bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transient outward potassium channel regulation in healthy and diabetic heartsThis article is one of a selection of papers from the NATO Advanced Research Workshop on Translational Knowledge for Heart Health (published in part 1 of a 2-part Special Issue).
Authors: Gallego Mónica , Alday Aintzane , Urrutia Janire , Casis Oscar 
Published: February 2009

Diabetic patients have a higher incidence of cardiac arrhythmias, including ventricular fibrillation and sudden death, and show important alterations in the electrocardiogram, most of these related to the repolarization. In myocytes isolated from diabetic hearts, the transient outward K+current (Ito) is the repolarizing current that is mainly affected. Type 1 diabetes alters Itoat 3 levels: the recovery of inactivation, the responsiveness to physiologic regulators, and the functional expression of the channel. Diabetes slows down Itorecovery of inactivation because it triggers the switching from fast-recovering Kv4.x channels to the slow-recovering Kv1.4. Diabetic animals also have decreased responsiveness of Itotowards the sympathetic nervous system; thus, the diabetic heart develops a resistance to its physiologic regulator. Finally, diabetes impairs support of various trophic factors required for the functional expression of the channel and reduces Itoamplitude by decreasing the amount of Kv4.2 and Kv4.3 proteins.
Timing of induction of cardiomyocyte differentiation for in vitro cultured mesenchymal stem cells: a perspective for emergenciesThis article is one of a selection of papers from the NATO Advanced Research Workshop on Translational Knowledge for Heart Health (published in part 1 of a 2-part Special Issue).
Authors: Tokcaer-Keskin Zeynep , Akar A. Ruchan , Ayaloglu-Butun Fatma , Terzioglu-Kara Ece , Durdu Serkan , Ozyurda Umit , Ugur Mehmet , Akcali Kamil C. 
Published: February 2009

Mesenchymal stem cells (MSCs) have the capacity to differentiate into osteoblasts, chondrocytes, adipocytes, myocytes, and cardiomyocytes. Several established methods are presently available for in vitro isolation of MSCs from bone marrow. However, the duration necessary to culture them can be a major handicap to cell-based therapies needed for such urgent cardiovascular conditions as acute myocardial infarction and acute hindlimb ischemia. The best timing of cardiomyocyte differentiation induction after MCS isolation and expansion is still an unresolved issue. Our goal was to investigate the possibility of obtaining functional cardiomyocytes from rat MSC within a shorter time period. We examined MSCs’ colony-forming capacity, CD90 and CD34 immunoreactivity during the 14 days of culturing. Cardiomyocyte differentiation was induced by 5-azacytidine. Immunohistochemic staining, together with intracellular Ca2+ measurement experiments, revealed that MSCs do not differentiate into any specific cell lineage but show the characteristics of MSCs on both the 9th and 14th days of the culture. To check the potential for differentiation into cardiomyocytes, experiments with caffeine application and depolarization with KCl were performed. The cells possessed some of the specific biochemical features of contracting cells, with slightly higher capacities on the 14th day. Cells from 9th and 14th days of the culture that were treated with 5-azacytidine had a higher expression of cardiac-specific markers such as troponin I, α-sarcomeric actin, and MEF2D compared with the control groups. This study illustrates that it is possible to get functional cardiomyocytes from in vitro MSC culture in a shorter time period than previously achieved. This reduction in time may provide emergency cases with access to cell-based therapies that may have previously been unavailable.
illa rudem cursu prima imbuit Amphitriten (Catul. 64.11): The Dynamic Intertextual Connotations of a Metonymy
Authors: Michalopoulos Andreas 
Published: February 2009

AbstractThis paper examines the role and importance of Amphitrite in Catullus c. 64, the epyllion on the wedding of Peleus and Thetis. Catullus intends to conjure up Amphitrite's rich mythological background for the needs of his poem. Amphitrite's story contains thematic elements that recur in both narratives of c. 64, namely the main story of Peleus and Thetis, and the embedded story of Theseus and Ariadne. At the same time Amphitrite's meaningful presence in the prologue of c. 64 is a pointer to Bacchylides' Dithyramb 17, which treats Theseus' outbound journey to Crete and the test of his divine paternity, imposed by Minos. The several points of contact between B. Dith. 17 and Catul. c. 64 show that this Greek poem is an important subtext for c. 64, which has gone unnoticed so far.
A HaemAtlas: characterizing gene expression in differentiated human blood cells
Authors: Watkins Nicholas A. , Gusnanto Arief , de Bono Bernard , De Subhajyoti , Miranda-Saavedra Diego , Hardie Debbie L. , Angenent Will G. J. , Attwood Antony P. , Ellis Peter D. , Erber Wendy , Foad Nicola S. , Garner Stephen F. , Isacke Clare M. , Jolley Jennifer , Koch Kerstin , Macaulay Iain C. , Morley Sarah L. , Rendon Augusto , Rice Kate M. , Taylor Niall , Thijssen-Timmer Daphne C. , Tijssen Marloes R. , van der Schoot C. Ellen , Wernisch Lorenz , Winzer Thilo , Dudbridge Frank , Buckley Christopher D. , Langford Cordelia F. , Teichmann Sarah , Göttgens Berthold , Ouwehand Willem H. 
Published: February 2009

Abstract
Hematopoiesis is a carefully controlled process that is regulated by complex networks of transcription factors that are, in part, controlled by signals resulting from ligand binding to cell-surface receptors. To further understand hematopoiesis, we have compared gene expression profiles of human erythroblasts, megakaryocytes, B cells, cytotoxic and helper T cells, natural killer cells, granulocytes, and monocytes using whole genome microarrays. A bioinformatics analysis of these data was performed focusing on transcription factors, immunoglobulin superfamily members, and lineage-specific transcripts. We observed that the numbers of lineage-specific genes varies by 2 orders of magnitude, ranging from 5 for cytotoxic T cells to 878 for granulocytes. In addition, we have identified novel coexpression patterns for key transcription factors involved in hematopoiesis (eg, GATA3-GFI1 and GATA2-KLF1). This study represents the most comprehensive analysis of gene expression in hematopoietic cells to date and has identified genes that play key roles in lineage commitment and cell function. The data, which are freely accessible, will be invaluable for future studies on hematopoiesis and the role of specific genes and will also aid the understanding of the recent genome-wide association studies.
Mantle cell lymphoma cells express high levels of CXCR4, CXCR5, and VLA-4 (CD49d): importance for interactions with the stromal microenvironment and specific targeting
Authors: Kurtova Antonina V. , Tamayo Archito T. , Ford Richard J. , Burger Jan A. 
Published: February 2009

Abstract
Mantle cell lymphoma (MCL) is characterized by an early, widespread dissemination and residual disease after conventional treatment, but the mechanisms responsible for lymphoma cell motility and drug resistance are largely unknown. There is growing evidence suggesting that chemokine receptors and adhesion molecules are critical for malignant B-cell trafficking and homing to supportive tissue microenvironments, where they receive survival and drug resistance signals. Therefore, we examined chemokine receptor and adhesion molecule expression and function in MCL cells and their importance for migration and adhesion to marrow stromal cells (MSCs). We found that MCL cells display high levels of functional CXCR4 and CXCR5 chemokine receptors and VLA-4 adhesion molecules. We also report that MCL cells adhere and spontaneously migrate beneath MSCs in a CXCR4- and VLA-4–dependent fashion (pseudoemperipolesis). Moreover, we demonstrate that MSCs confer drug resistance to MCL cells, particularly to MCL cells that migrate beneath MSC. To target MCL-MSC interactions, we tested Plerixafor, a CXCR4 antagonist, and natalizumab, a VLA-4 antibody. Both agents blocked functional responses to the respective ligands and inhibited adhesive interactions between MCL cells and MSCs. These findings provide a rationale to further investigate the therapeutic potential of these drugs in MCL.
Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia
Authors: Chen Rong , Wierda William G. , Chubb Sherri , Hawtin Rachael E. , Fox Judith A. , Keating Michael J. , Gandhi Varsha , Plunkett William 
Published: February 2009

AbstractInhibitors of cyclin-dependent kinases (Cdks) have been reported to have activities in chronic lymphocytic leukemia cells by inhibiting Cdk7 and Cdk9, which control transcription. Here we studied the novel Cdk inhibitor SNS-032, which exhibits potent and selective inhibitory activity against Cdk2, Cdk7, and Cdk9. We hypothesized that transient inhibition of transcription by SNS-032 would decrease antiapoptotic proteins, resulting in cell death. SNS-032 effectively killed chronic lymphocytic leukemia cells in vitro regardless of prognostic indicators and treatment history. This was associated with inhibition of phosphorylation of RNA polymerase II and inhibition of RNA synthesis. Consistent with the intrinsic turnover rates of their transcripts and proteins, antiapoptotic proteins, such as Mcl-1 and X-linked inhibitor of apoptosis protein (XIAP), were rapidly reduced on exposure to SNS-032, whereas Bcl-2 protein was not affected. The initial decrease of Mcl-1 protein was the result of transcriptional inhibition rather than cleavage by caspase. Compared with flavopiridol and roscovitine, SNS-032 was more potent, both in inhibition of RNA synthesis and at induction of apoptosis. SNS-032 activity was readily reversible; removal of SNS-032 reactivated RNA polymerase II, which led to resynthesis of Mcl-1 and cell survival. Thus, these data support the clinical development of SNS-032 in diseases that require short-lived oncoproteins for survival.
DNA phosphorothioation in Streptomyces lividans: mutational analysis of the dnd locus
Authors: Xu Tiegang , Liang Jingdan , Chen Shi , Wang Lianrong , He Xinyi , You Delin , Wang Zhijun , Li Aiying , Xu Zhongli , Zhou Xiufen , Deng Zixin 
Published: February 2009

Abstract

Background
A novel DNA phosphorothioate modification (DNA sulfur modification), in which one of the non-bridging oxygen atoms in the phosphodiester bond linking DNA nucleotides is exchanged by sulphur, was found to be genetically determined by dnd or dnd-counterpart loci in a wide spectrum of bacteria from diverse habitats. A detailed mutational analysis of the individual genes within the dnd locus in Streptomyces lividans responsible for DNA phosphorothioation was performed and is described here. It should be of great help for the mechanistic study of this intriguing system.

Results
A 6,665-bp DNA region carrying just five ORFs (dndA-E) was defined as the sole determinant for modification of the DNA backbone in S. lividans to form phosphorothioate. This provides a diagnostically reliable and easily assayable Dnd (DNA degradation) phenotype. While dndA is clearly transcribed independently, dndB-E constitute an operon, as revealed by RT-PCR analysis. An efficient mutation-integration-complementation system was developed to allow for detailed functional analysis of these dnd genes. The Dnd- phenotype caused by specific in-frame deletion of the dndA, C, D, and E genes or the enhanced Dnd phenotype resulting from in-frame deletion of dndB could be restored by expression vectors carrying the corresponding dnd genes. Interestingly, overdosage of DndC or DndD, but not other Dnd proteins, in vivo was found to be detrimental to cell viability.

Conclusion
DNA phosphorothioation is a multi-enzymatic and highly coordinated process controlled by five dnd genes. Overexpression of some proteins in vivo prevented growth of host strain, suggesting that expression of the gene cluster is strictly regulated in the native host.
Identification and validation of reference genes for quantitative RT-PCR normalization in wheat
Authors: Paolacci Anna R , Tanzarella Oronzo A , Porceddu Enrico , Ciaffi Mario 
Published: February 2009

Abstract

Background
Usually the reference genes used in gene expression analysis have been chosen for their known or suspected housekeeping roles, however the variation observed in most of them hinders their effective use. The assessed lack of validated reference genes emphasizes the importance of a systematic study for their identification. For selecting candidate reference genes we have developed a simple in silico method based on the data publicly available in the wheat databases Unigene and TIGR.

Results
The expression stability of 32 genes was assessed by qRT-PCR using a set of cDNAs from 24 different plant samples, which included different tissues, developmental stages and temperature stresses. The selected sequences included 12 well-known HKGs representing different functional classes and 20 genes novel with reference to the normalization issue. The expression stability of the 32 candidate genes was tested by the computer programs geNorm and NormFinder using five different data-sets. Some discrepancies were detected in the ranking of the candidate reference genes, but there was substantial agreement between the groups of genes with the most and least stable expression. Three new identified reference genes appear more effective than the well-known and frequently used HKGs to normalize gene expression in wheat. Finally, the expression study of a gene encoding a PDI-like protein showed that its correct evaluation relies on the adoption of suitable normalization genes and can be negatively affected by the use of traditional HKGs with unstable expression, such as actin and α-tubulin.

Conclusion
The present research represents the first wide screening aimed to the identification of reference genes and of the corresponding primer pairs specifically designed for gene expression studies in wheat, in particular for qRT-PCR analyses. Several of the new identified reference genes outperformed the traditional HKGs in terms of expression stability under all the tested conditions. The new reference genes will enable more accurate normalization and quantification of gene expression in wheat and will be helpful for designing primer pairs targeting orthologous genes in other plant species.
Phenotypic instability and epigenetic variability in a diploid potato of hybrid origin, Solanum ruiz-lealii
Authors: Marfil Carlos F , Camadro Elsa L , Masuelli Ricardo W 
Published: February 2009

Abstract

Background
The wild potato Solanum ruiz-lealii Brüch. (2n = 2x = 24), a species of hybrid origin, is endemic to Mendoza province, Argentina. Recurrent flower malformations, which varied among inflorescences of the same plant, were observed in a natural population. These abnormalities could be the result of genomic instabilities, nucleus-cytoplasmic incompatibility or epigenetic changes. To shed some light on their origin, nuclear and mitochondrial DNA of plants with normal and plants with both normal and malformed flowers (from here on designated as plants with normal and plants with abnormal flower phenotypes, respectively) were analyzed by AFLP and restriction analyses, respectively. Also, the wide genome methylation status and the level of methylation of a repetitive sequence were studied by MSAP and Southern blots analyses, respectively.

Results
AFLP markers and restriction patterns of mitochondrial DNA did not allow the differentiation of normal from abnormal flower phenotypes. However, methylation patterns of nuclear DNA discriminated normal and abnormal flower phenotypes into two different groups, indicating that abnormal phenotypes have a similar methylation status which, in turn, was different from the methylation patterns of normal phenotypes. The abnormal flower phenotype was obtained by treating a normal plant with 5-Azacytidine, a demethylating agent, giving support to the idea of the role of DNA methylation in the origin of flower abnormalities. In addition, the variability detected for DNA methylation was greater than the detected for nucleotide sequence.

Conclusion
The epigenetic nature of the observed flower abnormalities is consistent with the results and indicates that in the diploid hybrid studied, natural variation in methylation profiles of anonymous DNA sequences could be of biological significance.
Moderate alcohol consumption is associated with better endothelial function: a cross sectional study
Authors: Suzuki Keiko , Elkind Mitchell SV , Boden-Albala Bernadette , Jin Zhezhen , Berry Grace , Di Tullio Marco R , Sacco Ralph L , Homma Shunichi 
Published: February 2009

AbstractBackgroundModerate alcohol consumption is protective against coronary artery disease. Endothelial dysfunction contributes to atherosclerosis and the pathogenesis of cardiovascular disease. The effects of alcohol consumption on endothelial function may be relevant to these cardiovascular outcomes, but very few studies have examined the effect of alcohol consumption on endothelial function assessed by flow-mediated dilation (FMD) of the brachial artery in humans.MethodsIn the population-based Northern Manhattan Study (NOMAS), we performed a cross-sectional analysis of lifetime alcohol intake and brachial artery FMD during reactive hyperemia using high-resolution B-mode ultrasound images among 884 stroke-free participants (mean age 66.8 years, women 56.6%, Hispanic 67.4%, black 17.4%, and white 15.2%).ResultsThe mean brachial FMD was 5.7% and the median was 5.5%. Compared to non-drinkers, those who drank >1 drink/month to 2 drinks/day were more likely to have FMD above the median FMD (5.5%) (unadjusted OR 1.7, 95% CI 1.2–2.4, p = 0.005). In multivariate analysis, the relationship between moderate alcohol consumption and FMD remained significant after adjusting for multiple traditional cardiovascular risk factors, including sex, race-ethnicity, body mass index, diabetes mellitus, coronary artery disease, Framingham risk score, medication use (adjusted OR 1.8, 95%CI 1.1–3.0, p = 0.03). No beneficial effect on FMD was seen for those who drank more than 2 drinks/day.ConclusionIn conclusion, consumption of up to 2 alcoholic beverages per day was independently associated with better FMD compared to no alcohol consumption in this multiethnic population. This effect on FMD may represent an important mechanism in explaining the protective effect of alcohol intake on cardiovascular disease.
ARC (NSC 188491) has identical activity to Sangivamycin (NSC 65346) including inhibition of both P-TEFb and PKC
Authors: Stockwin Luke H , Yu Sherry X , Stotler Howard , Hollingshead Melinda G , Newton Dianne L 
Published: February 2009

AbstractBackgroundThe nucleoside analog, ARC (NSC 188491) is a recently characterized transcriptional inhibitor that selectively kills cancer cells and has the ability to perturb angiogenesisin vitro. In this study, the mechanism of action of ARC was further investigated by comparingin vitroandin vivoactivity with other anti-neoplastic purines.MethodsStructure-based homology searches were used to identify those compounds with similarity to ARC. Comparator compounds were then evaluated alongside ARC in the context of viability, cell cycle and apoptosis assays to establish any similarities. Following this, biological overlap was explored in detail using gene-expression analysis and kinase inhibition assays.ResultsResults demonstrated that sangivamycin, an extensively characterized pro-apoptotic nucleoside isolated fromStreptomyces, had identical activity to ARC in terms of 1) cytotoxicity assays, 2) ability to induce a G2/M block, 3) inhibitory effects on RNA/DNA/protein synthesis, 4) transcriptomic response to treatment, 5) inhibition of protein kinase C, 6) inhibition of positive transcription elongation factor b (P-TEFb), 7) inhibition of VEGF secretion, and 8) activity within hollow fiber assays. Extending ARC activity to PKC inhibition provides a molecular basis for ARC cancer selectivity and anti-angiogenic effects. Furthermore, functional overlap between ARC and sangivamycin suggests that development of ARC may benefit from a retrospective of previous sangivamycin clinical trials. However, ARC was found to be inactive in several xenograft models, likely a consequence of rapid serum clearance.ConclusionOverall, these data expand on the biological properties of ARC but suggest additional studies are required before it can be considered a clinical trials candidate.
Expression and biological significance of c-FLIP in human hepatocellular carcinomas
Authors: Du Xilin , Bao Guoqiang , He Xianli , Zhao Huadong , Yu Fang , Qiao Qing , Lu Jianguo , Ma Qingjiu 
Published: February 2009

AbstractBackgroundc-FLIP can be considered as a tumor-progression factor in regard to its anti-apoptotic functions. In the present study, we intended to investigate the expression of c-FLIP in human HCC tissues, and its relation with drug-induced cell apoptosis through the specific inhibition of c-FLIP expression by siRNA in 7721 cells.Methodsc-FLIP expression was quantified immunohistochemically in HCC tissues(eighty-six cases), and corresponding noncancerous tissues (fifty-seven cases). Patients with HCC were followed up for cancer recurrence. Then, the c-FLIP gene was silenced with specific siRNA in 7721 HCC cells. c-FLIP expression was detected by RT-PCR, Western Blot and immunocytochemical staining. The cellular viability and cell apoptosis were assayedin vitrowith cells treated with doxorubicin.ResultsPositive immunostaining was detected for c-FLIP in 83.72% (72/86) human HCC tissues, 14.81% (4/27) hepatic cirrhosis, 11.11% (2/18) hepatic hemangioma tissues, and absent in normal hepatic tissues. The overexpression(more than 50%) of c-FLIP in HCC adversely affected the recurrence-free survival. Through c-FLIP gene silencing with siRNA, the expressions of c-FLIP mRNA and protein were remarkably down-regulated in 7721 HCC cells. And doxorubicin showed apparent inhibition on cell proliferations, and induced more apoptosis.ConclusionThese results indicate that c-FLIP is frequently expressed in human HCCs, and its overexpression implied a lesser probability of recurrence-free survival. The specific silencing of c-FLIP gene can apparently up-regulate drug-induced HCC cell apoptosis, and may have therapeutic potential for the treatment of human HCC.