bluuebunny/crossref_metadata_2025_split huggingface dataset:
The protective effect of caffeic acid phenethyl ester (CAPE) on oxidative stress in rat liver exposed to the 900 MHz electromagnetic field
Authors: Koyu A , Ozguner F , Yilmaz HR , Uz E , Cesur G , Ozcelik N 
Published: August 2009

In this study, we aimed to investigate the possible protective effects of caffeic acid phenethyl ester (CAPE) on lipid peroxidation (LPO) and the activities of antioxidant enzymes in the liver of rats exposed to the 900 MHz electromagnetic field (EMF). EMF of cellular phones may affect biological systems by increasing free radical, which appear mainly to enhance LPO, and by changing the antioxidative activities of liver, thus leading to oxidative damage. CAPE, an active component of propolis extract, exhibits antioxidant properties and several studies suggest that supplementation with antioxidant can influence EMF exposure induced hepatotoxicity. Thirty male Sprague-Dawley rats were divided into three groups: control ( n = 10), 900 MHz EMF ( n = 10) and 900 MHz EMF + CAPE ( n = 10). CAPE was injected intraperitoneally for 30 days before exposure to EMF. Liver tissue was removed to study the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), xanthine oxidase (XO) and the levels of LPO. The activities of XO, CAT and level of LPO increased in the 900 MHz electromagnetic field (EMF) group compared with the control group, although XO, CAT activities and LPO levels were decreased by 900 MHz EMF + CAPE administration. The activities of SOD and GSH-Px decreased in the 900 MHz EMF group compared with the control group, although their levels were increased by EMF + CAPE administration. It can be concluded that CAPE may prevent the 900 MHz EMF-induced oxidative changes in liver by strengthening the antioxidant defense system by reducing reactive oxygen species and increasing antioxidant enzyme activities.
Walking and talking: an investigation of cognitive—motor dual tasking in multiple sclerosis
Authors: Hamilton F. , Rochester L. , Paul L. , Rafferty D. , O'Leary CP , Evans JJ 
Published: August 2009

Background: Deficits in motor functioning, including walking, and in cognitive functions, including attention, are known to be prevalent in multiple sclerosis (MS), though little attention has been paid to how impairments in these areas of functioning interact. Objectives: This study investigated the effects of performing a concurrent cognitive task when walking in people with MS. Level of task demand was manipulated to investigate whether this affected level of dual-task decrement. Method: Eighteen participants with MS and 18 healthy controls took part. Participants completed walking and cognitive tasks under single- and dual-task conditions. Results: Compared to healthy controls, MS participants showed greater decrements in performance under dual-task conditions in cognitive task performance, walking speed and swing time variability. In the MS group, the degree of decrement under dual-task conditions was related to levels of fatigue, a measure of general cognitive functioning and self-reported everyday cognitive errors, but not to measures of disease severity or duration. Conclusions: Difficulty with walking and talking in MS may be a result of a divided attention deficit or of overloading of the working memory system, and further investigation is needed. We suggest that difficulty with walking and talking in MS may lead to practical problems in everyday life, including potentially increasing the risk of falls. Clinical tools to assess cognitive—motor dual-tasking ability are needed.
Antiacquaporin 4 antibodies detection by different techniques in neuromyelitis optica patients
Authors: Fazio R. , Malosio ML , Lampasona V. , De Feo D. , Privitera D. , Marnetto F. , Centonze D. , Ghezzi A. , Comi G. , Furlan R. , Martino G. 
Published: August 2009

Background: Antibodies against aquaporin-4 (AQP4), a water channel particularly expressed on perivascular astrocytic podocytes, are proposed as a marker for the diagnosis of neuromyelitis optica (NMO). However, a consensus on seroprevalence and optimal detection method has not yet been reached. Objectives: To investigate the performance of different assays to detect anti-AQP4 antibodies. Methods: We set up five different assays. Two of them were capable to detect perivascular IgG reactivity on brain tissue by immunofluorescence (NMO-IgG). Other three assays have been set to detect anti-AQP4 antibodies: immunofluorescence and flow cytometry on AQP4-expressing cells, and a radioimmunoprecipitation assay. We assessed sensitivity and specificity of these assays by interrogating sera of 33 NMO patients, 13 patients at high risk to develop NMO (hrNMO), 6 patients affected by acute partial transverse myelitis (APTM), 20 patients with multiple sclerosis (MS), and 67 age- and sex-matched healthy controls. Results: We found that the presence of serum NMO-IgG and anti-AQP4 reactivity is almost exclusively restricted to patients with NMO and hrNMO. Seroprevalence and sensitivity ranged from 30 to 47%, depending on the assay. Specificity ranged from 95 to 100%. Comparing results obtained in the five assays, we noticed lack of concordance in some samples. Conclusions: Detection of NMO-IgG or anti-AQP4 antibodies may represent a valuable tool to assist neurologists in the differential diagnosis between patients with NMO, hrNMO, APTM, or MS. The current lack of a gold standard to detect anti-AQP4 antibodies implies the necessity to standardize the detection of these antibodies.
Self-reported chronic mental health problems and mental health service use in Spain
Authors: Girón Manuel , Nolasco Andreu , Pereyra-Zamora Pamela , Munarriz Mikel , Salazar José , Tabarés Rafael , Moncho-Vasallo Joaquín , Gómez-Beneyto Manuel 
Published: August 2009

Objectives: To determine the prevalence of self-reported chronic mental health problems (MHPs) and mental health service use and their determinants, among the Spanish population over 14 years of age. Methods: Data from the 1999 Spanish Survey on Disabilities, Deficiencies, and State of Health were used. The survey is a cross-sectional study based on a multi-stage stratified sample of all the non-institutionalized Spanish population aged over 14 years (n=59,101, 11% non-responders). Multivariate logistic regression analysis were used. Results: 10.7% of the Spanish population suffer from an MHP. The highest prevalences were found in women, divorced/separated persons, those with a lower level of education and income, and those suffering from a chronic somatic problem. The number of days of daily activity lost was 2-fold greater among those with an MHP than among those with a chronic somatic problem. Greater use of mental health services was associated with loss of daily activity, having a higher level of education, invalidity or disability. The probability of MHP being referred from primary to mental healthcare is reduced if somatic comorbidity is present. Conclusion: MHPs have a high prevalence and a significant repercussion on the patient’s life. An inverse relationship was found between certain risk factors for MHPs and the use of services, which suggests inequality. Problems of accessibility are identified.
Teaching and learning about chronic conditions management for undergraduate medical students: utilizing the patient-as-teacher approach
Authors: McKinlay E. , McBain L. , Gray B. 
Published: August 2009

Objectives: This study was undertaken to evaluate the impact on medical student learning of a revised chronic conditions teaching programme based on the chronic care model utilizing patients-as-teachers. Methods: A qualitative questionnaire was completed by students at the start of a primary healthcare rotation to determine existing impressions/understandings about chronic conditions. Following the revised teaching programme, a reflective essay about a home-visit to a person with chronic conditions was completed by students at the end of the rotation. Results: Analysis of the questionnaire at the start of the rotation showed students have some knowledge of the differences between acute and chronic care, have rather negative impressions of what it means to have chronic conditions and know little of overall patient management including the work of an interdisciplinary team. Analysis of the reflective essays completed by students at the end of the rotation showed an increased understanding of chronic conditions, what it means to have a chronic condition and who supports management. Discussion: A structured chronic conditions teaching programme including patient-as-teacher is an effective way of building knowledge and changing students’ impressions of what it means to have a chronic condition.
Tight control of MEK-ERK activation is essential in regulating proliferation, survival, and cytokine production of CD34+-derived neutrophil progenitors
Authors: Geest Christian R. , Buitenhuis Miranda , Groot Koerkamp Marian J. A. , Holstege Frank C. P. , Vellenga Edo , Coffer Paul J. 
Published: August 2009

AbstractA plethora of extracellular stimuli regulate growth, survival, and differentiation responses through activation of the MEK-ERK MAPK signaling module. Using CD34+ hematopoietic progenitor cells, we describe a novel role for the MEK-ERK signaling module in the regulation of proliferation, survival, and cytokine production during neutrophil differentiation. Addition of the specific MEK1/2 inhibitor U0126 resulted in decreased proliferation of neutrophil progenitors. Conversely, transient activation of a conditionally active MEK1 mutant resulted in the expansion of progenitor cells, which thereafter differentiated normally into mature neutrophils. In contrast, chronic MEK1 activation was found to induce cell death of CD34+ neutrophil progenitors. Microarray analysis of CD34+ progenitor cells showed that activation of MEK1 resulted in changes in expression of a variety of cell-cycle modulating genes. Furthermore, conditional activation of MEK1 resulted in a dramatic increase in the expression of mRNA transcripts encoding a large number of hematopoietic cytokines, chemokines, and growth factors. These findings identify a novel role for MEK-ERK signaling in regulating the balance between proliferation and apoptosis during neutrophil differentiation, and they suggest the need for tight control of MEK-ERK activation to prevent the development of bone marrow failure.
A novel role for c-Src and STAT3 in apoptotic cell–mediated MerTK-dependent immunoregulation of dendritic cells
Authors: Yi Zuoan , Li Li , Matsushima Glenn K. , Earp H. Shelton , Wang Bo , Tisch Roland 
Published: August 2009

AbstractDendritic cells (DCs) play an instrumental role in regulating tolerance to self-antigens and preventing autoimmunity. One mechanism by which “tolerogenic” DCs are established is through the inhibitory effects of apoptotic cells (ACs). Immature DCs encountering ACs are resistant to stimuli that activate and mature DCs. We have shown that the Mer receptor tyrosine kinase (MerTK) plays a key role in transducing inhibitory signals upon binding of ACs, which in turn involve the phosphatidylinositol 3-kinase (PI3K) pathway. Nevertheless, the molecular basis for AC-induced inhibition of DCs is ill defined. In the current study, the proximal signaling events induced by MerTK after AC binding were studied. AC treatment of bone marrow–derived or splenic DCs established a complex consisting of MerTK, the nonreceptor tyrosine kinase c-Src, the transcription factor STAT3, and PI3K. In contrast, AC treatment of DCs lacking MerTK expression failed to increase c-Src and STAT3 activation. In addition, the inhibitory effects of ACs were blocked by treating DCs with pharmacologic inhibitors or siRNA specific for c-Src and STAT3. These findings demonstrate that AC-induced inhibition of DCs requires MerTK-dependent activation of c-Src and STAT3, and provide evidence for novel roles for c-Src and STAT3 in the immunoregulation of DCs.
Efficient and stable transduction of resting B lymphocytes and primary chronic lymphocyte leukemia cells using measles virus gp displaying lentiviral vectors
Authors: Frecha Cecilia , Costa Caroline , Lévy Camille , Nègre Didier , Russell Stephen J. , Maisner Andrea , Salles Gilles , Peng Kah-Whye , Cosset Francois-Loïc , Verhoeyen Els 
Published: August 2009

AbstractUp to now, no lentiviral vector (LV) tool existed to govern efficient and stable gene delivery into quiescent B lymphocytes, which hampers its application in gene therapy and immunotherapy areas. Here, we report that LVs incorporating measles virus (MV) glycoproteins, H and F, on their surface allowed transduction of 50% of quiescent B cells, which are not permissive to VSVG-LV transduction. This high transduction level correlated with B-cell SLAM expression and was not at cost of cell-cycle entry or B-cell activation. Moreover, the naive and memory phenotypes of transduced resting B cells were maintained. Importantly, H/F-LVs represent the first tool permitting stable transduction of leukemic cancer cells, B-cell chronic lymphocytic leukemia cells, blocked in G0/G1 early phase of the cell cycle. Thus, H/F-LV transduction overcomes the limitations of current LVs by making B cell–based gene therapy and immunotherapy applications feasible. These new LVs will facilitate antibody production and the study of gene functions in these healthy and cancer immune cells.
Level and course of FEV1 in relation to polymorphisms in NFE2L2 and KEAP1 in the general population
Authors: Siedlinski Mateusz , Postma Dirkje S , Boer Jolanda MA , van der Steege Gerrit , Schouten Jan P , Smit Henriette A , Boezen H Marike 
Published: August 2009

Abstract

Background
The metabolism of xenobiotics plays an essential role in smoking related lung function loss and development of Chronic Obstructive Pulmonary Disease. Nuclear Factor Erythroid 2-Like 2 (NFE2L2 or NRF2) and its cytosolic repressor Kelch-like ECH-associated protein-1 (KEAP1) regulate transcription of enzymes involved in cellular detoxification processes and Nfe2l2-deficient mice develop tobacco-induced emphysema. We assessed the impact of Single Nucleotide Polymorphisms (SNPs) in both genes on the level and longitudinal course of Forced Expiratory Volume in 1 second (FEV1) in the general population.

Methods
Five NFE2L2 and three KEAP1 tagging SNPs were genotyped in the population-based Doetinchem cohort (n = 1,152) and the independent Vlagtwedde-Vlaardingen cohort (n = 1,390). On average 3 FEV1 measurements during 3 surveys, respectively 7 FEV1 measurements during 8 surveys were present. Linear Mixed Effect models were used to test cross-sectional and longitudinal genetic effects on repeated FEV1 measurements.

Results
In the Vlagtwedde-Vlaardingen cohort SNP rs11085735 in KEAP1 was associated with a higher FEV1 level (p = 0.02 for an additive effect), and SNP rs2364723 in NFE2L2 was associated with a lower FEV1 level (p = 0.06). The associations were even more significant in the pooled cohort analysis. No significant association of KEAP1 or NFE2L2 SNPs with FEV1 decline was observed.

Conclusion
This is the first genetic study on variations in key antioxidant transcriptional regulators KEAP1 and NFE2L2 and lung function in a general population. It identified 2 SNPs in NFE2L2 and KEAP1 which affect the level of FEV1 in the general population. It additionally shows that NFE2L2 and KEAP1 variations are unlikely to play a role in the longitudinal course of FEV1 in the general population.
Gain and loss of an intron in a protein-coding gene in Archaea: the case of an archaeal RNA pseudouridine synthase gene
Authors: Yokobori Shin-ichi , Itoh Takashi , Yoshinari Shigeo , Nomura Norimichi , Sako Yoshihiko , Yamagishi Akihiko , Oshima Tairo , Kita Kiyoshi , Watanabe Yoh-ichi 
Published: August 2009

AbstractBackgroundWe previously found the first examples of splicing of archaeal pre-mRNAs for homologs of the eukaryotic CBF5 protein (also known as dyskerin in humans) inAeropyrum pernix, Sulfolobus solfataricus, S. tokodaii, andS. acidocaldarirus, and also showed that crenarchaeal species in orders Desulfurococcales and Sulfolobales, except forHyperthermus butylicus, Pyrodictium occultum, Pyrolobus fumarii, andIgnicoccus islandicus, contain the (putative)cbf5intron. However, the exact timing of the intron insertion was not determined and verification of the putative secondary loss of the intron in some lineages was not performed.ResultsIn the present study, we determined approximately two-thirds of the entire coding region of crenarchaeal Cbf5 sequences from 43 species. A phylogenetic analysis of our data and information from the available genome sequences suggested that the (putative)cbf5intron existed in the common ancestor of the orders Desulfurococcales and Sulfolobales and that probably at least two independent lineages in the order Desulfurococcales lost the (putative) intron.ConclusionThis finding is the first observation of a lineage-specific loss of a pre-mRNA intron in Archaea. As the insertion or deletion of introns in protein-coding genes in Archaea has not yet been seriously considered, our finding suggests the possible difficulty of accurately and completely predicting protein-coding genes in Archaea.
Combined genome-wide expression profiling and targeted RNA interference in primary mouse macrophages reveals perturbation of transcriptional networks associated with interferon signalling
Authors: Lacaze Paul , Raza Sobia , Sing Garwin , Page David , Forster Thorsten , Storm Petter , Craigon Marie , Awad Tarif , Ghazal Peter , Freeman Tom C 
Published: August 2009

AbstractBackgroundInterferons (IFNs) are potent antiviral cytokines capable of reprogramming the macrophage phenotype through the induction of interferon-stimulated genes (ISGs). Here we have used targeted RNA interference to suppress the expression of a number of key genes associated with IFN signalling in murine macrophages prior to stimulation with interferon-gamma. Genome-wide changes in transcript abundance caused by siRNA activity were measured using exon-level microarrays in the presence or absence of IFNγ.ResultsTransfection of murine bone-marrow derived macrophages (BMDMs) with a non-targeting (control) siRNA and 11 sequence-specific siRNAs was performed using a cationic lipid transfection reagent (Lipofectamine2000) prior to stimulation with IFNγ. Total RNA was harvested from cells and gene expression measured on Affymetrix GeneChip Mouse Exon 1.0 ST Arrays. Network-based analysis of these data revealed six siRNAs to cause a marked shift in the macrophage transcriptome in the presence or absence IFNγ. These six siRNAs targeted the Ifnb1, Irf3, Irf5, Stat1, Stat2 and Nfkb2 transcripts. The perturbation of the transcriptome by the six siRNAs was highly similar in each case and affected the expression of over 600 downstream transcripts. Regulated transcripts were clustered based on co-expression into five major groups corresponding to transcriptional networks associated with the type I and II IFN response, cell cycle regulation, and NF-KB signalling. In addition we have observed a significant non-specific immune stimulation of cells transfected with siRNA using Lipofectamine2000, suggesting use of this reagent in BMDMs, even at low concentrations, is enough to induce a type I IFN response.ConclusionOur results provide evidence that the type I IFN response in murine BMDMs is dependent on Ifnb1, Irf3, Irf5, Stat1, Stat2 and Nfkb2, and that siRNAs targeted to these genes results in perturbation of key transcriptional networks associated with type I and type II IFN signalling and a suppression of macrophage M1 polarization.
Rapid identification of bacterial pathogens using a PCR- and microarray-based assay
Authors: Järvinen Anna-Kaarina , Laakso Sanna , Piiparinen Pasi , Aittakorpi Anne , Lindfors Merja , Huopaniemi Laura , Piiparinen Heli , Mäki Minna 
Published: August 2009

Abstract

Background
During the course of a bacterial infection, the rapid identification of the causative agent(s) is necessary for the determination of effective treatment options. We have developed a method based on a modified broad-range PCR and an oligonucleotide microarray for the simultaneous detection and identification of 12 bacterial pathogens at the species level. The broad-range PCR primer mixture was designed using conserved regions of the bacterial topoisomerase genes gyrB and parE. The primer design allowed the use of a novel DNA amplification method, which produced labeled, single-stranded DNA suitable for microarray hybridization. The probes on the microarray were designed from the alignments of species- or genus-specific variable regions of the gyrB and parE genes flanked by the primers. We included mecA-specific primers and probes in the same assay to indicate the presence of methicillin resistance in the bacterial species. The feasibility of this assay in routine diagnostic testing was evaluated using 146 blood culture positive and 40 blood culture negative samples.

Results
Comparison of our results with those of a conventional culture-based method revealed a sensitivity of 96% (initial sensitivity of 82%) and specificity of 98%. Furthermore, only one cross-reaction was observed upon investigating 102 culture isolates from 70 untargeted bacteria. The total assay time was only three hours, including the time required for the DNA extraction, PCR and microarray steps in sequence.

Conclusion
The assay rapidly provides reliable data, which can guide optimal antimicrobial treatment decisions in a timely manner.