bluuebunny/crossref_metadata_2025_split huggingface dataset:
Btk is a positive regulator in the TREM-1/DAP12 signaling pathway
Authors: Ormsby Tereza , Schlecker Eva , Ferdin Janina , Tessarz Anja Sibylle , Angelisová Pavla , Köprülü Afitap Derya , Borte Michael , Warnatz Klaus , Schulze Ilka , Ellmeier Wilfried , Hořejší Václav , Cerwenka Adelheid 
Published: June 2011

AbstractThe triggering receptor expressed on myeloid cells 1 (TREM-1) has been implicated in the production of proinflammatory cytokines and chemokines during bacterial infection and sepsis. For downstream signal transduction, TREM-1 is coupled to the ITAM-containing adaptor DAP12. Here, we demonstrate that Bruton tyrosine kinase (Btk), a member of the Tec kinases, becomes phosphorylated upon TREM-1 triggering. In U937-derived cell lines, in which expression of Btk was diminished by shRNA-mediated knockdown, phosphorylation of Erk1/2 and PLCγ1 and Ca2+ mobilization were reduced after TREM-1 stimulation. Importantly, TREM-1–induced production of the pro-inflammatory cytokines, TNF-α and IL-8, and up-regulation of activation/differentiation cell surface markers were impaired in Btk knockdown cells. Similar results were obtained upon TREM-1 stimulation of BMDCs of Btk−/− mice. The analysis of cells containing Btk mutants revealed that intact membrane localization and a functional kinase domain were required for TREM-1–mediated signaling. Finally, after TREM-1 engagement, TNF-α production by PBMCs was reduced in the majority of patients suffering from X-linked agammaglobulinemia (XLA), a rare hereditary disease caused by mutations in the BTK gene. In conclusion, our data identify Btk as a positive regulator in the ITAM-mediated TREM-1/DAP12 pathway and suggest its implication in inflammatory processes.
Alcohol drinking and risk of subsequent hospitalisation with pneumonia
Authors: Kornum J.B. , Due K.M. , Nørgaard M. , Tjønneland A. , Overvad K. , Sørensen H.T. , Thomsen R.W. 
Published: June 2011

The dose–response relationship between alcohol consumption and pneumonia risk in healthy individuals is poorly understood.We examined 22,485 males and 24,682 females from Denmark who were aged 50–64 yrs. Subjects were without major chronic diseases at baseline and had a median follow-up of 12 yrs for first-time hospitalisation with pneumonia.1,091 (males) and 944 (females) had pneumonia-related hospitalisation. Among males, the risk of pneumonia was increased for alcohol abstainers and those who drank large weekly amounts. The adjusted hazard ratios (HRs) for 0, 7–20, 21–34, 35–50 and >50 drinks·week−1were 1.49 (95% CI 1.00–2.21), 0.88 (95% CI 0.76–1.03), 0.87 (95% CI 0.72–1.05), 1.15 (95% CI 0.93–1.44) and 1.81 (95% CI 1.40–2.33), respectively, compared with 1–6 drinks·week−1. The association between high alcohol intake and pneumonia persisted after controlling for subsequent chronic diseases. Among females, HRs for 0, 7–20, 21–35 and >35 drinks·week−1were 1.26 (95% CI 0.89–1.79), 1.01 (95% CI 0.88–1.17), 1.10 (95% CI 0.88–1.37) and 0.54 (95% CI 0.29–1.01), respectively. For the same moderate to high weekly alcohol amount, infrequent intake yielded higher pneumonia HRs than more regular intake in both sexes.Regular moderate alcohol intake is not associated with increased risk of hospitalisation for pneumonia. High weekly alcohol consumption in males and infrequent heavy drinking in both sexes may increase pneumonia risk.
Exposure to thoracic dust, airway symptoms and lung function in cement production workers
Authors: Nordby K-C. , Fell A.K.M. , Notø H. , Eduard W. , Skogstad M. , Thomassen Y. , Bergamaschi A. , Kongerud J. , Kjuus H. 
Published: June 2011

Cement dust exposure has previously been associated with airway symptoms and ventilatory impairment. The aim of the present study was to examine lung function and airway symptoms among employees in different jobs and at different levels of exposure to thoracic dust in the cement production industry.At the start of a 4-yr prospective cohort study in 2007, exposure to cement dust, symptoms and lung function were recorded cross-sectionally in 4,265 employees in 24 European cement plants. Bronchial exposure was assessed by 2,670 full-shift dust samples with cyclones collecting the thoracic aerosol fraction. A job exposure matrix was constructed by grouping dust concentrations according to job type and plant.Elevated odds ratios for symptoms and airflow limitation (range 1.2–2.6 in the highest quartile), but not for chronic bronchitis, were found in the higher quartiles of exposure compared with the lowest quartile. Forced expiratory volume in 1 s (FEV1) showed an exposure–response relationship with a 270-mL deficit of FEV1(95% CI 190–300 mL) in the highest compared with the lowest exposure level.The results support the hypothesis that exposure to dust in cement production may lead to respiratory symptoms and airway obstruction.
Comparative cost and performance of light-emitting diode microscopy in HIV–tuberculosis-co-infected patients
Authors: Whitelaw A. , Peter J. , Sohn H. , Viljoen D. , Theron G. , Badri M. , Davids V. , Pai M. , Dheda K. 
Published: June 2011

Light-emitting diode (LED) microscopy has recently been endorsed by the World Health Organization (WHO). However, it is unclear whether LED is as accurate and cost-effective as Ziehl–Neelsen (ZN) microscopy or mercury vapour fluorescence microscopy (MVFM) in tuberculosis (TB)–HIV-co-infected subjects.Direct and concentrated sputum smears from TB suspects were evaluated using combinations of LED microscopy, ZN microscopy and MVFM. Median reading time per slide was recorded and a cost analysis performed. Mycobacterial culture served as the reference standard.647 sputum samples were obtained from 354 patients (88 (29.8%) were HIV-infected and 161 (26%) were culture-positive forMycobacterium tuberculosis).Although overall sensitivity of LED compared with ZN microscopy or MVFM was similar, sensitivity of all three modalities was lower in HIV-infected patients. In the HIV-infected group, the sensitivity of LED microscopy was higher than ZN microscopy using samples that were not concentrated (46versus39%; p=0.25), and better than MVFM using concentrated samples (56versus44; p=0.5). A similar trend was seen in the CD4 count <200 cells·mL−1subgroup. Median (interquartile range) reading time was quicker with LED compared with ZN microscopy (1.8 (1.7–1.9)versus2.5 (2.2–2.7) min; p≤0.001). Average cost per slide read was less for LED microscopy (US$1.63) compared with ZN microscopy (US$2.10).Among HIV–TB-co-infected patients, LED microscopy was cheaper and performed as well as ZN microscopy or MVFM independent of the staining (ZN or auramine O) or processing methods used.
Farming in childhood, diet in adulthood and asthma history
Authors: Varraso R. , Oryszczyn M.P. , Mathieu N. , Le Moual N. , Boutron-Ruault M.C. , Clavel-Chapelon F. , Romieu I. , Kauffmann F. 
Published: June 2011

The decrease in the number of children living on traditional farms in France during early childhood and changes in diet could both play a role in the increase in asthma prevalence over the last decades. This study aimed to assess 1) the association of farming lifestyle in childhood and asthma, and 2) whether diet in adulthood modifies the association between farming lifestyle in childhood and adult-onset asthma.In the French Etude Epidemiologique des Femmes de la Mutuelle Générale de l'Education Nationale (E3N) study (54,018 females; age 43–68 yrs), three indicators of farming lifestyle were defined: one using individual data (having farmer parents) and two using ecological data (born in a rural area and exposure to cattle).All farming lifestyle indicators were related to childhood- (<16 yrs) and adult-onset asthma (OR (95% CI) values for farmer parents were 0.54 (0.42–0.70) and 0.72 (0.62–0.84), respectively), and to diet in adulthood, in particular to high fruit and low wine intakes. The association between farmer parents and adult-onset asthma was not modified by diet in adulthood.Results extend previous observations in younger cohorts on the protective role of contact with livestock and farming lifestyle on asthma, in particular during childhood.
Renin is an angiotensin-independent profibrotic mediator: role in pulmonary fibrosis
Authors: Montes E. , Ruiz V. , Checa M. , Maldonado V. , Melendez-Zajgla J. , Montaño M. , Ordoñez-Razo R. , Cisneros J. , García-de-Alba C. , Pardo A. , Selman M. 
Published: June 2011

The pathogenesis of idiopathic pulmonary fibrosis (IPF) is probably the result of interplay between cytokines/chemokines and growth factors. The renin–angiotensin (Ang) system is involved, although its profibrotic effect is attributed to Ang II. However, recent studies suggest that renin, through a specific receptor, is implicated in fibrogenesis.In this study, the expression of renin and renin receptor was examined in normal and IPF lungs and fibroblasts. Normal human lung fibroblasts were stimulated with renin or transfected with renin small interfering RNA (siRNA), and the expression of transforming growth factor (TGF)-β1 and α-1-type I collagen was analysed.Normal lungs and lung fibroblasts expressed renin, which was strongly upregulated in IPF lungs and fibroblasts (∼10-fold increase; p<0.05). Immunocytochemistry showed intense renin staining in IPF fibroblasts. Renin-stimulated lung fibroblasts displayed an increase in the expression of TGF-β1 (mean±sd1.8×103±0.2×103versus1.2×103±0.3×103mRNA copies per 18S ribosomal RNA; p<0.01) and collagen (5.93×102±0.66×102versus3.28×102±0.5×102; p<0.01), while knocking down renin expression using siRNA provoked a strong decrease of both molecules. These effects were independent of Ang II, since neither losartan nor captopril decreased these effects. Renin also decreased matrix metalloprotease-1 expression and induced TGF-β1 activation (163±34versus110±15 pg active TGF-β1 per mg total protein).These findings highlight the possible role of renin as an Ang II-independent profibrotic factor in lung fibrosis.
High-resolution computed tomography and pulmonary function in children with common variable immunodeficiency
Authors: van Zeggeren L. , van de Ven A.A.J.M. , Terheggen-Lagro S.W.J. , Mets O.M. , Beek F.J. , van Montfrans J.M. , de Jong P.A. 
Published: June 2011

High-resolution computed tomography (HRCT) may be useful to monitor lung disease in children with common variable immunodeficiency disorder (CVID). We evaluated interobserver agreement and correlation with pulmonary function tests (PFTs) for automated quantification and visual scoring of air trapping and airway wall thickening on HRCT in paediatric CVID patients.In a cohort of 51 children with CVID, HRCT was analysed visually and automated for presence of air trapping and airway wall thickening. PFTs were expressed as % predicted. Disease duration, physician-diagnosed pneumonias and antibiotic prophylaxis were recorded.Interobserver agreement for automated airway wall thickening was good with an intra-class correlation coefficient of 0.88, compared with 0.51 for visual scoring. Presence of air trapping on HRCT correlated significantly with PFTs and disease duration, but was not associated with previous pneumonias. Airway wall thickening did not correlate significantly with PFTs or disease duration and was not associated with previous pneumonias or prophylactic antibiotic use.In children with CVID disorders, HRCT air trapping measurements are significantly correlated with PFTs and disease duration. Quantitative air trapping is a feasible and promising technique for small airway disease quantification that may be applied to monitor (silent) disease progression in CVID.
Identification of SNP and SSR markers in eggplant using RAD tag sequencing
Authors: Barchi Lorenzo , Lanteri Sergio , Portis Ezio , Acquadro Alberto , Valè Giampiero , Toppino Laura , Rotino Giuseppe Leonardo 
Published: June 2011

Abstract

Background
The eggplant (Solanum melongena L.) genome is relatively unexplored, especially compared to those of the other major Solanaceae crops tomato and potato. In particular, no SNP markers are publicly available; on the other hand, over 1,000 SSR markers were developed and publicly available. We have combined the recently developed Restriction-site Associated DNA (RAD) approach with Illumina DNA sequencing for rapid and mass discovery of both SNP and SSR markers for eggplant.

Results
RAD tags were generated from the genomic DNA of a pair of eggplant mapping parents, and sequenced to produce ~17.5 Mb of sequences arrangeable into ~78,000 contigs. The resulting non-redundant genomic sequence dataset consisted of ~45,000 sequences, of which ~29% were putative coding sequences and ~70% were in common between the mapping parents. The shared sequences allowed the discovery of ~10,000 SNPs and nearly 1,000 indels, equivalent to a SNP frequency of 0.8 per Kb and an indel frequency of 0.07 per Kb. Over 2,000 of the SNPs are likely to be mappable via the Illumina GoldenGate assay. A subset of 384 SNPs was used to successfully fingerprint a panel of eggplant germplasm, producing a set of informative diversity data. The RAD sequences also included nearly 2,000 putative SSRs, and primer pairs were designed to amplify 1,155 loci.

Conclusion
The high throughput sequencing of the RAD tags allowed the discovery of a large number of DNA markers, which will prove useful for extending our current knowledge of the genome organization of eggplant, for assisting in marker-aided selection and for carrying out comparative genomic analyses within the Solanaceae family.
Developing the clinical components of a complex intervention for a glaucoma screening trial: a mixed methods study
Authors:   The Glaucoma screening Platform Study group
Published: June 2011

Abstract

Background
Glaucoma is a leading cause of avoidable blindness worldwide. Open angle glaucoma is the most common type of glaucoma. No randomised controlled trials have been conducted evaluating the effectiveness of glaucoma screening for reducing sight loss. It is unclear what the most appropriate intervention to be evaluated in any glaucoma screening trial would be. The purpose of this study was to develop the clinical components of an intervention for evaluation in a glaucoma (open angle) screening trial that would be feasible and acceptable in a UK eye-care service.

Methods
A mixed-methods study, based on the Medical Research Council (MRC) framework for complex interventions, integrating qualitative (semi-structured interviews with 46 UK eye-care providers, policy makers and health service commissioners), and quantitative (economic modelling) methods. Interview data were synthesised and used to revise the screening interventions compared within an existing economic model.

Results
The qualitative data indicated broad based support for a glaucoma screening trial to take place in primary care, using ophthalmic trained technical assistants supported by optometry input. The precise location should be tailored to local circumstances. There was variability in opinion around the choice of screening test and target population. Integrating the interview findings with cost-effectiveness criteria reduced 189 potential components to a two test intervention including either optic nerve photography or screening mode perimetry (a measure of visual field sensitivity) with or without tonometry (a measure of intraocular pressure). It would be more cost-effective, and thus acceptable in a policy context, to target screening for open angle glaucoma to those at highest risk but for both practicality and equity arguments the optimal strategy was screening a general population cohort beginning at age forty.

Conclusions
Interventions for screening for open angle glaucoma that would be feasible from a service delivery perspective were identified. Integration within an economic modelling framework explicitly highlighted the trade-off between cost-effectiveness, feasibility and equity. This study exemplifies the MRC recommendation to integrate qualitative and quantitative methods in developing complex interventions. The next step in the development pathway should encompass the views of service users.
A qualitative study of older adults' responses to sitting-time questions: do we get the information we want?
Authors: van Uffelen Jannique GZ , Heesch Kristiann C , Hill Robert L , Brown Wendy J 
Published: June 2011

Abstract

Background
In the last decade, there has been increasing interest in the health effects of sedentary behavior, which is often assessed using self-report sitting-time questions. The aim of this qualitative study was to document older adults' understanding of sitting-time questions from the International Physical Activity (PA) Questionnaire (IPAQ) and the PA Scale for the Elderly (PASE).

Methods
Australian community-dwelling adults aged 65+ years answered the IPAQ and PASE sitting questions in face-to-face semi-structured interviews. IPAQ uses one open-ended question to assess sitting on a weekday in the last 7 days 'at work, at home, while doing coursework and during leisure time'; PASE uses a three-part closed question about daily leisure-time sitting in the last 7 days. Participants expressed their thoughts out loud while answering each question. They were then probed about their responses. Interviews were recorded, transcribed and coded into themes.

Results
Mean age of the 28 male and 27 female participants was 73 years (range 65-89). The most frequently reported activity was watching TV. For both questionnaires, many participants had difficulties understanding what activities to report. Some had difficulty understanding what activities should be classified as 'leisure-time sitting'. Some assumed they were being asked to only report activities provided as examples. Most reported activities they normally do, rather than those performed on a day in the previous week. Participants used a variety of strategies to select 'a day' for which they reported their sitting activities and to calculate sitting time on that day. Therefore, many different ways of estimating sitting time were used. Participants had particular difficulty reporting their daily sitting-time when their schedules were not consistent across days. Some participants declared the IPAQ sitting question too difficult to answer.

Conclusion
The accuracy of older adults' self-reported sitting time is questionable given the challenges they have in answering sitting-time questions. Their responses to sitting-time questions may be more accurate if our recommendations for clarifying the sitting domains, providing examples relevant to older adults and suggesting strategies for formulating responses are incorporated. Future quantitative studies should include objective criterion measures to assess validity and reliability of these questions.
Modification of the loops in the ligand-binding site turns avidin into a steroid-binding protein
Authors: Riihimäki Tiina A , Hiltunen Soili , Rangl Martina , Nordlund Henri R , Määttä Juha AE , Ebner Andreas , Hinterdorfer Peter , Kulomaa Markku S , Takkinen Kristiina , Hytönen Vesa P 
Published: June 2011

Abstract

Background
Engineered proteins, with non-immunoglobulin scaffolds, have become an important alternative to antibodies in many biotechnical and therapeutic applications. When compared to antibodies, tailored proteins may provide advantageous properties such as a smaller size or a more stable structure.

Results
Avidin is a widely used protein in biomedicine and biotechnology. To tailor the binding properties of avidin, we have designed a sequence-randomized avidin library with mutagenesis focused at the loop area of the binding site. Selection from the generated library led to the isolation of a steroid-binding avidin mutant (sbAvd-1) showing micromolar affinity towards testosterone (Kd ~ 9 μM). Furthermore, a gene library based on the sbAvd-1 gene was created by randomizing the loop area between β-strands 3 and 4. Phage display selection from this library led to the isolation of a steroid-binding protein with significantly decreased biotin binding affinity compared to sbAvd-1. Importantly, differential scanning calorimetry and analytical gel-filtration revealed that the high stability and the tetrameric structure were preserved in these engineered avidins.

Conclusions
The high stability and structural properties of avidin make it an attractive molecule for the engineering of novel receptors. This methodology may allow the use of avidin as a universal scaffold in the development of novel receptors for small molecules.
Lack of effect of apolipoprotein C3 polymorphisms on indices of liver steatosis, lipid profile and insulin resistance in obese Southern Europeans
Authors: Sentinelli Federica , Romeo Stefano , Maglio Cristina , Incani Michela , Burza Maria A , Scano Francesca , Coccia Federica , Cossu Efisio , Leonetti Frida , Baroni Marco G 
Published: June 2011

Abstract

Background
Apolipoprotein C3 (APOC3) is a component of triglyceride-rich lipoproteins, and APOC3 rs2854116 and rs2854117 polymorphisms have been associated with non-alcoholic fatty liver disease, hypertriglyceridaemia, and insulin-resistance.

Objective
To determine if the APOC3 variants alter the susceptibility of obese subjects to develop liver damage, hypertrigliceridaemia, and insulin-resistance.

Methods
The study was carried out on 585 unrelated obese Italians (median body mass index BMI = 41 kg/m2) who were genotyped for the rs2854116 and rs2854117 variants. All participants underwent oral glucose tolerance tests (OGTT), with measurement of glucose, insulin, lipid parameters. Indices of insulin-resistance (HOMA and ISI) were calculated. Alanine transaminase (ALT) and aspartate transaminase (AST) were used as markers of liver injury.

Results
The study subjects were divided into two groups: those homozygous for the wild-type alleles at both SNPs (-482C and -455T alleles) and those who were carriers of at least one variant allele or both (-482T, -455C or both). Also each SNP was analysed independently. No significant differences were found in ALT and AST levels and in the lipid profile between the two groups. Insulin concentrations, glucose tolerance and insulin sensitivity were similar in the two groups.

Conclusion
We did not identify any significant association between APOC3 polymorphisms and fatty liver disease, lipids, and insulin-resistance in obese subjects, thus not confirming the suggested role of these APOC3 gene sequence variants.