bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of CXCR4, VLA-1, LFA-3 and transducer of ERB in G-CSF-mobilised progenitor cells in acute myocardial infarction
Authors: Pogatsa-Murray Gisela , Wedel Jasper von , Steppich Birgit , Schömig Albert , Kastrati Adnan , Stein Andreas , Zohlnhöfer Dietlind , Ott Ilka 
Published: January 2010

SummaryG-CSF induced mobilisation of progenitor cells is a multistep processes involving chemokines, growth factors, matrix-degrading enzymes, and cell adhesive interactions mediated by specific receptors on haematopoietic cells. This study’s aim was to investigate progenitor cells mobilised during myocardial infarction after treatment with granulocyte-stimulating factor (G-CSF). In the randomised, double-blind, placebo-controlled REVIVAL-2 study, 114 patients with acute myocardial infarction were included. Five days after successful percutaneous coronary intervention patients received either 10 μg/kg G-CSF (n=56) or placebo (n=58) subcutaneously for five days. Venous blood samples were analysed on day(s) 1, 3, 5 and 7 after therapy, and progenitor cell mobilisation and surface expression of VLA-4, LFA-1 and CXCR-4 was measured on circulating progenitor cells using flow cytometry. G-CSF induced a significant increase in circulating progenitor cells (72 ± 20 cells/μl vs. 4.5 ± 0.8 cells/μl, p<0.05). Surface expression of LFA-1, VLA-4 and CXCR4 on progenitor cells was decreased by 44%, 49% and 60% after G-CSF as compared to placebo (p<0.05). In accordance, mRNA expression of CXCR4 was reduced. Moreover, anti-proliferative transducer of ERB (TOB) mRNA was decreased, suggesting an increased proliferative potential of the mobilised progenitor cells. Decreased expression of adhesion and chemokine receptors on G-CSF mobilised progenitor cells in acute myocardial infarction may alter the homing capacity of circulating cells to the myocardium.
The Detection of Weekly Preferential Occurrences with an Application to Rainfall
Authors: Marani Marco 
Published: January 2010

Abstract
The detection of weekly preferential occurrences in atmospheric and hydrologic processes has recently attracted much attention as a way to identify the signature of anthropogenic climatic changes. The interpretation of previous analyses, however, is not unequivocal, in part as a result of a lack of widely accepted statistical criteria. Here, a general and exact method to detect the presence of weekly preferential occurrences is developed and applied to long rainfall observations in Marghera, Italy; Philadelphia, Pennsylvania; and Portland, Maine. The method makes use of the fact that, under the null hypothesis of stationarity, the process of event occurrence in the different days of the week is equivalent to the random distribution of a number of balls (the wet days) in a set of boxes (the days of the week). The departure from a homogeneous distribution is then characterized through the probability of the maximum number of balls in a box, which can be computed exactly with no ad hoc assumptions. The new method shows that (i) preferential rainfall weekly occurrences emerge in all cases in the most recent period analyzed (1990–2006), while they are absent—or are too weak to be detected—in previous years (before 1989); and (ii) the balls-in-boxes approach appears to be more sensitive than Pearson’s test when deviations from homogeneity are associated with just one day of the week, a common occurrence in connection with day-of-the-week effects. The results presented help to reconcile previous contrasting studies and to contribute compelling evidence that anthropogenic changes in the local climate have occurred over the past century in urban and industrial areas.
A web-based clinical trial management system for a sham-controlled multicenter clinical trial in depression
Authors: Durkalski Valerie , Wenle Zhao  , Dillon Catherine , Kim Jaemyung 
Published: January 2010

Background Clinical trial investigators and sponsors invest vast amounts of resources and energy into conducting trials and often face daily challenges with data management, project management, and data quality control. Rather than waiting months for study progress reports, investigators need the ability to use real-time data for the coordination and management of study activities across all study team members including site investigators, oversight committees, data and safety monitoring boards, and medical safety monitors. Web-based data management systems are beginning to meet this need but what distinguishes one system from the other are user needs/requirements and cost. Purpose To illustrate the development and implementation of a web-based data and project management system for a multicenter clinical trial designed to test the superiority of repeated transcranial magnetic stimulation versus sham for the treatment of patients with major depression. Methods The authors discuss the reasons for not using a commercially available system for this study and describe the approach to developing their own web-based system for the OPT-TMS study. Timelines, effort, system architecture, and lessons learned are shared with the hope that this information will direct clinical trial researchers and software developers towards more efficient, user-friendly systems. Results The developers use a combination of generic and custom application code to allow for the flexibility to adapt the system to the needs of the study. Features of the system include: central participant registration and randomization; secure data entry at the site; participant progress/study calendar; safety data reporting; device accounting; monitor verification; and user-configurable generic reports and built-in customized reports. Limitations Hard coding was more time-efficient to address project-specific issues compared with the effort of creating a generic code application. As a consequence of this strategy, the required maintenance of the system is increased and the value of using this system for other trials is reduced. Conclusion Web-based central computerized systems offer time-saving, secure options for managing clinical trial data. The choice of a commercially available system or an internally developed system is determined by the requirements of the study and users. Pros and cons to both approaches were discussed. If the intention is to use the system for various trials (single and multi-center, phases I—III) across various therapeutic areas, then the overall design should be a generic structure that simplifies the general application with minimal loss of functionality.
Histidine-rich glycoprotein is a novel plasma pattern recognition molecule that recruits IgG to facilitate necrotic cell clearance via FcγRI on phagocytes
Authors: Poon Ivan K. H. , Hulett Mark D. , Parish Christopher R. 
Published: January 2010

AbstractUnder normal physiologic conditions, necrotic cells resulting from tissue injury are rapidly removed from the circulation and tissues by phagocytes, thus preventing the exposure of intracellular antigenic and immunostimulatory molecules that can aid the development of autoimmune disease. Histidine-rich glycoprotein (HRG), a relatively abundant plasma glycoprotein, has a multidomain structure that can interact with many ligands including components of the fibrinolytic and immune systems. Recently, it has been reported that HRG can bind strongly to cytoplasmic ligand(s) exposed in necrotic cells to enhance clearance by phagocytes. Here we describe the molecular mechanisms underpinning this process. A complex consisting of both HRG and immunoglobulin G (IgG) was found as necessary to aid necrotic cell uptake by monocytes, predominantly via an FcγRI-dependent mechanism. The findings in this study also show that HRG can potentially interact with anionic phospholipids exposed in necrotic cells. Furthermore, the enhanced phagocytosis of necrotic cells induced by HRG-IgG complexes triggers phagocytes to release proinflammatory cytokines such as interleukin-8 and tumor necrosis factor. Thus, HRG has the unique property of complexing with IgG and facilitating a proinflammatory innate immune response to promote the clearance of necrotic cells.
Genetic variations in the heparanase gene (HPSE) associate with increased risk of GVHD following allogeneic stem cell transplantation: effect of discrepancy between recipients and donors
Authors: Ostrovsky Olga , Shimoni Avichai , Rand Avital , Vlodavsky Israel , Nagler Arnon 
Published: January 2010

Abstract
Graft-versus-host disease (GVHD) is the most common cause of nonrelapse mortality and morbidity after hematopoietic stem cell transplantation (HSCT). The well-documented involvement of heparanase in the process of inflammation and autoimmunity led us to investigate an association between HPSE gene single-nucleotide polymorphisms (SNPs) and the risk of GVHD. The present study indicates a highly significant correlation of HPSE gene SNPs rs4693608 and rs4364254 and their combination with the risk of developing acute GVHD. Moreover, the study revealed that discrepancy between recipient and donor in these SNPs may elevate significantly the risk of acute GVHD. This association was statistically significant when the recipients possessed genotype combinations dictating higher levels of heparanase compared with their human leukocyte antigen (HLA)–matched donors. In addition, HPSE gene SNPs disclosed a correlation with extensive chronic GVHD, nonrelapse mortality, and overall survival. Our study indicates involvement of heparanase in the development of acute and extensive chronic GVHD. Moreover, it suggests a possible mechanism for the aggressive behavior of T lymphocytes leading to GVHD when the recipients possess genotype combinations that dictate high levels of heparanase mRNA compared with their HLA-matched donors expressing low levels of heparanase.
13q14 deletions in CLL involve cooperating tumor suppressors
Authors: Palamarchuk Alexey , Efanov Alexey , Nazaryan Natalya , Santanam Urmila , Alder Hansjuerg , Rassenti Laura , Kipps Thomas , Croce Carlo M. , Pekarsky Yuri 
Published: January 2010

AbstractB-cell chronic lymphocytic leukemia (CLL) is the most common human leukemia. 13q14 deletions are most common chromosomal alterations in CLL. We previously reported that miR-15/16 is a target of 13q14 deletions and plays a tumor suppressor role by targeting BCL2. Because DLEU7 is located near miR-15/16 and is also positioned within a minimal deleted region, we investigated whether DLEU7 could also play a tumor suppressor role. Recent studies of transgenic mouse models demonstrated the importance of the nuclear factor-κB (NF-κB) pathway in CLL. To examine the possible role of DLEU7 in CLL, we investigated the effect of DLEU7 expression on NF-κB and nuclear factor of activated T cells (NFAT) activity. We found that DLEU7 functions as a potent NF-κB and NFAT inhibitor by physically interacting and inhibiting TACI and BCMA, members of the tumor necrosis factor (TNF) receptor family involved in B-CLL. In addition, DLEU7 expression in A549 lung cancer cells resulted in a decrease in S phase and increased apoptosis. The results suggest that loss of DLEU7 may cooperate with the loss of miR-15/16 in the pathogenesis of CLL.
Active learning for human protein-protein interaction prediction
Authors: Mohamed Thahir P , Carbonell Jaime G , Ganapathiraju Madhavi K 
Published: January 2010

Abstract

Background
Biological processes in cells are carried out by means of protein-protein interactions. Determining whether a pair of proteins interacts by wet-lab experiments is resource-intensive; only about 38,000 interactions, out of a few hundred thousand expected interactions, are known today. Active machine learning can guide the selection of pairs of proteins for future experimental characterization in order to accelerate accurate prediction of the human protein interactome.

Results
Random forest (RF) has previously been shown to be effective for predicting protein-protein interactions. Here, four different active learning algorithms have been devised for selection of protein pairs to be used to train the RF. With labels of as few as 500 protein-pairs selected using any of the four active learning methods described here, the classifier achieved a higher F-score (harmonic mean of Precision and Recall) than with 3000 randomly chosen protein-pairs. F-score of predicted interactions is shown to increase by about 15% with active learning in comparison to that with random selection of data.

Conclusion
Active learning algorithms enable learning more accurate classifiers with much lesser labelled data and prove to be useful in applications where manual annotation of data is formidable. Active learning techniques demonstrated here can also be applied to other proteomics applications such as protein structure prediction and classification.
Elevated endogenous expression of the dominant negative basic helix-loop-helix protein ID1 correlates with significant centrosome abnormalities in human tumor cells
Authors: Manthey Carolin , Mern Demissew S , Gutmann Anja , Zielinski Anne J , Herz Corinna , Lassmann Silke , Hasskarl Jens 
Published: January 2010

Abstract

Background
ID proteins are dominant negative inhibitors of basic helix-loop-helix transcription factors that have multiple functions during development and cellular differentiation. Ectopic (over-)expression of ID1 extends the lifespan of primary human epithelial cells. High expression levels of ID1 have been detected in multiple human malignancies, and in some have been correlated with unfavorable clinical prognosis. ID1 protein is localized at the centrosomes and forced (over-)expression of ID1 results in errors during centrosome duplication.

Results
Here we analyzed the steady state expression levels of the four ID-proteins in 18 tumor cell lines and assessed the number of centrosome abnormalities. While expression of ID1, ID2, and ID3 was detected, we failed to detect protein expression of ID4. Expression of ID1 correlated with increased supernumerary centrosomes in most cell lines analyzed.

Conclusions
This is the first report that shows that not only ectopic expression in tissue culture but endogenous levels of ID1 modulate centrosome numbers. Thus, our findings support the hypothesis that ID1 interferes with centrosome homeostasis, most likely contributing to genomic instability and associated tumor aggressiveness.
Regulation of endocytic trafficking of transferrin receptor by optineurin and its impairment by a glaucoma-associated mutant
Authors: Nagabhushana Ananthamurthy , Chalasani Madhavi L , Jain Nishant , Radha Vegesna , Rangaraj Nandini , Balasubramanian Dorairajan , Swarup Ghanshyam 
Published: January 2010

Abstract

Background
Optineurin is a multifunctional protein involved in several functions such as vesicular trafficking from the Golgi to the plasma membrane, NF-κB regulation, signal transduction and gene expression. Mutations in optineurin are associated with glaucoma, a neurodegenerative eye disease that causes blindness. Genetic evidence suggests that the E50K (Glu50Lys) is a dominant disease-causing mutation of optineurin. However, functional alterations caused by mutations in optineurin are not known. Here, we have analyzed the role of optineurin in endocytic recycling and the effect of E50K mutant on this process.

Results
We show that the knockdown of optineurin impairs trafficking of transferrin receptor to the juxtanuclear region. A point mutation (D474N) in the ubiquitin-binding domain abrogates localization of optineurin to the recycling endosomes and interaction with transferrin receptor. The function of ubiquitin-binding domain of optineurin is also needed for trafficking of transferrin to the juxtanuclear region. A disease causing mutation, E50K, impairs endocytic recycling of transferrin receptor as shown by enlarged recycling endosomes, slower dynamics of E50K vesicles and decreased transferrin uptake by the E50K-expressing cells. This impaired trafficking by the E50K mutant requires the function of its ubiquitin-binding domain. Compared to wild type optineurin, the E50K optineurin shows enhanced interaction and colocalization with transferrin receptor and Rab8. The velocity of Rab8 vesicles is reduced by co-expression of the E50K mutant. These results suggest that the E50K mutant affects Rab8-mediated transferrin receptor trafficking.

Conclusions
Our results suggest that optineurin regulates endocytic trafficking of transferrin receptor to the juxtanuclear region. The E50K mutant impairs trafficking at the recycling endosomes due to altered interactions with Rab8 and transferrin receptor. These results also have implications for the pathogenesis of glaucoma caused by the E50K mutation because endocytic recycling is vital for maintaining homeostasis.
Non-consensus GLI binding sites in Hedgehog target gene regulation
Authors: Winklmayr Martina , Schmid Carmen , Laner-Plamberger Sandra , Kaser Alexandra , Aberger Fritz , Eichberger Thomas , Frischauf Anna-Maria 
Published: January 2010

Abstract

Background
The GLI transcription factors, mediators of the hedgehog signal bind with high affinity to the consensus sequence GACCACCCA. The affinity of variant single substitutions in GLI binding sites has been measured systematically, but the affinities of the variant binding sites appears low compared to the frequency of occurrence of variant sites in known GLI target gene promoters.

Results
We quantified transcriptional activation by GLI using PTCH1 promoter based luciferase reporters containing all single substitutions of the GLI consensus binding site. As expected variants with very low affinity did not activate the reporter. Many lower affinity binding sequences are, however, functional in the presence of moderate GLI concentration. Using two natural non-consensus GLI site promoters we showed that substitution of the variant sequences by consensus leads to comparable activity.

Conclusions
Variant GLI binding sites with relatively low affinity can within natural promoters lead to strong transcriptional activation. This may facilitate the identification of additional direct GLI target genes.
Differential requirement of the epidermal growth factor receptor for G protein-mediated activation of transcription factors by lysophosphatidic acid
Authors: Oyesanya Regina A , Greenbaum Susie , Dang David , Lee Zendra , Mukherjee Abir , Wu Jinhua , Dent Paul , Fang Xianjun 
Published: January 2010

AbstractBackgroundThe role of the epidermal growth factor receptor (EGFR) and other receptor tyrosine kinases (RTKs) in provoking biological actions of G protein-coupled receptors (GPCRs) has been one of the most disputed subjects in the field of GPCR signal transduction. The purpose of the current study is to identify EGFR-mediated mechanisms involved in activation of G protein cascades and the downstream transcription factors by lysophosphatidic acid (LPA).ResultsIn ovarian cancer cells highly responsive to LPA, activation of AP-1 by LPA was suppressed by inhibition of EGFR, an effect that could be reversed by co-stimulation of another receptor tyrosine kinase c-Met with hepatocyte growth factor, indicating that LPA-mediated activation of AP-1 requires activity of a RTK, not necessarily EGFR. Induction of AP-1 components by LPA lied downstream of Gi, G12/13, and Gq. Activation of the effectors of Gi, but not Gq or G12/13 was sensitive to inhibition of EGFR. In contrast, LPA stimulated another prominent transcription factor NF-κB via the Gq-PKC pathway in an EGFR-independent manner. Consistent with the importance of Gi-elicited signals in a plethora of biological processes, LPA-induced cytokine production, cell proliferation, migration and invasion require intact EGFR.ConclusionsAn RTK activity is required for activation of the AP-1 transcription factor and other Gi-dependent cellular responses to LPA. In contrast, activation of G12/13, Gq and Gq-elicited NF-κB by LPA is independent of such an input. These results provide a novel insight into the role of RTK in GPCR signal transduction and biological functions.
Physical activity correlates in young women with depressive symptoms: a qualitative study
Authors: Azar Denise , Ball Kylie , Salmon Jo , Cleland Verity J 
Published: January 2010

Abstract

Background
Young women are at high risk for developing depression and participation in physical activity may prevent or treat the disorder. However, the influences on physical activity behaviors of young women with depression are not well understood. The aim of this study was to gather in-depth information about the correlates of physical activity among young women with and without depressive symptoms.

Methods
A sample of 40 young women (aged 18-30 years), 20 with depressive symptoms (assessed using the CES-D 10) and 20 without depressive symptoms participated in one-on-one semi-structured interviews. A social-ecological framework was used, focusing on the individual, social and physical environmental influences on physical activity. Thematic analyses were performed on transcribed interview data.

Results
The results indicated several key themes that were unique to women with depressive symptoms. These women more often described negative physical activity experiences during their youth, more barriers to physical activity, participating in more spontaneous than planned activity, lower self-efficacy for physical activity and being influenced by their friends' and family's inactivity.

Conclusions
Interventions designed to promote physical activity in this important target group should consider strategies to reduce/overcome early life negative experiences, engage support from family and friends and plan for activity in advance.
Genetic and clinical peculiarities in a new family with hereditary hypophosphatemic rickets with hypercalciuria: a case report
Authors: Mejia-Gaviria Natalia , Gil-Peña Helena , Coto Eliecer , Pérez-Menéndez Teresa M , Santos Fernando 
Published: January 2010

Abstract
Hereditary hypophosphatemic rickets with hypercalciuria is a rare autosomal recessive disorder (OMIM #241530), characterized by decreased renal phosphate reabsorption that leads to hypophosphatemia, rickets, and bone pain; hypophosphatemia is believed to stimulate 1,25 dihydroxyvitamin D synthesis which, in turn, results in hypercalciuria. Hereditary hypophosphatemic rickets with hypercalciuria is caused by loss-of-function in the type 2c sodium phosphate cotransporter encoded by the SLC34A3 gene. This report shows a family with a non-previously identified mutation in the SLC34A3 gene and exhibiting mild and different manifestations of HHRH. The probandus had hypophosphatemia, elevated serum 1,25 dihydroxyvitamin D concentrations, high serum alkaline phosphatase levels, hypercalciuria and nephrocalcinosis. The other members of the family presented some of these alterations: the mother, hypercalciuria and high 1,25 dihydroxyvitamin D concentrations; the son, hypercalciuria, high 1,25 dihydroxyvitamin D values and elevated alkaline phosphatases; the father, high alkaline phosphatases. The genetic analysis revealed the existence of a single mutation (G78R) in heterozygosis in the SLC34A3 gene in the probandus, her mother and her brother, but not in the father. These findings suggest that he mutation in heterozygosis likely gave rise to a mild phenotype with different penetrance in the three relatives and also indicates that the elevation of 1,25 dihydroxyvitamin D does not result from hypophosphatemia. Thus, this family raises some issues on the transmission and pathophysiology of hereditary hypophosphatemic rickets with hypercalciuria.