bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression of Nonhomologous End Joining Repair by Overexpression of HMGA2
Authors: Li Angela Y.J. , Boo Lee Ming , Wang Shih-Ya , Lin H. Helen , Wang Clay C.C. , Yen Yun , Chen Benjamin P.C. , Chen David J. , Ann David K. 
Published: July 2009

Abstract
Understanding the molecular details associated with aberrant high mobility group A2 (HMGA2) gene expression is key to establishing the mechanism(s) underlying its oncogenic potential and effect on the development of therapeutic strategies. Here, we report the involvement of HMGA2 in impairing DNA-dependent protein kinase (DNA-PK) during the nonhomologous end joining (NHEJ) process. We showed that HMGA2-expressing cells displayed deficiency in overall and precise DNA end-joining repair and accumulated more endogenous DNA damage. Proper and timely activation of DNA-PK, consisting of Ku70, Ku80, and DNA-PKcs subunits, is essential for the repair of DNA double strand breaks (DSB) generated endogenously or by exposure to genotoxins. In cells overexpressing HMGA2, accumulation of histone 2A variant X phosphorylation at Ser-139 (γ-H2AX) was associated with hyperphosphorylation of DNA-PKcs at Thr-2609 and Ser-2056 before and after the induction of DSBs. Also, the steady-state complex of Ku and DNA ends was altered by HMGA2. Microirradiation and real-time imaging in living cells revealed that HMGA2 delayed the release of DNA-PKcs from DSB sites, similar to observations found in DNA-PKcs mutants. Moreover, HMGA2 alone was sufficient to induce chromosomal aberrations, a hallmark of deficiency in NHEJ-mediated DNA repair. In summary, a novel role for HMGA2 to interfere with NHEJ processes was uncovered, implicating HMGA2 in the promotion of genome instability and tumorigenesis. [Cancer Res 2009;69(14):5699–706]
Signaling Events Downstream of Mammalian Target of Rapamycin Complex 2 Are Attenuated in Cells and Tumors Deficient for the Tuberous Sclerosis Complex Tumor Suppressors
Authors: Huang Jingxiang , Wu Shulin , Wu Chin-Lee , Manning Brendan D. 
Published: July 2009

Abstract
Mutations in the TSC1 and TSC2 tumor suppressor genes give rise to the neoplastic disorders tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis. Their gene products form a complex that is a critical negative regulator of mammalian target of rapamycin (mTOR) complex 1 (mTORC1) and cell growth. We recently found that the TSC1-TSC2 complex promotes the activity of mTOR complex 2 (mTORC2), an upstream activator of Akt, and this occurs independent of its inhibitory effects on mTORC1. Loss of mTORC2 activity in cells lacking the TSC1-TSC2 complex, coupled with mTORC1-mediated feedback mechanisms, leads to strong attenuation of the growth factor–stimulated phosphorylation of Akt on S473. In this study, we show that both phosphatidylinositol 3-kinase–dependent and phosphatidylinositol 3-kinase–independent mTORC2 substrates are affected by loss of the TSC1-TSC2 complex in cell culture models and kidney tumors from both Tsc2+/- mice (adenoma) and TSC patients (angiomyolipoma). These mTORC2 targets are all members of the AGC kinase family and include Akt, protein kinase Cα, and serum and glucocorticoid-induced protein kinase 1. We also show that the TSC1-TSC2 complex can directly stimulate the in vitro kinase activity of mTORC2. The interaction between these two complexes is mediated primarily through regions on TSC2 and a core component of mTORC2 called Rictor. Hence, loss of the TSC tumor suppressors results in elevated mTORC1 signaling and attenuated mTORC2 signaling. These findings suggest that the TSC1-TSC2 complex plays opposing roles in tumor progression, both blocking and promoting specific oncogenic pathways through its effects on mTORC1 inhibition and mTORC2 activation, respectively. [Cancer Res 2009;69(15):6107–14]
Overexpression of Extracellular Superoxide Dismutase Attenuates Heparanase Expression and Inhibits Breast Carcinoma Cell Growth and Invasion
Authors: Teoh Melissa L.T. , Fitzgerald Matthew P. , Oberley Larry W. , Domann Frederick E. 
Published: July 2009

Abstract
Increased expression of heparanase stimulates the progression of various human cancers, including breast cancer. Therefore, a deeper understanding of the mechanisms involved in regulating heparanase is critical in developing effective treatments for heparanase-overexpressing cancers. In this study, we investigated the potential use of extracellular superoxide dismutase (EcSOD) to enhance the inhibitory effects of heparin/low molecular weight heparin (LMWH) in breast cancer cells. EcSOD binds to cell surfaces and the extracellular matrix through heparin-binding domain (HBD). Deleting this HBD rendered the protein a more potent inhibitor of breast cancer growth, survival, and invasion. Among the treatment combinations examined, EcSODΔHBD plus LMWH provided the best tumor suppressive effects in inhibiting breast cancer growth and invasion in vitro. We have further shown that overexpression of EcSOD decreased accumulation of vascular endothelial growth factor in the culture medium and increased the level of intact cell surface-associated heparan sulfate, thus implicating inhibition of heparanase expression as a potential mechanism. Overexpression of EcSOD inhibited steady-state heparanase mRNA levels by &gt;50% as determined by quantitative reverse transcription-PCR. Moreover, heparanase promoter activation was suppressed by EcSOD as indicated by a luciferase reporter assay. These findings reveal a previously unrecognized molecular pathway showing that regulation of heparanase transcription can be mediated by oxidative stress. Our study implies that overexpression of EcSOD is a promising strategy to enhance the efficacy of heparin/LMWH by inhibiting heparanase as a novel treatment for breast cancer. [Cancer Res 2009;69(15):6355–63]
High Levels of Circulating VEGFR2+ Bone Marrow–Derived Progenitor Cells Correlate with Metastatic Disease in Patients with Pediatric Solid Malignancies
Authors: Taylor Melissa , Rössler Jochen , Geoerger Birgit , Laplanche Agnès , Hartmann Olivier , Vassal Gilles , Farace Françoise 
Published: July 2009

Abstract
Purpose: Pediatric solid malignancies display important angiogenic potential, and blocking tumor angiogenesis represents a new therapeutic approach for these patients. Recent studies have evidenced rare circulating cells with endothelial features contributing to tumor neovascularization and have shown the pivotal role of bone marrow–derived (BMD) progenitor cells in metastatic disease progression. We measured these cells in patients with pediatric solid malignancies as a prerequisite to clinical trials with antiangiogenic therapy.
Patients and Methods: Peripheral blood was drawn from 45 patients with localized (n = 23) or metastatic (n = 22) disease, and 20 healthy subjects. Subsets of circulating vascular endothelial growth factor receptor (VEGFR)2+-BMD progenitor cells, defined as CD45−CD34+VEGFR2(KDR)+7AAD− and CD45dimCD34+VEGFR2+7AAD− events, were measured in progenitor-enriched fractions by flow cytometry. Mature circulating endothelial cells (CEC) were measured in whole blood as CD31+CD146+CD45−7AAD− viable events. Data were correlated with VEGF and sVEGFR2 plasma levels.
Results: The CD45−CD34+VEGFR2(KDR)+7AAD− subset represented &lt;0.003% of circulating BMD progenitor cells (≤0.05 cells/mL). However, the median level (range) of the CD45dimCD34+VEGFR2+7AAD− subset was higher in patients compared with healthy subjects, 1.5% (0%-10.3%) versus 0.3% (0%-1.6%) of circulating BMD progenitors (P &lt; 0.0001), and differed significantly between patients with localized and metastatic disease, 0.7% (0%-8.6%) versus 2.9% (0.6%-10.3%) of circulating BMD progenitors (P &lt; 0.001). Median CEC value was 7 cells/mL (0-152 cells/mL) and similar in all groups. Unlike VEGFR2+-BMD progenitors, neither CECs, VEGF, or sVEGFR2 plasma levels correlated with disease status.
Conclusion: High levels of circulating VEGFR2+-BMD progenitor cells correlated with metastatic disease. Our study provides novel insights for angiogenesis mechanisms in pediatric solid malignancies for which antiangiogenic targeting of VEGFR2+-BMD progenitors could be of interest.
Prediction of Muscle-invasive Bladder Cancer Using Urinary Proteomics
Authors: Schiffer Eric , Vlahou Antonia , Petrolekas Andreas , Stravodimos Konstantinos , Tauber Robert , Geschwend Jürgen E. , Neuhaus Jochen , Stolzenburg Jens-Uwe , Conaway Mark R. , Mischak Harald , Theodorescu Dan 
Published: July 2009

Abstract
Purpose: Minimally invasive methods of predicting the risk of muscle-invasive urothelial bladder carcinoma may expedite appropriate therapy and reduce morbidity and cost.
Experimental Design: Here, capillary electrophoresis coupled mass spectrometry was used to identify urinary polypeptide bladder cancer biomarkers in 127 patients. These markers were used to construct a panel discriminating muscle-invasive from noninvasive disease, which was refined in 297 additional samples from healthy volunteers, patients with malignant and nonmalignant genitourinary conditions. Sequencing of panel polypeptides was then done. Finally, the ability of the panel to predict muscle-invasive disease was evaluated prospectively in 130 bladder carcinoma patients. Four sequenced polypeptides formed a panel predictive of muscle-invasive disease.
Results: Prospective evaluation of this panel revealed a sensitivity of 81% [95% confidence interval (CI), 69-90] and specificity of 57% (95% CI, 45-69) for muscle-invasive disease. Multivariate analysis revealed the panel (P &lt; 0.0001) and tumor grade (P = 0.0001), but not urine cytology, predict muscle invasion. A model including grade and panel polypeptide levels improved sensitivity [92% (95% CI, 82-97)] and specificity [68% (95% CI, 55-79)] for muscle-invasive disease. A model score of &gt;0.88 provided a negative predictive value of 77% and positive predictive value of 90% for muscle invasion.
Conclusions: Use of urinary peptides seems promising in estimating the probability a patient harbors muscle-invasive urothelial bladder cancer. These peptides may also shed novel insights into the biology of bladder tumor progression not obtainable by other methods. Clinical trials seem warranted to evaluate the effect of this approach on practice.
Infographics in the United Arab Emirates newspapers
Authors: Bekhit Elsayed 
Published: July 2009

In recent years, the number of infographics in the United Arab Emirates1 (UAE) newspapers has generally increased. The newspapers publish different types of infographics, but not on a regular basis. This study examined 180 issues of six UAE newspapers, conducted a survey with 19 graphic journalists and interviewed their chief editors to explore the current uses of infographics, the factors affecting its use and graphic journalists' perceptions of infographics. The study shows that the UAE newspapers still lag behind in the use of infographics and do not utilize all types of infographics. They mainly outsource services for infographics packages or illustration-based graphics. They do not have separate or specialized departments for infographics.2 They rarely combine infographics with news stories, especially on the front pages. Type-based graphics are more frequently used than charts and illustration-based graphics. The study shows a significant difference between the UAE English and Arabic newspapers in the type of infographics used and in its use on the front page. The graphic journalists see infographics as supplementary to the text and not an essential part of the newspaper's content.
Linked region detection using high-density SNP genotype data via the minimum recombinant model of pedigree haplotype inference
Authors: Wang Lusheng , Wang Zhanyong , Yang Wanling 
Published: July 2009

Abstract

Background
With the rapid development of high-throughput genotyping technologies, efficient methods for identifying linked regions using high-density SNP genotype data have become more and more important. Recently, a deterministic method that works very well on SNP genotyping data has been developed (Lin et al. Bioinformatics 2008, 24(1): 86–93). However, that program can only work on a limited number of family structures. In particular, the results (if any) will be poor when the genotype data for the whole chromosome of one of the parents in a nuclear family is missing.

Results
We have developed a software package (LIden) for identifying linked regions using high-density SNP genotype data. We focus on handling the case where the genotype data for the whole chromosome of one of the parents in a nuclear family is missing. We use the minimum recombinant model for haplotype inference in pedigrees. Several local optimization algorithms are used to infer the haplotype of each individual and determine the linked regions based on the inferred haplotype data. We have developed a more flexible method to combine nuclear families to further refine (reduce the length of) the linked regions.

Conclusion
Our new package (LIden) is efficient software for linked region detection using high-density SNP genotype data. LIden can handle some important cases where the existing programs do not work well. In particular, the new package can handle many cases where the genotype data of one of the two parents is missing for the entire chromosome. The running time of the program is O(mn), where m is the number of members in the family and n is the number of SNP sites in the chromosome. LIden is specifically suitable for handling big sized families. This research also demonstrates another practical use of the minimum recombinant model for haplotype inference in pedigrees.
The software package can be downloaded at http://www.cs.cityu.edu.hk/~lwang/software/Link.
Impact of animal strain on gene expression in a rat model of acute cardiac rejection
Authors: Deans Katherine J , Minneci Peter C , Chen Hao , Kern Steven J , Logun Carolea , Alsaaty Sara , Norsworthy Kelly J , Theel Stephanie M , Sennesh Joel D , Barb Jennifer J , Munson Peter J , Danner Robert L , Solomon Michael A 
Published: July 2009

Abstract

Background
The expression levels of many genes show wide natural variation among strains or populations. This study investigated the potential for animal strain-related genotypic differences to confound gene expression profiles in acute cellular rejection (ACR). Using a rat heart transplant model and 2 different rat strains (Dark Agouti, and Brown Norway), microarrays were performed on native hearts, transplanted hearts, and peripheral blood mononuclear cells (PBMC).

Results
In heart tissue, strain alone affected the expression of only 33 probesets while rejection affected the expression of 1368 probesets (FDR 10% and FC ≥ 3). Only 13 genes were affected by both strain and rejection, which was < 1% (13/1368) of all probesets differentially expressed in ACR. However, for PBMC, strain alone affected 265 probesets (FDR 10% and FC ≥ 3) and the addition of ACR had little further effect. Pathway analysis of these differentially expressed strain effect genes connected them with immune response, cell motility and cell death, functional themes that overlap with those related to ACR. After accounting for animal strain, additional analysis identified 30 PBMC candidate genes potentially associated with ACR.

Conclusion
In ACR, genetic background has a large impact on the transcriptome of immune cells, but not heart tissue. Gene expression studies of ACR should avoid study designs that require cross strain comparisons between leukocytes.
A set of EST-SNPs for map saturation and cultivar identification in melon
Authors: Deleu Wim , Esteras Cristina , Roig Cristina , González-To Mireia , Fernández-Silva Iria , Gonzalez-Ibeas Daniel , Blanca José , Aranda Miguel A , Arús Pere , Nuez Fernando , Monforte Antonio J , Picó Maria Belén , Garcia-Mas Jordi 
Published: July 2009

Abstract

Background
There are few genomic tools available in melon (Cucumis melo L.), a member of the Cucurbitaceae, despite its importance as a crop. Among these tools, genetic maps have been constructed mainly using marker types such as simple sequence repeats (SSR), restriction fragment length polymorphisms (RFLP) and amplified fragment length polymorphisms (AFLP) in different mapping populations. There is a growing need for saturating the genetic map with single nucleotide polymorphisms (SNP), more amenable for high throughput analysis, especially if these markers are located in gene coding regions, to provide functional markers. Expressed sequence tags (ESTs) from melon are available in public databases, and resequencing ESTs or validating SNPs detected in silico are excellent ways to discover SNPs.

Results
EST-based SNPs were discovered after resequencing ESTs between the parental lines of the PI 161375 (SC) × 'Piel de sapo' (PS) genetic map or using in silico SNP information from EST databases. In total 200 EST-based SNPs were mapped in the melon genetic map using a bin-mapping strategy, increasing the map density to 2.35 cM/marker. A subset of 45 SNPs was used to study variation in a panel of 48 melon accessions covering a wide range of the genetic diversity of the species. SNP analysis correctly reflected the genetic relationships compared with other marker systems, being able to distinguish all the accessions and cultivars.

Conclusion
This is the first example of a genetic map in a cucurbit species that includes a major set of SNP markers discovered using ESTs. The PI 161375 × 'Piel de sapo' melon genetic map has around 700 markers, of which more than 500 are gene-based markers (SNP, RFLP and SSR). This genetic map will be a central tool for the construction of the melon physical map, the step prior to sequencing the complete genome. Using the set of SNP markers, it was possible to define the genetic relationships within a collection of forty-eight melon accessions as efficiently as with SSR markers, and these markers may also be useful for cultivar identification in Occidental melon varieties.
Uncovering the Arabidopsis thaliana nectary transcriptome: investigation of differential gene expression in floral nectariferous tissues
Authors: Kram Brian W , Xu Wayne W , Carter Clay J 
Published: July 2009

Abstract
Background
Many flowering plants attract pollinators by offering a reward of floral nectar. Remarkably, the molecular events involved in the development of nectaries, the organs that produce nectar, as well as the synthesis and secretion of nectar itself, are poorly understood. Indeed, to date, no genes have been shown to directly affect the de novo production or quality of floral nectar. To address this gap in knowledge, the ATH1 Affymetrix® GeneChip array was used to systematically investigate the Arabidopsis nectary transcriptome to identify genes and pathways potentially involved in nectar production.

Results
In this study, we identified a large number of genes differentially expressed between secretory lateral nectaries and non-secretory median nectary tissues, as well as between mature lateral nectaries (post-anthesis) and immature lateral nectaries (pre-anthesis). Expression within nectaries was also compared to thirteen non-nectary reference tissues, from which 270 genes were identified as being significantly upregulated in nectaries. The expression patterns of 14 nectary-enriched genes were also confirmed via RT PCR. Upon looking into functional groups of upregulated genes, pathways involved in gene regulation, carbohydrate metabolism, and lipid metabolism were particularly enriched in nectaries versus reference tissues.

Conclusion
A large number of genes preferentially expressed in nectaries, as well as between nectary types and developmental stages, were identified. Several hypotheses relating to mechanisms of nectar production and regulation thereof are proposed, and provide a starting point for reverse genetics approaches to determine molecular mechanisms underlying nectar synthesis and secretion.
Data enhancement for co-morbidity measurement among patients referred for sleep diagnostic testing: an observational study
Authors: Ronksley Paul E , Tsai Willis H , Quan Hude , Faris Peter , Hemmelgarn Brenda R 
Published: July 2009

Abstract

Background
Observational outcome studies of patients with obstructive sleep apnea (OSA) require adjustment for co-morbidity to produce valid results. The aim of this study was to evaluate whether the combination of administrative data and self-reported data provided a more complete estimate of co-morbidity among patients referred for sleep diagnostic testing.

Methods
A retrospective observational study of 2149 patients referred for sleep diagnostic testing in Calgary, Canada. Self-reported co-morbidity was obtained with a questionnaire; administrative data and validated algorithms (when available) were also used to define the presence of these co-morbid conditions within a two-year period prior to sleep testing.

Results
Patient self-report of co-morbid conditions had varying levels of agreement with those derived from administrative data, ranging from substantial agreement for diabetes (κ = 0.79) to poor agreement for cardiac arrhythmia (κ = 0.14). The enhanced measure of co-morbidity using either self-report or administrative data had face validity, and provided clinically meaningful trends in the prevalence of co-morbidity among this population.

Conclusion
An enhanced measure of co-morbidity using self-report and administrative data can provide a more complete measure of the co-morbidity among patients with OSA when agreement between the two sources is poor. This methodology will aid in the adjustment of these coexisting conditions in observational studies in this area.
Tularemia induces different biochemical responses in BALB/c mice and common voles
Authors: Bandouchova Hana , Sedlackova Jana , Pohanka Miroslav , Novotny Ladislav , Hubalek Martin , Treml Frantisek , Vitula Frantisek , Pikula Jiri 
Published: July 2009

Abstract

Background
Both BALB/c mice and common voles (Microtus arvalis) are considered highly susceptible to tularemia. However, the common vole is reported to harbour Francisella tularensis in European habitats as well as to survive longer with chronic shedding of the bacterium. The purpose of the present study was to compare the response of these two rodents to a wild Francisella tularensis subsp. holarctica strain infection.

Methods
Rodents were evaluated for differences in the total antioxidant capacity derived from low-molecular-weight antioxidants, biochemistry including lipid metabolism, tissue bacterial burdens and histopathology following experimental intraperitoneal infection with 160 colony forming units (CFU) pro toto.

Results
Bacterial burdens in common voles started to develop later post-exposure and amounted to lower levels than in BALB/c mice. Elevation of liver function enzymes was more pronounced in mice than common voles and there were marked differences in lipid metabolism in the course of tularemia in these two species. Hypertriglyceridemia and hypercholesterolemia developed in mice, while physiologically higher levels of triglycerides and cholesterol showed a decreasing tendency in common voles.
On the other hand, the total plasma antioxidant capacity gradually dropped to 81.5% in mice on day 5 post-infection, while it increased to 130% on day 6 post-infection in common voles. Significant correlations between tissue bacterial burdens and several biochemical parameters were found.

Conclusion
As differences in lipid metabolism and the total antioxidant capacity of highly susceptible rodent species were demonstrated, the role of triglycerides, cholesterol and antioxidants in tularemic sepsis should be further investigated.