bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the MyWellness Key accelerometer
Authors: Herrmann S D , Hart T L , Lee C D , Ainsworth B E 
Published: September 2009

ObjectiveTo examine the concurrent validity of the Technogym MyWellness Key accelerometer against objective and subjective physical activity (PA) measures.DesignRandomised, cross-sectional design with two phases. The laboratory phase compared the MyWellness Key with the ActiGraph GT1M and the Yamax SW200 Digiwalker pedometer during graded treadmill walking, increasing speed each minute. The free-living phase compared the MyWellness Key with the ActiGraph, Digiwalker, Bouchard Activity cord (BAR) and Global Physical Activity Questionnaire (GPAQ) for seven continuous days. Data were analysed using Spearman rank-order correlation coefficients for all comparisons.SettingLaboratory and free-living phases.ParticipantsSixteen participants randomly stratified from 41 eligible respondents by sex (n=8 men; n=8 women) and PA levels (n=4 low, n=8 middle and n=4 high active).ResultsThere was a strong association between the MyWellness Key and the ActiGraph accelerometer during controlled graded treadmill walking (r=0.91, p<0.01) and in free-living settings (r=0.73–0.76 for light to vigorous PA, respectively, p<0.01). No associations were observed between the MyWellness Key and the BAR and GPAQ (p>0.05).ConclusionsThe MyWellness Key has a high concurrent validity with the ActiGraph accelerometer to detect PA in both controlled laboratory and free-living settings.
Lung function and indicators of exposure to indoor and outdoor particulate matter among asthma and COPD patients
Authors: de Hartog J J , Ayres J G , Karakatsani A , Analitis A , Brink H ten , Hameri K , Harrison R , Katsouyanni K , Kotronarou A , Kavouras I , Meddings C , Pekkanen J , Hoek G 
Published: September 2009

Objectives:Misclassification of exposure related to the use of central sites may be larger for ultrafine particles than for particulate matter ⩽2.5 μm and ⩽10 μm (PM2.5and PM10) and may result in underestimation of health effects. This paper describes the relative strength of the association between outdoor and indoor exposure to ultrafine particles, PM2.5and PM10and lung function.Methods:In four European cities (Helsinki, Athens, Amsterdam and Birmingham), lung function (forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and peak expiratory flow (PEF)) was measured three times a day for 1 week in 135 patients with asthma or chronic obstructive pulmonary disease (COPD), covering study periods of >1 year. Daily concentrations of particle number, PM2.5and PM10were measured at a central site in each city and both inside and outside the subjects’ homes.Results:Daily average particle number concentrations ranged between 2100 and 66 100 particles/cm3. We found no association between 24 h average particle number or particle mass concentrations and FVC, FEV1and PEF. Substituting home outdoor or home indoor concentrations of particulate air pollution instead of the central site measurements did not change the observed associations. Analyses restricted to asthmatics also showed no associations.Conclusions:No consistent associations between lung function and 24 h average particle number or particle mass concentrations were found in panels of patients with mild to moderate COPD or asthma. More detailed exposure assessment did not change the observed associations. The lack of association could be due to the high prevalence of medication use, limited ability to assess lagged effects over several days or absence of an effect.
Circulating adhesion molecules after short-term exposure to particulate matter among welders
Authors: Fang S C , Eisen E A , Cavallari J M , Mittleman M A , Christiani D C 
Published: September 2009

Background:Studies from several countries indicate that welders experience increased risk of mortality and morbidity from ischaemic heart disease. Although the underlying mechanisms are unclear, vascular responses to particulate matter contained in welding fumes may play a role. To investigate this, we studied the acute effects of welding fume exposure on the endothelial component of vascular function, as measured by circulating adhesion molecules involved in leukocyte adhesion (sICAM-1 and sVCAM-1) and coagulation (vWF).Methods:A panel of 26 male welders was studied repeatedly across a 6 h work-shift on a high exposure welding day and/or a low exposure non-welding day. Personal PM2.5exposure was measured throughout the work-shift. Blood samples were collected in the morning (baseline) prior to the exposure period, immediately after the exposure period, and the following morning. To account for the repeated measurements, we used linear mixed models to evaluate the effects of welding (binary) and PM2.5(continuous) exposure on each blood marker, adjusting for baseline blood marker concentration, smoking, age and time of day.Results:Welding and PM2.5exposure were significantly associated with a decrease in sVCAM-1 in the afternoon and the following morning and an increase in vWF in the afternoon.Conclusions:The data suggest that welding and short-term occupational exposure to PM2.5may acutely affect the endothelial component of vascular function.
Anaerobic Oxidation of Methane: Progress with an Unknown Process
Authors: Knittel Katrin , Boetius Antje 
Published: September 2009

Methane is the most abundant hydrocarbon in the atmosphere, and it is an important greenhouse gas, which has so far contributed an estimated 20% of postindustrial global warming. A great deal of biogeochemical research has focused on the causes and effects of the variation in global fluxes of methane throughout earth's history, but the underlying microbial processes and their key agents remain poorly understood. This is a disturbing knowledge gap because 85% of the annual global methane production and about 60% of its consumption are based on microbial processes. Only three key functional groups of microorganisms of limited diversity regulate the fluxes of methane on earth, namely the aerobic methanotrophic bacteria, the methanogenic archaea, and their close relatives, the anaerobic methanotrophic archaea (ANME). The ANME represent special lines of descent within the Euryarchaeota and appear to gain energy exclusively from the anaerobic oxidation of methane (AOM), with sulfate as the final electron acceptor according to the net reaction:[Formula: see text]This review summarizes what is known and unknown about AOM on earth and its key catalysts, the ANME clades and their bacterial partners.
Study of TiOxNy MOS Capacitors
Authors: Albertin Katia F. , Niwa Takuya , Nobaro Bruno A. , Souza Denise C. , Zuñiga Alejandro , Pereyra Inés 
Published: September 2009

A set of TiOxNy films was deposited by reactive RF magnetron sputtering varying the nitrogen partial pressure in a Ar/N2 gaseous mixture. Utilizing these films as gate dielectric layer MOS capacitors were fabricated and characterized.	The TiOxNy films were characterized by Fourier Transform Infrared Spectroscopy (FTIR), Rutherford Backscattering (RBS), optical absorption, and High Resolution Transmission Electron Microscopy (HRTEM).	Capacitance-voltage (1MHz) and current-voltage measurements were used to obtain the effective dielectric constant, the effective oxide thickness (EOT), the leakage current density, and the interface quality.	MOS capacitors results show that the TiOxNy films present a dielectric constant varying from 28 to 80, good interface quality with silicon, and a leakage current density of approximately 0.25 mA/cm2 for VG = -1V, which is acceptable for high performance logic circuits and low power circuits fabrication. The leakage current density is reduced in 3 orders of magnitude with an increase in nitrogen concentration.
Adaptor Protein Crk Induces Src-Dependent Activation of p38 MAPK in Regulation of Synovial Sarcoma Cell Proliferation
Authors: Watanabe Takuya , Tsuda Masumi , Tanaka Shinya , Ohba Yusuke , Kawaguchi Hideaki , Majima Tokifumi , Sawa Hirofumi , Minami Akio 
Published: September 2009

Abstract
The adaptor protein Crk mediates intracellular signaling related to cell motility and proliferation and is implicated in human tumorigenesis. The role of Crk in the growth of human sarcoma has remained unclear, however. The present study shows that Crk-induced activation of Src and subsequent signaling by p38 mitogen-activated protein kinase (MAPK) contribute to the enhanced proliferation of human synovial sarcoma cells. Depletion of Crk by RNA interference markedly inhibited proliferation of the synovial sarcoma cell lines HS-SYII, SYO-1, and Fuji as well as prevented anchorage-independent growth. Conversely, reconstitution with CrkII by authentic small interfering RNA–resistant Crk gene restored proliferation in Crk-silenced SYO-1 cells. Crk-depleted synovial sarcoma cells manifested enhanced transcriptional activity and expression of the p16INK4A gene, resulting in their accumulation in G1 phase of the cell cycle. In response to hepatocyte growth factor stimulation, Crk prominently induced the tyrosine phosphorylation of Grb2-associated binder 1 through activation of Src and focal adhesion kinase, and the Src family kinase inhibitor PP2 almost completely inhibited the proliferation of SYO-1 cells. Crk also induced the phosphorylation of p38 MAPK, and SB203580, a p38 MAPK–specific inhibitor, increased expression of p16INK4A gene in SYO-1 cells. Furthermore, SB203580 or depletion of p38 MAPK by small interfering RNA suppressed both the phosphorylation of Akt triggered by hepatocyte growth factor and the proliferation of SYO-1 cells. These results suggest that Crk promotes proliferation of human synovial sarcoma cells through activation of Src and its downstream signaling by a novel p38 MAPK-Akt pathway, with these signaling molecules providing potent new targets for molecular therapeutics. (Mol Cancer Res 2009;7(9):1582–92)
Mutations in Multiple Domains of c-Myb Disrupt Interaction with CBP/p300 and Abrogate Myeloid Transforming Ability
Authors: Pattabiraman Diwakar R. , Sun Jane , Dowhan Dennis H. , Ishii Shunsuke , Gonda Thomas J. 
Published: September 2009

Abstract
The c-myb proto-oncogene is a key regulator of hematopoietic cell proliferation and differentiation. MYB mRNA is expressed at high levels in, and is required for the proliferation of, most human myeloid and acute lymphoid leukemias. Recently, chromosomal translocation and genomic duplications of c-MYB have been identified in human T-cell acute leukemia. The present work focuses on the effects of mutations in different domains of the murine c-Myb protein on its transforming ability as defined by suppression of myelomonocytic differentiation and continued proliferation. Using both a novel myeloid cell line–based assay and a primary hematopoietic cell assay, we have shown that mutation of single residues in the transactivation domain important for CBP/p300 binding leads to complete loss of transforming ability. We also simultaneously mutated residues in the DNA-binding domain and the negative regulatory domain of the protein. These double mutants, but not the corresponding single mutants, show a complete loss of transforming activity. Surprisingly, these double mutants show severely impaired transactivation and are also defective for CBP/p300 binding. Our results imply that multiple Myb domains influence its interaction with CBP/p300, highlight the importance of this interaction for myeloid transformation, and suggest an approach for molecular targeting of Myb in leukemia. (Mol Cancer Res 2009;7(9):1477–86)
Anxiety and the management of asthma in an adult outpatient population
Authors: Cordina Maria , Fenech Anthony G. , Vassallo Josanne , Cacciottolo Joseph M. 
Published: September 2009

Background: Review of the literature suggests that anxiety is more common among patients with asthma than among the general population, yet it does not appear to be given the attention it deserves as part of the overall management of asthma. The aim of this study was to investigate the relationship between anxiety and asthma management, in terms of Global Initiative for Asthma steps, lung function and medication. Methods: A total of 201 consecutive patients with respiratory physician-diagnosed asthma were recruited from an adult outpatient asthma clinic. Participants underwent a sociodemographic review, and a medical interview which included a detailed drug history. Forced expiratory volume in 1 second (FEV1) and peak expiratory flow (PEF) values were recorded using a Micro Medical® portable spirometer. The level of anxiety was assessed using the Beck Anxiety Inventory (BAI). Results: A total of 51.5% of participants registered clinically significant levels of anxiety. Of these only 21% had already been diagnosed and were receiving treatment. Females reported significantly higher BAI scores than males ( p < 0.01). More females (66.3%) registered clinically significant levels of anxiety as compared with males (33.7%) ( p < 0.05). There was a positive correlation between the BAI score and the prescribed dose of inhaled glucocorticoids ( rs = 0.150, p < 0.05) and between anxiety and GINA treatment step ( rs = 0.139, p < 0.05). There was also a positive correlation between anxiety and the number of medicines taken by patients ( rs = 0.259, p < 0.001). Conclusions: Physicians treating patients with asthma should be sensitised to the association between asthma and anxiety, and should also consider assessing patients for the possibility of anxiety disorders as part of asthma management plans.
Interleukin-21 restores immunoglobulin production ex vivo in patients with common variable immunodeficiency and selective IgA deficiency
Authors: Borte Stephan , Pan-Hammarström Qiang , Liu Chonghai , Sack Ulrich , Borte Michael , Wagner Ulf , Graf Dagmar , Hammarström Lennart 
Published: September 2009

Abstract
Interleukin-21 (IL-21) is an important promoter for differentiation of human B cells into immunoglobulin (Ig)–secreting cells. The objective of this study was to evaluate an IL-21–based approach to induce immunoglobulin production in B cells from patients with common variable immunodeficiency (CVID) or selective IgA deficiency (IgAD). We show that a combination of IL-21, IL-4, and anti-CD40 stimulation induces class-switch recombination to IgG and IgA and differentiation of Ig-secreting cells, consisting of both surface IgG+ (sIgG+) and sIgA+ B cells and CD138+ plasma cells, in patients with CVID or IgAD. Stimulation with IL-21 was far more effective than stimulation with IL-4 or IL-10. Moreover, spontaneous apoptosis of CD19+ B cells from patients with CVID or IgAD was prevented by a combination of IL-21, IL-4, and anti-CD40 stimulation. Analysis of IL-21 and IL-21 receptor (IL-21R) mRNA expression upon anti-CD3 stimulation of T cells, however, showed no evidence for defective IL-21 expression in CVID patients and sequencing of the coding regions of the IL21 gene did not reveal any mutations, suggesting a regulatory defect. Thus, our work provides an initial basis for a potential therapeutic role of IL-21 to reconstitute immunoglobulin production in CVID and IgAD.
Wild-type FOXP3 is selectively active in CD4+CD25hi regulatory T cells of healthy female carriers of different FOXP3 mutations
Authors: Di Nunzio Sara , Cecconi Massimiliano , Passerini Laura , McMurchy Alicia N. , Baron Udo , Turbachova Ivana , Vignola Silvia , Valencic Erica , Tommasini Alberto , Junker Anne , Cazzola Giantonio , Olek Sven , Levings Megan K. , Perroni Lucia , Roncarolo Maria Grazia , Bacchetta Rosa 
Published: September 2009

Abstract
Forkhead box P3 (FOXP3) is constitutively expressed by CD4+CD25hi regulatory T cells (nTregs). Mutations of FOXP3 cause a severe autoimmune syndrome known as immune dysregulation polyendocrinopathy enteropathy X-linked, in which nTregs are absent or dysfunctional. Whether FOXP3 is essential for both differentiation and function of human nTreg cells remains to be demonstrated. Because FOXP3 is an X-linked gene subject to X-chromosome inactivation (XCI), we studied 9 healthy female carriers of FOXP3 mutations to investigate the role of wild-type (WT) versus mutated FOXP3 in different cell subsets. Analysis of active WT versus mutated (mut)–FOXP3 allele distribution revealed a random pattern of XCI in peripheral blood lymphocytes and in naive and memory CD4+T cells, whereas nTregs expressed only the active WT-FOXP3. These data demonstrate that expression of WT-FOXP3 is indispensable for the presence of a normal nTreg compartment and suggest that FOXP3 is not necessary for effector T-cell differentiation in humans.
The persistence of immunophenotypically normal residual bone marrow plasma cells at diagnosis identifies a good prognostic subgroup of symptomatic multiple myeloma patients
Authors: Paiva Bruno , Vidriales Maria-Belén , Mateo Gema , Pérez Jose J. , Montalbán Maria Angeles , Sureda Anna , Montejano Laura , Gutiérrez Norma C. , García de Coca Alfonso , de las Heras Natalia , Mateos Maria Victoria , López-Berges Maria Consuelo , García-Boyero Raimundo , Galende Josefina , Hernández Jose , Palomera Luis , Carrera Dolores , Martínez Rafael , de la Rubia Javier , Martín Alejandro , González Yolanda , Bladé Joan , Lahuerta Juan José , Orfao Alberto , San-Miguel Jesús F. ,   on behalf of the GEM (Grupo Español de MM)/PETHEMA (Programa para el Estudio de la Terapéutica en Hemopatías Malignas) Cooperative Study Groups
Published: September 2009

Abstract
Multiparameter flow cytometry immunophenotyping allows discrimination between normal (N-) and myelomatous (MM-) plasma cells (PCs) within the bone marrow plasma cell compartment (BMPCs). Here we report on the prognostic relevance of detecting more than 5% residual normal plasma cells from all bone marrow plasma cells (N-PCs/BMPCs) by multiparameter flow cytometry in a series of 594 newly diagnosed symptomatic MM patients, uniformly treated according to the Grupo Español de MM 2000 (GEM2000) protocol. Our results show that symptomatic MM patients with more than 5% N-PCs/BMPCs (n = 80 of 594; 14%) have a favorable baseline clinical prospect, together with a significantly lower frequency of high-risk cytogenetic abnormalities and higher response rates. Moreover, this group of patients had a significantly longer progression-free survival (median, 54 vs 42 months, P = .001) and overall survival (median, not reached vs 89 months, P = .04) than patients with less than or equal to 5% N-PCs/BMPCs. Our findings support the clinical value of detecting residual normal PCs in MM patients at diagnosis because this reveals a good prognostic category that could benefit from specific therapeutic approaches. This trial was registered at www.clinicaltrials.gov as NCT00560053.
Downregulation of protease activated receptor expression and cytokine production in P815 cells by RNA interference
Authors: Qiao Liya , Zhang Huiyun , Wu Shandong , He Shaoheng 
Published: September 2009

AbstractBackgroundProtease-activated receptors (PAR) are seven transmembrane G-coupled receptors comprising four genes (PAR-1 ~ PAR-4). Mast cell has been identified to be able to express PARs and release an array of cytokines upon activation. Recently, it was reported that interleukin (IL)-12 could regulate the expression of PARs in mast cells, and tryptase could induce IL-4 and IL-6 release from mast cells. In order to further investigate the issues, RNA interference (RNAi) technique was employed and small interfering RNAs (siRNA) of PARs were transfected in P815 cells.ResultsThe results showed that siRNAs for PAR-1, PAR-2 and PAR-4 significantly downregulated expression of PAR-1, PAR-2 and PAR-4 mRNAs and proteins in P815 cells at 24, 48 and 72 h following transfection. siRNA PAR-1.2 and siRNA PAR-4.2 significantly reduced IL-12 induced upregulation of PAR-1 and PAR-4 expression, respectively when P815 cells were transfected with them for 48 h. siRNA PAR-2.3 blocked IL-12 induced downregulation of PAR-2 expression on both mRNA and protein levels. It was also observed that siRNA PAR-2.3 and siRNA PAR-1.2 reduced trypsin induced IL-4 release by approximately 92.6% and 65.3%, and SLIGKV-NH2induced IL-4 release by 82.1% and 60.1%, respectively. Similarly, siRNA PAR-2.3 eliminated tryptase-induced IL-4 release by 75.3%, and siRNA PAR-1.2 diminished SFLLR-NH2induced IL-4 release by 79.3%. However, siRNA PAR-1.2, siRNA PAR-2.3 and siRNA PAR-4.3 at 10 nM did not show any effect on tryptase-induced IL-6 release from P815 cells.ConclusionIn conclusion, siRNAs of PARs can modulate PAR expression and PAR related cytokine production in mast cells, confirming that PARs are likely to play a role in allergic reactions.
The identification and functional implications of human-specific "fixed" amino acid substitutions in the glutamate receptor family
Authors: Goto Hiroki , Watanabe Kazunori , Araragi Naozumi , Kageyama Rui , Tanaka Kunika , Kuroki Yoko , Toyoda Atsushi , Hattori Masahira , Sakaki Yoshiyuki , Fujiyama Asao , Fukumaki Yasuyuki , Shibata Hiroki 
Published: September 2009

Abstract

Background
The glutamate receptors (GluRs) play a vital role in the mediation of excitatory synaptic transmission in the central nervous system. To clarify the evolutionary dynamics and mechanisms of the GluR genes in the lineage leading to humans, we determined the complete sequences of the coding regions and splice sites of 26 chimpanzee GluR genes.

Results
We found that all of the reading frames and splice sites of these genes reported in humans were completely conserved in chimpanzees, suggesting that there were no gross structural changes in humans after their divergence from the human-chimpanzee common ancestor. We observed low K

A
/K

S
ratios in both humans and chimpanzees, and we found no evidence of accelerated evolution. We identified 30 human-specific "fixed" amino acid substitutions in the GluR genes by analyzing 80 human samples of seven different populations worldwide. Grantham's distance analysis showed that GRIN2C and GRIN3A are the most and the second most diverged GluR genes between humans and chimpanzees. However, most of the substitutions are non-radical and are not clustered in any particular region. Protein motif analysis assigned 11 out of these 30 substitutions to functional regions. Two out of these 11 substitutions, D71G in GRIN3A and R727H in GRIN3B, caused differences in the functional assignments of these genes between humans and other apes.

Conclusion
We conclude that the GluR genes did not undergo drastic changes such as accelerated evolution in the human lineage after the divergence of chimpanzees. However, there remains a possibility that two human-specific "fixed" amino acid substitutions, D71G in GRIN3A and R727H in GRIN3B, are related to human-specific brain function.
Comparative analysis of the mammalian WNT4 promoter
Authors: Yu Hongshi , Pask Andrew J , Shaw Geoffrey , Renfree Marilyn B 
Published: September 2009

AbstractBackgroundWNT4 is a critical signalling molecule in embryogenesis and homeostasis, but the elements that control its transcriptional regulation are largely unknown. This study uses comparative cross species sequence and functional analyses between humans and a marsupial (the tammar wallaby,Macropus eugenii) to refine the mammalianWnt4promoter.ResultsWe have defined a highly conserved 89 bp minimal promoter region in humanWNT4by comparative analysis with the tammar wallaby. There are many conserved transcription factor binding sites in the proximal promoter region, including SP1, MyoD, NFκB and AP2, as well as highly conserved CpG islands within the human, mouse and marsupial promoters, suggesting that DNA methylation may play an important role inWNT4transcriptional regulation.ConclusionUsing a marsupial model, we have been able to provide new information on the transcriptional regulators in the promoter of this essential mammalian developmental gene,WNT4. These transcription factor binding sites and CpG islands are highly conserved in two disparate mammals, and are likely key controlling elements in the regulation of this essential developmental gene.