bluuebunny/crossref_metadata_2025_split huggingface dataset:
BK channels in innate immune functions of neutrophils and macrophages
Authors: Essin Kirill , Gollasch Maik , Rolle Susanne , Weissgerber Patrick , Sausbier Matthias , Bohn Erwin , Autenrieth Ingo B. , Ruth Peter , Luft Friedrich C. , Nauseef William M. , Kettritz Ralph 
Published: December 2008

Abstract
Oxygen-dependent antimicrobial activity of human polymorphonuclear leukocytes (PMNs) relies on the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to generate oxidants. As the oxidase transfers electrons from NADPH the membrane will depolarize and concomitantly terminate oxidase activity, unless there is charge translocation to compensate. Most experimental data implicate proton channels as the effectors of this charge compensation, although large-conductance Ca2+-activated K+ (BK) channels have been suggested to be essential for normal PMN antimicrobial activity. To test this latter notion, we directly assessed the role of BK channels in phagocyte function, including the NADPH oxidase. PMNs genetically lacking BK channels (BK−/−) had normal intracellular and extracellular NADPH oxidase activity in response to both receptor-independent and phagocytic challenges. Furthermore, NADPH oxidase activity of human PMNs and macrophages was normal after treatment with BK channel inhibitors. Although BK channel inhibitors suppressed endotoxin-mediated tumor necrosis factor-α secretion by bone marrow-derived macrophages (BMDMs), BMDMs of BK−/− and wild-type mice responded identically and exhibited the same ERK, PI3K/Akt, and nuclear factor-κB activation. Based on these data, we conclude that the BK channel is not required for NADPH oxidase activity in PMNs or macrophages or for endotoxin-triggered tumor necrosis factor-α release and signal transduction BMDMs.
Relative contribution of CYP2C9 and VKORC1 genotypes and early INR response to the prediction of warfarin sensitivity during initiation of therapy
Authors: Li Chun , Schwarz Ute I. , Ritchie Marylyn D. , Roden Dan M. , Stein C. Michael , Kurnik Daniel 
Published: December 2008

Abstract
Genetic variants in CYP2C9 and VKORC1 strongly affect steady-state warfarin dose. However, these variants also affect early international normalized ratio (INR) values during warfarin initiation. We examined whether CYP2C9/VKORC1 genotypes provide information about warfarin sensitivity additional to that provided by early INR responses. In 214 patients starting warfarin with INR-guided dose adjustments, we determined whether CYP2C9 and VKORC1 genotypes were associated with early measures of warfarin sensitivity (time to INR ≥ lower limit of therapeutic range; time to INR > 4; and first stable warfarin dose) after adjusting for early (days 4-6) and week 1 (days 7-9) INR values. Early INRs were associated with all outcomes (all P < .001) and were more informative than genotypes. For time to INR more than or equal to the lower limit of therapeutic range, adding either early INRs or genotypes to a baseline model (clinical variables only) increased the goodness-of-fit (R2) from 0.05 to 0.42 and 0.19, respectively (full model, R2 = 0.46). For first stable warfarin dose, adding either early INRs or genotypes to the baseline model increased the R2 from 0.08 to 0.32 and 0.27, respectively (full model, R2 = 0.40). After inclusion of week 1 INRs, CYP2C9 (P = .08) and VKORC1 (P = .30) were not associated with stable warfarin dose. Thus, much of the information provided by CYP2C9 and VKORC1 genotypes during warfarin initiation is captured by the early INR response.
Molecular docking studies of dithionitrobenzoic acid and its related compounds to protein disulfide isomerase: computational screening of inhibitors to HIV-1 entry
Authors: Gowthaman Uthaman , Jayakanthan Mannu , Sundar Durai 
Published: December 2008

Abstract

Background
Entry of HIV-1 into human lymphoid requires activities of viral envelope glycoproteins gp120 and gp41, and two host-cell proteins, the primary receptor CD4 and a chemokine co-receptor. In addition, a third cell-surface protein called protein disulfide isomerase (PDI) is found to play a major role in HIV-1 entry. PDI is capable of mediating thio-disulfide interchange reactions and could enable the reduction of gp120 disulfide bonds, which triggers the major conformational changes in gp120 and gp41 required for virus entry. In this scenario, inhibition of HIV-1 entry can be brought about by introducing agents that can block thiol-disulfide interchange reaction of cell surface PDI. There have been studies with agents that inhibit PDI activity, but the exact mode of binding remains to be elucidated; this might provide insights to develop new drugs to target PDI. This study attempts to perceive the mode of binding of dithionitrobenzoic acid (DTNB), and its structurally related compounds on PDI enzyme.

Results
We performed molecular docking simulation with six different inhibitors (ligand), which includes DTNB, NSC695265, thionitrobenzoic acid, 2-nitro-5-thiocyanobenzoic acid, 2-nitro-5-sulfo-sulfonyl-benzoic acid and NSC517871 into the redox-active site [C37-G38-H39-C40] of the PDI enzyme and the activity was inferred by redox inhibitory models. All ligands showed favorable interactions and most of them seemed to bind to hydrophobic amino acids Ala34, Trp36, Cys37, Cys40, His39, Thr68 and Phe80. The redox inhibitory conformations were energetically and statistically favored and supported the evidence from wet laboratory experiments reported in the literature.

Conclusion
We demonstrated that in silico docking experiment can be effectively carried out to recognize the redox inhibitory models of PDI with inhibitor molecules. Interestingly we found that number of docked clusters with each ligand varies in the range of five to eight and conveys that the binding specificity of each inhibitor varies for PDI. We also identified that Cys37 of the enzyme plays an important role in hydrogen bonding with inhibitors. This residue can be considered to being an active site for anti-HIV drug design. Therefore, by inhibiting PDI, one can, not only prevent the viral entry but also circumvent the problem of viral resistance
Predicted mouse peroxisome-targeted proteins and their actual subcellular locations
Authors: Mizuno Yumi , Kurochkin Igor V , Herberth Marlis , Okazaki Yasushi , Schönbach Christian 
Published: December 2008

Abstract

Background
The import of most intraperoxisomal proteins is mediated by peroxisome targeting signals at their C-termini (PTS1) or N-terminal regions (PTS2). Both signals have been integrated in subcellular location prediction programs. However their present performance, particularly of PTS2-targeting did not seem fitting for large-scale screening of sequences.

Results
We modified an earlier reported PTS1 screening method to identify PTS2-containing mouse candidates using a combination of computational and manual annotation. For rapid confirmation of five new PTS2- and two previously identified PTS1-containing candidates we developed the new cell line CHO-perRed which stably expresses the peroxisomal marker dsRed-PTS1. Using CHO-perRed we confirmed the peroxisomal localization of PTS1-targeted candidate Zadh2. Preliminary characterization of Zadh2 expression suggested non-PPARα mediated activation. Notably, none of the PTS2 candidates located to peroxisomes.

Conclusion
In a few cases the PTS may oscillate from "silent" to "functional" depending on its surface accessibility indicating the potential for context-dependent conditional subcellular sorting. Overall, PTS2-targeting predictions are unlikely to improve without generation and integration of new experimental data from location proteomics, protein structures and quantitative Pex7 PTS2 peptide binding assays.
Filtering of false positive microRNA candidates by a clustering-based approach
Authors: Leung Wing-Sze , Lin Marie CM , Cheung David W , Yiu SM 
Published: December 2008

Abstract

Background
MicroRNAs are small non-coding RNA gene products that play diversified roles from species to species. The explosive growth of microRNA researches in recent years proves the importance of microRNAs in the biological system and it is believed that microRNAs have valuable therapeutic potentials in human diseases. Continual efforts are therefore required to locate and verify the unknown microRNAs in various genomes. As many miRNAs are found to be arranged in clusters, meaning that they are in close proximity with their neighboring miRNAs, we are interested in utilizing the concept of microRNA clustering and applying it in microRNA computational prediction.

Results
We first validate the microRNA clustering phenomenon in the human, mouse and rat genomes. There are 45.45%, 51.86% and 48.67% of the total miRNAs that are clustered in the three genomes, respectively. We then conduct sequence and secondary structure similarity analyses among clustered miRNAs, non-clustered miRNAs, neighboring sequences of clustered miRNAs and random sequences, and find that clustered miRNAs are structurally more similar to one another, and the RNAdistance score can be used to assess the structural similarity between two sequences. We therefore design a clustering-based approach which utilizes this observation to filter false positives from a list of candidates generated by a selected microRNA prediction program, and successfully raise the positive predictive value by a considerable amount ranging from 15.23% to 23.19% in the human, mouse and rat genomes, while keeping a reasonably high sensitivity.

Conclusion
Our clustering-based approach is able to increase the effectiveness of currently available microRNA prediction program by raising the positive predictive value while maintaining a high sensitivity, and hence can serve as a filtering step. We believe that it is worthwhile to carry out further experiments and tests with our approach using data from other genomes and other prediction software tools. Better results may be achieved with fine-tuning of parameters.
Analysis of chromatin boundary activity in Drosophila cells
Authors: Li Mo , Belozerov Vladimir E , Cai Haini N 
Published: December 2008

Abstract

Background
Chromatin boundaries, also known as insulators, regulate gene activity by organizing active and repressive chromatin domains and modulate enhancer-promoter interactions. However, the mechanisms of boundary action are poorly understood, in part due to our limited knowledge about insulator proteins, and a shortage of standard assays by which diverse boundaries could be compared.

Results
We report here the development of an enhancer-blocking assay for studying insulator activity in Drosophila cultured cells. We show that the activities of diverse Drosophila insulators including suHw, SF1, SF1b, Fab7 and Fab8 are supported in these cells. We further show that double stranded RNA (dsRNA)-mediated knockdown of SuHw and dCTCF factors disrupts the enhancer-blocking function of suHw and Fab8, respectively, thereby establishing the effectiveness of using RNA interference in our cell-based assay for probing insulator function.

Conclusion
The novel boundary assay provides a quantitative and efficient method for analyzing insulator mechanism and can be further exploited in genome-wide RNAi screens for insulator components. It provides a useful tool that complements the transgenic and genetic approaches for studying this important class of regulatory elements.
Granulosa cells express three inositol 1,4,5-trisphosphate receptor isoforms: cytoplasmic and nuclear Ca2+ mobilization
Authors: Díaz-Muñoz Mauricio , de la Rosa Santander Patricia , Juárez-Espinosa Anna Berenice , Arellano Rogelio O , Morales-Tlalpan Verónica 
Published: December 2008

Abstract

Background
Granulosa cells play an important endocrine role in folliculogenesis. They mobilize Ca2+ from intracellular stores by a coordinated action between 1,4,5 inositol trisphosphate and ryanodine receptors (IP3R and RyR). The aim of this study was to explore the isoforms of IP3Rs expressed in mouse C57BL/6 NHsd granulosa cells, characterizing their intranuclear localization and the relation with other Ca2+-handling proteins.

Methods
Ovarian tissue and granulosa cells were analyzed by multiphotonic and confocal microscopy to determine the intracellular presence of IP3R types 1, 2 and 3, RyR, thapsigargin-sensitive Ca2+-ATPase, and endomembranes. Cellular fractionation and Western blot assays were also used to further confirm the nuclear occurrence of the three IP3R isoforms. Free nuclear and cytosolic Ca2+ concentrations were measured using Fluo-4 AM by confocal microscopy.

Results
By using antibodies and specific fluorophores, was shown that granulosa cells endomembranes contain three isoforms of IP3R, the RyR, and the thapsigargin-sensitive Ca2+-ATPase (SERCA). Interestingly, all these proteins were also detected in the nuclear envelope and in well-defined intranuclear structures. Microsomal membranes depicted characteristic bands of the 3 types of IP3R, but also variants of lower molecular weight. Analysis of nuclear membranes and nucleoplasmic fraction confirmed the nuclear localization of the IP3R types 1, 2 and 3. We demonstrated ATP-induced Ca2+ transients in the nuclear and cytoplasmic compartments. Remarkably, the inhibitory effect on ATP-induced Ca2+ mobilization of brefeldin A was more accentuated in the cytoplasm than in the nucleus.

Conclusion
These findings provide evidence that granulosa cells, including nuclei, express the Ca2+-handling proteins that allow Ca2+ mobilization. All three IP3R were also detected in ovarian slices, including the nuclei of granulosa cells, suggesting that these cells use the three IP3R in situ to achieve their physiological responses.
Differences in physical activity and sedentary time in relation to weight in 8–9 year old children
Authors: Purslow Lisa R , Hill Claire , Saxton Jenny , Corder Kirsten , Wardle Jane 
Published: December 2008

Abstract

Background
The health benefits of physical activity for children are well established. Although objective measures of physical activity are increasingly used there is still a lack of adequate data on physical activity in children. Sex differences in physical activity have been consistently demonstrated and lower levels of physical activity in obese than non-obese children have been shown. However, differences across the whole weight spectrum have not been examined in detail. The aim of this study was to assess associations between physical activity and sedentary time across the weight spectrum in children, and to determine whether the associations differed by sex.

Methods
Participants in the current study were 176 boys and 169 girls aged 8–9 years old taking part in a longitudinal study of associations between eating behaviours, physical activity and weight gain during childhood. Height, weight and waist circumference were measured, and physical activity data were collected using an Actigraph model GT1M worn for 5 consecutive days. Associations between sex, weight and physical activity were analysed using linear regression models.

Results
Boys had higher total activity (mean difference = 119, p < 0.001) and more minutes of moderate and vigorous physical activity (MVPA) (mean difference = 25, p < 0.001) than girls. A higher percentage of boys (72%) than girls (30%) met current physical activity guidelines of 60 minutes MVPA per day. In boys, weight status significantly predicted total activity (p = 0.001) and MVPA (p = 0.001) but there were no significant associations in girls. There was no significant difference in time spent sedentary between boys and girls, and weight status did not predict sedentary time.

Conclusion
In boys, physical activity was progressively lower across the weight spectrum, but in girls physical activity was consistently low across all weight categories. Intervention is required prior to 8 years old to prevent weight-related declines in physical activity in boys and further research is required to determine at what age, if ever, weight related differences in physical activity are apparent in girls.
Excess circulating angiopoietin-2 is a strong predictor of mortality in critically ill medical patients
Authors: Kümpers Philipp , Lukasz Alexander , David Sascha , Horn Rüdiger , Hafer Carsten , Faulhaber-Walter Robert , Fliser Danilo , Haller Hermann , Kielstein Jan T 
Published: December 2008

Abstract
Introduction
The endothelial specific angiopoietin (Ang)-Tie2 ligand-receptor system has been identified as a non-redundant mediator of endothelial activation in experimental sepsis. Binding of circulating Ang-1 to the Tie2 receptor protects the vasculature from inflammation and leakage, whereas binding of Ang-2 antagonises Tie2 signalling and disrupts endothelial barrier function. Here, we examine whether circulating Ang-1 and/or Ang-2 independently predict mortality in a cohort of critically ill medical patients.

Methods
Circulating vascular endothelial growth factor (VEGF), Ang-1 and Ang-2 were prospectively measured in sera from 29 healthy controls and 43 medical ICU patients by immunoradiometric assay (IRMA) and ELISA, respectively. Survival after 30 days was the primary outcome studied.

Results
Median serum Ang-2 concentrations were increasingly higher across the following groups: healthy controls, patients without sepsis, patients with sepsis and patients with septic shock. In contrast, Ang-1 and VEGF concentrations were significantly lower in all patient groups compared with healthy controls. Ang-2 correlated with partial pressure of oxygen in arterial blood (PaO2)/fraction of inspired oxygen (FiO2), tissue hypoxia, Sequential Organ Failure Assessment (SOFA) and Physiology and Chronic Health Evaluation II (APACHE II) score. Multivariate Cox regression analyses confirmed a strong independent prognostic impact of high Ang-2 as a novel marker of 30-day survival.

Conclusions
A marked imbalance of the Ang-Tie system in favour of Ang-2 is present in critically ill medical patients. Our findings highlight the independent prognostic impact of circulating Ang-2 in critical illness. Ang-2 may be used as a readily available powerful predictor of outcome and may open new perspectives to individualise treatment in the ICU.
Tribology of the ring—bore conjunction subject to a mixed regime of lubrication
Authors: Mishra P C , Rahnejat H , King P D 
Published: December 2008

This paper provides a detailed analysis of the compression ring—bore/liner conjunction. The analysis includes ring—bore conformability and global in-plane deformation of ring fitted in situ. The analysis for fitted ring in an out-of-round bore shows very good agreement with precise measurements, using a coordinate measuring machine. The analysis also includes the lubricated conjunction under a transient regime of lubrication, taking into account combined elastohydrodynamics and asperity interactions. The transient nature of the tribological conjunction has been demonstrated, particularly the prevalent mixed/boundary regime of lubrication at the top and bottom dead centres. The analysis is applied to a high performance motorbike engine subjected to very high impact loads and engine speeds of the order of 13 000 r/min. Furthermore, the predictions of the model show good conformance to the measurements of friction reported by other research workers.
Noncovalent Z···Z (Z=O, S, Se, and Te) Interactions: How Do They Operate to Control Fine Structures of 1,8-Dichalcogene-Substituted Naphthalenes?
Authors: Hayashi Satoko , Nakanishi Waro 
Published: December 2008

Abstract
Homonuclear Z···Z (Z=O, S, Se, and Te) interactions are investigated employing naphthalene 1,8-positions in 1,8-(MeZ)2C10H6 (1a–1d: Z=O (a), S (b), Se (c), and Te (d)), 1-MeZ-8-PhZC10H6 (2a–2c), and 1,8-(PhZ)2C10H6 (3a–3d). Three types of structures are detected for 1a–3d: BB for 1a, CC for 1b, 1c, 2c, and 3d, and AB for 2a, 2b, and 3a–3c, in our definition, by X-ray crystallographic analysis, although some have already been reported. Quantum chemical calculations are performed on 1a–1d and 3c, together with model c, Me(H)Se···Se(H)Me, to elucidate how the fine structures are controlled by the interactions. AB are stabilized by the np(Z)···σ*(Z–C) 3c–4e interactions for Z=S, Se, and Te. While CC are substantially stabilized by the n(Z)···σ*(Z–C) interactions, they are well summarized as the disappearance of the nodal plane in π*(Z···Z). Factors to control the fine structures are clarified and visualized using the HOMO or HOMO−1 of model c. The energy profile of model c helps us to imagine the whole picture of the noncovalent Se···Se interactions.
C-Reactive Protein Stimulates Myeloperoxidase Release from Polymorphonuclear Cells and Monocytes: Implications for Acute Coronary Syndromes
Authors: Singh Uma , Devaraj Sridevi , Jialal Ishwarlal 
Published: December 2008

Abstract
Background: C-reactive protein (CRP), the prototypic marker of inflammation, is present in atherosclerotic plaques and appears to promote atherogenesis. Also, CRP has been localized to monocytes and tissue macrophages, which are present in the necrotic core of lesions prone to plaque rupture. Leukocyte-derived myeloperoxidase (MPO), primarily hosted in human polymorphonuclear cells (PMNs), has also been shown to be present in human atherosclerotic lesions. Because MPO and CRP concentrations are increased in acute coronary syndrome (ACS) patients and predict poor outcomes, we tested the effect of CRP on MPO release from PMNs and monocytes.
Methods: We treated human PMNs and monocytes with CRP (25 and 50 mg/L for 6 h) and measured MPO release as total mass and activity in culture supernatants. We also measured nitro-tyrosinylation (NO2-Tyr) of LDL as an indicator of biological activity of CRP-mediated MPO release. Furthermore, we explored the effect of human CRP on MPO release in the rat sterile pouch model.
Results: CRP treatment significantly increased release of MPO (both mass and activity) from human PMNs as well as monocytes (P &lt; 0.05) and caused NO2-Tyr of LDL. Human CRP injection in rats resulted in increased concentrations of MPO in pouch exudates (P &lt; 0.05), thus confirming our in vitro data.
Conclusions: CRP stimulates MPO release both in vitro and in vivo, providing further cogent data for the proinflammatory effect of CRP. These results might further support the role of CRP in ACS.
Seasonal Change in Forage Value of Rangeland Weeds in Northern Idaho
Authors: Frost Rachel A. , Wilson Linda M. , Launchbaugh Karen L. , Hovde Elayne M. 
Published: December 2008

AbstractPrescribed grazing is an effective tool for controlling some rangeland weeds. Forage quality of eight nonnative rangeland weeds common to northern Idaho was determined. Five collection sites were established for each weed species: rush skeletonweed, meadow hawkweed, houndstongue, sulfur cinquefoil, yellow starthistle, Dalmatian toadflax, hoary cress, and tansy ragwort. Plants were collected at rosette, bolt, flower, and seed set stages; dried and separated into leaves, stems, flowers, or seed; and analyzed separately for crude protein (CP), neutral detergent fiber (NDF), and mineral content (ash). As expected, plants became more fibrous as they matured because stems increased in NDF value throughout the season and the leaf : stem ratio of most weeds we examined decreased throughout the season. In general, the weeds we examined expressed only moderate fiber levels, beginning the season with NDF values near 34% in the rosette stage and becoming near 52% NDF in the seed set stage. CP values were near 25% in the rosette stage for houndstongue, rush skeletonweed, and hoary cress whereas other weeds we examined had about 15% CP in the rosette. As the season advanced, all plants lost protein content and ended the season with CP values from 5 to 8% at seed set. Ash values declined for all species as the season progressed. Our results indicate that these weeds have forage values similar to many native plants and could be reasonable forage resources for livestock. We did not examine the content of secondary compounds in these weeds that may render them unpalatable and limit their forage value.