bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced Control of Pathogenic Simian Immunodeficiency Virus SIVmac239 Replication in Macaques Immunized with an Interleukin-12 Plasmid and a DNA Prime-Viral Vector Boost Vaccine Regimen
Authors: Winstone Nicola , Wilson Aaron J. , Morrow Gavin , Boggiano Cesar , Chiuchiolo Maria J. , Lopez Mary , Kemelman Marina , Ginsberg Arielle A. , Mullen Karl , Coleman John W. , Wu Chih-Da , Narpala Sandeep , Ouellette Ian , Dean Hansi J. , Lin Feng , Sardesai Niranjan Y. , Cassamasa Holly , McBride Dawn , Felber Barbara K. , Pavlakis George N. , Schultz Alan , Hudgens Michael G. , King C. Richter , Zamb Timothy J. , Parks Christopher L. , McDermott Adrian B. 
Published: July 2011

ABSTRACT

DNA priming has previously been shown to elicit augmented immune responses when administered by electroporation (EP) or codelivered with a plasmid encoding interleukin-12 (pIL-12). We hypothesized that the efficacy of a DNA prime and recombinant adenovirus 5 boost vaccination regimen (DNA/rAd5) would be improved when incorporating these vaccination strategies into the DNA priming phase, as determined by pathogenic simian immunodeficiency virus SIVmac239 challenge outcome. The whole SIVmac239 proteome was delivered in 5 separate DNA plasmids (pDNA-SIV) by EP with or without pIL-12, followed by boosting 4 months later with corresponding rAd5-SIV vaccine vectors. Remarkably, after repeated low-dose SIVmac239 mucosal challenge, we demonstrate 2.6 and 4.4 log reductions of the median SIV peak and set point viral loads in rhesus macaques (RMs) that received pDNA-SIV by EP with pIL-12 compared to the median peak and set point viral loads in mock-immunized controls (
P
< 0.01). In 5 out of 6 infected RMs, strong suppression of viremia was observed, with intermittent “blips” in virus replication. In 2 RMs, we could not detect the presence of SIV RNA in tissue and lymph nodes, even after 13 viral challenges. RMs immunized without pIL-12 demonstrated a typical maximum of 1.5 log reduction in virus load. There was no significant difference in the overall magnitude of SIV-specific antibodies or CD8 T-cell responses between groups; however, pDNA delivery by EP with pIL-12 induced a greater magnitude of SIV-specific CD4 T cells that produced multiple cytokines. This vaccine strategy is relevant for existing vaccine candidates entering clinical evaluation, and this model may provide insights into control of retrovirus replication.
Direct and Specific Binding of the UL16 Tegument Protein of Herpes Simplex Virus to the Cytoplasmic Tail of Glycoprotein E
Authors: Yeh Pei-Chun , Han Jun , Chadha Pooja , Meckes David G. , Ward Michael D. , Semmes O. John , Wills John W. 
Published: July 2011

ABSTRACT

The UL16 tegument protein of herpes simplex virus (HSV) is conserved throughout all of the herpesvirus families. Previous studies have shown that the binding of HSV to heparan sulfate molecules on the host cell triggers the release of UL16 from the capsid, but the mechanism by which the signal is sent from the virion surface into the tegument is unknown. Here, we report that a glutathione
S
-transferase chimera bearing the cytoplasmic tail of viral glycoprotein E (gE) is capable of binding to UL16 in lysates of eukaryotic cells or purified from bacteria. Moreover, mass spectrometry studies of native-UL16 complexes purified from infected cells also revealed the presence of gE. Proof that UL16-gE can interact within cells required the fortuitous discovery of a mutant possessing only the first 155 residues of UL16. Confocal microscopy of cotransfected cells revealed that this mutant colocalized with gE in the cytoplasm, whereas it was found throughout the cytoplasm and nucleus when expressed alone. In contrast, the full-length UL16 molecule was very poorly capable of finding gE. Moreover, membrane flotation assays showed that UL16(1-155) was able to float to the top of sucrose step gradients when coexpressed with gE, whereas full-length UL16 was not. Thus, the discovery of the UL16(1-155) mutant confirmed the specific
in vitro
interaction with gE and provides evidence that a binding domain at the N terminus of UL16 may be controlled by a regulatory domain within the C terminus. These findings suggest the possibility that the UL16-gE interaction may play roles in the tegument signaling mechanism, virus budding, and the gE-mediated mechanism of cell-to-cell spread.
Genome-wide Profiling of Chromatin Signatures Reveals Epigenetic Regulation of MicroRNA Genes in Colorectal Cancer
Authors: Suzuki Hiromu , Takatsuka Shintaro , Akashi Hirofumi , Yamamoto Eiichiro , Nojima Masanori , Maruyama Reo , Kai Masahiro , Yamano Hiro-o , Sasaki Yasushi , Tokino Takashi , Shinomura Yasuhisa , Imai Kohzoh , Toyota Minoru 
Published: July 2011

Abstract
Altered expression of microRNAs (miRNA) occurs commonly in human cancer, but the mechanisms are generally poorly understood. In this study, we examined the contribution of epigenetic mechanisms to miRNA dysregulation in colorectal cancer by carrying out high-resolution ChIP-seq. Specifically, we conducted genome-wide profiling of trimethylated histone H3 lysine 4 (H3K4me3), trimethylated histone H3 lysine 27 (H3K27me3), and dimethylated histone H3 lysine 79 (H3K79me2) in colorectal cancer cell lines. Combining miRNA expression profiles with chromatin signatures enabled us to predict the active promoters of 233 miRNAs encoded in 174 putative primary transcription units. By then comparing miRNA expression and histone modification before and after DNA demethylation, we identified 47 miRNAs encoded in 37 primary transcription units as potential targets of epigenetic silencing. The promoters of 22 transcription units were associated with CpG islands (CGI), all of which were hypermethylated in colorectal cancer cells. DNA demethylation led to increased H3K4me3 marking at silenced miRNA genes, whereas no restoration of H3K79me2 was detected in CGI-methylated miRNA genes. DNA demethylation also led to upregulation of H3K4me3 and H3K27me3 in a number of CGI-methylated miRNA genes. Among the miRNAs we found to be dysregulated, many of which are implicated in human cancer, miR-1-1 was methylated frequently in early and advanced colorectal cancer in which it may act as a tumor suppressor. Our findings offer insight into the association between chromatin signatures and miRNA dysregulation in cancer, and they also suggest that miRNA reexpression may contribute to the effects of epigenetic therapy. Cancer Res; 71(17); 5646–58. ©2011 AACR.
Frailty Modeling of the Bimodal Age–Incidence of Hodgkin Lymphoma in the Nordic Countries
Authors: Grotmol Tom , Bray Freddie , Holte Harald , Haugen Marion , Kunz Lauren , Tretli Steinar , Aalen Odd O. , Moger Tron A. 
Published: July 2011

Abstract
Background: The bimodality of the age–incidence curve of Hodgkin lymphoma (HL) has been ascribed to the existence of subgroups with distinct etiologies. Frailty models can be usefully applied to age–incidence curves of cancer to aid the understanding of biological phenomena in these instances. The models imply that for a given disease, a minority of individuals are at high risk, compared with the low-risk majority.
Methods: Frailty modeling is applied to interpret HL incidence on the basis of population-based cancer registry data from the five Nordic countries for the period 1993 to 2007. There were a total of 8,045 incident cases and 362,843,875 person-years at risk in the study period.
Results: A bimodal frailty analysis provides a reasonable fit to the age–incidence curves, employing 2 prototype models, which differ by having the sex covariate included in the frailty component (model 1) or in the baseline Weibull hazard (model 2). Model 2 seemed to fit better with our current understanding of HL than model 1 for the male-to-female ratio, number of rate-limiting steps in the carcinogenic process, and proportion of susceptibles; whereas model 1 performed better related to the heterogeneity in HL among elderly males.
Conclusion: The present analysis shows that HL age–incidence data are consistent with a bimodal frailty model, indicating that heterogeneity in cancer susceptibility may give rise to bimodality at the population level, although the individual risk remains simple and monotonically increasing by age.
Impact: Frailty modeling adds to the existing body of knowledge on the heterogeneity in risk of acquiring HL. Cancer Epidemiol Biomarkers Prev; 20(7); 1350–7. ©2011 AACR.
B-Cell Stimulatory Cytokines and Markers of Immune Activation Are Elevated Several Years Prior to the Diagnosis of Systemic AIDS–Associated Non-Hodgkin B-Cell Lymphoma
Authors: Breen Elizabeth Crabb , Hussain Shehnaz K. , Magpantay Larry , Jacobson Lisa P. , Detels Roger , Rabkin Charles S. , Kaslow Richard A. , Variakojis Daina , Bream Jay H. , Rinaldo Charles R. , Ambinder Richard F. , Martinez-Maza Otoniel 
Published: July 2011

AbstractBackground: The risk of developing non-Hodgkin lymphoma (NHL) is greatly increased in HIV infection. The aim of this study was to determine whether elevated serum levels of molecules associated with B-cell activation precede the diagnosis of AIDS-associated NHL (AIDS-NHL).Methods: Serum levels of B-cell activation–associated molecules, interleukin (IL)6, IL10, soluble CD23 (sCD23), sCD27, sCD30, C-reactive protein (CRP), and immunoglobulin E were determined in 179 NHL cases and HIV+ controls in the Multicenter AIDS Cohort Study, collected at up to 3 time points per subject, 0 to 5 years prior to AIDS-NHL diagnosis.Results: Serum IL6, IL10, CRP, sCD23, sCD27, and sCD30 levels were all significantly elevated in the AIDS-NHL group, when compared with HIV+ controls or with AIDS controls, after adjusting for CD4 T-cell number. Elevated serum levels of B-cell activation–associated molecules were seen to be associated with the development of systemic [non-CNS (central nervous system)] NHL, but not with the development of primary CNS lymphoma.Conclusions: Levels of certain B-cell stimulatory cytokines and molecules associated with immune activation are elevated for several years preceding the diagnosis of systemic AIDS-NHL. This observation is consistent with the hypothesis that chronic B-cell activation contributes to the development of these hematologic malignancies.Impact: Marked differences in serum levels of several molecules are seen for several years prediagnosis in those who eventually develop AIDS-NHL. Some of these molecules may serve as candidate biomarkers and provide valuable information to better define the etiology of NHL. Cancer Epidemiol Biomarkers Prev; 20(7); 1303–14. ©2011 AACR.
Variation in TP63 is Associated with Lung Adenocarcinoma in the UK Population
Authors: Wang Yufei , Broderick Peter , Matakidou Athena , Vijayakrishnan Jayaram , Eisen Timothy , Houlston Richard S. 
Published: July 2011

Abstract
Background: Variation at TP63 has recently been shown to be associated with lung adenocarcinoma in the Asian population.
Methods: To investigate how this finding translates to the European population we compared the genotypes of SNPs annotating the TP63 locus at 3q28 in 4,462 lung cancer patients, including 911 with adenocarcinoma, and 8,235 controls from the United Kingdom.
Results: A statistically significant association between adenocarcinoma risk and SNP genotype was shown: rs10937405, OR = 1.21, P = 1.82 × 10−4; rs17429138, OR = 1.23, P = 7.49 × 10−5; and rs4396880, OR = 1.21, P = 2.03 × 10−4. Haplotype analysis was consistent with a single TP63 risk locus defined by SNPs rs10937405, rs17429138, and rs4396880. While no association between SNPs and small cell lung cancer was shown, the rs10937405 and rs439680 associations were significant for squamous cancer (respective P-values, 0.0022 and 0.02).
Conclusions: These findings show TP63 variation is a risk factor for the development of lung adenocarcinoma in the UK population. Furthermore, they provide additional insight into the subtype-specificity of the 3q28 lung cancer association.
Impact: Our data confirm the association of 3q28 with lung adenocarcinoma and that this association is not confined to the Asian population. Elucidating the functional basis of this association will be contingent on future fine mapping of the TP63 loci. Cancer Epidemiol Biomarkers Prev; 20(7); 1453–62. ©2011 AACR.
Detection of Bladder Cancer Using Novel DNA Methylation Biomarkers in Urine Sediments
Authors: Chung Woonbok , Bondaruk Jolanta , Jelinek Jaroslav , Lotan Yair , Liang Shoudan , Czerniak Bogdan , Issa Jean-Pierre J. 
Published: July 2011

Abstract
Background: Bladder cancer (BCa) remains a lethal malignancy that can be cured if detected early. DNA hypermethylation is a common epigenetic abnormality in cancer that may serve as a marker of disease activity.
Methods: We selected 10 novel candidate genes from the most frequently hypermethylated genes detected by DNA microarray and bisulfite pyrosequencing of bladder cancers and applied them to detect bladder cancer in urine sediments. We analyzed DNA methylation in the candidate genes by quantitative methylation-specific real-time PCR (qMSP) to detect bladder cancer in urine sediments from 128 bladder cancer patients and 110 age-matched control subjects.
Results: Based on a multigene predictive model, we discovered 6 methylation markers (MYO3A, CA10, SOX11, NKX6-2, PENK, and DBC1) as most promising for detecting bladder cancer. A panel of 4 genes (MYO3A, CA10, NKX6-2, and DBC1 or SOX11) had 81% sensitivity and 97% specificity, whereas a panel of 5 genes (MYO3A, CA10, NKX6-2, DBC1, and SOX11 or PENK) had 85% sensitivity and 95% specificity for detection of bladder cancer (area under curve = 0.939). By analyzing the data by cancer invasiveness, detection rate was 47 of 58 (81%) in non-muscle invasive tumors (pTa, Tis, and pT1) and 62 of 70 (90%) in muscle invasive tumors (T2, T3, and T4).
Conclusions: This biomarker panel analyzed by qMSP may help the early detection of bladder tumors in urine sediments with high accuracy.
Impact: The panel of biomarker deserves validation in a large well-controlled prospectively collected sample set. Cancer Epidemiol Biomarkers Prev; 20(7); 1483–91. ©2011 AACR.
Inactivation of Tautomerase Activity of Macrophage Migration Inhibitory Factor by Sulforaphane: a Potential Biomarker for Anti-inflammatory Intervention
Authors: Healy Zachary R. , Liu Hua , Holtzclaw W. David , Talalay Paul 
Published: July 2011

Abstract
Background: Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine with keto–enol tautomerase activity, rises rapidly in response to inflammation and is elevated in many chronic diseases. Isothiocyanates, such as sulforaphane from broccoli, are very potent inactivators of MIF tautomerase activity. A simple rapid method for determining this activity in tissues and body fluids may therefore be valuable for assessing severity of inflammation and efficacy of intervention.
Methods: Existing spectrophotometric assays of MIF, based on conversion of methyl L-dopachrome to methyl 5,6-dihydroxyindole-2-carboxylate and associated loss of absorption at 475 nm, lack sensitivity. Assay sensitivity and efficiency were markedly improved by reducing the nonenzymatic rate, by lowering pH to 6.2, replacing phosphate (which catalyzes the reaction) with Bis-Tris buffer, and converting to a microtiter plate format.
Results: A structure-potency study of MIF tautomerase inactivation by isothiocyanates showed that sulforaphane, benzyl, n-hexyl, and phenethyl isothiocyanates were especially potent. MIF tautomerase could be readily quantified in human urine concentrated by ultrafiltration. This activity comprised: (i) a heat-labile, sulforaphane-inactivated macromolecular fraction (presumably MIF) that was concentrated during ultrafiltration; (ii) a flow-through fraction, with constant activity during filtration, that was heat stable and insensitive to sulforaphane. Administration of the sulforaphane precursor glucoraphanin to human volunteers almost completely abolished urinary tautomerase activity, which recovered over many hours.
Conclusion: A simple, rapid, quantitative MIF tautomerase assay has been developed as a potential biomarker for assessing inflammatory severity and effectiveness of intervention.
Impact: An improved assay for measuring MIF tautomerase activity and its applications are described. Cancer Epidemiol Biomarkers Prev; 20(7); 1516–23. ©2011 AACR.
Smoking and Passive Smoking in Cervical Cancer Risk: Pooled Analysis of Couples from the IARC Multicentric Case–Control Studies
Authors: Louie Karly S. , Castellsague Xavier , de Sanjose Silvia , Herrero Rolando , Meijer Chris J. , Shah Keerti , Munoz Nubia , Bosch F. Xavier 
Published: July 2011

Abstract
Background: The independent role of tobacco smoking in invasive cervical cancer (ICC) has been established. We evaluated the potential impact of passive smoking (PS).
Methods: A pooled analysis of 1,919 couples enrolled in one of seven case–control studies involving cervical carcinoma in situ (CIS) or ICC was investigated. Information on smoking and sexual behavior was collected from interviews. Specimens were taken from the cervix and penis for human papillomavirus (HPV) DNA testing. Three PS risk models were constructed with all couples, couples with monogamous women, and couples with lifetime nonsmoking monogamous women. For the third model, the analysis considered potential misclassification of smoking status and was restricted to the risk period for which the woman was exposed to both HPV, a necessary cause of ICC, and PS. Multivariable unconditional logistic regression was used to estimate associations between CIS or ICC and PS.
Results: An increased risk was found among couples with both ever smoking men and women (OR = 2.26; 95% CI: 1.40–3.64). No statistically increased risk of CIS was found with PS in the models analyzed. Similar significant increased risks of ICC with PS was found among all couples (OR = 1.57; 95% CI: 1.15–2.15) and couples with monogamous women (OR = 1.55; 95% CI: 1.07–2.23) but not among lifetime nonsmoking monogamous women married to ever smoking men.
Conclusion: PS could not be detected as an independent risk factor of ICC in the absence of active smoking.
Impact: The combined effects of exposure to active and PS suggest its potential adverse role in cervical carcinogenesis. Cancer Epidemiol Biomarkers Prev; 20(7); 1379–90. ©2011 AACR.
1α,25(OH)2-Vitamin D and a Nongenomic Vitamin D Analogue Inhibit Ultraviolet Radiation–Induced Skin Carcinogenesis
Authors: Dixon Katie M. , Norman Anthony W. , Sequeira Vanessa B. , Mohan Ritu , Rybchyn Mark S. , Reeve Vivienne E. , Halliday Gary M. , Mason Rebecca S. 
Published: July 2011

Abstract
Exposure to ultraviolet radiation (UVR) can lead to a range of deleterious responses in the skin. An important form of damage is the DNA photolesion cyclobutane pyrimidine dimer (CPD). CPDs can be highly mutagenic if not repaired prior to cell division and can lead to UV-induced immunosuppression, making them potentially carcinogenic. UVR exposure also produces vitamin D, a prehormone. Different shapes of the steroid hormone 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] can produce biological responses through binding either to its cognate nuclear receptor (VDR) to regulate gene transcription or to the VDR associated with plasma membrane caveolae to produce, via signal transduction, nongenomic physiologic responses. Here, we show that both 1,25(OH)2D3 and 1α,25(OH)2-lumisterol (JN), a conformationally restricted analogue that can generate only nongenomic responses, are effective inhibitors of UV damage in an immunocompetent mouse (Skh:hr1) model susceptible to UV-induced tumors. Both 1,25(OH)2D3 and JN significantly reduced UVR-induced CPD, apoptotic sunburn cells, and immunosuppression. Furthermore, these compounds inhibited skin tumor development, both papillomas and squamous cell carcinomas, in these mice. The observed reduction of these UV-induced effects by 1,25(OH)2D3 and JN suggests a role for these compounds in prevention against skin carcinogenesis. To the best of our knowledge, this is the first comprehensive report of an in vivo long-term biological response generated by chronic dosing with a nongenomic-selective vitamin D steroid. Cancer Prev Res; 4(9); 1485–94. ©2011 AACR.
Enhanced Passive and Active Processing of Syllables in Musician Children
Authors: Chobert Julie , Marie Céline , François Clément , Schön Daniele , Besson Mireille 
Published: July 2011

Abstract
The aim of this study was to examine the influence of musical expertise in 9-year-old children on passive (as reflected by MMN) and active (as reflected by discrimination accuracy) processing of speech sounds. Musician and nonmusician children were presented with a sequence of syllables that included standards and deviants in vowel frequency, vowel duration, and VOT. Both the passive and the active processing of duration and VOT deviants were enhanced in musician compared with nonmusician children. Moreover, although no effect was found on the passive processing of frequency, active frequency discrimination was enhanced in musician children. These findings are discussed in terms of common processing of acoustic features in music and speech and of positive transfer of training from music to the more abstract phonological representations of speech units (syllables).
Similarity between Brain Activity at Encoding and Retrieval Predicts Successful Realization of Delayed Intentions
Authors: Gilbert Sam J. , Armbruster Diana J. N. , Panagiotidi Maria 
Published: July 2011

Abstract
Remembering delayed intentions can be highly demanding. Accuracy in laboratory paradigms assessing prospective memory (PM) is typically well below ceiling, and failure to remember intended behaviors after a delay is a common occurrence in everyday life. However, relatively little is known of the potential differences in brain activity that distinguish successful versus unsuccessful PM. In this fMRI study, participants repeatedly encoded, stored, and then had the opportunity to retrieve intended behaviors while engaged in a distracting ongoing task. This yielded a success rate of approximately two thirds. Overall levels of brain activity distinguished successful versus unsuccessful trials at all three stages (encoding, storage, and retrieval), suggesting multiple neural determinants of PM success. In addition, the voxelwise similarity between patterns of brain activity at encoding and retrieval was greater for successful than unsuccessful trials. This was true even in posterior cingulate, which showed opposite patterns of signal change between encoding and retrieval. Thus, successful realization of delayed intentions may be associated with reinstatement of encoding context at the time of retrieval.