bluuebunny/crossref_metadata_2025 huggingface dataset:
GARNET – gene set analysis with exploration of annotation relations
Authors: Rho Kyoohyoung , Kim Bumjin , Jang Youngjun , Lee Sanghyun , Bae Taejeong , Seo Jihae , Seo Chaehwa , Lee Jihyun , Kang Hyunjung , Yu Ungsik , Kim Sunghoon , Lee Sanghyuk , Kim Wan Kyu
Published: February 2011

Background

Gene set analysis is a powerful method of deducing biological meaning for an a priori defined set of genes. Numerous tools have been developed to test statistical enrichment or depletion in specific pathways or gene ontology (GO) terms. Major difficulties towards biological interpretation are integrating diverse types of annotation categories and exploring the relationships between annotation terms of similar information.

Results

GARNET (Gene Annotation Relationship NEtwork Tools) is an integrative platform for gene set analysis with many novel features. It includes tools for retrieval of genes from annotation database, statistical analysis & visualization of annotation relationships, and managing gene sets. In an effort to allow access to a full spectrum of amassed biological knowledge, we have integrated a variety of annotation data that include the GO, domain, disease, drug, chromosomal location, and custom-defined annotations. Diverse types of molecular networks (pathways, transcription and microRNA regulations, protein-protein interaction) are also included. The pair-wise relationship between annotation gene sets was calculated using kappa statistics. GARNET consists of three modules - gene set manager, gene set analysis and gene set retrieval, which are tightly integrated to provide virtually automatic analysis for gene sets. A dedicated viewer for annotation network has been developed to facilitate exploration of the related annotations.

Conclusions

GARNET (gene annotation relationship network tools) is an integrative platform for diverse types of gene set analysis, where complex relationships among gene annotations can be easily explored with an intuitive network visualization tool (http://garnet.isysbio.org/ or http://ercsb.ewha.ac.kr/garnet/).
Reconstructing phylogeny from metabolic substrate-product relationships
Authors: Chang Che-Wei , Lyu Ping-Chiang , Arita Masanori
Published: February 2011

Background

Many approaches utilize metabolic pathway information to reconstruct the phyletic tree of fully sequenced organisms, but how metabolic networks can add information to original genomic annotations has remained open.

Methods

We translated enzyme reactions assigned in 1075 organisms into substrate-product relationships to represent the metabolic information at a finer resolution than enzymes and compounds. Each organism was represented as a vector of substrate-product relationships and the phyletic tree was reconstructed by a simple hierarchical method. Obtained results were compared with several other approaches that use genome information and network properties.

Results

Phyletic trees without consideration of network properties can already extract organisms in anomalous environments. This efficient method can add insights to traditional genome-based phylogenetic reconstruction.

Conclusions

Structural relationship among metabolites can highlight parasitic or symbiont species such as spirochaete and clamydia. The method assists understanding of species-environment interaction when used in combination with traditional phylogenetic methods.
Potent bace-1 inhibitor design using pharmacophore modeling, in silico screening and molecular docking studies
Authors: John Shalini , Thangapandian Sundarapandian , Sakkiah Sugunadevi , Lee Keun Woo
Published: February 2011

Background

Beta-site amyloid precursor protein cleaving enzyme (BACE-1) is a single-membrane protein belongs to the aspartyl protease class of catabolic enzymes. This enzyme involved in the processing of the amyloid precursor protein (APP). The cleavage of APP by BACE-1 is the rate-limiting step in the amyloid cascade leading to the production of two peptide fragments Aβ40 and Aβ42. Among two peptide fragments Aβ42 is the primary species thought to be responsible for the neurotoxicity and amyloid plaque formation that lead to memory and cognitive defects in Alzheimer’s disease (AD). AD is a ravaging neurodegenerative disorder for which no disease-modifying treatment is currently available. Inhibition of BACE-1 is expected to stop amyloid plaque formation and emerged as an interesting and attractive therapeutic target for AD.

Methods

Ligand-based computational approach was used to identify the molecular chemical features required for the inhibition of BACE-1 enzyme. A training set of 20 compounds with known experimental activity was used to generate pharmacophore hypotheses using 3D QSAR Pharmacophore Generation module available in Discovery studio. The hypothesis was validated by four different methods and the best hypothesis was utilized in database screening of four chemical databases like Maybridge, Chembridge, NCI and Asinex. The retrieved hit compounds were subjected to molecular docking study using GOLD 4.1 program.

Results

Among ten generated pharmacophore hypotheses, Hypo 1 was chosen as best pharmacophore hypothesis. Hypo 1 consists of one hydrogen bond donor, one positive ionizable, one ring aromatic and two hydrophobic features with high correlation coefficient of 0.977, highest cost difference of 121.98 bits and lowest RMSD value of 0.804. Hypo 1 was validated using Fischer randomization method, test set with a correlation coefficient of 0.917, leave-one-out method and decoy set with a goodness of hit score of 0.76. The validated Hypo 1 was used as a 3D query in database screening and retrieved 773 compounds with the estimated activity value <100 nM. These hits were docked into the active site of BACE-1 and further refined based on molecular interactions with the essential amino acids and good GOLD fitness score.

Conclusion

The best pharmacophore hypothesis, Hypo 1, with high predictive ability contains chemical features required for the effective inhibition of BACE-1. Using Hypo 1, we have identified two compounds with diverse chemical scaffolds as potential virtual leads which, as such or upon further optimization, can be used in the designing of new BACE-1 inhibitors.
GOChase-II: correcting semantic inconsistencies from Gene Ontology-based annotations for gene products
Authors: Park Yu Rang , Kim Jihun , Lee Hye Won , Yoon Young Jo , Kim Ju Han
Published: February 2011

Background

The Gene Ontology (GO) provides a controlled vocabulary for describing genes and gene products. In spite of the undoubted importance of GO, several drawbacks associated with GO and GO-based annotations have been introduced. We identified three types of semantic inconsistencies in GO-based annotations; semantically redundant, biological-domain inconsistent and taxonomy inconsistent annotations.

Methods

To determine the semantic inconsistencies in GO annotation, we used the hierarchical structure of GO graph and tree structure of NCBI taxonomy. Twenty seven biological databases were collected for finding semantic inconsistent annotation.

Results

The distributions and possible causes of the semantic inconsistencies were investigated using twenty seven biological databases with GO-based annotations. We found that some evidence codes of annotation were associated with the inconsistencies. The numbers of gene products and species in a database that are related to the complexity of database management are also in correlation with the inconsistencies. Consequently, numerous annotation errors arise and are propagated throughout biological databases and GO-based high-level analyses. GOChase-II is developed to detect and correct both syntactic and semantic errors in GO-based annotations.

Conclusions

We identified some inconsistencies in GO-based annotation and provided software, GOChase-II, for correcting these semantic inconsistencies in addition to the previous corrections for the syntactic errors by GOChase-I.
Fast and accurate clustering of noncoding RNAs using ensembles of sequence alignments and secondary structures
Authors: Saito Yutaka , Sato Kengo , Sakakibara Yasubumi
Published: February 2011

Background

Clustering of unannotated transcripts is an important task to identify novel families of noncoding RNAs (ncRNAs). Several hierarchical clustering methods have been developed using similarity measures based on the scores of structural alignment. However, the high computational cost of exact structural alignment requires these methods to employ approximate algorithms. Such heuristics degrade the quality of clustering results, especially when the similarity among family members is not detectable at the primary sequence level.

Results

We describe a new similarity measure for the hierarchical clustering of ncRNAs. The idea is that the reliability of approximate algorithms can be improved by utilizing the information of suboptimal solutions in their dynamic programming frameworks. We approximate structural alignment in a more simplified manner than the existing methods. Instead, our method utilizes all possible sequence alignments and all possible secondary structures, whereas the existing methods only use one optimal sequence alignment and one optimal secondary structure. We demonstrate that this strategy can achieve the best balance between the computational cost and the quality of the clustering. In particular, our method can keep its high performance even when the sequence identity of family members is less than 60%.

Conclusions

Our method enables fast and accurate clustering of ncRNAs. The software is available for download at http://bpla-kernel.dna.bio.keio.ac.jp/clustering/.
TRAM (Transcriptome Mapper): database-driven creation and analysis of transcriptome maps from multiple sources
Authors: Lenzi Luca , Facchin Federica , Piva Francesco , Giulietti Matteo , Pelleri Maria Chiara , Frabetti Flavia , Vitale Lorenza , Casadei Raffaella , Canaider Silvia , Bortoluzzi Stefania , Coppe Alessandro , Danieli Gian Antonio , Principato Giovanni , Ferrari Sergio , Strippoli Pierluigi
Published: February 2011

Background

Several tools have been developed to perform global gene expression profile data analysis, to search for specific chromosomal regions whose features meet defined criteria as well as to study neighbouring gene expression. However, most of these tools are tailored for a specific use in a particular context (e.g. they are species-specific, or limited to a particular data format) and they typically accept only gene lists as input.

Results

TRAM (Transcriptome Mapper) is a new general tool that allows the simple generation and analysis of quantitative transcriptome maps, starting from any source listing gene expression values for a given gene set (e.g. expression microarrays), implemented as a relational database. It includes a parser able to assign univocal and updated gene symbols to gene identifiers from different data sources. Moreover, TRAM is able to perform intra-sample and inter-sample data normalization, including an original variant of quantile normalization (scaled quantile), useful to normalize data from platforms with highly different numbers of investigated genes. When in 'Map' mode, the software generates a quantitative representation of the transcriptome of a sample (or of a pool of samples) and identifies if segments of defined lengths are over/under-expressed compared to the desired threshold. When in 'Cluster' mode, the software searches for a set of over/under-expressed consecutive genes. Statistical significance for all results is calculated with respect to genes localized on the same chromosome or to all genome genes. Transcriptome maps, showing differential expression between two sample groups, relative to two different biological conditions, may be easily generated. We present the results of a biological model test, based on a meta-analysis comparison between a sample pool of human CD34+ hematopoietic progenitor cells and a sample pool of megakaryocytic cells. Biologically relevant chromosomal segments and gene clusters with differential expression during the differentiation toward megakaryocyte were identified.

Conclusions

TRAM is designed to create, and statistically analyze, quantitative transcriptome maps, based on gene expression data from multiple sources. The release includes FileMaker Pro database management runtime application and it is freely available at http://apollo11.isto.unibo.it/software/, along with preconfigured implementations for mapping of human, mouse and zebrafish transcriptomes.
GC content around splice sites affects splicing through pre-mRNA secondary structures
Authors: Zhang Jing , Kuo CC Jay , Chen Liang
Published: February 2011

Background

Alternative splicing increases protein diversity by generating multiple transcript isoforms from a single gene through different combinations of exons or through different selections of splice sites. It has been reported that RNA secondary structures are involved in alternative splicing. Here we perform a genomic study of RNA secondary structures around splice sites in humans (Homo sapiens), mice (Mus musculus), fruit flies (Drosophila melanogaster), and nematodes (Caenorhabditis elegans) to further investigate this phenomenon.

Results

We observe that GC content around splice sites is closely associated with the splice site usage in multiple species. RNA secondary structure is the possible explanation, because the structural stability difference among alternative splice sites, constitutive splice sites, and skipped splice sites can be explained by the GC content difference. Alternative splice sites tend to be GC-enriched and exhibit more stable RNA secondary structures in all of the considered species. In humans and mice, splice sites of first exons and long exons tend to be GC-enriched and hence form more stable structures, indicating the special role of RNA secondary structures in promoter proximal splicing events and the splicing of long exons. In addition, GC-enriched exon-intron junctions tend to be overrepresented in tissue-specific alternative splice sites, indicating the functional consequence of the GC effect. Compared with regions far from splice sites and decoy splice sites, real splice sites are GC-enriched. We also found that the GC-content effect is much stronger than the nucleotide-order effect to form stable secondary structures.

Conclusion

All of these results indicate that GC content is related to splice site usage and it may mediate the splicing process through RNA secondary structures.
T cells fail to develop in the human skin-cell explants system; an inconvenient truth
Authors: Meek Bob , Van Elssen Catharina HMJ , Huijskens Mirelle JAJ , van der Stegen Sjoukje JC , Tonnaer Siebe , Lumeij Stijn BJ , Vanderlocht Joris , Kirkland Mark A , Hesselink Reinout , Germeraad Wilfred TV , Bos Gerard MJ
Published: February 2011

Background

Haplo-identical hematopoietic stem cell (HSC) transplantation is very successful in eradicating haematological tumours, but the long post-transplant T-lymphopenic phase is responsible for high morbidity and mortality rates. Clark et al. have described a skin-explant system capable of producing host-tolerant donor-HSC derived T-cells. Because this T-cell production platform has the potential to replenish the T-cell levels following transplantation, we set out to validate the skin-explant system.

Results

Following the published procedures, while using the same commercial components, it was impossible to reproduce the skin-explant conditions required for HSC differentiation towards mature T-cells. The keratinocyte maturation procedure resulted in fragile cells with minimum expression of delta-like ligand (DLL). In most experiments the generated cells failed to adhere to carriers or were quickly outcompeted by fibroblasts. Consequently it was not possible to reproduce cell-culture conditions required for HSC differentiation into functional T-cells. Using cell-lines over-expressing DLL, we showed that the antibodies used by Clark et al. were unable to detect native DLL, but instead stained 7AAD+ cells. Therefore, it is unlikely that the observed T-lineage commitment from HSC is mediated by DLL expressed on keratinocytes. In addition, we did confirm expression of the Notch-ligand Jagged-1 by keratinocytes.

Conclusions

Currently, and unfortunately, it remains difficult to explain the development or growth of T-cells described by Clark et al., but for the fate of patients suffering from lymphopenia it is essential to both reproduce and understand how these co-cultures really "work". Fortunately, alternative procedures to speed-up T-cell reconstitution are being established and validated and may become available for patients in the near future.
The effect of experimental warming on leaf functional traits, leaf structure and leaf biochemistry in Arabidopsis thaliana
Authors: Jin Biao , Wang Li , Wang Jing , Jiang Ke-Zhen , Wang Yang , Jiang Xiao-Xue , Ni Cheng-Yang , Wang Yu-Long , Teng Nian-Jun
Published: February 2011

Background

The leaf is an important plant organ, and how it will respond to future global warming is a question that remains unanswered. The effects of experimental warming on leaf photosynthesis and respiration acclimation has been well studied so far, but relatively little information exists on the structural and biochemical responses to warming. However, such information is very important to better understand the plant responses to global warming. Therefore, we grew Arabidopsis thaliana at the three day/night temperatures of 23/18°C (ambient temperature), 25.5/20.5°C (elevated by 2.5°C) and 28/23°C (elevated by 5°C) to simulate the middle and the upper projected warming expected within the 21st century for this purpose.

Results

The 28/23°C treatment significantly reduced the life span, total biomass and total weight of seeds compared with the other two temperatures. Among the three temperature regimes, the concentrations of starch, chlorophyll, and proline were the lowest at 28/23°C, whereas the total weight of seeds, concentrations of chlorophyll and proline, stomatal density (SD), stomatal conductance (gs), net CO2 assimilation rate (A) and transpiration rate (E) were the highest at 25.5/20.5°C. Furthermore, the number of chloroplasts per cell and mitochondrial size were highest at 25.5/20.5°C and lowest at 28/23°C.

Conclusions

The conditions whereby the temperature was increased by 2.5°C were advantageous for Arabidopsis. However, a rise of 5°C produced negative effects, suggesting that lower levels of warming may benefit plants, especially those which belong to the same functional group as Arabidopsis, whereas higher levels of warming may produce negative affects. In addition, the increase in A under moderately warm conditions may be attributed to the increase in SD, chlorophyll content, and number of chloroplasts. Furthermore, starch accumulation in chloroplasts may be the main factor influencing chloroplast ultrastructure, and elevated temperature regulates plant respiration by probably affecting mitochondrial size. Finally, high SOD and CAT activities may enable plants grown at elevated temperatures to exhibit relatively high tolerance to temperature stress, thus alleviating the harmful effects of superoxide anion radicals and hydrogen peroxide.
Trends in self-reported prevalence and management of hypertension, hypercholesterolemia and diabetes in Swiss adults, 1997-2007
Authors: Estoppey Daniel , Paccaud Fred , Vollenweider Peter , Marques-Vidal Pedro
Published: February 2011

Background

Switzerland has a low mortality rate from cardiovascular diseases, but little is known regarding prevalence and management of cardiovascular risk factors (CV RFs: hypertension, hypercholesterolemia and diabetes) in the general population. In this study, we assessed 10-year trends in self-reported prevalence and management of cardiovascular risk factors in Switzerland.

Methods

data from three national health interview surveys conducted between 1997 and 2007 in representative samples of the Swiss adult population (49,261 subjects overall). Self-reported CV RFs prevalence, treatment and control levels were computed. The sample was weighted to match the sex - and age distribution, geographical location and nationality of the entire adult population of Switzerland.

Results

self-reported prevalence of hypertension, hypercholesterolemia and diabetes increased from 22.1%, 11.9% and 3.3% in 1997 to 24.1%, 17.4% and 4.8% in 2007, respectively. Prevalence of self-reported treatment among subjects with CV RFs also increased from 52.1%, 18.5% and 50.0% in 1997 to 60.4%, 38.8% and 53.3% in 2007 for hypertension, hypercholesterolemia and diabetes, respectively. Self-reported control levels increased from 56.4%, 52.9% and 50.0% in 1997 to 80.6%, 75.1% and 53.3% in 2007 for hypertension, hypercholesterolemia and diabetes, respectively. Finally, screening during the last 12 months increased from 84.5%, 86.5% and 87.4% in 1997 to 94.0%, 94.6% and 94.1% in 2007 for hypertension, hypercholesterolemia and diabetes, respectively.

Conclusion

in Switzerland, the prevalences of self-reported hypertension, hypercholesterolemia and diabetes have increased between 1997 and 2007. Management and screening have improved, but further improvements can still be achieved as over one third of subjects with reported CV RFs are not treated.
Toward nanofluids of ultra-high thermal conductivity
Authors: Wang Liqiu , Fan Jing
Published: February 2011

The assessment of proposed origins for thermal conductivity enhancement in nanofluids signifies the importance of particle morphology and coupled transport in determining nanofluid heat conduction and thermal conductivity. The success of developing nanofluids of superior conductivity depends thus very much on our understanding and manipulation of the morphology and the coupled transport. Nanofluids with conductivity of upper Hashin-Shtrikman (H-S) bound can be obtained by manipulating particles into an interconnected configuration that disperses the base fluid and thus significantly enhancing the particle-fluid interfacial energy transport. Nanofluids with conductivity higher than the upper H-S bound could also be developed by manipulating the coupled transport among various transport processes, and thus the nature of heat conduction in nanofluids. While the direct contributions of ordered liquid layer and particle Brownian motion to the nanofluid conductivity are negligible, their indirect effects can be significant via their influence on the particle morphology and/or the coupled transport.
Interplay between HIV Entry and Transportin-SR2 Dependency
Authors: Thys Wannes , De Houwer Stéphanie , Demeulemeester Jonas , Taltynov Oliver , Vancraenenbroeck Renée , Gérard Melanie , De Rijck Jan , Gijsbers Rik , Christ Frauke , Debyser Zeger
Published: February 2011

Background

Transportin-SR2 (TRN-SR2, TNPO3, transportin 3) was previously identified as an interaction partner of human immunodeficiency virus type 1 (HIV-1) integrase and functions as a nuclear import factor of HIV-1. A possible role of capsid in transportin-SR2-mediated nuclear import was recently suggested by the findings that a chimeric HIV virus, carrying the murine leukemia virus (MLV) capsid and matrix proteins, displayed a transportin-SR2 independent phenotype, and that the HIV-1 N74D capsid mutant proved insensitive to transportin-SR2 knockdown.

Results

Our present analysis of viral specificity reveals that TRN-SR2 is not used to the same extent by all lentiviruses. The DNA flap does not determine the TRN-SR2 requirement of HIV-1. We corroborate the TRN-SR2 independent phenotype of the chimeric HIV virus carrying the MLV capsid and matrix proteins. We reanalyzed the HIV-1 N74D capsid mutant in cells transiently or stably depleted of transportin-SR2 and confirm that the N74D capsid mutant is independent of TRN-SR2 when pseudotyped with the vesicular stomatitis virus glycoprotein (VSV-G). Remarkably, although somewhat less dependent on TRN-SR2 than wild type virus, the N74D capsid mutant carrying the wild type HIV-1 envelope required TRN-SR2 for efficient replication. By pseudotyping with envelopes that mediate pH-independent viral uptake including HIV-1, measles virus and amphotropic MLV envelopes, we demonstrate that HIV-1 N74D capsid mutant viruses retain partial dependency on TRN-SR2. However, this dependency on TRN-SR2 is lost when the HIV N74D capsid mutant is pseudotyped with envelopes mediating pH-dependent endocytosis, such as the VSV-G and Ebola virus envelopes.

Conclusion

Here we discover a link between the viral entry of HIV and its interaction with TRN-SR2. Our data confirm the importance of TRN-SR2 in HIV-1 replication and argue for careful interpretation of experiments performed with VSV-G pseudotyped viruses in studies on early steps of HIV replication including the role of capsid therein.
Vaccination with live attenuated simian immunodeficiency virus causes dynamic changes in intestinal CD4+CCR5+ T cells
Authors: Li Bo , Berry Neil , Ham Claire , Ferguson Deborah , Smith Deborah , Hall Joanna , Page Mark , Quartey-Papafio Ruby , Elsley William , Robinson Mark , Almond Neil , Stebbings Richard
Published: February 2011

Background

Vaccination with live attenuated SIV can protect against detectable infection with wild-type virus. We have investigated whether target cell depletion contributes to the protection observed. Following vaccination with live attenuated SIV the frequency of intestinal CD4+CCR5+ T cells, an early target of wild-type SIV infection and destruction, was determined at days 3, 7, 10, 21 and 125 post inoculation.

Results

In naive controls, modest frequencies of intestinal CD4+CCR5+ T cells were predominantly found within the LPL TTrM-1 and IEL TTrM-2 subsets. At day 3, LPL and IEL CD4+CCR5+ TEM cells were dramatically increased whilst less differentiated subsets were greatly reduced, consistent with activation-induced maturation. CCR5 expression remained high at day 7, although there was a shift in subset balance from CD4+CCR5+ TEM to less differentiated TTrM-2 cells. This increase in intestinal CD4+CCR5+ T cells preceded the peak of SIV RNA plasma loads measured at day 10. Greater than 65.9% depletion of intestinal CD4+CCR5+ T cells followed at day 10, but overall CD4+ T cell homeostasis was maintained by increased CD4+CCR5- T cells. At days 21 and 125, high numbers of intestinal CD4+CCR5- naive TN cells were detected concurrent with greatly increased CD4+CCR5+ LPL TTrM-2 and IEL TEM cells at day 125, yet SIV RNA plasma loads remained low.

Conclusions

This increase in intestinal CD4+CCR5+ T cells, following vaccination with live attenuated SIV, does not correlate with target cell depletion as a mechanism of protection. Instead, increased intestinal CD4+CCR5+ T cells may correlate with or contribute to the protection conferred by vaccination with live attenuated SIV.
Relative survival: a useful tool to assess generalisability in longitudinal studies of health in older persons
Authors: Hockey Richard , Tooth Leigh , Dobson Annette
Published: February 2011

Background

Generalisability of longitudinal studies is threatened by issues such as choice of sampling frame, representativeness of the initial sample, and attrition. To determine representativeness, cohorts are often compared with the population of interest at baseline on demographic and health characteristics. This study illustrates the use of relative survival as a tool for assessing generalisability of results from a cohort of older people among whom death is a potential threat to generalisability.

Methods

The authors used data from the 1921-26 cohort (n = 12,416, aged 70-75 in 1996) of the Australian Longitudinal Study on Women's Health (ALSWH). Vital status was determined by linkage to the National Death Index, and expected deaths were derived using Australian life tables. Relative survival was estimated using observed survival in the cohort divided by expected survival among women of the same age and State or Territory.

Results

Overall, the ALSWH women showed relative survival 9.5% above the general population. Within States and Territories, the relative survival advantage varied from 6% to 23%. The interval-specific relative survival remained relatively constant over the 12 years (1996-2008) under review, indicating that the survival advantage of the cohort has not diminished over time.

Conclusion

This study demonstrates that relative survival can be a useful measure of generalisability in a longitudinal study of the health of the general population, particularly when participants are older.
Spatial and temporal EEG dynamics of dual-task driving performance
Authors: Lin Chin-Teng , Chen Shi-An , Chiu Tien-Ting , Lin Hong-Zhang , Ko Li-Wei
Published: February 2011

Background

Driver distraction is a significant cause of traffic accidents. The aim of this study is to investigate Electroencephalography (EEG) dynamics in relation to distraction during driving. To study human cognition under a specific driving task, simulated real driving using virtual reality (VR)-based simulation and designed dual-task events are built, which include unexpected car deviations and mathematics questions.

Methods

We designed five cases with different stimulus onset asynchrony (SOA) to investigate the distraction effects between the deviations and equations. The EEG channel signals are first converted into separated brain sources by independent component analysis (ICA). Then, event-related spectral perturbation (ERSP) changes of the EEG power spectrum are used to evaluate brain dynamics in time-frequency domains.

Results

Power increases in the theta and beta bands are observed in relation with distraction effects in the frontal cortex. In the motor area, alpha and beta power suppressions are also observed. All of the above results are consistently observed across 15 subjects. Additionally, further analysis demonstrates that response time and multiple cortical EEG power both changed significantly with different SOA.

Conclusions

This study suggests that theta power increases in the frontal area is related to driver distraction and represents the strength of distraction in real-life situations.
The effects of attention capacity on dynamic balance control following concussion
Authors: Catena Robert D , van Donkelaar Paul , Chou Li-Shan
Published: February 2011

The purpose of this study was to examine how individuals modulate attention in a gait/cognition dual task during a 4-week period following a concussion. Ten individuals suffering from a grade 2 concussion and 10 matched controls performed a single task of level walking, a seated auditory Stroop task and a simultaneous auditory Stroop and walking task. Reaction time and accuracy were measured from the Stroop task. Dynamic balance control during gait was measured by the interaction (displacement and velocity) between the center of mass (CoM) and center of pressure (CoP) in the coronal and sagittal planes. Concussed individuals shifted from conservative control of balance (shorter separation between CoM and CoP) immediately after injury to normal balance control over 28 days post-injury. Immediately after injury, correlations analyses using each subject on each testing day as a data point showed that there was a spectrum of deficient performance among concussed individuals on the first testing day. Within a testing session, deficiencies in reaction time of processing involved in the Stroop task were commonly seen with reduce dynamic balance control. However, the prioritization was not always towards the same task between trials. There were no correlations in the control group. Information provided in this study would enhance our understanding of the interaction between attention and gait following concussion.
Licorice consumption as a cause of posterior reversible encephalopathy syndrome: a case report
Authors: van Beers Eduard J , Stam Jan , van den Bergh Walter M
Published: February 2011

Introduction

A 49-year-old woman was admitted to our hospital because of thunderclap headache and blurred vision. At the time of presentation, her blood pressure was 219/100 mmHg, her arterial pH was 7.64 and her potassium level was 2.7 mM/l.

Methods

The combination of sequential computed tomography (CT) and the triad of hypertension, hypokalemia and metabolic alkalosis in this patient suggested the diagnosis. Supplementary anamnesis and long-term follow-up confirmed it.

Results

Brain computed tomography imaging showed minor bleeding in the left Sylvian fissure and bilateral occipital edema, suggestive of posterior reversible encephalopathy syndrome (PRES). Repeated brain CT after 10 days showed a complete resolution of radiological signs. The patient informed us that she had quit smoking 2 weeks ago and had started consuming large amounts of licorice instead of smoking. After she abandoned licorice consumption, her blood pressure normalized. Her latest blood pressure reading was 106/60 mmHg without the use of any antihypertensive drugs.

Conclusions

To the best of our knowledge, this is the first case report describing licorice consumption as a cause of PRES. Glycyrrhizic acid, a component of licorice, inhibits 11β-hydroxysteroid dehydrogenase and subsequently causes mineralocorticoid excess. Mineralocorticoid excess in turn causes high blood pressure and ultimately gives rise to malignant hypertension. Physicians should remember that licorice use is a very easy-to-treat cause of hypertension, hypertensive encephalopathy and PRES.
CD154-CD40 interactions in the control of murine B cell hematopoiesis
Authors: Carlring Jennifer , Altaher Hala M , Clark Susan , Chen Xi , Latimer Sarah L , Jenner Tracey , Buckle Anne-Marie , Heath Andrew W
Published: February 2011

Interactions between CD40 and CD154 play a very important role in control of immune responses, including the delivery of T cell help to B cells and other APCs. Thus far, there has been no role postulated for CD40-CD154 interactions in hematopoiesis. We show here that CD40 is expressed on murine pro-B cells and that its ligation enhances pro-B cell proliferation in vitro and in vivo. In addition, CD154 mRNA is present in the BM. Moreover, we show that a deficiency in CD154 expression has effects on B cell hematopoiesis. Aged, CD154-deficient mice have significantly lower levels of B hematopoietic subsets downstream of pro-B cells in the BM. In addition, B lineage cells reconstitute more slowly following BMT into CD154-deficient recipients. We hypothesize that CD154 is expressed by radio-resistant cells in the BM and plays a role in fine-tuning B cell hematopoiesis.
Simvastatin antagonizes CD40L secretion, CXC chemokine formation, and pulmonary infiltration of neutrophils in abdominal sepsis
Authors: Zhang Su , Rahman Milladur , Zhang Songen , Qi Zhongquan , Thorlacius Henrik
Published: February 2011

Statins have been reported to exert anti-inflammatory actions and protect against septic organ dysfunction. Herein, we hypothesized that simvastatin may attenuate neutrophil activation and lung damage in abdominal sepsis. Male C57BL/6 mice were pretreated with simvastatin (0.5 or 10 mg/kg) before CLP. In separate groups, mice received an anti-CD40L antibody or a CXCR2 antagonist (SB225002) prior to CLP. BALF and lung tissue were harvested for analysis of neutrophil infiltration, as well as edema and CXC chemokine formation. Blood was collected for analysis of Mac-1 and CD40L expression on neutrophils and platelets, as well as soluble CD40L in plasma. Simvastatin decreased CLP-induced neutrophil infiltration and edema formation in the lung. Moreover, Mac-1 expression increased on septic neutrophils, which was significantly attenuated by simvastatin. Inhibition of CD40L reduced CLP-induced up-regulation of Mac-1 on neutrophils. Simvastatin prevented CD40L shedding from the surface of platelets and reduced circulating levels of CD40L in septic mice. CXC chemokine-induced migration of neutrophils in vitro was decreased greatly by simvastatin. Moreover, simvastatin abolished CLP-evoked formation of CXC chemokines in the lung, and a CXCR2 antagonist attenuated pulmonary accumulation of neutrophils. Our data suggest that the inhibitory effect of simvastatin on pulmonary accumulation of neutrophils may be related to a reduction of CD40L secretion into the circulation, as well as a decrease in CXC chemokine formation in the lung. Thus, these protective mechanisms help to explain the beneficial actions exerted by statins, such as simvastatin, in sepsis.
IL-23R and TCR signaling drives the generation of neonatal Vγ9Vδ2 T cells expressing high levels of cytotoxic mediators and producing IFN-γ and IL-17
Authors: Moens Emmanuelle , Brouwer Margreet , Dimova Tanya , Goldman Michel , Willems Fabienne , Vermijlen David
Published: February 2011

The immune system in early life is regarded as immature. However, the IL-12 family member IL-23 is highly produced upon TLR stimulation by neonatal DCs. Human adult Vγ9Vδ2 T cells can be stimulated specifically via their TCR by phosphoantigens (as the pathogen-derived HMB-PP) or agents and infections that lead to their endogenous accumulation (as the aminobisphosphonate zoledronate). As increasing evidence indicates that γδ T cells are especially important in early life, we investigated the effect of IL-23 on neonatal Vγ9Vδ2 T cells stimulated via their TCR. Zoledronate induced clear proliferation and IFN-γ production in neonatal Vγ9Vδ2 T cells. In contrast, HMB-PP did not elicit a distinct response unless at high concentrations. Addition of IL-23 to zoledronate enhanced the expression of IFN-γ and generated a distinct, IFN-γ-negative, neonatal Vγ9Vδ2 T cell population producing IL-17. Furthermore, IL-23 significantly enhanced the expression of a range of cytotoxic mediators (perforin, granzymes, granulysin). Although the costimulatory effect of IL-23 on IFN-γ and cytotoxic mediators was also observed within adult Vγ9Vδ2 T cells, the induction of an IL-17+IFN-γ– subset was unique to neonatal Vγ9Vδ2 T cells. In conclusion, neonatal DC-derived IL-23 combined with specific TCR signaling drives the generation of neonatal Vγ9Vδ2 T cells equipped with a range of cytotoxic mediators and distinct subpopulations producing IFN-γ and IL-17.
Exocytosis of azurophil and arginase 1-containing granules by activated polymorphonuclear neutrophils is required to inhibit T lymphocyte proliferation
Authors: Rotondo Rita , Bertolotto Maria , Barisione Gaia , Astigiano Simonetta , Mandruzzato Susanna , Ottonello Luciano , Dallegri Franco , Bronte Vincenzo , Ferrini Silvano , Barbieri Ottavia
Published: February 2011

ARG1, expressed by human PMNs, inhibits T cell proliferation by depleting extracellular l-arginine. Here, we report that ARG1, released from gelatinase granules by PMNs, is inactive at physiological pH unless activated by factor(s) stored in azurophil granules. Whereas ARG1 exocytosis was induced by TNF-α or ionomycin, only the latter mediated the release of both granules, resulting in extracellular ARG enzyme activity at physiological pH. Furthermore, after fractionation of the different classes of granules, only the mixture of gelatinase and azurophil granules resulted in ARG1 activity at physiological pH. The use of protease inhibitors indicated the involvement of a PMSF- and leupeptin-susceptible serine protease in ARG1 processing and activation. Finally, the supernatant of viable PMNs undergoing frustrated phagocytosis, which mediates gelatinase and azurophil granule release, inhibited T cell proliferation through ARG-dependent mechanisms. In vivo, high ARG1 concentrations and increased ARG enzyme activity, sufficient to inhibit T cell proliferation, were observed in synovial fluids from RA. These findings suggest that PMNs, recruited at sites of immune complex deposition, induce ARG1-dependent immune suppression through concomitant exocytosis of gelatinase and azurophil granules.
Interleukin-27 and interleukin-23 modulate human plasmacell functions
Authors: Cocco Claudia , Morandi Fabio , Airoldi Irma
Published: February 2011

This study tested the hypothesis that IL-27 and IL-23, two heterodimeric cytokines involved in physiological immune responses and immunological disorders, may function on human PC and plasmablasts. It was reported that IL-27 acts on human mature B cells, but the role of IL-27 and IL-23 in human PC remains to be established. Thus, we have asked whether these cytokines may modulate human PC functions using human PPC generated in vitro, PC isolated from tonsils, and BM. Here, we show for the first time that PC and PPC express complete IL-27R and that IL-27 exerts chemotactic properties on these cells and modulates different chemokines/chemokine receptors and secretion of IgM and IgG. Furthermore, we demonstrated that PC and PPC express both chains of IL-23R and IL-23 and exerted similar activity to IL-27 in terms of Ig production, while not inducing PC chemotaxis. These results may provide novel insight into the role of IL-27 and IL-23 in human B cell immune responses.
Injuries Associated With Cribs, Playpens, and Bassinets Among Young Children in the US, 1990–2008
Authors: Yeh Elaine S. , Rochette Lynne M. , McKenzie Lara B. , Smith Gary A.
Published: February 2011

OBJECTIVE:

To describe the epidemiology of injuries related to cribs, playpens, and bassinets among young children in the United States.

METHODS:

A retrospective analysis was done using data from the National Electronic Injury Surveillance System for children younger than 2 years of age treated in emergency departments in the United States from 1990 through 2008 for an injury associated with cribs, playpens, and bassinets.

RESULTS:

An estimated 181 654 (95% confidence interval: 148 548–214 761) children younger than 2 years of age were treated in emergency departments in the United States for injuries related to cribs, playpens, and bassinets during the 19-year study period. There was an average of 9561 cases per year or an average of 12.1 injuries per 10 000 children younger than 2 years old per year. Most of the injuries involved cribs (83.2%), followed by playpens (12.6%) and bassinets (4.2%). The most common mechanism of injury was a fall from a crib, playpen, or bassinet, representing 66.2% of injuries. Soft-tissue injuries comprised the most common diagnosis (34.1%), and the most frequently injured body region was the head or neck (40.3%). Patients with fractures were admitted 14.0% of the time, making them 5.45 (95% confidence interval: 3.80–7.80) times more likely to be hospitalized than patients with other types of injury. Children younger than 6 months were 2.97 (95% confidence interval: 2.07–4.24) times more likely to be hospitalized than older children.

CONCLUSIONS:

This study is the first to use a nationally representative sample to examine injuries associated with cribs, playpens, and bassinets. Given the consistently high number of observed injuries, greater efforts are needed to ensure safety in the design and manufacture of these products, ensure their proper usage in the home, and increase awareness of their potential dangers to young children.
Microbial Diversity of Peri-Implant Biofilms on Implant Fixed Bar and Telescopic Double Crown Attachments
Authors: Heuer Wieland , Kettenring Andreas , Demling Anton , Stumpp Sascha Nico , Gellermann Eva , Winkel Andreas , Stiesch Meike
Published: February 2011

One of the principal problems in oral implantation is inflammation of peri-implant hard and soft tissues caused by bacterial biofilms. The purpose of the present study was to evaluate the microbial diversity of peri-implant biofilms on 2 different implant-anchored attachment types in vivo. Samples of peri-implant sulcus fluid were collected from 8 patients with implant-supported bar attachments and 8 patients with implant-anchored telescopic double crown attachments. Samples of sulcus fluid of the adjacent teeth were also collected from the partially edentulous patients with implant fixed telescopic double crowns. The mixed amplicons of 16S rRNA fragments of different bacterial origins were separated by use of single-strand conformation polymorphism analysis to identify the predominant bacterial genera. With 3.5 ± 2.1 different predominant bacterial genera in the sulcus fluid surrounding implant-supported bar attachments and 6.3 ± 3.1 different predominant genera in the sulcular fluid of implant-anchored double crown attachments, the differences were not statistically significant (P = .11). The microbial diversity in the sulcus fluid surrounding the remaining dentition was similar to that of the implant fixed telescopic attachments (6.3 ± 2.1). Aside from host response and other individual factors, the microbial diversity of peri-implant biofilms seems to be impaired by cofactors such as the possibility of cleaning the implant-supported supraconstructions and the different plaque-retaining sites. Nevertheless, these differences do not lead to statistically significant differences in the microbial diversity of peri-implant plaques.
Linkage Mapping and QTL Analysis of Agronomic Traits in Tetraploid Potato (Solanum tuberosum subsp. tuberosum)
Authors: McCord Per H. , Sosinski Bryon R. , Haynes Kathleen G. , Clough Mark E. , Yencho G. Craig
Published: February 2011

Potato (Solanum tuberosum L.) is one of the world's most important crops. Using a tetraploid population, we developed a linkage map using amplified fragment length polymorphism and simple sequence repeat (SSR) markers, and searched for quantitative trait loci (QTL) via interval mapping and single‐marker analysis of variance. Quantitative trait loci were detected for flower color, foliage maturity, tuber skin texture, dry matter content, specific gravity, and yield. Most linkage groups were anchored to Solanum chromosomes using SSRs. The most significant QTL detected was for flower color. It was located on chromosome II and explained over 40% of the variation for this trait. This QTL most likely corresponds to the R locus for red anthocyanin production. We also confirmed the presence of QTL for foliage maturity on chromosomes III and V. For skin texture, a trait that has not been previously mapped in potato, we detected multiple QTL. One of these, found on chromosome III, explained 20% of the variation. By measuring specific gravity and dry matter independently we were able to detect QTL for these traits that did not co‐locate, even though the traits are strongly correlated. Yield QTL were detected on multiple chromosomes, including a novel one on chromosome III. Many QTL could be modeled as simplex or duplex with dominant effects, but a large number displayed additive or interallelic interactive effects. The mapping and modeling of traits in this tetraploid population could be improved by the use of more codominant markers, such as single nucleotide polymorphisms.
Molecular Marker Dissection of Ryegrass Plant Development and its Response to Growth Environments and Foliage Cuts
Authors: Kobayashi Sohei , Humphreys Mervyn O. , Tase Kazuhiro , Sanada Yasuharu , Yamada Toshihiko
Published: February 2011

For perennial forage grasses, tillering and shoot elongation are important developmental events to determine grassland production. To thoroughly identify and characterize quantitative trait locus (QTL) regions controlling the events, a perennial ryegrass (Lolium perenne L.) mapping population comprising 188 F2 individuals was evaluated for tiller number (TN), plant length (PL), and leaf length (LL) over 12 cuts in replicated field and pot experiments in Sapporo, Japan, during 2 yr. Quantitative trait loci were repeatedly detected in 16 genomic regions. Based on the QTL, 10 regions affected both shoot elongation (PL and LL) and tillering (TN), whereas only six regions had a single effect on either event. Five QTL regions mapped on linkage groups 1, 2, 5, and 6, explaining at maximum 34 to 56% phenotypic variance, likely contain key genes for plant development. Profiles (e.g., direction and magnitude) of QTL effects differed greatly among most regions, indicating a large diversity among the genes involved. Statistical tests revealed significant interaction effects of genotype with growth condition and cut for all QTL regions. The QTL positions were compared with those reported for ryegrass and rice, suggesting the presence of genes identical to the current population and semiwild perennial forage grasses. The current QTL analysis indicated that the control of ryegrass plant development involves diverse, unique genes whose effects are enhanced or suppressed by growth environment and foliage cutting.