bluuebunny/crossref_metadata_2025_split huggingface dataset:
Procaterol Upregulates Peroxisome Proliferator-Activated Receptor-γ Expression in Human Eosinophils
Authors: Ueki Shigeharu , Usami Atsuko , Oyamada Hajime , Saito Norihiro , Chiba Takahito , Mahemuti Gulixian , Ito Wataru , Kato Hikari , Kayaba Hiroyuki , Chihara Junichi 
Published: June 2006

Peroxisome proliferator-activated receptor-γ (PPARγ) is a nuclear receptor that regulates immune reaction. We have previously demonstrated that human eosinophils express PPARγ and that stimulation with a synthetic agonist for PPARγ attenuated the factor-induced eosinophil activations. However, the modulator of PPARγ expression in eosinophils has not yet been studied. In this study, we investigated the effect of procaterol, the synthetic β<sub>2</sub>-adrenoceptor agonist widely used as bronchodilators in asthma, on the PPARγ expression in eosinophils. Purified human peripheral blood eosinophil and the eosinophilic cell line EoL-1 were cultured with procaterol. This was followed by PPARγ measurement using flow cytometer and quantitative real-time RT-PCR. We observed that PPARγ was constitutively expressed by EoL-1 and the purified eosinophils and that the therapeutic concentration (10<sup>–9</sup><i>M</i>) of procaterol markedly enhanced PPARγ protein expression, which was reversed by the selective β<sub>2</sub>-adrenoceptor antagonist ICI-118551. The PPARγ mRNA expression in EoL-1 and eosinophils was also induced by procaterol. These findings suggest that procaterol could modulate the eosinophil function by increasing the expression of PPARγ.
Consistent Effects of Genes Involved in Reverse Cholesterol Transport on Plasma Lipid and Apolipoprotein Levels in CARDIA Participants
Authors: Klos Kathy L.E. , Sing Charles F. , Boerwinkle Eric , Hamon Sara C. , Rea Thomas J. , Clark Andrew , Fornage Myriam , Hixson James E. 
Published: June 2006

Objective—To identify common variations in genes in the reverse cholesterol transport pathway with nongender-specific influence on plasma lipid and apolipoprotein levels.Methods and Results—An average of 5 single nucleotide polymorphisms (SNPs) were genotyped within each of 45 genomic regions (54 genes) in blacks (1131 females and 812 males) and whites (1102 females and 954 males) from the Coronary Artery Risk Development in Young Adults (CARDIA) study. SNPs and gene-based 3-SNP haplotypes were evaluated for their ability to predict variation in plasma apolipoproteins (apo) A-I and apoB, total cholesterol (TC), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides (TG). We identified 14 SNPs in 6 candidate gene regions that explained statistically significant variation in the same trait in both genders of at least one race and with evidence of consistent genotype mean trend across gender within race. Haplotype analyses identified 9 candidate gene regions that explained statistically significant variation in one or both races.Conclusion—Four gene regions,ABCA1, APOA1/C3/A4/A5, APOE/C1/C4/C2, andCETP, explained plasma lipoprotein variation most consistently across strata. Other gene regions that influence plasma lipid and apolipoprotein levels within race includeCYP7A1,LPL, PPARA, SOAT1, andSREBF2.
Simultaneous activation of multiple signal transduction pathways confers poor prognosis in acute myelogenous leukemia
Authors: Kornblau Steven M. , Womble Matthew , Qiu Yi Hua , Jackson C. Ellen , Chen Wenjing , Konopleva Marina , Estey Elihu H. , Andreeff Michael 
Published: June 2006

AbstractDeregulation of signal transduction pathways (STPs) may promote leukemogenesis by conferring cell proliferation and survival advantages in acute myelogenous leukemia (AML). Several agents targeting STPs are under development; however, redundancy and cross-talk between STPs could activate multiple downstream effectors and this could negate the effect of single-target inhibition. The frequency of concurrent activation of multiple STPs in AML and the prognostic relevance of STP activation in AML are unknown. STP protein expression (PKCα, ERK2, pERK2, AKT, and pAKT) was measured by Western blot in samples from 188 patients with newly diagnosed, untreated AML. In univariate and multivariate analysis high levels of PKCα, ERK, pERK, and pAKT, but not AKT, were adverse factors for survival as was the combination variable PKCα-ERK2&pERK2-pAKT. Survival progressively decreased as the number of activated pathways increased. Patients were more likely to have none or all 3 pathways activated than was predicted based on the frequency of individual pathway activation, strongly suggesting that cross-activation occurred. Simultaneous activation of multiple STPs is common in AML and has a progressively worse adverse effect on prognosis. It is thus likely that only combinations of agents that target the multiply activated STPs will be beneficial for patients with AML.
Patterns of MADS-box gene expression mark flower-type development in Gerbera hybrida(Asteraceae)
Authors: Laitinen Roosa AE , Broholm Suvi , Albert Victor A , Teeri Teemu H , Elomaa Paula 
Published: June 2006

Abstract

Background
The inflorescence of the cut-flower crop Gerbera hybrida (Asteraceae) consists of two principal flower types, ray and disc, which form a tightly packed head, or capitulum. Despite great interest in plant morphological evolution and the tractability of the gerbera system, very little is known regarding genetic mechanisms involved in flower type specification. Here, we provide comparative staging of ray and disc flower development and microarray screening for differentially expressed genes, accomplished via microdissection of hundreds of coordinately developing flower primordia.

Results
Using a 9K gerbera cDNA microarray we identified a number of genes with putative specificity to individual flower types. Intrestingly, several of these encode homologs of MADS-box transcription factors otherwise known to regulate flower organ development. From these and previously obtained data, we hypothesize the functions and protein-protein interactions of several gerbera MADS-box factors.

Conclusion
Our RNA expression results suggest that flower-type specific MADS protein complexes may play a central role in differential development of ray and disc flowers across the gerbera capitulum, and that some commonality is shared with known protein functions in floral organ determination. These findings support the intriguing conjecture that the gerbera flowering head is more than a mere floral analog at the level of gene regulation.
Identification of multi-drug resistant Pseudomonas aeruginosa clinical isolates that are highly disruptive to the intestinal epithelial barrier
Authors: Zaborina Olga , Kohler Jonathan E , Wang Yingmin , Bethel Cindy , Shevchenko Olga , Wu Licheng , Turner Jerrold R , Alverdy John C 
Published: June 2006

Abstract

Background
Multi-drug resistant Pseudomonas aeruginosa nosocomial infections are increasingly recognized worldwide. In this study, we focused on the virulence of multi-drug resistant clinical strains P. aeruginosa against the intestinal epithelial barrier, since P. aeruginosa can cause lethal sepsis from within the intestinal tract of critically ill and immuno-compromised patients via mechanisms involving disruption of epithelial barrier function.

Methods
We screened consecutively isolated multi-drug resistant P. aeruginosa clinical strains for their ability to disrupt the integrity of human cultured intestinal epithelial cells (Caco-2) and correlated these finding to related virulence phenotypes such as adhesiveness, motility, biofilm formation, and cytotoxicity.

Results
Results demonstrated that the majority of the multi-drug resistant P. aeruginosa clinical strains were attenuated in their ability to disrupt the barrier function of cultured intestinal epithelial cells. Three distinct genotypes were found that displayed an extreme epithelial barrier-disrupting phenotype. These strains were characterized and found to harbor the exoU gene and to display high swimming motility and adhesiveness.

Conclusion
These data suggest that detailed phenotypic analysis of the behavior of multi-drug resistant P. aeruginosa against the intestinal epithelium has the potential to identify strains most likely to place patients at risk for lethal gut-derived sepsis. Surveillance of colonizing strains of P. aeruginosa in critically ill patients beyond antibiotic sensitivity is warranted.
Interactions between Nef and AIP1 proliferate multivesicular bodies and facilitate egress of HIV-1
Authors: Costa Luciana J , Chen Nan , Lopes Adriana , Aguiar Renato S , Tanuri Amilcar , Plemenitas Ana , Peterlin B Matija 
Published: June 2006

Abstract

Background
Nef is an accessory protein of primate lentiviruses, HIV-1, HIV-2 and SIV. Besides removing CD4 and MHC class I from the surface and activating cellular signaling cascades, Nef also binds GagPol during late stages of the viral replicative cycle. In this report, we investigated further the ability of Nef to facilitate the replication of HIV-1.

Results
To this end, first the release of new viral particles was much lower in the absence of Nef in a T cell line. Since the same results were obtained in the absence of the viral envelope using pseudo-typed viruses, this phenomenon was independent of CD4 and enhanced infectivity. Next, we found that Nef not only possesses a consensus motif for but also binds AIP1 in vitro and in vivo. AIP1 is the critical intermediate in the formation of multivesicular bodies (MVBs), which play an important role in the budding and release of viruses from infected cells. Indeed, Nef proliferated MVBs in cells, but only when its AIP1-binding site was intact. Finally, these functions of Nef were reproduced in primary macrophages, where the wild type but not mutant Nef proteins led to increased release of new viral particles from infected cells.

Conclusion
We conclude that by binding GagPol and AIP1, Nef not only proliferates MVBs but also contributes to the egress of viral particles from infected cells.
CHARITY: Cha gas car diomyopathy bi soprolol int ervention study: a randomized double-blind placebo force-titration controlled study with Bisoprolol in patients with chronic heart failure secondary to Chagas cardiomyopathy [NCT00323973]
Authors: Quiros Franklin R , Morillo Carlos A , Casas Juan P , Cubillos Luz A , Silva Federico A 
Published: June 2006

AbstractBackgroundChagas' disease is the major cause of disability secondary to tropical diseases in young adults from Latin America, and around 20 million people are currently infected byT. cruzi. Heart failure due to Chagas cardiomyopathy is the main clinical presenation in Colombia. Heart failure due to Chagas' disease may respond to digoxin, diuretics and vasodilator therapy. Beta-adrenoreceptor antagonism seems to protect against the increased risk of cardiac arrhythmia and sudden death due to chronic sympathetic stimulation. The aim of this study is to evaluate the effects of the selective beta-adrenergic receptor blocker Bisoprolol on cardiovascular mortality, hospital readmission due to progressive heart failure and functional status in patients with heart failure secondary to Chagas' cardiomyopathy.Methods/designA cohort of 500T. cruziseropositive patients (250 per arm) will be selected from several institutions in Colombia. During the pretreatment period an initial evaluation visit will be scheduled in which participants will sign consent forms and baseline measurements and tests will be conducted including blood pressure measurements, twelve-lead ECG and left ventricular ejection fraction assessment by 2D echocardiography. Quality of life questionnaire will be performed two weeks apart during baseline examination using the "Minnesota living with heart failure" questionnaire. A minimum of two 6 minutes corridor walk test once a week over a two-week period will be performed to measure functional class. During the treatment period patients will be randomly assigned to receive Bisoprolol or placebo, initially taking a total daily dose of 2.5 mgrs qd. The dose will be increased every two weeks to 5, 7.5 and 10 mgrs qd (maximum maintenance dose). Follow-up assessment will include clinical check-up, and blood collection for future measurements of inflammatory reactants and markers. Quality of life measurements will be obtained at six months. This study will allow us to explore the effect of beta-blockers in chagas' cardiomyopathy.
The effect of open lung ventilation on right ventricular and left ventricular function in lung-lavaged pigs
Authors: Reis Miranda Dinis , Klompe Lennart , Cademartiri Filippo , Haitsma Jack J , Palumbo Alessandro , Takkenberg Johanna JM , Lachmann Burkhard , Bogers Ad JJC , Gommers Diederik 
Published: June 2006

Abstract
Introduction
Ventilation according to the open lung concept (OLC) consists of recruitment maneuvers, followed by low tidal volume and high positive end-expiratory pressure, aiming at minimizing atelectasis. The minimization of atelectasis reduces the right ventricular (RV) afterload, but the increased intrathoracic pressures used by OLC ventilation could increase the RV afterload. We hypothesize that when atelectasis is minimized by OLC ventilation, cardiac function is not affected despite the higher mean airway pressure.

Methods
After repeated lung lavage, each pig (n = 10) was conventionally ventilated and was ventilated according to OLC in a randomized cross-over setting. Conventional mechanical ventilation (CMV) consisted of volume-controlled ventilation with 5 cmH2O positive end-expiratory pressure and a tidal volume of 8–10 ml/kg. No recruitment maneuvers were performed. During OLC ventilation, recruitment maneuvers were applied until PaO2/FiO2 > 60 kPa. The peak inspiratory pressure was set to obtain a tidal volume of 6–8 ml/kg. The cardiac output (CO), the RV preload, the contractility and the afterload were measured with a volumetric pulmonary artery catheter. A high-resolution computed tomography scan measured the whole lung density and left ventricular (LV) volumes.

Results
The RV end-systolic pressure–volume relationship, representing RV afterload, during steady-state OLC ventilation (2.7 ± 1.2 mmHg/ml) was not significantly different compared with CMV (3.6 ± 2.5 mmHg/ml). Pulmonary vascular resistance (OLC, 137 ± 49 dynes/s/cm5 versus CMV, 130 ± 34 dynes/s/cm5) was comparable between groups. OLC led to a significantly lower amount of atelectasis (13 ± 2% of the lung area) compared with CMV (52 ± 3% of the lung area). Atelectasis was not correlated with pulmonary vascular resistance or end-systolic pressure–volume relationship.
The LV contractility and afterload during OLC was not significantly different compared with CMV. Compared with baseline, the LV end-diastolic volume (66 ± 4 ml) decreased significantly during OLC (56 ± 5 ml) ventilation and not during CMV (61 ± 3 ml). Also, CO was significantly lower during OLC ventilation (OLC, 4.1 ± 0.3 l/minute versus CMV, 4.9 ± 0.3 l/minute).

Conclusion
In this experimental study, OLC resulted in significantly improved lung aeration. Despite the use of elevated airway pressures, no evidence was found for a negative effect of OLC on RV afterload or LV afterload, which might be associated with a loss of hypoxic pulmonary vasoconstriction due to alveolar recruitment. The reductions in the CO and in the mean pulmonary artery pressure were consequences of a reduced preload.
Slow, stochastic transgene repression with properties of a timer
Authors: Wang Clifford L , Yang Desirée C , Wabl Matthias 
Published: June 2006

Abstract
Background
When gene expression varies unpredictably between genetically identical organisms, this is sometimes ascribed as stochastic. With the prevalence of retroviral vectors, stochastic repression is often observed and can complicate the interpretation of outcomes. But it may also faithfully reflect characteristics of sites in the genome.

Results
We created and identified several cell clones in which, within a given cell, retroviral transcription of a transgene was repressed heritably and essentially irreversibly. This repression was relatively slow; total repression in all cells took months. We observed the dynamics of repression and found that they were ergodic, that is, tending with a probability to a final state independent of previous conditions. Different positions of the transgene in the genome demonstrated different dynamics. At a position on mouse chromosome 9, repression abided by near perfect first-order kinetics and was highly reproducible, even under conditions where the number of cell generations per day varied.

Conclusion
We propose that such a cell division independent 'off' mechanism could play a role in endogenous gene expression, potentially providing an epigenetically based timer for extended periods.
Effective elasticity of rocks with closely spaced and intersecting cracks
Authors: Grechka Vladimir , Kachanov Mark 
Published: June 2006

The noninteraction approximation (NIA) is the simplest effective media theory that describes the overall elasticity of fractured rocks. If the NIA is used for fracture characterization, its accuracy and the range of applicability must be estimated. We do it by performing a series of 3D finite element simulations of effective elasticity for models that contain several sets of fractures embedded in otherwise isotropic host rock. We intentionally place the cracks close to each other to create strong interactions in their local stress fields. In addition, we allow the cracks to intersect in such a way that they do not break a rock specimen apart. Perhaps surprisingly, we find that fracture interactions and intersections have little influence on the effective elasticity, and the NIA performs well in all cases. While it has a tendency to slightly underestimate the effective stiffnesses, the incurred errors are small; their typical magnitudes are just a few percent in the entire range of the crack densities expected in naturally fractured formations. In our view, this makes the noninteraction approximation the method of choice for fracture characterization.
Progesterone Receptors (PR)-B and -A Regulate Transcription by Different Mechanisms: AF-3 Exerts Regulatory Control over Coactivator Binding to PR-B
Authors: Tung Lin , Abdel-Hafiz Hany , Shen Tianjie , Harvell Djuana M. E. , Nitao Lisa K. , Richer Jennifer K. , Sartorius Carol A. , Takimoto Glenn S. , Horwitz Kathryn B. 
Published: June 2006

AbstractThe two, nearly identical, isoforms of human progesterone receptors (PR), PR-B and -A, share activation functions (AF) 1 and 2, yet they possess markedly different transcriptional profiles, with PR-B being much stronger transactivators. Their differences map to a unique AF3 in the B-upstream segment (BUS), at the far N terminus of PR-B, which is missing in PR-A. Combined mutation of two LXXLL motifs plus tryptophan 140 in BUS, to yield PR-BdL140, completely destroys PR-B activity, because strong AF3 synergism with downstream AF1 and AF2 is eliminated. This synergism involves cooperative interactions among receptor multimers bound at tandem hormone response elements and is transferable to AFs of other nuclear receptors. Other PR-B functions—N-/C-terminal interactions, steroid receptor coactivator-1 coactivation, ligand-dependent down-regulation—also require an intact BUS. All three are autonomous in PR-A, and map to N-terminal regions common to both PR. This suggests that the N-terminal structure adopted by the two PR is different, and that for PR-B, this is controlled by BUS. Indeed, gene expression profiling of breast cancer cells stably expressing PR-B, PR-BdL140, or PR-A shows that mutation of AF3 destroys PR-B-dependent gene transcription without converting PR-B into PR-A. In sum, AF3 in BUS plays a critical modulatory role in PR-B, and in doing so, defines a mechanism for PR-B function that is fundamentally distinct from that of PR-A.
TGF-β1, TGF-β2, and TGF-β3 Exhibit Distinct Patterns of Expression During Cranial Suture Formation and Obliteration In Vivo and In Vitro
Authors: Opperman Lynne A. , Nolen Amber A. , Ogle Roy C. 
Published: June 2006

Abstract
Cranial sutures function as bone growth centers while themselves remaining unossified. Rat frontonasal sutures become obliterated by neonatal day 21 (N21), while coronal sutures do not fuse over the life of the animal. Coronal sutures induced to undergo osseous obliteration in vitro after removal of the dura mater were found to require soluble, heparin-binding factors present in dura mater to resist osseous obliteration. Transforming growth factor β1 (TGF-β1), β2, and β3, heparin-binding factors known to regulate bone cell proliferation and differentiation, were considered likely candidates. The presence and distribution of these factors in calvarial tissues both in vivo and in vitro were established by immunohistochemical analysis, while reverse transcription followed by polymerase chain reaction (RT/PCR) was employed to determine the presence of transcripts for these factors in mRNA isolated from microdissected dura mater. Results indicated that the presence of TGF-β1 and TGF-β2 were associated with developing coronal and frontonasal sutures, and that the continued presence of these factors was associated with osseous obliteration of the frontonasal suture. However, increased TGF-β3 immunoreactivity was associated with the coronal suture remaining unossified. RT/PCR demonstrated the presence of transcripts for TGF-β1, β2, and β3 in dural tissues isolated from rat calvaria. These data support the notion of a role for TGF-βs in regulating cranial suture morphogenesis and establish the in vitro model as a valid system for examining mechanisms by which growth factors regulate both suture morphogenesis and bone growth at the suture site.