bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward a Cultural Perspective and Understanding of the Disability and Deaf Experience in Special and Multicultural Education
Authors: Johnson John R. , McIntosh Angela S.
Published: November 2008

This position paper provides a rationale for infusing cultural perspectives and understandings of the Disability and Deaf experiences into special and multicultural education teacher preparation programs. Substantial evidence of well-established features of the Disability community and Deaf community that meet definitional criteria for culture as conveyed in the multicultural education literature is presented. The extent that Disability and Deaf cultures have been reflected in special and multicultural education textbooks is addressed to validate the need for the incorporation of cultural perspectives of Disability and Deaf experiences into teacher preparation programs. A conspicuous absence of discussion about the culture of Disability and Deafness from the perspectives of members of these communities is reported. Implications of these findings for teacher preparation programs and for educational policy, practice, and research are discussed. Recommendations for the acknowledgement and support of cultural perspectives and understandings related to the Disability and Deaf experiences are offered.
Gender-related differences in MS: a study of conventional and nonconventional MRI measures
Authors: Antulov R , Weinstock-Guttman B , Cox JL , Hussein S , Durfee J , Caiola C , Dwyer MG , Bergsland N , Abdelrahman N , Stosic M , Hojnacki D , Munschauer FE , Miletic D , Zivadinov R
Published: November 2008

Background

Studies showed gender-associated differences in multiple sclerosis (MS) disease evolution and in the evolution of conventional magnetic resonance imaging (MRI) findings.

Objective

The aim of this study was to investigate gender differences according to a number of conventional and nonconventional MRI measures in patients with MS.

Methods

We examined 763 consecutive patients with MS [499 (19.2% men) relapsing-remitting (RR), 230 (24.8% men) secondary-progressive, and 34 (44.1% men) primary-progressive], 32 (21.9% men) patients with clinically isolated syndrome (CIS), and 101 (30.7% men) normal controls (NC). Patients were assessed using conventional and nonconventional MRI measures. Gender-related MRI differences were investigated using general linear model analysis, corrected for MS disease type.

Results

In the total MS group, male patients showed lower normalized peripheral gray matter (GM) ( P < 0.001) and normalized GM ( P = 0.011) volumes than female patients. Female patients presented lower normalized white matter (WM) volumes ( P = 0.011). These gender effects were not observed in NC. Male patients also showed more advanced central atrophy ( P = 0.022). In RRMS male patients, there was also a higher lateral ventricle volume ( P = 0.001). The GM-WM normalized ratio was lower for male patients with MS compared with male NC (0.97 vs. 1.09, P < 0.001) but not in patients with CIS compared with NC.

Conclusions

There were no significant gender-related differences regarding nonconventional MRI measures. GM and central atrophy are more advanced in male patients, whereas WM atrophy is more advanced in female patients. These gender-related MRI differences may be explained by the effect of sex hormones on brain damage and repair mechanisms.
Welding repair by linear friction in titanium alloys
Authors: Mateo A. , Corzo M. , Anglada M. , Mendez J. , Villechaise P. , Ferte J.-P. , Roder O.
Published: November 2008

Gas turbines for aeroengines are generally manufactured by attaching individual blades into slots in the disk. However, an alternative design consists in producing bladed disks, where disk and blades are a single piece. Previous studies have shown that linear friction welding is a technology which fits well for this application. On the other hand, bladed disks can experience in service damages and therefore affordable repair technology must be available. The present paper presents the microstructural and mechanical evaluation of double and triple welds produced to simulate replacements of damaged blades. The results show that, even though the successive welds induce a small strength decrease, both tensile and fatigue failures always initiated far away of the weld zone.
RUNX1/AML1 DNA-binding domain and ETO/MTG8 NHR2-dimerization domain are critical to AML1-ETO9a leukemogenesis
Authors: Yan Ming , Ahn Eun-Young , Hiebert Scott W. , Zhang Dong-Er
Published: November 2008

The 8;21 translocation, which involves the gene encoding the RUNX family DNA-binding transcription factor AML1 (RUNX1) on chromosome 21 and the ETO (MTG8) gene on chromosome 8, generates AML1-ETO fusion proteins. Previous analyses have demonstrated that full-length AML1-ETO blocks AML1 function and requires additional mutagenic events to promote leukemia. More recently, we have identified an alternatively spliced form of AML1-ETO, AML1-ETO9a, from t(8;21) acute myeloid leukemia (AML) patient samples. AML1-ETO9a lacks the C-terminal NHR3 and NHR4 domains of AML1-ETO and is highly leukemogenic in the mouse model. Here, we report that the AML1 DNA-binding domain and the ETO NHR2-dimerization domain, but not the ETO NHR1 domain, are critical for the induction of AML by AML1-ETO9a. A region between NHR1 and NHR2 affects latency of leukemogenesis. These results provide valuable insight into further analysis of the molecular mechanism of t(8;21) in leukemogenesis.
ExonMiner: Web service for analysis of GeneChip Exon array data
Authors: Numata Kazuyuki , Yoshida Ryo , Nagasaki Masao , Saito Ayumu , Imoto Seiya , Miyano Satoru
Published: November 2008

Background

Some splicing isoform-specific transcriptional regulations are related to disease. Therefore, detection of disease specific splice variations is the first step for finding disease specific transcriptional regulations. Affymetrix Human Exon 1.0 ST Array can measure exon-level expression profiles that are suitable to find differentially expressed exons in genome-wide scale. However, exon array produces massive datasets that are more than we can handle and analyze on personal computer.

Results

We have developed ExonMiner that is the first all-in-one web service for analysis of exon array data to detect transcripts that have significantly different splicing patterns in two cells, e.g. normal and cancer cells. ExonMiner can perform the following analyses: (1) data normalization, (2) statistical analysis based on two-way ANOVA, (3) finding transcripts with significantly different splice patterns, (4) efficient visualization based on heatmaps and barplots, and (5) meta-analysis to detect exon level biomarkers. We implemented ExonMiner on a supercomputer system in order to perform genome-wide analysis for more than 300,000 transcripts in exon array data, which has the potential to reveal the aberrant splice variations in cancer cells as exon level biomarkers.

Conclusion

ExonMiner is well suited for analysis of exon array data and does not require any installation of software except for internet browsers. What all users need to do is to access the ExonMiner URL http://ae.hgc.jp/exonminer. Users can analyze full dataset of exon array data within hours by high-level statistical analysis with sound theoretical basis that finds aberrant splice variants as biomarkers.
CORE_TF: a user-friendly interface to identify evolutionary conserved transcription factor binding sites in sets of co-regulated genes
Authors: Hestand Matthew S , van Galen Michiel , Villerius Michel P , van Ommen Gert-Jan B , den Dunnen Johan T , 't Hoen Peter AC
Published: November 2008

Background

The identification of transcription factor binding sites is difficult since they are only a small number of nucleotides in size, resulting in large numbers of false positives and false negatives in current approaches. Computational methods to reduce false positives are to look for over-representation of transcription factor binding sites in a set of similarly regulated promoters or to look for conservation in orthologous promoter alignments.

Results

We have developed a novel tool, "CORE_TF" (Conserved and Over-REpresented Transcription Factor binding sites) that identifies common transcription factor binding sites in promoters of co-regulated genes. To improve upon existing binding site predictions, the tool searches for position weight matrices from the TRANSFACRdatabase that are over-represented in an experimental set compared to a random set of promoters and identifies cross-species conservation of the predicted transcription factor binding sites. The algorithm has been evaluated with expression and chromatin-immunoprecipitation on microarray data. We also implement and demonstrate the importance of matching the random set of promoters to the experimental promoters by GC content, which is a unique feature of our tool.

Conclusion

The program CORE_TF is accessible in a user friendly web interface athttp://www.LGTC.nl/CORE_TF. It provides a table of over-represented transcription factor binding sites in the users input genes' promoters and a graphical view of evolutionary conserved transcription factor binding sites. In our test data sets it successfully predicts target transcription factors and their binding sites.
PlantPAN: Plant promoter analysis navigator, for identifying combinatorial cis-regulatory elements with distance constraint in plant gene groups
Authors: Chang Wen-Chi , Lee Tzong-Yi , Huang Hsien-Da , Huang His-Yuan , Pan Rong-Long
Published: November 2008

Background

The elucidation of transcriptional regulation in plant genes is important area of research for plant scientists, following the mapping of various plant genomes, such as A. thaliana, O. sativa and Z. mays. A variety of bioinformatic servers or databases of plant promoters have been established, although most have been focused only on annotating transcription factor binding sites in a single gene and have neglected some important regulatory elements (tandem repeats and CpG/CpNpG islands) in promoter regions. Additionally, the combinatorial interaction of transcription factors (TFs) is important in regulating the gene group that is associated with the same expression pattern. Therefore, a tool for detecting the co-regulation of transcription factors in a group of gene promoters is required.

Results

This study develops a database-assisted system, PlantPAN (Plant Promoter Analysis Navigator), for recognizing combinatorial cis-regulatory elements with a distance constraint in sets of plant genes. The system collects the plant transcription factor binding profiles from PLACE, TRANSFAC (public release 7.0), AGRIS, and JASPER databases and allows users to input a group of gene IDs or promoter sequences, enabling the co-occurrence of combinatorial transcription factor binding sites (TFBSs) within a defined distance (20 bp to 200 bp) to be identified. Furthermore, the new resource enables other regulatory features in a plant promoter, such as CpG/CpNpG islands and tandem repeats, to be displayed. The regulatory elements in the conserved regions of the promoters across homologous genes are detected and presented.

Conclusion

In addition to providing a user-friendly input/output interface, PlantPAN has numerous advantages in the analysis of a plant promoter. Several case studies have established the effectiveness of PlantPAN. This novel analytical resource is now freely available at http://PlantPAN.mbc.nctu.edu.tw.
Frequency and predictors of miliary tuberculosis in patients with miliary pulmonary nodules in South Korea: A retrospective cohort study
Authors: Jin Sang-Man , Lee Hyun Ju , Park Eun-Ah , Lee Ho Yun , Lee Sang-Min , Yang Seok-Chul , Yoo Chul-Gyu , Kim Young Whan , Han Sung Koo , Shim Young-Soo , Yim Jae-Joon
Published: November 2008

Background

Miliary pulmonary nodules are commonly caused by various infections and cancers. We sought to identify the relative frequencies of various aetiologies and the clinical and radiographic predictors of miliary tuberculosis (TB) in patients with miliary pulmonary nodules.

Methods

We performed a retrospective cohort study of patients who presented with micronodules occupying more than two-thirds of the lung volume, based on computed tomography (CT) of the chest, between November 2001 and April 2007, in a tertiary referral hospital in South Korea.

Results

We analyzed 76 patients with miliary pulmonary nodules. Their median age was 52 years and 38 (50%) were males; 18 patients (24%) had a previous or current malignancy and five (7%) had a history of TB. The most common diagnoses of miliary nodules were miliary TB (41 patients, 54%) and miliary metastasis of malignancies (20 patients, 26%). Multivariate analysis revealed that age ≤30 years, HIV infection, corticosteroid use, bronchogenic spread of lesions, and ground-glass opacities occupying >25% of total lung volume increased the probability of miliary TB. However, a history of malignancy decreased the probability of miliary TB.

Conclusion

Miliary TB accounted for approximately half of all causes of miliary pulmonary nodules. Young age, an immune-compromised state, and several clinical and radiographic characteristics increased the probability of miliary TB.
Gene expression profile of cervical and skin tissues from human papillomavirus type 16 E6 transgenic mice
Authors: Mendoza-Villanueva D , Diaz-Chavez J , Uribe-Figueroa L , Rangel-Escareão C , Hidalgo-Miranda A , March-Mifsut S , Jimenez-Sanchez G , Lambert PF , Gariglio P
Published: November 2008

Background

Although K14E6 transgenic mice develop spontaneous tumors of the skin epithelium, no spontaneous reproductive tract malignancies arise, unless the transgenic mice were treated chronically with 17β-estradiol. These findings suggest that E6 performs critical functions in normal adult cervix and skin, highlighting the need to define E6-controlled transcriptional programs in these tissues.

Methods

We evaluated the expression profile of 14,000 genes in skin or cervix from young K14E6 transgenic mice compared with nontransgenic. To identify differentially expressed genes a linear model was implemented using R and the LIMMA package. Two criteria were used to select the set of relevant genes. First a set of genes with a Log-odds ≥ 3 were selected. Then, a hierarchical search of genes was based on Log Fold Changes.

Results

Microarray analysis identified a total of 676 and 1154 genes that were significantly up and down-regulated, respectively, in skin from K14E6 transgenic mice. On the other hand, in the cervix from K14E6 transgenic mice we found that only 97 and 252 genes were significantly up and down-regulated, respectively. One of the most affected processes in the skin from K14E6 transgenic mice was the cell cycle. We also found that skin from transgenic mice showed down-regulation of pro-apoptotic genes and genes related to the immune response. In the cervix of K14E6 transgenic mice, we could not find affected any gene related to the cell cycle and apoptosis pathways but did observe alterations in the expression of immune response genes. Pathways such as angiogenesis, cell junction and epidermis development, also were altered in their gene expression profiles in both tissues.

Conclusion

Expression of the HPV16 E6 oncoprotein in our model alters expression of genes that fell into several functional groups providing insights into pathways by which E6 deregulate cell cycle progression, apoptosis, the host resistance to infection and immune function, providing new opportunities for early diagnostic markers and therapeutic drug targets.
Evaluation of efficacy and safety of gefitinib as monotherapy in Chinese patients with advanced non-small cell lung cancer and very poor performance status
Authors: Wei Zhong , Mengzhao Wang , Li Zhang , Longyun Li , Xiaotong Zhang
Published: November 2008

Background

This paper reports the outcome of gefitinib for Chinese advanced NSCLC patients with poor performance status (PS) at the Peking Union Medical College Hospital.

Methods

From Oct 2002 to Apr. 2006, 42 advanced NSCLC patients with PS 3/4 received gefitinib 250 mg/day treatment. Median survival (MS) were calculated using the Kaplan-Meier method and a Cox regression model was used to find main factors affecting MS.

Results

Adverse events (AEs) were generally mild (grade 1 and 2) and reversible. The most frequent AEs were rash 72.2% (26/42) and diarrhea 44.4% (26/42). The objective tumor response rate and stable disease rate were 40.5% and 26.2% respectively, and median survival(MS) of all patients was 10.1 months (95% confidential interval CI, 3.4 ~ 16.8), and progression-free survival(PFS) was 5.7 months (95% CI, 4.5 ~ 6.9). The MS were significantly related with objective response of gefitinib. Objective responses was significantly related with rashes induced with gefitinib.

Conclusion

Our study suggest that treatment with gefitinib may be well tolerated and beneficial for Chinese patients with poor PS, and the safety and efficacy were similar to patients with good PS.
Y-box binding protein-1 serine 102 is a downstream target of p90 ribosomal S6 kinase in basal-like breast cancer cells
Authors: Stratford Anna L , Fry Christopher J , Desilets Curtis , Davies Alastair H , Cho Yong Y , Li Yvonne , Dong Zigang , Berquin Isabelle M , Roux Philippe P , Dunn Sandra E
Published: November 2008

Introduction

Basal-like breast cancers (BLBC) frequently overexpress the epidermal growth factor receptor (EGFR) and subsequently have high levels of signaling through the MAP kinase pathway, which is thought to contribute to their aggressive behavior. While we have previously reported the expression of Y-box binding protein-1 (YB-1) in 73% of BLBC, it is unclear whether it can be regulated by a component of the MAP kinase signaling pathway. Phosphorylation of YB-1 at the serine 102 residue is required for transcriptional activation of growth-enhancing genes, such as EGFR. Using Motifscan we identified p90 ribosomal S6 kinase (RSK) as a potential candidate for activating YB-1.

Methods

Inhibition of RSK1 and RSK2 was achieved using siRNA and the small molecule SL0101. RSK1, RSK2, activated RSK and kinase-dead RSK were expressed in HCC1937 cells. Kinase assays were performed to illustrate direct phosphorylation of YB-1 by RSK. The impact of inhibiting RSK on YB-1 function was measured by luciferase assays and chromatin immunoprecipitation.

Results

Using an in vitro kinase assay, RSK1 and RSK2 were shown to directly phosphorylate YB-1. Interestingly, they were more effective activators of YB-1 than AKT or another novel YB-1 kinase, PKCα. Phosphorylation of YB-1 (serine 102 residue) is blocked by inhibition of the MAP kinase pathway or by perturbing RSK1/RSK2 with siRNA or SL0101. In immortalized breast epithelial cells where RSK is active yet AKT is not, YB-1 is phosphorylated. Supporting this observation, RSK2-/- mouse embryo fibroblasts lose the ability to phosphorylate YB-1 in response to epidermal growth factor. This subsequently interfered with the ability of YB-1 to regulate the expression of EGFR. The RSK inhibitor SL0101 decreased the ability of YB-1 to bind the promoter, transactivate and ultimately reduce EGFR expression. In concordance with these results the expression of constitutively active RSK1 increased YB-1 phosphorylation, yet the kinase-dead RSK did not.

Conclusions

We therefore conclude that RSK1/RSK2 are novel activators of YB-1, able to phosphorylate the serine 102 residue. This provides a newly described mechanism whereby YB-1 is activated in breast cancer. This implicates the EGFR/RSK/YB-1 pathway as an important component of BLBC, providing an important opportunity for therapeutic intervention.
Studying host-pathogen interactions and innate immunity in Caenorhabditis elegans
Authors: Kim Dennis
Published: November 2008

The genetic analysis of mechanisms of pathogen resistance in the nematode Caenorhabditis elegans has revealed a role for evolutionarily conserved signaling pathways that are required for innate immunity in a wide range of organisms, from worms to mammals. C. elegans represents one of the more simple host organisms in which mechanisms of host defense can be dissected, and the use of C. elegans presents the researcher with a wide array of genetic and genomic tools to probe the host-pathogen interface. The study of host defense mechanisms in C. elegans continues to provide an ancient evolutionary perspective on innate immunity, which may generate insights into the conserved processes in phylogenetically diverse host organisms, including humans.
Mouse models of allergic asthma: acute and chronic allergen challenge
Authors: Nials Anthony T. , Uddin Sorif
Published: November 2008

Asthma is defined as a chronic inflammatory disease of the airways; however, the underlying physiological and immunological processes are not fully understood. Animal models have been used to elucidate asthma pathophysiology, and to identify and evaluate novel therapeutic targets. Several recent review articles (Epstein, 2004; Lloyd, 2007; Boyce and Austen, 2005; Zosky and Sly, 2007) have discussed the potential value of these models. Allergen challenge models reproduce many features of clinical asthma and have been widely used by investigators; however, the majority involve acute allergen challenge procedures. It is recognised that asthma is a chronic inflammatory disease resulting from continued or intermittent allergen exposure, usually via inhalation, and there has been a recent focus on developing chronic allergen exposure models, predominantly in mice. Here, we review the acute and chronic exposure mouse models, and consider their potential role and impact in the field of asthma research.
Research on animal model organisms funded by the European Commission’s framework programmes
Authors: Desaintes Christian
Published: November 2008

Recognising the crucial role of model organisms in exploring the causes of human disease and in developing safe treatments, the European Commission has invested €180 million in collaborative research projects on model organisms since 2002. Further financial support is planned for the future. Projects supported by the European Commission are playing an important role in structuring the research landscape in Europe and creating the knowledge base to understand health and disease. Furthermore, they are generating important and freely available data and/or animal resources that will catalyse progress in biomedical research. This paper focuses on animal model organisms and includes the rodents, mouse and rat, other vertebrates such as zebrafish and frog, and also invertebrates such as nematodes. Research on other model organisms, including yeast, bacteria and plants, is also being supported and this is providing knowledge on basic cellular and molecular processes, as well as on host-microorganism interactions.
Promoting translational research at Vanderbilt University’s CTSA institute
Authors: Kain Kristin
Published: November 2008

As part of a national consortium to efficiently advance patient care, Vanderbilt University is approaching translational medicine in creative new ways. Kristin Kain investigates.
The first transgenic mice: an interview with Mario Capecchi
Authors: Kain Kristin
Published: November 2008

Mario Capecchi recently won the Nobel Prize for contributions to genetics that have catapulted the mouse to the status of the most valuable of all animal models. He has a personal story that is as rich and interesting as his science. Here, he discusses the journey that led him to gene targeting and his vision for the future.
Extensive-Form Correlated Equilibrium: Definition and Computational Complexity
Authors: von Stengel Bernhard , Forges Françoise
Published: November 2008

This paper defines the extensive-form correlated equilibrium (EFCE) for extensive games with perfect recall. The EFCE concept extends Aumann's strategic-form correlated equilibrium (CE). Before the game starts, a correlation device generates a move for each information set. This move is recommended to the player only when the player reaches the information set. In two-player perfect-recall extensive games without chance moves, the set of EFCE can be described by a polynomial number of consistency and incentive constraints. Assuming P is not equal to NP, this is not possible for the set of CE, or if the game has chance moves.
Development and validation of a unifactorial measure of citizenship performance
Authors: Poropat Arthur E. , Jones Liz
Published: November 2008

Citizenship Performance has long been accepted as an important aspect of performance, but there has been little consensus on how best to measure this construct. Previous measures have assessed as many as five sub‐factors, yet recent meta‐analyses have indicated that citizenship is largely unifactorial. At the same time, none of the previously developed unifactorial Citizenship Performance scales have been adequately validated. Consequently, this article reports the development of a unifactorial measure of Citizenship Performance, which was found to have good criterion validity. The unifactorial scale also had superior convergent and divergent validity, and better internal factor structure, than the commonly‐used Job Dedication and Interpersonal Facilitation scales, developed by Van Scotter and Motowidlo (1996).
Using Median Regression to Obtain Adjusted Estimates of Central Tendency for Skewed Laboratory and Epidemiologic Data
Authors: McGreevy Katharine M , Lipsitz Stuart R , Linder Jeffrey A , Rimm Eric , Hoel David G
Published: November 2008

Background: Laboratory studies often involve analyses of highly skewed data for which means are not an adequate measure of central tendency because they are sensitive to outliers. Attempts to transform skewed data to symmetry are not always successful, and medians are better measures of central tendency for such skewed distributions. When medians are compared across groups, confounding can be an issue, so there is a need for adjusted medians.

Methods: We illustrate the use of quantile regression to obtain adjusted medians. The method is illustrated by use of skewed nutrient data obtained from black and white men attending a prostate cancer screening. For 3 nutrients, saturated fats, caffeine, and vitamin K, we obtained medians adjusted by age, body mass index, and calories for men in each race group.

Results: Quantile regression, linear regression, and log-normal regression produced substantially different adjusted estimates of central tendency for saturated fats, caffeine, and vitamin K.

Conclusions: Our method was useful for analysis of skewed and other nonnormally distributed continuous outcome data and for calculation of adjusted medians.
Quantification of 8 HIV-Protease Inhibitors and 2 Nonnucleoside Reverse Transcriptase Inhibitors by Ultra-Performance Liquid Chromatography with Diode Array Detection
Authors: Elens Laure , Veriter Sophie , Di Fazio Vincent , Vanbinst Roger , Boesmans Daniel , Wallemacq Pierre , Haufroid Vincent
Published: November 2008

Background: Most HPLC-UV methods for therapeutic drug monitoring of anti-HIV drugs have long run times, which reduce their applicability for high-throughput analysis. We developed an ultra-performance liquid chromatography (UPLC)–diode array detection method for the simultaneous quantification of the HIV-protease inhibitors (PIs) amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, and tipranavir (TPV), and the nonnucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz and nevirapine.

Methods: Solid-phase extraction of 1 mL plasma was performed with Waters HLB cartridges. After 3 wash steps, we eluted the drugs with methanol, evaporated the alcohol, and reconstituted the residue with 50 μL methanol. We injected a 4-μL volume into the UPLC system (Waters ACQUITY UPLC BEH C8 column maintained at 60 °C) and used a linear gradient of 50 mmol/L ammonium acetate and 50 mmol/L formic acid in water versus acetonitrile to achieve chromatographic separation of the drugs and internal standard (A-86093). Three wavelengths (215, 240, and 260 nm) were monitored.

Results: All drugs were eluted within 15 min. Calibration curves with concentrations of 0.025–10 mg/L (1.875–75 mg/L for TPV) showed coefficients of determination (r2) between 0.993 and 0.999. The lower limits of quantification were well below the trough concentrations reported in the literature. Inter- and intraassay CVs and the deviations between the nominal and measured concentrations were <15%. The method was validated by successful participation in an international interlaboratory QC program.

Conclusions: This method allows fast and simultaneous quantification of all commercially available PIs and NNRTIs for therapeutic drug monitoring.
Only Large Reductions in Concentrations of Natriuretic Peptides (BNP and NT-proBNP) Are Associated with Improved Outcome in Ambulatory Patients with Chronic Heart Failure
Authors: Miller Wayne L , Hartman Karen A , Grill Diane E , Burnett John C , Jaffe Allan S
Published: November 2008

Background: Concentrations of B-type natriuretic peptides (BNPs), including N-terminal pro-B-type natriuretic peptide (NT-proBNP), can be used to estimate prognosis in chronic heart failure. Large biologic variability, however, limits the usefulness of serial measurements in individual patients. As a result, the magnitude of change in peptide concentrations that is clinically meaningful remains to be established.

Methods: We studied 172 New York Heart Association class III–IV outpatients. Primary endpoints were death/transplantation or heart failure hospitalization. The magnitude of peptide changes was categorized as no change (<20% increase or decrease from enrollment), ≥20% to ≤80% increase or decrease; and >80% increase or decrease. Changes were also assessed using cutpoints (500 ng/L for BNP and 1000 ng/L for NT-proBNP).

Results: Fifty-two patients died or received transplants during the course of the study. Risk reduction for heart failure hospitalization was demonstrated only for BNP decreases of >80% from enrollment [hazard ratio (HR) 0.318, P = 0.0315]. BNP increases from less than to more than the prespecified cutpoint of 500 ng/L were associated with increased mortality risk (HR 2.101, P = 0.0069), whereas decreases from more than to less than the cutpoint did not reduce risk. NT-proBNP decreases from more than to less than the cutpoint of 1000 ng/L were associated with reduced risk of death/transplantation (HR 0.119, P = 0.0354).

Conclusions: BNP increases from less than to more than the cutpoint were associated with increased risk of events, whereas further increases did not add to risk. In contrast, only substantial natriuretic peptide decreases (>80%) reduced risk. These data suggest that only robust decreases in natriuretic peptide concentrations should be targeted to reduce mortality and heart failure-related hospitalizations.
Intermethod Variability in TSH-Receptor Antibody Measurement: Implication for the Diagnosis of Graves Disease and for the Follow-Up of Graves Ophthalmopathy
Authors: Massart Catherine , Sapin Rémy , Gibassier Jacqueline , Agin Arnaud , d'Herbomez Michèle
Published: November 2008

Background: We compared the analytical and clinical performance of 3 porcine thyroid receptor antibody (TRAb) methods (1 second- and 2 new third-generation systems) with the conventional TRAb assay based on the human recombinant TSH receptor (hTRAK).

Patients and Methods: We obtained sera from 86 patients with untreated Graves disease (GD) and 71 healthy controls. We measured TRAb concentrations by radioreceptor assay using the hTRAK (Brahms) or the porcine TSH receptor (pRRA) from Beckman-Coulter, by electrochemiluminescence immunoassay (ECLIA) with the Elecsys/Cobas (Roche), and by ELISA using the Medizym TRAb clone (Medipan).

Results: Between-run assay imprecision was ≤10% and ≤7.6% for hTRAK and ECLIA, but reached 14% and 14.9% for ELISA and pRRA, respectively. Maximal specificity and sensitivity close to 100% were obtained for hTRAK, ECLIA, and ELISA. pRRA failed to detect positive TRAbs in 5 GD patients. Although calibrated against the same reference standard 90/672, the assays displayed a high intermethod variability. The results were significantly higher by ECLIA and lower by ELISA and pRRA compared with hTRAK. Patients with ophthalmopathy had higher TRAb results by ELISA and pRRA than those without eye disease.

Conclusions: Second- and third-generation TRAb assays had similar diagnostic sensitivities in the diagnostic evaluation of GD. Despite the use of the same reference standard for calibration, high intermethod variability in TRAb assay results was seen in untreated GD patients. Assay harmonization is necessary for correct interpretation in the follow-up of Graves ophthalmopathy.
Decoding Trajectories from Posterior Parietal Cortex Ensembles
Authors: Mulliken Grant H. , Musallam Sam , Andersen Richard A.
Published: November 2008

High-level cognitive signals in the posterior parietal cortex (PPC) have previously been used to decode the intended endpoint of a reach, providing the first evidence that PPC can be used for direct control of a neural prosthesis (Musallam et al., 2004). Here we expand on this work by showing that PPC neural activity can be harnessed to estimate not only the endpoint but also to continuously control the trajectory of an end effector. Specifically, we trained two monkeys to use a joystick to guide a cursor on a computer screen to peripheral target locations while maintaining central ocular fixation. We found that we could accurately reconstruct the trajectory of the cursor using a relatively small ensemble of simultaneously recorded PPC neurons. Using a goal-based Kalman filter that incorporates target information into the state-space, we showed that the decoded estimate of cursor position could be significantly improved. Finally, we tested whether we could decode trajectories during closed-loop brain control sessions, in which the real-time position of the cursor was determined solely by a monkey's neural activity in PPC. The monkey learned to perform brain control trajectories at 80% success rate (for 8 targets) after just 4–5 sessions. This improvement in behavioral performance was accompanied by a corresponding enhancement in neural tuning properties (i.e., increased tuning depth and coverage of encoding parameter space) as well as an increase in off-line decoding performance of the PPC ensemble.
Disruption ofNectin-Like 1Cell Adhesion Molecule Leads to Delayed Axonal Myelination in the CNS
Authors: Park Jinsil , Liu Ben , Chen Tao , Li Hong , Hu Xuemei , Gao Jing , Zhu Ying , Zhu Qiang , Qiang Boqin , Yuan Jiangang , Peng Xiaozhong , Qiu Mengsheng
Published: November 2008

Nectin-like 1 (Necl-1)is a neural-specific cell adhesion molecule that is expressed in both the CNS and PNS. Previousin vitrostudies suggested thatNecl-1expression is essential for the axon-glial interaction and myelin sheath formation in the PNS. To investigate thein vivorole ofNecl-1in axonal myelination of the developing nervous system, we generated theNecl-1mutant mice by replacing axons 2–5 with the LacZ reporter gene. Expression studies revealed thatNecl-1is exclusively expressed by neurons in the CNS. Disruption ofNecl-1resulted in developmental delay of axonal myelination in the optic nerve and spinal cord, suggesting thatNecl-1plays an important role in the initial axon-oligodendrocyte recognition and adhesion in CNS myelination.
The Smooth Monostratified Ganglion Cell: Evidence for Spatial Diversity in the Y-Cell Pathway to the Lateral Geniculate Nucleus and Superior Colliculus in the Macaque Monkey
Authors: Crook Joanna D. , Peterson Beth B. , Packer Orin S. , Robinson Farrel R. , Gamlin Paul D. , Troy John B. , Dacey Dennis M.
Published: November 2008

In the primate visual system approximately 20 morphologically distinct pathways originate from retinal ganglion cells and project in parallel to the lateral geniculate nucleus (LGN) and/or the superior colliculus. Understanding of the properties of these pathways and the significance of such extreme early pathway diversity for later visual processing is limited. In a companion study we found that the magnocellular LGN-projecting parasol ganglion cells also projected to the superior colliculus and showed Y-cell receptive field structure supporting the hypothesis that the parasol cells are analogous to the well studied alpha-Y cell of the cat's retina. We here identify a novel ganglion cell class, the smooth monostratified cells, that share many properties with the parasol cells. Smooth cells were retrogradely stained from tracer injections made into either the LGN or superior colliculus and formed inner-ON and outer-OFF populations with narrowly monostratified dendritic trees that surprisingly appeared to perfectly costratify with the dendrites of parasol cells. Also like parasol cells, smooth cells summed input from L- and M-cones, lacked measurable S-cone input, showed high spike discharge rates, high contrast and temporal sensitivity, and a Y-cell type nonlinear spatial summation. Smooth cells were distinguished from parasol cells however by smaller cell body and axon diameters but ∼2 times larger dendritic tree and receptive field diameters that formed a regular but lower density mosaic organization. We suggest that the smooth and parasol populations may sample a common presynaptic circuitry but give rise to distinct, parallel achromatic spatial channels in the primate retinogeniculate pathway.
Serotonergic Transcription of HumanFEVReveals Direct GATA Factor Interactions and Fate ofPet-1-Deficient Serotonin Neuron Precursors
Authors: Krueger Katherine C. , Deneris Evan S.
Published: November 2008

Altered expression of the humanFEV(fifth Ewing variant) ETS transcription factor gene impacts the level of CNS serotonin (5-HT) neuron gene expression and maternal nurturing. However, the regulatory mechanisms that determineFEVexpression are poorly understood. Here, we investigated thecis-regulatory control ofFEVto begin to identify the upstream transcription factors that restrictFEVexpression to 5-HT neurons. We find that sequences extending only 275 bp upstream of theFEV5′ untranslated region are sufficient to directFEVtransgene expression to embryonic 5-HT neurons, although sequences farther upstream are required for maintenance in adult 5-HT neurons. Two highly conserved consensus GATA factor binding sites within the 275 bp region interact with GATA factorsin vitro. Chromatin immunoprecipitations with embryonic hindbrain demonstrated Gata-2 interactions with the orthologous mousePet-1ETScis-regulatory region. Mutagenesis of GATA sites revealed that one or the other site is required for serotonergicFEVtransgene expression. Unexpectedly,FEV–LacZ transgenes enabled determination of 5-HT neuron precursor fate in the adultPet-1−/−dorsal and median raphe nuclei and thus provided additional insight intoFEV/Pet-1function. Comparable numbers ofFEV–LacZ-positive cells were detected inPet-1+/−andPet-1−/−adult dorsal raphe nuclei, indicating that the majority of mutant serotonergic precursors are not fated to apoptosis. However, B7 dorsal raphe cells were aberrantly distributed, suggesting a role forFEV/Pet-1in their midline organization. Our findings identify a direct transcriptional interaction between Gata-2 andFEVand a unique marker for new insight intoFEV/Pet-1function in 5-HT neuron development.
Experience-Dependent Eye Movements Reflect Hippocampus-Dependent (Aware) Memory
Authors: Smith Christine N. , Squire Larry R.
Published: November 2008

We investigated the relationship between experience-dependent eye movements, hippocampus-dependent memory, and aware memory. We measured eye movements in young adults, older adults, and memory-impaired patients with damage to the medial temporal lobe as they viewed 120 novel scenes and 120 previously viewed scenes. Participants indicated if each scene was old or new and also gave a confidence rating for the memory judgment. Young adults and older adults explored old scenes less than they explored new scenes, but the patients did not. For the young and older adults, this effect was observed only when participants were aware of the scene's familiar or novel status. In a second experiment, young adults viewed scenes that were either new, had been viewed previously, or had been viewed previously but had been changed (i.e., an object within the scene was either added or removed). The only instructions were to pay attention to the scenes and view each scene as it appeared, and there was no expectation that memory would be tested. Directly after the first altered scene was presented, participants were asked to classify the scene as new, old, or old but changed. Participants who were aware of the manipulation preferentially viewed the changed region, but participants who were unaware did not. These findings suggest that experience-dependent eye movements reflect hippocampus-dependent (and aware) memory, even when participants have no expectation that memory is being tested; and they are consistent with the view that awareness of what is learned is a fundamental characteristic of hippocampus-dependent memory.
Polyglutamine-Modulated Striatal Calpain Activity in YAC Transgenic Huntington Disease Mouse Model: Impact on NMDA Receptor Function and Toxicity
Authors: Cowan Catherine M. , Fan Mannie M. Y. , Fan Jing , Shehadeh Jacqueline , Zhang Lily Y. J. , Graham Rona K. , Hayden Michael R. , Raymond Lynn A.
Published: November 2008

Huntington disease (HD), caused by CAG expansion in the ubiquitously expressed huntingtin gene, is characterized by early dysfunction and death of striatal medium-sized spiny neurons (MSNs). Previous work has shown MSN-specific alterations in NMDA receptor (NMDAR) expression and cell death signaling. Furthermore, studies in HD human brain tissue and a knock-in mouse model demonstrate increases in calpain activity, which can be stimulated by NMDARs and contribute to excitotoxicity. Here, we report increased calpain activity in MSNs from the yeast artificial chromosome (YAC) transgenic mouse model of HD, expressing human full-length huntingtin with 128 polyglutamine repeats (YAC128), compared with wild type. Moreover, the calpain-cleaved product of NMDAR subunit NR2B is increased early, and NR2B expression levels are reduced, in YAC128 striatum. Although steady-state NMDAR surface expression is similar in wild-type and YAC128 MSNs, the rate of loss of NR2B-containing surface receptors is enhanced in YAC128 MSNs, suggesting that NMDAR forward trafficking to the surface is also faster, as previously reported for YAC72 MSNs. Calpain inhibitor-1 treatment normalized the loss rate of surface NMDARs in YAC128 MSNs to that of wild type, and significantly increased surface NMDAR expression in YAC128, but not in wild type or YAC72. With acute NMDAR overstimulation, the increase in calpain activity correlated with polyglutamine length, and calpain inhibitor treatment reduced NMDA-induced apoptosis in YAC72 and YAC128 MSNs to wild-type levels. Thus, the cumulative effect of increasing huntingtin polyglutamine length is to enhance MSN sensitivity to excitotoxicity at least in part by calpain-mediated cell death signaling.
Traumatic Brain Injury-Induced Hippocampal Neurogenesis Requires Activation of Early Nestin-Expressing Progenitors
Authors: Yu Tzong-Shiue , Zhang Gui , Liebl Daniel J. , Kernie Steven G.
Published: November 2008

It is becoming increasingly clear that brain injuries from a variety of causes stimulate neurogenesis within the hippocampus. It remains unclear, however, how robust this response may be and what primary cell types are involved. Here, using a controlled cortical impact model of traumatic brain injury on a previously characterized transgenic mouse line that expresses enhanced green fluorescent protein (eGFP) under the control of the nestin promoter, we demonstrate that it is the earliest type-1 quiescent progenitor cells that are induced to proliferate and migrate outside the subgranular layer of the dentate gyrus. This type-1 cell activation occurs at the same time that we observe adjacent but more differentiated doublecortin-expressing progenitors (type-2 cells) being eliminated. Also, although type-2 cells remain intact in the contralateral (uninjured) dentate gyrus, the type-1 cells there are also activated and result in increased numbers of the doublecortin-expressing type-2 cells. In addition, we have generated a novel mouse transgenic that expresses a modified version of the herpes simplex virus thymidine kinase along with eGFP that allows for the visualization and inducible ablation of early dividing progenitors by exposing them to ganciclovir. Using this transgenic in the context of traumatic brain injury, we demonstrate that these early progenitors are required for injury-induced remodeling to occur. This work suggests that injury-induced hippocampal remodeling following brain injury likely requires sustained activation of quiescent early progenitors.
Apatite-forming ability on titanium surface modified by hydrothermal treatment and ultraviolet irradiation
Authors: Obata Akiko , Zhai Tianshu , Kasuga Toshihiro
Published: November 2008

Titania coatings with various morphologies were formed on titanium surfaces by hydrothermal treatment using a dilute alkaline solution and evaluated in their hydroxyapatite (HA)-forming abilities in simulated body fluid (1.5SBF) under ultraviolet (UV) irradiation. The HA formation on the titania coating in 1.5SBF was enhanced by UV irradiation. The amount of phosphate groups adsorbed on the titania, after soaking in 1.5SBF for 24 h under UV irradiation, was estimated to be larger than that of calcium ions, whereas that of calcium ions on the titania, after soaking without UV irradiation, was larger than that of phosphate groups. It was suggested that the titania generated much basic Ti–OH groups at its surface by UV irradiation and subsequently adsorbed phosphate groups, such as H2PO4−, resulting in the formation of a new surface rich in the amount of the groups, which eventually enhanced the HA formation in 1.5SBF.
Synthesis of hierarchical mesoporous zirconia fiber by using collagen fiber as a template
Authors: Deng Dehui , Liao Xuepin , Liu Xin , Shi Bi
Published: November 2008

Ordered hierarchical mesoporous zirconia fiber was prepared by using collagen fiber as a template, and it was characterized by scanning electron microscopy, transmission electron microscopy, N2 adsorption techniques, x-ray photoelectron spectroscopy, x-ray diffraction, and elemental analysis. It was found that the zirconia fiber obtained is approximately 1–4 μm in outer diameter and 0.5–1 mm in length, and the surface of the fiber exhibits unique corncob-like mesoporous morphology. This study indicates that collagen fiber, with hierarchical supermolecular structures, could be used as an ideal template to prepare porous metal oxide fibers.
Photophysical and photocatalytic properties of Li2M(WO4)2 (M = Co and Ni)
Authors: Lv Jun , Yuan Yupeng , Huang Xianli , Shi Haifeng , Tian Hanmin , Li Zhaosheng , Yu Tao , Ye Jinhua , Zou Zhigang
Published: November 2008

Li2M(WO4)2 (M = Co and Ni) were synthesized by a conventional solid-state reaction method and characterized by powder x-ray diffraction, Brunauer-Emmet-Teller (BET) measurement, ultraviolet-visible (UV-vis) diffuse reflectance spectra, Raman spectroscopy, and photocatalytic evaluation measurements. Photocatalytic water splitting results showed that Li2M(WO4)2 (M = Co and Ni) exhibited abilities for H2 evolution with Pt cocatalyst from an aqueous methanol solution and for O2 evolution from an aqueous AgNO3 solution under UV light irradiation. Theoretical calculation, absorbance analysis, and photocatalytic H2 evolution experiment revealed that the position of W 5d level shifted to the negative side with respect to the reduced potential of H+/H2. The photocatalytic H2 evolution over Li2M(WO4)2 is discussed from the view of crystal and electronic structure point.