bluuebunny/crossref_metadata_2025_split huggingface dataset:
miRNA expression in diffuse large B-cell lymphoma treated with chemoimmunotherapy
Authors: Montes-Moreno Santiago , Martinez Nerea , Sanchez-Espiridión Beatriz , Díaz Uriarte Ramon , Rodriguez Maria Elena , Saez Anabel , Montalbán Carlos , Gomez Gonzalo , Pisano David G. , García Juan Fernando , Conde Eulogio , Gonzalez-Barca Eva , Lopez Andres , Mollejo Manuela , Grande Carlos , Martinez Miguel Angel , Dunphy Cherie , Hsi Eric D. , Rocque Gabrielle B. , Chang Julie , Go Ronald S. , Visco Carlo , Xu-Monette Zijun , Young Ken H. , Piris Miguel A. 
Published: June 2011

Abstract
Diffuse large B-cell lymphoma (DLBCL) prognostication requires additional biologic markers. miRNAs may constitute markers for cancer diagnosis, outcome, or therapy response. In the present study, we analyzed the miRNA expression profile in a retrospective multicenter series of 258 DLBCL patients uniformly treated with chemoimmunotherapy. Findings were correlated with overall survival (OS) and progression-free survival (PFS). miRNA and gene-expression profiles were studied using microarrays in an initial set of 36 cases. A selection of miRNAs associated with either DLBCL molecular subtypes (GCB/ABC) or clinical outcome were studied by multiplex RT-PCR in a test group of 240 cases with available formalin-fixed, paraffin-embedded (FFPE) diagnostic samples. The samples were divided into a training set (123 patients) and used to derive miRNA-based and combined (with IPI score) Cox regression models in an independent validation series (117 patients). Our model based on miRNA expression predicts OS and PFS and improves upon the predictions based on clinical variables. Combined models with IPI score identified a high-risk group of patients with a 2-year OS and a PFS probability of < 50%. In summary, a precise miRNA signature is associated with poor clinical outcome in chemoimmunotherapy-treated DLBCL patients. This information improves upon IPI-based predictions and identifies a subgroup of candidate patients for alternative therapeutic regimens.
Irgm1 protects hematopoietic stem cells by negative regulation of IFN signaling
Authors: King Katherine Y. , Baldridge Megan T. , Weksberg David C. , Chambers Stuart M. , Lukov Georgi L. , Wu Shihua , Boles Nathan C. , Jung Sung Yun , Qin Jun , Liu Dan , Songyang Zhou , Eissa N. Tony , Taylor Gregory A. , Goodell Margaret A. 
Published: June 2011

Abstract
The IFN-inducible immunity-related p47 GTPase Irgm1 has been linked to Crohn disease as well as susceptibility to tuberculosis. Previously we demonstrated that HSC quiescence and function are aberrant in mice lacking Irgm1. To investigate the molecular basis for these defects, we conducted microarray expression profiling of Irgm1-deficient HSCs. Cell-cycle and IFN-response genes are up-regulated in Irgm1−/− HSCs, consistent with dysregulated IFN signaling. To test the hypothesis that Irgm1 normally down-regulates IFN signaling in HSCs, we generated Irgm1−/−Ifngr1−/− and Irgm1−/−Stat1−/− double-knockout animals. Strikingly, hyperproliferation, self-renewal, and autophagy defects in Irgm1−/− HSCs were normalized in double-knockout animals. These defects were also abolished in Irgm1−/−Irgm3−/− double-knockout animals, indicating that Irgm1 may regulate Irgm3 activity. Furthermore, the number of HSCs was reduced in aged Irgm1−/− animals, suggesting that negative feedback inhibition of IFN signaling by Irgm1 is necessary to prevent hyperproliferation and depletion of the stem cell compartment. Collectively, our results indicate that Irgm1 is a powerful negative regulator of IFN-dependent stimulation in HSCs, with an essential role in preserving HSC number and function. The deleterious effects of excessive IFN signaling may explain how hematologic abnormalities arise in patients with inflammatory conditions.
SUMO conjugation of STAT1 protects cells from hyperresponsiveness to IFNγ
Authors: Begitt Andreas , Droescher Mathias , Knobeloch Klaus-Peter , Vinkemeier Uwe 
Published: June 2011

AbstractThe biologic effects of IFNγ are mediated by the transcription factor STAT1. The activity of STAT1 is inhibited by small ubiquitin-like modifier (SUMO) conjugation. This occurs both directly through decreasing STAT1 tyrosine phosphorylation and indirectly by facilitating STAT1 dephosphorylation consequential to increased STAT1 solubility because of suppressed paracrystal assembly. However, the physiologic implications of SUMO conjugation have remained unclear. Here, we used fibroblasts and bone marrow–derived macrophages (BMMs) from knockin mice expressing SUMO-free STAT1 to explore the consequences of STAT1 sumoylation for IFNγ signaling. Our experiments demonstrated buffer property of paracrystals for activated STAT1, such that SUMO-mediated paracrystal dispersal profoundly reduced phosphorylation of STAT1, which affected both the activating tyrosine 701 and the transcription-enhancing serine 727. Accordingly, the curtailed STAT1 activity in the nucleus caused by SUMO conjugation resulted in diminished transcription of IFNγ-responsive genes; and increased the IFNγ concentration more than 100-fold required to trigger lipopolysaccharide-induced cytotoxicity in bone marrow–derived macrophages. These experiments identify SUMO conjugation of STAT1 as a mechanism to permanently attenuate the IFNγ sensitivity of cells, which prevents hyperresponsiveness to this cytokine and its potentially self-destructive consequences. This sets the mode of SUMO-mediated inhibition apart from the other negative STAT regulators known to date.
Neorickettsia risticii surface-exposed proteins: proteomics identification, recognition by naturally-infected horses, and strain variations
Authors: Gibson Kathryn E , Pastenkos Gabrielle , Moesta Susanne , Rikihisa Yasuko 
Published: June 2011

AbstractNeorickettsia risticiiis the Gram-negative, obligate, and intracellular bacterial pathogen responsible for Potomac horse fever (PHF): an important acute systemic disease of horses.N. risticiisurface proteins, critical for immune recognition, have not been thoroughly characterized. In this paper, we identified the 51-kDa antigen (P51) as a major surface-exposed outer membrane protein of older and contemporary strains ofN. risticiithrough mass spectrometry of streptavidin-purified biotinylated surface-labeled proteins. Western blot analysis of sera from naturally-infected horses demonstrated universal and strong recognition of recombinant P51 over otherNeorickettsiarecombinant proteins. Comparisons of amino acid sequences for predicted secondary structures of P51, as well asNeorickettsiasurface proteins 2 (Nsp2) and 3 (Nsp3) amongN. risticiistrains from horses with PHF during a 26-year period throughout the United States revealed that the majority of variations among strains were concentrated in regions predicted to be external loops of their β-barrel structures. Large insertions or deletions occurred within a tandem-repeat region in Ssa3. These data demonstrate patterns of geographical association for P51 and temporal associations for Nsp2, Nsp3, and Ssa3, indicating evolutionary trends for theseNeorickettsiasurface antigen genes. This study showedN. risticiisurface protein population dynamics, providing groundwork for designing immunodiagnostic targets for PHF.
ngs_backbone: a pipeline for read cleaning, mapping and SNP calling using Next Generation Sequence
Authors: Blanca Jose M , Pascual Laura , Ziarsolo Peio , Nuez Fernando , Cañizares Joaquin 
Published: June 2011

Abstract

Background
The possibilities offered by next generation sequencing (NGS) platforms are revolutionizing biotechnological laboratories. Moreover, the combination of NGS sequencing and affordable high-throughput genotyping technologies is facilitating the rapid discovery and use of SNPs in non-model species. However, this abundance of sequences and polymorphisms creates new software needs. To fulfill these needs, we have developed a powerful, yet easy-to-use application.

Results
The ngs_backbone software is a parallel pipeline capable of analyzing Sanger, 454, Illumina and SOLiD (Sequencing by Oligonucleotide Ligation and Detection) sequence reads. Its main supported analyses are: read cleaning, transcriptome assembly and annotation, read mapping and single nucleotide polymorphism (SNP) calling and selection. In order to build a truly useful tool, the software development was paired with a laboratory experiment. All public tomato Sanger EST reads plus 14.2 million Illumina reads were employed to test the tool and predict polymorphism in tomato. The cleaned reads were mapped to the SGN tomato transcriptome obtaining a coverage of 4.2 for Sanger and 8.5 for Illumina. 23,360 single nucleotide variations (SNVs) were predicted. A total of 76 SNVs were experimentally validated, and 85% were found to be real.

Conclusions
ngs_backbone is a new software package capable of analyzing sequences produced by NGS technologies and predicting SNVs with great accuracy. In our tomato example, we created a highly polymorphic collection of SNVs that will be a useful resource for tomato researchers and breeders. The software developed along with its documentation is freely available under the AGPL license and can be downloaded from http://bioinf.comav.upv.es/ngs_backbone/ or http://github.com/JoseBlanca/franklin.
Systematic review and meta-analysis comparing land and aquatic exercise for people with hip or knee arthritis on function, mobility and other health outcomes
Authors: Batterham Stephanie I , Heywood Sophie , Keating Jennifer L 
Published: June 2011

Abstract

Background
Aquatic and land based exercise are frequently prescribed to maintain function for people with arthritis. The relative efficacy of these rehabilitation strategies for this population has not been established.
This review investigated the effects of aquatic compared to land based exercise on function, mobility or participants' perception of programs for people with arthritis.

Methods
Medline, CINAHL, AMED and the Cochrane Central Register of Controlled Clinical Trials were searched up to July 2010. Ten randomised, controlled clinical trials that compared land to aquatic exercise for adults with arthritis were included. Study quality was assessed with the PEDro scale. Data relevant to the review question were systematically extracted by two independent reviewers. Standardised mean differences between groups for key outcomes were calculated. Meta-analyses were performed for function, mobility and indices that pooled health outcomes across multiple domains.

Results
No differences in outcomes were observed for the two rehabilitation strategies in meta-analysis. There was considerable variability between trials in key program characteristics including prescribed exercises and design quality. Components of exercise programs were poorly reported by the majority of trials. No research was found that examined participant preferences for aquatic compared to land based exercise, identifying this as an area for further research.

Conclusion
Outcomes following aquatic exercise for adults with arthritis appear comparable to land based exercise. When people are unable to exercise on land, or find land based exercise difficult, aquatic programs provide an enabling alternative strategy.
Coffee and tea consumption in relation to inflammation and basal glucose metabolism in a multi-ethnic Asian population: a cross-sectional study
Authors: Rebello Salome A , Chen Cynthia H , Naidoo Nasheen , Xu Wang , Lee Jeannette , Chia Kee Seng , Tai E Shyong , van Dam Rob M 
Published: June 2011

Abstract

Background
Higher coffee consumption has been associated with a lower risk of type 2 diabetes in cohort studies, but the physiological pathways through which coffee affects glucose metabolism are not fully understood. The aim of this study was to evaluate the associations between habitual coffee and tea consumption and glucose metabolism in a multi-ethnic Asian population and possible mediation by inflammation.

Methods
We cross-sectionally examined the association between coffee, green tea, black tea and Oolong tea consumption and glycemic (fasting plasma glucose, HOMA-IR, HOMA-beta, plasma HbA1c) and inflammatory (plasma adiponectin and C-reactive protein) markers in a multi-ethnic Asian population (N = 4139).

Results
After adjusting for multiple confounders, we observed inverse associations between coffee and HOMA-IR (percent difference: - 8.8% for ≥ 3 cups/day versus rarely or never; P

trend
= 0.007), but no significant associations between coffee and inflammatory markers. Tea consumption was not associated with glycemic markers, but green tea was inversely associated with plasma C-reactive protein concentrations (percent difference: - 12.2% for ≥ 1 cup/day versus < 1 cup/week; P

trend
= 0.042).

Conclusions
These data provide additional evidence for a beneficial effect of habitual caffeinated coffee consumption on insulin sensitivity, and suggest that this effect is unlikely to be mediated by anti-inflammatory mechanisms.
Hysteresis loops of individual Co nanostripes measured by magnetic force microscopy
Authors: Jaafar Miriam , Serrano-Ramón Luis , Iglesias-Freire Oscar , Fernández-Pacheco Amalio , Ibarra Manuel Ricardo , De Teresa Jose Maria , Asenjo Agustina 
Published: June 2011

Abstract
High-resolution magnetic imaging is of utmost importance to understand magnetism at the nanoscale. In the present work, we use a magnetic force microscope (MFM) operating under in-plane magnetic field in order to observe with high accuracy the domain configuration changes in Co nanowires as a function of the externally applied magnetic field. The main result is the quantitative evaluation of the coercive field of the individual nanostructures. Such characterization is performed by using an MFM-based technique in which a map of the magnetic signal is obtained as a function of both the lateral displacement and the magnetic field.
Concurrent detection of autolysosome formation and lysosomal degradation by flow cytometry in a high-content screen for inducers of autophagy
Authors: Hundeshagen Phillip , Hamacher-Brady Anne , Eils Roland , Brady Nathan R 
Published: June 2011

Abstract

Background
Autophagy mediates lysosomal degradation of cytosolic components. Recent work has associated autophagic dysfunction with pathologies, including cancer and cardiovascular disease. To date, the identification of clinically-applicable drugs that modulate autophagy has been hampered by the lack of standardized assays capable of precisely reporting autophagic activity.

Results
We developed and implemented a high-content, flow-cytometry-based screening approach for rapid, precise, and quantitative measurements of pharmaceutical control over autophagy. Our assay allowed for time-resolved individual measurements of autolysosome formation and degradation, and endolysosomal activities under both basal and activated autophagy conditions. As proof of concept, we analyzed conventional autophagy regulators, including cardioprotective compounds aminoimidazole carboxamide ribonucleotide (AICAR), rapamycin, and resveratrol, and revealed striking conditional dependencies of rapamycin and autophagy inhibitor 3-methyladenine (3-MA). To identify novel autophagy modulators with translational potential, we screened the Prestwick Chemical Library of 1,120 US Food and Drug Administration (FDA)-approved compounds for impact on autolysosome formation. In all, 38 compounds were identified as potential activators, and 36 as potential inhibitors of autophagy. Notably, amongst the autophagy enhancers were cardiac glycosides, from which we selected digoxin, strophanthidin, and digoxigenin for validation by standard biochemical and imaging techniques. We report the induction of autophagic flux by these cardiac glycosides, and the concentrations allowing for specific enhancement of autophagic activities without impact on endolysosomal activities.

Conclusions
Our systematic analysis of autophagic and endolysosomal activities outperformed conventional autophagy assays and highlights the complexity of drug influence on autophagy. We demonstrate conditional dependencies of established regulators. Moreover, we identified new autophagy regulators and characterized cardiac glycosides as novel potent inducers of autophagic flux.
P2X7 receptor activation ameliorates CA3 neuronal damage via a tumor necrosis factor-α-mediated pathway in the rat hippocampus following status epilepticus
Authors: Kim Ji-Eun , Ryu Hea Jin , Kang Tae-Cheon 
Published: June 2011

Abstract

Background
The release of tumor necrosis factor-α (TNF-α) appears depend on the P2X7 receptor, a purinergic receptor. In the present study, we addressed the question of whether P2X7 receptor-mediated TNF-α regulation is involved in pathogenesis and outcome of status epilepticus (SE).

Methods
SE was induced by pilocarpine in rats that were intracerebroventricularly infused with saline-, 2',3'-O-(4-benzoylbenzoyl)-adenosine 5'-triphosphate (BzATP), adenosine 5'-triphosphate-2',3'-dialdehyde (OxATP), A-438079, or A-740003 prior to SE induction. Thereafter, we performed Fluoro-Jade B staining and immunohistochemical studies for TNF-α and NF-κB subunit phosphorylations.

Results
Following SE, P2X7 receptor agonist (BzATP) infusion increased TNF-α immunoreactivity in dentate granule cells as compared with that in saline-infused animals. In addition, TNF-α immunoreactivity was readily apparent in the mossy fibers, while TNF-α immunoreactivity in CA1-3 pyramidal cells was unaltered. However, P2X7 receptor antagonist (OxATP-, A-438079, and A-740003) infusion reduced SE-induced TNF-α expression in dentate granule cells. In the CA3 region, BzATP infusion attenuated SE-induced neuronal damage, accompanied by enhancement of p65-Ser276 and p65-Ser311 NF-κB subunit phosphorylations. In contrast, OxATP-, A-438079, and A-740003 infusions increased SE-induced neuronal death. Soluble TNF p55 receptor (sTNFp55R), and cotreatment with BzATP and sTNFp55R infusion also increased SE-induced neuronal damage in CA3 region. However, OxATP-, sTNFp55R or BzATP+sTNFp55R infusions could not exacerbate SE-induced neuronal damages in the dentate gyrus and the CA1 region, as compared to BzATP infusion.

Conclusions
These findings suggest that TNF-α induction by P2X7 receptor activation may ameliorate SE-induced CA3 neuronal damage via enhancing NF-κB p65-Ser276 and p65-Ser311 phosphorylations.
Distinctions in gastric cancer gene expression signatures derived from laser capture microdissection versushistologic macrodissection
Authors: Kim Hark Kyun , Kim Joseph , Korolevich Susie , Choi Il Ju , Kim Chang Hee , Munroe David J , Green Jeffrey E 
Published: June 2011

Abstract

Background
Gastric cancer samples obtained by histologic macrodissection contain a relatively high stromal content that may significantly influence gene expression profiles. Differences between the gene expression signature derived from macrodissected gastric cancer samples and the signature obtained from isolated gastric cancer epithelial cells from the same biopsies using laser-capture microdissection (LCM) were evaluated for their potential experimental biases.

Methods
RNA was isolated from frozen tissue samples of gastric cancer biopsies from 20 patients using both histologic macrodissection and LCM techniques. RNA from LCM was subject to an additional round of T7 RNA amplification. Expression profiling was performed using Affymetrix HG-U133A arrays. Genes identified in the expression signatures from each tissue processing method were compared to the set of genes contained within chromosomal regions found to harbor copy number aberrations in the tumor samples by array CGH and to proteins previously identified as being overexpressed in gastric cancer.

Results
Genes shown to have increased copy number in gastric cancer were also found to be overexpressed in samples obtained by macrodissection (LS P value < 10-5), but not in array data generated using microdissection. A set of 58 previously identified genes overexpressed in gastric cancer was also enriched in the gene signature identified by macrodissection (LS P < 10-5), but not in the signature identified by microdissection (LS P = 0.013). In contrast, 66 genes previously reported to be underexpressed in gastric cancer were enriched in the gene signature identified by microdissection (LS P < 10-5), but not in the signature identified by macrodissection (LS P = 0.89).

Conclusions
The tumor sampling technique biases the microarray results. LCM may be a more sensitive collection and processing method for the identification of potential tumor suppressor gene candidates in gastric cancer using expression profiling.
Cotreatment with Pegvisomant and a Somatostatin Analog (SA) in SA-Responsive Acromegalic Patients
Authors: Madsen Michael , Poulsen Per L. , Ørskov Hans , Møller Niels , Jørgensen Jens O. L. 
Published: June 2011

Abstract

Context:
Cotreatment of acromegaly with pegvisomant and a somatostatin analog (SA) has proven feasible. Previous studies in the field have focused on patients with an insufficient response to SA monotherapy in whom pegvisomant was added without changing the SA dose.

Objective:
The objective of the study was to study whether patients sufficiently controlled on SA monotherapy can be transferred to combination therapy with low-dose pegvisomant and a reduced SA dose.

Design:
Eighteen acromegalic patients well controlled on SA monotherapy, mean ± se aged 54 ± 3 yr, were randomized in a parallel study over 24 wk to unchanged SA monotherapy or cotreatment with pegvisomant (15–30 mg twice a week) and SA (half the usual dosage).

Setting:
This was an investigator-initiated study in a single tertiary referral center.

Main Outcome Measures:
Glucose tolerance, substrate metabolism, insulin sensitivity, body composition, and quality of life were measured.

Results:
Median pegvisomant dose was 52.5 mg/wk (range 30–60). IGF-I (micrograms per liter) was comparable both at baseline (P = 0.88) and after 24 wk of treatment (P = 0.48). The change in IGF-I between baseline and wk 24 also did not differ between groups (P = 0.15). Apart from increased peak insulin levels during the oral glucose tolerance test in the cotreatment group, no substantial differences between the two groups were detected. Moderately elevated liver enzymes were found in 17% of the patients on pegvisomant therapy.

Conclusion:
Acromegalic patients well controlled on SA monotherapy can maintain safe IGF-I levels during 24 wk of cotreatment with low-dose pegvisomant and a 50% reduced SA dose. This treatment modality, however, does not seem to provide significant benefits for the patients.