bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aluminum triggers NFκB signalling, inflammatory and apoptotic gene expression in human neural cells
Authors: Lukiw W. J. , Bazan N. G. 
Published: July 2010

Aluminum, the most abundant neurotoxic metal in the biosphere, has been implicated in the etiology of neurodegenerative disorders including Alzheimers disease (AD). To further understand aluminum's influence on brain gene expression we examined 2360 RNA message levels in normal human neural progenitor (NHNP) cells using DNA microarrays. Of the 53 gene expression levels that were altered by a factor of >3‐fold (p < 0.05) over control, 44 were down‐regulated. This group included transcripts encoding 17 transcription factors (TFs) or TF kinases, 12 membrane receptors, genes encoding 10 growth factors, neurotransmitters, DNA ligase, DNA repair enzymes and antiapoptotic factors such as bcl‐2. The only TFs found to be consistently induced by aluminum on these panels were members of the pro‐inflammatory (PI) NFκB gene family. As verified independently by RT–PCR, eight of the nine genes found to be induced by aluminum encoded PI or proapoptotic signalling elements, including NFκB p52/p65, IL‐1 precursor, COX‐2 and DAXX, a FAS binding protein known to induce apoptosis and repress transcription. These PI gene promoters contain multiple NFκB binding sites; electrophoretic mobility shift assay and [kB]4 vector transfection analysis indicated that aluminum strongly induced NFκB‐DNA binding, suggesting a role for aluminum and NFκB in driving PI gene expression in neural cells. Interestingly, many aluminum‐induced PI genes are also elevated in AD. These data show that aluminum triggered NHNP cells emulate many of the gene expression patterns observed in AD including the rampant up‐regulation of NFκB‐sensitive and PI signalling genes.Acknowledgements:  Supported in part by NIH AG18031, NS23002 and the EENT Foundation.
Mechanisms of inflammation in spinal cord injury
Authors: Rafati D. S. , Perez‐Polo J. R. 
Published: July 2010

The inflammatory response initiated after spinal cord injury (SCI) is characterized by an increase in cytokines, notably IL‐1β. Among its effects are the transcriptional control of cyclooxygenase 2 (COX‐2) and the inducible form of nitric oxide synthase (iNOS). While they may ameliorate inflammation, they may also cause cellular damage via production of reactive oxygen species (O2 − ., OH·, NO·). The transcription factor NF‐κB is a key intermediary in the signalling pathways leading from IL‐1β expression to COX‐2 and iNOS stimulation. Binding of NF‐κB can be abrogated by the use of oligonucleotide ‘decoys’ that compete for the cognate endogenous NF‐κB proteins. Using injections of fluorescent ‘decoy’ oligonucleotides into two‐month‐old‐male rats after SCI into the site of injury, we found prompt, robust and transient uptake of labelled ‘decoys’ into both cytoplasm and nuclei of resident cells. Injection of ‘decoys’ containing the NF‐κB binding sequences present in the COX‐2 promoter region, together with a ‘nonsense’ sequence, showed selective effects on iNOS expression at the site of injury. These results are consistent with the hypothesis that NF‐κB transcriptional regulation of COX‐2 and iNOS are linked and may be an element in the pathophysiology and recovery of mammalian spinal cord after contusion injury.Acknowledgements:  Supported in part by NINDS Grant NS‐39161 and Shriners Hospital Grant 8710.
Sphingolipids in rat model of transient focal cerebral ischemia: implication for stroke injury
Authors: Khan M. , Sekhon B. K. , Sekhon C. S. , Singh I. , Singh A. K. 
Published: July 2010

Lipids are essential for signal transduction in response to trauma leading to neurodegeneration. Ceramide is an important mediator of apoptosis and cell proliferation. We studied the involvement of ceramide/sphingomyelin pathway in rat brain (stroke model) after 45 min ischemia followed by 24‐h reperfusion. Ischemia was performed through occlusion of right middle cerebral artery (MCA). The level of ceramide was found increased (70–100% in ischemic side of brain v/s contralateral side of brain). Sphingomyelin levels were also decreased by 20–25% in ischemic brain v/s contralateral side of brain. Increase in ceramide and decrease in sphingomyelin were in good agreement with observed apoptotic cell loss (TUNEL assay) and decrease in the level of cardiolipin (a mitochondrian specific phospholipids) in affected ischemic brain. N‐acetyl cysteine (NAC), a therapeutic agent recognized as potent antioxidant provided protective effect. Pretreatment with NAC before ischemia reduced the infarct volume size, suppressed apoptosis, restored cardiolipin level and decreased the levels of free fatty acids. However, NAC did not normalize the ceramide level. These interesting observations raise a question about the role of ceramide and its relationship with apoptosis and oxidative stress in rat brain ischemia.Acknowledgements:  Supported by NIH grants NS‐40144, NS‐40810, NS‐22576, NS‐34741 and NS‐37766.
Diazepam prevents changes in intracellular Cl− and Ca2+ and restores neuronal activity after ischemia in vitro
Authors: Galeffi F. , Sah R. , Schwartz‐Bloom R. D. 
Published: July 2010

We have shown that diazepam (DZ) protects hippocampal neurons when administered early after transient cerebral ischemia. To examine mechanisms of DZ action, in the absence of systemic effects, we used an in vitro model of ischemia [oxygen‐glucose deprivation (OGD)] in the adult hippocampal slice. We are interested in determining if DZ can prevent upstream events such as loss of ionic homeostasis and its consequences on neuronal transmission. We measured the effect of OGD on changes in intracellular Cl− and Ca2+. Application of DZ after OGD prevented the increase in intracellular Cl− in area CA1 pyramidal neurons, measured by optical imaging with the Cl− sensitive fluorescent probe, MEQ. The increase in intracellular Cl− after OGD led to a reduction in GABA responses 2 h later, measured in the presence of the GABA agonist, muscimol. When DZ was added for 1 h after OGD, muscimol responses were restored completely. To measure changes in intracellular Ca2+ after OGD, we bath‐loaded adult hippocampal slices with calcium green‐1 AM. OGD increased intracellular Ca2+ in CA1 pyramidal neurons. The addition of DZ prior to OGD reduced the increase in intracellular Ca2+ by approximately 50%. To determine the effect of DZ on neuronal transmission within the hippocampus, we measured field responses in area CA1 pyramidal neurons. Area CA1 population spikes were suppressed by OGD and they did not recover 1 h later. When DZ was included in the reoxygenation buffer for only 30 min, it restored the population spike amplitude to within 85% of that in normal slices. Thus, after OGD, DZ restores ionic homeostasis, preserves GABA responses and restores neuronal activity within the hippocampus.Acknowledgements:  Supported by NIH grant #NS28791.
Neuroprotection with caspase‐9 inhbition against in vitro and in vivo trauma
Authors: Wallis R. A. , Panizzon K. L. , Shin D. 
Published: July 2010

Objective:  To evaluate the neuroprotective efficacy of the cell‐permeable caspase‐9 inhibitor, LEHD‐CHO, against in vitro and in vivo traumatic neuronal injury.Methods:  The neuroprotective potential of LEHD‐CHO was assessed in vitro using rat hippocampal slices. CA1 orthodromic and antidromic population spike (PS) amplitude was monitored before and after fluid percussion injury in slices treated with or without LEHD‐CHO. Final recovery of PS amplitude was assessed 95 min after trauma. Studies of in vivo neuroprotection with LEHD‐CHO utilized a model of controlled cortical impact (CCI). Rats were given either LEHD‐CHO (10 nmol icv) or an equal volume of vehicle at 5 min following CCI. Rats were perfused 24 h after CCI and brains were processed for histological examination.Results:  LEHD‐CHO provided significant protection against loss of CA1 evoked response after fluid percussion. The EC50 for LEHD‐CHO protection of CA1 orthodromic and antidromic PS amplitude against trauma was 2.1 μm and 2.3 μm. Protection extended to preservation of LTP after trauma. In vivo treatment with LEHD‐CHO significantly decreased the appearance of eosinophilic cells in the CA1 region after CCI from 131 ± 23 cells in vehicle‐treated animals to 24 ± 5 in LEHD‐CHO treated animals. Extensive labelling with TUNEL staining was seen in vehicle‐treated animals, whereas sections from LEHD‐CHO treated animals demonstrated little staining.Conclusions:  These findings indicate that the caspase 9 inhibitor LHED‐CHO provides concentration‐dependent protection against in vitro CA1 neuronal injury, which extends to protection against in vivo CA1 injury from CCI. They further suggest that inhibition of caspase 9 may be a useful treatment strategy for traumatic brain injury.Acknowledgement:  Supported by VA Research and UCLA BIRC.
Neurotrophic factor gene delivery supports axonal regeneration after injury
Authors: Shine H. D. , Zhou L. , Grider M. H. , McGowen L. R. , Menesses‐Diaz D. A. , Zheng X. , Le W‐D. , Mamounas L. 
Published: July 2010

A successful treatment for spinal cord injury (SCI) must include means to induce axonal regeneration and synaptogenesis. Though much research has demonstrated the effectiveness of neurotrophic factors (NFs) in supporting axonal regeneration, systemic delivery of doses sufficient to reach therapeutic concentrations and overcome their short half‐lives has caused adverse effects. Local expression of NFs would overcome these limitations. We tested whether local expression of NFs would induce axonal regeneration without adverse effects in two models of neural injury. In a chemical injury model the rat serotonergic system was lesioned with p‐chloroamphetamine. When an adenoviral vector carrying the gene for brain‐derived neurotrophic factor (BDNF) was injected into the denervated cortex BDNF expressed by the transfected cells induced serotonergic axon reinnervation only in area around the injection site. In a mechanical injury model the cortical spinal tract (CST) in rats was lesioned unilaterally at the level of the hindbrain. Neurotorphin‐3 (NT‐3) was expressed locally in the spinal cord either by direct injection of an adenoviral vector carrying the gene for NT‐3 or by retrograde delivery of the vector from the sciatic nerve. Axons were observed growing from the unlesioned CST across the midline to the denervated side. These data demonstrate that local expression of NFs will induce and support axonal regeneration in a circumscribed area after injury without adverse effects and suggest that a therapy for SCI based upon this strategy may include NF gene delivery.Acknowledgements:  Supported by NIH grant NS35280 and Mission Connect of the TIRR Foundation.
RPPanalyzer: Analysis of reverse-phase protein array data
Authors: Mannsperger Heiko A. , Gade Stephan , Henjes Frauke , Beissbarth Tim , Korf Ulrike 
Published: July 2010

Abstract
Summary: RPPanalyzer is a statistical tool developed to read reverse-phase protein array data, to perform the basic data analysis and to visualize the resulting biological information. The R-package provides different functions to compare protein expression levels of different samples and to normalize the data. Implemented plotting functions permit a quality control by monitoring data distribution and signal validity. Finally, the data can be visualized in heatmaps, boxplots, time course plots and correlation plots. RPPanalyzer is a flexible tool and tolerates a huge variety of different experimental designs.
Availability: The RPPAanalyzer is open source and freely available as an R-Package on the CRAN platform http://cran.r-project.org/
Contact: h.mannsperger@dkfz.de
Supplementary information: Supplementary data are available at Bioinformatics online.
LocusZoom: regional visualization of genome-wide association scan results
Authors: Pruim Randall J. , Welch Ryan P. , Sanna Serena , Teslovich Tanya M. , Chines Peter S. , Gliedt Terry P. , Boehnke Michael , Abecasis Gonçalo R. , Willer Cristen J. 
Published: July 2010

Abstract
Summary: Genome-wide association studies (GWAS) have revealed hundreds of loci associated with common human genetic diseases and traits. We have developed a web-based plotting tool that provides fast visual display of GWAS results in a publication-ready format. LocusZoom visually displays regional information such as the strength and extent of the association signal relative to genomic position, local linkage disequilibrium (LD) and recombination patterns and the positions of genes in the region.
Availability: LocusZoom can be accessed from a web interface at http://csg.sph.umich.edu/locuszoom. Users may generate a single plot using a web form, or many plots using batch mode. The software utilizes LD information from HapMap Phase II (CEU, YRI and JPT+CHB) or 1000 Genomes (CEU) and gene information from the UCSC browser, and will accept SNP identifiers in dbSNP or 1000 Genomes format. Single plots are generated in ∼20 s. Source code and associated databases are available for download and local installation, and full documentation is available online.
Contact: cristen@umich.edu
Mannose-binding lectin and susceptibility to tuberculosis: a meta-analysis
Authors: Denholm J T , McBryde E S , Eisen D P 
Published: July 2010

SummaryIt has been proposed that mannose-binding lectin (MBL) levels may impact upon host susceptibility to tuberculosis (TB) infection; however, evidence to date has been conflicting. We performed a literature review and meta-analysis of 17 human trials considering the effect of MBL2 genotype and/or MBL levels and TB infection. No significant association was demonstrated between MBL2 genotype and pulmonary TB infection. However, the majority of studies did not report MBL2 haplotype inclusive of promoter polymorphisms. Serum MBL levels were shown to be consistently elevated in the setting of TB infection. While this may indicate that high MBL levels protect against infection with TB, the increase was also of a degree consistent with the acute-phase reaction. This analysis suggests that the relatively poorly characterized MBL2 genotypes reported are not associated significantly with susceptibility to pulmonary TB infection, but high MBL serum levels may be.
Establishment of an efficient multiplex real‐time PCR assay for human papillomavirus genotyping in cervical cytology specimens: comparison with hybrid capture II
Authors: Lee J.‐H. , Lee N.‐W. , Hong S.‐W. , Nam Y.‐S. , Choi J.‐W. , Kim Y.‐S. 
Published: July 2010

J.‐H. Lee, N.‐W. Lee, S.‐W. Hong, Y.‐S. Nam, J.‐W. Choi and Y.‐S. Kim Establishment of an efficient multiplex real‐time PCR assay for human papillomavirus genotyping in cervical cytology specimens: comparison with hybrid capture II Objective:  To establish an efficient multiplex real‐time PCR assay for 15 human papillomavirus (HPV) genotypes, we designed multiplexing parameters and compared our PCR system with the hybrid capture (HC) II test using cervical cytology samples.Methods:  For preventing cross‐reactive amplifications, variable HPV genes (E1, E2, E6, E7 and L1) were targeted. The melting temperatures of all primers and probes, and the size of the PCR product were optimized for the multiplex PCR. Our PCR system was compared with the HC II assays in the detection and genotyping of HPV infection using 173 cytology smears. Discordant cases between the two assays were verified by direct HPV DNA sequencing.Results:  Of 173 women, 93 (53.8%) were HPV‐positive by the HC II assay and/or the multiplex real‐time PCR assay. The HPV genotypes were determined in 92 (98.9%) of 93 cases by the multiplex real‐time PCR and/or DNA sequencing. The agreement rate between multiplex PCR and HC II methods was 91.9% (kappa = 0.84). Although the sample size of this study needs to be increased to have epidemiological significance, multiple infections and HPV 16 were the predominant type. HPV 58, 52 and 18 accounted for 25% of HPV infections. HPV 52, 58 and 31 constituted 30% of CIN 2/3.Conclusion:  The multiplex real‐time PCR system shows a good and reliable clinical performance. This in house PCR assay is fast and cost‐effective for HPV genotyping and the detection of HPV co‐infection in the post‐HPV vaccination era.
Activation of caspase‐3 in the skeletal muscle during haemodialysis
Authors: Boivin Michel A. , Battah Shadi I. , Dominic Elizabeth A. , Kalantar‐Zadeh Kamyar , Ferrando Arny , Tzamaloukas Antonios H. , Dwivedi Rama , Ma Thomas A. , Moseley Pope , Raj Dominic S. C. 
Published: July 2010

Eur J Clin Invest 2010; 40 (10): 903–910AbstractBackground and Objective  Muscle atrophy in end‐stage renal disease (ESRD) may be due to the activation of apoptotic and proteolytic pathways. We hypothesized that activation of caspase‐3 in the skeletal muscle mediates apoptosis and proteolysis during haemodialysis (HD).Materials and Methods  Eight ESRD patients were studied before (pre‐HD) and during HD and the findings were compared with those from six healthy volunteers. Protein kinetics was determined by primed constant infusion of L‐(ring 13C6) Phenylalanine.Results  Caspase‐3 activity in the skeletal muscle was higher in ESRD patients pre‐HD than in controls (24966·0 ± 4023·9 vs. 15293·3 ± 2120·0 units, P < 0·01) and increased further during HD (end‐HD) (37666·6 ± 4208·3 units) (P < 0·001). Actin fragments (14 kDa) generated by caspase‐3 mediated cleavage of actomyosin was higher in the skeletal muscle pre‐HD (68%) and during HD (164%) compared with controls. The abundance of ubiquitinized carboxy‐terminal actin fragment was also significantly increased during HD. Skeletal muscle biopsies obtained at the end of HD exhibited augmented apoptosis, which was higher than that observed in pre‐HD and control samples (P < 0·001). IL‐6 content in the soluble fraction of the muscle skeletal muscle was increased significantly during HD. Protein kinetic studies showed that catabolism was higher in ESRD patients during HD compared with pre‐HD and control subjects. Muscle protein catabolism was positively associated with caspase‐3 activity and skeletal muscle IL‐6 content.Conclusion  Muscle atrophy in ESRD may be due to IL‐6 induced activation of caspase‐3 resulting in apoptosis as well as muscle proteolysis during HD.
Assessment of structural variation and molecular mapping of insertion sites of Desmar‐like elements in the Hessian fly genome
Authors: Behura S. K. , Shukle R. H. , Stuart J. J. 
Published: July 2010

AbstractThe Hessian fly (Mayetiola destructor) is an agriculturally important pest of wheat. A mariner element (Desmar1) has been previously identified in the Hessian fly genome. Using Desmar1 as a probe, we isolated individual copies of Desmar‐like elements from the Hessian fly genome cloned in bacterial artificial chromosomes (BACs) and studied their structural variability and flanking DNA sequences. The partial Desmar‐like copies are relatively more abundant (∼64%) than full length copies (∼36%) in the Hessian fly genome. Most of the full length copies are consistently flanked by an EcoRI restriction site that occurs 32 bp from one end and 66 bp from the other end of the mariner. Using an amplified fragment length polymorphism‐PCR (AFLP‐PCR) based method, we identified segregating polymorphisms associated with Desmar elements in a F2 mapping population. We were able to use the segregation data to localize the chromosomal position of three Desmar elements by linkage analysis. As paternal chromosomes are eliminated in the Hessian fly during early embryogenesis, two‐thirds of the AFLPs were expected to be polymorphic in the mapping population and this was observed for AFLPs anchored to full length Desmar copies but not to the partial copies. Thus, our data indicate that dead and partial Desmar‐like copies are probably associated with less polymorphic regions and may represent mariner graveyards in the Hessian fly genome.
Swiss Cancer League communication skills training programme for oncology nurses: an evaluation
Authors: Langewitz Wolf , Heydrich Lukas , Nübling Matthias , Szirt Linda , Weber Heidemarie , Grossman Paul 
Published: July 2010

langewitz w., heydrich l., nübling m., szirt l., weber h. & grossman p. (2010) Swiss Cancer League communication skills training programme for oncology nurses: an evaluation. Journal of Advanced Nursing 66(10), 2266–2277.AbstractAim.  This paper is a report of an evaluation of the effectiveness of a communication skills training programme for oncology nurses.Background.  Clinical care for patients with cancer is increasingly being divided between nurses and physicians, with nurses being responsible for the continuity of patient care, and oncologists choosing and explaining the basics of anti‐cancer therapy. Therefore, oncology nurses will profit from evidence‐based communication skills training to allow them to perform in a professional way.Methods.  Between 2003 and 2006 pre‐ and post‐intervention videos of interviews with simulated patients were compared using the Roter Interaction Analysis System. Patient centeredness was assessed by counting segments of appropriate mutual responding to cues and by calculating length of uninterrupted patient speech.Findings.  Appropriate empathic (1·6% vs. 3·2%), reassuring statements (2·3% vs. 3·4%), questions concerning psychosocial information (2·8% vs. 4·0%) increased statistically significantly; utterances containing medical information decreased on the part of nurses (17·8% vs. 13·3%) and patients (8·1% vs. 6·7%); and patients provided more psychosocial information (3·3% vs. 5·7%). The level of congruence and empathic responses to patients’ emotional cues increased statistically significantly, as did the length of uninterrupted speech (3·7–4·3 utterances; all P < 0·05).Conclusion.  The communication skills training of the Swiss Cancer League could be used as a model to achieve substantial improvements in patient‐centred communication. Sequence analysis of utterances from patient‐provider interaction should be used to assess the amount of patient‐centred talk.
Case management educational intervention with public health nurses: cluster randomized controlled trial
Authors: Liu Wen‐I. , Edwards Helen , Courtney Mary 
Published: July 2010

liu w.‐i., edwards h. & courtney m. (2010) Case management educational intervention with public health nurses: cluster randomized controlled trial. Journal of Advanced Nursing 66(10), 2234–2244.AbstractAim.  This paper is a report of a study conducted to determine the effectiveness of a community case management collaborative education intervention in terms of satisfaction, learning and performance among public health nurses.Background.  Previous evaluation studies of case management continuing professional education often failed to demonstrate effectiveness across a range of outcomes and had methodological weaknesses such as small convenience samples and lack of control groups.Method.  A cluster randomized controlled trial was conducted between September 2005 and February 2006. Ten health centre clusters (five control, five intervention) recruited 163 public health nurses in Taiwan to the trial. After pre‐tests for baseline measurements, public health nurses in intervention centres received an educational intervention of four half‐day workshops. Post‐tests for both groups were conducted after the intervention. Two‐way repeated measures analysis of variance was performed to evaluate the effect of the intervention on target outcomes.Results.  A total of 161 participants completed the pre‐ and post‐intervention measurements. This was almost a 99% response rate. Results revealed that 97% of those in the experimental group were satisfied with the programme. There were statistically significant differences between the two groups in knowledge (P = 0·001), confidence in case management skills (P = 0·001), preparedness for case manager role activities (P = 0·001), self‐reported frequency in using skills (P = 0·001) and role activities (P = 0·004).Conclusion.  Collaboration between academic and clinical nurses is an effective strategy to prepare nurses for rapidly changing roles.