bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stabilization of Quercetin Paradoxically Reduces Its Proapoptotic Effect on UVB-Irradiated Human Keratinocytes
Authors: Olson Erik R. , Melton Tania , Dong Zigang , Bowden G. Tim 
Published: October 2008

Abstract
UVB light promotes survival of initiated keratinocytes, in part, by the direct activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Novel chemopreventative agents targeting UVB-induced signaling pathways are needed to reduce the incidence of nonmelanoma skin cancer. Quercetin (Qu) is a dietary flavonoid and a known inhibitor of PI3K. We determined that Qu degrades rapidly when diluted in DMEM and incubated under normal cell culture conditions. Degradation was delayed by supplementing the medium with 1 mmol/L ascorbic acid (AA), and as expected, stabilization actually increased the effectiveness of Qu as a PI3K inhibitor because basal and UVB-induced Akt phosphorylation were reduced compared with Qu treatment in the absence of AA. Although AA stabilization increased Qu-induced apoptosis in mock-irradiated HaCaT cells, consistent with it acting as a PI3K inhibitor (13.4% Annexin V–positive cells for AA-stabilized Qu versus 6.3% for Qu), AA stabilization of Qu actually reduced the ability of the compound to induce apoptosis of UVB-irradiated HaCaTs (29.7% of Qu-treated cells versus 15.5% of AA + Qu–treated cells). Similar trends were seen in the analysis of caspase-3 and poly(ADP-ribose) polymerase cleavage. Qu is known to oxidize to form reactive products, and we found that dihydroethidium is oxidized by Qu regardless of whether or not it was stabilized. Although redox cycling occurs even in the presence of AA, stabilization reduces the accumulation of reactive Qu products that contribute to the proapoptotic effect of the compound, and thus reduces the ability of the compound to induce apoptosis of UVB-irradiated HaCaT cells.
Adenosine A3Receptor Deficiency Exerts Unanticipated Protective Effects on the Pressure-Overloaded Left Ventricle
Authors: Lu Zhongbing , Fassett John , Xu Xin , Hu Xinli , Zhu Guangshuo , French Joel , Zhang Ping , Schnermann Jurgen , Bache Robert J. , Chen Yingjie 
Published: October 2008

Background—Endogenous adenosine can protect the overloaded heart against the development of hypertrophy and heart failure, but the contribution of A1receptors (A1R) and A3receptors (A3R) is not known.Methods and Results—To test the hypothesis that A1R and A3R can protect the heart against systolic overload, we exposed A3R gene-deficient (A3R knockout [KO]) mice and A1R KO mice to transverse aortic constriction (TAC). Contrary to our hypothesis, A3R KO attenuated 5-week TAC-induced left ventricular hypertrophy (ratio of ventricular mass/body weight increased to 7.6±0.3 mg/g in wild-type mice compared with 6.3±0.4 mg/g in KO mice), fibrosis, and dysfunction (left ventricular ejection fraction decreased to 43±2.5% and 55±4.2% in wild-type and KO mice, respectively). A3R KO also attenuated the TAC-induced increases of myocardial atrial natriuretic peptide and the oxidative stress markers 3′-nitrotyrosine and 4-hydroxynonenal. In contrast, A1R KO increased TAC-induced mortality but did not alter ventricular hypertrophy or dysfunction compared with wild-type mice. In mice in which extracellular adenosine production was impaired by CD73 KO, TAC caused greater hypertrophy and dysfunction and increased myocardial 3′-nitrotyrosine. In neonatal rat cardiomyocytes induced to hypertrophy with phenylephrine, the adenosine analogue 2-chloroadenosine reduced cell area, protein synthesis, atrial natriuretic peptide, and 3′-nitrotyrosine. Antagonism of A3R significantly potentiated the antihypertrophic effects of 2-chloroadenosine.Conclusions—Adenosine exerts protective effects on the overloaded heart, but the A3R acts counter to the protective effect of adenosine. The data suggest that selective attenuation of A3R activity might be a novel approach to treat pressure overload-induced left ventricular hypertrophy and dysfunction.
Do Contributors to Intellect Explain the Moral Judgment Abilities of Gifted Youth?
Authors: Derryberry W. Pitt , Barger Brian 
Published: October 2008

To assess reaction time and attributional complexity as factors contributing to the relatively high moral judgment of gifted youth, a sample of 30 gifted youth and 30 college students responded to a computerized measure of moral judgment development, which also indexed reaction time. Additionally, participants completed a measurement of attributional complexity and reported American College Test (ACT) scores. Statistically significant differences favored the gifted in moral judgment development, reaction time, and attributional complexity. Regression analysis revealed that attributional complexity explained a significant amount of variance, whereas ACT scores and reaction times accounted for minimal variance. Although reaction time did not predict moral judgment developmental difference, discussion is offered to suggest how gifted youth, such as those in this study, might benefit from using their reaction time when considering moral situations. Putting the Research to Use: The results of this study support the view that complex information processing and reaction time abilities of gifted youth are transferred to their moral judgment development. In sum, in comparison with a control group of college students, the gifted youth considered in this study appeared to process reasons for moral decisions in a more in-depth manner and were able to do so in a more efficient manner. Currently, it is unknown why and how this occurs, whether obstacles exist that could block this process, and whether practices exist that could help to facilitate these areas. Applications of these findings should therefore expound on these issues so that the utility of research on gifted moral judgment ability is increased. Applied research should also focus on transferring this understanding to general populations in the hopes of affecting the understanding of moral judgment development overall.
A Study of Differentiated Instructional Change Over 3 Years
Authors: VanTassel-Baska Joyce , Xuemei Feng Annie , Brown Elissa , Bracken Bruce , Stambaugh Tamra , French Heather , McGowan Susan , Worley Bess , Quek Chwee , Wenyu Bai  
Published: October 2008

This study examines Title 1 heterogeneous classroom teachers' instructional behavior change through implementing well-designed research-based curriculum units and attending regular professional development activities across 3 years. Employing an experimental design, this study compares experimental and comparison teachers' behavioral changes as measured by an observation scale of differentiated teaching strategies across 3 years. The results show that experimental teachers received statistically significant and educationally important higher ratings than comparison teachers on differentiated strategy use and effectiveness across 3 years. The study corroborates the research literature that shows that teachers' instructional improvement takes 2 years to manifest its effectiveness and to shape belief in student learning benefits. Putting the Research to Use: This study suggests several areas of practical application. One area is in the reality versus the myth of professional development. These data suggest the need for multiple years of professional development, interspersed with observations that track the frequency and efficacy of targeting instructional behaviors. Thus, educational reformers must be clear about what change they want teachers to achieve and set about a 2- to 3-year plan for making it happen at the school level. This study also lends support to more systematic approaches to encouraging differentiation. It highlights the need for monitoring classroom implementation. The use of a well-validated observation tool such as the Classroom Observation Scale—Revised provides a venue for ongoing instructional monitoring and improvement. Moreover, embedding content pedagogy in actual curriculum for training reduces the chance for inaccurate teacher inferencing about how to employ a strategy effectively.
Exploring the experiences and perspectives of families using a children’s hospice and professionals providing hospice care to identify future research priorities for children’s hospice care
Authors: Malcolm C , Forbat L , Knighting K , Kearney N 
Published: October 2008

The main objective of this study is to generate a list of priority topics for children’s hospice care research in Scotland from the perspective of its key stakeholders. The method consists of qualitative semi-structured interviews with families using hospice services ( n = 5), four focus groups with hospice staff and volunteers ( n = 44) and telephone interviews with professionals associated with the hospice ( n = 18). Fourteen broad themes emerged following thematic content and interpretive analysis of the interview data. Some of the research themes were specific to certain stakeholder groups, whereas other themes were identified unanimously across all the stakeholder groups as being priority areas for future research. Increasing awareness of and improving access to children’s hospice care, hospice and respite care needs of young people, community/home care and issues related to supporting the wider family arose, independently, in all three stakeholder groups as being priority topics for future research. In conclusion, a greater evidence base is required in the field of children’s palliative care and the topics researched should be identified and led by those most closely involved in the hospices. Engaging families and care providers in the process of identifying research priorities resulted in the development of an extensive research agenda, which will contribute to quality hospice care for children and families.
SHD1 is a novel cytokine-inducible, negative feedback regulator of STAT5-dependent transcription
Authors: Nakajima Hideaki , Tamura Toshiki , Ito Miyuki , Shibata Fumi , Kuroda Kana , Fukuchi Yumi , Watanabe Naohide , Kitamura Toshio , Ikeda Yasuo , Handa Makoto 
Published: October 2008

AbstractSTAT5 is a critical mediator of a variety of cytokine signaling whose transcriptional activity is regulated by associating with various proteins. During a search for STAT5-interacting proteins, we identified SHD1, a mammalian homologue of yeast gene Sac3, as a potential interacter. SHD1 was localized in the nucleus, and induced by cytokines that activate STAT5, such as erythropoietin, interleukin-2 (IL-2), or IL-3. SHD1 interacted specifically with STAT5A and STAT5B, and interestingly, it specifically repressed STAT5-dependent transcription in vitro without affecting the stability or phosphorylation of STAT5 protein. Gene disruption study revealed that T, B, or bone marrow cells from mice lacking SHD1 were hyperresponsive to T-cell–receptor engagement, or stimulation with various STAT5-activating cytokines. These results suggest that SHD1 is a novel cytokine-inducible negative feedback regulator of STAT5.
The GPIIb/IIIa (integrin αIIbβ3) odyssey: a technology-driven saga of a receptor with twists, turns, and even a bend
Authors: Coller Barry S. , Shattil Sanford J. 
Published: October 2008

AbstractStarting 90 years ago with a clinical description by Glanzmann of a bleeding disorder associated with a defect in platelet function, technologic advances helped investigators identify the defect as a mutation(s) in the integrin family receptor, αIIbβ3, which has the capacity to bind fibrinogen (and other ligands) and support platelet-platelet interactions (aggregation). The receptor's activation state was found to be under exquisite control, with activators, inhibitors, and elaborate inside-out signaling mechanisms controlling its conformation. Structural biology has produced high-resolution images defining the ligand binding site at the atomic level. Research on αIIbβ3 has been bidirectional, with basic insights resulting in improved Glanzmann thrombasthenia carrier detection and prenatal diagnosis, assays to identify single nucleotide polymorphisms responsible for alloimmune neonatal thrombocytopenia, and the development of αIIbβ3 antagonists, the first rationally designed antiplatelet agents, to prevent and treat thrombotic cardiovascular disease. The future looks equally bright, with the potential for improved drugs and the application of gene therapy and stem cell biology to address the genetic abnormalities. The αIIbβ3 saga serves as a paradigm of rigorous science growing out of careful clinical observations of a rare disorder yielding both important new scientific information and improved diagnosis, therapy, and prevention of other disorders.
A comprehensive analysis of the CDKN2A gene in childhood acute lymphoblastic leukemia reveals genomic deletion, copy number neutral loss of heterozygosity, and association with specific cytogenetic subgroups
Authors: Sulong Sarina , Moorman Anthony V. , Irving Julie A. E. , Strefford Jonathan C. , Konn Zoe J. , Case Marian C. , Minto Lynne , Barber Kerry E. , Parker Helen , Wright Sarah L. , Stewart Adam R. M. , Bailey Simon , Bown Nick P. , Hall Andrew G. , Harrison Christine J. 
Published: October 2008

AbstractInactivation of the tumor suppressor gene, CDKN2A, can occur by deletion, methylation, or mutation. We assessed the principal mode of inactivation in childhood acute lymphoblastic leukemia (ALL) and frequency in biologically relevant subgroups. Mutation or methylation was rare, whereas genomic deletion occurred in 21% of B-cell precursor ALL and 50% of T-ALL patients. Single nucleotide polymorphism arrays revealed copy number neutral (CNN) loss of heterozygosity (LOH) in 8% of patients. Array-based comparative genomic hybridization demonstrated that the mean size of deletions was 14.8 Mb and biallelic deletions composed a large and small deletion (mean sizes, 23.3 Mb and 1.4 Mb). Among 86 patients, only 2 small deletions were below the resolution of detection by fluorescence in situ hybridization. Patients with high hyperdiploidy, ETV6-RUNX1, or 11q23/MLL rearrangements had low rates of deletion (11%, 15%, 13%), whereas patients with t(9;22), t(1;19), TLX3, or TLX1 rearrangements had higher frequencies (61%, 42%, 78%, and 89%). In conclusion, CDKN2A deletion is a significant secondary abnormality in childhood ALL strongly correlated with phenotype and genotype. The variation in the incidence of CDKN2A deletions by cytogenetic subgroup may explain its inconsistent association with outcome. CNN LOH without apparent CDKN2A inactivation suggests the presence of other relevant genes in this region.
A method for analyzing censored survival phenotype with gene expression data
Authors: Wu Tongtong , Sun Wei , Yuan Shinsheng , Chen Chun-Houh , Li Ker-Chau 
Published: October 2008

AbstractBackgroundSurvival time is an important clinical trait for many disease studies. Previous works have shown certain relationship between patients' gene expression profiles and survival time. However, due to the censoring effects of survival time and the high dimensionality of gene expression data, effective and unbiased selection of a gene expression signature to predict survival probabilities requires further study.MethodWe propose a method for an integrated study of survival time and gene expression. This method can be summarized as a two-step procedure: in the first step, a moderate number of genes are pre-selected using correlation or liquid association (LA). Imputation and transformation methods are employed for the correlation/LA calculation. In the second step, the dimension of the predictors is further reduced using the modified sliced inverse regression for censored data (censorSIR).ResultsThe new method is tested via both simulated and real data. For the real data application, we employed a set of 295 breast cancer patients and found a linear combination of 22 gene expression profiles that are significantly correlated with patients' survival rate.ConclusionBy an appropriate combination of feature selection and dimension reduction, we find a method of identifying gene expression signatures which is effective for survival prediction.
Improved generation of rat gene knockouts by target-selected mutagenesis in mismatch repair-deficient animals
Authors: van Boxtel Ruben , Toonen Pim W , Verheul Mark , van Roekel Henk S , Nijman Isaac J , Guryev Victor , Cuppen Edwin 
Published: October 2008

Abstract

Background
The laboratory rat (Rattus norvegicus) is one of the preferred model organisms in physiological and pharmacological research, although the availability of specific genetic models, especially gene knockouts, is limited. N-ethyl-N-nitrosourea (ENU)-driven target-selected mutagenesis is currently the most successful method in rats, although it is still very laborious and expensive.

Results
As ENU-induced DNA damage is normally recognized by the mismatch repair (MMR) system, we hypothesized that the effectiveness of the target-selected mutagenesis approach could be improved by using a MMR-deficient genetic background. Indeed, Msh6 knockout rats were found to be more sensitive to ENU treatment and the germ line mutation rate was boosted more than two-fold to 1 mutation per 585 kb. In addition, the molecular mutation spectrum was found to be changed in favor of generating knockout-type alleles by ~20%, resulting in an overall increase in efficiency of ~2.5 fold. The improved effectiveness was demonstrated by high throughput mutation discovery in 70 Mb of sequence in a set of only 310 mutant F1 rats. This resulted in the identification of 89 mutations of which four introduced a premature stopcodon and 64 resulted in amino acid changes.

Conclusion
Taken together, we show that the use of a MMR-deficient background considerably improves ENU-driven target-selected mutagenesis in the rat, thereby reducing animal use as well as screening costs. The use of a mismatch repair-deficient genetic background for improving mutagenesis and target-selected knockout efficiency is in principle applicable to any organism of interest.
DroID: the Drosophila Interactions Database, a comprehensive resource for annotated gene and protein interactions
Authors: Yu Jingkai , Pacifico Svetlana , Liu Guozhen , Finley Russell L 
Published: October 2008

Abstract

Background
Charting the interactions among genes and among their protein products is essential for understanding biological systems. A flood of interaction data is emerging from high throughput technologies, computational approaches, and literature mining methods. Quick and efficient access to this data has become a critical issue for biologists. Several excellent multi-organism databases for gene and protein interactions are available, yet most of these have understandable difficulty maintaining comprehensive information for any one organism. No single database, for example, includes all available interactions, integrated gene expression data, and comprehensive and searchable gene information for the important model organism, Drosophila melanogaster.

Description
DroID, the Drosophila Interactions Database, is a comprehensive interactions database designed specifically for Drosophila. DroID houses published physical protein interactions, genetic interactions, and computationally predicted interactions, including interologs based on data for other model organisms and humans. All interactions are annotated with original experimental data and source information. DroID can be searched and filtered based on interaction information or a comprehensive set of gene attributes from Flybase. DroID also contains gene expression and expression correlation data that can be searched and used to filter datasets, for example, to focus a study on sub-networks of co-expressed genes. To address the inherent noise in interaction data, DroID employs an updatable confidence scoring system that assigns a score to each physical interaction based on the likelihood that it represents a biologically significant link.

Conclusion
DroID is the most comprehensive interactions database available for Drosophila. To facilitate downstream analyses, interactions are annotated with original experimental information, gene expression data, and confidence scores. All data in DroID are freely available and can be searched, explored, and downloaded through three different interfaces, including a text based web site, a Java applet with dynamic graphing capabilities (IM Browser), and a Cytoscape plug-in. DroID is available at http://www.droidb.org.
High-resolution array CGH clarifies events occurring on 8p in carcinogenesis
Authors: Cooke Susanna L , Pole Jessica CM , Chin Suet-Feung , Ellis Ian O , Caldas Carlos , Edwards Paul AW 
Published: October 2008

Abstract

Background
Rearrangement of the short arm of chromosome 8 (8p) is very common in epithelial cancers such as breast cancer. Usually there is an unbalanced translocation breakpoint in 8p12 (29.7 Mb – 38.5 Mb) with loss of distal 8p, sometimes with proximal amplification of 8p11-12. Rearrangements in 8p11-12 have been investigated using high-resolution array CGH, but the first 30 Mb of 8p are less well characterised, although this region contains several proposed tumour suppressor genes.

Methods
We analysed the whole of 8p by array CGH at tiling-path BAC resolution in 32 breast and six pancreatic cancer cell lines. Regions of recurrent rearrangement distal to 8p12 were further characterised, using regional fosmid arrays. FISH, and quantitative RT-PCR on over 60 breast tumours validated the existence of similar events in primary material.

Results
We confirmed that 8p is usually lost up to at least 30 Mb, but a few lines showed focal loss or copy number steps within this region. Three regions showed rearrangements common to at least two cases: two regions of recurrent loss and one region of amplification. Loss within 8p23.3 (0 Mb – 2.2 Mb) was found in six cell lines. Of the genes always affected, ARHGEF10 showed a point mutation of the remaining normal copies in the DU4475 cell line. Deletions within 12.7 Mb – 19.1 Mb in 8p22, in two cases, affected TUSC3. A novel amplicon was found within 8p21.3 (19.1 Mb – 23.4 Mb) in two lines and one of 98 tumours.

Conclusion
The pattern of rearrangements seen on 8p may be a consequence of the high density of potential targets on this chromosome arm, and ARHGEF10 may be a new candidate tumour suppressor gene.