bluuebunny/crossref_metadata_2025_split huggingface dataset:
Granzyme B produced by human plasmacytoid dendritic cells suppresses T-cell expansion
Authors: Jahrsdörfer Bernd , Vollmer Angelika , Blackwell Sue E. , Maier Julia , Sontheimer Kai , Beyer Thamara , Mandel Birgit , Lunov Oleg , Tron Kyrylo , Nienhaus G. Ulrich , Simmet Thomas , Debatin Klaus-Michael , Weiner George J. , Fabricius Dorit 
Published: December 2009

AbstractHuman plasmacytoid dendritic cells (pDCs) are crucially involved in the modulation of adaptive T-cell responses in the course of neoplastic, viral, and autoimmune disorders. In several of these diseases elevated extracellular levels of the serine protease granzyme B (GrB) are observed. Here we demonstrate that human pDCs can be an abundant source of GrB and that such GrB+ pDCs potently suppress T-cell proliferation in a GrB-dependent, perforin-independent manner, a process reminiscent of regulatory T cells. Moreover, we show that GrB expression is strictly regulated on a transcriptional level involving Janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), and STAT5 and that interleukin-3 (IL-3), a cytokine secreted by activated T cells, plays a central role for GrB induction. Moreover, we find that the immunosuppressive cytokine IL-10 enhances, while Toll-like receptor agonists and CD40 ligand strongly inhibit, GrB secretion by pDCs. GrB-secreting pDCs may play a regulatory role for immune evasion of tumors, antiviral immune responses, and autoimmune processes. Our results provide novel information about the complex network of pDC–T-cell interactions and may contribute to an improvement of prophylactic and therapeutic vaccinations.
Recombinant porcine rotavirus VP4 and VP4-LTB expressed in Lactobacillus casei induced mucosal and systemic antibody responses in mice
Authors: Qiao Xinyuan , Li Guiwei , Wang Xiangqing , Li Xiaojing , Liu Min , Li Yijing 
Published: December 2009

AbstractBackgroundPorcine rotavirus infection is a significant cause of morbidity and mortality in the swine industry necessitating the development of effective vaccines for the prevention of infection. Immune responses associated with protection are primarily mucosal in nature and induction of mucosal immunity is important for preventing porcine rotavirus infection.ResultsLactobacillus caseiexpressing the major protective antigen VP4 of porcine rotavirus (pPG612.1-VP4) or VP4-LTB (heat-labile toxin B subunit fromEcherichia coli) (pPG612.1-VP4-LTB) fusion protein was used to immunize mice orally. The expression of recombinant pPG612.1-VP4 and pPG612.1-VP4-LTB was confirmed by SDS-PAGE and Western blot analysis and surface-displayed expression onL. caseiwas verified by immunofluorescence. Mice orally immunized with recombinant protein-expressingL. caseiproduced high levels of serum immunoglobulin G (IgG) and mucosal IgA. The IgA titters from mice immunized with pPG612.1-VP4-LTB were higher than titters from pPG612.1-VP4-immunized mice. The induced antibodies demonstrated neutralizing effects on RV infection.ConclusionThese results demonstrated that VP4 administered in the context of anL. caseiexpression system is an effective method for stimulating mucosal immunity and that LTB served to further stimulate mucosal immunity suggesting that this strategy can be adapted for use in pigs.
Let the sun shine in: effects of ultraviolet radiation on invasive pneumococcal disease risk in Philadelphia, Pennsylvania
Authors: White Alexander NJ , Ng Victoria , Spain C Victor , Johnson Caroline C , Kinlin Laura M , Fisman David N 
Published: December 2009

AbstractBackgroundStreptococcus pneumoniaeis a common cause of community acquired pneumonia and bacteremia. Excess wintertime mortality related to pneumonia has been noted for over a century, but the seasonality of invasive pneumococcal disease (IPD) has been described relatively recently and is poorly understood. Improved understanding of environmental influence on disease seasonality has taken on new urgency due to global climate change.MethodsWe evaluated 602 cases of IPD reported in Philadelphia County, Pennsylvania, from 2002 to 2007. Poisson regression models incorporating seasonal smoothers were used to identify associations between weekly weather patterns and case counts. Associations between acute (day-to-day) environmental fluctuations and IPD occurrence were evaluated using a case-crossover approach. Effect modification across age and sex strata was explored, and meta-regression models were created using stratum-specific estimates for effect.ResultsIPD incidence was greatest in the wintertime, and spectral decomposition revealed a peak at 51.0 weeks, consistent with annual periodicity. After adjustment for seasonality, yearly increases in reporting, and temperature, weekly incidence was found to be associated with clear-sky UV index (IRR per unit increase in index: 0.70 [95% CI 0.54-0.91]). The effect of UV index was highest among young strata and decreased with age. At shorter time scales, only an association with increases in ambient sulphur oxides was linked to disease risk (OR for highest tertile of exposure 0.75, 95% CI 0.60 to 0.93).ConclusionWe confirmed the wintertime predominance of IPD in a major urban center. The major predictor of IPD in Philadelphia is extended periods of low UV radiation, which may explain observed wintertime seasonality. The mechanism of action of diminished light exposure on disease occurrence may be due to direct effects on pathogen survival or host immune function via altered 1,25-(OH)2-vitamin-D metabolism. These findings may suggest less diminution in future IPD risk with climate change than would be expected if wintertime seasonality was driven by temperature.
Association of vitamin D receptor polymorphisms with the risk of prostate cancer in the Han population of Southern China
Authors: Bai Yongheng , Yu Yaping , Yu Bin , Ge Jianrong , Ji Jingzhang , Lu Hong , Wei Jia , Weng Zhiliang , Tao Zhihua , Lu Jianxin 
Published: December 2009

AbstractBackgroundMolecular epidemiological studies have shown that gene polymorphisms of vitamin D receptor (VDR) are associated with prostate cancer risks. However, previous results from many molecular studies remain inconsistent.MethodsBlood samples were collected from 122 prostate cancer patients and 130 age-matched control subjects in the Han population of Southern China. The differences ofVDRgene polymorphism between cancer cases and controls were determined by PCR-RFLP, examimingFokI (exon 2),BsmI,Tru9I,ApaI (intron 9), andTaqI (exon 9). Associations between theVDRgene polymorphism and prostate cancer risk were calculated in an unconditional logistic regression model. Linkage disequilibrium and haplotypes were analyzed with the SHEsis software.ResultsOf five polymorphisms,BsmI was shown to associate with prostate cancer, whileFokI,Tru9I,ApaI, andTaqI did not show any significant association. After adjustment for age, theBsmI 'B' allele was associated with an almost 1/3-fold risk (OR = 0.35, 95%CI: 0.15-0.80) of the occurrence of prostate cancer, a 1/5-fold risk (OR = 0.20, 95%CI: 0.06-0.68) of poorly differentiated prostate cancer, and a 1/10-fold risk (OR = 0.10, 95%CI: 0.01-0.78) of aggressive prostate cancer compared with the 'b' allele, especially among older men (>71 years). In addition, haplotype analysis revealed that the'F-b-U-A-T' was more frequent found in cases than in controls (3.4%vs0.0%,P= 0.0035), while the frequency of haplotype 'F-B-U-a-T' was 0.8% in cases, significantly lower than in controls (3.9%,P= 0.019).ConclusionOur experiments provide evidences that genetic polymorphisms in theVDRgene may be potential risk factors for prostate cancer in the Han population of southern China and the susceptibility to prostate cancer is associated with ethnicity and geographic location.
Power of multifactor dimensionality reduction and penalized logistic regression for detecting gene-gene Interaction in a case-control study
Authors: He Hua , Oetting William S , Brott Marcia J , Basu Saonli 
Published: December 2009

AbstractBackgroundThere is a growing awareness that interaction between multiple genes play an important role in the risk of common, complex multi-factorial diseases. Many common diseases are affected by certain genotype combinations (associated with some genes and their interactions). The identification and characterization of these susceptibility genes and gene-gene interaction have been limited by small sample size and large number of potential interactions between genes. Several methods have been proposed to detect gene-gene interaction in a case control study. The penalized logistic regression (PLR), a variant of logistic regression withL2regularization, is a parametric approach to detect gene-gene interaction. On the other hand, the Multifactor Dimensionality Reduction (MDR) is a nonparametric and genetic model-free approach to detect genotype combinations associated with disease risk.MethodsWe compared the power of MDR and PLR for detecting two-way and three-way interactions in a case-control study through extensive simulations. We generated several interaction models with different magnitudes of interaction effect. For each model, we simulated 100 datasets, each with 200 cases and 200 controls and 20 SNPs. We considered a wide variety of models such as models with just main effects, models with only interaction effects or models with both main and interaction effects. We also compared the performance of MDR and PLR to detect gene-gene interaction associated with acute rejection(AR) in kidney transplant patients.ResultsIn this paper, we have studied the power of MDR and PLR for detecting gene-gene interaction in a case-control study through extensive simulation. We have compared their performances for different two-way and three-way interaction models. We have studied the effect of different allele frequencies on these methods. We have also implemented their performance on a real dataset. As expected, none of these methods were consistently better for all data scenarios, but, generally MDR outperformed PLR for more complex models. The ROC analysis on the real dataset suggests that MDR outperforms PLR in detecting gene-gene interaction on the real dataset.ConclusionAs one might expect, the relative success of each method is context dependent. This study demonstrates the strengths and weaknesses of the methods to detect gene-gene interaction.
Fat free mass and obesity in relation to educational level
Authors: Seppänen-Nuijten Elina , Lahti-Koski Marjaana , Männistö Satu , Knekt Paul , Rissanen Harri , Aromaa Arpo , Heliövaara Markku 
Published: December 2009

Abstract

Background
The aim of the study was to describe the body composition of Finnish adults, especially by education, and to investigate whether fat-free mass (FFM) can explain educational gradients relating to body mass index (BMI) and waist-to-hip ratio (WHR).

Methods
Data for this cross-sectional study were based on data collected in 2000-2001 for the Health 2000 Survey. Of the nationally representative sample of 8,028 Finnish men and women aged 30 years and older, 6,300 (78.5%) were included in the study. Body composition measurements were carried out in the health examination, where FFM was assessed with eight-polar bioelectrical impedance analysis. Questions on education were included in the health interview.

Results
The mean FFM varied by education in older (≥ 65 y.) men only. In the middle-aged group (30-64 y.), highly educated men were less likely to belong to the lowest quintile of FFM (OR 0.67, 95%CI 0.48-0.93) compared with the least educated subjects. The level of education was inversely associated with the prevalence of high BMI and WHR in middle-aged men. In women, the respective associations were found both in middle-aged women and their older counterparts. Adjustment for FFM slightly strengthened the associations of education with BMI and WHR.

Conclusions
The association between education and FFM is weak. Educational gradients of high BMI and high WHR cannot be explained by FFM.
Temporal development and collapse of an Arctic plant-pollinator network
Authors: Pradal Clementine , Olesen Jens M , Wiuf Carsten 
Published: December 2009

Abstract

Background
The temporal dynamics and formation of plant-pollinator networks are difficult to study as it requires detailed observations of how the networks change over time. Understanding the temporal dynamics might provide insight into sustainability and robustness of the networks and how they react to environmental changes, such as global warming. Here we study an Arctic plant-pollinator network in two consecutive years using a simple mathematical model and describe the temporal dynamics (daily assembly and disassembly of links) by random mechanisms.

Results
We develop a mathematical model with parameters governed by the probabilities for entering, leaving and making connections in the network and demonstrate that A. The dynamics is described by very similar parameters in both years despite a strong turnover in the composition of the pollinator community and different climate conditions, B. There is a drastic change in the temporal behaviour a few days before the end of the season in both years. This change leads to the collapse of the network and does not correlate with weather parameters, C. We estimate that the number of available pollinator species is about 80 species of which 75-80% are observed in each year, D. The network does not reach an equilibrium state (as defined by our model) before the collapse set in and the season is over.

Conclusion
We have shown that the temporal dynamics of an Arctic plant-pollinator network can be described by a simple mathematical model and that the model allows us to draw biologically interesting conclusions. Our model makes it possible to investigate how the network topology changes with changes in parameter values and might provide means to study the effect of climate on plant-pollinator networks.
Bioavailability of ibuprofen following oral administration of standard ibuprofen, sodium ibuprofen or ibuprofen acid incorporating poloxamer in healthy volunteers
Authors: Dewland Peter M , Reader Sandie , Berry Phillip 
Published: December 2009

Abstract

Background
The aim of this study was to compare the pharmacokinetic properties of sodium ibuprofen and ibuprofen acid incorporating poloxamer with standard ibuprofen acid tablets.

Methods
Twenty-two healthy volunteers were enrolled into this randomised, single-dose, 3-way crossover, open-label, single-centre, pharmacokinetic study. After 14 hours' fasting, participants received a single dose of 2 × 200 mg ibuprofen acid tablets (standard ibuprofen), 2 × 256 mg ibuprofen sodium dihydrate tablets (sodium ibuprofen; each equivalent to 200 mg ibuprofen acid) and 2 × 200 mg ibuprofen acid incorporating 60 mg poloxamer 407 (ibuprofen/poloxamer). A washout period of 2-7 days separated consecutive dosing days. On each of the 3 treatment days, blood samples were collected post dose for pharmacokinetic analyses and any adverse events recorded. Plasma concentration of ibuprofen was assessed using a liquid chromatographic-mass spectrometry procedure in negative ion mode. A standard statistical ANOVA model, appropriate for bioequivalence studies, was used and ratios of 90% confidence intervals (CIs) were calculated.

Results
Tmax for sodium ibuprofen was less than half that of standard ibuprofen (median 35 min vs 90 min, respectively; P = 0.0002) and Cmax was significantly higher (41.47 μg/mL vs 31.88 μg/mL; ratio test/reference = 130.06%, 90% CI 118.86-142.32%). Ibuprofen/poloxamer was bioequivalent to the standard ibuprofen formulation, despite its Tmax being on average 20 minutes shorter than standard ibuprofen (median 75 mins vs 90 mins, respectively; P = 0.1913), as the ratio of test/reference = 110.48% (CI 100.96-120.89%), which fell within the 80-125% limit of the CPMP and FDA guidelines for bioequivalence. The overall extent of absorption was similar for the three formulations, which were all well tolerated.

Conclusion
In terms of Tmax, ibuprofen formulated as a sodium salt was absorbed twice as quickly as from standard ibuprofen acid. The addition of poloxamer to ibuprofen acid did not significantly affect absorption.
Access and care issues in urban urgent care clinic patients
Authors: Scott David R , Batal Holly A , Majeres Sharon , Adams Jill C , Dale Rita , Mehler Philip S 
Published: December 2009

Abstract

Background
Although primary care should be the cornerstone of medical practice, inappropriate use of urgent care for non-urgent patients is a growing problem that has significant economic and healthcare consequences. The characteristics of patients who choose the urgent care setting, as well as the reasoning behind their decisions, is not well established. The purpose of this study was to determine the motivation behind, and characteristics of, adult patients who choose to access health care in our urgent care clinic. The relevance of understanding the motivation driving this patient population is especially pertinent given recent trends towards universal healthcare and the unclear impact it may have on the demands of urgent care.

Methods
We conducted a cross-sectional survey of patients seeking care at an urgent care clinic (UCC) within a large acute care safety-net urban hospital over a six-week period. Survey data included demographics, social and economic information, reasons that patients chose a UCC, previous primary care exposure, reasons for delaying care, and preventive care needs.

Results
A total of 1, 006 patients were randomly surveyed. Twenty-five percent of patients identified Spanish as their preferred language. Fifty-four percent of patients reported choosing the UCC due to not having to make an appointment, 51.2% because it was convenient, 43.9% because of same day test results, 42.7% because of ability to get same-day medications and 15.1% because co-payment was not mandatory. Lack of a regular physician was reported by 67.9% of patients and 57.2% lacked a regular source of care. Patients reported delaying access to care for a variety of reasons.

Conclusion
Despite a common belief that patients seek care in the urgent care setting primarily for economic reasons, this study suggests that patients choose the urgent care setting based largely on convenience and more timely care. This information is especially applicable to the potential increase in urgent care volume in a universal healthcare system. Additionally, this study adds to the body of literature supporting the important role of timely primary care in healthcare maintenance.
Profound human/mouse differences in alpha-dystrobrevin isoforms: a novel syntrophin-binding site and promoter missing in mouse and rat
Authors: Böhm Sabrina V , Constantinou Panayiotis , Tan Sipin , Jin Hong , Roberts Roland G 
Published: December 2009

Abstract

Background

The dystrophin glycoprotein complex is disrupted in Duchenne muscular dystrophy and many other neuromuscular diseases. The principal heterodimeric partner of dystrophin at the heart of the dystrophin glycoprotein complex in the main clinically affected tissues (skeletal muscle, heart and brain) is its distant relative, α-dystrobrevin. The α-dystrobrevin gene is subject to complex transcriptional and post-transcriptional regulation, generating a substantial range of isoforms by alternative promoter use, alternative polyadenylation and alternative splicing. The choice of isoform is understood, amongst other things, to determine the stoichiometry of syntrophins (and their ligands) in the dystrophin glycoprotein complex.

Results

We show here that, contrary to the literature, most α-dystrobrevin genes, including that of humans, encode three distinct syntrophin-binding sites, rather than two, resulting in a greatly enhanced isoform repertoire. We compare in detail the quantitative tissue-specific expression pattern of human and mouse α-dystrobrevin isoforms, and show that two major gene features (the novel syntrophin-binding site-encoding exon and the internal promoter and first exon of brain-specific isoforms α-dystrobrevin-4 and -5) are present in most mammals but specifically ablated in mouse and rat.

Conclusion

Lineage-specific mutations in the murids mean that the mouse brain has fewer than half of the α-dystrobrevin isoforms found in the human brain. Our finding that there are likely to be fundamental functional differences between the α-dystrobrevins (and therefore the dystrophin glycoprotein complexes) of mice and humans raises questions about the current use of the mouse as the principal model animal for studying Duchenne muscular dystrophy and other related disorders, especially the neurological aspects thereof.
Impact of environmental inputs on reverse-engineering approach to network structures
Authors: Wu Jianhua , Sinfield James L , Buchanan-Wollaston Vicky , Feng Jianfeng 
Published: December 2009

Abstract

Background
Uncovering complex network structures from a biological system is one of the main topic in system biology. The network structures can be inferred by the dynamical Bayesian network or Granger causality, but neither techniques have seriously taken into account the impact of environmental inputs.

Results
With considerations of natural rhythmic dynamics of biological data, we propose a system biology approach to reveal the impact of environmental inputs on network structures. We first represent the environmental inputs by a harmonic oscillator and combine them with Granger causality to identify environmental inputs and then uncover the causal network structures. We also generalize it to multiple harmonic oscillators to represent various exogenous influences. This system approach is extensively tested with toy models and successfully applied to a real biological network of microarray data of the flowering genes of the model plant Arabidopsis Thaliana. The aim is to identify those genes that are directly affected by the presence of the sunlight and uncover the interactive network structures associating with flowering metabolism.

Conclusion
We demonstrate that environmental inputs are crucial for correctly inferring network structures. Harmonic causal method is proved to be a powerful technique to detect environment inputs and uncover network structures, especially when the biological data exhibit periodic oscillations.