bluuebunny/crossref_metadata_2025_split huggingface dataset:
A SNP in a let-7 microRNA Complementary Site in the KRAS 3′ Untranslated Region Increases Non–Small Cell Lung Cancer Risk
Authors: Chin Lena J. , Ratner Elena , Leng Shuguang , Zhai Rihong , Nallur Sunitha , Babar Imran , Muller Roman-Ulrich , Straka Eva , Su Li , Burki Elizabeth A. , Crowell Richard E. , Patel Rajeshvari , Kulkarni Trupti , Homer Robert , Zelterman Daniel , Kidd Kenneth K. , Zhu Yong , Christiani David C. , Belinsky Steven A. , Slack Frank J. , Weidhaas Joanne B. 
Published: October 2008

Abstract
Lung cancer is the leading cause of cancer deaths worldwide, yet few genetic markers of lung cancer risk useful for screening exist. The let-7 family-of-microRNAs (miRNA) are global genetic regulators important in controlling lung cancer oncogene expression by binding to the 3′ untranslated regions of their target mRNAs. The purpose of this study was to identify single nucleotide polymorphisms (SNP) that could modify let-7 binding and to assess the effect of such SNPs on target gene regulation and risk for non–small cell lung cancer (NSCLC). let-7 complementary sites (LCS) were sequenced in the KRAS 3′ untranslated region from 74 NSCLC cases to identify mutations and SNPs that correlated with NSCLC. The allele frequency of a previously unidentified SNP at LCS6 was characterized in 2,433 people (representing 46 human populations). The frequency of the variant allele is 18.1% to 20.3% in NSCLC patients and 5.8% in world populations. The association between the SNP and the risk for NSCLC was defined in two independent case-control studies. A case-control study of lung cancer from New Mexico showed a 2.3-fold increased risk (confidence interval, 1.1–4.6; P = 0.02) for NSCLC cancer in patients who smoked &lt;40 pack-years. This association was validated in a second independent case-control study. Functionally, the variant allele results in KRAS overexpression in vitro. The LCS6 variant allele in a KRAS miRANA complementary site is significantly associated with increased risk for NSCLC among moderate smokers and represents a new paradigm for let-7 miRNAs in lung cancer susceptibility. [Cancer Res 2008;68(20):8535–40]
Activation of Apoptosis by 1-Hydroxy-5,7-Dimethoxy-2-Naphthalene-Carboxaldehyde, a Novel Compound from Aegle marmelos
Authors: Subramaniam Dharmalingam , Giridharan Periyasamy , Murmu Nabendu , Shankaranarayanan Nallakandy P. , May Randal , Houchen Courtney W. , Ramanujam Rama P. , Balakrishnan Arun , Vishwakarma Ram A. , Anant Shrikant 
Published: October 2008

Abstract
We have identified a natural compound that activates apoptosis of epithelial cancer cells through activation of tumor necrosis factor-α (TNF-α), TNF receptor (TNFR)-associated death domain (TRADD), and caspases. The molecule 1-hydroxy-5,7-dimethoxy-2-naphthalene-carboxaldehyde (HDNC, marmelin) was isolated and characterized from ethyl acetate fraction of extracts of Aegle marmelos. HDNC treatment inhibited the growth of HCT-116 colon cancer tumor xenografts in vivo. Immunostaining for CD31 showed that there was a significant reduction in microvessels in the HDNC-treated animals, coupled with decreased cyclooxygenase-2, interleukin-8, and vascular endothelial growth factor mRNA. Using hexoseaminidase assay, we determined that HDNC inhibits proliferation of HCT-116 colon and HEp-2 alveolar epithelial carcinoma cells. Furthermore, the cancer cells showed increased levels of activated caspase-3 and induced G1 cell cycle arrest, which was suppressed by caspase-3 inhibitors. HDNC induced TNF-α, TNFR1, and TRADD mRNA and protein expression. Moreover, caspase-8 and Bid activation, and cytochrome c release, were observed, suggesting the existence of a cross-talk between death receptor and the mitochondrial pathways. HDNC inhibited AKT and extracellular signal-regulated kinase phosphorylation both in cells in culture and in tumor xenografts. In addition, electrophoretic mobility shift assay and luciferase reporter assays showed that HDNC significantly suppressed TNF-α–mediated activation and translocation of nuclear factor-κB (NF-κB). This was further confirmed by Western blot analysis of nuclear extracts wherein levels of RelA, the p65 component of NF-κB, were significantly less in cells treated with HDNC. Together, the data suggest that the novel compound HDNC (marmelin) is a potent anticancer agent that induces apoptosis during G1 phase of the cell cycle and could be a potential chemotherapeutic candidate. [Cancer Res 2008;68(20):8573–81]
Association of HDM2 Transcript Levels with Age of Onset and Prognosis in Soft Tissue Sarcomas
Authors: Taubert Helge , Bartel Frank , Greither Thomas , Bache Matthias , Kappler Matthias , Köhler Thomas , Böhnke Anja , Lautenschläger Christine , Schmidt Hannelore , Holzhausen Hans-Jürgen , Hauptmann Steffen , Würl Peter 
Published: October 2008

Abstract
The p53 stress response is crucial for the prevention of tumor formation. The oncogene HDM2 is one of the key negative regulators of p53 and is a central node in the p53 pathway. P53 and HDM2 form an oscillating feedback loop. HDM2 expression is regulated by different promoters. To evaluate its clinical relevance, we determined the levels of HDM2 transcripts originating from the constitutive P1 and p53-sensitive P2 promoter in 133 soft tissue sarcomas and correlated the results with the age of diagnosis and the patients' outcome. We show that only high levels of the HDM2-P1 transcript but not the P2 transcript are associated with an 11-year earlier age of onset (50.5 years) compared with low P1 levels (61.5 years; P &lt; 0.0001, t test). In addition, low P1 and P2 mRNA expression levels were independent predictors of poor outcome for patients with soft tissue sarcomas (low P1: relative risk, 3.7; P &lt; 0.0001; low P2: relative risk, 2.5; P = 0.001). A change in the expression levels of the HDM2 transcripts originating from the two HDM2 promoters could disrupt the oscillating P53-HDM2 feedback loop in a way that elevated levels of HDM2-P1 transcript are associated with an earlier age of tumor onset and that reduced levels of HDM2-P1 or HDM2-P2 transcripts are correlated with poor prognosis of patients with soft tissue sarcomas. (Mol Cancer Res 2008;6(10):1575–81)
Focal Adhesion Kinase Controls Aggressive Phenotype of Androgen-Independent Prostate Cancer
Authors: Johnson Thomas R. , Khandrika Lakshmipathi , Kumar Binod , Venezia Sarah , Koul Sweaty , Chandhoke Ryan , Maroni Paul , Donohue Robert , Meacham Randall B. , Koul Hari K. 
Published: October 2008

AbstractOverexpression of focal adhesion kinase (FAK) has been well correlated with tumor development and/or the maintenance of tumor phenotype. In addition, inappropriate activation of the extracellular regulated kinase (ERK) signaling pathway is common to many human cancers. In the present study, we investigated the interplay between FAK and ERK in androgen-independent prostate cancer cells (PC3 and DU145 cells). We observed that suppression of FAK expression using small interfering RNA–mediated knockdown decreased the clonogenic activity, whereas overexpression of FAK increased it. We also observed that detachment of PC3 and DU145 cells from their substrate induced tyrosine phosphorylation of FAK. ERK knockdown diminished FAK protein levels and tyrosine phosphorylation of FAK as well as FAK promoter-reporter activity. We also tested the effect of MEK inhibitors and small interfering RNA–mediated knockdown of ERK1 and/or ERK2 on cell proliferation, invasiveness, and growth in soft agar of PC3 and DU145 cells. Inhibition of ERK signaling grossly impaired clonogenicity as well as invasion through Matrigel. However, inhibition of ERK signaling resulted in only a modest inhibition of 3H-thymidine incorporation and no effect on overall viability of the cells or increased sensitivity to anoikis. Taken together, these data show, for the first time, a requirement for FAK in aggressive phenotype of prostate cancer cells; reveal interdependence of FAK and ERK1/2 for clonogenic and invasive activity of androgen-independent prostate cancer cells; suggest a role for ERK regulation of FAK in substrate-dependent survival; and show for the first time, in any cell type, the regulation of FAK expression by ERK signaling pathway. (Mol Cancer Res 2008;6(10):1639–48)
Suppression of hPOT1 in Diploid Human Cells Results in an hTERT-Dependent Alteration of Telomere Length Dynamics
Authors: Possemato Richard , Timmons Jamie C. , Bauerlein Erica L. , Wada Naoya , Baldwin Amy , Masutomi Kenkichi , Hahn William C. 
Published: October 2008

Abstract
POT1 is a 3′ telomeric single-stranded overhang binding protein that has been implicated in chromosome end protection, the regulation of telomerase function, and defining the 5′ chromosome terminus. In human cancer cells that exhibit constitutive hTERT activity, hPOT1 exerts control over telomere length. Primary human fibroblasts express low levels of catalytically active hTERT in an S-phase–restricted manner that fails to counteract telomere attrition with cell division. Here, we show that diploid human fibroblasts in which hPOT1 expression has been suppressed harbor telomeres that are longer than control cells. This difference in telomere length delays the onset of replicative senescence and is dependent on S-phase–restricted hTERT expression. These findings are consistent with the view that hPOT1 promotes a nonextendable telomere state resistant to extension by S-phase–restricted telomerase. Manipulating this function of hPOT1 may thus hasten the cytotoxic effects of telomerase inhibition. (Mol Cancer Res 2008;6(10):1582–93)
Muslim Families Comprising Pakistani Fathers and Japanese Mothers: Focusing on the Educational Problems of their Children
Authors: Takeshita Shuko 
Published: October 2008

AbstractRecently, the educational problems of children with non-Japanese Muslim fathers and Japanese mothers have come to light in Japan. There has been an increase in the number of transnational families in which the Japanese mother and children have moved to an Islamic country for the Islamic education of the children while the non-Japanese father remains in Japan to work. In this paper, I conduct a case study analysis of families comprising Pakistani husbands and Japanese wives, who selected Sharjah in the United Arab Emirates (UAE) as the new place of residence for the wife and children, in view of the difficulties in transmitting Islamic values to the children while living in Japan. In this paper, I focus on the educational problems among Muslim children, and attempt to clarify the types of educational strategy that have been developed using social capital arising from social networks. They have selected an educational strategy with a view toward a transnational social space.
Using a Low-Order Model to Detect and Characterize Tornadoes in Multiple-Doppler Radar Data
Authors: Potvin Corey K. , Shapiro Alan , Yu Tian-You , Gao Jidong , Xue Ming 
Published: October 2008

Abstract
A new multiple-Doppler radar analysis technique is presented for the objective detection and characterization of tornado-like vortices. The technique consists of fitting radial wind data from two or more radars to a simple analytical model of a vortex and its near-environment. The model combines a uniform flow, linear shear flow, linear divergence flow (all of which compose a broadscale flow), and a modified combined Rankine vortex (representing the tornado). The vortex and its environment are allowed to translate. The parameters in the low-order model are determined by minimizing a cost function that accounts for the discrepancy between the model and observed radial winds. Since vortex translation is taken into account, the cost function can be evaluated over time as well as space, and thus the observations can be used at the actual times and locations where they were acquired. The technique is first tested using analytically simulated observations whose wind field and error characteristics are systematically varied. An Advanced Regional Prediction System (ARPS) high-resolution numerical simulation of a supercell and associated tornado is then used to emulate an observation dataset. The method is tested with two virtual radars for several radar-sampling strategies. Finally, the technique is applied to a dataset of real dual-Doppler observations of a tornado that struck central Oklahoma on 8 May 2003. The method shows skill in retrieving the tornado path and radar-grid-scale features of the horizontal wind field in the vicinity of the tornado. The best results are obtained using a two-step procedure in which the broadscale flow is retrieved first.
Advances and Challenges at the National Hurricane Center
Authors: Rappaport Edward N. , Franklin James L. , Avila Lixion A. , Baig Stephen R. , Beven John L. , Blake Eric S. , Burr Christopher A. , Jiing Jiann-Gwo , Juckins Christopher A. , Knabb Richard D. , Landsea Christopher W. , Mainelli Michelle , Mayfield Max , McAdie Colin J. , Pasch Richard J. , Sisko Christopher , Stewart Stacy R. , Tribble Ahsha N. 
Published: October 2008

Abstract
The National Hurricane Center issues analyses, forecasts, and warnings over large parts of the North Atlantic and Pacific Oceans, and in support of many nearby countries. Advances in observational capabilities, operational numerical weather prediction, and forecaster tools and support systems over the past 15–20 yr have enabled the center to make more accurate forecasts, extend forecast lead times, and provide new products and services. Important limitations, however, persist. This paper discusses the current workings and state of the nation’s hurricane warning program, and highlights recent improvements and the enabling science and technology. It concludes with a look ahead at opportunities to address challenges.
A conifer genomics resource of 200,000 spruce (Picea spp.) ESTs and 6,464 high-quality, sequence-finished full-length cDNAs for Sitka spruce (Picea sitchensis)
Authors: Ralph Steven G , Chun Hye Jung E , Kolosova Natalia , Cooper Dawn , Oddy Claire , Ritland Carol E , Kirkpatrick Robert , Moore Richard , Barber Sarah , Holt Robert A , Jones Steven JM , Marra Marco A , Douglas Carl J , Ritland Kermit , Bohlmann Jörg 
Published: October 2008

Abstract

Background
Members of the pine family (Pinaceae), especially species of spruce (Picea spp.) and pine (Pinus spp.), dominate many of the world's temperate and boreal forests. These conifer forests are of critical importance for global ecosystem stability and biodiversity. They also provide the majority of the world's wood and fiber supply and serve as a renewable resource for other industrial biomaterials. In contrast to angiosperms, functional and comparative genomics research on conifers, or other gymnosperms, is limited by the lack of a relevant reference genome sequence. Sequence-finished full-length (FL)cDNAs and large collections of expressed sequence tags (ESTs) are essential for gene discovery, functional genomics, and for future efforts of conifer genome annotation.

Results
As part of a conifer genomics program to characterize defense against insects and adaptation to local environments, and to discover genes for the production of biomaterials, we developed 20 standard, normalized or full-length enriched cDNA libraries from Sitka spruce (P. sitchensis), white spruce (P. glauca), and interior spruce (P. glauca-engelmannii complex). We sequenced and analyzed 206,875 3'- or 5'-end ESTs from these libraries, and developed a resource of 6,464 high-quality sequence-finished FLcDNAs from Sitka spruce. Clustering and assembly of 147,146 3'-end ESTs resulted in 19,941 contigs and 26,804 singletons, representing 46,745 putative unique transcripts (PUTs). The 6,464 FLcDNAs were all obtained from a single Sitka spruce genotype and represent 5,718 PUTs.

Conclusion
This paper provides detailed annotation and quality assessment of a large EST and FLcDNA resource for spruce. The 6,464 Sitka spruce FLcDNAs represent the third largest sequence-verified FLcDNA resource for any plant species, behind only rice (Oryza sativa) and Arabidopsis (Arabidopsis thaliana), and the only substantial FLcDNA resource for a gymnosperm. Our emphasis on capturing FLcDNAs and ESTs from cDNA libraries representing herbivore-, wound- or elicitor-treated induced spruce tissues, along with incorporating normalization to capture rare transcripts, resulted in a rich resource for functional genomics and proteomics studies. Sequence comparisons against five plant genomes and the non-redundant GenBank protein database revealed that a substantial number of spruce transcripts have no obvious similarity to known angiosperm gene sequences. Opportunities for future applications of the sequence and clone resources for comparative and functional genomics are discussed.
Identification of drought-responsive genes in roots of upland rice (Oryza sativa L)
Authors: Rabello Aline R , Guimarães Cléber M , Rangel Paulo HN , da Silva Felipe R , Seixas Daniela , de Souza Emanuel , Brasileiro Ana CM , Spehar Carlos R , Ferreira Márcio E , Mehta Ângela 
Published: October 2008

Abstract

Background
Rice (Oryza sativa L.) germplasm represents an extraordinary source of genes that control traits of agronomic importance such as drought tolerance. This diversity is the basis for the development of new cultivars better adapted to water restriction conditions, in particular for upland rice, which is grown under rainfall. The analyses of subtractive cDNA libraries and differential protein expression of drought tolerant and susceptible genotypes can contribute to the understanding of the genetic control of water use efficiency in rice.

Results
Two subtractive libraries were constructed using cDNA of drought susceptible and tolerant genotypes submitted to stress against cDNA of well-watered plants. In silico analysis revealed 463 reads, which were grouped into 282 clusters. Several genes expressed exclusively in the tolerant or susceptible genotypes were identified. Additionally, proteome analysis of roots from stressed plants was performed and 22 proteins putatively associated to drought tolerance were identified by mass spectrometry.

Conclusion
Several genes and proteins involved in drought-response, as well as genes with no described homologs were identified. Genes exclusively expressed in the tolerant genotype were, in general, related to maintenance of turgor and cell integrity. In contrast, in the susceptible genotype, expression of genes involved in protection against cell damage was not detected. Several protein families identified in the proteomic analysis were not detected in the cDNA analysis. There is an indication that the mechanisms of susceptibility to drought in upland rice are similar to those of lowland varieties.
Acid stress damage of DNA is prevented by Dps binding in Escherichia coliO157:H7
Authors: Jeong Kwang Cheol , Hung Kai Foong , Baumler David J , Byrd Jeffrey J , Kaspar Charles W 
Published: October 2008

Abstract

Background
Acid tolerance in Escherichia coli O157:H7 contributes to persistence in its bovine host and is thought to promote passage through the gastric barrier of humans. Dps (DNA-binding protein in starved cells) mutants of E. coli have reduced acid tolerance when compared to the parent strain although the role of Dps in acid tolerance is unclear. This study investigated the mechanism by which Dps contributes to acid tolerance in E. coli O157:H7.

Results
The results from this study showed that acid stress lead to damage of chromosomal DNA, which was accentuated in dps and recA mutants. The use of Bal31, which cleaves DNA at nicks and single-stranded regions, to analyze chromosomal DNA extracted from cells challenged at pH 2.0 provided in vivo evidence of acid damage to DNA. The DNA damage in a recA mutant further corroborated the hypothesis that acid stress leads to DNA strand breaks. Under in vitro assay conditions, Dps was shown to bind plasmid DNA directly and protect it from acid-induced strand breaks. Furthermore, the extraction of DNA from Dps-DNA complexes required a denaturing agent at low pH (2.2 and 3.6) but not at higher pH (>pH4.6). Low pH also restored the DNA-binding activity of heat-denatured Dps. Circular dichroism spectra revealed that at pH 3.6 and pH 2.2 Dps maintains or forms α-helices that are important for Dps-DNA complex formation.

Conclusion
Results from the present work showed that acid stress results in DNA damage that is more pronounced in dps and recA mutants. The contribution of RecA to acid tolerance indicated that DNA repair was important even when Dps was present. Dps protected DNA from acid damage by binding to DNA. Low pH appeared to strengthen the Dps-DNA association and the secondary structure of Dps retained or formed α-helices at low pH. Further investigation into the precise interplay between DNA protection and damage repair pathways during acid stress are underway to gain additional insight.
Identification of biomarkers in ductal carcinoma in situ of the breast with microinvasion
Authors: Okumura Yasuhiro , Yamamoto Yutaka , Zhang Zhenhuan , Toyama Tatsuya , Kawasoe Teru , Ibusuki Mutsuko , Honda Yumi , Iyama Ken-ichi , Yamashita Hiroko , Iwase Hirotaka 
Published: October 2008

Abstract

Background
Widespread use of mammography in breast cancer screening has led to the identification of increasing numbers of patients with ductal carcinoma in situ (DCIS). DCIS of the breast with an area of focal invasion 1 mm or less in diameter is defined as DCIS with microinvasion, DCIS-Mi. Identification of biological differences between DCIS and DCIS-Mi may aid in understanding of the nature and causes of the progression of DCIS to invasiveness.

Methods
In this study, using resected breast cancer tissues, we compared pure DCIS (52 cases) and DCIS-Mi (28 cases) with regard to pathological findings of intraductal lesions, biological factors, apoptosis-related protein expression, and proliferative capacity through the use of immunohistochemistry and the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method.

Results
There were no differences in biological factors between DCIS and DCIS-Mi, with respect to levels of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2. The frequency of necrosis and positive expression ratio of survivin and Bax were significantly higher in DCIS-Mi than in DCIS. In addition, apoptotic index, Ki-67 index, and positive Bcl-2 immunolabeling tended to be higher in DCIS-Mi than in DCIS. Multivariate analysis revealed that the presence of necrosis and positive survivin expression were independent factors associated with invasion.

Conclusion
Compared with DCIS, DCIS-Mi is characterized by a slightly elevated cell proliferation capacity and enhanced apoptosis within the intraductal lesion, both of which are thought to promote the formation of cell necrotic foci. Furthermore, the differential expression of survivin may serve in deciding the response to therapy and may have some prognostic significance.