bluuebunny/crossref_metadata_2025_split huggingface dataset:
cis
-Acting Sequences That Contribute to Synthesis of Minus-Strand DNA Are Not Conserved between Hepadnaviruses
Authors: Maguire Megan L. , Loeb Daniel D. 
Published: October 2010

ABSTRACT

Hepadnaviruses are DNA viruses that are found in several mammalian and avian species. These viruses replicate their genome through reverse transcription of an RNA intermediate termed pregenomic RNA (pgRNA). pgRNA is reverse transcribed by the viral polymerase into a minus-strand DNA, followed by synthesis of the plus-strand DNA. There are multiple
cis
-acting sequences that contribute to the synthesis of minus-strand DNA for human hepatitis B virus (HBV). Less is known about the
cis
-acting sequences of avian hepadnaviruses that contribute to synthesis of minus-strand DNA. To identify
cis
-acting sequences of duck hepatitis B virus (DHBV) and heron hepatitis B virus (HHBV), we analyzed variants containing 200-nucleotide (nt) deletions. Most variants of DHBV synthesized minus-strand DNA to 50 to 100% of the wild-type (WT) level, while two variants synthesized less than 50%. For HHBV, most variants synthesized minus-strand DNA to less than 50% the WT level. These results differ from those for HBV, where most of the genome can be removed with little consequence. HBV contains a sequence, φ, that contributes to the synthesis of minus-strand DNA. It has been proposed that DHBV has an analogous sequence. We determined that the proposed φ sequence of DHBV does not contribute to the synthesis of minus-strand DNA. Finally, we found that the DR2 sequence present in all hepadnaviruses is important for synthesis of minus-strand DNA in both DHBV and HHBV but not in HBV. These differences in
cis
-acting sequences suggest that the individual hepadnaviruses have evolved differences in their mechanisms for synthesizing minus-strand DNA, more so than for other steps in replication.
Efficient Activation of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein by the Transmembrane Protease TMPRSS2
Authors: Matsuyama Shutoku , Nagata Noriyo , Shirato Kazuya , Kawase Miyuki , Takeda Makoto , Taguchi Fumihiro 
Published: October 2010

ABSTRACTThe distribution of the severe acute respiratory syndrome coronavirus (SARS-CoV) receptor, an angiotensin-converting enzyme 2 (ACE2), does not strictly correlate with SARS-CoV cell tropism in lungs; therefore, other cellular factors have been predicted to be required for activation of virus infection. In the present study, we identified transmembrane protease serine 2 (TMPRSS2), whose expression does correlate with SARS-CoV infection in the upper lobe of the lung. In Vero cells expressing TMPRSS2, large syncytia were induced by SARS-CoV infection. Further, the lysosome-tropic reagents failed to inhibit, whereas the heptad repeat peptide efficiently inhibited viral entry into cells, suggesting that TMPRSS2 affects the S protein at the cell surface and induces virus-plasma membrane fusion. On the other hand, production of virus in TMPRSS2-expressing cells did not result in S-protein cleavage or increased infectivity of the resulting virus. Thus, TMPRSS2 affects the entry of virus but not other phases of virus replication. We hypothesized that the spatial orientation of TMPRSS2 vis-a-vis S protein is a key mechanism underling this phenomenon. To test this, the TMPRSS2 and S proteins were expressed in cells labeled with fluorescent probes of different colors, and the cell-cell fusion between these cells was tested. Results indicate that TMPRSS2 needs to be expressed in the opposing (target) cell membrane to activate S protein rather than in the producer cell, as found for influenza A virus and metapneumoviruses. This is the first report of TMPRSS2 being required in the target cell for activation of a viral fusion protein but not for the S protein synthesized in and transported to the surface of cells. Our findings suggest that the TMPRSS2 expressed in lung tissues may be a determinant of viral tropism and pathogenicity at the initial site of SARS-CoV infection.
Association of Potent Human Antiviral Cytidine Deaminases with 7SL RNA and Viral RNP in HIV-1 Virions
Authors: Zhang Wenyan , Du Juan , Yu Kevin , Wang Tao , Yong Xiong , Yu Xiao-Fang 
Published: October 2010

ABSTRACT

7SL RNA promotes the formation of the signal recognition particle that targets secretory and membrane proteins to the endoplasmic reticulum. 7SL RNA is also selectively packaged by many retroviruses, including HIV-1. Here, we demonstrate that 7SL RNA is an integral component of the viral ribonucleoprotein (RNP) complex containing Gag, viral genomic RNA, and

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. Only the potent anti-HIV-1 cytidine deaminases can bind to 7SL RNA and target to HIV-1 RNP. A conserved motif in the amino-terminal region of A3G is important for 7SL RNA interaction. The weak anti-HIV-1 A3C did not interact with 7SL RNA and failed to target to viral RNPs, despite efficient virion packaging. However, a chimeric construct of A3C plus the 7SL-binding amino terminus of A3G did target to viral RNPs and showed enhanced anti-HIV-1 activity. 7SL RNA binding is a conserved feature of human anti-HIV-1 cytidine deaminases. Thus, potent anti-HIV-1 cytidine deaminases have evolved to possess a unique RNA-binding ability for precise HIV-1 targeting and viral inhibition.
Beyond the neglect of psychological consequences: post-traumatic stress disorder increases the non-fatal burden of injury by more than 50%
Authors: Haagsma Juanita A , Polinder Suzanne , Toet Hidde , Panneman Martien , Havelaar Arie H , Bonsel Gouke J , van Beeck Ed F 
Published: October 2010

BackgroundPsychological consequences such as post-traumatic stress disorder (PTSD) are currently neglected in burden-of-injury calculations.AimTo assess the disease burden of PTSD due to unintentional injury and compare this health loss with physical injury consequences.MethodsFrom literature sources, the prevalence of PTSD at four follow-up periods (<3 months, 3–6 months, 7–12 months and >12 months) was estimated. The uncertainty of the estimated PTSD prevalence was modelled by a Bayesian approach. The prevalence rates were then linked to national data on unintentional injury, disability weights and duration to estimate the incidence and disability-adjusted life years (DALY) resulting from PTSD in addition to physical injury consequences.ResultsThe data suggest that PTSD prevalence among injury victims decreases over time. The average PTSD prevalence at <3 months follow-up was 21% (90% credibility interval (CI) 17% to 24%) for patients presenting at the emergency department and 30% (90% CI 27% to 33%) for patients who were hospitalised, tapering down after 12 months to 4% (90% CI 3% to 5%) and 6% (90% CI 4% to 10%), respectively. These estimates translate into 191 000 (90% CI 161 000 to 222 000) cases of PTSD per year in the Dutch population (1.2%) due to unintentional injury. Including PTSD increases the non-fatal burden of disease of unintentional injuries by 53% (from 116 000 to 178 000 DALYs (90% CI 150 000 to 217 000)).ConclusionsIgnoring PTSD in burden-of-injury studies results in a considerable underestimation of the burden of injury. This may affect resource allocation and the identification of important prevention priorities.
Oncogene-Driven Intrinsic Inflammation Induces Leukocyte Production of Tumor Necrosis Factor That Critically Contributes to Mammary Carcinogenesis
Authors: Sangaletti Sabina , Tripodo Claudio , Ratti Chiara , Piconese Silvia , Porcasi Rossana , Salcedo Rosalba , Trinchieri Giorgio , Colombo Mario P. , Chiodoni Claudia 
Published: October 2010

Abstract
Oncogene activation promotes an intrinsic inflammatory pathway that is crucial for cancer development. Here, we have investigated the actual effect of the inflammatory cytokine tumor necrosis factor (TNF) on the natural history of spontaneous mammary cancer in the HER2/neuT (NeuT) transgenic mouse model. Bone marrow transplantation from TNF knockout mice into NeuT recipients significantly impaired tumor growth, indicating that the source of TNF fostering tumor development was of bone marrow origin. We show that the absence of leukocyte-derived TNF disarranged the tumor vasculature, which lacked pericyte coverage and structural integrity, leading to diffuse vascular hemorrhage and stromal necrosis. In addition, tumor-associated Tie2–expressing monocytes were reduced and cytokine expression skewed from Th2 to Th1 type. Treatment of NeuT mice with anti-TNF antibody partially phenocopied the antitumor effect of TNF-deficient bone marrow cell transplantation, providing a strong preclinical background and rationale for the introduction of TNF antagonists in the treatment of human breast cancer, including basal-like samples for which consolidated targeted therapies do not exist. Cancer Res; 70(20); 7764–75. ©2010 AACR.
Microtentacles Tip the Balance of Cytoskeletal Forces in Circulating Tumor Cells
Authors: Matrone Michael A. , Whipple Rebecca A. , Balzer Eric M. , Martin Stuart S. 
Published: October 2010

Abstract
Detection of circulating tumor cells (CTC) is advancing as an effective predictor of patient outcome and therapeutic response. Unfortunately, our knowledge of CTC biology remains limited, and the impact of drug treatments on CTC metastatic potential is currently unclear. Improved CTC imaging in vivo and analysis of free-floating tumor cells now show that cytoskeletal regulation in CTCs contrasts starkly with tumor cells attached to extracellular matrix. In this review, we examine how persistent microtubule stabilization promotes the formation of microtentacles on the surface of detached breast tumor cells and enhances metastatic potential. Cancer Res; 70(20); 7737–41. ©2010 AACR.
Expression of the Transcriptional Repressor Gfi-1 Is Regulated by C/EBPα and Is Involved in Its Proliferation and Colony Formation–Inhibitory Effects in p210BCR/ABL-Expressing Cells
Authors: Lidonnici Maria Rosa , Audia Alessandra , Soliera Angela Rachele , Prisco Marco , Ferrari-Amorotti Giovanna , Waldron Todd , Donato Nick , Zhang Ying , Martinez Robert V. , Holyoake Tessa L. , Calabretta Bruno 
Published: October 2010

Abstract
Ectopic expression of CAAT/enhancer binding protein α (C/EBPα) in p210BCR/ABL-expressing cells induces granulocytic differentiation, inhibits proliferation, and suppresses leukemogenesis. To dissect the molecular mechanisms underlying these biological effects, C/EBPα-regulated genes were identified by microarray analysis in 32D-p210BCR/ABL cells. One of the genes whose expression was activated by C/EBPα in a DNA binding–dependent manner in BCR/ABL-expressing cells is the transcriptional repressor Gfi-1. We show here that C/EBPα interacts with a functional C/EBP binding site in the Gfi-1 5′-flanking region and enhances the promoter activity of Gfi-1. Moreover, in K562 cells, RNA interference–mediated downregulation of Gfi-1 expression partially rescued the proliferation-inhibitory but not the differentiation-inducing effect of C/EBPα. Ectopic expression of wild-type Gfi-1, but not of a transcriptional repressor mutant (Gfi-1P2A), inhibited proliferation and markedly suppressed colony formation but did not induce granulocytic differentiation of BCR/ABL-expressing cells. By contrast, Gfi-1 short hairpin RNA–tranduced CD34+ chronic myeloid leukemia cells were markedly more clonogenic than the scramble-transduced counterpart. Together, these studies indicate that Gfi-1 is a direct target of C/EBPα required for its proliferation and survival-inhibitory effects in BCR/ABL-expressing cells. Cancer Res; 70(20); 7949–59. ©2010 AACR.
Method of Detection and Breast Cancer Survival Disparities in Hispanic Women
Authors: Hill Deirdre A. , Nibbe Andrea , Royce Melanie E. , Wallace Anne Marie , Kang Huining , Wiggins Charles L. , Rosenberg Robert D. 
Published: October 2010

Abstract
Background: Hispanic women in New Mexico (NM) are more likely than non-Hispanic women to die of breast cancer–related causes. We determined whether survival differences between Hispanic and non-Hispanic women might be attributable to the method of detection, an independent breast cancer prognostic factor in previous studies.
Methods: White women diagnosed with invasive breast cancer from 1995 through 2004 were identified from NM Surveillance Epidemiology End Results (SEER) files (n = 5,067) and matched to NM Mammography Project records. Method of cancer detection was categorized as “symptomatic” or “screen-detected.” The proportion of Hispanic survival disparity accounted for by included variables was assessed using Cox models.
Results: In the median follow-up of 87 months, 490 breast cancer deaths occurred. Symptomatic versus screen-detection was classifiable for 3,891 women (76.8%), and was independently related to breast cancer-specific survival [hazard ratio (HR), 1.6; 95% confidence interval (95% CI), 1.3-2.0]. Hispanic women had a 1.5-fold increased risk of breast cancer–related death, relative to non-Hispanic women (95% CI, 1.2-1.8). After adjustment for detection method, the Hispanic HR declined from 1.50 to 1.45 (10%), but after inclusion of other prognostic indicators the Hispanic HR equaled 1.23 (95% CI, 1.01-1.48).
Conclusions: Although the Hispanic HR declined 50% after adjustment, the decrease was largely due to adverse tumor prognostic characteristics.
Impact: Reduction of disparate survival in Hispanic women may rely not only on increased detection of tumors when asymptomatic but on the development of greater understanding of biological factors that predispose to poor prognosis tumors. Cancer Epidemiol Biomarkers Prev; 19(10); 2453–60. ©2010 AACR.
Association of Insurance and Race/Ethnicity with Disease Severity among Men Diagnosed with Prostate Cancer, National Cancer Database 2004-2006
Authors: Fedewa Stacey A. , Etzioni Ruth , Flanders W. Dana , Jemal Ahmedin , Ward Elizabeth M. 
Published: October 2010

Abstract
Background: Previous studies documenting variations in severity of prostate cancer at diagnosis by race/ethnicity and insurance status have been limited to small sample sizes and patients ≥65 years of age. This study examines disease severity among patients ages 18 to 99 from the National Cancer Database (NCDB).
Methods: Patients diagnosed between 2004 and 2006 with prostate cancer were selected from the NCDB (n = 312,339). We evaluated the association among three disease severity measures: prostate specific antigen (PSA) level, Gleason score 8 to 10, and clinical T-stage 3/4, by race/ethnicity and insurance while adjusting for sociodemographic and clinical factors.
Results: Uninsured and Medicaid-insured patients had elevated PSA levels, higher odds of advanced Gleason score [uninsured odds ratio (OR), 1.97; 95% confidence interval (95% CI), 1.82-2.12; Medicaid OR, 1.67; 95% CI, 1.55-1.79], and advanced clinical T stage (uninsured OR, 1.85; 95% CI, 1.69-2.03; Medicaid OR, 1.49; 95% CI, 1.35-1.63) compared with privately insured patients. Black (OR, 1.19; 95% CI, 1.15-1.23), Hispanic (OR, 1.16; 95% CI, 1.10-1.23), and Asian patients (OR, 1.22; 95% CI, 1.24-1.43) had higher odds of advanced Gleason score and similar odds of advanced stage of disease relative to whites.
Conclusion: Insurance status is strongly associated with disease severity among prostate cancer patients.
Impact: Strong associations between insurance and disease severity may be related to lack of access to preventive services such as PSA screening and barriers to medical evaluation. Although the risks and benefits of PSA screening have not been fully elucidated, it is important that all men have the opportunity to be informed about this option and preventative medical services. Cancer Epidemiol Biomarkers Prev; 19(10); 2437–44. ©2010 AACR.
Five-Year and Lifetime Risk of Breast Cancer among U.S. Subpopulations: Implications for Magnetic Resonance Imaging Screening
Authors: Graubard Barry I. , Freedman Andrew N. , Gail Mitchell H. 
Published: October 2010

Abstract
Background: Guidelines from the American Cancer Society recommend annual breast magnetic resonance imaging (MRI) screening for women with a projected lifetime risk of ≥20% based on risk models that use family history. Because MRI screening is costly and has limited specificity, estimates of the numbers of U.S. women with ≥20% breast cancer risk would be useful.
Methods: We used data from the 2000 and 2005 National Health Interview Survey and the National Cancer Institute (NCI) Breast Cancer Risk Assessment Tool (i.e., Gail model 2 with a revision for African Americans) to calculate estimates of U.S. women by age and race/ethnicity categories with a lifetime absolute breast cancer risk of ≥20%. Distributions of 5-year and lifetime absolute risk of breast cancer were compared across demographic groups.
Results: We estimated that 1.09% (95% confidence interval, 0.95-1.24%) of women age 30 to 84 years have a lifetime absolute breast cancer risk of ≥20%, which translates to 880,063 U.S. women eligible for MRI screening. The 5-year risks are highest for white non-Hispanics and lowest for Hispanics. The lifetime risks decrease with age and are generally highest for white non-Hispanics, lower for African American non-Hispanic, and lowest for Hispanics.
Conclusion: We provide national estimates of the number of U.S. women who would be eligible for MRI breast screening and distributions of 5-year and lifetime risks of breast cancer using the NCI Breast Cancer Risk Assessment Tool.
Impact: These estimates inform the potential resources and public health demand for MRI screening and chemopreventive interventions that might be required for U.S. women. Cancer Epidemiol Biomarkers Prev; 19(10); 2430–6. ©2010 AACR.
Identification of a Novel Biomarker, SEMA5A, for Non–Small Cell Lung Carcinoma in Nonsmoking Women
Authors: Lu Tzu-Pin , Tsai Mong-Hsun , Lee Jang-Ming , Hsu Chung-Ping , Chen Pei-Chun , Lin Chung-Wu , Shih Jin-Yuan , Yang Pan-Chyr , Hsiao Chuhsing Kate , Lai Liang-Chuan , Chuang Eric Y. 
Published: October 2010

Abstract
Background: Although cigarette smoking is the major risk factor for lung cancer, only 7% of female lung cancer patients in Taiwan have a history of smoking. The genetic mechanisms of carcinogenesis in nonsmokers are unclear, but semaphorins have been suggested to play a role as lung tumor suppressors. This report is a comprehensive analysis of the molecular signature of nonsmoking female lung cancer patients in Taiwan, with a particular focus on the semaphorin gene family.
Methods: Sixty pairs of tumor and adjacent normal lung tissue specimens were analyzed by using Affymetrix U133plus2.0 expression arrays. Differentially expressed genes in tumor tissues were identified by a paired t test and validated by reverse transcriptase-PCR and immunohistochemistry. Functional analysis was conducted by using Ingenuity Pathway Analysis as well as gene set enrichment analysis and sigPathway algorithms. Kaplan-Meier survival analyses were used to evaluate the association of SEMA5A expression and clinical outcome.
Results: We identified 687 differentially expressed genes in non–small cell lung carcinoma (NSCLC). Many of these genes, most notably the semaphorin family, were participants in the axon guidance signaling pathway. The downregulation of SEMA5A in tumor tissue, both at the transcriptional and translational levels, was associated with poor survival among nonsmoking women with NSCLC.
Conclusions: In summary, several semaphorin gene family members were identified as potential therapeutic targets, and SEMA5A may be useful as a prognostic biomarker for NSCLC, which may also be gender specific in Taiwanese patients.
Impact: A novel biomarker for NSCLC is identified. Cancer Epidemiol Biomarkers Prev; 19(10); 2590–7. ©2010 AACR.
Carbamazepine but Not Valproate Induces CYP2A6 Activity in Smokers with Mental Illness
Authors: Williams Jill M. , Gandhi Kunal K. , Benowitz Neal L. 
Published: October 2010

Abstract
Background: Antiepileptic drugs (AED) are being increasingly used in the management of serious mental illness, but their effects on nicotine metabolism have not been studied.
Methods: This study investigated the effects of three AEDs (carbamazepine, oxcarbazepine, and valproic acid) on nicotine and nicotine metabolite levels in 149 smokers with schizophrenia and bipolar disorder who participated in an afternoon blood draw for nicotine, cotinine, and 3′-hydroxycotinine (3HC). The ratio of 3HC to cotinine was calculated as a marker of CYP2A6 metabolic activity. Among the participants, 8 smokers were taking carbamazepine, 6 were taking oxcarbazepine, and 40 were taking valproic acid.
Results: The 3HC/cotinine ratio was significantly higher in individuals taking carbamazepine or oxcarbazepine (combined, n = 14) versus those not taking either (mean 0.993 versus 0.503; P &lt; 0.001). The cotinine/cigarette per day ratio was significantly lower in individuals taking carbamazepine or oxcarbazepine. The 3HC/cotinine ratios were also significantly higher in the subgroup of individuals taking carbamazepine (n = 8) versus those not taking it. There were no significant differences in nicotine or cotinine levels or 3HC/cotinine ratios in individuals taking valproic acid versus those not taking it. We conducted backward stepwise linear regression models to identify predictors of the log transformed 3HC/cotinine ratios. Taking carbamazepine and number of cigarettes smoked per day were significant determinants of log 3HC/cotinine.
Conclusions: Carbamazepine likely induces hepatic metabolism via CYP2A6 and is associated with increased 3HC/cotinine ratios.
Impact: Increased nicotine metabolism in individuals using AED has implications for increased smoking behavior and exposure to more tobacco toxins, which warrants further study. Cancer Epidemiol Biomarkers Prev; 19(10); 2582–9. ©2010 AACR.