bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Adenovirus E4 ORF3 Protein Binds and Reorganizes the TRIM Family Member Transcriptional Intermediary Factor 1 Alpha
Authors: Yondola Mark A. , Hearing Patrick 
Published: February 2007

ABSTRACT
One of the most interesting functions attributed to the adenovirus early region 4 open reading frame 3 (E4 ORF3) protein is its reorganization of promyelocytic leukemia (PML) protein nuclear bodies. These normally punctate structures are reorganized by E4 ORF3 into tracks that eventually surround viral replication centers. PML rearrangement is an evolutionarily conserved function of E4 ORF3, yet its cause and functional relevance remain mysteries. The E4 ORF3 protein coimmunoprecipitates with the PML protein, yet E4 ORF3 still forms tracks in cells that lack PML. The PML protein is a member of a larger protein family termed tripartite motif (TRIM) proteins. TRIM proteins contain a tripartite domain structure in proximity to their N termini that consists of a RING finger domain, followed by one or two B box domains and a C-terminal coiled-coil domain (collectively termed the RBCC domain). The order and spacing of these domains are evolutionarily conserved and thought to mediate protein-protein interactions and other functions. We implemented a proteomic approach to isolate cellular proteins that bind to E4 ORF3. We identified a novel interaction between E4 ORF3 and another TRIM family member, transcriptional intermediary factor 1 alpha (TIF1α). TIF1α functions by recruiting coactivators and/or corepressors to modulate transcription. The interaction between E4 ORF3 and TIF1α was validated by coimmunoprecipitation and binding of recombinant proteins. Indirect immunofluorescence assays demonstrated that TIF1α is reorganized into track structures that contain PML upon E4 ORF3 expression. The RBCC domain of TIF1α is sufficient for E4 ORF3-induced rearrangement, and TIF1α reorganization is conserved across adenovirus serotypes.
Phenotypic and Genotypic Comparisons of Human T-Cell Leukemia Virus Type 1 Reverse Transcriptases from Infected T-Cell Lines and Patient Samples
Authors: Mitchell Michael S. , Bodine Ellen T. , Hill Shawn , Princler Gerald , Lloyd Patricia , Mitsuya Hiroaki , Matsuoka Masao , Derse David 
Published: February 2007

ABSTRACT

It is well established that cell-free infection with human T-cell leukemia virus type 1 (HTLV-1) is less efficient than that with other retroviruses, though the specific infectivities of only a limited number of HTLV-1 isolates have been quantified. Earlier work indicated that a postentry step in the infectious cycle accounted for the poor cell-free infectivity of HTLV-1. To determine whether variations in the
pol
gene sequence correlated with virus infectivity, we sequenced and phenotypically tested
pol
genes from a variety of HTLV-1 isolates derived from primary sources, transformed cell lines, and molecular clones. The
pol
genes and deduced amino acid sequences from 23 proviruses were sequenced and compared with 14 previously published sequences, revealing a limited number of amino acid variations among isolates. The variations appeared to be randomly dispersed among primary isolates and proviruses from cell lines and molecular clones. In addition, there was no correlation between reverse transcriptase sequence and the disease phenotype of the original source of the virus isolate. HTLV-1
pol
gene fragments encoding reverse transcriptase were amplified from a variety of isolates and were subcloned into HTLV-1 vectors for both single-cycle infection and spreading-infection assays. Vectors carrying
pol
genes that matched the consensus sequence had the highest titers, and those with the largest number of variations from the consensus had the lowest titers. The molecular clone from CS-1 cells had four amino acid differences from the consensus sequence and yielded infectious titers that were approximately eight times lower than those of vectors encoding a consensus reverse transcriptase.
Multiple Roles of Epstein-Barr Virus SM Protein in Lytic Replication
Authors: Han Zhao , Marendy Elessa , Wang Yong-Dong , Yuan Jing , Sample Jeffery T. , Swaminathan Sankar 
Published: February 2007

ABSTRACT
The effect of Epstein-Barr virus (EBV) SM protein on EBV gene expression was examined using a recombinant EBV strain with the SM gene deleted and DNA microarrays representing all known EBV coding regions. Induction of lytic EBV replication in the absence of SM led to expression of approximately 40% of EBV genes, but a block in expression of over 50% of EBV genes. Contrary to previous findings, several early genes were SM dependent, and lytic EBV DNA replication did not occur in the absence of SM. Notably, two genes essential for lytic EBV DNA replication, BSLF1 and BALF5, encoding EBV DNA primase and polymerase, respectively, were SM dependent. Lytic DNA replication was partially rescued by ectopic expression of EBV primase and polymerase, but virion production was not. Rescue of DNA replication only enhanced expression of a subset of late genes, consistent with a direct requirement for SM for late gene expression in addition to its contribution to DNA replication. Therefore, while SM is essential for most late gene expression, the proximate block to virion production by the EBV SM deletion strain is an inability to replicate linear DNA. The block to DNA replication combined with the direct effect of SM on late gene expression leads to a global deficiency of late gene expression. SM also inhibited BHRF1 expression during productive replication in comparison to that of cells induced into lytic replication in the absence of SM. Thus, SM plays a role in multiple steps of lytic cycle EBV gene expression and that it is transcript-specific in both activation and repression functions.
Gene Expression Signatures for Tumor Progression, Tumor Subtype, and Tumor Thickness in Laser-Microdissected Melanoma Tissues
Authors: Jaeger Jochen , Koczan Dirk , Thiesen Hans-Juergen , Ibrahim Saleh M. , Gross Gerd , Spang Rainer , Kunz Manfred 
Published: February 2007

Abstract
Purpose: To better understand the molecular mechanisms of malignant melanoma progression and metastasis, gene expression profiling was done of primary melanomas and melanoma metastases.
Experimental Design: Tumor cell–specific gene expression in 19 primary melanomas and 22 melanoma metastases was analyzed using oligonucleotide microarrays after laser-capture microdissection of melanoma cells. Statistical analysis was done by random permutation analysis and support vector machines. Microarray data were further validated by immunohistochemistry and immunoblotting.
Results: Overall, 308 genes were identified that showed significant differential expression between primary melanomas and melanoma metastases (false discovery rate ≤ 0.05). Significantly overrepresented gene ontology categories in the list of 308 genes were cell cycle regulation, mitosis, cell communication, and cell adhesion. Overall, 47 genes showed up-regulation in metastases. These included Cdc6, Cdk1, septin 6, mitosin, kinesin family member 2C, osteopontin, and fibronectin. Down-regulated genes included E-cadherin, fibroblast growth factor binding protein, and desmocollin 1 and desmocollin 3, stratifin/14-3-3σ, and the chemokine CCL27. Using support vector machine analysis of gene expression data, a performance of &gt;85% correct classifications for primary melanomas and metastases was reached. Further analysis showed that subtypes of primary melanomas displayed characteristic gene expression patterns, as do thin tumors (≤1.0 mm Breslow thickness) compared with intermediate and thick tumors (&gt;2.0 mm Breslow thickness).
Conclusions: Taken together, this large-scale gene expression study of malignant melanoma identified molecular signatures related to metastasis, melanoma subtypes, and tumor thickness. These findings not only provide deeper insights into the pathogenesis of melanoma progression but may also guide future research on innovative treatments.
Expression of Voltage-Gated Potassium Channels in Human and Mouse Colonic Carcinoma
Authors: Ousingsawat Jiraporn , Spitzner Melanie , Puntheeranurak Supaporn , Terracciano Luigi , Tornillo Luigi , Bubendorf Lukas , Kunzelmann Karl , Schreiber Rainer 
Published: February 2007

Abstract
Purpose: Voltage-gated Kv potassium channels, like ether a go-go (EAG) channels, have been recognized for their oncogenic potential in breast cancer and other malignant tumors.
Experimental Design: We examined the molecular and functional expression of Kv channels in human colonic cancers and colon of mice treated with the chemical carcinogens dimethylhydrazine and N-methyl-N-nitrosourea. The data were compared with results from control mice and animals with chemically induced DSS colitis.
Results: Electrogenic salt transport by amiloride-sensitive Na+ channels and cyclic AMP–activated cystic fibrosis transmembrane conductance regulator Cl− channels were attenuated during tumor development and colitis, whereas Ca2+-dependent transport remained unchanged. Kv channels, in particular Eag-1, were enhanced during carcinogenesis. Multiplex reverse transcription-PCR showed increased mRNA expression for Kv1.3, Kv1.5, Kv3.1, and members of the Eag channel family, after dimethylhydrazine and N-methyl-N-nitrosourea treatment. Eag-1 protein was detected in the malignant mouse colon and human colonic cancers. Genomic amplification of Eag-1 was found in 3.4% of all human colorectal adenocarcinoma and was an independent marker of adverse prognosis.
Conclusions: The study predicts an oncogenic role of Kv and Eag channels for the development of colonic cancer. These channels may represent an important target for a novel pharmacotherapy of colonic cancer.
WWOX Expression in Different Histologic Types and Subtypes of Non–Small Cell Lung Cancer
Authors: Donati Valentina , Fontanini Gabriella , Dell'Omodarme Matteo , Prati Maria Cristina , Nuti Simona , Lucchi Marco , Mussi Alfredo , Fabbri Muller , Basolo Fulvio , Croce Carlo Maria , Aqeilan Rami Ishaq 
Published: February 2007

Abstract
Purpose: Non–small cell lung cancer (NSCLC) has heterogeneous histopathologic classification and clinical behavior and very low survival rate. WWOX (WW domain-containing oxidoreductase) is a tumor suppressor gene, and its expression is altered in several cancers. The purpose of this study is to better define the role of WWOX in NSCLC tumorigenesis and progression by determining its pathogenetic and prognostic significance.
Experimental Design: WWOX protein expression was evaluated by immunohistochemistry in 170 patients with NSCLC (101 squamous cell carcinomas, 66 adenocarcinomas, 3 large cell carcinomas) and was correlated with histopathologic (histotype, subtype, grade, tumor-node-metastasis, stage, index of cell proliferation Ki67/MIB1) and clinical (age, gender, local recurrences, distant metastases, overall survival, and disease-free survival) characteristics.
Results: WWOX expression was absent/reduced in 84.9% of NSCLCs, whereas it was normal in 80.5% of adjacent normal lung tissues. WWOX expression was strongly associated with tumor histology (P = 1.1 × 10−5) and histologic grade (P = 0.0081): the percentage of cases with absent/strongly reduced WWOX expression was higher in squamous cell carcinomas and in poorly differentiated tumors. Regarding adenocarcinoma, bronchioloalveolar pattern showed normal WWOX expression in 62.5% of the cases, whereas in solid and acinar patterns, a prevalence of cases with absent/very low WWOX expression was observed (79.2% and 50%, respectively). Finally, weak WWOX staining intensity was related to the high index of cell proliferation (P = 0.0012).
Conclusions: Our results suggest that the loss of WWOX expression plays different roles in tumorigenesis of distinct histotypes and subtypes of NSCLC and is related to high aggressiveness (G3; high proliferating activity) of tumors.
Tropical Atmospheric Variability Forced by Oceanic Internal Variability
Authors: Jochum Markus , Deser Clara , Phillips Adam 
Published: February 2007

Abstract
Atmospheric general circulation model experiments are conducted to quantify the contribution of internal oceanic variability in the form of tropical instability waves (TIWs) to interannual wind and rainfall variability in the tropical Pacific. It is found that in the tropical Pacific, along the equator, and near 25°N and 25°S, TIWs force a significant increase in wind and rainfall variability from interseasonal to interannual time scales. Because of the stochastic nature of TIWs, this means that climate models that do not take them into account will underestimate the strength and number of extreme events and may overestimate forecast capability.
No detectable effect of RNA-binding protein Hfq absence in Staphylococcus aureus
Authors: Bohn Chantal , Rigoulay Candice , Bouloc Philippe 
Published: February 2007

Abstract

Background
The RNA-binding protein Hfq is involved in stress and virulence of several pathogens, probably due to its role as mediator in small RNA (sRNA)-mRNA interactions. In this study, we investigate the function of Hfq in the Gram-positive pathogen Staphylococcus aureus, by constructing hfq null mutant derivatives.

Results
We report that unexpectedly, in S. aureus, Hfq does not seem to play a crucial role in stress response, RNAIII or spa mRNA quantity and exoprotein expression, as tested in three virulent genetic backgrounds. Moreover, a global analysis of the RN6390 hfq mutant, which tests ~ 2000 phenotypes, supports our results concerning the non-implication of Hfq in stress response, and shows that Hfq is also not involved in resistance to several chemical agents and antibiotics and does not seem to be implicated in metabolic pathways.

Conclusion
Our data suggest that although sRNA-mRNA interactions in S. aureus are decisive for gene expression regulation, they do not require the RNA-chaperone protein Hfq. These interactions possibly require an RNA-chaperone protein other than Hfq, which remains to be found.
Continued spread of HIV among injecting drug users in southern Sichuan Province, China
Authors: Yin Lu , Qin Guangming , Qian Han-Zhu , Zhu Yu , Hu Wei , Zhang Li , Chen Kanglin , Wang Yunxia , Liu Shizhu , Zhou Feng , Xing Hui , Ruan Yuhua , Wang Ning , Shao Yiming 
Published: February 2007

Abstract

Objective
To estimate HIV prevalence among injecting drug users (IDUs) in a drug trafficking city in southwest Sichuan Province, China.

Methods
A total of 314 IDUs was invited to participate in the cross-sectional survey in 2004 through community outreach recruitment and peer referrals. Blood sample was taken for HIV antibody testing and a structured questionnaire was administered to collect information on socio-demographics, drug using and sexual behaviors.

Results
HIV prevalence among IDUs was 17.8% (56/314), about one half higher than that in previous survey in 2002 (11.3%, 43/379). Yi and other minority ethnicity (Odds ratio [OR], 3.1; 95% confidence interval [CI], 1.7–5.8; P < 0.001), and total times of sharing injecting equipments 1–9 times versus none, OR, 2.7; 95% CI 1.2–6.2; P = 0.02; and ≥10 times versus none, OR, 7.5; 95% CI, 3.2–17.7; P < 0.001) were independent risk factors for HIV infection.

Conclusion
IDUs with high prevalence rates of HIV and equipment sharing behavior in the drug trafficking city may serve a source for further spread of HIV to other areas in China. The increasing trend of HIV epidemic among IDUs underscores the urgency of scaling up interventions.
Complementary and Alternative Medicine Among Advanced Cancer Patients Enrolled on Phase I Trials: A Study of Prognosis, Quality of Life, and Preferences for Decision Making
Authors: Hlubocky Fay J. , Ratain Mark J. , Wen Ming , Daugherty Christopher K. 
Published: February 2007

PurposeWe sought to describe complementary and alternative medicine (CAM) usage among phase I trial participants and to describe these patients' treatment decision-making preferences, awareness of prognosis, survival, and quality of life.Patients and MethodsAdvanced cancer patients enrolling onto phase I trials were surveyed regarding biologically based CAM use. Decision-making preferences and awareness of prognosis were assessed using validated and/or standardized instruments. The Functional Assessment of Cancer Therapy–General instrument was used to assess quality of life. Univariate and multivariate analyses were performed to detect differences between CAM users and nonusers.ResultsOf 212 interviewed patients, 34% (n = 72) described taking biologically based CAM. Median age of those taking biologically based CAM was 55 years, compared with 62 years for nonusers (P < .005). There were no statistically significant differences found between CAM usage and preferences for degree of patient involvement in medical decision making. Those patients who acknowledged that their deaths were likely to occur within 1 year were more likely to admit to prior CAM use (70% v 34%; P = .02). CAM users had poorer overall quality of life compared with nonusers (87.0 ± 12.4 v 91.2 ± 14.7; P = .007). No differences in survival were identified.ConclusionPrior CAM use among phase I cancer trial patients studied was common and associated with age, stated acknowledgment of prognosis, and quality of life. Patients enrolling onto early-phase trials should be questioned about CAM use. Additional study is needed to determine the frequency of use of those biologically based CAM agents that threaten the accuracy of early-phase cancer trial data.
Developing Biotechnology Legal Systems in Developing Countries: The Case for Malaysia (Part II)
Authors: Jusoh Sufian 
Published: February 2007

AbstractAmong the rights are to exploit the patented invention; to assign or transmit the patent; and, to conclude licence contracts without the consent of the patent owner. Exploitation includes, in relation to a products, to make, import, offer for sale sell or use such products; stocking such product for the purpose of offering for sale, selling or using it; and in respect of a process, exploitation means using the process and doing any acts referred to above in respect of a product obtained directly as a result of the process.
Legal Limitations on Genetic Research and the Commercialisation of its Results in the Republic of Croatia
Authors: Mutabzija Jasmina , Kunda Ivana 
Published: February 2007

AbstractFreedom of research is the underlining principle of any scientific activity. It has been restated in many international and national legal instruments. Thus, Article 15 of the Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine of 1997 (hereinafter: the Convention on Human Rights and Biomedicine), lays down the general rule:
Reduced X-Linked Diversity in Derived Populations of House Mice
Authors: Baines John F , Harr Bettina 
Published: February 2007

Abstract
Contrasting patterns of X-linked vs. autosomal diversity may be indicative of the mode of selection operating in natural populations. A number of observations have shown reduced X-linked (or Z-linked) diversity relative to autosomal diversity in various organisms, suggesting a large impact of genetic hitchhiking. However, the relative contribution of other forces such as population bottlenecks, variation in reproductive success of the two sexes, and differential introgression remains unclear. Here, we survey 13 loci, 6 X-linked and 7 autosomal, in natural populations of the house mouse (Mus musculus) subspecies complex. We studied seven populations of three different subspecies, the eastern house mouse M. musculus castaneus, the central house mouse M. m. musculus, and the western house mouse M. m. domesticus, including putatively ancestral and derived populations for each. All populations display lower diversity on the X chromosomes relative to autosomes, and this effect is most pronounced in derived populations. To assess the role of demography, we fit the demographic parameters that gave the highest likelihood of the data using coalescent simulations. We find that the reduction in X-linked diversity is too large to be explained by a simple demographic model in at least two of four derived populations. These observations are also not likely to be explained by differences in reproductive success between males and females. They are consistent with a greater impact of positive selection on the X chromosome, and this is supported by the observation of an elevated KA and elevated KA/KS ratios on the rodent X chromosome. A second contribution may be that the X chromosome less readily introgresses across subspecies boundaries.
Adult Mouse Myometrial Label-Retaining Cells Divide in Response to Gonadotropin Stimulation
Authors: Szotek Paul P. , Chang Henry L. , Zhang LiHua , Preffer Frederic , Dombkowski David , Donahoe Patricia K. , Teixeira Jose 
Published: February 2007

Abstract
Conditional deletion of β-catenin in the Müllerian duct mesenchyme results in a degenerative uterus characterized by replacement of the myometrial smooth muscle with adipose tissue. We hypothesized that the mouse myometrium houses somatic smooth muscle progenitor cells that are hormonally responsive and necessary for remodeling and regeneration during estrous cycling and pregnancy. We surmise that the phenotype observed in β-catenin conditionally deleted mice is the result of dysregulation of these progenitor cells. The objective of this study was to identify the mouse myometrial smooth muscle progenitor cell and its niche, define the surface marker phenotype, and show a functional response of these cells to normal myometrial cycling. Uteri were labeled with 5-bromo-2′-deoxyuridine (BrdU) and chased for up to 14 weeks. Myometrial label-retaining cells (LRCs) were observed in the myometrium and stroma throughout the chase period. After 12 weeks, phenotypic analysis of the LRCs by immunofluorescence demonstrated that the majority of LRCs colocalized with α-smooth muscle actin, estrogen receptor-α, and β-catenin. Flow cytometry of myometrial cells identified a myometrial Hoechst 33342 effluxing “side population” that expresses MISRII-Cre-driven YFP. Functional response of LRCs was investigated by human chorionic gonadotropin stimulation of week 12 chase mice and demonstrated sequential proliferation of LRCs in the endometrial stroma, followed by the myometrium. These results suggest that conventional myometrial regeneration and repair is executed by hormonally responsive stem or progenitor cells derived from the Müllerian duct mesenchyme.
Disclosure of potential conflicts of interest is found at the end of this article.
VI.—The Author of the Pearl, Considered in the Light of his Theological Opinions
Authors: Brown Carleton F. 
Published: February 2007

Among the English poets of the fourteenth century the one who deserves the seat next to Chaucer is the anonymous author of the four poems: Sir Gawayne and the Green Knight, The Pearl, Cleanness, and Patience. The singular beauty of these poems has long stimulated scholars to the most diligent efforts to discover their author.The first attempt to identify the unknown poet was made in 1838 by Dr. Edwin Guest, who confidently assigned these poems to Huchown, the mysterious Scotch poet mentioned by the chronicler Wyntoun. At one time or another, almost every piece of fourteenth century verse which shows a northerly dialect has been ascribed to Huchown; this identification of our author was therefore natural, if not inevitable. In the following year Sir Frederic Madden, in his edition of Sir Gawayne, accepted Dr. Guest's opinion that Huchown was its author. At the same time he recognized the fact that the poem in its present form is not in the Scotch dialect, and suggested as an explanation that it had been rewritten “by a scribe of the Midland counties.” With this recognition that Sir Gawayne as we have it is in the Midland rather than the Scottish dialect, there was manifestly slender reason for continuing to suppose that Huchown was the author.