bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-Gout Agent Allopurinol Exerts Cytotoxicity to Human Hormone-Refractory Prostate Cancer Cells in Combination with Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand
Authors: Yasuda Takashi , Yoshida Tatsushi , Goda Ahmed E. , Horinaka Mano , Yano Kimihiro , Shiraishi Takumi , Wakada Miki , Mizutani Yoichi , Miki Tsuneharu , Sakai Toshiyuki 
Published: December 2008

Abstract
Allopurinol has been used for the treatment of gout and conditions associated with hyperuricemia for several decades. We explored the potential of allopurinol on cancer treatment. Allopurinol did not expose cytotoxicity as a single treatment in human hormone refractory prostate cancer cell lines, PC-3 and DU145. However, allopurinol drastically induced apoptosis of PC-3 and DU145 in combination with tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), which is a promising candidate for anticancer agent but its efficacy is limited by the existence of resistant cancer cells. We examined the underlying mechanism by which allopurinol overcomes the resistance of prostate cancer cells to TRAIL. Allopurinol up-regulated the expression of a proapoptotic TRAIL receptor, death receptor 5 (DR5). Allopurinol increased DR5 protein, mRNA, and promoter activity. Using DR5 small interfering RNA (siRNA), we showed that allopurinol-mediated DR5 up-regulation contributed to the enhancement of TRAIL effect by allopurinol. Furthermore, we examined the mechanism of allopurinol-mediated DR5 up-regulation. DR5 promoter activity induced by allopurinol was diminished by a mutation of a CAAT/enhancer binding protein homologous protein (CHOP)-binding site. In addition, allopurinol also increased CHOP expression, suggesting that allopurinol induced DR5 expression via CHOP. Allopurinol possesses the activity of a xanthine oxidase (XO) inhibitor. We used XO siRNA instead of allopurinol. XO siRNA also up-regulated DR5 and CHOP expression and sensitized the prostate cancer cells to TRAIL-induced apoptosis. Here, we show the novel potential of allopurinol in cancer treatment and indicate that the combination of allopurinol with TRAIL is effective strategy to expand the TRAIL-mediated cancer therapy. (Mol Cancer Res 2008;6(12):1852–60)
Hedgehog-Induced Survival of B-Cell Chronic Lymphocytic Leukemia Cells in a Stromal Cell Microenvironment: A Potential New Therapeutic Target
Authors: Hegde Ganapati V. , Peterson Katie J. , Emanuel Katy , Mittal Amit K. , Joshi Avadhut D. , Dickinson John D. , Kollessery Gayathri J. , Bociek Robert G. , Bierman Philip , Vose Julie M. , Weisenburger Dennis D. , Joshi Shantaram S. 
Published: December 2008

Abstract
B-cell chronic lymphocytic leukemia (B-CLL) is characterized by an accumulation of neoplastic B cells due to their resistance to apoptosis and increased survival. Among various factors, the tumor microenvironment is known to play a role in the regulation of cell proliferation and survival of many cancers. However, it remains unclear how the tumor microenvironment contributes to the increased survival of B-CLL cells. Therefore, we studied the influence of bone marrow stromal cell–induced hedgehog (Hh) signaling on the survival of B-CLL cells. Our results show that a Hh signaling inhibitor, cyclopamine, inhibits bone marrow stromal cell–induced survival of B-CLL cells, suggesting a role for Hh signaling in the survival of B-CLL cells. Furthermore, gene expression profiling of primary B-CLL cells (n = 48) indicates that the expression of Hh signaling molecules, such as GLI1, GLI2, SUFU, and BCL2, is significantly increased and correlates with disease progression of B-CLL patients with clinical outcome. In addition, SUFU and GLI1 transcripts, as determined by real-time PCR, are significantly overexpressed and correlate with adverse indicators of clinical outcome in B-CLL patients, such as cytogenetics or CD38 expression. Furthermore, selective down-regulation of GLI1 by antisense oligodeoxynucleotides (GLI1-ASO) results in decreased BCL2 expression and cell survival, suggesting that GLI1 may regulate BCL2 and, thereby, modulate cell survival in B-CLL. In addition, there was significantly increased apoptosis of B-CLL cells when cultured in the presence of GLI1-ASO and fludarabine. Together, these results reveal that Hh signaling is important in the pathogenesis of B-CLL and, hence, may be a potential therapeutic target. (Mol Cancer Res 2008;6(12):1928–36)
Neural Stem Cell Tropism to Glioma: Critical Role of Tumor Hypoxia
Authors: Zhao Donghong , Najbauer Joseph , Garcia Elizabeth , Metz Marianne Z. , Gutova Margarita , Glackin Carlotta A. , Kim Seung U. , Aboody Karen S. 
Published: December 2008

Abstract
Hypoxia is a critical aspect of the microenvironment in glioma and generally signifies unfavorable clinical outcome. Effective targeting of hypoxic areas in gliomas remains a significant therapeutic challenge. New therapeutic platforms using neural stem cells (NSC) for tumor-targeted drug delivery show promise in treatment of cancers that are refractory to traditional therapies. However, the molecular mechanisms of NSC targeting to hypoxic tumor areas are not well understood. Therefore, we investigated the role of hypoxia in directed migration of NSCs to glioma and identified the specific signaling molecules involved. Our data showed that hypoxia caused increased migration of human HB1.F3 NSCs to U251 human glioma-conditioned medium in vitro. In HB1.F3 NSCs, hypoxia led to up-regulation of CXCR4, urokinase-type plasminogen activator receptor (uPAR), vascular endothelial growth factor receptor 2 (VEGFR2), and c-Met receptors. Function-inhibiting antibodies to these receptors inhibited the migration of HB1.F3 cells to glioma-conditioned medium. Small interfering RNA knockdown of hypoxia-inducible factor-1α in glioma cells blocked the hypoxia-induced migration of NSCs, which was due to decreased expression of stromal cell–derived factor-1 (SDF-1), uPA, and VEGF in glioma cells. Our in vivo data provided direct evidence that NSCs preferentially distributed to hypoxic areas inside intracranial glioma xenografts, as detected by pimonidazole hypoxia probe, as well as to the tumor edge, and that both areas displayed high SDF-1 expression. These observations indicate that hypoxia is a key factor in determining NSC tropism to glioma and that SDF-1/CXCR4, uPA/uPAR, VEGF/VEGFR2, and hepatocyte growth factor/c-Met signaling pathways mediate increased NSC-to-glioma tropism under hypoxia. These results have significant implications for development of stem cell–mediated tumor-selective gene therapies. (Mol Cancer Res 2008;6(12):1819–29)
Mutations in theSOD2Promoter Reveal a Molecular Basis for an Activating Protein 2-Dependent Dysregulation of Manganese Superoxide Dismutase Expression in Cancer Cells
Authors: Xu Yong , Fang Fang , Dhar Sanjit K. , Bosch Antonio , St. Clair William H. , Kasarskis Edward J. , St. Clair Daret K. 
Published: December 2008

AbstractA primary antioxidant enzyme in mitochondria, manganese superoxide dismutase (MnSOD), plays a critical role in the survival of aerobic life. It is well documented that, compared with normal cell counterparts, MnSOD level is decreased in neoplastic transformed cells but is increased in aggressive cancers. However, the underlying mechanism for the observed dysregulation of MnSOD in cancer is unknown. We have identified previously a unique set of mutations located in the promoter region of the SOD2 gene in several types of cancer cells. We found that a C-to-T transition at -102 and an insertion of A at -93 down-regulate MnSOD transcription by interrupting the formation of a single-stranded loop that is essential for a high level of promoter activity. Here, we show that the additional downstream mutation, C-to-G transversion at -38, creates a binding site for the transcription factors specificity protein 1 (Sp1) and activating protein 2 (AP-2). The promoter function is regulated by the relative levels of Sp1 and AP-2. In cytokine-induced expression of the SOD2 gene, Sp1 cooperates with a transcriptional complex containing nuclear factor-κB and nucleophosmin. The presence of AP-2 attenuates this induction. Our results suggest that the high level of MnSOD observed in aggressive cancer cells may be due, in part, to the absence of AP-2 transcriptional repression. (Mol Cancer Res 2008;6(12):1881–93)
Functional Neuroanatomy of Contextual Acquisition of Concrete and Abstract Words
Authors: Mestres-Missé Anna , Münte Thomas F. , Rodriguez-Fornells Antoni 
Published: December 2008

Abstract
The meaning of a novel word can be acquired by extracting it from linguistic context. Here we simulated word learning of new words associated to concrete and abstract concepts in a variant of the human simulation paradigm that provided linguistic context information in order to characterize the brain systems involved. Native speakers of Spanish read pairs of sentences in order to derive the meaning of a new word that appeared in the terminal position of the sentences. fMRI revealed that learning the meaning associated to concrete and abstract new words was qualitatively different and recruited similar brain regions as the processing of real concrete and abstract words. In particular, learning of new concrete words selectively boosted the activation of the ventral anterior fusiform gyrus, a region driven by imageability, which has previously been implicated in the processing of concrete words.
Lesion Evidence That Two Distinct Regions within Prefrontal Cortex are Critical for n-Back Performance in Humans
Authors: Tsuchida Ami , Fellows Lesley K. 
Published: December 2008

Abstract
Although prefrontal cortex is clearly important in executive function, the specific processes carried out by particular regions within human prefrontal cortex remain a matter of debate. A rapidly growing corpus of functional imaging work now implicates various areas within prefrontal cortex in a wide range of “executive” tasks. Loss-of-function studies can help constrain the interpretation of such evidence by testing to what extent particular brain areas are necessary for a given cognitive process. Here we apply a component process analysis to understand prefrontal contributions to the n-back task, a widely used test of working memory, in a cohort of patients with focal prefrontal damage. We investigated letter 2-back task performance in 27 patients with focal damage to various regions within prefrontal cortex, compared to 29 demographically matched control subjects. Both “behavior-defined” approaches, using qualitative lesion analyses and voxel-based lesion–symptom mapping methods, and more conventional “lesion-defined” groupwise comparisons were undertaken to determine the relationships between specific sites of damage within prefrontal cortex and particular aspects of n-back task performance. We confirmed a critical role for left lateral prefrontal cortex in letter 2-back performance. We also identified a critical role for medial prefrontal cortex in this task: Damage to dorsal anterior cingulate cortex and adjacent dorsal fronto-medial cortex led to a pattern of impairment marked by high false alarm rates, distinct from the impairment associated with lateral prefrontal damage. These findings provide converging support for regionally specific models of human prefrontal function.
Sources of Top–Down Control in Visual Search
Authors: Weidner Ralph , Krummenacher Joseph , Reimann Brit , Müller Hermann J. , Fink Gereon R. 
Published: December 2008

Abstract
Endogenous control of visual search can influence search guidance at the level of a supradimensional topographic saliency map [Wolfe, J. M. Guided Search 2.0: A revised model of visual search. Psychonomic Bulletin & Review, 1, 202–238, 1994], and modulate nonspatial mechanisms coding saliency in dimension-specific input modules [Müller, H. J., Reimann, B., & Krummenacher, J. Visual search for singleton feature targets across dimensions: Stimulus- and expectancy-driven effects in dimensional weighting. Journal of Experimental Psychology: Human Perception and Performance, 29, 1021–1035, 2003]. The current experiment used fMRI to dissociate these mechanisms in a singleton feature search task in which the likely target dimension (color or orientation) was semantically precued and target saliency in each dimension was varied parametrically. BOLD signal increases associated with increased demands for top–down guidance were observed within the fronto-parietal attention network and in the right anterior middle frontal gyrus. Decreasing requirements for top–down control led to BOLD signal increases in medial anterior prefrontal cortex, consistent with a gating mechanism in favor of stimulus-related processing [Burgess, P. W., Dumontheil, I., & Gilbert, S. J. The gateway hypothesis of rostral prefrontal cortex (area 10) function. Trends in Cognitive Sciences, 11, 290–298, 2007]. Another network of brain areas consisting of left lateral fronto-polar cortex, the left supramarginal gyrus, and the cerebellum, as well as a bilateral network consisting of the posterior orbital gyrus, the inferior frontal gyrus, and the pre-SMA were associated with top–down dimensional (re-) orienting. These data argue in favor of distinct endogenous control systems for visuospatial and dimension-based attentional processing. Finally, cue validity modulated saliency processing in the left temporo-parietal junction (TPJ), pointing to a crucial role of the left TPJ in integrating an endogenous dimension-based attention set with bottom–up saliency signals.
Co-localization of Stroop and Syntactic Ambiguity Resolution in Broca's Area: Implications for the Neural Basis of Sentence Processing
Authors: January David , Trueswell John C. , Thompson-Schill Sharon L. 
Published: December 2008

Abstract
For over a century, a link between left prefrontal cortex and language processing has been accepted, yet the precise characterization of this link remains elusive. Recent advances in both the study of sentence processing and the neuroscientific study of frontal lobe function suggest an intriguing possibility: The demands to resolve competition between incompatible characterizations of a linguistic stimulus may recruit top–down cognitive control processes mediated by prefrontal cortex. We use functional magnetic resonance imaging to test the hypothesis that individuals use shared prefrontal neural circuitry during two very different tasks—color identification under Stroop conflict and sentence comprehension under conditions of syntactic ambiguity—both of which putatively rely on cognitive control processes. We report the first demonstration of within-subject overlap in neural responses to syntactic and nonsyntactic conflict. These findings serve to clarify the role of Broca's area in, and the neural and psychological organization of, the language processing system.
On the Influence of Random Wind Stress Errors on the Four-Dimensional, Midlatitude Ocean Inverse Problem
Authors: Wakamatsu Tsuyoshi , Foreman Michael G. G. , Cummins Patrick F. , Cherniawsky Josef Y. 
Published: December 2008

Abstract
The effects of the parameterized wind stress error covariance function on the a priori error covariance of an ocean general circulation model (OGCM) are examined. These effects are diagnosed by computing the projection of the a priori model state error covariance matrix to sea surface height (SSH). The sensitivities of the a priori error covariance to the wind stress curl error are inferred from the a priori SSH error covariance and are shown to differ between the subpolar and subtropical gyres because of different contributions from barotropic and baroclinic ocean dynamics. The spatial structure of the SSH error covariance due to the wind stress error indicates that the a priori model state error is determined indirectly by the wind stress curl error. The impact of this sensitivity on the solution of a four-dimensional inverse problem is inferred.
Parent Perspectives of Diabetes Management in Schools
Authors: Jacquez Farrah , Stout Stacey , Alvarez-Salvat Rose , Fernandez Michelle , Villa Manuela , Sanchez Janine , Eidson Margaret , Nemery Robin , Delamater Alan 
Published: December 2008

Purpose The purpose of this study is to investigate parent reports of the diabetes care support their children receive in school, their concerns about diabetes management in school, and their knowledge of federal laws that protect children with diabetes. In addition, the study explores ethnic and socioeconomic status differences in diabetes management in school. Methods An ethnically heterogeneous sample of 309 parents of children with diabetes was recruited from a community-based and a university-based diabetes outpatient clinic. Parents completed a survey assessing supports their child's school provides for diabetes care, worries about diabetes care in school, and awareness of federal laws that pertain to children with diabetes. Results Many children did not have a written care plan or a nurse at school, but significantly more white children had these supports than Hispanic or black children. Most children were not allowed to check blood glucose levels or administer insulin in class. Most parents were worried about hyperglycemia and hypoglycemia in school, and most were not at all or only a little confident in the school's ability to care for diabetes. Most parents were not aware of federal laws, but high-income and white parents were more likely to be aware. Conclusions According to parents in the current study, children receive inadequate diabetes management support in schools. Minority children are less likely to receive supports than white children. Parents are worried about diabetes management in school, but most do not have the knowledge of federal laws necessary to protect their children.
Affecting Behavior Change in Individuals With Diabetes Findings From the Study to Help Improve Early Evaluation and Management of Risk Factors Leading to Diabetes (SHIELD)
Authors: Bazata Debbra D. , Robinson Jennifer G. , Fox Kathleen M. , Grandy Susan , SHIELD Study Group  
Published: December 2008

Purpose This study evaluated whether health knowledge, attitudes, and behaviors of individuals with type 1 (T1DM) or type 2 (T2DM) diabetes mellitus and those at high or low risk of T2DM were reflected in healthy behaviors and whether these attributes differed for T2DM respondents who did or did not see a health educator. Methods SHIELD, a U.S. population-based study, included respondents (‡18 years of age) with T1DM (n = 366), T2DM (n = 3897), high risk (HR, n = 5449) defined as ‡3 of the following: abdominal obesity, high body mass index, dyslipidemia, hypertension, cardiovascular disease, and low risk (LR, n = 5725) defined as £2 factors. Results T2DM respondents were more likely to receive health care professional recommendations to change their lifestyle habits (56%-62%) during their average 11 visits annually than the other groups (P < .0001). More T2DM and HR respondents tried losing weight, but fewer exercised regularly than T1DM and LR (P < .0001). T2DM respondents who saw a dietitian or health educator reported better current health and expectations for better future health, tried to make healthy food choices, and followed a prescribed eating plan than those who did not see these providers (P < .01). However, £30% of these T2DM respondents exercised regularly, or maintained desired weight. Conclusions SHIELD findings show that respondents know and understand that improving their diet or exercise will affect their health, but the majority of respondents have not translated it into a behavior. Interaction with health educators and patient-empowering support may improve the transition to behavior change.
A critical role for DAP10 and DAP12 in CD8+ T cell–mediated tissue damage in large granular lymphocyte leukemia
Authors: Chen Xianghong , Bai Fanqi , Sokol Lubomir , Zhou Junmin , Ren Amy , Painter Jeffrey S. , Liu Jinhong , Sallman David A. , Chen Y. Ann , Yoder Jeffrey A. , Djeu Julie Y. , Loughran Thomas P. , Epling-Burnette Pearlie K. , Wei Sheng 
Published: December 2008

Abstract
Large granular lymphocyte (LGL) leukemia, or LGLL, is characterized by increased numbers of circulating clonal LGL cells in association with neutropenia, anemia, rheumatoid arthritis, and pulmonary artery hypertension (PAH). Emerging evidence suggests that LGLL cells with a CD8+CD28null phenotype induce these clinical manifestations through direct destruction of normal tissue. Compared with CD8+CD28null T cells from healthy controls, CD8+CD28null T cells from LGLL patients have acquired the ability to directly lyse pulmonary artery endothelial cells and human synovial cells. Here, we show that LGLL cells from patients possess enhanced cytotoxic characteristics and express elevated levels of activating natural killer receptors as well as their signaling partners, DAP10 and DAP12. Moreover, downstream targets of DAP10 and DAP12 are constitutively activated in LGLL cells, and expression of dominant-negative DAP10 and DAP12 dramatically reduces their lytic capacity. These are the first results to show that activating NKR-ligand interactions play a critical role in initiating the DAP10 and DAP12 signaling events that lead to enhanced lytic potential of LGLL cells. Results shown suggest that inhibitors of DAP10 and DAP12 or other proteins involved in this signaling pathway will be attractive therapeutic targets for the treatment of LGLL and other autoimmune diseases and syndromes.
Synthesis of an Organic-soluble π-Conjugated [1]Rotaxane
Authors: Tsuda Susumu , Terao Jun , Kambe Nobuaki 
Published: December 2008

Abstract
An organic-soluble π-conjugated [1]rotaxane has been synthesized by intramolecular self-inclusion of a lipophilic permethylated α-cyclodextrin bearing a rigid π-conjugated system as a guest moiety. End-capping has been achieved successfully by connecting an aniline moiety without using bulky stoppers. The structure of the [1]rotaxane was determined by 2D NMR spectroscopy.
Aerosol-assisted Fabrication of Porous Silica Spheres with a Hierarchical Pore System through Multicomponent Assembly
Authors: Yamauchi Yusuke , Gupta Prashant , Fukata Naoki , Sato Keisuke 
Published: December 2008

Abstract
Hierarchical porous silica spheres with a trimodal pore system are prepared through multicomponent assembly, which is a facile one-pot fabrication and can best be employed for industrial mass-scale production.
Air permeability in longitudinal and radial directions of compression wood of Picea abies L. and tension wood of Fagus sylvatica L.
Authors: Tarmian Asghar , Perré Patrick 
Published: December 2008

Abstract
The air permeability in longitudinal and radial directions of compression wood in spruce (Picea abies) and tension wood in beech (Fagus sylvatica) was compared with that of the corresponding normal wood. The primary aim of the present study was to explain why the reaction woods dry more slowly than the normal woods in the domain of free water. A number of boards conventionally dried to an average final moisture content of 12% were chosen to perform the measurements. Bordered pits on the radial walls of longitudinal tracheids in the compression and normal wood and intervessel or intervascular pits in the tension and normal wood were also examined. The reaction wood of both species is less permeable than the normal wood, both in longitudinal and radial directions. The difference in permeability was more pronounced between compression and normal wood of spruce, especially in longitudinal direction. From an anatomical point of view, this is likely related to some differences in anatomical characteristics affecting the airflow paths, such as the pit features. Such results can explain the difference in drying kinetics of the reaction and normal woods in the capillary regime of drying.