms that regulate endoderm development.
Phenoxodiol protects against Cisplatin induced neurite toxicity in a PC-12 cell model
Authors: Klein Reuben , Brown David , Turnley Ann M 
Published: August 2007

Abstract

Background
Many commonly used chemotherapeutic agents, such as Cisplatin, are restricted in their potential anti-neoplastic effectiveness by their side effects, with one of the most problematic being induction of peripheral neuropathy. Although a number of different neurotrophic, neuroprotective or anti-oxidant treatments have been tried in order to prevent or treat the neuropathies, to date they have met with limited success. Phenoxodiol is a new chemotherapeutic agent that has anti-proliferative and apoptotic effects on a range of cancer cells. PC12 cells are a commonly used neuronal cell model for examination of neurite outgrowth. In this study we examined whether phenoxodiol could protect against Cisplatin induced neurite inhibition in PC12 cells as an indication of the potential to protect against neuropathy.

Results
Using the PC12 neuronal cell line, concentrations of Cisplatin were chosen that induced moderate or strong neurite toxicity within 24 hrs but were not cytotoxic. The effect of Phenoxodiol on Cisplatin induced neurite toxicity was assessed by measurement of neurite outgrowth. Addition of phenoxodiol at 100 nM or 1 μM showed no cytotoxicity and blocked the Cisplatin induced neurite toxicity, while phenoxodiol at 10 μM was cytotoxic and enhanced neurite toxicity of Cisplatin. When Cisplatin was added for 24 hrs, then washed out and the cells allowed to recover for 48 hrs, neurite outgrowth was not restored and addition of phenoxodiol did not further promote recovery or restore the Cisplatin treated cells.

Conclusion
In addition to its potential as a chemotherapeutic agent Phenoxodiol may thus also have the potential to be used in conjunction with Cisplatin chemotherapy to prevent induction of neuropathy.
Inducible gene inactivation in neurons of the adult mouse forebrain
Authors: Erdmann Gitta , Schütz Günther , Berger Stefan 
Published: August 2007

Abstract

Background
The analysis of the role of genes in important brain functions like learning, memory and synaptic plasticity requires gene inactivation at the adult stage to exclude developmental effects, adaptive changes or even lethality. In order to achieve temporally controlled somatic mutagenesis, the Cre/loxP-recombination system has been complemented with the tamoxifen-inducible fusion protein consisting of Cre recombinase and the mutated ligand binding domain of the human estrogen receptor (CreERT2). To induce recombination of conditional alleles in neurons of the adult forebrain, we generated a bacterial artificial chromosome-derived transgene expressing the CreERT2 fusion protein under control of the regulatory elements of the CaMKIIα gene (CaMKCreERT2 transgene).

Results
We established three mouse lines harboring one, two and four copies of the CaMKCreERT2 transgene. The CaMKCreERT2 transgene displayed reliable and copy number-dependent expression of Cre recombinase specifically in neurons of the adult forebrain. Using Cre reporter mice we show very low background activity of the transgene in absence of the ligand and efficient induction of recombination upon tamoxifen treatment in all three lines. In addition, we demonstrate in mice harboring two conditional glucocorticoid receptor (GR) alleles and the CaMKCreERT2 transgene spatially restricted loss of GR protein expression in neurons of the adult forebrain upon tamoxifen treatment.

Conclusion
This is to our knowledge the first approach allowing highly efficient inducible gene inactivation in neurons of the adult mouse forebrain. This new approach will be a useful tool to dissect the function of specific genes in the adult forebrain. Effects of gene inactivation on pre- and postnatal brain development and compensatory mechanisms elicited by an early onset of gene inactivation can now be excluded.
Design of a randomized controlled trial on the effects of Counseling of mental health problems by Occupational Physicians on return to work: the CO-OP-study
Authors: Rebergen David S , Bruinvels David J , van der Beek Allard J , van Mechelen Willem 
Published: August 2007

Abstract

Background
Mental health problems often lead to prolonged sick leave. In primary care, the usual approach towards these patients was the advice to take rest and not return to work before all complaints had disappeared. When complaints persist, these patients are often referred to psychologists from primary and specialized secondary care. As an alternative, ways have been sought to activate the Dutch occupational physician (OP) in primary care. Early 2000, the Dutch Association of Occupational Physicians (NVAB) published a guideline concerning the management by OPs of employees with mental health problems. The guideline received positive reactions from employees, employers and Dutch OPs. This manuscript describes the design of a study, which aims to assess the effects of the guideline, compared with usual care.

Methods/Design
In a randomized controlled trial (RCT), subjects in the intervention group were treated according to the guideline. The control group received usual care, with minimal involvement of the OP and easy access to a psychologist. Subjects were recruited from two Dutch police departments. The primary outcomes of the study are return to work and treatment satisfaction by the employee, employer, and OP. A secondary outcome is cost-effectiveness of the intervention, compared with usual care. Furthermore, prognostic measures are taken into account as potential confounders. A process evaluation will be done by means of performance indicators, based on the guideline.

Discussion
In this pragmatic trial, effectiveness instead of efficacy is studied. We will evaluate what is possible in real clinical practice, rather than under ideal circumstances. Many requirements for a high quality trial are being met. Results of this study will contribute to treatment options in occupational health practice for employees on sick leave due to mental health problems. Additionally, they may contribute to new and better-suited guidelines and stepped care. Results will become available during 2007.

Trial registration
Current Controlled Trials ISRCTN34887348
Evidence based practice in postgraduate healthcare education: A systematic review
Authors: Flores-Mateo Gemma , Argimon Josep M 
Published: August 2007

Abstract
Background
Training in Evidence-Based Practice (EBP) has been widely implemented throughout medical school and residency curricula. The aim of this study is to systematically review studies that assessed the effectiveness of EBP teaching to improve knowledge, skills, attitudes and behavior of postgraduate healthcare workers, and to describe instruments available to evaluate EBP teaching.

Methods
The design is a systematic review of randomized, non-randomized, and before-after studies. The data sources were MEDLINE, Cochrane Library, EMBASE, CINAHL and ERIC between 1966 and 2006. Main outcomes were knowledge, skills, attitudes and behavior towards EBP. Standardized effect sizes (E-S) were calculated. The E-S was categorized as small (E-S < 0.2), small to moderate (E-S between 0.2 and 0.5), moderate to large (E-S between 0.51 and 0.79), large (E-S > 0.79). Reliability and validity of instruments for evaluating education were assessed. Studies excluded were those that were not original, performed in medical students, focused on prescribing practices, specific health problems, theoretical reviews of different components of EBP, continuing medical education, and testing the effectiveness of implementing guidelines.

Results
Twenty-four studies met our inclusion criteria. There were 15 outcomes within the 10 studies for which E-S could be calculated. The E-S ranged from 0.27 (95%CI: -0.05 to 0.59) to 1.32 (95%CI: 1.11 to 1.53). Studies assessing skills, behavior and/or attitudes had a "small to moderate" E-S. Only 1 of the 2 studies assessing knowledge had E-S of 0.57 (95 CI: 0.32 to 0.82) and 2 of the 4 studies that assessed total test score outcomes had "large" E-S. There were 22 instruments used, but only 10 had 2 or more types of validity or reliability evidence.

Conclusion
Small improvements in knowledge, skills, attitudes or behavior are noted when measured alone. A large improvement in skills and knowledge in EBP is noted when measured together in a total test score. Very few studies used validated measures tests.
Health equity issues at the local level: Socio-geography, access, and health outcomes in the service area of the Hôpital Albert Schweitzer-Haiti
Authors: Perry Henry B , King-Schultz Leslie W , Aftab Asma S , Bryant John H 
Published: August 2007

Abstract

Background
Although health equity issues at regional, national and international levels are receiving increasing attention, health equity issues at the local level have been virtually overlooked. Here, we describe here a comprehensive equity assessment carried out by the Hôpital Albert Schweitzer-Haiti (HAS) in 2003. HAS has been operating health and development programs in the Artibonite Valley of Haiti for 50 years.

Methods
We reviewed all available information arising from a comprehensive evaluation of the programs of HAS carried out in 1999 and 2000. As part of this evaluation, two demographic and health surveys were carried out. We carried out exit interviews with clients receiving primary health care, observations within health facilities, interviews with households related to quality of care, and focus group discussions with community-based health workers. A special study was carried out in 2003 to assess factors determining the use of prenatal care services. Finally, selected findings were obtained from the HAS information system.

Results
We found markedly reduced access to health services in the peripheral mountainous areas compared to the central plains. The quality of services was more deficient and the coverage of key services was lower in the mountains. Finally, health status, as measured by under-five mortality rates and levels of childhood malnutrition, was also worse in the mountains.

Conclusion
These findings indicate that local health programs need to give attention to monitoring the health status as well as the quality and coverage of basic services among marginalized groups within the program service area. Health inequities will not be overcome until such monitoring occurs and leaders of health programs ensure that inequities identified are addressed in the local programming of activities. It is quite likely that, within relatively small geographic areas in resource-poor settings around the world, similar, if not even greater, levels of health inequities exist. These inequities need to be measured and addressed in order for health programs to achieve equity and maximum improvement in health status within the population.
Major HGF-mediated regenerative pathways are similarly affected in human and canine cirrhosis
Authors: Spee Bart , Arends Brigitte , van den Ingh Ted SGAM , Roskams Tania , Rothuizen Jan , Penning Louis C 
Published: August 2007

Abstract

Background
The availability of non-rodent animal models for human cirrhosis is limited. We investigated whether privately-owned dogs (Canis familiaris) are potential model animals for liver disease focusing on regenerative pathways. Several forms of canine hepatitis were examined: Acute Hepatitis (AH), Chronic Hepatitis (CH), Lobular Dissecting Hepatitis (LDH, a specific form of micronodulair cirrhosis), and Cirrhosis (CIRR). Canine cirrhotic samples were compared to human liver samples from cirrhotic stages of alcoholic liver disease (hALC) and chronic hepatitis C infection (hHC).

Results
Canine specific mRNA expression of the regenerative hepatocyte growth factor (HGF) signaling pathway and relevant down-stream pathways were measured by semi-quantitative PCR and Western blot (STAT3, PKB, ERK1/2, and p38-MAPK). In all canine groups, levels of c-MET mRNA (proto-oncogenic receptor for HGF) were significantly decreased (p < 0.05). Surprisingly, ERK1/2 and p38-MAPK were increased in CH and LDH. In the human liver samples Western blotting indicated a high homology of down-stream pathways between different etiologies (hALC and hHC). Similarly activated pathways were found in CIRR, hALC, and hHC.

Conclusion
In canine hepatitis and cirrhosis the major regenerative downstream pathways were activated. Signaling pathways are similarly activated in human cirrhotic liver samples, irrespective of the differences in etiology in the human samples (alcohol abuse and HCV-infection). Therefore, canine hepatitis and cirrhosis could be an important clinical model to evaluate novel interventions prior to human clinical trials.
Differential mortality in Iran
Authors: Khosravi Ardeshir , Taylor Richard , Naghavi Mohsen , Lopez Alan D 
Published: August 2007

Abstract

Background
Among the available data provided by health information systems, data on mortality are commonly used not only as health indicators but also as socioeconomic development indices. Recognizing that in Iran accurate data on causes of death were not available, the Deputy of Health in the Ministry of Health and Medical Education (MOH&ME) established a new comprehensive system for death registration which started in one province (Bushehr) as a pilot in 1997, and was subsequently expanded to include all other provinces, except Tehran province. These data can be used to investigate the nature and extent of differences in mortality in Iran. The objective of this paper is to estimate provincial differences in the level of mortality using this death registration system.

Methods
Data from the death registration system for 2004 for each province were evaluated for data completeness, and life tables were created for provinces after correction for under-enumeration of death registration. For those provinces where it was not possible to adjust the data on adult deaths by using the Brass Growth Balance method, adult mortality was predicted based on adult literacy using information from provinces with reliable data.

Results
Child mortality (risk of a newborn dying before age 5, or 5q0) in 2004 varied between 47 per 1000 live births for both sexes in Sistan and Baluchistan province, and 25 per 1000 live births in Tehran and Gilan provinces. For adults, provincial differences in mortality were much greater for males than females. Adult mortality (risk of dying between ages 15 and 60, or 45q15) for females varied between 0.133 in Kerman province and 0.117 in Tehran province; for males the range was from 0.218 in Kerman to 0.149 in Tehran province. Life expectancy for females was highest in Tehran province (73.8 years) and lowest in Sistan and Baluchistan (70.9 years). For males, life expectancy ranged from 65.7 years in Sistan and Baluchistan province to 70.9 years in Tehran.

Conclusion
Substantial differences in survival exist among the provinces of Iran. While the completeness of the death registration system operated by the Iranian MOH&ME appears to be acceptable in the majority of provinces, further efforts are needed to improve the quality of data on mortality in Iran, and to expand death registration to Tehran province.