bluuebunny/crossref_metadata_2025_split huggingface dataset:
Airway inflammation in cement production workers
Authors: Fell Anne Kristin M , Sikkeland Liv Ingunn B , Svendsen Martin Veel , Kongerud Johny 
Published: October 2009

ObjectiveCement aerosol exposure is associated with increased morbidity of airway disease among exposed workers. Our aim was to compare levels of inflammatory cells and soluble inflammatory markers in induced sputum samples from cement production workers between exposed and unexposed periods, and to compare these variables between cement workers and references.Methods35 healthy, non-smoking aerosol-exposed cement production workers from Norway provided a blood sample and performed induced sputum and spirometry after 5 days without exposure and during a period of exposure. These values were compared with those from an internal low-exposed reference group of 15 office workers and an external reference group of 39 non-exposed workers. Differential cell counts and inflammatory markers were assessed.ResultsMedian thoracic aerosol concentration over one work shift (8 h) was 0.6 mg/m3(range 0.2–8.1) in maintenance workers and 1.75 mg/m3(0.2–15.5) in furnace department workers. The median percentage of airway neutrophils in both groups combined was 51% (32–66) in the exposed period, which was significantly higher than in both the unexposed period (38%; 23–55) (p=0.04) and the external reference group (30%; 19–44) (p=0.001). Median interleukin-1β concentration was elevated compared with both office workers (p=0.05) and the external reference group (p=0.006).ConclusionsA significantly higher percentage of neutrophils was observed in cement production workers during the exposed period compared with both the non-exposed period and the external reference group, and corresponded with elevated IL-1β concentration. These data indicate that cement aerosol exposure in concentrations below the Norwegian occupational limits (respirable dust 5 mg/m3; total dust 10 mg/m3) may cause airway inflammation.
A New System of Generalized Nonlinear Mixed Variational Inclusions in Banach Spaces
Authors: Peng JianWen 
Published: October 2009

AbstractWe introduce and study a new system of generalized nonlinear mixed variational inclusions in real "Equation missing"-uniformly smooth Banach spaces. We prove the existence and uniqueness of solution and the convergence of some new "Equation missing"-step iterative algorithms with or without mixed errors for this system of generalized nonlinear mixed variational inclusions. The results in this paper unify, extend, and improve some known results in literature.
BCL6 modulates tonic BCR signaling in diffuse large B-cell lymphomas by repressing the SYK phosphatase, PTPROt
Authors: Juszczynski Przemyslaw , Chen Linfeng , O'Donnell Evan , Polo Jose M. , Ranuncolo Stella M. , Dalla-Favera Riccardo , Melnick Ari , Shipp Margaret A. 
Published: October 2009

Abstract
Tonic B-cell receptor (BCR) signaling is a key survival pathway during normal B-cell ontogenesis and in a subset of diffuse large B-cell lymphomas (DLBCLs). We previously demonstrated that BCR-dependent DLBCL cell lines and primary tumors underwent apoptosis after treatment with an ATP-competitive inhibitor of the BCR-associated spleen tyrosine kinase (SYK). These “BCR-type” tumors also have more abundant expression of the transcriptional repressor, BCL6, and increased sensitivity to BCL6 inhibition. Herein, we evaluated potential connections between BCL6-mediated transcriptional repression and SYK-dependent BCR signaling. In transcriptionally profiled normal B-cell subsets (naive, germinal center, and memory B cells) and in primary DLBCLs, there were reciprocal patterns of expression of BCL6 and the SYK tyrosine phosphatase PTPROt. BCL6 repressed PTPROt transcription via a direct interaction with functional BCL6 binding sites in the PTPROt promoter. Enforced expression of BCL6 in normal naive B cells and RNAi-mediated depletion of BCL6 in germinal center B cells directly modulated PTPROt expression. In “BCR-type” DLBCLs, BCL6 depletion increased PTPROt expression and decreased phosphorylation of SYK and the downstream adaptor protein BLNK. Because BCL6 augments BCR signaling and BCL6 and SYK are both promising therapeutic targets in many DLBCLs, combined inhibition of these functionally related pathways warrants further study.
Specific promoter methylation identifies different subgroups of MLL-rearranged infant acute lymphoblastic leukemia, influences clinical outcome, and provides therapeutic options
Authors: Stumpel Dominique J. P. M. , Schneider Pauline , van Roon Eddy H. J. , Boer Judith M. , de Lorenzo Paola , Valsecchi Maria G. , de Menezes Renee X. , Pieters Rob , Stam Ronald W. 
Published: October 2009

AbstractMLL-rearranged infant acute lymphoblastic leukemia (ALL) remains the most aggressive type of childhood leukemia, displaying a unique gene expression profile. Here we hypothesized that this characteristic gene expression signature may have been established by potentially reversible epigenetic modifications. To test this hypothesis, we used differential methylation hybridization to explore the DNA methylation patterns underlying MLL-rearranged ALL in infants. The obtained results were correlated with gene expression data to confirm gene silencing as a result of promoter hypermethylation. Distinct promoter CpG island methylation patterns separated different genetic subtypes of MLL-rearranged ALL in infants. MLL translocations t(4;11) and t(11;19) characterized extensively hypermethylated leukemias, whereas t(9;11)-positive infant ALL and infant ALL carrying wild-type MLL genes epigenetically resembled normal bone marrow. Furthermore, the degree of promoter hypermethylation among infant ALL patients carrying t(4;11) or t(11;19) appeared to influence relapse-free survival, with patients displaying accentuated methylation being at high relapse risk. Finally, we show that the demethylating agent zebularine reverses aberrant DNA methylation and effectively induces apoptosis in MLL-rearranged ALL cells. Collectively these data suggest that aberrant DNA methylation occurs in the majority of MLL-rearranged infant ALL cases and guides clinical outcome. Therefore, inhibition of aberrant DNA methylation may be an important novel therapeutic strategy for MLL-rearranged ALL in infants.
Immunoregulatory functions of KLRG1 cadherin interactions are dependent on forward and reverse signaling
Authors: Banh Cindy , Fugère Céline , Brossay Laurent 
Published: October 2009

AbstractKLRG1 is an inhibitory receptor expressed on a subset of mature T and NK cells. Recently, E-, N-, and R-cadherin have been identified as ligands for KLRG1. Cadherins are a large family of transmembrane or membrane-associated glycoproteins that were thought to only bind specifically to other cadherins to mediate specific cell-to-cell adhesion in a Ca2+-dependent manner. The consequences of cadherin KLRG1 molecular interactions are not well characterized. Here, we report that the first 2 extracellular domains of cadherin are sufficient to initiate a KLRG1-dependent signaling. We also demonstrate that KLRG1 engagement inhibits cadherin-dependent cellular adhesion and influences dendritic cell secretion of inflammatory cytokines, thereby exerting immunosuppressive effects. Consistent with this, engagement of cadherin by KLRG1 molecule induces cadherin tyrosine phosphorylation. Therefore, KLRG1/cadherin interaction leads to the generation of a bidirectional signal in which both KLRG1 and cadherin activate downstream signaling cascades simultaneously. Taken together, our results provide novel insights on how KLRG1 and E-cadherin interactions are integrated to differentially regulate not only KLRG1+ cells, but also E-cadherin–expressing cells, such as dendritic cells.
Asthma and genes encoding components of the vitamin D pathway
Authors: Bossé Yohan , Lemire Mathieu , Poon Audrey H , Daley Denise , He Jian-Qing , Sandford Andrew , White John H , James Alan L , Musk William Arthur , Palmer Lyle J , Raby Benjamin A , Weiss Scott T , Kozyrskyj Anita L , Becker Allan , Hudson Thomas J , Laprise Catherine 
Published: October 2009

Abstract

Background
Genetic variants at the vitamin D receptor (VDR) locus are associated with asthma and atopy. We hypothesized that polymorphisms in other genes of the vitamin D pathway are associated with asthma or atopy.

Methods
Eleven candidate genes were chosen for this study, five of which code for proteins in the vitamin D metabolism pathway (CYP27A1, CYP27B1, CYP2R1, CYP24A1, GC) and six that are known to be transcriptionally regulated by vitamin D (IL10, IL1RL1, CD28, CD86, IL8, SKIIP). For each gene, we selected a maximally informative set of common SNPs (tagSNPs) using the European-derived (CEU) HapMap dataset. A total of 87 SNPs were genotyped in a French-Canadian family sample ascertained through asthmatic probands (388 nuclear families, 1064 individuals) and evaluated using the Family Based Association Test (FBAT) program. We then sought to replicate the positive findings in four independent samples: two from Western Canada, one from Australia and one from the USA (CAMP).

Results
A number of SNPs in the IL10, CYP24A1, CYP2R1, IL1RL1 and CD86 genes were modestly associated with asthma and atopy (p < 0.05). Two-gene models testing for both main effects and the interaction were then performed using conditional logistic regression. Two-gene models implicating functional variants in the IL10 and VDR genes as well as in the IL10 and IL1RL1 genes were associated with asthma (p < 0.0002). In the replicate samples, SNPs in the IL10 and CYP24A1 genes were again modestly associated with asthma and atopy (p < 0.05). However, the SNPs or the orientation of the risk alleles were different between populations. A two-gene model involving IL10 and VDR was replicated in CAMP, but not in the other populations.

Conclusion
A number of genes involved in the vitamin D pathway demonstrate modest levels of association with asthma and atopy. Multilocus models testing genes in the same pathway are potentially more effective to evaluate the risk of asthma, but the effects are not uniform across populations.
Whole-genome analysis of pseudorabies virus gene expression by real-time quantitative RT-PCR assay
Authors: Tombácz Dóra , Tóth Judit S , Petrovszki Pál , Boldogkői Zsolt 
Published: October 2009

Abstract

Background
Pseudorabies virus (PRV), a neurotropic herpesvirus of pigs, serves as an excellent model system with which to investigate the herpesvirus life cycle both in cultured cells and in vivo. Real-time RT-PCR is a very sensitive, accurate and reproducible technique that can be used to detect very small amounts of RNA molecules, and it can therefore be applied for analysis of the expression of herpesvirus genes from the very early period of infection.

Results
In this study, we have developed and applied a quantitative reverse transcriptase-based real-time PCR technique in order to profile transcription from the whole genome of PRV after lytic infection in porcine kidney cells. We calculated the relative expression ratios in a novel way, which allowed us to compare different PRV genes with respect to their expression dynamics, and to divide the PRV genes into distinct kinetic classes. This is the first publication on the whole-genome analysis of the gene expression of an alpha-herpesvirus by qRT2-PCR. We additionally established the kinetic properties of uncharacterized PRV genes and revised or confirmed data on PRV genes earlier examined by traditional methods such as Northern blot analysis. Our investigations revealed that genes with the same expression properties form clusters on the PRV genome: nested overlapping genes belong in the same kinetic class, while most convergent genes belong in different kinetic classes. Further, we detected inverse relationships as concerns the expressions of EP0 and IE180 mRNAs and their antisense partners.

Conclusion
Most (if not all) PRV genes begin to be expressed from the onset of viral expression. No sharp boundary was found between the groups of early and late genes classified on the basis of their requirement for viral DNA synthesis. The expressions of the PRV genes were analyzed, categorized and compared by qRT2-PCR assay, with the average of the minimum cycle threshold used as a control for the calculation of a particular R value. In principle, this new calculation technique is applicable for the analysis of gene expression in all temporally changing genetic systems.
Quality control in microarray assessment of gene expression in human airway epithelium
Authors: Raman Tina , O'Connor Timothy P , Hackett Neil R , Wang Wei , Harvey Ben-Gary , Attiyeh Marc A , Dang David T , Teater Matthew , Crystal Ronald G 
Published: October 2009

AbstractBackgroundMicroarray technology provides a powerful tool for defining gene expression profiles of airway epithelium that lend insight into the pathogenesis of human airway disorders. The focus of this study was to establish rigorous quality control parameters to ensure that microarray assessment of the airway epithelium is not confounded by experimental artifact. Samples (total n = 223) of trachea, large and small airway epithelium were collected by fiberoptic bronchoscopy of 144 individuals and hybridized to Affymetrix microarrays. The pre- and post-chip quality control (QC) criteria established, included: (1) RNA quality, assessed by RNA Integrity Number (RIN) ≥ 7.0; (2) cRNA transcript integrity, assessed by signal intensity ratio of GAPDH 3' to 5' probe sets ≤ 3.0; and (3) the multi-chip normalization scaling factor ≤ 10.0.ResultsOf the 223 samples, all three criteria were assessed in 191; of these 184 (96.3%) passed all three criteria. For the remaining 32 samples, the RIN was not available, and only the other two criteria were used; of these 29 (90.6%) passed these two criteria. Correlation coefficients for pairwise comparisons of expression levels for 100 maintenance genes in which at least one array failed the QC criteria (average Pearson r = 0.90 ± 0.04) were significantly lower (p < 0.0001) than correlation coefficients for pairwise comparisons between arrays that passed the QC criteria (average Pearson r = 0.97 ± 0.01). Inter-array variability was significantly decreased (p < 0.0001) among samples passing the QC criteria compared with samples failing the QC criteria.ConclusionBased on the aberrant maintenance gene data generated from samples failing the established QC criteria, we propose that the QC criteria outlined in this study can accurately distinguish high quality from low quality data, and can be used to delete poor quality microarray samples before proceeding to higher-order biological analyses and interpretation.
Selenium deficiency impairs host innate immune response and induces susceptibility to Listeria monocytogenes infection
Authors: Wang Chengmin , Wang Haijing , Luo Jing , Hu Yi , Wei Lei , Duan Mingxing , He Hongxuan 
Published: October 2009

Abstract

Background
Susceptibility or resistance to infection with Listeria monocytogenes correlates with Selenium (Se) deficiency in response to infection.

Results
Se-deficient mouse models of listeriosis were used to study the innate immune response during the course of L. monocytogenes infection. Blood samples from mouse models were used for Se status. The concentration of MDA, SOD, GPx and CAT in blood has revealed that lower Se level exist in Se-deficient mice. Intestine, mesenteric lymph node, liver, spleen and brain from each mouse were to study the bacterial burden in organs. The analysis of cell types of spleen from Se-deficient mice revealed that the ability of the host to elicit a rapid recruitment and activation of systemic innate immune response to infection was to a certain extent compromised under conditions of Se deficiency. The cytokine levels in the serum and cytokine expression levels in the livers from Se-deficient mice revealed that the innate immune response of Se-deficient mice was impaired throughout the course of infection. These results suggest that innate immune response is altered by Se deficiency after infection with L. monocytogenes.

Conclusion
In conclusion, induced susceptibility of host resistance is associated with an impaired innate immune response following infection with L. monocytogenes in C57BL/6 Se-deficient mice.
Acupuncture for pain and osteoarthritis of the knee: a pilot study for an open parallel-arm randomised controlled trial
Authors: Lansdown Harriet , Howard Katie , Brealey Stephen , MacPherson Hugh 
Published: October 2009

Abstract

Background
There is some evidence that acupuncture for pain and osteoarthritis (OA) of the knee is more than a placebo, and short term clinical benefits have been observed when acupuncture is compared to usual care. However there is insufficient evidence on whether clinical benefits of acupuncture are sustained over the longer term. In this study our key objectives are to inform the design parameters for a fully powered pragmatic randomised controlled trial. These objectives include establishing potential recruitment rates, appropriate validated outcome measures, attendance levels for acupuncture treatment, loss to follow up and the sample size for a full scale trial.

Methods
Potential participants aged over 50 with pain and osteoarthritis of the knee were identified from a GP database. Eligible patients were randomised to either 'acupuncture plus usual care' and 'usual care' alone, with allocation appropriately concealed. Acupuncture consisted of up to 10 sessions usually weekly. Outcome measures included Western Ontario and McMaster Universities (WOMAC) index with the sample size for a full scale trial determined from the variance.

Results
From the GP database of 15,927 patients, 335 potential trial participants were identified and invited to participate. After screening responses, 78 (23%) were identified as eligible and 30 patients who responded most promptly were randomised to 'acupuncture plus usual care' (15 patients) and 'usual care' alone (15 patients). Attendance for acupuncture appointments was high at 90% of the maximum. Although the trial was not powered to detect significant changes in outcome, the WOMAC pain index showed a statistically significant reduction at 3 months in the acupuncture group compared to usual care. This was not sustained at 12 months. The sample size for a fully powered two-arm trial was estimated to be 350.

Conclusion
This pilot study provided the evidence that a fully powered study to explore the longer term impact of acupuncture would be worthwhile, and relevant design features for such a trial were determined.

Trial registration number
ISRCTN25134802.
Structural insights into the substrate tunnel of Saccharomyces cerevisiae carbonic anhydrase Nce103
Authors: Teng Yan-Bin , Jiang Yong-Liang , He Yong-Xing , He Wei-Wei , Lian Fu-Ming , Chen Yuxing , Zhou Cong-Zhao 
Published: October 2009

Abstract

Background
The carbonic anhydrases (CAs) are involved in inorganic carbon utilization. They have been classified into six evolutionary and structural families: α-, β-, γ-, δ-, ε-, ζ- CAs, with β-CAs present in higher plants, algae and prokaryotes. The yeast Saccharomyces cerevisiae encodes a single copy of β-CA Nce103/YNL036W.

Results
We determined the crystal structure of Nce103 in complex with a substrate analog at 2.04 Å resolution. It assembles as a homodimer, with the active site located at the interface between two monomers. At the bottom of the substrate pocket, a zinc ion is coordinated by the three highly conserved residues Cys57, His112 and Cys115 in addition to a water molecule. Residues Asp59, Arg61, Gly111, Leu102, Val80, Phe75 and Phe97 form a tunnel to the bottom of the active site which is occupied by a molecule of the substrate analog acetate. Activity assays of full length and two truncated versions of Nce103 indicated that the N-terminal arm is indispensable.

Conclusion
The quaternary structure of Nce103 resembles the typical plant type β-CAs of known structure, with an N-terminal arm indispensable for the enzymatic activity. Comparative structure analysis enables us to draw a possible tunnel for the substrate to access the active site which is located at the bottom of a funnel-shaped substrate pocket.
Liposarcoma of the colon presenting as an endoluminal mass
Authors: D'Annibale Marco , Cosimelli Maurizio , Covello Renato , Stasi Elisa 
Published: October 2009

AbstractBackgroundLiposarcoma is one of the most common soft tissue sarcoma of adult life, usually occurring in the retroperitoneum and the extremities. Primary liposarcoma of the colon is very rare. The optimal treatment has not been established due to the small number of cases reported. We report a case of primary liposarcoma of the colon presenting as a massive intraluminal lesion.Case presentationA 79-year-old woman presented with abdominal pain, progressive constipation and weight loss. A CT scan and a colonoscopy revealed an intraluminal mass in the transverse colon and multiple intraperitoneal lesions. The patient underwent surgical resection of the lesions. Pathologic examination was consistent with pleomorphic liposarcoma of the colon.ConclusionAlthough no guidelines are available for the management of liposarcoma of the colon, surgical resection should be performed when feasible. Our patient's overall survival was satisfactory in spite of the multiple negative prognostic factors.
CD44 expression positively correlates with Foxp3 expression and suppressive function of CD4+ Treg cells
Authors: Liu Tie , Soong Lynn , Liu Gang , König Rolf , Chopra Ashok K 
Published: October 2009

Abstract

Background
CD4+CD25+ regulatory T (Treg) cells develop in the thymus and can suppress T cell proliferation, modulated by Foxp3 and cytokines; however, the relevance of CD44 in Treg cell development is less clear. To address this issue, we analyzed Foxp3 expression in CD44+ Treg cells by using multiple parameters, measured the levels of the immunoregulatory cytokine interleukin (IL)-10 in various thymocyte subsets, and determined the suppressor activity in different splenic Treg cell populations.

Results
Within mouse thymocytes, we detected Treg cells with two novel phenotypes, namely the CD4+CD8-CD25+CD44+ and CD4+CD8-CD25+CD44- staining features. Additional multi-parameter analyses at the single-cell and molecular levels suggested to us that CD44 expression positively correlated with Foxp3 expression in thymocytes, the production of IL-10, and Treg activity in splenic CD4+CD25+ T cells. This suppressive effect of Treg cells on T cell proliferation could be blocked by using anti-IL-10 neutralizing antibodies. In addition, CD4+CD25+CD44+ Treg cells expressed higher levels of IL-10 and were more potent in suppressing effector T cell proliferation than were CD4+CD25+CD44- cells.

Conclusion
This study indicates the presence of two novel phenotypes of Treg cells in the thymus, the functional relevance of CD44 in defining Treg cell subsets, and the role of both IL-10 and Foxp3 in modulating the function of Treg cells.

Reviewers
This article was reviewed by Dr. M. Lenardo, Dr. L. Klein & G. Wirnsberger (nominated by Dr. JC Zungia-Pfluker), and Dr. E.M. Shevach.