bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokine-mediated increases in fetal hemoglobin are associated with globin gene histone modification and transcription factor reprogramming
Authors: Sripichai Orapan , Kiefer Christine M. , Bhanu Natarajan V. , Tanno Toshihiko , Noh Seung-Jae , Goh Sung-Ho , Russell J. Eric , Rognerud Cheryl L. , Ou Ching-Nan , Oneal Patricia A. , Meier Emily R. , Gantt Nicole M. , Byrnes Colleen , Lee Y. Terry , Dean Ann , Miller Jeffery L. 
Published: July 2009

AbstractTherapeutic regulation of globin genes is a primary goal of translational research aimed toward hemoglobinopathies. Signal transduction was used to identify chromatin modifications and transcription factor expression patterns that are associated with globin gene regulation. Histone modification and transcriptome profiling were performed using adult primary CD34+ cells cultured with cytokine combinations that produced low versus high levels of gamma-globin mRNA and fetal hemoglobin (HbF). Embryonic, fetal, and adult globin transcript and protein expression patterns were determined for comparison. Chromatin immunoprecipitation assays revealed RNA polymerase II occupancy and histone tail modifications consistent with transcriptional activation only in the high-HbF culture condition. Transcriptome profiling studies demonstrated reproducible changes in expression of nuclear transcription factors associated with high HbF. Among the 13 genes that demonstrated differential transcript levels, 8 demonstrated nuclear protein expression levels that were significantly changed by cytokine signal transduction. Five of the 8 genes are recognized regulators of erythropoiesis or globin genes (MAFF, ID2, HHEX, SOX6, and EGR1). Thus, cytokine-mediated signal transduction in adult erythroid cells causes significant changes in the pattern of globin gene and protein expression that are associated with distinct histone modifications as well as nuclear reprogramming of erythroid transcription factors.
Ethyl acetate extracts of alfalfa (Medicago sativa L.) sprouts inhibit lipopolysaccharide-induced inflammation in vitro and in vivo
Authors: Hong Yong-Han , Chao Wen-Wan , Chen Miaw-Ling , Lin Bi-Fong 
Published: July 2009

AbstractThis study aimed to investigate if food components that exert anti-inflammatory effects may be used for inflammatory disorders by examining alfalfa sprout ethyl acetate extract (ASEA). The cytokine profile and life span of BALB/c mice with acute inflammation after intra-peritoneal (ip) injection of 15 mg/kg BW lipopolysaccharide (LPS) were determined. The results showed that the life span of LPS-induced inflammatory mice were negatively correlated with serum levels of TNF-α, IL-6, and IL-1β at 9 hr after LPS-injection, which indicated that suppressing these cytokines in the late phase of inflammation may be beneficial for survival. Thein vitroexperiment then showed that ASEA significantly reduced IL-6 and IL-1β production and the NF-κB trans-activation activity of mitogen-stimulated RAW264.7 cells. To further evaluate the anti-inflammatory effects of ASEAin vivo, BALB/c mice were tube-fed with 25 mg ASEA/kg BW/day in 50 μl sunflower oil, while the control and PDTC (pyrrolidine dithiocarbamate, an anti-inflammatory agent) groups were tube-fed with 50 μl sunflower oil/day only. After one week of tube-feeding, the PDTC group was injected with 50 mg/kg BW PDTC and one hour later, all of the mice were injected with 15 mg/kg BW LPS. The results showed that the ASEA and PDTC groups had significantly lower serum TNF-α, IL-6, and IL-1β levels at 9 hr after LPS challenge, and significantly higher survival rates than the control group. This study suggests that ASEA supplementation can suppress the production of pro-inflammatory cytokines and alleviate acute inflammatory hazards.
Gene expression responses in male fathead minnows exposed to binary mixtures of an estrogen and antiestrogen
Authors: Garcia-Reyero Natàlia , Kroll Kevin J , Liu Li , Orlando Edward F , Watanabe Karen H , Sepúlveda María S , Villeneuve Daniel L , Perkins Edward J , Ankley Gerald T , Denslow Nancy D 
Published: July 2009

AbstractBackgroundAquatic organisms are continuously exposed to complex mixtures of chemicals, many of which can interfere with their endocrine system, resulting in impaired reproduction, development or survival, among others. In order to analyze the effects and mechanisms of action of estrogen/anti-estrogen mixtures, we exposed male fathead minnows (Pimephales promelas) for 48 hours via the water to 2, 5, 10, and 50 ng 17α-ethinylestradiol (EE2)/L, 100 ng ZM 189,154/L (a potent antiestrogen known to block activity of estrogen receptors) or mixtures of 5 or 50 ng EE2/L with 100 ng ZM 189,154/L. We analyzed gene expression changes in the gonad, as well as hormone and vitellogenin plasma levels.ResultsSteroidogenesis was down-regulated by EE2as reflected by the reduced plasma levels of testosterone in the exposed fish and down-regulation of genes in the steroidogenic pathway. Microarray analysis of testis of fathead minnows treated with 5 ng EE2/L or with the mixture of 5 ng EE2/L and 100 ng ZM 189,154/L indicated that some of the genes whose expression was changed by EE2were blocked by ZM 189,154, while others were either not blocked or enhanced by the mixture, generating two distinct expression patterns. Gene ontology and pathway analysis programs were used to determine categories of genes for each expression pattern.ConclusionOur results suggest that response to estrogens occurs via multiple mechanisms, including canonical binding to soluble estrogen receptors, membrane estrogen receptors, and other mechanisms that are not blocked by pure antiestrogens.
BioNetBuilder2.0: bringing systems biology to chicken and other model organisms
Authors: Konieczka Jay H , Drew Kevin , Pine Alex , Belasco Kevin , Davey Sean , Yatskievych Tatiana A , Bonneau Richard , Antin Parker B 
Published: July 2009

Abstract

Background
Systems Biology research tools, such as Cytoscape, have greatly extended the reach of genomic research. By providing platforms to integrate data with molecular interaction networks, researchers can more rapidly begin interpretation of large data sets collected for a system of interest. BioNetBuilder is an open-source client-server Cytoscape plugin that automatically integrates molecular interactions from all major public interaction databases and serves them directly to the user's Cytoscape environment. Until recently however, chicken and other eukaryotic model systems had little interaction data available.

Results
Version 2.0 of BioNetBuilder includes a redesigned synonyms resolution engine that enables transfer and integration of interactions across species; this engine translates between alternate gene names as well as between orthologs in multiple species. Additionally, BioNetBuilder is now implemented to be part of the Gaggle, thereby allowing seamless communication of interaction data to any software implementing the widely used Gaggle software. Using BioNetBuilder, we constructed a chicken interactome possessing 72,000 interactions among 8,140 genes directly in the Cytoscape environment. In this paper, we present a tutorial on how to do so and analysis of a specific use case.

Conclusion
BioNetBuilder 2.0 provides numerous user-friendly systems biology tools that were otherwise inaccessible to researchers in chicken genomics, as well as other model systems. We provide a detailed tutorial spanning all required steps in the analysis. BioNetBuilder 2.0, the tools for maintaining its data bases, standard operating procedures for creating local copies of its back-end data bases, as well as all of the Gaggle and Cytoscape codes required, are open-source and freely available at http://err.bio.nyu.edu/cytoscape/bionetbuilder/.
Synergistic effect of imp/ostA and msbA in hydrophobic drug resistance of Helicobacter pylori
Authors: Chiu Hung-Chuan , Lin Tzu-Lung , Yang Jyh-Chin , Wang Jin-Town 
Published: July 2009

Abstract

Background
Contamination of endoscopy equipment by Helicobacter pylori (H. pylori) frequently occurs after endoscopic examination of H. pylori-infected patients. In the hospital, manual pre-cleaning and soaking in glutaraldehyde is an important process to disinfect endoscopes. However, this might not be sufficient to remove H. pylori completely, and some glutaraldehyde-resistant bacteria might survive and be passed to the next patient undergoing endoscopic examination through unidentified mechanisms. We identified an Imp/OstA protein associated with glutaraldehyde resistance in a clinical strain, NTUH-C1, from our previous study. To better understand and manage the problem of glutaraldehyde resistance, we further investigated its mechanism.

Results
The minimal inhibitory concentrations (MICs) of glutaraldehyde andexpression of imp/ostA RNA in 11 clinical isolates from the National Taiwan University Hospital were determined. After glutaraldehyde treatment, RNA expression in the strains with the MICs of 4–10 μg/ml was higher than that in strains with the MICs of 1–3 μg/ml. We examined the full-genome expression of strain NTUH-S1 after glutaraldehyde treatment using a microarray and found that 40 genes were upregulated and 31 genes were downregulated. Among the upregulated genes, imp/ostA and msbA, two putative lipopolysaccharide biogenesis genes, were selected for further characterization. The sensitivity to glutaraldehyde or hydrophobic drugs increased in both of imp/ostA and msbA single mutants. The imp/ostA and msbA double mutant was also hypersensitive to these chemicals. The lipopolysaccharide contents decreased in individual imp/ostA and msbA mutants and dramatically reduced in the imp/ostA and msbA double mutant. Outer membrane permeability assay demonstrated that the imp/ostA and msbA double mutation resulted in the increase of outer membrane permeability. Ethidium bromide accumulation assay demonstrated that MsbA was involved in efflux of hydrophobic drugs.

Conclusion
The expression levels of imp/ostA and msbA were correlated with glutaraldehyde resistance in clinical isolates after glutaraldehyde treatment. Imp/OstA and MsbA play a synergistic role in hydrophobic drugs resistance and lipopolysaccharide biogenesis in H. pylori.
Intracellular Mycoplasma genitalium infection of human vaginal and cervical epithelial cells elicits distinct patterns of inflammatory cytokine secretion and provides a possible survival niche against macrophage-mediated killing
Authors: McGowin Chris L , Popov Vsevolod L , Pyles Richard B 
Published: July 2009

Abstract

Background

Mycoplasma genitalium is an emerging sexually transmitted pathogen that has been associated with significant reproductive tract inflammatory syndromes in women. In addition, the strong association between severity of M. genitalium infection and Human Immunodeficiency Virus type 1 (HIV-1) shedding from the cervix suggests that innate responses to M. genitalium may influence pathogenesis of other sexually transmitted infections. Epithelial cells (ECs) of the reproductive mucosa are the first cells contacted by sexually transmitted pathogens. Therefore, we first characterized the dynamics of intracellular and extracellular localization and resultant innate immune responses from human vaginal, ecto- and endocervical ECs to M. genitalium type strain G37 and a low-pass contemporary isolate, M2300.

Results
Both M. genitalium strains rapidly attached to vaginal and cervical ECs by 2 h post-infection (PI). By 3 h PI, M. genitalium organisms also were found in intracellular membrane-bound vacuoles of which approximately 60% were adjacent to the nucleus. Egress of M. genitalium from infected ECs into the culture supernatant was observed but, after invasion, viable intracellular titers were significantly higher than extracellular titers at 24 and 48 h PI. All of the tested cell types responded by secreting significant levels of pro-inflammatory cytokines and chemokines in a pattern consistent with recruitment and stimulation of monocytes and macrophages. Based on the elaborated cytokines, we next investigated the cellular interaction of M. genitalium with human monocyte-derived macrophages and characterized the resultant cytokine responses. Macrophages rapidly phagocytosed M. genitalium resulting in a loss of bacterial viability and a potent pro-inflammatory response that included significant secretion of IL-6 and other cytokines associated with enhanced HIV-1 replication. The macrophage-stimulating capacity of M. genitalium was independent of bacterial viability but was sensitive to heat denaturation and proteinase-K digestion suggesting that M. genitalium protein components are the predominant mediators of inflammation.

Conclusion
Collectively, the data indicated that human genital ECs were susceptible and immunologically responsive to M. genitalium infection that likely induced cellular immune responses. Although macrophage phagocytosis was an effective method for M. genitalium killing, intracellular localization within vaginal and cervical ECs may provide M. genitalium a survival niche and protection from cellular immune responses thereby facilitating the establishment and maintenance of reproductive tract infection.
Selection and validation of a set of reliable reference genes for quantitative RT-PCR studies in the brain of the Cephalopod Mollusc Octopus vulgaris
Authors: Sirakov Maria , Zarrella Ilaria , Borra Marco , Rizzo Francesca , Biffali Elio , Arnone Maria Ina , Fiorito Graziano 
Published: July 2009

Abstract

Background
Quantitative real-time polymerase chain reaction (RT-qPCR) is valuable for studying the molecular events underlying physiological and behavioral phenomena. Normalization of real-time PCR data is critical for a reliable mRNA quantification. Here we identify reference genes to be utilized in RT-qPCR experiments to normalize and monitor the expression of target genes in the brain of the cephalopod mollusc Octopus vulgaris, an invertebrate. Such an approach is novel for this taxon and of advantage in future experiments given the complexity of the behavioral repertoire of this species when compared with its relatively simple neural organization.

Results
We chose 16S, and 18S rRNA, actB, EEF1A, tubA and ubi as candidate reference genes (housekeeping genes, HKG). The expression of 16S and 18S was highly variable and did not meet the requirements of candidate HKG. The expression of the other genes was almost stable and uniform among samples. We analyzed the expression of HKG into two different set of animals using tissues taken from the central nervous system (brain parts) and mantle (here considered as control tissue) by BestKeeper, geNorm and NormFinder. We found that HKG expressions differed considerably with respect to brain area and octopus samples in an HKG-specific manner. However, when the mantle is treated as control tissue and the entire central nervous system is considered, NormFinder revealed tubA and ubi as the most suitable HKG pair. These two genes were utilized to evaluate the relative expression of the genes FoxP, creb, dat and TH in O. vulgaris.

Conclusion
We analyzed the expression profiles of some genes here identified for O. vulgaris by applying RT-qPCR analysis for the first time in cephalopods. We validated candidate reference genes and found the expression of ubi and tubA to be the most appropriate to evaluate the expression of target genes in the brain of different octopuses. Our results also underline the importance of choosing a proper normalization strategy when analyzing gene expression by qPCR taking into appropriate account the experimental setting and variability of the sample of animals (and tissues), thus providing a set of HGK which expression appears to be unaffected by the experimental factor(s).
Association between ACEgene I/D polymorphisms and hyperandrogenism in women with Polycystic Ovary Syndrome (PCOS) and controls
Authors: sun Jing , fan Haijian , Che Yena , Cao Yunxia , Wu Xiaoke , Sun Hai-xiang , Liang Fengjing , Yi Long , Wang Yong 
Published: July 2009

Abstract

Background
I/D polymorphisms of ACE are associated with the plasma ACE concentration. The ACE is associated with the angiogenesis of ovarian endothelium in vitro as well as steroidogenesis and follicular growth in cattle. Since ACE induces a high blood supply and hypersteroidogenesis in the ovary, it may be associated with polycystic ovary syndrome (PCOS) which exhibits hyperplasia, hypervascularity of the ovarian theca interna and stroma, as well as disorderd steroidogenesis. Therefore, we hypothesized that the ACE plays some roles in the human ovary. To investigate whether the ACE I/D polymorphisms are associated with the steroidogenesis disorder in PCOS and contribute to the susceptibility of PCOS in Chinese women, we designed a case-controlled association study in 582 individuals.

Methods
The ACE I/D polymorphisms were assessed in 582 reproductive-age women. Genotyping and frequency of ACE I/D polymorphisms were obtained by PCR amplification that was performed on genomic DNA isolated from blood leucocytes. Results were analyzed in respect to clinical test results.

Results
The frequencies of the D allele and the genotypic distributions (DD, ID and II) in the women with PCOS did not differ from those in controls (P = 0.458). However, there were significant differences in the concentrations of testosterone among three genotypes both in the PCOS patients and controls (P = 0.0045, P = 0.0052, respectively). Differences were also found between these groups with distinct genotypes: DD versus II and DI versus II in the PCOS patients as well as DD versus DI and DD versus II in the controls. There were significant differences in the ratio of LH/FSH among three genotypes in the patients (P = 0.01). However, there were no statistical differences in the BMI, AAM, E2 concentrations and other serum hormone concentrations among the three genotypes both in the PCOS patients and controls.

Conclusion
The ACE I/D polymorphisms were not associated with the pathogenesis of PCOS. However, the polymorphisms were associated with the steroidogenesis in the ovary. The observation indicated that the ACE I/D polymorphisms were not the key etiological factor, which in stead may be associated with the aggravated clinical manifestations of PCOS.
Dual role of macrophage migration inhibitory factor (MIF) in human breast cancer
Authors: Verjans Eva , Noetzel Erik , Bektas Nuran , Schütz Anke K , Lue Hongqi , Lennartz Birgitt , Hartmann Arndt , Dahl Edgar , Bernhagen Jürgen 
Published: July 2009

AbstractBackgroundMacrophage migration inhibitory factor (MIF) is a pleiotropic cytokine and mediator of acute and chronic inflammatory diseases. MIF is overexpressed in various tumours and has been suggested as a molecular link between chronic inflammation and cancer. MIF overexpression is observed in breast cancer but its causal role in the development of this tumour entity is unclear.MethodsMIF levels in breast cancer cell lines were determined by ELISA and Western blot. CD74 was measured by Western blot, fluorescence microscopy and flow cytometry. Cell proliferation was studied by BrdU incorporation, cell adhesion by Matrigel adhesion assay, and cell invasion by migration assay through Matrigel-coated filters using the Transwell system. MIF expression in primary human breast cancers was measured by tissue microarray and a semi-quantitative immunoreactivity score (IRS) and comparison with histopathological parameters and patient outcome data.ResultsMIF was abundantly expressed in the non-invasive breast cancer cell lines MDA-MB-468 and ZR-75-1, but not in invasive MDA-MB-231 cells, which in turn expressed higher levels of the MIF-receptor CD74. Stimulation with exogenous MIF led to a dramatic upregulation of MIF secretion (50-fold) in MDA-MB-231 cells. Autocrine MIF promoted tumour cell proliferation, as indicated by blockade of MIF or CD74 in MDA-MB-231 and MDA-MB-468, and MDA-MB-231 invasiveness was enhanced by exogenous MIF. We correlated the expression of MIF with histopathological parameters and patient outcome data, using a tissue microarray of 175 primary invasive breast cancers and 35 normal control tissues. MIF was upregulated in breast cancer versus normal tissue (median IRS = 8 versus 6). MIF expression showed positive correlations with progesterone (p = 0.006) and estrogen (p = 0.028) receptor expression, markers of a favourable prognosis and a negative correlation to tumour size (p = 0.007). In line with these data, disease-specific overall (OS) as well as recurrence-free (RFS) survival was significantly improved in breast cancer patients with abundant cytosolic MIF expression compared to MIF low expressers (5-year OS = 67% versus 50%, p = 0.0019; 5-year RFS = 52% versus 36%, p = 0.0327).ConclusionWe conclude that intracellular expression of MIF in breast cancer cells is beneficial, whereas extracellular MIF may play a pro-oncogenic role in promoting breast cancer cell-stroma interactions.
Return-to-work of sick-listed workers without an employment contract – what works?
Authors: Vermeulen Sylvia J , Tamminga Sietske J , Schellart Antonius JM , Ybema Jan Fekke , Anema Johannes R 
Published: July 2009

Abstract

Background
In the past decade flexible labour market arrangements have emerged as a significant change in the European Union labour market. Studies suggest that these new types of labour arrangements may be linked to ill health, an increased risk for work disability, and inadequate vocational rehabilitation. Therefore, the objectives of this study were: 1. to examine demographic characteristics of workers without an employment contract sick-listed for at least 13 weeks, 2. to describe the content and frequency of occupational health care (OHC) interventions for these sick-listed workers, and 3. to examine OHC interventions as possible determinants for return-to-work (RTW) of these workers.

Methods
A cohort of 1077 sick-listed workers without an employment contract were included at baseline, i.e. 13 weeks after reporting sick. Demographic variables were available at baseline. Measurement of cross-sectional data took place 4–6 months after inclusion. Primary outcome measures were: frequency of OHC interventions and RTW-rates. Measured confounding variables were: gender, age, type of worker (temporary agency worker, unemployed worker, or remaining worker without employment contract), level of education, reason for absenteeism (diagnosis), and perceived health. The association between OHC interventions and RTW was analysed with a logistic multiple regression analysis.

Results
At 7–9 months after the first day of reporting sick only 19% of the workers had (partially or completely) returned to work, and most workers perceived their health as fairly poor or poor. The most frequently reported (49%) intervention was 'the OHC professional discussed RTW'. However, the intervention 'OHC professional made and discussed a RTW action plan' was reported by only 19% of the respondents. The logistic multiple regression analysis showed a significant positive association between RTW and the interventions: 'OHC professional discussed RTW'; and 'OHC professional made and discussed a RTW action plan'. The intervention 'OHC professional referred sick-listed worker to a vocational rehabilitation agency' was significantly associated with no RTW.

Conclusion
This is the first time that characteristics of a large cohort of sick-listed workers without an employment contract were examined. An experimental or prospective study is needed to explore the causal nature of the associations found between OHC interventions and RTW.