bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted Deletion of Regions Rich in Immune-Evasive Genes from the Cytomegalovirus Genome as a Novel Vaccine Strategy
Authors: Čičin-Šain Luka , Bubić Ivan , Schnee Margit , Ruzsics Zsolt , Mohr Christian , Jonjić Stipan , Koszinowski Ulrich H. 
Published: October 2007

ABSTRACT
Human cytomegalovirus (CMV), a ubiquitous human pathogen, is a leading cause of congenital infections and represents a serious health risk for the immunosuppressed patient. A vaccine against CMV is currently not available. CMV is characterized by its large genome and by multiple genes modulating the immunity of the host, which cluster predominantly at genome termini. Here, we tested whether the deletion of gene blocks rich in immunomodulatory genes could be used as a novel concept in the generation of immunogenic but avirulent, herpesvirus vaccines. To generate an experimental CMV vaccine, we selectively deleted 32 genes from the mouse cytomegalovirus (MCMV) genome. The resulting mutant grew to titers similar to that of wild-type MCMV in vitro. In vivo, the mutant was 10,000-fold attenuated and well tolerated, even by highly susceptible mice deficient for B, T, and NK cells or for the interferon type I receptor. Equally relevant for safety concerns, immune suppression did not lead to the mutant's reactivation from latency. Immunization with the replication-competent mutant, but not with inactivated virus, resulted in protective immunity, which increased over time. Vaccination induced MCMV-specific antibodies and a strong T-cell response. We propose that a targeted and rational approach can improve future herpesvirus vaccines and vaccine vectors.
Expression of epidermal growth factor (EGF)/transforming growth factor-α by human lung cancer cells determines their response to EGF receptor tyrosine kinase inhibition in the lungs of mice
Authors: Wu Wenjuan , O'Reilly Michael S. , Langley Robert R. , Tsan Rachel Z. , Baker Cheryl H. , Bekele Neby , Tang Xi Ming , Onn Amir , Fidler Isaiah J. , Herbst Roy S. 
Published: October 2007

AbstractEpidermal growth factor receptor (EGFR) has been extensively targeted in the treatment of non–small cell lung cancer, producing responses in a small number of patients. To study the role of ligand expression in mediating response to EGFR antagonism, we injected NCI-H441 [EGFR and EGF/transforming growth factor-α (TGF-α) positive] or PC14-PE6 (EGFR positive and EGF/TGF-α negative) human lung adenocarcinoma cells into the lungs of nude mice. We randomized the mice to receive treatment with the EGFR tyrosine kinase inhibitors gefitinib or AEE788 or vehicle. Treatment of mice bearing NCI-H441 but not PC14-PE6 lung tumors resulted in a significant reduction in primary tumor growth, pleural effusion, and lymph node metastasis. Immunohistochemical analyses revealed that NCI-H441 and PC14-PE6 cells expressed EGFR but that the expression of EGF/TGF-α was high in NCI-H441 cells and very low in PC14-PE6 cells. Consequently, EGFR was activated in both tumor and tumor-associated endothelial cells in the NCI-H441 tumors but not in the PC14-PE6 tumors. Antagonism of EGFR signaling by treatment of mice with AEE788 decreased proliferation and increased apoptosis of both tumor cells and tumor-associated endothelial cells in NCI-H441 tumors but not in PC14-PE6 tumors. However, after transfection of PC14-PE6 cells with TGF-α, lung tumors derived from the transfected cells expressed and activated EGFR in both tumor and tumor-associated endothelial cells and tumors responded to treatment with AEE788. Collectively, these results strongly suggest that the response of human lung cancers growing orthotopically in mice to the inhibition of EGFR signaling is determined by ligand (EGF/TGF-α) expression by tumor cells. Our findings provide an additional explanation for the susceptibility of lung cancers to treatment with EGFR tyrosine kinase inhibitors. [Mol Cancer Ther 2007;6(10):2652–63]
Synergistic cytotoxicity between tamoxifen and the plant toxin persin in human breast cancer cells is dependent on Bim expression and mediated by modulation of ceramide metabolism
Authors: Roberts Caroline G. , Gurisik Ebru , Biden Trevor J. , Sutherland Robert L. , Butt Alison J. 
Published: October 2007

Abstract
Phytochemicals have provided an abundant source of novel therapeutics for the treatment of human cancers. We have previously described a novel plant toxin, persin, derived from avocado leaves, which has unique in vivo actions in the mammary epithelium and Bim-dependent, cytotoxic effects in human breast cancer cells in vitro. Compounds structurally similar to persin, such as the polyunsaturated fatty acid, conjugated linoleic acid, can attenuate steroid hormone receptor signaling and modulate the response of breast cancer cells to antiestrogens. Here, we provide evidence that persin may have similar effects by showing its potent proapoptotic synergy with the antiestrogen 4-hydroxytamoxifen. However, although persin transcriptionally down-regulates estrogen receptor (ER) expression, unlike conjugated linoleic acid, it also shows efficacy in ER-negative breast cancer cells, both alone and in combination with 4-hydroxytamoxifen, whereas normal breast epithelial cells are unaffected, suggesting it may act via a distinct, ER-independent mechanism. These proapoptotic synergistic interactions are associated with increased de novo ceramide synthesis and are dependent on expression of the proapoptotic protein Bim. These data show that persin should be further investigated as a potential novel cancer therapeutic agent because it significantly enhances the sensitivity of breast cancer cells to the cytotoxic effects of tamoxifen, regardless of their ER status, while displaying apparent specificity for the malignant phenotype. [Mol Cancer Ther 2007;6(10):2777–85]
Can microsatellite markers resolve phylogenetic relationships between closely related crested newt species (Triturus cristatus superspecies)?
Authors: Mikulícek Peter , Crnobrnja-Isailovic Jelka , Piálek Jaroslav 
Published: October 2007

AbstractTheoretical and empirical studies revealed that fast evolving microsatellite markers might be successfully employed in phylogenetic reconstruction. In this study we used seven highly polymorphic microsatellite loci and six different genetic distances to infer the performance of microsatellites in estimation of phylogenetic relationships between closely related crested newt species (Triturus cristatus superspecies). Many intraspecific distances exceeded interspecific values likely due to loss of genetic distance linearity in time, revealing that none of them was able to estimate divergence between the species. The Neighbor-joining trees constructed on the basis of genetic distances showed trichotomies (three-way polychotomies) and low bootstrap support at the species level. This study thus revealed limits of microsatellites to estimate phylogenetic relationships between the crested newt taxa.
Head morphological variation in Podarcis muralis and Podarcis sicula: a landmark-based approach
Authors: Bruner Emiliano , Costantini David 
Published: October 2007

Abstract
The geometry of the cephalic scales in lizards is easily represented by using
landmark based approaches. The cephalic scales may prove useful structures
in the investigation of the evolution and morphogenesis of lizards because
of their biomechanical relationships with the underlying bones and muscular
anatomy. In the present paper the head morphology in Podarcis muralis and
Podarcis sicula is compared by using geometric morphometrics and Euclidean
distance matrix analysis. The head shape in these two species is largely
influenced by a shared allometric pattern, with P. sicula displaying a
reduced range of variation. This pattern is probably influenced by the
cranial morphogenesis at the fronto-parietal suture, and by the
parieto-occipital musculature involved in diet and social behaviours. Minor
species-specific differences are evidenced, and should be further
investigated.
Interleukin-3 prevents neuronal death induced by amyloid peptide
Authors: Zambrano Angara , Otth Carola , Mujica Lorena , Concha Ilona I , Maccioni Ricardo B 
Published: October 2007

AbstractBackgroundInterleukin-3 (IL-3) is an important glycoprotein involved in regulating biological responses such as cell proliferation, survival and differentiation. Its effects are mediated via interaction with cell surface receptors. Several studies have demonstrated the expression of IL-3 in neurons and astrocytes of the hippocampus and cortices in normal mouse brain, suggesting a physiological role of IL-3 in the central nervous system. Although there is evidence indicating that IL-3 is expressed in some neuronal populations, its physiological role in these cells is poorly known.ResultsIn this study, we demonstrated the expression of IL-3 receptor in cortical neurons, and analyzed its influence on amyloid β (Aβ)-treated cells. In these cells, IL-3 can activate at least three classical signalling pathways, Jak/STAT, Ras/MAP kinase and the PI 3-kinase. Viability assays indicated that IL-3 might play a neuroprotective role in cells treated with Aβ fibrils. It is of interest to note that our results suggest that cell survival induced by IL-3 required PI 3-kinase and Jak/STAT pathway activation, but not MAP kinase. In addition, IL-3 induced an increase of the anti-apoptotic protein Bcl-2.ConclusionAltogether these data strongly suggest that IL-3 neuroprotects neuronal cells against neurodegenerative agents like Aβ.
Involvement of LTB4 in zymosan-induced joint nociception in mice: participation of neutrophils and PGE2
Authors: Guerrero Ana T G , Verri Waldiceu A , Cunha Thiago M , Silva Tarcilia A , Schivo Ieda R S , Dal-Secco Daniela , Canetti Claudio , Rocha Francisco A C , Parada Carlos A , Cunha Fernando Q , Ferreira Sérgio H 
Published: October 2007

AbstractLeukotriene B4 (LTB4) mediates different inflammatory events such as neutrophil migration and pain. The present study addressed the mechanisms of LTB4-mediated joint inflammation-induced hypernociception. It was observed that zymosan-induced articular hypernociception and neutrophil migration were reduced dose-dependently by the pretreatment with MK886 (1–9 mg/kg; LT synthesis inhibitor) as well as in 5-lypoxygenase-deficient mice (5LO−/−) or by the selective antagonist of the LTB4 receptor (CP105696; 3 mg/kg). Histological analysis showed reduced zymosan-induced articular inflammatory damage in 5LO−/− mice. The hypernociceptive role of LTB4 was confirmed further by the demonstration that joint injection of LTB4 induces a dose (8.3, 25, and 75 ng)-dependent articular hypernociception. Furthermore, zymosan induced an increase in joint LTB4 production. Investigating the mechanism underlying LTB4 mediation of zymosan-induced hypernociception, LTB4-induced hypernociception was reduced by indomethacin (5 mg/kg), MK886 (3 mg/kg), celecoxib (10 mg/kg), antineutrophil antibody (100 μg, two doses), and fucoidan (20 mg/kg) treatments as well as in 5LO−/− mice. The production of LTB4 induced by zymosan in the joint was reduced by the pretreatment with fucoidan or antineutrophil antibody as well as the production of PGE2 induced by LTB4. Therefore, besides reinforcing the role of endogenous LTB4 as an important mediator of inflamed joint hypernociception, these results also suggested that the mechanism of LTB4-induced articular hypernociception depends on prostanoid and neutrophil recruitment. Furthermore, the results also demonstrated clearly that LTB4-induced hypernociception depends on the additional release of endogenous LTs. Concluding, targeting LTB4 synthesis/action might constitute useful therapeutic approaches to inhibit articular inflammatory hypernociception.
Pivotal Advance: Inhibition of HMGB1 nuclear translocation as a mechanism for the anti-rheumatic effects of gold sodium thiomalate
Authors: Zetterström Cecilia K , Jiang Weiwen , Wähämaa Heidi , Östberg Therese , Aveberger Ann-Charlotte , Schierbeck Hanna , Lotze Michael T , Andersson Ulf , Pisetsky David S , Erlandsson Harris Helena 
Published: October 2007

AbstractGold compounds such as gold sodium thiomalate (GST) can reduce the symptoms of rheumatoid arthritis (RA), although their mechanism of action is not well defined. As the proinflammatory mediator high mobility group box chromosomal protein 1 (HMGB1) may play a role in the pathogenesis of RA, we have performed in vitro studies to investigate whether GST inhibits HMGB1 release as the basis of its mode of action. Murine RAW 264.7 or human THP-1 macrophage cells were stimulated in culture with agents causing extracellular HMGB1 release, including LPS, IFN-γ, polyinosinic:polycytidylic acid, IFN-β, or NO in the presence of GST, ranging from 0 μM to 250 μM. Secretion and intracellular location of HMGB1 were assessed by Western blotting, HMGB1-specific ELISPOT assay, and immunofluorescent staining. In parallel, TNF and IFN-β levels were analyzed by ELISPOT and/or ELISA. Supernatant NO production was analyzed by the Griess method. At pharmacologically relevant doses, GST inhibited the extracellular release of HMGB1 from activated macrophages and caused the nuclear retention of this protein; in contrast, no effects were observed on the secretion or production of TNF. Release of the key endogenous mediators of HMGB1 translocation, IFN-β and NO, was inhibited by GST. This inhibition required gold, as sodium thiomalate did not affect the responses measured. Furthermore, gold chloride also inhibited release of HMGB1. Together, these results suggest a new mechanism for the anti-rheumatic effects of gold salts in RA and the potential of drugs, which interfere with intracellular HMGB1 transport mechanisms, as novel agents to treat RA.
Roles of integrin activation in eosinophil function and the eosinophilic inflammation of asthma
Authors: Barthel Steven R , Johansson Mats W , McNamee Dawn M , Mosher Deane F 
Published: September 2007

AbstractEosinophilic inflammation is a characteristic feature of asthma. Integrins are highly versatile cellular receptors that regulate extravasation of eosinophils from the postcapillary segment of the bronchial circulation to the airway wall and airspace. Such movement into the asthmatic lung is described as a sequential, multistep paradigm, whereby integrins on circulating eosinophils become activated, eosinophils tether in flow and roll on bronchial endothelial cells, integrins on rolling eosinophils become further activated as a result of exposure to cytokines, eosinophils arrest firmly to adhesive ligands on activated endothelium, and eosinophils transmigrate to the airway in response to chemoattractants. Eosinophils express seven integrin heterodimeric adhesion molecules: α4β1 (CD49d/29), α6β1 (CD49f/29), αMβ2 (CD11b/18), αLβ2 (CD11a/18), αXβ2 (CD11c/18), αDβ2 (CD11d/18), and α4β7 (CD49d/β7). The role of these integrins in eosinophil recruitment has been elucidated by major advances in the understanding of integrin structure, integrin function, and modulators of integrins. Such findings have been facilitated by cellular experiments of eosinophils in vitro, studies of allergic asthma in humans and animal models in vivo, and crystal structures of integrins. Here, we elaborate on how integrins cooperate to mediate eosinophil movement to the asthmatic airway. Antagonists that target integrins represent potentially promising therapies in the treatment of asthma.
District Heating as a Secure Heat Supply—A Question of Regulation
Authors: Palm Jenny 
Published: September 2007

The trend in the district heating industry is toward increased privatization and openness to competition, which bring with them other phenomena associated with civil law, such as bankruptcies. Vingåker was one of six Swedish municipalities whose district heating companies went bankrupt in 2004. The bankruptcy caused major disruptions in Vingåker, not least as a result of the unregulated legal framework that has long prevailed in the area of district heating, where there is essentially no consumer protection. A distinguishing feature of Vingåker, and one that may be assumed to apply to other smaller municipalities as well, is the fact that the municipality was the totally dominant customer in the district heating system. In its negotiations, the municipality was able to exploit this position of strength by refusing to pay the district heating price set by the trustee in bankruptcy while still continuing to have district heat delivered. At the same time, the case of Vingåker also shows that, in their procurement processes, municipalities need to conduct a thorough analysis of the ownership structures of the bidding companies, and determine the extent to which each company is established in the industry. Yet another lesson to be taken from this case is that changes in external factors such as fuel costs and taxes, which are difficult for local actors to influence, create a need to draw up short-term contracts that allow for adjustments in the district heating rates.
Characterization of Louisiana Asphalt Mixtures Using Simple Performance Tests
Authors: Mohammad Louay N. , Saadeh Shadi , Obulareddy Sandeep , Cooper Sam 
Published: October 2007

Abstract
The main objective of this study was to characterize the performance of HMA mixes based on four laboratory tests, including three simple performance tests (SPTs) dynamic modulus ∣E∗∣, flow time (Ft), flow number (FN), and a Loaded Wheel Tracking (LWT) test. In addition, two dynamic modulus prediction models, namely Witczak and Hirsch, were evaluated. Thirteen plant-produced HMA mixtures were selected in this study. Laboratory characterization tests included the dynamic modulus ∣E∗∣, flow number (FN), and Hamburg-Type LWT tests. Test results indicated that the ∣E∗∣ test was sensitive to the nominal maximum aggregate size (NMAS) in the HMA mixture. Larger aggregates combined with recycled asphalt (RAP) tended to have high ∣E∗∣ values at high temperatures. Both the Witczak and Hirsch models could predict the dynamic modulus ∣E∗∣ values with a reasonable reliability. However, the Witczak model reliability increases for higher NMAS. On the other hand, the Hirsch model reliability increases for lower NMAS. The general ranking of the SPTs and LWT test was similar. In addition, this ranking was consistent with the field use of those mixtures in terms of their design traffic volume.
Review Essay
Authors: Isendahl Christian 
Published: September 2007

The Mesoamerican ExperienceThe Memory of Bones: Body, Being, and Experience among the Classic Maya. David Stuart and Karl Taube, eds., Austin: University of Texas Press, 2006. 324 pp.The Social Experience of Childhood in Ancient Mesoamerica. Traci Ardren and Scott R. Hutson, eds., Boulder: University Press of Colorado, 2006. 309 pp.
Subepithelial Connective Tissue Graft for Root Coverage: A Case Report of an Unusual Late Complication of Epithelial Origin
Authors: Parashis Andreas O. , Tatakis Dimitris N. 
Published: October 2007

Background: The subepithelial connective tissue graft (SCTG) is one of the most used and predictable periodontal plastic surgery procedures; reports of late complications are very rare. This article presents an SCTG case with a previously unreported late complication of epithelial origin, and we suggest a potential link between the patient's dermatologic condition and this complication. Late SCTG complications also are reviewed.Methods: A 19‐year‐old female presented with a 3‐mm deep Miller Class I recession defect on the mandibular right central incisor. An SCTG procedure was performed for root coverage, with uneventful initial postoperative healing that resulted in complete root coverage. At 4 months, an asymptomatic solid white discharge was observed at sites along the original graft margin without evidence of inflammation. A month later, the somewhat reduced but still evident discharge was collected and submitted for microscopic examination.Results: Cytologic examination revealed the discharge to be normal epithelial cells, suggesting a proliferative epithelial response. Follow‐up indicated that the discharge was self‐limiting and was no longer present at 9 months after surgery. This unusual late SCTG complication is consistent with reported epithelial invaginations and projections between graft and overlying flap. The patient had acne, a disease whose pathogenesis includes host predisposition to epithelial hyperproliferation; therefore, a possible association of this SCTG complication with the patient's systemic health is proposed.Conclusion: Epithelial cell discharge is a hitherto unreported, self‐limiting, late complication of the SCTG procedure, and a potential association between this complication and the patient's dermatologic condition is suggested.
Effect of Two Different Bioabsorbable Collagen Membranes on Guided Bone Regeneration: A Comparative Histomorphometric Study in the Dog Mandible
Authors: Bornstein Michael M. , Bosshardt Dieter , Buser Daniel 
Published: October 2007

Background: This study compared bone regeneration following guided bone regeneration with two bioabsorbable collagen membranes in saddle‐type bone defects in dog mandibles.Methods: Three standardized defects were created, filled with bone chips and deproteinized bovine bone mineral (DBBM), and covered by three different methods: control = no membrane; test 1 = collagen membrane; and test 2 = cross‐linked collagen membrane (CCM). Each side of the mandible was allocated to one of two healing periods (8 or 16 weeks). The histomorphometric analysis assessed the percentage of bone, soft tissue, and DBBM in the regenerate; the absolute area in square millimeters of the bone regenerate; and the distance in millimeters from the bottom of the defect to the highest point of the regenerate.Results: In the 8‐week healing group, two dehiscences occurred with CCM. After 8 weeks, all treatment modalities showed no significant differences in the percentage of bone regenerate. After 16 weeks, the percentage of bone had increased for all treatment modalities without significant differences. For all groups, the defect fill height increased between weeks 8 and 16. The CCM group showed a statistically significant (P = 0.0202) increase over time and the highest value of all treatment modalities after 16 weeks of healing.Conclusions: The CCM showed a limited beneficial effect on bone regeneration in membrane‐protected defects in dog mandibles when healing was uneventful. The observed premature membrane exposures resulted in severely compromised amounts of bone regenerate. This increased complication rate with CCM requires a more detailed preclinical and clinical examination before any clinical recommendations can be made.
Minimally Invasive Antral Membrane Balloon Elevation: Report of 36 Procedures
Authors: Kfir Efraim , Kfir Vered , Eliav Eli , Kaluski Edo 
Published: October 2007

Background: The posterior maxillary segment frequently has insufficient bone mass to support dental implants. This registry evaluated the feasibility and safety of minimally invasive antral membrane balloon elevation (MIAMBE), followed by bone augmentation and implant fixation.Methods: Thirty‐six consecutive patients referred for posterior maxillary bone augmentation underwent alveolar crest exposure and implant osteotomy followed by MIAMBE (>10 mm). Fibrin and bone particles were injected beneath the antral membrane, implants were placed into the osteotomies, and primary closure was executed at the same sitting.Results: All 36 patients successfully concluded the procedure with no significant procedural complications or discomfort. Procedure time was 48 ± 15 minutes. Incremental bone height consistently exceeded 8 mm, and implant survival of 97% was observed at 6 to 8 months.Conclusions: MIAMBE resulted in high procedural success and satisfactory bone augmentation implant survival and complication rates. Because it is minimally invasive, this procedure may be an alternative to the currently used surgical methods.