bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD47 Regulates Bone Mass and Tumor Metastasis to Bone
Authors: Uluçkan Özge , Becker Stephanie N. , Deng Hongju , Zou Wei , Prior Julie L. , Piwnica-Worms David , Frazier William A. , Weilbaecher Katherine N. 
Published: March 2009

Abstract
CD47, also called integrin-associated protein, plays a critical role in the innate immune response and is an atypical member of the immunoglobulin superfamily that interacts with and activates β3 integrins. β3 integrin−/− mice have defective platelet and osteoclast function and are protected from bone metastasis. The role of CD47 in skeletal homeostasis and bone metastasis has not been described. CD47−/− mice had increased bone mass and defective osteoclast function in vivo. Although the number of functional osteoclasts formed by differentiating CD47−/− bone marrow macrophages was decreased, high doses of RANKL rescued differentiation and function of CD47−/− osteoclasts ex vivo and rescued the osteoclast defect in CD47−/− mice. Inhibition of nitric oxide (NO) synthase, which is expressed at higher levels in CD47−/− osteoclasts, also rescued the osteoclast defect in CD47−/− cells. We then examined the consequences of this osteoclast defect in bone metastasis. In a model of tumor metastasis to bone, bone tumor burden was decreased in the CD47−/− mice compared with wild-type (WT) controls, with no decrease in s.c. tumor growth in CD47−/− mice. There was decreased tumor-associated bone destruction in the CD47−/− mice compared with WT controls, consistent with a defect in osteoclast function that was not rescued by the presence of tumor. Our data show that CD47 regulates osteoclastogenesis, in part, via regulation of NO production, and its disruption leads to a decrease in tumor bone metastasis. CD47 is a novel therapeutic target to strengthen bone mass and diminish metastatic tumor growth in bone. [Cancer Res 2009;69(7):3196–204]
NADPH Oxidase 4 Contributes to Transformation Phenotype of Melanoma Cells by Regulating G2-M Cell Cycle Progression
Authors: Yamaura Maki , Mitsushita Junji , Furuta Shuichi , Kiniwa Yukiko , Ashida Atsuko , Goto Yasuhumi , Shang Wei H. , Kubodera Makoto , Kato Masayoshi , Takata Minoru , Saida Toshiaki , Kamata Tohru 
Published: March 2009

Abstract
Generation of reactive oxygen species (ROS) has been implicated in carcinogenic development of melanoma, but the underlying molecular mechanism has not been fully elucidated. We studied the expression and function of the superoxide-generating NADPH oxidase (Nox)4 in human melanoma cells. Nox4 was up-regulated in 13 of 20 melanoma cell lines tested. Silencing of Nox4 expression in melanoma MM-BP cells by small interfering RNAs decreased ROS production and thereby inhibited anchorage-independent cell growth and tumorigenecity in nude mice. Consistently, a general Nox inhibitor, diphenylene iodonium, and antioxidants vitamine E and pyrrolidine dithiocarbamate blocked cell proliferation of MM-BP cells. Flow cytometric analysis indicated that Nox4 small interfering RNAs and diphenylene iodonium induced G2-M cell cycle arrest, which was also observed with another melanoma cell line, 928mel. This was accompanied by induction of the Tyr-15 phosphorylated, inactive form of cyclin-dependent kinase 1 (a hallmark of G2-M checkpoint) and hyperphosphorylation of cdc25c leading to its increased binding to 14-3-3 proteins. Ectopic expression of catalase, a scavenger of ROS, also caused accumulation of cells in G2-M phase. Immunohistochemistry revealed that expression of Nox4 was detected in 31.0% of 13 melanoma patients samples, suggesting the association of Nox4 expression with some steps of melanoma development. The findings suggest that Nox4-generated ROS are required for transformation phenotype of melanoma cells and contribute to melanoma growth through regulation of G2-M cell cycle progression. [Cancer Res 2009;69(6):2647–54]
Identification of a small molecule class to enhance cell-cell adhesion and attenuate prostate tumor growth and metastasis
Authors: Shah Girish V. , Muralidharan Anbalagan , Thomas Shibu , Gokulgandhi Mitan , Mudit Mudit , Khanfar Mohammad , El Sayed Khalid 
Published: March 2009

Abstract
Expression of calcitonin (CT) and its receptor (CTR) is elevated in advanced prostate cancer, and activated CT-CTR autocrine axis plays a pivotal role in tumorigenicity and metastatic potential of multiple prostate cancer cell lines. Recent studies suggest that CT promotes prostate cancer metastasis by reducing cell-cell adhesion through the disassembly of tight and adherens junctions and activation of β-catenin signaling. We attempted to identify a class of molecules that enhances cell-cell adhesion of prostate cells and reverses the disruptive actions of CT on tight and adherens junctions. Screening several compounds led to the emergence of phenyl-methylene hydantoin (PMH) as a lead candidate that can augment cell-cell adhesion and abolish disruptive actions of CT on junctional complexes. PMH reduced invasiveness of PC-3M cells and abolished proinvasive actions of CT. Importantly, PMH did not display significant cytotoxicity on PC-3M cells at the tested doses. I.p. administered PMH and its S-ethyl derivative remarkably decreased orthotopic tumor growth and inhibited the formation of tumor micrometastases in distant organs of nude mice. PMH treatment also reduced the growth of spontaneous tumors in LPB-Tag mice to a significant extent without any obvious cytotoxic effects. By virtue of its ability to stabilize cell junctions, PMH could reverse the effect of CT on junctional disruption and metastasis, which strengthens the possibility of using PMH as a potential drug candidate for CT-positive androgen-independent prostate cancers. [Mol Cancer Ther 2009;8(3):509–20]
Planetary Scale Selection of the Madden–Julian Oscillation*
Authors: Li Tim , Zhou Chunhua 
Published: March 2009

Abstract
Numerical experiments with a 2.5-layer and a 2-level model are conducted to examine the mechanism for the planetary scale selection of the Madden–Julian oscillation (MJO). The strategy here is to examine the evolution of an initial perturbation that has a form of the equatorial Kelvin wave at zonal wavenumbers of 1 to 15. In the presence of a frictional boundary layer, the most unstable mode prefers a short wavelength under a linear heating; but with a nonlinear heating, the zonal wavenumber 1 grows fastest. This differs significantly from a model without the boundary layer, in which neither linear nor nonlinear heating leads to the long wave selection. Thus, the numerical simulations point out the crucial importance of the combined effect of the nonlinear heating and the frictional boundary layer in the MJO planetary scale selection.
The cause of this scale selection under the nonlinear heating is attributed to the distinctive phase speeds between the dry Kelvin wave and the wet Kelvin–Rossby wave couplet. The faster dry Kelvin wave triggered by a convective branch may catch up and suppress another convective branch, which travels ahead of it at the phase speed of the wet Kelvin–Rossby wave couplet if the distance between the two neighboring convective branches is smaller than a critical distance (about 16 000 km). The interference between the dry Kelvin wave and the wet Kelvin–Rossby wave couplet eventually dissipates and “filters out” shorter wavelength perturbations, leading to a longwave selection. The boundary layer plays an important role in destabilizing the MJO through frictional moisture convergences and in retaining the in-phase zonal wind–pressure structure.
North Pacific Gyre Oscillation Synchronizes Climate Fluctuations in the Eastern and Western Boundary Systems*
Authors: Ceballos Lina I. , Di Lorenzo Emanuele , Hoyos Carlos D. , Schneider Niklas , Taguchi Bunmei 
Published: March 2009

Abstract
Recent studies have identified the North Pacific Gyre Oscillation (NPGO) as a mode of climate variability that is linked to previously unexplained fluctuations of salinity, nutrient, and chlorophyll in the northeast Pacific. The NPGO reflects changes in strength of the central and eastern branches of the subtropical gyre and is driven by the atmosphere through the North Pacific Oscillation (NPO), the second dominant mode of sea level pressure variability in the North Pacific. It is shown that Rossby wave dynamics excited by the NPO propagate the NPGO signature in the sea surface height (SSH) field from the central North Pacific into the Kuroshio–Oyashio Extension (KOE), and trigger changes in the strength of the KOE with a lag of 2–3 yr. This suggests that the NPGO index can be used to track changes in the entire northern branch of the North Pacific subtropical gyre. These results also provide a physical mechanism to explain coherent decadal climate variations and ecosystem changes between the North Pacific eastern and western boundaries.
A Nonlinear Theory of the Kuroshio Extension Bimodality
Authors: Pierini Stefano , Dijkstra Henk A. , Riccio Angelo 
Published: March 2009

AbstractThe Kuroshio Extension (KE) flow in the North Pacific Ocean displays a very distinctive decadal variability of bimodal character involving two completely different states (a large-meander “elongated” state and a small-meander “contracted” state) connected by very asymmetric temporal transitions. Although such a flow has been widely studied by means of a suite of mathematical models and by using several observational platforms, a satisfactory theoretical framework answering quite elementary questions is still lacking, the main question being whether such variability is induced by a time-varying wind forcing or, rather, by intrinsic oceanic mechanisms. In this context, the chaotic relaxation oscillation produced by a process-oriented model of the KE low-frequency variability, with steady climatological wind forcing, was recently recognized to be in substantial agreement with altimeter data. Here those model results are further compared with a comprehensive altimeter dataset. The positive result of such a comparison allows the conclusion that a minimal model for the KE bimodality has been identified and that, consequently, nonlinear intrinsic oceanic mechanisms are likely to be the main cause of the observed variability. By applying the methods of nonlinear dynamical systems theory, relevant dynamical features of the modeled flow are then explained, such as the origin of the relaxation oscillation as a consequence of a homoclinic bifurcation, the spatiotemporal character of the bimodal behavior, and the degree of predictability of the flow in the different stages of the oscillation (evaluated through a field of finite-time Lyapunov exponents and the corresponding Lagrangian time series).
Characteristics of Nocturnal Low-Level Jets Observed in the North Florida Area
Authors: Karipot Anandakumar , Leclerc Monique Y. , Zhang Gengsheng 
Published: March 2009

Abstract
The seasonal and interannual variability of the nocturnal low-level jets over the north Florida region are investigated using sodar measurements spanning 540 nights. On average, jets are present in 62% of the nocturnal periods examined. The observed jet speeds range between 3 and 21 m s−1 and heights are between 80 and 700 m. Observations show that the low-level jet occurs more frequently (70% of the nocturnal periods) during the colder months November–February in contrast with the warmer months June–August (∼47%). The presence of southerly jets dominates the summer months, whereas northerly jets are more frequent during winter. Colder months frequently exhibit jets with speeds exceeding 14 m s−1, often associated with the passage of frontal systems. The interannual variability observed using the North American Regional Reanalysis (NARR) wind profile data during a 4-yr period shows only minimal differences in jet characteristics. A comparison of jet heights with NARR planetary boundary layer heights suggests that jets at the north Florida location frequently occur within the planetary boundary layer. The occurrence and speed of observed low-level jets are linked to both the land–ocean temperature contrast and to the strength and orientation of surface pressure gradients over the region. A high occurrence of large-amplitude oscillations with approximately a 24-h period near the jet height is shown using the Hilbert–Huang transform analysis, suggesting that inertial oscillations are one possible cause of jet formation in north Florida.
Oncocytic, focally anaplastic, thyroid cancer responding to erlotinib
Authors: Hogan Thomas , Jing Jie Yu  , Williams H James , Altaha Ramin , Xiaobing Liang  , Qi He  
Published: March 2009

Objective. To highlight the molecular findings and clinical response of a patient with rapidly progressing, focally anaplastic, oncocytic thyroid carcinoma (OTC) treated with erlotinib. Case Summary. A 69-year-old woman with recurrent, focally anaplastic OTC was given a therapeutic trial of erlotinib, a small molecule inhibitor of epidermal growth factor receptor (EGFR). Formalin-fixed, paraffin-embedded portions of the tumor were analyzed for EGFR expression, and tumor genomic DNA was amplified by polymerase chain reaction (PCR) and subjected to EGFR mutation analysis. Discussion. An early and dramatic response was achieved with erlotinib. The tumor was focally positive for EGFR by immunostaining and two point mutations were identified, one on exon 18 and one on exon 20 in the tyrosine kinase (TK) domain. Conclusion. Erlotinib or other novel protein kinase pathway inhibitors should be evaluated further in patients with aggressive thyroid cancer variants, who may exhibit these and perhaps other tyrosine kinase mutations. J Oncol Pharm Practice (2009) 15: 111—117.
Assessment of gentamicin 7 mg/kg once daily for pediatric patients with febrile neutropenia: a pilot project
Authors: Newby Brandi , Prevost Derek , Lotocka-Reysner Hanna 
Published: March 2009

Context. Use of once daily aminoglycosides continues to increase for the pediatric population, including oncology patients. Concerns have been identified and still need to be resolved including the optimal dose, frequency, and monitoring parameters. Objective. We completed a study to determine if empiric use of gentamicin 7 mg/kg once daily in pediatric patients admitted with febrile neutropenia provided extrapolated peaks and drug-free intervals consistent with suggested preferred levels. Design. A review of the patient’s chart was completed following their discharge from the hospital between September 2006 and October 2007. Setting. A community hospital. Patients. A consecutive sample of 17 encounters for pediatric patients admitted for febrile neutropenia that received once daily gentamicin. Main outcome measures. Extrapolated peak levels and drug-free intervals. Results. There were seven patients with a total of 17 encounters. The mean extrapolated peak level was 16.9 mg/L. The mean drug-free interval was 15.7 h. Both target peak and drug-free interval were obtained for two encounters (12%), which was one patient. Conclusion. Gentamicin 7 mg/kg/dose once daily does not provide preferred levels for all pediatric febrile neutropenic patients. Further investigation is required to ensure that once daily gentamicin regimens for pediatric oncology patients provide adequate clinical success. J Oncol Pharm Practice (2009) 15: 211—216.
Dynamics of central and peripheral immunomodulation in a murine glioma model
Authors: Kennedy Benjamin C , Maier Lisa M , D'Amico Randy , Mandigo Christopher E , Fontana Elizabeth J , Waziri Allen , Assanah Marcela C , Canoll Peter , Anderson Richard CE , Anderson David E , Bruce Jeffrey N 
Published: March 2009

Abstract

Background
Immunosuppression by gliomas contributes to tumor progression and treatment resistance. It is not known when immunosuppression occurs during tumor development but it likely involves cross-talk among tumor cells, tumor-associated macrophages and microglia (TAMs), and peripheral as well as tumor-infiltrating lymphocytes (TILs).

Results
We have performed a kinetic study of this immunomodulation, assessing the dynamics of immune infiltration and function, within the central nervous system (CNS) and peripherally. PDGF-driven murine glioma cells were injected into the white matter of 13 mice. Four mice were sacrificed 13 days post-injection (dpi), four mice at 26 dpi, and five mice at 40 dpi. Using multiparameter flow cytometry, splenic T cells were assessed for FoxP3 expression to identify regulatory T cells (Tregs) and production of IFN-γ and IL-10 after stimulation with PMA/ionomycin; within the CNS, CD4+ TILs were quantified, and TAMs were quantified and assessed for TNF-α and IL-10 production after stimulation with LPS. Peripheral changes associated with tumor development were noted prior to effects within the CNS. The percentage of FoxP3+ regulatory T cells (Tregs) increased by day 26, with elevated frequencies throughout the duration of the study. This early increase in Tregs was paralleled by an increase in IL-10 production from Tregs. At the final time points examined (tumor morbidity or 40 dpi), there was an increase in the frequency of TAMs with decreased capacity to secrete TNF-α. An increase in TIL frequency was also observed at these final time points.

Conclusion
These data provide insight into the kinetics of the immunosuppressive state associated with tumor growth in a murine model of human gliomas. Functional impairment of TAMs occurs relatively late in the course of GBM tumor growth, potentially providing a window of opportunity for therapeutic strategies directed towards preventing their functional impairment.
Diversity and transcription of proteases involved in the maturation of hydrogenases in Nostoc punctiforme ATCC 29133 and Nostocsp. strain PCC 7120
Authors: Devine Ellenor , Holmqvist Marie , Stensjö Karin , Lindblad Peter 
Published: March 2009

Abstract

Background
The last step in the maturation process of the large subunit of [NiFe]-hydrogenases is a proteolytic cleavage of the C-terminal by a hydrogenase specific protease. Contrary to other accessory proteins these hydrogenase proteases are believed to be specific whereby one type of hydrogenases specific protease only cleaves one type of hydrogenase. In cyanobacteria this is achieved by the gene product of either hupW or hoxW, specific for the uptake or the bidirectional hydrogenase respectively. The filamentous cyanobacteria Nostoc punctiforme ATCC 29133 and Nostoc sp strain PCC 7120 may contain a single uptake hydrogenase or both an uptake and a bidirectional hydrogenase respectively.

Results
In order to examine these proteases in cyanobacteria, transcriptional analyses were performed of hupW in Nostoc punctiforme ATCC 29133 and hupW and hoxW in Nostoc sp. strain PCC 7120. These studies revealed numerous transcriptional start points together with putative binding sites for NtcA (hupW) and LexA (hoxW). In order to investigate the diversity and specificity among hydrogeanse specific proteases we constructed a phylogenetic tree which revealed several subgroups that showed a striking resemblance to the subgroups previously described for [NiFe]-hydrogenases. Additionally the proteases specificity was also addressed by amino acid sequence analysis and protein-protein docking experiments with 3D-models derived from bioinformatic studies. These studies revealed a so called "HOXBOX"; an amino acid sequence specific for protease of Hox-type which might be involved in docking with the large subunit of the hydrogenase.

Conclusion
Our findings suggest that the hydrogenase specific proteases are under similar regulatory control as the hydrogenases they cleave. The result from the phylogenetic study also indicates that the hydrogenase and the protease have co-evolved since ancient time and suggests that at least one major horizontal gene transfer has occurred. This co-evolution could be the result of a close interaction between the protease and the large subunit of the [NiFe]-hydrogenases, a theory supported by protein-protein docking experiments performed with 3D-models. Finally we present data that may explain the specificity seen among hydrogenase specific proteases, the so called "HOXBOX"; an amino acid sequence specific for proteases of Hox-type. This opens the door for more detailed studies of the specificity found among hydrogenase specific proteases and the structural properties behind it.
High-throughput mutational analysis of TOR1A in primary dystonia
Authors: Xiao Jianfeng , Bastian Robert W , Perlmutter Joel S , Racette Brad A , Tabbal Samer D , Karimi Morvarid , Paniello Randal C , Blitzer Andrew , Batish Sat Dev , Wszolek Zbigniew K , Uitti Ryan J , Hedera Peter , Simon David K , Tarsy Daniel , Truong Daniel D , Frei Karen P , Pfeiffer Ronald F , Gong Suzhen , Zhao Yu , LeDoux Mark S 
Published: March 2009

Abstract

Background
Although the c.904_906delGAG mutation in Exon 5 of TOR1A typically manifests as early-onset generalized dystonia, DYT1 dystonia is genetically and clinically heterogeneous. Recently, another Exon 5 mutation (c.863G>A) has been associated with early-onset generalized dystonia and some ΔGAG mutation carriers present with late-onset focal dystonia. The aim of this study was to identify TOR1A Exon 5 mutations in a large cohort of subjects with mainly non-generalized primary dystonia.

Methods
High resolution melting (HRM) was used to examine the entire TOR1A Exon 5 coding sequence in 1014 subjects with primary dystonia (422 spasmodic dysphonia, 285 cervical dystonia, 67 blepharospasm, 41 writer's cramp, 16 oromandibular dystonia, 38 other primary focal dystonia, 112 segmental dystonia, 16 multifocal dystonia, and 17 generalized dystonia) and 250 controls (150 neurologically normal and 100 with other movement disorders). Diagnostic sensitivity and specificity were evaluated in an additional 8 subjects with known ΔGAG DYT1 dystonia and 88 subjects with ΔGAG-negative dystonia.

Results
HRM of TOR1A Exon 5 showed high (100%) diagnostic sensitivity and specificity. HRM was rapid and economical. HRM reliably differentiated the TOR1A ΔGAG and c.863G>A mutations. Melting curves were normal in 250/250 controls and 1012/1014 subjects with primary dystonia. The two subjects with shifted melting curves were found to harbor the classic ΔGAG deletion: 1) a non-Jewish Caucasian female with childhood-onset multifocal dystonia and 2) an Ashkenazi Jewish female with adolescent-onset spasmodic dysphonia.

Conclusion
First, HRM is an inexpensive, diagnostically sensitive and specific, high-throughput method for mutation discovery. Second, Exon 5 mutations in TOR1A are rarely associated with non-generalized primary dystonia.