bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promoting Physical Activity for Persons With Diabetes
Authors: Diedrich Andrea , Munroe Donna J. , Romano Melissa 
Published: December 2009

Purpose The purpose of this study was to evaluate the effectiveness of a self-help physical activity program for persons with type 2 diabetes. Effectiveness was measured by cardiovascular indicators, hemoglobin A1C, anthropometric indicators, and activity levels. Methods This intervention study included 53 individuals with type 2 diabetes. Participants were randomly assigned. Participants in the intervention group attended the usual Diabetes Self-Management Education Program (DSMEP) and received a copy of the book, Manpo-kei; a concise handout summarizing the key points of Manpo-kei; and a pedometer. Participants not assigned to the intervention attended the usual DSMEP only. Data collection was completed at the beginning of the study and 3 months later using a lifestyle and diabetes questionnaire, a physical activity questionnaire, and cardiovascular and anthropometric measures. Results Those who participated in the intervention demonstrated a significant decrease in hemoglobin A1C, weight, and body fat. In addition, they increased their number of daily steps as measured by the pedometer. The control group also demonstrated a significant decrease in hemoglobin A1C and weight. Both groups demonstrated increases in their regular weekly activity. At the end of the study period, the intervention group had a significantly lower diastolic blood pressure than the control group. Conclusions Pedometers can be a helpful strategy to motivate persons with diabetes to increase physical activity. However, it appears that attendance at DSMEP alone may be enough to increase physical activity for persons with type 2 diabetes.
IL-6 and MYC collaborate in plasma cell tumor formation in mice
Authors: Rutsch Sebastian , Neppalli Vishala T. , Shin Dong-Mi , DuBois Wendy , Morse Herbert C. , Goldschmidt Hartmut , Janz Siegfried 
Published: December 2009

Abstract
Interleukin-6 (IL-6) plays a critical role in the natural history of human plasma cell neoplasms (PCNs), such as plasma cell myeloma and plasmacytoma (PCT). IL-6 is also at the center of neoplastic plasma cell transformation in BALB/c (C) mice carrying a transgene, H2-Ld-IL6, that encodes human IL-6 under control of the major histocompatibility complex H2-Ld promoter: strain C.H2-Ld-IL6. These mice are prone to PCT, but tumor development is incomplete with long latencies (∼ 40% PCT at 12 months of age). To generate a more robust mouse model of IL-6–dependent PCN, we intercrossed strain C.H2-Ld-IL6 with strains C.iMycEμ or C.iMycCα, 2 interrelated gene-insertion models of the chromosomal T(12;15) translocation causing deregulated expression of Myc in mouse PCT. Deregulation of MYC is also a prominent feature of human PCN. We found that double-transgenic C.H2-Ld-IL6/iMycEμ and C.H2-Ld-IL6/iMycCα mice develop PCT with full penetrance (100% tumor incidence) and short latencies (3-6 months). The mouse tumors mimic molecular hallmarks of their human tumor counterparts, including elevated IL-6/Stat3/Bcl-XL signaling. The newly developed mouse strains may provide a good preclinical research tool for the design and testing of new approaches to target IL-6 in treatment and prevention of human PCNs.
The protein C pathway in tissue inflammation and injury: pathogenic role and therapeutic implications
Authors: Danese Silvio , Vetrano Stefania , Zhang Li , Poplis Victoria A. , Castellino Francis J. 
Published: December 2009

AbstractInflammation and coagulation are closely linked interdependent processes. Under physiologic conditions, the tissue microcirculation functions in anticoagulant and anti-inflammatory fashions. However, when inflammation occurs, coagulation is also set in motion and actively participates in enhancing inflammation. Recently, novel and unexpected roles of hemostasis in the humoral and cellular components of innate immunity have been described. In particular, the protein C system, besides its well-recognized role in anticoagulation, plays a crucial role in inflammation. Indeed, the protein C system is now emerging as a novel participant in the pathogenesis of acute and chronic inflammatory diseases, such as sepsis, asthma, inflammatory bowel disease, atherosclerosis, and lung and heart inflammation, and may emerge as unexpected therapeutic targets for intervention.
Circulating microvesicles in B-cell chronic lymphocytic leukemia can stimulate marrow stromal cells: implications for disease progression
Authors: Ghosh Asish K. , Secreto Charla R. , Knox Traci R. , Ding Wei , Mukhopadhyay Debabrata , Kay Neil E. 
Published: December 2009

Abstract
Microvesicles (MVs) released by malignant cancer cells constitute an important part of the tumor microenvironment. They can transfer various messages to target cells and may be critical to disease progression. Here, we demonstrate that MVs circulating in plasma of B-cell chronic lymphocytic leukemia (CLL) patients exhibit a phenotypic shift from predominantly platelet derived in early stage to leukemic B-cell derived at advanced stage. Furthermore, the total MV level in CLL was significantly greater compared with healthy subjects. To understand the functional implication, we examined whether MVs can interact and modulate CLL bone marrow stromal cells (BMSCs) known to provide a “homing and nurturing” environment for CLL B cells. We found that CLL-MV can activate the AKT/mammalian target of rapamycin/p70S6K/hypoxia-inducible factor-1α axis in CLL-BMSCs with production of vascular endothelial growth factor, a survival factor for CLL B cells. Moreover, MV-mediated AKT activation led to modulation of the β-catenin pathway and increased expression of cyclin D1 and c-myc in BMSCs. We found MV delivered phospho-receptor tyrosine kinase Axl directly to the BMSCs in association with AKT activation. This study demonstrates the existence of separate MV phenotypes during leukemic disease progression and underscores the important role of MVs in activation of the tumor microenvironment.
Inhibiting toll-like receptor 4 signaling ameliorates pulmonary fibrosis during acute lung injury induced by lipopolysaccharide: an experimental study
Authors: He ZhengYu , Zhu YeSen , Jiang Hong 
Published: December 2009

Abstract

Background
Toll-like receptor 4 (TLR4) is essential in lipopolysaccharide (LPS)-induced fibroblast activation and collagen secretion in vitro. However, its effects on the process of lung fibroblast activation and fibrosis initiation during LPS induced acute lung injury (ALI) remain unknown. The goal of the present study was to determine the effect of inhibiting TLR4 on LPS-induced ALI and fibrosis in vivo.

Methods
The ALI model was established by intraperitoneal injection of LPS in mice. TLR4-small hairpin RNA (shRNA) lentivirus was injected intravenously into the mice to inhibit TLR4 expression. mRNA and protein levels were detected by real-time PCR and Western-blot analysis, respectively. The contents of the C-terminal propeptide of type I procollagen (PICP) in bronchoalveolar lavage fluid (BALF) were detected by ELISA, and the degree of fibrosis was detected by van Gieson collagen staining, the hydroxyproline assay, and alpha smooth muscle actin (α-SMA) immunohistochemical staining.

Results
Overexpression of TLR4, type I procollagen, alpha-SMA, and p-AKT in murine pulmonary tissue after intraperitoneal injection of LPS at 72 hours and 28 days were detected. Moreover, the degree of fibrosis was shown to increase by ELISA analysis of PICP in BALF, van Gieson collagen staining, the hydroxyproline assay, and α-SMA immunohistochemical staining. All of these changes were alleviated by intravenous infection with TLR4-shRNA lentivirus.

Conclusions
Inhibiting TLR4 signaling could ameliorate fibrosis at the early stage of ALI induced by LPS.
Comparison of the receptor FGFRL1 from sea urchins and humans illustrates evolution of a zinc binding motif in the intracellular domain
Authors: Zhuang Lei , Karotki Andrei V , Bruecker Philip , Trueb Beat 
Published: December 2009

Abstract

Background
FGFRL1, the gene for the fifth member of the fibroblast growth factor receptor (FGFR) family, is found in all vertebrates from fish to man and in the cephalochordate amphioxus. Since it does not occur in more distantly related invertebrates such as insects and nematodes, we have speculated that FGFRL1 might have evolved just before branching of the vertebrate lineage from the other invertebrates (Beyeler and Trueb, 2006).

Results
We identified the gene for FGFRL1 also in the sea urchin Strongylocentrotus purpuratus and cloned its mRNA. The deduced amino acid sequence shares 62% sequence similarity with the human protein and shows conservation of all disulfides and N-linked carbohydrate attachment sites. Similar to the human protein, the S. purpuratus protein contains a histidine-rich motif at the C-terminus, but this motif is much shorter than the human counterpart. To analyze the function of the novel motif, recombinant fusion proteins were prepared in a bacterial expression system. The human fusion protein bound to nickel and zinc affinity columns, whereas the sea urchin protein barely interacted with such columns. Direct determination of metal ions by atomic absorption revealed 2.6 mole zinc/mole protein for human FGFRL1 and 1.7 mole zinc/mole protein for sea urchin FGFRL1.

Conclusion
The FGFRL1 gene has evolved much earlier than previously assumed. A comparison of the intracellular domain between sea urchin and human FGFRL1 provides interesting insights into the shaping of a novel zinc binding domain.
Characterization of the stem cell system of the acoel Isodiametra pulchra
Authors: De Mulder Katrien , Kuales Georg , Pfister Daniela , Willems Maxime , Egger Bernhard , Salvenmoser Willi , Thaler Marlene , Gorny Anne-Kathrin , Hrouda Martina , Borgonie Gaëtan , Ladurner Peter 
Published: December 2009

Abstract

Background
Tissue plasticity and a substantial regeneration capacity based on stem cells are the hallmark of several invertebrate groups such as sponges, cnidarians and Platyhelminthes. Traditionally, Acoela were seen as an early branching clade within the Platyhelminthes, but became recently positioned at the base of the Bilateria. However, little is known on how the stem cell system in this new phylum is organized. In this study, we wanted to examine if Acoela possess a neoblast-like stem cell system that is responsible for development, growth, homeostasis and regeneration.

Results
We established enduring laboratory cultures of the acoel Isodiametra pulchra (Acoela, Acoelomorpha) and implemented in situ hybridization and RNA interference (RNAi) for this species. We used BrdU labelling, morphology, ultrastructure and molecular tools to illuminate the morphology, distribution and plasticity of acoel stem cells under different developmental conditions. We demonstrate that neoblasts are the only proliferating cells which are solely mesodermally located within the organism. By means of in situ hybridisation and protein localisation we could demonstrate that the piwi-like gene ipiwi1 is expressed in testes, ovaries as well as in a subpopulation of somatic stem cells. In addition, we show that germ cell progenitors are present in freshly hatched worms, suggesting an embryonic formation of the germline. We identified a potent stem cell system that is responsible for development, homeostasis, regeneration and regrowth upon starvation.

Conclusions
We introduce the acoel Isodiametra pulchra as potential new model organism, suitable to address developmental questions in this understudied phylum. We show that neoblasts in I. pulchra are crucial for tissue homeostasis, development and regeneration. Notably, epidermal cells were found to be renewed exclusively from parenchymally located stem cells, a situation known only from rhabditophoran flatworms so far. For further comparison, it will be important to analyse the stem cell systems of other key-positioned understudied taxa.
A practical comparison of methods for detecting transcription factor binding sites in ChIP-seq experiments
Authors: Laajala Teemu D , Raghav Sunil , Tuomela Soile , Lahesmaa Riitta , Aittokallio Tero , Elo Laura L 
Published: December 2009

AbstractBackgroundChromatin immunoprecipitation coupled with massively parallel sequencing (ChIP-seq) is increasingly being applied to study transcriptional regulation on a genome-wide scale. While numerous algorithms have recently been proposed for analysing the large ChIP-seq datasets, their relative merits and potential limitations remain unclear in practical applications.ResultsThe present study compares the state-of-the-art algorithms for detecting transcription factor binding sites in four diverse ChIP-seq datasets under a variety of practical research settings. First, we demonstrate how the biological conclusions may change dramatically when the different algorithms are applied. The reproducibility across biological replicates is then investigated as an internal validation of the detections. Finally, the predicted binding sites with each method are compared to high-scoring binding motifs as well as binding regions confirmed in independent qPCR experiments.ConclusionsIn general, our results indicate that the optimal choice of the computational approach depends heavily on the dataset under analysis. In addition to revealing valuable information to the users of this technology about the characteristics of the binding site detection approaches, the systematic evaluation framework provides also a useful reference to the developers of improved algorithms for ChIP-seq data.
Developmental iodine deficiency resulting in hypothyroidism reduces hippocampal ERK1/2 and CREB in lactational and adolescent rats
Authors: Dong Jing , Liu Wanyang , Wang Yi , Hou Yi , Xi Qi , Chen Jie 
Published: December 2009

Abstract

Background
Developmental iodine deficiency (ID) leads to inadequate thyroid hormone that impairs learning and memory with an unclear mechanism. Here, we show that hippocampal extracellular signal-regulated kinase (ERK1/2) and cAMP response element-binding protein (CREB) are implicated in the impaired learning and memory in lactational and adolescent rat hippocampus following developmental ID and hypothyroidism.

Methods
Three developmental rat models were created by administrating dam rats with either iodine-deficient diet or propylthiouracil (PTU, 5 ppm or 15 ppm)-added drinking water from gestational day (GD) 6 till postnatal day (PN) 28. Then, the total and phorsporylated ERK1/2 and total and phorsporylated CREB in the hippocampus were detected with western blot on PN14, PN21, PN28 and PN42.

Results
The iodine-deficient and hypothyroid pups showed lower serum FT3 and FT4 levels, smaller body size, and delayed eyes opening. The mean number of surviving cells in the hippocampus of the iodine-deficient and 15 ppm PTU-treated rats was significantly reduced compared to controls (P < 0.05). Iodine-deficient and 15 ppm PTU-treatment groups demonstrated significantly lower level of total and phosphorylated ERK1/2 and CREB than the controls on PN14, PN21 and PN28 (P < 0.05, respectively). The reduction of ERK1/2 and CREB was not reversible with the restoration of serum thyroid hormone concentrations on PN42.

Conclusions
Developmental ID and hypothyroidism down-regulate hippocampal ERK1/2 and CREB in lactational and adolescent rats.
Over-expression of miR172 causes loss of spikelet determinacy and floral organ abnormalities in rice (Oryza sativa)
Authors: Zhu Qian-Hao , Upadhyaya Narayana M , Gubler Frank , Helliwell Chris A 
Published: December 2009

Abstract

Background
Regulation of gene expression by microRNAs (miRNAs) plays a crucial role in many developmental and physiological processes in plants. miRNAs act to repress expression of their target genes via mRNA cleavage or translational repression. Dozens of miRNA families have been identified in rice, 21 of which are conserved between rice and Arabidopsis. miR172 is a conserved miRNA family which has been shown to regulate expression of APETALA2 (AP2)-like transcription factors in Arabidopsis and maize. The rice genome encodes five AP2-like genes predicted to be targets of miR172. To determine whether these rice AP2-like genes are regulated by miR172 and investigate the function of the target genes, we studied the effect of over-expressing two members of the miR172 family on rice plant development.

Results
Analysis of miR172 expression showed that it is most highly expressed in late vegetative stages and developing panicles. Analyses of expression of three miR172 targets showed that SUPERNUMERARY BRACT (SNB) and Os03g60430 have high expression in developing panicles. Expression of miR172 was not inversely correlated with expression of its targets although miR172-mediated cleavage of SNB was detected by 5' rapid amplification of cDNA ends (RACE). Over-expression of miR172b in rice delayed the transition from spikelet meristem to floral meristem, and resulted in floral and seed developmental defects, including changes to the number and identity of floral organs, lower fertility and reduced seed weight. Plants over-expressing miR172b not only phenocopied the T-DNA insertion mutant of SNB but showed additional defects in floret development not seen in the snb mutant. However SNB expression was not reduced in the miR172b over-expression plants.

Conclusions
The phenotypes resulting from over-expression of miR172b suggests it represses SNB and at least one of the other miR172 targets, most likely Os03g60430, indicating roles for other AP2-like genes in rice floret development. miR172 and the AP2-like genes had overlapping expression patterns in rice and their expression did not show an obvious negative correlation. There was not a uniform decrease in the expression of the AP2-like miR172 target mRNAs in the miR172b over-expression plants. These observations are consistent with miR172 functioning via translational repression or with expression of the AP2-like genes being regulated by a negative feedback loop.
Gene expression relationship between prostate cancer cells of Gleason 3, 4 and normal epithelial cells as revealed by cell type-specific transcriptomes
Authors: Pascal Laura E , Vêncio Ricardo ZN , Page Laura S , Liebeskind Emily S , Shadle Christina P , Troisch Pamela , Marzolf Bruz , True Lawrence D , Hood Leroy E , Liu Alvin Y 
Published: December 2009

Abstract

Background
Prostate cancer cells in primary tumors have been typed CD10-/CD13-/CD24hi/CD26+/CD38lo/CD44-/CD104-. This CD phenotype suggests a lineage relationship between cancer cells and luminal cells. The Gleason grade of tumors is a descriptive of tumor glandular differentiation. Higher Gleason scores are associated with treatment failure.

Methods
CD26+ cancer cells were isolated from Gleason 3+3 (G3) and Gleason 4+4 (G4) tumors by cell sorting, and their gene expression or transcriptome was determined by Affymetrix DNA array analysis. Dataset analysis was used to determine gene expression similarities and differences between G3 and G4 as well as to prostate cancer cell lines and histologically normal prostate luminal cells.

Results
The G3 and G4 transcriptomes were compared to those of prostatic cell types of non-cancer, which included luminal, basal, stromal fibromuscular, and endothelial. A principal components analysis of the various transcriptome datasets indicated a closer relationship between luminal and G3 than luminal and G4. Dataset comparison also showed that the cancer transcriptomes differed substantially from those of prostate cancer cell lines.

Conclusions
Genes differentially expressed in cancer are potential biomarkers for cancer detection, and those differentially expressed between G3 and G4 are potential biomarkers for disease stratification given that G4 cancer is associated with poor outcomes. Differentially expressed genes likely contribute to the prostate cancer phenotype and constitute the signatures of these particular cancer cell types.
Comparing methods for identifying patients with heart failure using electronic data sources
Authors: Alqaisi Fadi , Williams L Keoki , Peterson Edward L , Lanfear David E 
Published: December 2009

Abstract

Background
Accurately indentifying heart failure (HF) patients from administrative claims data is useful for both research and quality of care efforts. Yet, there are few comparisons of the various claims data criteria (also known as claims signatures) for identifying HF patients. We compared various HF claim signatures to assess their relative accuracy.

Methods
In this retrospective study, we identified 4174 patients who received care from a large health system in southeast Michigan and who had ≥1 HF encounter between January 1, 2004 and December 31, 2005. Four hundred patients were chosen at random and a detailed chart review was performed to assess which met the Framingham HF criteria. The sample was divided into 300 subjects for derivation and 100 subjects for validation. Sensitivity, specificity,, and area under the curve (AUC) were determined for the various claim signatures. The criteria with the highest AUC were retested in the validation set.

Results
Of the 400 patients sampled, 65% met Framingham HF criteria, and 56% had at least one B-type Natriuretic Peptide (BNP) measurement. There was substantial variation between claims signatures in terms of sensitivity (range 15%-77%) and specificity (range 69%-100%). The best performing criteria in the derivation set was if patients met any one of the following: ≥2 HF encounters, any hospital discharge diagnosis of HF, or a BNP ≥200 pg/ml. These criteria showed a sensitivity of 76%, specificity of 75%, and AUC of 0.754 for meeting the Framingham HF criteria. This claims signature performed similarly in the validation set.

Conclusion
Claim signatures for HF vary greatly in their relative sensitivity and specificity. These findings may facilitate efforts to identify HF patients for research and quality improvement efforts.