bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noninvasive Visualization of Adenovirus Replication with a Fluorescent Reporter in the E3 Region
Authors: Ono Hidetaka A. , Le Long P. , Davydova Julia G. , Gavrikova Tatyana , Yamamoto Masato 
Published: November 2005

Abstract
To overcome the inefficacy and undesirable side effects of current cancer treatment strategies, conditionally replicative adenoviruses have been developed to exploit the unique mechanism of oncolysis afforded by tumor-specific viral replication. Despite rapid translation into clinical trials and the established safety of oncolytic adenoviruses, the in vivo function of these agents is not well understood due to lack of a noninvasive detection system for adenovirus replication. To address this issue, we propose the expression of a reporter from the adenovirus E3 region as a means to monitor replication. Adenovirus replication reporter vectors were constructed with the enhanced green fluorescent protein (EGFP) gene placed in the deleted E3 region under the control of the adenoviral major late promoter while retaining expression of the adenovirus death protein to conserve the native oncolytic capability of the virus. Strong EGFP fluorescence was detected from these vectors in a replication-dependent manner, which correlated with viral DNA replication. Fluorescence imaging in vivo confirmed the ability to noninvasively detect fluorescent signal during replication, which generally corresponded with the underlying level of viral DNA replication. EGFP representation of viral replication was further confirmed by Western blot comparison with the viral DNA content in the tumors. Imaging reporter expression controlled by the adenoviral major late promoter provides a viable approach to noninvasively monitor adenovirus replication in preclinical studies and has the potential for human application with clinically relevant imaging reporters.
Identification of an Inactivating Cysteine Switch in Protein Kinase Cε, a Rational Target for the Design of Protein Kinase Cε–Inhibitory Cancer Therapeutics
Authors: Chu Feng , Koomen John M. , Kobayashi Ryuji , O'Brian Catherine A. 
Published: November 2005

Abstract
Critical roles played by some protein kinases in neoplastic transformation and progression provide a rationale for developing selective, small-molecule kinase inhibitors as antineoplastic drugs. Protein kinase Cε (PKCε) is a rational target for cancer therapy, because it is oncogenic and prometastatic in transgenic mouse models. PKCε is activated by sn-1,2-diacylglycerol (DAG). Attempts to develop selective PKCε inhibitors that block activation by DAG or compete with ATP have not yet met with success, suggesting a need for new strategies. We previously reported that cystamine and a metabolic cystine precursor inactivate PKCε in cells in a thiol-reversible manner. In this report, we first determined that PKCε became resistant to inactivation by disulfides when Cys452 was replaced with alanine by site-specific mutagenesis of human PKCε or a constitutively active PKCε mutant. These results showed that the disulfides inactivated PKCε by thiol-disulfide exchange, either upon Cys452 S-thiolation or by rearrangement to an intra-protein disulfide. Mass spectrometric analysis of peptide digests of cystamine-inactivated, carbamidomethylated PKCε detected a peptide S-cysteaminylated at Cys452, indicating that Cys452 S-cysteaminylation is a stable modification. Furthermore, PKCε inactivation by N-ethylmaleimide was Cys452 dependent, providing corroborative evidence that PKCε inhibitors can be designed by targeting Cys452 with small molecules that stably modify the residue. Cys452 is an active site residue that is conserved in only 11 human protein kinase genes. Therefore, the PKCε-inactivating Cys452 switch is a rational target for the design of antineoplastic drugs that selectively inhibit PKCε.
Transcription Repressor Activity of Spleen Tyrosine Kinase Mediates Breast Tumor Suppression
Authors: Wang Lei , Devarajan Eswaran , He Jin , Reddy Sekhar P. , Dai Jia Le 
Published: November 2005

AbstractSpleen tyrosine kinase (SYK) is a candidate tumor suppressor gene in breast. Loss of SYK expression in breast tumors as a result of DNA hypermethylation promotes tumor cell proliferation and invasion and predicts shorter survival of breast cancer patients. We previously reported that, in addition to its well-known cytoplasmic localization, the full-length Syk is also present in the nucleus and that Syk nuclear translocation is a rate-limiting step to determine Syk tumor suppressor function. Here, we show that the full-length form of Syk acts as a transcription repressor in the cell nucleus. Ectopic expression of Syk down-regulates the transcription of FRA1 and cyclin D1 oncogenes. This transcription-repressing activity of Syk is associated with its binding to members of the histone deacetylase family. Syk interacts with transcription factor Sp1 at the Sp1 DNA-binding site in the FRA1 promoter to repress Sp1-activated FRA1 transcription. Thus, breast tumorigenesis and progression resulting from the loss of SYK are underscored by the derepression of Sp1-mediated oncogene transcription.
Enhanced DDB2 Expression Protects Mice from Carcinogenic Effects of Chronic UV-B Irradiation
Authors: Alekseev Sergey , Kool Hanneke , Rebel Heggert , Fousteri Maria , Moser Jill , Backendorf Claude , de Gruijl Frank R. , Vrieling Harry , Mullenders Leon H.F. 
Published: November 2005

Abstract
UV-damaged DNA-binding protein (UV-DDB) is essential for global genome repair (GGR) of UV-induced cyclobutane pyrimidine dimers (CPD). Unlike human cells, rodent epidermal cells are deficient in GGR of CPDs and express a subunit of UV-DDB, DDB2, at a low level. In this study, we generated mice (K14-DDB2) ectopically expressing mouse DDB2 at elevated levels. Enhanced expression of DDB2 both delayed the onset of squamous cell carcinoma and decreased the number of tumors per mouse in chronically UV-B light-exposed hairless mice. Enhanced expression of DDB2 improved repair of both CPDs and pyrimidine(6-4)pyrimidone photoproducts (6-4PP) in dermal fibroblasts. However, GGR of CPDs in K14-DDB2 mice did not reach the level of efficiency of human cells, suggesting that another repair protein may become rate limiting when DDB2 is abundantly present. To complement these studies, we generated mice in which the DDB2 gene was disrupted. DDB2−/− and DDB2+/− mice were found to be hypersensitive to UV-induced skin carcinogenesis. On the cellular level, we detected a delay in the repair of 6-4PPs in DDB2−/− dermal fibroblasts. Neither the absence nor the enhanced expression of DDB2 affected the levels of UV-induced apoptosis in epidermal keratinocytes or cultured dermal fibroblasts. Our results show an important role for DDB2 in the protection against UV-induced cancer and indicate that this protection is most likely mediated by accelerating the repair of photolesions.
Natural history of Phelsuma madagascariensis kochi from a dry forest in Madagascar
Authors: Ikeuchi Isami , Mori Akira , Hasegawa Masami 
Published: November 2005

AbstractNatural history of the diurnal gecko, Phelsuma madagascariensis kochi, was investigated with mark-and-recapture and census methods from the end of the dry season to the middle of the rainy season in a dry forest of Madagascar. Males were larger than females in snout-vent length, tail length, and body mass, and also had relatively larger head widths. Hatchlings were observed only in the rainy season. The geckos passively followed ambient temperatures, rarely basked, but had lower cloacal temperature than air temperature at high air temperatures. They preferred high and thick trees. The frequency of sighting decreased in the rainy season. Foraging mode was sit-and-wait. Home ranges of male P. madagascariensis kochi did not overlap with each other, but partially overlapped with those of females and unsexed individuals. Several ecological traits of P. madagascariensis kochi such as male-biased sexual size dimorphism and possible home range defense, seemed more similar to those of diurnal, arboreal lizards (some iguanids and agamids) relying on the visual modality, rather than to those of nocturnal geckos.
Reproduction of the water snake Helicops infrataeniatus (Colubridae) in southern Brazil
Authors: de Aguiar Luís Felipe Schmidt , Di-Bernardo Marcos 
Published: November 2005

AbstractThe reproductive cycle, sexual maturity, fecundity, and sexual dimorphism of Helicops infrataeniatus Jan, 1865, were inferred from the analysis of 374 preserved specimens (110 males, 140 females) from the eastern Central Depression of Rio Grande do Sul, Brazil. There was no statistical difference between the SVL of newborn males and females, but mature females attained greater length than mature males. The tail of mature individuals was proportionally longer in males than in females. Males matured at a smaller size than females. The reproductive cycle of this species was longer than what is known for oviparous colubrids from subtropical and temperate zones of Brazil. In the studied population, vitellogenesis occurred from September to February. Oviductal embryos were found from September to May. Births took place in September, January, February and March, and occurred in two peaks. Litter size ranged from 5 to 22 offspring. The differences between the number of vitellogenic follicles and embryos, and between embryos and newborns were not significant, thus practically all follicles were generally converted into embryos and embryos into newborns.
Morphological integration of cranium and postcranial skeleton during ontogeny of facultative paedomorphic European newts (Triturus vulgaris and T. alpestris)
Authors: Ivanović Ana , Kalezić Miloš , Aleksić Ivan 
Published: November 2005

AbstractThe patterns of ontogenetic and interspecific variation of morphological integration (the relationships and correlation patterns of functionally and developmentally related morphological traits) in facultative paedomorphic species of two European newts (Triturus vulgaris and T. alpestris) were examined. The degree of morphological integration differed among ontogenetic stages. Variation in the level of morphological integration of cranium and postcranial skeleton during ontogeny of paedomorphic newts had the same pattern in both analysed species. The lowest level of cranium morphological integration characterises the larvae and the juveniles. Individuals that follow alternative life-history path (paedomorphs) remain at a relatively low level of morphological integration, while integration highly increased in metamorphosed adult individuals. Limb skeleton also showed a lower level of integration in paedomorphs in comparison with metamorphosed individuals. The hypothesis of morphological integration was confirmed for all stages of T. vulgaris, while the same hypothesis was confirmed only for larval and paedomorphic stages of T. alpestris. In T. vulgaris, metamorphosis changes the pattern of correlation among the cranial traits, while in T. alpestris, the patterns of phenotypic correlation among the cranial traits remain substantially similar for all analysed ontogenetic stages.
Chorus tenure and estimates of population size of male European tree frogs Hyla arborea: implications for conservation
Authors: Grafe T. Ulmar , Meuche Ivonne 
Published: November 2005

AbstractChorusing male anurans typically spend only a part of the breeding season calling although chorus tenure is often the best predictor of mating success. We determined the number of nights males attended a chorus (chorus tenure) and its influence on mating success in the European tree frog, Hyla arborea. The median chorus tenure was 7.5 nights out of a study season of 38 nights. Males that spent more than two nights in the chorus were present for an average of 47% of the nights between their first and last night in the chorus. Minimum daily temperature, ambient temperature at initiation of calling, and daily rainfall explained 37.8% of the variance in male attendance. Twenty-five males were calling on the night of peak activity, a fraction of the 44 males marked. This suggests that estimates of male population size based on peak activity, widely used by conservation biologists, are inaccurate. We suggest that, when mark-recapture methods cannot be used, male population size be calculated by using a regression model based on the peak number of calling males that can be further developed as more data accumulates.
Hispanic physicians' tobacco intervention practices: a cross-sectional survey study
Authors: Soto Mas Francisco G , Papenfuss Richard L , Jacobson Holly E , Ed Hsu Chiehwen , Urrutia-Rojas Ximena , Kane William M 
Published: November 2005

Abstract

Background
U.S. Hispanic physicians constitute a considerable professional collective, and they may be most suited to attend to the health education needs of the growing U.S. Hispanic population. These educational needs include tobacco use prevention and smoking cessation. However, there is a lack of information on Hispanic physicians' tobacco intervention practices, their level of awareness and use of cessation protocols, and the type of programs that would best address their tobacco training needs. The purpose of this study was to assess the tobacco intervention practices and training needs of Hispanic physicians.

Methods
Data was collected through a validated survey instrument among a cross-sectional sample of self-reported Hispanic physicians. Data analyses included frequencies, descriptive statistics, and factorial analyses of variance.

Results
The response rate was 55.5%. The majority of respondents (73.3%) were middle-age males. Less than half of respondents routinely performed the most basic intervention: asking patients about smoking status (44.4%) and advising smoking patients to quit (42.2%). Twenty-five percent assisted smoking patients by talking to them about the health risks of smoking, providing education materials or referring them to cessation programs. Only 4.4% routinely arranged follow-up visits or phone calls for smoking patients. The majority of respondents (64.4%) indicated that they prescribe cessation treatments to less than 20% of smoking patients. A few (4.4%) routinely used behavioral change techniques or programs. A minority (15.6%) indicated that they routinely ask their patients about exposure to tobacco smoke, and 6.7% assisted patients exposed to secondhand smoke in understanding the health risks associated with environmental tobacco smoke (ETS). The most frequently encountered barriers preventing respondents from intervening with patients who smoke included: time, lack of training, lack of receptivity by patients, and lack of reimbursement by third party payers. There was no significant main effect of type of physician, nor was there an interaction effect (gender by type of physician), on tobacco-related practices.

Conclusion
The results indicate that Hispanic physicians, similarly to U.S. physicians in general, do not meet the level of intervention recommended by health care agencies. The results presented will assist in the development of tobacco training initiatives for Hispanic physicians.
Mitogen‐Activated Protein Kinases Regulate Platelet‐Activating Factor‐Induced Hyperpermeability
Authors: YU PENG , HATAKEYAMA TAKUYA , ARAMOTO HARUO , MIYATA TETSURO , SHIGEMATSU HIROSHI , NAGAWA HIROKAZU , HOBSON ROBERT W. , DURÁN WALTER N. 
Published: November 2005

ABSTRACTObjective: The authors tested the hypothesis that p42/44‐ (ERK‐1/2) and/or p38‐mitogen‐activated protein kinases (MAPK) are in vivo regulatory elements in the platelet‐activating factor (PAF) activated signaling cascade that stimulates microvascular hyperpermeability.Methods: FITC‐dextran 70 was used as the macromolecular tracer for microvascular permeability in the mouse mesenteric fat tissue. Interstitial integrated optical intensity (IOI) was used as an index of permeability.Results: An application of 10−7 M PAF increased IOI from 23.1 ± 3.6 to 70.8 ± 7.4 (mean ± SEM). Inhibition of ERK‐1/2 with 3 μM and 30 μM AG126 reduced IOI to 32.3 ± 2.5. Similarly, inhibition of p38‐MAPK with 6 nM, 60 nM and 600 nM SB203580 lowered IOI to 29.1 ± 2.4.Conclusions: The results demonstrate that ERK‐1/2 and p38MAPK participate in the signaling cascade that regulates PAF‐induced microvascular hyperpermeability in vivo.
Inferring functional information from domain co-evolution
Authors: Kim Yohan , Koyutürk Mehmet , Topkara Umut , Grama Ananth , Subramaniam Shankar 
Published: November 2005

Abstract
Motivation: Co-evolution is a powerful mechanism for understanding protein function. Prior work in this area has shown that co-evolving proteins are more likely to share the same function than those that do not because of functional constraints. Many of the efforts founded on this observation, however, are at the level of entire sequences, implicitly assuming that the complete protein sequence follows a single evolutionary trajectory. Since it is well known that a domain can exist in various contexts, this assumption is not valid for numerous multi-domain proteins. Motivated by these observations, we introduce a novel technique called Coevolutionary-Matrix that captures co-evolution between regions of two proteins. Instead of using existing domain information, the method exploits residue-level conservation to identify co-evolving regions that might correspond to domains.
Results: We show that the Coevolutionary-Matrix method can detect greater number of known functional associations for the Escherichia coli proteins when compared with earlier implementations of phylogenetic profiles. Furthermore, co-evolving regions of proteins detected by our method enable us to make hypotheses about their specific functions, many of which are supported by existing biochemical studies.
Contact: shankar@sdsc.edu
The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling
Authors: Arnold Konstantin , Bordoli Lorenza , Kopp Jürgen , Schwede Torsten 
Published: November 2005

Abstract
Motivation: Homology models of proteins are of great interest for planning and analysing biological experiments when no experimental three-dimensional structures are available. Building homology models requires specialized programs and up-to-date sequence and structural databases. Integrating all required tools, programs and databases into a single web-based workspace facilitates access to homology modelling from a computer with web connection without the need of downloading and installing large program packages and databases.
Results: SWISS-MODEL workspace is a web-based integrated service dedicated to protein structure homology modelling. It assists and guides the user in building protein homology models at different levels of complexity. A personal working environment is provided for each user where several modelling projects can be carried out in parallel. Protein sequence and structure databases necessary for modelling are accessible from the workspace and are updated in regular intervals. Tools for template selection, model building and structure quality evaluation can be invoked from within the workspace. Workflow and usage of the workspace are illustrated by modelling human Cyclin A1 and human Transmembrane Protease 3.
Availability: The SWISS-MODEL workspace can be accessed freely at
Contact: Torsten.Schwede@unibas.ch
Supplementary information: Supplementary data are available at Bioinformatics online.
Association between early postoperative coagulation activation and peri‐operative myocardial ischaemia in patients undergoing vascular surgery
Authors: Böttiger B. W. , Snyder‐Ramos S. A. , Lapp W. , Motsch J. , Aulmann M. , Schweizer M. , Layug E. L. , Martin E. , Mangano D. T. ,   the investigators of the Multicenter Study of Perioperative Ischemia (MCSPI) Research Group, Inc. and the Ischemia Research and Education Foundation
Published: November 2005

SummaryWe investigated the association of peri‐operative myocardial ischaemia with activation of coagulation and endogenous fibrinolysis in patients undergoing vascular surgery. In 50 patients, continuous Holter monitoring was performed to assess peri‐operative myocardial ischaemia and 12‐lead electrocardiography was recorded preoperatively and 72 h postoperatively to assess myocardial infarction. Serial blood samples were drawn peri‐operatively to determine the concentrations of fibrin monomers (for activation of coagulation), d‐dimer (for endogenous fibrinolysis) and cardiac troponin T and I. Patients with myocardial ischaemia showed higher concentrations of fibrin monomers at 48 h, and higher concentrations of d‐dimer preoperatively and at 24 and 48 h postoperatively. In patients with peri‐operative myocardial ischaemia, strong positive correlations were observed between fibrin monomer and d‐dimer concentrations at 15 min and 4 h postoperatively, and cardiac troponins at 15 min and at 4, 24, 48 and 72 h postoperatively. Early postoperative activation of coagulation and fibrinolysis is associated with peri‐operative myocardial cell damage among patients who are at risk for, or have a history of, coronary artery disease plus peri‐operative myocardial ischaemia.
Linkage of Sevier thrusting episodes and Late Cretaceous foreland basin megasequences across southern Wyoming (USA)
Authors: Liu Shao‐Feng , Nummedal Dag , Yin Pei‐Gui , Luo Hong‐Jun 
Published: November 2005

ABSTRACTDeposition and subsidence analysis, coupled with previous structural studies of the Sevier thrust belt, provide a means of reconstructing the detailed kinematic history of depositional response to episodic thrusting in the Cordilleran foreland basin of southern Wyoming, western interior USA. The Upper Cretaceous basin fill is divided into five megasequences bounded by unconformities. The Sevier thrust belt in northern Utah and southwestern Wyoming deformed in an eastward progression of episodic thrusting. Three major episodes of displacement on the Willard‐Meade, Crawford and ‘early’ Absaroka thrusts occurred from Aptian to early Campanian, and the thrust wedge gradually became supercritically tapered. The Frontier Formation conglomerate, Echo Canyon and Weber Canyon Conglomerates and Little Muddy Creek Conglomerate were deposited in response to these major thrusting events. Corresponding to these proximal conglomerates within the thrust belt, Megasequences 1, 2 and 3 were developed in the distal foreland of southern Wyoming. Two‐dimensional (2‐D) subsidence analyses show that the basin was divided into foredeep, forebulge and backbulge depozones. Foredeep subsidence in Megasequences 1, 2 and 3, resulting from Willard‐Meade, Crawford and ‘early’ Absaroka thrust loading, were confined to a narrow zone in the western part of the basin. Subsidence in the broad region east of the forebulge was dominantly controlled by sediment loading and inferred dynamic subsidence. Individual subsidence curves are characterized by three stages from rapid to slow. Controlled by relationships between accommodation and sediment supply, the basin was filled with retrogradational shales during periods of rapid subsidence, followed by progradational coarse clastic wedges during periods of slow subsidence. During middle Campanian time (ca. 78.5–73.4 Ma), the thrust wedge was stalled because of wedge‐top erosion and became subcritical, and the foredeep zone eroded and rebounded because of isostasy. The eroded sediments were transported far from the thrust belt, and constitute Megasequence 4 that was mostly composed of fluvial and coastal plain depositional systems. Subsidence rates were very slow, because of post‐thrusting rebound, and the resulting 2‐D subsidence was lenticular in an east–west direction. During late Campanian to early Maastrichtian time, widespread deposits of coarse sediment (the Hams Fork Conglomerate) aggraded the top of the thrust wedge after it stalled, prior to initiation of ‘late’ Absaroka thrusting. Meanwhile Megasequence 5 was deposited in the Wyoming foreland under the influence of both the intraforeland Wind River basement uplift and the Sevier thrust belt.