bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased expression of the androgen receptor with p300 and interleukin-6 coactivators compensate for oligonucleotide suppression of bcl-2: no increased CREB binding protein or interleukin-4 expression
Authors: Rubenstein Marvin , Hollowell Courtney M.P. , Guinan Patrick 
Published: November 2012

Background: Antisense oligonucleotides (oligos) have been employed against in vivo and in vitro prostate cancer models targeting growth regulatory proteins. While most oligos have targeted growth factors or their receptors, others have been directed against inhibitors of apoptosis and mediators of androgen action. We previously evaluated a set of oligos which targeted and comparably suppressed the expression of the apoptosis inhibitor protein bcl-2. LNCaP cells adapted to this restoration of apoptosis with suppression of caspase 3 (an apoptosis promoter) and an enhanced expression of the androgen receptor (AR), suggesting an increased sensitivity to androgens. Methods and results: In a continuation of this study, we evaluated the expression of AR coactivators p300, its homolog CREB binding protein (CREBBP) and cytokines interleukin (IL)-4 and IL-6, finding p300 and IL-6 similarly enhanced. Conclusions: LNCaP cells are hormone sensitive and untreated cells express minimal p300 activity. Therefore, the enhanced expression which followed oligo treatment makes its induction more impressive and implies a pattern of gene expression more associated with later stage (androgen insensitive) disease. This suggests that oligo treatment directed against bcl-2 can be evaded through compensatory changes in AR expression and some coactivators, promoting tumor growth, and may promote transformation of the tumor to a more aggressive phenotype.
Age and height dependence of lung clearance index and functional residual capacity
Authors: Lum Sooky , Stocks Janet , Stanojevic Sanja , Wade Angie , Robinson Paul , Gustafsson Per , Brown Meghan , Aurora Paul , Subbarao Padmaja , Hoo Ah-fong , Sonnappa Samatha 
Published: November 2012

The lung clearance index (LCI) is more sensitive than spirometry in detecting abnormal lung function in children with cystic fibrosis. LCI is thought to be independent of age, but recent evidence suggests that the upper limit of normal is higher in infants and preschool children than in older subjects. This study examines whether LCI remains independent of body size throughout childhood.Multiple-breath washout data from healthy children and adolescents were collated from three centres using the mass spectrometer system and the inert gas sulfur hexafluoride. Reference equations for LCI and functional residual capacity (FRC) were constructed using the LMS (lambda–mu–sigma) method.Data were available from 497 subjects (2 weeks to 19 years of age) tested on 659 occasions. LCI was dependent on body size, decreasing in a nonlinear pattern as height increased. Changes were particularly marked in the first 5 years of life. Height, age and sex were all independent predictors of FRC. Minimal between-centre differences allowed unified reference equations to be developed.LCI is not independent of body size. Although a constant upper normal limit would suffice for cross-sectional clinical assessments from 6 years of age, appropriate reference equations are essential for accurate interpretation of results during early childhood.
Resting heart rate is a predictor of mortality in COPD
Authors: Jensen Magnus Thorsten , Marott Jacob L. , Lange Peter , Vestbo Jørgen , Schnohr Peter , Nielsen Olav Wendelboe , Jensen Jan Skov , Jensen Gorm B. 
Published: November 2012

The clinical significance of high heart rate in chronic obstructive pulmonary disease (COPD) is unexplored. We investigated the association between resting heart rate, pulmonary function, and prognosis in subjects with COPD.16 696 subjects aged ≥40 years from the Copenhagen City Heart Study, a prospective study of the general population, were followed for 35.3 years, 10 986 deaths occurred. Analyses were performed using time-dependent Cox-models and net reclassification index (NRI).Resting heart rate increased with severity of COPD (p<0.001). Resting heart rate was associated with both cardiovascular and all-cause mortality across all stages of COPD (p<0.001). Within each stage of COPD, resting heart rate improved prediction of median life expectancy; the difference between <65 bpm and >85 bpm was 5.5 years without COPD, 9.8 years in mild (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I), 6.7 years in moderate (GOLD stage II) and 5.9 years in severe/very severe COPD (GOLD stage III/IV), (p<0.001). Resting heart rate significantly improved risk prediction when added to GOLD stage (categorical NRI 4.9%, p = 0.01; category less NRI 23.0%, p<0.0001) or forced expiratory volume in 1 s % predicted (categorical NRI 7.8%, p = 0.002; category less NRI 24.1%, p<0.0001).Resting heart rate increases with severity of COPD. Resting heart rate is a readily available clinical variable that improves risk prediction in patients with COPD above and beyond that of pulmonary function alone. Resting heart rate may be a potential target for intervention in COPD.
Criteria for clinical stability in hospitalised patients with community-acquired pneumonia
Authors: Aliberti Stefano , Zanaboni Anna Maria , Wiemken Tim , Nahas Ahmed , Uppatla Srinivas , Morlacchi Letizia Corinna , Peyrani Paula , Blasi Francesco , Ramirez Julio 
Published: November 2012

The American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) suggested two sets of criteria in 2001 and 2007 to define clinical stability in community-acquired pneumonia (CAP). The present study aimed to evaluate the level of agreement between these two sets of criteria and how well they can predict clinical outcomes.A retrospective cohort study was carried out of 487 consecutive patients hospitalised with CAP. Level of agreement was tested using a survival curve analysis, while prediction of outcomes at 30-day follow-up was evaluated through receiver operating characteristic (ROC) analysis.A discrepancy between ATS 2001 and ATS/IDSA 2007 criteria in identifying clinical stability was detected in 62% of the patients. The median (interquartile range) time to clinical stability was 2 (1–4) days based on ATS 2001 and 3 (2–5) days based on ATS/IDSA 2007 criteria (p = 0.012). The daily distribution of patients who reached clinical stability evaluated with both sets was different (p = 0.002). The ROC analysis showed an area under the curve of 0.705 for the ATS 2001 criteria and 0.714 for ATS/IDSA 2007 criteria (p = 0.645).ATS 2001 and ATS/IDSA 2007 criteria for clinical stability in hospitalised patients with CAP are clinically equivalent and both can be used in clinical practice as well as in clinical research.
Targeting iron uptake to controlPseudomonas aeruginosainfections in cystic fibrosis
Authors: Smith Daniel J. , Lamont Iain L. , Anderson Greg J. , Reid David W. 
Published: November 2012

The aerobic Gram-negative bacteriumPseudomonas aeruginosais an opportunistic pathogen responsible for life-threatening acute and chronic infections in humans. As part of chronic infectionP. aeruginosaforms biofilms, which shield the encased bacteria from host immune clearance and provide an impermeable and protective barrier against currently available antimicrobial agents.P. aeruginosahas an absolute requirement for iron for infection success. By influencing cell–cell communication (quorum sensing) and virulence factor expression, iron is a powerful regulator ofP. aeruginosabehaviour. Consequently, the imposed perturbation of iron acquisition systems has been proposed as a novel therapeutic approach to the treatment ofP. aeruginosabiofilm infection.In this review, we explore the influence of iron availability onP. aeruginosainfection in the lungs of the people with the autosomal recessive condition cystic fibrosis as an archetypal model of chronicP. aeruginosabiofilm infection. Novel therapeutics aimed at disruptingP. aeruginosaare discussed, with an emphasis placed on identifying the barriers that need to be overcome in order to translate these promisingin vitroagents into effective therapies in human pulmonary infections.
Reduced neonatal lung function and wheezing illnesses during the first 5 years of life
Authors: van der Gugten Anne C. , Uiterwaal Cuno S.P.M. , van Putte-Katier Nienke , Koopman Marije , Verheij Theo J.M. , van der Ent Cornelis K. 
Published: November 2012

Studies of reduced neonatal lung function and wheezing illnesses during childhood show conflicting results. The aim of our study was to assess the association between resistance (Rrs) and compliance (Crs) of the respiratory system by using the single occlusion technique (SOT) and prospectively collected wheezing illnesses during the first 5 years of life in a large birth cohort.SOT was performed during natural sleep before the age of 2 months. Information about wheezing illnesses was collected from the electronic patient file.549 infants had a successful SOT measurement and complete medical records. Every kPa·L−1·s−1increase inRrswas associated with 10% more consultations in the first 3 years of life. Every 10 mL·kPa−1increase inCrswas associated with a 14% reduction in consultations in the first 3 years of life, 27% in the fourth to fifth years of life, and a lower probability of having asthma at the age of 5 years (OR 0.66). Children with late-onset or persistent wheezing had significant lowerCrsvalues than their peers.An increased neonatal resistance is associated with more wheezing illnesses during infancy, while a reduced neonatal compliance is associated with more wheezing illnesses during the first 5 years of life, a late-onset or persistent wheezing phenotype, and asthma.
The unique architecture and function of cellulose-interacting proteins in oomycetes revealed by genomic and structural analyses
Authors: Larroque Mathieu , Barriot Roland , Bottin Arnaud , Barre Annick , Rougé Pierre , Dumas Bernard , Gaulin Elodie 
Published: November 2012

Abstract

Background
Oomycetes are fungal-like microorganisms evolutionary distinct from true fungi, belonging to the Stramenopile lineage and comprising major plant pathogens. Both oomycetes and fungi express proteins able to interact with cellulose, a major component of plant and oomycete cell walls, through the presence of carbohydrate-binding module belonging to the family 1 (CBM1). Fungal CBM1-containing proteins were implicated in cellulose degradation whereas in oomycetes, the Cellulose Binding Elicitor Lectin (CBEL), a well-characterized CBM1-protein from Phytophthora parasitica, was implicated in cell wall integrity, adhesion to cellulosic substrates and induction of plant immunity.

Results
To extend our knowledge on CBM1-containing proteins in oomycetes, we have conducted a comprehensive analysis on 60 fungi and 7 oomycetes genomes leading to the identification of 518 CBM1-containing proteins. In plant-interacting microorganisms, the larger number of CBM1-protein coding genes is expressed by necrotroph and hemibiotrophic pathogens, whereas a strong reduction of these genes is observed in symbionts and biotrophs. In fungi, more than 70% of CBM1-containing proteins correspond to enzymatic proteins in which CBM1 is associated with a catalytic unit involved in cellulose degradation. In oomycetes more than 90% of proteins are similar to CBEL in which CBM1 is associated with a non-catalytic PAN/Apple domain, known to interact with specific carbohydrates or proteins. Distinct Stramenopile genomes like diatoms and brown algae are devoid of CBM1 coding genes. A CBM1-PAN/Apple association 3D structural modeling was built allowing the identification of amino acid residues interacting with cellulose and suggesting the putative interaction of the PAN/Apple domain with another type of glucan. By Surface Plasmon Resonance experiments, we showed that CBEL binds to glycoproteins through galactose or N-acetyl-galactosamine motifs.

Conclusions
This study provides insight into the evolution and biological roles of CBM1-containing proteins from oomycetes. We show that while CBM1s from fungi and oomycetes are similar, they team up with different protein domains, either in proteins implicated in the degradation of plant cell wall components in the case of fungi or in proteins involved in adhesion to polysaccharidic substrates in the case of oomycetes. This work highlighted the unique role and evolution of CBM1 proteins in oomycete among the Stramenopile lineage.
A novel analytical method, Birth Date Selection Mapping, detects response of the Angus (Bos taurus) genome to selection on complex traits
Authors: Decker Jared E , Vasco Daniel A , McKay Stephanie D , McClure Matthew C , Rolf Megan M , Kim JaeWoo , Northcutt Sally L , Bauck Stewart , Woodward Brent W , Schnabel Robert D , Taylor Jeremy F 
Published: November 2012

AbstractBackgroundSeveral methods have recently been developed to identify regions of the genome that have been exposed to strong selection. However, recent theoretical and empirical work suggests that polygenic models are required to identify the genomic regions that are more moderately responding to ongoing selection on complex traits. We examine the effects of multi-trait selection on the genome of a population of US registered Angus beef cattle born over a 50-year period representing approximately 10 generations of selection. We present results from the application of a quantitative genetic model, called Birth Date Selection Mapping, to identify signatures of recent ongoing selection.ResultsWe show that US Angus cattle have been systematically selected to alter their mean additive genetic merit for most of the 16 production traits routinely recorded by breeders. Using Birth Date Selection Mapping, we estimate the time-dependency of allele frequency for 44,817 SNP loci using genomic best linear unbiased prediction, generalized least squares, and BayesCπ analyses. Finally, we reconstruct the primary phenotypes that have historically been exposed to selection from a genome-wide analysis of the 16 production traits and gene ontology enrichment analysis.ConclusionsWe demonstrate that Birth Date Selection Mapping utilizing mixed models corrects for time-dependent pedigree sampling effects that lead to spurious SNP associations and reveals genomic signatures of ongoing selection on complex traits. Because multiple traits have historically been selected in concert and most quantitative trait loci have small effects, selection has incrementally altered allele frequencies throughout the genome. Two quantitative trait loci of large effect were not the most strongly selected of the loci due to their antagonistic pleiotropic effects on strongly selected phenotypes. Birth Date Selection Mapping may readily be extended to temporally-stratified human or model organism populations.
Disability and schizophrenia: a systematic review of experienced psychosocial difficulties
Authors: Świtaj Piotr , Anczewska Marta , Chrostek Anna , Sabariego Carla , Cieza Alarcos , Bickenbach Jerome , Chatterji Somnath 
Published: November 2012

Abstract

Background
Schizophrenia is a significantly disabling disease that affects all major areas of life. There is a lack of comprehensive synthesis of research findings on the full extent of psychosocial difficulties (PSDs) experienced by people living with schizophrenia. This paper provides a systematic review of the literature concerning PSDs and their associated factors in schizophrenia. PSDs were conceptualized in accordance with the International Classification of Functioning, Disability and Health (ICF) as disabilities, in particular impairments of mental functions, activity limitations and participation restrictions.

Methods
An electronic search using MEDLINE and PsychINFO plus a manual search of the literature was performed for qualitative and longitudinal studies published in English between 2005 and 2010 that examined PSDs in persons with schizophrenia. The ICF was used as a conceptual framework.

Results
A total of 104 papers were included. The most frequent PSDs addressed in the literature were not specific ones, directly linkable to the ICF categories of mental functions, activity limitations or participation restrictions, but broad areas of psychosocial functioning, such as psychopathological symptoms (53% of papers) or global disability and functioning (37%). Among mental functions, the most extensively studied were cognitive functions (27%) and emotional functions (27%). Within the domain of activities and participation, the most widely investigated were difficulties in relationships with others (31%) and employment (20%). Of the factors associated with the intensity or course of PSDs, the most commonly identified were treatment modalities (56%), psychopathological symptoms (26%), and socio-demographic variables (24%). Medication tended to improve the most relevant PSD, but at the same time was the only consistently reported determinant of onset of PSDs (emerging as unwanted side-effects).

Conclusions
The present review illustrates the remarkably broad scope and diversity of psychosocial areas affected in schizophrenia and shows how these areas are interconnected and how they interact with contextual factors. The need for a shift in focus of schizophrenia research is suggested – from an excessive reliance on global measures of psychopathology and disability for defining outcomes to the creation of profiles of specific PSDs that have a more direct bearing on the disabling experience and real-world functioning of patients and can serve to guide interventions and monitoring over time.
Potential of primary kidney cells for somatic cell nuclear transfer mediated transgenesis in pig
Authors: Richter Anne , Kurome Mayuko , Kessler Barbara , Zakhartchenko Valeri , Klymiuk Nikolai , Nagashima Hiroshi , Wolf Eckhard , Wuensch Annegret 
Published: November 2012

Abstract

Background
Somatic cell nuclear transfer (SCNT) is currently the most efficient and precise method to generate genetically tailored pig models for biomedical research. However, the efficiency of this approach is crucially dependent on the source of nuclear donor cells. In this study, we evaluate the potential of primary porcine kidney cells (PKCs) as cell source for SCNT, including their proliferation capacity, transfection efficiency, and capacity to support full term development of SCNT embryos after additive gene transfer or homologous recombination.

Results
PKCs could be maintained in culture with stable karyotype for up to 71 passages, whereas porcine fetal fibroblasts (PFFs) and porcine ear fibroblasts (PEFs) could be hardly passaged more than 20 times. Compared with PFFs and PEFs, PKCs exhibited a higher proliferation rate and resulted in a 2-fold higher blastocyst rate after SCNT and in vitro cultivation. Among the four transfection methods tested with a GFP expression plasmid, best results were obtained with the NucleofectorTM technology, resulting in transfection efficiencies of 70% to 89% with high fluorescence intensity, low cytotoxicity, good cell proliferation, and almost no morphological signs of cell stress. Usage of genetically modified PKCs in SCNT resulted in approximately 150 piglets carrying at least one of 18 different transgenes. Several of those pigs originated from PKCs that underwent homologous recombination and antibiotic selection before SCNT.

Conclusion
The high proliferation capacity of PKCs facilitates the introduction of precise and complex genetic modifications in vitro. PKCs are thus a valuable cell source for the generation of porcine biomedical models by SCNT.
Novel antiviral activity of baicalein against dengue virus
Authors: Zandi Keivan , Teoh Boon-Teong , Sam Sing-Sin , Wong Pooi-Fong , Mustafa Mohd Rais , AbuBakar Sazaly 
Published: November 2012

AbstractBackgroundDengue is a serious arboviral disease currently with no effective antiviral therapy or approved vaccine available. Therefore, finding the effective compound against dengue virus (DENV) replication is very important. Among the natural compounds, bioflavonoids derived mainly from plants are of interest because of their biological and medicinal benefits.MethodsIn the present study, antiviral activity of a bioflavonoid, baicalein, was evaluated against different stages of dengue virus type 2 (DENV-2) replication in Vero cells using focus forming unit reduction assay and quantitative RT-PCR.ResultsBaicalein inhibited DENV-2 replication in Vero cells with IC50= 6.46 μg/mL and SI= 17.8 when added after adsorption to the cells. The IC50against DENV-2 was 5.39 μg/mL and SI= 21.3 when cells were treated 5 hours before virus infection and continuously up to 4 days post infection. Baicalein exhibited direct virucidal effect against DENV-2 with IC50= 1.55 μg/mL and showed anti-adsorption effect with IC50= 7.14 μg/mL.ConclusionsFindings presented here suggest that baicalein exerts potent antiviral activity against DENV. Baicalein possesses direct virucidal activity against DENV besides its effects against dengue virus adsorption and intracellular replication of DENV-2. Baicalein, hence, should be considered forin vivoevaluation in the development of an effective antiviral compound against DENV.
Cost-effectiveness of new pneumococcal conjugate vaccines in Turkey: a decision analytical model
Authors: Bakır Mustafa , Türel Özden , Topachevskyi Oleksandr 
Published: November 2012

AbstractBackgroundStreptococcus pneumoniaeinfections, which place a considerable burden on healthcare resources, can be reduced in a cost-effective manner using a 7-valent pneumococcal conjugate vaccine (PCV-7). We compare the cost effectiveness of a 13-valent PCV (PCV-13) and a 10-valent pneumococcal non-typeableHaemophilus influenzaeprotein D conjugate vaccine (PHiD-CV) with that of PCV-7 in Turkey.MethodsA cost-utility analysis was conducted and a decision analytical model was used to estimate the proportion of the Turkish population <10 years old that would experience 10 mutually exclusive outcomes over the course of 1 year from a perspective of a healthcare system. Model outcomes were adjusted according to the population demographics and region-specific serotype distribution in Turkey. Health outcomes and direct healthcare costs were simulated for PCV-7, PCV-13 and PHiD-CV.ResultsPCV-13 and PHiD-CV are projected to have a substantial impact on pneumococcal disease in Turkey versus PCV-7, with 2,223 and 3,156 quality-adjusted life years (QALYs) and 2,146 and 2,081 life years, respectively, being saved under a 3+1 schedule. Projections of direct medical costs showed that a PHiD-CV vaccination programme would provide the greatest cost savings, offering additional savings of US$11,718,813 versus PCV-7 and US$8,235,010 versus PCV-13. Probabilistic sensitivity analysis showed that PHiD-CV dominated PCV-13 in terms of QALYs gained and cost savings in 58.3% of simulations.ConclusionUnder the modeled conditions, PHiD-CV would provide the most cost-effective intervention for reducing pneumococcal disease in Turkish children.