bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Pinin in neural crest, dorsal dermis, and axial skeleton development and its involvement in the regulation of Tcf/Lef activity in mice
Authors: Joo Jeong‐Hoon , Lee Young Jae , Munguba Gustavo C. , Park Sean , Taxter Timothy J. , Elsagga Mohamed Y. , Jackson Moira R. , Oh S. Paul , Sugrue Stephen P. 
Published: July 2007

AbstractPrevious in vitro studies have indicated multiple and varied roles of Pinin (PNN); however, its in vivo role has remained unclear. Here, we report generation of null, hypomorphic, and conditional Pnn alleles in mice. We found that insertion of neomycin‐resistance cassette into intron 8 of Pnn resulted in knockdown of Pnn, which allowed Pnn hypomorphic embryos to pass peri‐implantation lethality. These mice are lethal at perinatal stages and exhibit defects in the cardiac outflow tract, palate, dorsal dermis, and axial skeleton. Since Wnt/β‐catenin signaling has been shown to play pivotal roles in development of all tissues affected by Pnn hypomorphism, we speculated that Pnn may affect Wnt/β‐catenin signaling. Supporting this view, we demonstrate abnormal activities of Tcf/Lef transcription factors, and alterations in β‐catenin level in multiple Pnn hypomorphic tissues. Taken together, the data suggest that Pnn plays important roles during mouse development through its involvement in regulation of Tcf/Lef activity. Developmental Dynamics 236:2147–2158, 2007. © 2007 Wiley‐Liss, Inc.
Phenotypic analysis of a novel chordin mutant in medaka
Authors: Takashima Shigeo , Shimada Atsuko , Kobayashi Daisuke , Yokoi Hayato , Narita Takanori , Jindo Tomoko , Kage Takahiro , Kitagawa Tadao , Kimura Tetsuaki , Sekimizu Koshin , Miyake Akimitsu , Setiamarga Davin H.E. , Murakami Ryohei , Tsuda Sachiko , Ooki Shinya , Kakihara Ken , Hojo Motoki , Naruse Kiyoshi , Mitani Hiroshi , Shima Akihiro , Ishikawa Yuji , Araki Kazuo , Saga Yumiko , Takeda Hiroyuki 
Published: July 2007

AbstractWe have isolated and characterized a ventralized mutant in medaka (the Japanese killifish; Oryzias latipes), which turned out to have a mutation in the chordin gene. The mutant exhibits ventralization of the body axis, malformation of axial bones, over‐bifurcation of yolk sac blood vessels, and laterality defects in internal organs. The mutant exhibits variability of phenotypes, depending on the culture temperature, from embryos with a slightly ventralized phenotype to those without any head and trunk structures. Taking advantages of these variable and severe phenotypes, we analyzed the role of Chordin‐dependent tissues such as the notochord and Kupffer's vesicle (KV) in the establishment of left–right axis in fish. The results demonstrate that, in the absence of the notochord and KV, the medaka lateral plate mesoderm autonomously and bilaterally expresses spaw gene in a default state. Developmental Dynamics 236:2298–2310, 2007. © 2007 Wiley‐Liss, Inc.
Differential subcellular sequestration of proapoptotic and antiapoptotic proteins and colocalization of Bcl‐xL with the germ plasm, in Xenopus laevis oocytes
Authors: Kloc Malgorzata , Shirato Yuri , Bilinski Szczepan , Browder Leon W. , Johnston Jillian 
Published: July 2007

AbstractApoptosis is an important element of normal embryonic development and gametogenesis in invertebrate and vertebrate species. Although the components of apoptotic machinery are present in Xenopus laevis fully grown stage VI oocytes and eggs, apoptosis in the developing Xenopus ovary is limited to the somatic cells with no indication of apoptosis in the germ cells. Considering the possibility that Xenopus previtellogenic oocytes might lack the components of the apoptotic pathway, we analyzed Xenopus Stage I oocytes for the presence of the proapoptotic factors Bax and tumor suppressor p53, and antiapoptotic factors Bcl‐xL and mitochondrial heat shock protein 60 (Hsp60). We found that pro‐ and antiapoptotic proteins are present in Xenopus oocytes but, surprisingly, they are located in distinct subcellular compartments with proapoptotic proteins Bax and p53 being sequestered in the oocyte nucleus and antiapoptotic protein Bcl‐xL sequestered in the cytoplasm and highly enriched in the METRO region of the mitochondrial cloud, where it colocalized with the germ plasm, and Hsp60 colocalizing with all mitochondria. The absence of apoptosis in Xenopus early oogenesis is maybe due to differential sequestration of pro‐ and antiapoptotic molecules. genesis 45:523–531, 2007. © 2007 Wiley‐Liss, Inc.
220,000‐r/min, 2‐kW PM motor drive for turbocharger
Authors: Noguchi Toshihiko , Takata Yosuke , Pyamashita Yukio , Komatsu Yoshimi , Ibaraki Seiichi 
Published: July 2007

AbstractThis paper describes an ultrahigh‐speed permanent‐magnet synchronous motor drive, which is embedded in a turbocharger of an internal‐combustion engine. The electrical drive makes it possible to enhance output power of the turbocharger in a motoring mode and to retrieve combustion energy from exhaust gas in a regenerating mode. Computer simulations and experimental tests are conducted to examine various operation characteristics of a prototype. The experimental data demonstrate 220,000‐r/min operation at 2.2‐kW inverter output power, in good agreement with the simulation results and proving the feasibility of the proposed system. © 2007 Wiley Periodicals, Inc. Electr Eng Jpn, 161(3): 31–40, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20408
Synthesis and Characterisation of Semi‐Bridging Molybdenum Borylene Complexes
Authors: Braunschweig Holger , Radacki Krzysztof , Uttinger Katharina 
Published: July 2007

AbstractInvestigation of the reactivity of the molybdenum borylene complex [(OC)5Mo=B=N(SiMe3)2] towards the late transition metal complexes [M(PCy3)2] (M = Pd, Pt) indicated the formation of [(OC)4Mo(μ‐CO){μ‐BN(SiMe3)2}Pd(PCy3)] and [(Cy3P)(OC)3Mo(μ‐CO){μ‐BN(SiMe3)2}Pt(PCy3)], respectively, as the first Mo‐based semi‐bridging borylene complexes. The new complexes were fully characterised spectroscopically and analysed by X‐ray diffraction. The conclusions drawn from the experimental data for the ligand‐metal interactions for this particular coordination mode of a borylene group were supported by DFT computations.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
New [4.4]Cyclophane Diketals, Monoketones, and Diketones: Design, Synthesis, and Structural Analysis
Authors: Bogdan Niculina , Grosu Ion , Condamine Eric , Toupet Loïc , Ramondenc Yvan , Silaghi‐Dumitrescu Ioan , Plé Gérard , Bogdan Elena 
Published: July 2007

AbstractThe synthesis of some new [4.4]cyclophane diketals, monoketones, and diketones in good yields is reported along with the unusually low reactivity towards hydrolysis of the spiro‐1,3‐dioxane rings connected to the cyclophane bridges. The structural analysis carried out by X‐ray diffraction, NMR spectroscopy, and mass spectrometry shows significant intra‐ and intermolecular π–π and C–H–π interactions. The rotation of the aromatic rings and the flipping of the bridges have been investigated by molecular modeling and variable‐temperature NMR experiments. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Formal Synthesis of (+)‐ and (–)‐Ferruginine
Authors: Piccardi Riccardo , Renaud Philippe 
Published: July 2007

AbstractA formal synthesis of the naturally occurring (+)‐ferrugine and of its enantiomer starting from the commercially available tropinone is reported. The desymmetrization of tropinone was achieved through formation of diastereomeric unsaturated sulfoxides using the Andersen procedure. Introduction of the acetyl C(2) side chain was achieved by conjugate addition of lithiated ethyl vinyl ether to an unsaturated sulfone. N‐Boc‐Norferruginine, an advanced intermediate for the synthesis of ferruginine, was prepared in six steps and 19 % overall yield. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Multiple genomic alterations on 21q22 predict various TMPRSS2/ERG fusion transcripts in human prostate cancers
Authors: Liu Wennuan , Ewing Charles M , Chang Bao‐Li , Li Tao , Sun Jishan , Turner Aubrey R. , Dimitrov Latchezar , Zhu Yi , Sun Jielin , Kim Jin Woo , Zheng S. Lilly , Isaacs William B. , Xu Jianfeng 
Published: July 2007

AbstractA number of TMPRSS2/ERG fusion transcripts have been reported since the discovery that recurrent genomic rearrangements result in the fusion of TMPRSS2 and ETS family member genes. In this article we present evidence demonstrating that multiple genomic alterations contribute to the formation of various TMPRSS2/ERG transcripts. Using allele‐specific analysis of the data generated from the GeneChip 500K SNP array we observed both hemizygous and homozygous deletions occurring at different locations between and within TMPRSS2 and ERG in prostate cancers. The 500K SNP array enabled us to fine map the start and end of each deletion to specific introns of these two genes, and to predict a variety of fusion transcripts, including a new form which was confirmed by sequence analysis of the fusion transcripts in various tumors. We also inferred that translocation is an additional mechanism of fusion for these two genes in some tumors, based on largely diploid genomic DNA between TMPRSS and ERG, and different fusion transcripts produced in these tumors. Using a bioinformatics approach, we then uncovered the consensus sequences in the regions harboring the breakpoints of the deletions. These consensus sequences were homologous to the human Alu‐Sq and Alu‐Sp subfamily consensus sequences, with more than 80% homology. The presence/absence of Alu family consensus sequence in the introns of TMPRSS2 and ERG correlates with the presence/absence of fusion transcripts of theses two genes, indicating that these consensus sequences may contribute to genomic deletions and the fusion of TMPRSS2 and ERG in prostate cancer. © 2007 Wiley‐Liss, Inc.
Frequency and characterization of HMGA2 and HMGA1 rearrangements in mesenchymal tumors of the lower genital tract
Authors: Medeiros Fabiola , Erickson‐Johnson Michele R. , Keeney Gary L. , Clayton Amy C. , Nascimento Antonio G. , Wang Xiaoke , Oliveira Andre M. 
Published: July 2007

AbstractMesenchymal tumors of the lower genital tract predominantly occur in women of reproductive age and are mainly represented by aggressive angiomyxoma (AAM) and angiomyofibroblastoma (AMF). Whether these tumors are different phenotypic expressions of the same biological entity is still debatable. Genetic rearrangements of HMGA2 have been reported in a few cases of AAM but its frequency and clinicobiological implications have not been studied systematically. We evaluated 90 cases of mesenchymal tumors of the lower genital tract that comprised 42 AAMs, 18 AMFs, 6 cellular angiofibromas, 5 fibroepithelial stromal polyps, 15 genital leiomyomas, 3 superficial angiomyxomas, and 1 spindle cell lipoma. Fluorescence in situ hybridization was used to identify rearrangements of HMGA2 and its homologue HMGA1. HMGA2 rearrangements were identified in 14 AAMs (33%) and in 1 vaginal leiomyoma. All other tumors were negative for HMGA2 rearrangements. HMGA1 rearrangement was not found in any of the cases. RT‐PCR confirmed transcriptional upregulation of HMGA2 only in tumors with HMGA2 rearrangements. Standard cytogenetic analyses were performed in two AAMs and one AMF. One AAM had a t(1;12)(p32;q15); the other tumors had normal karyotypes. Mapping and sequence analysis of the breakpoint showed fusion to the 3′ untranslated region of HMGA2 to genomic sequences derived from the contig NT 032977.8 on chromosome 1p32. Our findings support the hypothesis that AAM and AMF are distinct biological entities. The diagnostic usefulness of HMGA2 rearrangements to differentiate between AAM and other tumors of the lower genital tract may be limited due to the their low frequency. © 2007 Wiley‐Liss, Inc.
Hierarchical Bayes prioritization of marker associations from a genome‐wide association scan for further investigation
Authors: Lewinger Juan Pablo , Conti David V. , Baurley James W. , Triche Timothy J. , Thomas Duncan C. 
Published: July 2007

AbstractWe describe a hierarchical regression modeling approach to selection of a subset of markers from the first stage of a genomewide association scan to carry forward to subsequent stages for testing on an independent set of subjects. Rather than simply selecting a subset of most significant marker‐disease associations at some cutoff chosen to maximize the cost efficiency of a multistage design, we propose a prior model for the true noncentrality parameters of these associations composed of a large mass at zero and a continuous distribution of nonzero values. The prior probability of nonzero values and their prior means can be functions of various covariates characterizing each marker, such as their location relative to genes or evolutionary conserved regions, or prior linkage or association data. We propose to take the top ranked posterior expectations of the noncentrality parameters for confirmation in later stages of a genomewide scan. The statistical performance of this approach is compared with the traditional p‐value ranking by simulation studies. We show that the ranking by posterior expectations performs better at selecting the true positive association than a simple ranking of p‐values if at least some of the prior covariates have predictive value. Genet. Epidemiol. 31, 2007. © 2007 Wiley‐Liss, Inc.
MAC1 mediates LPS‐induced production of superoxide by microglia: The role of pattern recognition receptors in dopaminergic neurotoxicity
Authors: Pei Zhong , Pang Hao , Qian Li , Yang Sufen , Wang Tonggauang , Zhang Wei , Wu Xeufei , Dallas Shannon , Wilson Belinda , Reece Jeffrey M. , Miller David S. , Hong Jau‐Shyong , Block Michelle L. 
Published: July 2007

AbstractMicroglia‐derived superoxide is critical for the inflammation‐induced selective loss of dopaminergic (DA) neurons, but the underlying mechanisms of microglial activation remain poorly defined. Using neuron‐glia and microglia‐enriched cultures from mice deficient in the MAC1 receptor (MAC1−/−), we demonstrate that lipopolysaccharide (LPS) treatment results in lower TNFα response, attenuated loss of DA neurons, and absence of extracellular superoxide production in MAC1−/−cultures. Microglia accumulated fluorescently labeled LPS in punctate compartments associated with the plasma membrane, intracellular vesicles, and the Golgi apparatus. Cytochalasin D (CD), an inhibitor of phagocytosis, blocked LPS internalization. However, microglia derived from Toll‐like receptor 4 deficient mice and MAC1−/−mice failed to show a significant decrease in intracellular accumulation of labeled LPS, when compared with controls. Pretreatment with the scavenger receptor inhibitor, fucoidan, inhibited 79% of LPS accumulation in microglia without affecting superoxide, indicating that LPS internalization and superoxide production are mediated by separate phagocytosis receptors. Together, these data demonstrate that MAC1 is essential for LPS‐induced superoxide from microglia, implicating MAC1 as a critical trigger of microglial‐derived oxidative stress during inflammation‐mediated neurodegeneration. © 2007 Wiley‐Liss, Inc.
Efficacy of a novel histone deacetylase inhibitor in murine models of hepatocellular carcinoma
Authors: Lu Yen-Shen , Kashida Yoko , Kulp Samuel K. , Wang Yu-Chieh , Wang Dasheng , Hung Jui-Hsiang , Tang Monica , Lin Zhong-Zhe , Chen Te-Jung , Cheng Ann-Lii , Chen Ching-Shih 
Published: July 2007

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, yet effective therapeutic options for advanced HCC are limited. This study was aimed at assessing the antitumor effect of a novel phenylbutyrate-derived histone deacetylase (HDAC) inhibitor, OSU-HDAC42, vis-à-vis suberoylanilide hydroxamic acid (SAHA), in

in vitro

and

in vivo

models of human HCC. OSU-HDAC42 was several times more potent than SAHA in suppressing the viability of PLC5, Huh7, and Hep3B cells with submicromolar median inhibitory concentration (IC50) values. With respect to SAHA, OSU-HDAC42 exhibited greater apoptogenic potency, which was associated with reduced levels of the apoptotic regulators phosphorylated Akt B-cell lymphoma-xL, survivin, cellular inhibitor of apoptosis protein 1, and cellular inhibitor of apoptosis protein 2. The

in vivo

efficacy of OSU-HDAC42 versus SAHA was assessed in orthotopic and subcutaneous xenograft tumor models in athymic nude mice. Daily oral treatments with OSU-HDAC42 and SAHA, both at 25 mg/kg, suppressed the growth of orthotopic PLC5 tumor xenografts by 91% and 66%, respectively, and of established subcutaneous PLC5 tumor xenografts by 85% and 56%, respectively. This differential tumor suppression correlated with the modulation of intratumoral biomarkers associated with HDAC inhibition and apoptosis regulation. Moreover, the oral administration of OSU-HDAC42 at 50 mg/kg every other day markedly suppressed ectopic tumor growth in mice bearing large tumor burdens (500 mm3) at the start of treatment.

Conclusion:

OSU-HDAC42 is a potent, orally bioavailable inhibitor of HDAC with a broad spectrum of antitumor activity that includes targets regulating multiple aspects of cancer cell survival. These results suggest that OSU-HDAC42 has clinical value in therapeutic strategies for HCC. (HEPATOLOGY 2007.)
Liposome‐encapsulated doxorubicin in combination with cyclophosphamide, vincristine, prednisone and rituximab in patients with lymphoma and concurrent cardiac diseases or pre‐treated with anthracyclines
Authors: Rigacci Luigi , Mappa Silvia , Nassi Luca , Alterini Renato , Carrai Valentina , Bernardi Franco , Bosi Alberto 
Published: July 2007

AbstractBackgroundTo assess the efficacy and safety of the combination of non‐pegylated liposome‐encapsulated doxorubicin (Myocet®) with cyclophosphamide, vincristine, prednisone and rituximab (R‐COMP) in patients with aggressive non‐Hodgkin's B‐cell lymphomas.MethodsTwenty‐one patients were selected for the presence of negative concurrent clinical features such as cardiac comorbidity and/or previous treatment with anthracycline‐based regimens. Liposome‐encapsulated doxorubicin at a dose of 50 mg/m2 was administered in association with cyclophosphamide (750 mg/m2), vincristine (1.4 mg/m2), prednisone (40 mg/m2) and rituximab (375 mg/m2) every 21 days for four to six cycles unless progression or unacceptable toxicity occurred.ResultsA complete response (CR) was obtained in 16/21 patients (76%), three patients achieved a partial response (14%), with an overall response rate of 90%. Two patients (10%) did not respond to therapy. After a median follow‐up of 13 months (range 2–36 months), 2/16 CR patients relapsed, with a disease‐free survival (DFS) of 78%.ConclusionsThe replacement of doxorubicin with its non‐pegylated liposomal pharmaceutical analogue was well tolerated and highly effective in inducing remission in this group of patients at high risk for cardiac toxicity or previously treated with anthracyclines. Its high tolerability and low incidence of cardiac events (only one patient) warrants further studies to confirm the clinical benefits of liposomal doxorubicin in this subset of patients. Copyright © 2007 John Wiley & Sons, Ltd.
WebProp: Web interface forab initiocalculation of molecular one‐electron properties
Authors: Ganesh V. , Kavathekar Ritwik , Rahalkar Anuja , Gadre Shridhar R. 
Published: July 2007

AbstractThis note describes the features and implementation issues of WebProp, a web‐based interface for evaluatingab initioquality one‐electron properties. The interface code is written in HTML and Python, while the backend is handled using Python and our indigenously developed code INDPROP for property evaluation. A novel feature of this setup is that it provides a simple interface for computing first principle one‐electron properties of small to medium sized molecules. To facilitate computation of otherwise expensive calculations on large molecular systems, we employ the Molecular Tailoring Approach (MTA) developed in our laboratory to obtain the density matrix (DM). This DM is then employed for computing the one‐electron properties of these systems. The backend transparently handles jobs submitted by the user and runs them either on a single machine or over a grid of compute nodes. The results of the calculations, which include the summary and the files necessary for visualization of one‐electron properties, are e‐mailed to the user. The user can either directly use the data or visualize it using visualization tools such as UNIVIS‐2000 or Drishti. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
Acute intermittent porphyria: vector optimization for gene therapy
Authors: Yasuda Makiko , Domaradzki Maciej E. , Armentano Donna , Cheng Seng H. , Bishop David F. , Desnick Robert J. 
Published: July 2007

AbstractBackgroundAcute intermittent porphyria (AIP) is an autosomal dominant disorder caused by the half‐normal activity of hydroxymethylbilane synthase (HMB‐synthase). Affected individuals can experience episodic, life‐threatening, acute neurological attacks that are precipitated by various drugs, dieting, and hormonal changes. Intravenous hematin is used to treat the attacks, but a more effective, preventive therapy is needed, especially for patients with frequent attacks. Since the disease is a hepatic encephalopathy, efforts were focused towards evaluating four different combinations of liver‐specific enhancers and promoters for maximal hepatic HMB‐synthase expression.MethodsFour different mammalian expression vectors, each carrying a unique combination of liver‐specific enhancers and promoters driving murine HMB‐synthase cDNA expression, were transiently transfected into HepG2 cells. The vectors included: HMBS‐1; human α1‐microglobulin enhancer/α1‐antityrpsin promoter (α1Me/α1ATp), HMBS‐2; α1Me/human serum albumin promoter (α1Me/SAp), HMBS‐3; human prothrombin enhancer/SAp (PTe/SAp), and HMBS‐4; (PTe/α1ATp). Each HMB‐synthase construct and a luciferase reporter construct were hydrodynamically coinjected into mice with HMB‐synthase deficiency and evaluated for hepatic expression 24 h post‐injection, the time‐point of peak hepatic HMB‐synthase expression.ResultsFollowing transient transfection into HepG2 cells, HMBS‐1 (α1Me/α1ATp) had the highest HMB‐synthase expression level, with an ∼8‐fold increase over endogenous cellular activities. Construct HMBS‐1 also had the highest hepatic HMB‐synthase activity following hydrodynamic delivery into HMB‐synthase deficient mice, with a ∼6‐fold increase over saline‐treated mice.ConclusionsThese studies support the use of a gene therapy vector containing the α1Me/α1ATp combination for preclinical studies of the efficacy and safety of liver‐targeted gene therapy for AIP. Copyright © 2007 John Wiley & Sons, Ltd.