bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bortezomib up-regulates activated signal transducer and activator of transcription-3 and synergizes with inhibitors of signal transducer and activator of transcription-3 to promote head and neck squamous cell carcinoma cell death
Authors: Li Changyou , Zang Yan , Sen Malabika , Leeman-Neill Rebecca J. , Man David SK. , Grandis Jennifer R. , Johnson Daniel E. 
Published: July 2009

AbstractHead and neck squamous cell carcinomas (HNSCC) are commonly resistant to conventional chemotherapy drugs and exhibit overexpression of signal transducer and activator of transcription 3 (STAT3). STAT3 promotes both the proliferation and survival of HNSCC cells. Recent studies have shown that the proteasome inhibitor bortezomib shows cytotoxic activity against HNSCC in vitro and in vivo. We report that treatment of HNSCC cells with bortezomib led to up-regulation of total STAT3 protein and the phosphorylated/activated form of STAT3, as well as an increase in cellular STAT3 activity. This suggested that the ability of bortezomib to kill HNSCC cells may be blunted due to induction of STAT3, and inhibition of STAT3 may be a useful means for improving bortezomib efficacy. Indeed, forced expression of dominant-active STAT3 inhibited bortezomib-induced cell death, whereas expression of dominant-negative STAT3 served to enhance killing by this compound. In addition, specific inhibition of STAT3 with the use of a STAT3 decoy oligonucleotide resulted in enhancement of bortezomib-induced apoptosis signaling and loss of clonogenic survival. Cotreatment of HNSCC cells with bortezomib and guggulsterone, a naturally occurring compound known to inhibit STAT3 activation, led to synergistic activation of cell death and loss of clonogenic survival. In summary, these studies show that bortezomib induces the expression of active STAT3, a key growth- promoting protein in HNSCC cells. Furthermore, our findings suggest that the therapeutic activity of bortezomib against HNSCC may be markedly improved by cotreatment with molecular targeting agents against STAT3. [Mol Cancer Ther 2009;8(8):2211–20]
Identification of Gene Signatures and Molecular Markers for Human Lung Cancer Prognosis using anIn vitroLung Carcinogenesis System
Authors: Kadara Humam , Lacroix Ludovic , Behrens Carmen , Solis Luisa , Gu Xuemin , Lee J. Jack , Tahara Eiji , Lotan Dafna , Hong Waun Ki , Wistuba Ignacio I. , Lotan Reuben 
Published: July 2009

AbstractLung cancer continues to be a major deadly malignancy. The mortality of this disease could be reduced by improving the ability to predict cancer patients' survival. We hypothesized that genes differentially expressed among cells constituting an in vitro human lung carcinogenesis model consisting of normal, immortalized, transformed, and tumorigenic bronchial epithelial cells are relevant to the clinical outcome of non–small cell lung cancer (NSCLC). Multidimensional scaling, microarray, and functional pathways analyses of the transcriptomes of the above cells were done and combined with integrative genomics to incorporate the microarray data with published NSCLC data sets. Up-regulated (n = 301) and down-regulated genes (n = 358) displayed expression level variation across the in vitro model with progressive changes in cancer-related molecular functions. A subset of these genes (n = 584) separated lung adenocarcinoma clinical samples (n = 361) into two clusters with significant survival differences. Six genes, UBE2C, TPX2, MCM2, MCM6, FEN1, and SFN, selected by functional array analysis, were also effective in prognosis. The mRNA and protein levels of one these genes—UBE2C—were significantly up-regulated in NSCLC tissue relative to normal lung and increased progressively in lung lesions. Moreover, stage I NSCLC patients with positive UBE2C expression exhibited significantly poorer overall and progression-free survival than patients with negative expression. Our studies with this in vitro model have lead to the identification of a robust six-gene signature, which may be valuable for predicting the survival of lung adenocarcinoma patients. Moreover, one of those genes, UBE2C, seems to be a powerful biomarker for NSCLC survival prediction.
Profiles in Variation: Lung Carcinogenesis
Authors: Carbone David P. 
Published: July 2009

Abstract
This perspective on Kadara et al. (beginning on p. 702 in this issue of the journal) examines the critical development of genomic and proteomic signatures of lung cancer risk, prognosis, and sensitivity to chemoprevention or chemotherapy. The novel work of Kadara et al. represents the first demonstration that a molecular signature developed in a premalignancy model (in this case, cultured normal human bronchial epithelial cells and increasingly transformed derivative cells) is clinically relevant to invasive lung cancer.
Economics Imperialism and Solution Concepts in Political Science
Authors: Kuorikoski Jaakko , Lehtinen Aki 
Published: July 2009

Political science and economic science . . . make use of the same language, the same mode of abstraction, the same instruments of thought and the same method of reasoning. (Black 1998, 354) Proponents as well as opponents of economics imperialism agree that imperialism is a matter of unification; providing a unified framework for social scientific analysis. Uskali Mäki distinguishes between derivational and ontological unification and argues that the latter should serve as a constraint for the former. We explore whether, in the case of rational-choice political science, self-interested behavior can be seen as a common causal element and solution concepts as the common derivational element, and whether the former constraints the use of the latter. We find that this is not the case. Instead, what is common to economics and rational-choice political science is a set of research heuristics and a focus on institutions with similar structures and forms of organization.
Heat demand and air exchange in a multifamily building — simulation with elements of validation
Authors: Baranowski A. , Ferdyn-Grygierek J. 
Published: July 2009

The experiment providing data on the energy demand and air exchange in the flat located in the multifamily building is presented in the paper. The measurement was carried out during 3 weeks in winter. The total energy consumption necessary for flat heating was measured continuously. During the same time air change rate in the flat was measured by means of tracer gas concentration decay methods. After measurements were finished the energy demand and ventilating airflows were calculated assuming the same weather data variation as measured during the experiment, using the ESP-r software. Contam program was used for the air infiltration simulation, giving more detailed results about the ventilation airflows within the tested object. Comparison was made between numerical results and measured data over the given cycle and a good correlation of results has been achieved. Practical applications: Simulation methods can be an alternative to the assessment of energy consumption or heat demand in buildings when the direct measurement is impossible or difficult. A good agreement of simulation and measurement results is reached when the average values of the results are compared for a longer period of time.
Aggressive statin therapy in multicenter and effectiveness for the reduction of intra-myocardial damage caused by non-ST elevation acute coronary syndrome: AMERICA study
Authors: Hara Hidehiko , Nakamura Masato , Yokouchi Itaru , Kimura Keiko , Nemoto Naohiko , Ito Shingo , Ono Tsuyoshi , Itaya Hideki , Shiba Masanori , Wada Masamichi , Iijima Raisuke , Yamamoto Masaya , Yamamoto Masato , Hara Hisao , Takagi Takuro , Asahara Toshiyuki , Mitsuo Kazuhisa , Kobayashi Nobuyuki , Sugi Kaoru 
Published: July 2009

Background: While preprocedural statin treatment for acute coronary syndrome (ACS) is widely regarded as beneficial, there has been no prospective randomized multicenter trial of patients with non-ST elevation ACS in the Japanese population to examine the efficacy of preprocedural aggressive statin use. The aim of this study was to confirm this effect by prospective randomized multicenter design. Methods: Fifty patients who presented with non-ST elevation ACS were enrolled, and randomly assigned to aggressive statin administration before percutaneous coronary intervention (PCI). Troponin-T (TnT), creatine phosphokinase (CK), CK-myocardial band (CK-MB), high-sense C-reactive protein (hs-CRP), and brain natriuretic peptide (BNP) were measured at baseline and/ or after procedure. Results: Three days after PCI, the statin group had significantly less CK elevation compared with the nonstatin group (84±17 IU/l versus 180±68 IU/l, respectively, p = 0.02). CK-MB elevation also tended to be lower in the statin group than in the nonstatin group (3.2±1.9 versus. 7.0±3.0, respectively, p = 0.07), as was BNP level (3.2±1.9 versus 7.0±3.0 pg/ml, respectively, p = 0.07). The change of serum LDL cholesterol was significantly correlated with CK ( p = 0.01) and TnT ( p = 0.02) at 1 day after PCI. Conclusions: Aggressive statin usage before PCI to Japanese patients with non-ST elevation ACS appears to reduce myocardial damage after procedure. The degree of serum lipid level reduction may reflect the vulnerability of atheromatous plaques that could cause cardiac damage after PCI.
Concussion in Sports: The Sideline Assessment
Authors: Broglio Steven P. , Guskiewicz Kevin M. 
Published: July 2009

Context: The vast differences between individual athletes makes identifying and evaluating sports-related concussion one of the most complex and perplexing injuries faced by medical personnel. Evidence Acquisition: This review summarizes the existing literature supporting the use of a multifaceted approach to concussion evaluation on the sideline of the athletic field. Information was drawn from a PubMed search (MEDLINE) for the terms sport concussion for the most recent and relevant literature. Conclusions: By using a standardized clinical examination that is supported by objective measures of concussion-related symptoms, mental status, and postural control, the medical professional becomes well equipped to make an informed diagnosis.
Combined epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A and the histone deacetylase inhibitor panobinostat against human AML cells
Authors: Fiskus Warren , Wang Yongchao , Sreekumar Arun , Buckley Kathleen M. , Shi Huidong , Jillella Anand , Ustun Celalettin , Rao Rekha , Fernandez Pravina , Chen Jianguang , Balusu Ramesh , Koul Sanjay , Atadja Peter , Marquez Victor E. , Bhalla Kapil N. 
Published: July 2009

Abstract
The polycomb repressive complex (PRC) 2 contains 3 core proteins, EZH2, SUZ12, and EED, in which the SET (suppressor of variegation–enhancer of zeste-trithorax) domain of EZH2 mediates the histone methyltransferase activity. This induces trimethylation of lysine 27 on histone H3, regulates the expression of HOX genes, and promotes proliferation and aggressiveness of neoplastic cells. In this study, we demonstrate that treatment with the S-adenosylhomocysteine hydrolase inhibitor 3-deazaneplanocin A (DZNep) depletes EZH2 levels, and inhibits trimethylation of lysine 27 on histone H3 in the cultured human acute myeloid leukemia (AML) HL-60 and OCI-AML3 cells and in primary AML cells. DZNep treatment induced p16, p21, p27, and FBXO32 while depleting cyclin E and HOXA9 levels. Similar findings were observed after treatment with small interfering RNA to EZH2. In addition, DZNep treatment induced apoptosis in cultured and primary AML cells. Furthermore, compared with treatment with each agent alone, cotreatment with DZNep and the pan-histone deacetylase inhibitor panobinostat caused more depletion of EZH2, induced more apoptosis of AML, but not normal CD34+ bone marrow progenitor cells, and significantly improved survival of nonobese diabetic/severe combined immunodeficiency mice with HL-60 leukemia. These findings indicate that the combination of DZNep and panobinostat is effective and relatively selective epigenetic therapy against AML cells.
Evolution of a subtilisin-like protease gene family in the grass endophytic fungus Epichloë festucae
Authors: Bryant Michelle K , Schardl Christopher L , Hesse Uljana , Scott Barry 
Published: July 2009

Abstract

Background
Subtilisin-like proteases (SLPs) form a superfamily of enzymes that act to degrade protein substrates. In fungi, SLPs can play either a general nutritive role, or may play specific roles in cell metabolism, or as pathogenicity or virulence factors.

Results
Fifteen different genes encoding SLPs were identified in the genome of the grass endophytic fungus Epichloë festucae. Phylogenetic analysis indicated that these SLPs belong to four different subtilisin families: proteinase K, kexin, pyrolysin and subtilisin. The pattern of intron loss and gain is consistent with this phylogeny. E. festucae is exceptional in that it contains two kexin-like genes. Phylogenetic analysis in Hypocreales fungi revealed an extensive history of gene loss and duplication.

Conclusion
This study provides new insights into the evolution of the SLP superfamily in filamentous fungi.
Horizontal gene transfer of zinc and non-zinc forms of bacterial ribosomal protein S4
Authors: Chen Ke , Roberts Elijah , Luthey-Schulten Zaida 
Published: July 2009

Abstract

Background
The universal ribosomal protein S4 is essential for the initiation of small subunit ribosomal assembly and translational accuracy. Being part of the information processing machinery of the cell, the gene for S4 is generally thought of as being inherited vertically and has been used in concatenated gene phylogenies. Here we report the evolution of ribosomal protein S4 in relation to a broad sharing of zinc/non-zinc forms of the gene and study the scope of horizontal gene transfer (HGT) of S4 during bacterial evolution.

Results
In this study we present the complex evolutionary history of ribosomal protein S4 using 660 bacterial genomes from 16 major bacterial phyla. According to conserved characteristics in the sequences, S4 can be classified into C+ (zinc-binding) and C- (zinc-free) variants, with 26 genomes (mainly from the class Clostridia) containing genes for both. A maximum likelihood phylogenetic tree of the S4 sequences was incongruent with the standard bacterial phylogeny, indicating a departure from strict vertical inheritance. Further analysis using the genome content near the S4 genes, which are usually located in a conserved gene cluster, showed not only that HGT of the C- gene had occurred at various stages of bacterial evolution, but also that both the C- and C+ genes were present before the individual phyla diverged. To explain the latter, we theorize that a gene pool existed early in bacterial evolution from which bacteria could sample S4 gene variants, according to environmental conditions. The distribution of the C+/- variants for seven other zinc-binding ribosomal proteins in these 660 bacterial genomes is consistent with that seen for S4 and may shed light on the evolutionary pressures involved.

Conclusion
The complex history presented for "core" protein S4 suggests the existence of a gene pool before the emergence of bacterial lineages and reflects the pervasive nature of HGT in subsequent bacterial evolution. This has implications for both theoretical models of evolution and practical applications of phylogenetic reconstruction as well as the control of zinc economy in bacterial cells.
QTL analyses of temporal and intensity components of home-cage activity in KJR and C57BL/6J strains
Authors: Umemori Juzoh , Nishi Akinori , Lionikas Arimantas , Sakaguchi Takayuki , Kuriki Satoshi , Blizard David A , Koide Tsuyoshi 
Published: July 2009

Abstract

Background
A variety of mouse strains exhibit diversity in spontaneous activity consistent with an important genetic contribution. To date, many studies have defined spontaneous home-cage activity as total distance or total counts of activity within a test period. However, spontaneous activity is, in fact, a composite of elements of 'temporal' and 'intensity' that is similar to 'velocity'. Here, we report on quantitative trait loci for different components of spontaneous activity, an important step towards dissection of the underlying genetic mechanisms.

Results
In the analysis of total home-cage activity (THA) after habituation in female mice, KJR strain exhibit higher activity than C57BL/6J (B6). In this study, THA was partitioned into two components: active time (AT) was an index of the 'temporal element' of THA, average activity during active time (AA) was an index of 'intensity'. Correlation analysis using B6xKJR F2 female mice indicated that AA is a major component of THA, whereas AA and AT were associated to a lesser degree. To explore the genetic basis of the activity differences, we conducted quantitative trait loci (QTL) analysis on data of THA and its components, AT and AA. Three significant QTL affecting variation of different components of home cage activity were identified, two linked QTL Hylaq1 and Hylaq2 on Chr 2, and Hylaq3 on Chr 10. Chromosomal positions of these QTL were previously implicated in locomotor activity (Chr 2) or open-field ambulation (Chr 10). The results indicated that Hylaq1 influences AT, Hylaq2, AA, while Hylaq3 is associated with both AA and AT.

Conclusion
Through this study, we found that variation in total home cage activity over a 3 day period is affected by variation in active time and intensity of activity. The latter two variables are distinct components of home cage activity with only partially overlapping genetic architecture.
Generation and analysis of a 29,745 unique Expressed Sequence Tags from the Pacific oyster (Crassostrea gigas) assembled into a publicly accessible database: the GigasDatabase
Authors: Fleury Elodie , Huvet Arnaud , Lelong Christophe , de Lorgeril Julien , Boulo Viviane , Gueguen Yannick , Bachère Evelyne , Tanguy Arnaud , Moraga Dario , Fabioux Caroline , Lindeque Penelope , Shaw Jenny , Reinhardt Richard , Prunet Patrick , Davey Grace , Lapègue Sylvie , Sauvage Christopher , Corporeau Charlotte , Moal Jeanne , Gavory Frederick , Wincker Patrick , Moreews François , Klopp Christophe , Mathieu Michel , Boudry Pierre , Favrel Pascal 
Published: July 2009

Abstract

Background
Although bivalves are among the most-studied marine organisms because of their ecological role and economic importance, very little information is available on the genome sequences of oyster species. This report documents three large-scale cDNA sequencing projects for the Pacific oyster Crassostrea gigas initiated to provide a large number of expressed sequence tags that were subsequently compiled in a publicly accessible database. This resource allowed for the identification of a large number of transcripts and provides valuable information for ongoing investigations of tissue-specific and stimulus-dependant gene expression patterns. These data are crucial for constructing comprehensive DNA microarrays, identifying single nucleotide polymorphisms and microsatellites in coding regions, and for identifying genes when the entire genome sequence of C. gigas becomes available.

Description
In the present paper, we report the production of 40,845 high-quality ESTs that identify 29,745 unique transcribed sequences consisting of 7,940 contigs and 21,805 singletons. All of these new sequences, together with existing public sequence data, have been compiled into a publicly-available Website http://public-contigbrowser.sigenae.org:9090/Crassostrea_gigas/index.html. Approximately 43% of the unique ESTs had significant matches against the SwissProt database and 27% were annotated using Gene Ontology terms. In addition, we identified a total of 208 in silico microsatellites from the ESTs, with 173 having sufficient flanking sequence for primer design. We also identified a total of 7,530 putative in silico, single-nucleotide polymorphisms using existing and newly-generated EST resources for the Pacific oyster.

Conclusion
A publicly-available database has been populated with 29,745 unique sequences for the Pacific oyster Crassostrea gigas. The database provides many tools to search cleaned and assembled ESTs. The user may input and submit several filters, such as protein or nucleotide hits, to select and download relevant elements. This database constitutes one of the most developed genomic resources accessible among Lophotrochozoans, an orphan clade of bilateral animals. These data will accelerate the development of both genomics and genetics in a commercially-important species with the highest annual, commercial production of any aquatic organism.
High frequencies of elevated alkaline phosphatase activity and rickets exist in extremely low birth weight infants despite current nutritional support
Authors: Mitchell Shannon M , Rogers Stefanie P , Hicks Penni D , Hawthorne Keli M , Parker Bruce R , Abrams Steven A 
Published: July 2009

Abstract

Background
Osteopenia and rickets are common among extremely low birth weight infants (ELBW, <1000 g birth weight) despite current practices of vitamin and mineral supplementation. Few data are available evaluating the usual course of markers of mineral status in this population. Our objectives in this study were to determine the relationship between birth weight (BW) and peak serum alkaline phosphatase activity (P-APA) in ELBW infants and evaluate our experience with the diagnosis of rickets in these infants.

Methods
We evaluated all ELBW infants admitted to Texas Children's Hospital NICU in 2006 and 2007. Of 211 admissions, we excluded 98 patients who were admitted at >30 days of age or did not survive/stay for >6 weeks. Bone radiographs obtained in 32 infants were reviewed by a radiologist masked to laboratory values.

Results
In this cohort of 113 infants, P-APA was found to have a significant inverse relationship with BW, gestational age and serum phosphorus. In paired comparisons, P-APA of infants <600 g (957 ± 346 IU/L, n = 20) and infants 600–800 g (808 ± 323 IU/L, n = 43) were both significantly higher than P-APA of infants 800–1000 g (615 ± 252 IU/L, n = 50), p < 0.01. Thirty-two patients had radiographic evaluation for evidence of rickets, based on P-APA greater than 800 IU/L, parenteral nutrition greater than 3 to 4 weeks, or clinical suspicion. Of these, 18 showed radiologic rickets and 14 showed osteopenia without rickets. Infants with BW <600 g were more likely to have radiologic rickets (10/20 infants) compared to those with BW 600–800 g (6/43 infants) and BW 800–1000 g (2/50 infants), p < 0.01 for each. P-APA was not significantly higher in infants with radiologic rickets (1078 ± 356 IU/L) compared to those without radiologic evidence of rickets (943 ± 346, p = 0.18).

Conclusion
Elevation of P-APA >600 IU/L was very common in ELBW infants. BW was significantly inversely related to both P-APA and radiologic rickets. No single value of P-APA was related to radiological findings of rickets. Given the very high risk of osteopenia and rickets among ELBW infants, we recommend consideration of early screening and early mineral supplementation, especially among infants <600 g BW.