bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitogen-activated protein kinase kinase signaling promotes growth and vascularization of fibrosarcoma
Authors: Ding Yan , Boguslawski Elissa A. , Berghuis Bree D. , Young John J. , Zhang Zhongfa , Hardy Kim , Furge Kyle , Kort Eric , Frankel Arthur E. , Hay Rick V. , Resau James H. , Duesbery Nicholas S. 
Published: March 2008

Abstract
We hypothesized that signaling through multiple mitogen-activated protein kinase (MAPK) kinase (MKK) pathways is essential for the growth and vascularization of soft-tissue sarcomas, which are malignant tumors derived from mesenchymal tissues. We tested this using HT-1080, NCI, and Shac fibrosarcoma-derived cell lines and anthrax lethal toxin (LeTx), a bacterial toxin that inactivates MKKs. Western blots confirmed that LeTx treatment reduced the levels of phosphorylated extracellular signal-regulated kinase and p38 MAPK in vitro. Although short treatments with LeTx only modestly affected cell proliferation, sustained treatment markedly reduced cell numbers. LeTx also substantially inhibited the extracellular release of angioproliferative factors including vascular endothelial growth factor, interleukin-8, and basic fibroblast growth factor. Similar results were obtained with cell lines derived from malignant fibrous histiocytomas, leiomyosarcomas, and liposarcomas. In vivo, LeTx decreased MAPK activity and blocked fibrosarcoma growth. Growth inhibition correlated with decreased cellular proliferation and extensive necrosis, and it was accompanied by a decrease in tumor mean vessel density as well as a reduction in serum expression of angioproliferative cytokines. Vital imaging using high-resolution ultrasound enhanced with contrast microbubbles revealed that the effects of LeTx on tumor perfusion were remarkably rapid (&lt;24 h) and resulted in a marked reduction of perfusion within the tumor but not in nontumor tissues. These results are consistent with our initial hypothesis and lead us to propose that MKK inhibition by LeTx is a broadly effective strategy for targeting neovascularization in fibrosarcomas and other similar proliferative lesions. [Mol Cancer Ther 2008;7(3):648–58]
MODIS-Derived Spatially Complete Surface Albedo Products: Spatial and Temporal Pixel Distribution and Zonal Averages
Authors: Moody Eric G. , King Michael D. , Schaaf Crystal B. , Platnick Steven 
Published: March 2008

Abstract
Five years (2000–04) of spatially complete snow-free land surface albedo data have been produced using high-quality-flagged diffuse bihemispherical (white sky) and direct-beam directional hemispherical (black sky) land surface albedo data derived from observations taken by the Moderate-Resolution Imaging Spectroradiometer (MODIS) instrument aboard the NASA Terra satellite platform (MOD43B3, collection 4). In addition, a spatially complete snow-free aggregate albedo climatological product was generated. These spatially complete products were prepared using an ecosystem-dependent temporal interpolation technique that retrieves missing data within 3%–8% error. These datasets have already been integrated into research and operational projects that require snow-free land surface albedo. As such, this paper provides details regarding the spatial and temporal distribution of the filled versus the original MOD43B3 data. The paper also explores the intra- and interannual variation in the 5-yr data record and provides a qualitative comparison of zonal averages and annual cycles of the filled versus the original MOD43B3 data. The analyses emphasize the data’s inter- and intraannual variation and show that the filled data exhibit large- and small-scale phenological behavior that is qualitatively similar to that of the original MOD43B3. These analyses thereby serve to showcase the inherent spectral, spatial, and temporal variability in the MOD43B3 data as well as the ability of the fill technique to preserve these unique regional and pixel-level phenological characteristics.
Arthroscopic Repair of Isolated Meniscal Tears in Patients 18 Years and Younger
Authors: Krych Aaron J. , McIntosh Amy L. , Voll Anthony E. , Stuart Michael J. , Dahm Diane L. 
Published: March 2008

Background Isolated meniscal tears in the skeletally immature patient are infrequent but well-recognized injuries. Although few studies have evaluated the pediatric and adolescent population, arthroscopic surgical repair remains the standard of care for Patients in this age group with unstable meniscal tears. Purpose To review our results of arthroscopic repair of isolated meniscal tears in pediatric and adolescent patients to further define future management of these injuries. Study Design Case series; Level of evidence, 4. Methods The records of all patients 18 years old or younger who underwent isolated meniscal repair between 1990 and 2005 were retrospectively reviewed. Forty-four patients (6 girls, 38 boys) with an average age of 15.8 years (range, 9.9-18.7 years) were included in this study, for a total of 45 isolated meniscal tears. Clinical examinations were performed, International Knee Documentation Committee forms were administered, and Tegner scores were determined at an average of 5.8 years (range, 2.5 months-13.8 years) postoperative follow-up. Three patients were lost to follow-up. Results The clinical success rate of arthroscopic meniscal repair was 80% for simple tears, 68% for displaced bucket-handle tears, and 13% for complex tears. Seventeen menisci (38% overall) failed initial repair at a mean of 17 months (range, 3-61 Months) postoperatively and underwent repeat arthroscopic surgery (15 partial meniscectomies, 2 rerepair). The average Tegner and International Knee Documentation Committee scores were 8 (range, 5-9) and 89.4 (range, 79-99), respectively, at the time of final follow-up. Risk factors for failure included complex tears and rim width greater than 3 mm. Conclusion Clinically successful repair of an isolated meniscal tear in patients 18 years or younger was variable depending on tear type, with complex tears and rim width 3 mm or greater being negative prognostic factors.
A role for interleukin-12/23 in the maturation of human natural killer and CD56+ T cells in vivo
Authors: Guia Sophie , Cognet Céline , de Beaucoudrey Ludovic , Tessmer Marlowe S. , Jouanguy Emmanuelle , Berger Claire , Filipe-Santos Orchidée , Feinberg Jacqueline , Camcioglu Yildiz , Levy Jacob , Al Jumaah Suliman , Al-Hajjar Sami , Stephan Jean-Louis , Fieschi Claire , Abel Laurent , Brossay Laurent , Casanova Jean-Laurent , Vivier Eric 
Published: March 2008

AbstractNatural killer (NK) cells have been originally defined by their “naturally occurring” effector function. However, only a fraction of human NK cells is reactive toward a panel of prototypical tumor cell targets in vitro, both for the production of interferon-γ (IFN-γ) and for their cytotoxic response. In patients with IL12RB1 mutations that lead to a complete IL-12Rβ1 deficiency, the size of this naturally reactive NK cell subset is diminished, in particular for the IFN-γ production. Similar data were obtained from a patient with a complete deficit in IL-12p40. In addition, the size of the subset of effector memory T cells expressing CD56 was severely decreased in IL-12Rβ1– and IL-12p40–deficient patients. Human NK cells thus require in vivo priming with IL-12/23 to acquire their full spectrum of functional reactivity, while T cells are dependent upon IL-12/23 signals for the differentiation and/or the maintenance of CD56+ effector memory T cells. The susceptibility of IL-12/23 axis–deficient patients to Mycobacterium and Salmonella infections in combination with the absence of mycobacteriosis or salmonellosis in the rare cases of human NK cell deficiencies point to a role for CD56+ T cells in the control of these infections in humans.
Common variable immunodeficiency disorders: division into distinct clinical phenotypes
Authors: Chapel Helen , Lucas Mary , Lee Martin , Bjorkander Janne , Webster David , Grimbacher Bodo , Fieschi Claire , Thon Vojtech , Abedi Mohammad R. , Hammarstrom Lennart 
Published: March 2008

AbstractThe European Common Variable Immunodeficiency Disorders registry was started in 1996 to define distinct clinical phenotypes and determine overlap within individual patients. A total of 7 centers contributed patient data, resulting in the largest cohort yet reported. Patients (334), validated for the diagnosis, were followed for an average of 25.6 years (9461 patient-years). Data were used to define 5 distinct clinical phenotypes: no complications, autoimmunity, polyclonal lymphocytic infiltration, enteropathy, and lymphoid malignancy. A total of 83% of patients had only one of these phenotypes. Analysis of mortality showed a considerable reduction in the last 15 years and that different phenotypes were associated with different survival times. Types of complications and clinical phenotypes varied significantly between countries, indicating the need for large, international registries. Ages at onset of symptoms and diagnosis were shown to have a Gaussian distribution, but were not useful predictors of phenotype. The only clinical predictor was polyclonal lymphocytic infiltration, which was associated with a 5-fold increased risk of lymphoid malignancy. There was widespread variation in the levels of serum immunoglobulin isotypes as well as in the percentages and absolute numbers of B cells, confirming the heterogeneity of these conditions. Higher serum IgM and lower circulating CD8 proportions were found to be predictive markers for polyclonal lymphocytic infiltration and autoimmunity, respectively.
A critical role of Rap1b in B-cell trafficking and marginal zone B-cell development
Authors: Chen Yuhong , Yu Mei , Podd Andrew , Wen Renren , Chrzanowska-Wodnicka Magdalena , White Gilbert C. , Wang Demin 
Published: March 2008

AbstractB-cell development is orchestrated by complex signaling networks. Rap1 is a member of the Ras superfamily of small GTP-binding proteins and has 2 isoforms, Rap1a and Rap1b. Although Rap1 has been suggested to have an important role in a variety of cellular processes, no direct evidence demonstrates a role for Rap1 in B-cell biology. In this study, we found that Rap1b was the dominant isoform of Rap1 in B cells. We discovered that Rap1b deficiency in mice barely affected early development of B cells but markedly reduced marginal zone (MZ) B cells in the spleen and mature B cells in peripheral and mucosal lymph nodes. Rap1b-deficient B cells displayed normal survival and proliferation in vivo and in vitro. However, Rap1b-deficient B cells had impaired adhesion and reduced chemotaxis in vitro, and lessened homing to lymph nodes in vivo. Furthermore, we found that Rap1b deficiency had no marked effect on LPS-, BCR-, or SDF-1–induced activation of mitogen-activated protein kinases and AKT but clearly impaired SDF-1–mediated activation of Pyk-2, a key regulator of SDF-1–mediated B-cell migration. Thus, we have discovered a critical and distinct role of Rap1b in mature B-cell trafficking and development of MZ B cells.
Normalization of oligonucleotide arrays based on the least-variant set of genes
Authors: Calza Stefano , Valentini Davide , Pawitan Yudi 
Published: March 2008

Abstract

Background
It is well known that the normalization step of microarray data makes a difference in the downstream analysis. All normalization methods rely on certain assumptions, so differences in results can be traced to different sensitivities to violation of the assumptions. Illustrating the lack of robustness, in a striking spike-in experiment all existing normalization methods fail because of an imbalance between up- and down-regulated genes. This means it is still important to develop a normalization method that is robust against violation of the standard assumptions

Results
We develop a new algorithm based on identification of the least-variant set (LVS) of genes across the arrays. The array-to-array variation is evaluated in the robust linear model fit of pre-normalized probe-level data. The genes are then used as a reference set for a non-linear normalization. The method is applicable to any existing expression summaries, such as MAS5 or RMA.

Conclusion
We show that LVS normalization outperforms other normalization methods when the standard assumptions are not satisfied. In the complex spike-in study, LVS performs similarly to the ideal (in practice unknown) housekeeping-gene normalization. An R package called lvs is available in http://www.meb.ki.se/~yudpaw.
Enhancing the prediction of protein pairings between interacting families using orthology information
Authors: Izarzugaza Jose MG , Juan David , Pons Carles , Pazos Florencio , Valencia Alfonso 
Published: March 2008

Abstract

Background
It has repeatedly been shown that interacting protein families tend to have similar phylogenetic trees. These similarities can be used to predicting the mapping between two families of interacting proteins (i.e. which proteins from one family interact with which members of the other). The correct mapping will be that which maximizes the similarity between the trees. The two families may eventually comprise orthologs and paralogs, if members of the two families are present in more than one organism. This fact can be exploited to restrict the possible mappings, simply by impeding links between proteins of different organisms. We present here an algorithm to predict the mapping between families of interacting proteins which is able to incorporate information regarding orthologues, or any other assignment of proteins to "classes" that may restrict possible mappings.

Results
For the first time in methods for predicting mappings, we have tested this new approach on a large number of interacting protein domains in order to statistically assess its performance. The method accurately predicts around 80% in the most favourable cases. We also analysed in detail the results of the method for a well defined case of interacting families, the sensor and kinase components of the Ntr-type two-component system, for which up to 98% of the pairings predicted by the method were correct.

Conclusion
Based on the well established relationship between tree similarity and interactions we developed a method for predicting the mapping between two interacting families using genomic information alone. The program is available through a web interface.
Glycosyltransferase efficiently controls phenylpropanoid pathway
Authors: Aksamit-Stachurska Anna , Korobczak-Sosna Alina , Kulma Anna , Szopa Jan 
Published: March 2008

Abstract

Background
In a previous study, anthocyanin levels in potato plants were increased by manipulating genes connected with the flavonoid biosynthesis pathway. However, starch content and tuber yield were dramatically reduced in the transgenic plants, which over-expressed dihydroflavonol reductase (DFR).

Results
Transgenic plants over-expressing dihydroflavonol reductase (DFR) were subsequently transformed with the cDNA coding for the glycosyltransferase (UGT) of Solanum sogarandinum in order to obtain plants with a high anthocyanin content without reducing tuber yield and quality. Based on enzyme studies, the recombinant UGT is a 7-O-glycosyltransferase whose natural substrates include both anthocyanidins and flavonols such as kaempferol and quercetin. In the super-transformed plants, tuber production was much higher than in the original transgenic plants bearing only the transgene coding for DFR, and was almost the same as in the control plants. The anthocyanin level was lower than in the initial plants, but still higher than in the control plants. Unexpectedly, the super-transformed plants also produced large amounts of kaempferol, chlorogenic acid, isochlorogenic acid, sinapic acid and proanthocyanins.

Conclusion
In plants over-expressing both the transgene for DFR and the transgene for UGT, the synthesis of phenolic acids was diverted away from the anthocyanin branch. This represents a novel approach to manipulating phenolic acids synthesis in plants.
Retinoic Acid Stimulation of the Sodium/Iodide Symporter in MCF-7 Breast Cancer Cells Is Meditated by the Insulin Growth Factor-I/Phosphatidylinositol 3-Kinase and p38 Mitogen-Activated Protein Kinase Signaling Pathways
Authors: Kogai Takahiko , Ohashi Emi , Jacobs Megan S. , Sajid-Crockett Saima , Fisher Myrna L. , Kanamoto Yoko , Brent Gregory A. 
Published: March 2008

Abstract
Context: All-trans retinoic acid (tRA) induces differentiation in MCF-7 breast cancer cells, stimulates sodium/iodide symporter (NIS) gene expression, and inhibits cell proliferation. Radioiodine administration after systemic tRA treatment has been proposed as an approach to image and treat some differentiated breast cancer.
Objective: The objective of this work was to study the relative role of genomic and nongenomic pathways in tRA stimulation of NIS expression in MCF-7 cells.
Design: We inspected the human NIS gene locus for retinoic acid-responsive elements and tested them for function. The effects of signal transduction pathway inhibitors were also tested in tRA-treated MCF-7 cells and TSH-stimulated FRTL-5 rat thyroid cells, followed by iodide uptake assay, quantitative RT-PCR of NIS, and cell cycle phase analysis.
Results: Multiple retinoic acid response elements around the NIS locus were identified by sequence inspection, but none of them was a functional tRA-induced element in MCF-7 cells. Inhibitors of the IGF-I receptor, Janus kinase, and phosphatidylinositol 3-kinase (PI3K), significantly reduced NIS mRNA expression and iodide uptake in tRA-stimulated MCF-7 cells but not FRTL-5 cells. An inhibitor of p38 MAPK significantly reduced iodide uptake in both tRA-stimulated MCF-7 cells and TSH-stimulated FRTL-5 cells. IGF-I and PI3K inhibitors did not significantly reduce the basal NIS mRNA expression in MCF-7 cells. Despite the chronic inhibitory effects on cell proliferation, tRA did not reduce the S-phase distribution of MCF-7 cells during the period of NIS induction.
Conclusion: The IGF-I receptor/PI3K pathway mediates tRA-stimulated NIS expression in MCF-7 but not FRTL-5 thyroid cells.
Insulin-Induced Gene 2 Involvement in Human Adipocyte Metabolism and Body Weight Regulation
Authors: Krapivner Sergey , Popov Sergej , Chernogubova Ekaterina , Hellénius Mai-Lis , Fisher Rachel M. , Hamsten Anders , van't Hooft Ferdinand M. 
Published: March 2008

AbstractBackground: Insulin-induced genes (INSIGs) encode proteins that block proteolytic activation of sterol regulatory element-binding proteins, transcription factors that regulate lipogenic enzymes, and adipocyte differentiation.Objective: Here, we analyzed the relative significance of INSIG1 and INSIG2 in human liver and adipocyte metabolism, and defined a novel, functional polymorphism in the promoter of INSIG2 associated with body mass index.Research Methods: Variations in gene expression of different human tissues, of hepatoma cells exposed to INSIG1 and INSIG2 gene silencing probes, and of differentiating 3T3-L1 adipocytes were determined by real-time quantitative PCR. The functional significance of a novel polymorphism in the promoter of INSIG2 was analyzed using in vitro methods and gene expression analysis of human adipose tissue, whereas the phenotype associated with this polymorphism was studied in two cohorts of middle-aged men.Results: Gene expression analysis of 17 human tissues demonstrated that INSIG1 is highly expressed in the liver, whereas INSIG2 is ubiquitously expressed. Gene silencing experiments confirmed that INSIG1, but not INSIG2, regulates the expression of sterol regulatory element-binding proteins target genes in human hepatoma cells. In contrast, adipocyte differentiation of 3T3-L1 cells was associated with a 13-fold increase in expression of INSIG2. Significant relationships between the INSIG2–102G/A polymorphism and body mass index were observed in two cohorts of middle-aged men (ANOVA P = 0.017 and 0.044, respectively). In vitro studies and analysis of allele-specific expression in human adipose tissue substantiated the functional significance of the INSIG2–102G/A polymorphism.Conclusion: INSIG2 is involved in adipocyte metabolism and body weight regulation.
Does Osteoprotegerin or Receptor Activator of Nuclear Factor-κB Ligand Mediate the Association between Bone and Coronary Artery Calcification?
Authors: Bakhireva Ludmila N. , Laughlin Gail A. , Bettencourt Ricki , Barrett-Connor Elizabeth 
Published: March 2008

Abstract
Context: Accumulating evidence indicates that vascular and bone mineralization may be related, although the exact mechanism remains unknown.
Objective: Our objective was to investigate whether an observed inverse association between bone mineral density (BMD) and coronary artery calcification (CAC) in postmenopausal women currently taking estrogen therapy is mediated by osteoprotegerin (OPG) or receptor activator of nuclear factor-κB ligand (RANKL).
Design: Participants were 92 postmenopausal women (aged 58–81 yr) taking estrogen therapy who had hip and spine BMD assessed by dual-energy x-ray absorptiometry and CAC measured by electron-beam computed tomography in 1998–2002 and serum RANKL and OPG levels measured in samples collected in 1997–1999. Total CAC score was dichotomized as none/minimal (≤10) vs. some (&gt;10).
Results: OPG serum levels were higher in women who had some CAC compared with those who had none/minimal (126.8 ± 1.08 vs. 102.9 ± 1.07 pg/ml, respectively, P = 0.03); these differences became nonsignificant after adjustment for age and other risk factors (P = 0.51). A 1 sd increase in hip BMD was associated with significantly lower odds of having CAC &gt; 10 (odds ratio = 0.52; 95% confidence interval = 0.29–0.93) independent of age, fat-free mass, high-density lipoprotein cholesterol, current smoking, and use of cholesterol-lowering medications. Other skeletal sites demonstrated a similar pattern. Addition of RANKL and/or OPG to the model had minimal effect on the magnitude or statistical significance of the BMD-CAC association. Additionally, a test of interaction indicated that RANKL and OPG are not significant effect modifiers.
Conclusions: Serum OPG and RANKL do not account for the observed association between bone and coronary artery calcification among postmenopausal women using hormone therapy.