bluuebunny/crossref_metadata_2025_split huggingface dataset:
Viral complementation allows HIV-1 replication without integration
Authors: Gelderblom Huub C , Vatakis Dimitrios N , Burke Sean A , Lawrie Steven D , Bristol Gregory C , Levy David N 
Published: July 2008

Abstract

Background
The integration of HIV-1 DNA into cellular chromatin is required for high levels of viral gene expression and for the production of new virions. However, the majority of HIV-1 DNA remains unintegrated and is generally considered a replicative dead-end. A limited amount of early gene expression from unintegrated DNA has been reported, but viral replication does not proceed further in cells which contain only unintegrated DNA. Multiple infection of cells is common, and cells that are productively infected with an integrated provirus frequently also contain unintegrated HIV-1 DNA. Here we examine the influence of an integrated provirus on unintegrated HIV-1 DNA (uDNA).

Results
We employed reporter viruses and quantitative real time PCR to examine gene expression and virus replication during coinfection with integrating and non-integrating HIV-1. Most cells which contained only uDNA displayed no detected expression from fluorescent reporter genes inserted into early (Rev-independent) and late (Rev-dependent) locations in the HIV-1 genome. Coinfection with an integrated provirus resulted in a several fold increase in the number of cells displaying uDNA early gene expression and efficiently drove uDNA into late gene expression. We found that coinfection generates virions which package and deliver uDNA-derived genomes into cells; in this way uDNA completes its replication cycle by viral complementation. uDNA-derived genomes undergo recombination with the integrated provirus-derived genomes during second round infection.

Conclusion
This novel mode of retroviral replication allows survival of viruses which would otherwise be lost because of a failure to integrate, amplifies the effective amount of cellular coinfection, increases the replicating HIV-1 gene pool, and enhances the opportunity for diversification through errors of polymerization and recombination.
Regulation of primate lentiviral RNA dimerization by structural entrapment
Authors: Baig Tayyba T , Strong Christy L , Lodmell J Stephen , Lanchy Jean-Marc 
Published: July 2008

Abstract

Background
Genomic RNA dimerization is an important process in the formation of an infectious lentiviral particle. One of the signals involved is the stem-loop 1 (SL1) element located in the leader region of lentiviral genomic RNAs which also plays a role in encapsidation and reverse transcription. Recent studies revealed that HIV types 1 and 2 leader RNAs adopt different conformations that influence the presentation of RNA signals such as SL1. To determine whether common mechanisms of SL1 regulation exist among divergent lentiviral leader RNAs, here we compare the dimerization properties of SIVmac239, HIV-1, and HIV-2 leader RNA fragments using homologous constructs and experimental conditions. Prior studies from several groups have employed a variety of constructs and experimental conditions.

Results
Although some idiosyncratic differences in the dimerization details were observed, we find unifying principles in the regulation strategies of the three viral RNAs through long- and short-range base pairing interactions. Presentation and efficacy of dimerization through SL1 depends strongly upon the formation or dissolution of the lower stem of SL1 called stem B. SL1 usage may also be down-regulated by long-range interactions involving sequences between SL1 and the first codons of the gag gene.

Conclusion
Despite their sequence differences, all three lentiviral RNAs tested in this study showed a local regulation of dimerization through the stabilization of SL1.
Integrated modeling and experimental approach for determining transcription factor profiles from fluorescent reporter data
Authors: Huang Zuyi , Senocak Fatih , Jayaraman Arul , Hahn Juergen 
Published: July 2008

Abstract

Background
The development of quantitative models of signal transduction, as well as parameter estimation to improve existing models, depends on the ability to obtain quantitative information about various proteins that are part of the signaling pathway. However, commonly-used measurement techniques such as Western blots and mobility shift assays provide only qualitative or semi-quantitative data which cannot be used for estimating parameters. Thus there is a clear need for techniques that enable quantitative determination of signal transduction intermediates.

Results
This paper presents an integrated modeling and experimental approach for quantitatively determining transcription factor profiles from green fluorescent protein (GFP) reporter data. The technique consists of three steps: (1) creating data sets for green fluorescent reporter systems upon stimulation, (2) analyzing the fluorescence images to determine fluorescence intensity profiles using principal component analysis (PCA) and K-means clustering, and (3) computing the transcription factor concentration from the fluorescence intensity profiles by inverting a model describing transcription, translation, and activation of green fluorescent proteins.
We have used this technique to quantitatively characterize activation of the transcription factor NF-κB by the cytokine TNF-α. In addition, we have applied the quantitative NF-κB profiles obtained from our technique to develop a model for TNF-α signal transduction where the parameters were estimated from the obtained data.

Conclusion
The technique presented here for computing transcription factor profiles from fluorescence microscopy images of reporter cells generated quantitative data on the magnitude and dynamics of NF-κB activation by TNF-α. The obtained results are in good agreement with qualitative descriptions of NF-κB activation as well as semi-quantitative experimental data from the literature. The profiles computed from the experimental data have been used to re-estimate parameters for a NF-κB model and the results of additional experiments are predicted very well by the model with the new parameter values. While the presented approach has been applied to NF-κB and TNF-α signaling, it can be used to determine the profile of any transcription factor as long as GFP reporter fluorescent profiles are available.
Brain-derived neurotrophic factor and its receptor in the human and the sand rat intervertebral disc
Authors: Gruber Helen E , Ingram Jane A , Hoelscher Gretchen , Zinchenko Natalia , Norton H James , Hanley Edward N 
Published: July 2008

Abstract
Introduction
Brain-derived neurotrophic factor (BDNF) was first identified in the intervertebral disc (IVD) when its molecular upregulation was observed in sections of nucleus pulposus cultured under conditions of increased osmolarity. BDNF is now known to be involved in a number of biologic functions, including regulation of differentiation/survival of sensory neurons, regulation of nociceptive function and central pain modulation, and modulation of inflammatory pain hypersensitivity. In addition, more recent investigations show that BDNF can induce the recruitment of endothelial cells and the formation of vascular structures. The objectives of the present study were to use immunocytochemistry to determine the distribution of BDNF and its receptor (BDNF-tropomyosine receptor kinase B) in the human IVD, and to test for gene expression of BDNF and its receptor in cultured human annulus fibrosus cells.

Methods
We studied immunohistochemical localization of BDNF and its receptor in the human annulus, quantified the percentage of outer annulus and inner annulus cells and nucleus cells positive for BDNF immunolocalization, and studied the gene expression of BDNF and its receptor using microarray analysis.

Results
The percentage (mean ± standard error of the mean) of cells positive for BDNF localization was significantly greater in the outer annulus (32.3 ± 2.7%, n = 22) compared with either the inner annulus (8.1 ± 1.5%, n = 6) or the nucleus (10.4 ± 2.8%, n = 3) (P < 0.0001). BDNF-receptor immunolocalization showed a pattern similar to that of BDNF, but was not quantitatively assessed. BDNF gene expression levels from cultured annulus cells showed a significant positive correlation with increasing levels of IVD degeneration (P = 0.011).

Conclusion
These findings provide data on the presence of BDNF and its receptor in the human IVD at the translational level, and on the expression of BDNF and its receptor by cultured human annulus cells. Our findings point to the need for further studies to define the role of BDNF in the human IVD and to investigate regulatory events within the disc that control the expression of BDNF and its receptor.
Human dendritic cell activities are modulated by the omega-3 fatty acid, docosahexaenoic acid, mainly through PPARγ:RXR heterodimers: comparison with other polyunsaturated fatty acids
Authors: Zapata-Gonzalez Fernando , Rueda Felix , Petriz Jordi , Domingo Pere , Villarroya Francesc , Diaz-Delfin Julieta , de Madariaga Maria A , Domingo Joan C 
Published: July 2008

AbstractThere is accumulating evidence that omega-3 fatty acids may modulate immune responses. When monocytes were differentiated to dendritic cells (DCs) in the presence of docosahexaenoic acid (DHA), the expression of costimulatory and antigen presentation markers was altered in a concentration-dependent way, positively or negatively, depending on the markers tested and the maturation stage of the DCs. Changes induced by eicosapentaenoic acid and linoleic acid were similar but less intense than those of DHA, whereas oleic acid had almost no effect. DHA-treated, mature DCs showed inhibition of IL-6 expression and IL-10 and IL-12 secretion, and their lymphoproliferative stimulation capacity was impaired. The phenotypic alterations of DCs induced by DHA were similar to those already reported for Rosiglitazone (Rosi), a peroxisome proliferator-activated receptor γ (PPARγ) activator, and the retinoid 9-cis-retinoic acid (9cRA), a retinoid X receptor (RXR) activator. Moreover, DHA induced the expression of PPARγ target genes pyruvate dehydrogenase kinase-4 and aP-2 in immature DCs. The combination of DHA with Rosi or 9cRA produced additive effects. Furthermore, when DCs were cultured in the presence of a specific PPARγ inhibitor, all of the changes induced by DHA were blocked. Together, these results strongly suggest that the PPARγ:RXR heterodimer is the pathway component activated by DHA to induce its immunomodulatory effect on DCs.
Dual acylation and lipid raft association of Src-family protein tyrosine kinases are required for SDF-1/CXCL12-mediated chemotaxis in the Jurkat human T cell lymphoma cell line
Authors: Zaman Sabiha N , Resek Mary E , Robbins Stephen M 
Published: July 2008

AbstractChemokines play pivotal roles in regulating a wide variety of biological processes by modulating cell migration and recruitment. Deregulation of chemokine signaling can alter cell recruitment, contributing to the pathogenic states associated with autoimmune disease, inflammatory disorders, and sepsis. During chemotaxis, lipid rafts and their resident signaling molecules have been demonstrated to partition to different parts of the cell. Herein, we investigated the role of lipid raft resident Src-family kinases (SFK) in stromal cell-derived factor 1/CXCL12-mediated chemotaxis. We have shown that Lck-deficient J. CaM 1.6 cells are defective in CXCL12-mediated chemotaxis in contrast to their parental counterpart, Jurkat cells. Ectopic expression of the SFK hematopoietic cell kinase (Hck) in J. CaM 1.6 cells reconstituted CXCL12 responsiveness. The requirement of lipid raft association of SFK was assessed using both isoforms of Hck: the dually acylated p59Hck isoform that is targeted to lipid rafts and the monoacylated p61Hck isoform that is nonraft-associated. We have shown using several gain and loss of acylation alleles that dual acylation of Hck was required for CXCL12-mediated chemotaxis in J. CaM 1.6 cells. These results highlight the importance of the unique microenvironment provided by lipid rafts and their specific contribution in providing specificity to CXCL12 signaling.
DNA Damage and Repair Capacity in Patients With Lung Cancer: Prediction of Multiple Primary Tumors
Authors: Orlow Irene , Park Bernard J. , Mujumdar Urvi , Patel Himali , Siu-Lau Puiki , Clas Brian A. , Downey Robert , Flores Raja , Bains Manjit , Rizk Nabil , Dominguez Gemma , Jani Jen , Berwick Marianne , Begg Colin B. , Kris Mark G. , Rusch Valerie W. 
Published: July 2008

PurposePatients who survive one occurrence of non–small-cell lung cancer (NSCLC) are at higher risk of a second malignancy. Capacity to repair damaged DNA may modulate individual susceptibility to develop lung cancer. Therefore, we evaluated constitutive and induced DNA damage, and repair capacity, in patients with multiple NSCLCs (cases) and compared the results to those obtained in patients with a single NSCLC (controls).Patients and MethodsOne hundred eight cases and 99 controls matched by age, sex, and time since diagnosis were studied. DNA damage was assessed on peripheral blood lymphocytes by the comet assay before and after exposing cells to a tobacco-derived carcinogen, using the tail moment and the tail intensity as measures to assess baseline damage, induced damage and repair capacity.ResultsConstitutive DNA damage, benzo(a)pyrene diol epoxide–induced damage, and repair after BPDE-induced damage were all significantly higher in cases than in controls. These results were confirmed in regression analyses adjusted for potential confounders.ConclusionDNA damage as measured by the comet assay is associated with the development of multiple primary tumors in individuals with NSCLC.
Lymphedema After Breast Cancer: Incidence, Risk Factors, and Effect on Upper Body Function
Authors: Hayes Sandra C. , Janda Monika , Cornish Bruce , Battistutta Diana , Newman Beth 
Published: July 2008

Purpose Secondary lymphedema is associated with adverse physical and psychosocial consequences among women with breast cancer (BC). This article describes the prevalence and incidence of lymphedema between 6 and 18 months after BC treatment; personal, treatment, and behavioral correlates of lymphedema status; and the presence of other upper-body symptoms (UBS) and function (UBF). Patients and Methods A population-based sample of Australian women (n = 287) with recently diagnosed, invasive BC were evaluated on five occasions using bioimpedance spectroscopy. Lymphedema was diagnosed when the ratio of impedance values, comparing treated and untreated sides, was three standard deviations more than normative data. UBF was assessed using the validated Disability of the Arm, Shoulder, and Hand questionnaire. Results From 6 to 18 months after surgery, 33% (n = 62) of the sample were classified as having lymphedema; of these, 40% had long-term lymphedema. Although older age, more extensive surgery or axillary node dissection, and experiencing one or more treatment-related complication(s) or symptom(s) at baseline were associated with increased odds, lower socioeconomic status, having a partner, greater child care responsibilities, being treated on the dominant side, participation in regular activity, and having good UBF were associated with decreased odds of lymphedema. Not surprisingly, lymphedema leads to reduced UBF; however, BC survivors report high prevalences of other UBS (34% to 62%), irrespective of their lymphedema status. Conclusion Lymphedema is a public health issue deserving greater attention. More systematic surveillance for earlier detection and the potential benefits of physical activity to prevent lymphedema and mitigate symptoms warrant further clinical integration and research.
American Society of Clinical Oncology/National Comprehensive Cancer Network Quality Measures
Authors: Desch Christopher E. , McNiff Kristen K. , Schneider Eric C. , Schrag Deborah , McClure Joan , Lepisto Eva , Donaldson Molla S. , Kahn Katherine L. , Weeks Jane C. , Ko Clifford Y. , Stewart Andrew K. , Edge Stephen B. 
Published: July 2008

Purpose
The National Cancer Policy Board recommended the creation of quality measures and a national reporting system in 1999. Representatives from the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) collaborated to create metrics suitable for national performance measurement.

Methods
Content and methodology experts nominated by ASCO and NCCN met to select and refine metrics for breast, colon, and rectal cancer based on National Initiative for Cancer Care Quality and NCCN measures and NCCN and ASCO guidelines. Measures were selected based on their impact on disease free and overall survival, the degree to which opportunities for improvement exist, and the feasibility of data collection.

Results
Three breast cancer measures and four colorectal cancer measures were chosen. Measures for breast cancer included adjuvant hormone therapy for hormone receptor–positive tumors, chemotherapy for hormone receptor–negative cancer, and radiation after lumpectomy. Colorectal measures included adjuvant radiation and chemotherapy for rectal cancer, and adjuvant chemotherapy for colon cancer. All but one were recommended as accountability measures and one for quality improvement (removal and examination of 12 or more lymph nodes in colon cancer). Specifications were developed for each measure using tumor registries as the data source.

Conclusion
ASCO/NCCN measures can be implemented by health systems, provider groups or payors for improvement or accountability using local tumor registries to furnish data on staging and treatment.
Finite element analysis of wear and its effect on squeal generation
Authors: Abu Bakar A R , Ouyang H , James S , Li L 
Published: July 2008

In the past, wear at the pad interface of disc brakes has rarely been accounted for in studies of brake squeal using the finite element method, and its effect on disc brake squeal has been investigated largely through experimental methods. In the present paper, wear taking place at this interface over time is simulated using a modified wear rate formula. The surface topographies of two new and unworn pairs of brake pads are measured. The same brake pads are tested under braking applications of three time durations. For each braking application, the static contact pressure distribution is measured using pressure-indicating film. The results are used to compare with the simulated results predicted by the three-dimensional finite element model of a real disc brake. The paper also investigates squeal generation due to the above braking applications using complex eigenvalue analysis that is available in a commercial software package. It is found that the predicted unstable frequency is very close to the observed squeal frequency and that they take place in the same braking duration.
A potential role for tissue kallikrein-related peptidases in human cervico-vaginal physiology
Authors: Shaw Julie L.V. , Diamandis Eleftherios P. 
Published: July 2008

AbstractHuman tissue kallikrein-related peptidases (KLK) are a family of 15 genes located on chromosome 19q13.4 that encode secreted serine proteases with trypsin- and/or chymotrypsin-like activity. Relatively large levels of many KLKs are present in human cervico-vaginal fluid (CVF) and in the supernatant of cultured human vaginal epithelial cells. Many KLKs are also hormonally regulated in vaginal epithelial cells, particularly by glucocorticoids and estrogens. The physiological role of KLK in the vagina is currently unknown; however, analysis of the CVF proteome has revealed clues for potential KLK functions in this environment. Here, we detail potential roles for KLKs in cervico-vaginal physiology. First, we suggest that KLKs play a role in the vagina similar to their role in skin physiology: (1) in the desquamation of vaginal epithelial cells, similar to their activity in the desquamation of skin corneocytes; and (2) in their ability to activate antimicrobial proteins in CVF as they do in sweat. Consequently, we hypothesize that dysregulated KLK expression in the vagina could lead to the development of pathological conditions such as desquamative inflammatory vaginitis. Second, we propose that KLKs may play a role in premature rupture of membranes and pre-term birth through their cleavage of fetal membrane extracellular matrix proteins.
Doxorubicin cardiomyopathy-induced inflammation and apoptosis are attenuated by gene deletion of the kinin B1 receptor
Authors: Westermann Dirk , Lettau Olga , Sobirey Meike , Riad Alexander , Bader Michael , Schultheiss Heinz-Peter , Tschöpe Carsten 
Published: July 2008

Abstract
Clinical use of the anthracycline doxorubicin (DOX) is limited by its cardiotoxic effects, which are attributed to the induction of apoptosis. To elucidate the possible role of the kinin B1 receptor (B1R) during the development of DOX cardiomyopathy, we studied B1R knockout mice (B1R-/-) by investigating cardiac inflammation and apoptosis after induction of DOX-induced cardiomyopathy. DOX control mice showed cardiac dysfunction measured by pressure-volume loops in vivo. This was associated with a reduced activation state of AKT, as well as an increased bax/bcl2 ratio in Western blots, indicating cardiac apoptosis. Furthermore, mRNA levels of the proinflammatory cytokine interleukin 6 were increased in the cardiac tissue. In DOX B1R-/- mice, cardiac dysfunction was improved compared to DOX control mice, which was associated with normalization of the bax/bcl-2 ratio and interleukin 6, as well as AKT activation state. These findings suggest that B1R is detrimental in DOX cardiomyopathy in that it mediates the inflammatory response and apoptosis. These insights might have useful implications for future studies utilizing B1R antagonists for treatment of human DOX cardiomyopathy.
An AKT activity threshold regulates androgen-dependent and androgen-independent PSA expression in prostate cancer cell lines
Authors: Paliouras Miltiadis , Diamandis Eleftherios P. 
Published: July 2008

Abstract
The androgen receptor (AR) plays an important role in early prostate cancer by activating transcription of a number of genes participating in cell proliferation and growth and cancer progression. However, as the cancer progresses, prostate cancer cells transform from an androgen-dependent to an androgen-independent state. Androgen-independent prostate cancer can manifest itself in several forms, including a percentage of cancers that show reduced levels of prostate-specific antigen (PSA) and can progress without the need for the ligand or active receptor. Therefore, our goal was to examine the role of intracellular signaling pathways in an androgen-independent prostate cancer in vitro model. Using the cell line PC3(AR)2, we stimulated cells with 5-α-dihydrotestosterone (DHT) and epidermal growth factor (EGF) and then analyzed PSA expression. We observed lower PSA expression when cells were jointly stimulated with DHT and EGF, and this was associated with an increase in AKT activity. We examined the role of AKT in AR activity and PSA expression by creating stable PC3(AR)2 cell lines transfected with a PI3K-Ras-effector loop mutant. These cell lines showed lower DHT-stimulated PSA expression that correlated to changes in the phosphorylated state of AR. Therefore, we propose an in vitro androgen-independent model in which a PI3K/AKT activity threshold and subsequent AR transactivation regulate PSA expression.