bluuebunny/crossref_metadata_2025_split huggingface dataset:
Newcastle Disease Virus-Vectored Rabies Vaccine Is Safe, Highly Immunogenic, and Provides Long-Lasting Protection in Dogs and Cats
Authors: Ge Jinying , Wang Xijun , Tao Lihong , Wen Zhiyuan , Feng Na , Yang Songtao , Xia Xianzhu , Yang Chinglai , Chen Hualan , Bu Zhigao 
Published: June 2011

ABSTRACT

Effective, safe, and affordable rabies vaccines are still being sought. Newcastle disease virus (NDV), an avian paramyxovirus, has shown promise as a vaccine vector for mammals. Here, we generated a recombinant avirulent NDV La Sota strain expressing the rabies virus glycoprotein (RVG) and evaluated its potential to serve as a vaccine against rabies. The recombinant virus, rL-RVG, retained its high-growth property in chicken eggs, with titers of up to 10
9.8
50% egg infective doses (EID
50
)/ml of allantoic fluid. RVG expression enabled rL-RVG to spread from cell to cell in a rabies virus-like manner, and RVG was incorporated on the surface of the rL-RVG viral particle. RVG incorporation did not alter the trypsin-dependent infectivity of the NDV vector in mammalian cells. rL-RVG and La Sota NDV showed similar levels of sensitivity to a neutralization antibody against NDV and similar levels of resistance to a neutralization antibody against rabies virus. Animal studies demonstrated that rL-RVG is safe in several species, including cats and dogs, when administered as multiple high doses of recombinant vaccine. Intramuscular vaccination with rL-RVG induced a substantial rabies virus neutralization antibody response and provided complete protection from challenge with circulating rabies virus strains. Most importantly, rL-RVG induced strong and long-lasting protective neutralization antibody responses to rabies virus in dogs and cats. A low vaccine dose of 10
8.3
EID
50
completely protected dogs from challenge with a circulating strain of rabies virus for more than a year. This is the first study to demonstrate that immunization with an NDV-vectored vaccine can induce long-lasting, systemic protective immunity against rabies.
Structure of the Three N-Terminal Immunoglobulin Domains of the Highly Immunogenic Outer Capsid Protein from a T4-Like Bacteriophage
Authors: Fokine Andrei , Islam Mohammad Z. , Zhang Zhihong , Bowman Valorie D. , Rao Venigalla B. , Rossmann Michael G. 
Published: June 2011

ABSTRACT

The head of bacteriophage T4 is decorated with 155 copies of the highly antigenic outer capsid protein (Hoc). One Hoc molecule binds near the center of each hexameric capsomer. Hoc is dispensable for capsid assembly and has been used to display pathogenic antigens on the surface of T4. Here we report the crystal structure of a protein containing the first three of four domains of Hoc from bacteriophage RB49, a close relative of T4. The structure shows an approximately linear arrangement of the protein domains. Each of these domains has an immunoglobulin-like fold, frequently found in cell attachment molecules. In addition, we report biochemical data suggesting that Hoc can bind to
Escherichia coli
, supporting the hypothesis that Hoc could attach the phage capsids to bacterial surfaces and perhaps also to other organisms. The capacity for such reversible adhesion probably provides survival advantages to the bacteriophage.
Herpes Simplex Virus Immediate-Early Protein ICP0 Is Targeted by SIAH-1 for Proteasomal Degradation
Authors: Nagel Claus-Henning , Albrecht Nina , Milovic-Holm Kristijana , Mariyanna Lakshmikanth , Keyser Britta , Abel Bettina , Weseloh Britta , Hofmann Thomas G. , Eibl Martha M. , Hauber Joachim 
Published: June 2011

ABSTRACT

Herpes simplex virus (HSV) immediate-early protein ICP0 is a transcriptional activator with E3 ubiquitin ligase activity that induces the degradation of ND10 proteins, including the promyelocytic leukemia protein (PML) and Sp100. Moreover, ICP0 has a role in the derepression of viral genomes and in the modulation of the host interferon response to virus infection. Here, we report that ICP0 interacts with SIAH-1, a cellular E3 ubiquitin ligase that is involved in multiple cellular pathways and is itself capable of mediating PML degradation. This novel virus-host interaction profoundly stabilized SIAH-1 and recruited this cellular E3 ligase into ICP0-containing nuclear bodies. Moreover, SIAH-1 mediated the polyubiquitination of HSV ICP0
in vitro
and
in vivo
. After infection of SIAH-1 knockdown cells with HSV, higher levels of ICP0 were produced, ICP0 was less ubiquitinated, and the half-life of this multifunctional viral regulatory protein was increased. These results indicate an inhibitory role of SIAH-1 during lytic infection by targeting ICP0 for proteasomal degradation.
Shared Ancestry between a Newfound Mole-Borne Hantavirus and Hantaviruses Harbored by Cricetid Rodents
Authors: Kang Hae Ji , Bennett Shannon N. , Hope Andrew G. , Cook Joseph A. , Yanagihara Richard 
Published: June 2011

ABSTRACT

Discovery of genetically distinct hantaviruses in multiple species of shrews (order Soricomorpha, family Soricidae) and moles (family Talpidae) contests the conventional view that rodents (order Rodentia, families Muridae and Cricetidae) are the principal reservoir hosts and suggests that the evolutionary history of hantaviruses is far more complex than previously hypothesized. We now report on Rockport virus (RKPV), a hantavirus identified in archival tissues of the eastern mole (
Scalopus aquaticus
) collected in Rockport, TX, in 1986. Pairwise comparison of the full-length S, M, and L genomic segments indicated moderately low sequence similarity between RKPV and other soricomorph-borne hantaviruses. Phylogenetic analyses, using maximum-likelihood and Bayesian methods, showed that RKPV shared a most recent common ancestor with cricetid-rodent-borne hantaviruses. Distributed widely across the eastern United States, the fossorial eastern mole is sympatric and syntopic with cricetid rodents known to harbor hantaviruses, raising the possibility of host-switching events in the distant past. Our findings warrant more-detailed investigations on the dynamics of spillover and cross-species transmission of present-day hantaviruses within communities of rodents and moles.
Economic burden of injuries in South Korea
Authors: Lim Seung-Ji , Chung Woo-Jin , Cho Woo-Hyun 
Published: May 2011

BackgroundStudies on the cost of injury are useful in setting research and policy priorities and it is valuable to observe differences in the economic burden of injuries across countries.ObjectiveTo estimate the treated prevalence rate, economic burden and gender- and age-specific costs of injuries in Korea in 2006.DesignAnnual direct healthcare costs associated with injuries were estimated from the National Health Insurance, Medical Aid and Automobile Insurance databases. Annual direct non-health costs were estimated for transport and caregiver's costs. Indirect costs were estimated for premature death, absence from work and disability. Costs were adjusted to 2006 levels using the healthcare component of the Consumer Price Index.Main outcome measuresPrevalence-based direct costs, incidence-based indirect costs and total costs for injuries, stratified by gender, age group and type of injury.ResultsThe treated prevalence rate of injury in 2006 of the Korean population was 26.5 per 100, resulting in an annual economic burden of $39 837 million ($4703 million in direct and $35 134 million in indirect costs). The cost of medical treatment associated with injuries accounted for 9.5% of the total health expenditure in Korea. The cost of premature death was the largest contributor to the total and automobile-related injuries accounted for 30.3% of total costs.ConclusionsThe estimates were considerably understated because they did not include losses in household production and quality of life. Nevertheless, the size and main components of the injury burden were identified; this information should aid decision-making about research priorities and improve monitoring of the effects of policy initiatives.
A qualitative investigation of selecting surrogate decision-makers
Authors: Edwards Sarah J L , Brown Patrick , Twyman Matt Amon , Christie Deborah , Rakow Tim 
Published: May 2011

BackgroundEmpirical studies of surrogate decision-making tend to assume that surrogates should make only a 'substituted judgement'—that is, judge what the patient would want if they were mentally competent.ObjectivesTo explore what people want in a surrogate decision-maker whom they themselves select and to test the assumption that people want their chosen surrogate to make only a substituted judgement.Methods30 undergraduate students were recruited. They were presented with a hypothetical scenario about their expected loss of mental capacity in the future and asked to answer some questions about their choice of surrogate. These data were analysed qualitatively using thematic content analysis.ResultsMost respondents talked about choosing someone who was caring and competent in certain ways, giving interesting evidence for their judgements. Surprisingly few highlighted how well they thought their chosen surrogate knew their preferences and would be able to make a substituted judgement. Moreover, few specified that their chosen surrogate had similar attitudes and values to their own and so would make a similar decision to theirs in the circumstances presented. Some respondents also referred to the social role of their chosen surrogate or the social dynamics of their situation which influenced their choices, as well as to ideas of reciprocity and characteristics of honesty and loyalty.ConclusionIn the event that they lose mental capacity, many people will not select a surrogate to decide about medical treatments on their behalf solely on the basis that they expect their surrogate to make a substituted judgement.
Aptamer selection for the detection ofEscherichia coliK88
Authors: Li Hua , Ding Xinghua , Peng Zhihui , Deng Le , Wang Dan , Chen Hui , He Qizhi 
Published: June 2011

In this study, the first group of single-stranded DNA aptamers that are highly specific to enterotoxigenic Escherichia coli (ETEC) K88 was obtained from an enriched oligonucleotide pool by the SELEX (Systematic Evolution of Ligands by Exponential Enrichment) procedure, during which the K88 fimbriae protein was used as the target and bovine serum albumin as counter targets. These aptamers were applied successfully in the detection of ETEC K88. They were then grouped under different families based on the similarity of their secondary structure and the homology of their primary sequence. Four sequences from different families were deliberately chosen for further characterization by fluorescence analysis. Having the advantage of high sensitivity, fluorescence photometry was selected as single-stranded DNA quantification method during the SELEX process. Aptamers with the highest specificity and affinity were analyzed to evaluate binding ability with E. coli. Since ETEC K88 is the only type of bacterium that expressed abundant K88 fimbriae, the selected aptamers against the K88 fimbriae protein were able to specifically identify ETEC K88 among other bacteria. This method of detecting ETEC K88 by aptamers can also be applied to bacteria other than ETEC K88.
Phosphatidylinositol phospholipase C mediates carbon sensing and vegetative nuclear duplication rates inAspergillus nidulans
Authors: Vanzela Ana Paula de Figueiredo Conte , Said Suraia , Prade Rolf Alexander 
Published: June 2011

In this work, we disrupted one of three putative phosphatidylinositol phospholipase C genes of Aspergillus nidulans and studied its effect on carbon source sensing linked to vegetative mitotic nuclear division. We showed that glucose does not affect nuclear division rates during early vegetative conidial germination (6–7 h) in either the wild type or the plcA-deficient mutant. Only after 8 h of cultivation on glucose did the mutant strain present some decrease in nuclear duplication. However, decreased nuclear division rates were observed in the wild type when cultivated in media amended with polypectate, whereas our plcA-deficient mutant did not show slow nuclear duplication rates when grown on this carbon source, even though it requires induction and secretion of multiple pectinolytic enzymes to be metabolized. Thus, plcA appears to be directly linked to high-molecular-weight carbon source sensing.
Caveolin-1 Upregulation Mediates Suppression of Primary Breast Tumor Growth and Brain Metastases by Stat3 Inhibition
Authors: Chiu Wen-Tai , Lee Hsueh-Te , Huang Feng-Ju , Aldape Kenneth D. , Yao Jun , Steeg Patricia S. , Chou Cheng-Yang , Lu Zhimin , Xie Keping , Huang Suyun 
Published: May 2011

Abstract
Stat3 activation has been implicated as an important driver of brain metastasis in breast cancer, but the critical targets of Stat3 in this process are yet to be fully defined. In this study, we identified the lipid raft organizing protein Caveolin-1 (Cav-1) as a critical genetic target of Stat3 in this process. In human breast cancers, we found that activated Stat3 correlated with attenuation of Cav-1 in brain metastases relative to primary tumors. Cav-1 promoter activity and gene expression were increased by overexpressing an activated form of Stat3 but decreased by attenuation of Stat3 activity or expression. We identified putative Stat3-binding elements in the Cav-1 promoter and showed a direct repression of Cav-1 transcription by Stat3. Reciprocally, we showed that strategies to increase or decrease Cav-1 expression were sufficient to attenuate or promote breast cancer cell invasion. Furthermore, increased expression of Cav-1 phenocopied the effects of Stat3 activation in blocking primary tumor growth and abrogating formation of brain metastases. Collectively, our findings provide clinical and mechanistic evidence that Cav-1 is a critical target for suppression by Stat3 in driving invasion and metastasis of breast cancer cells. Cancer Res; 71(14); 4932–43. ©2011 AACR.
Sorafenib Enhances Pemetrexed Cytotoxicity through an Autophagy-Dependent Mechanism in Cancer Cells
Authors: Bareford M. Danielle , Park Margaret A. , Yacoub Adly , Hamed Hossein A. , Tang Yong , Cruickshanks Nichola , Eulitt Patrick , Hubbard Nisan , Tye Gary , Burow Matthew E. , Fisher Paul B. , Moran Richard G. , Nephew Kenneth P. , Grant Steven , Dent Paul 
Published: May 2011

Abstract
Pemetrexed (ALIMTA, Lilly) is a folate antimetabolite that has been approved by the U.S. Food and Drug Administration for the treatment of non–small cell lung cancer and has been shown to stimulate autophagy. In the present study, we sought to further understand the role of autophagy in response to pemetrexed and to test if combination therapy could enhance the level of toxicity through altered autophagy in tumor cells. The multikinase inhibitor sorafenib (Nexavar, Bayer), used in the treatment of renal and hepatocellular carcinoma, suppresses tumor angiogenesis and promotes autophagy in tumor cells. We found that sorafenib interacted in a greater than additive fashion with pemetrexed to increase autophagy and to kill a diverse array of tumor cell types. Tumor cell types that displayed high levels of cell killing after combination treatment showed elevated levels of AKT, p70 S6K, and/or phosphorylated mTOR, in addition to class III receptor tyrosine kinases such as platelet-derived growth factor receptor beta and VEGF receptors, known in vivo targets of sorafenib. In xenograft and in syngeneic animal models of mammary carcinoma and glioblastoma, the combination of sorafenib and pemetrexed suppressed tumor growth without deleterious effects on normal tissues or animal body mass. Taken together, the data suggest that premexetred and sorafenib act synergistically to enhance tumor killing via the promotion of a toxic form of autophagy that leads to activation of the intrinsic apoptosis pathway, and predict that combination treatment represents a future therapeutic option in the treatment of solid tumors. Cancer Res; 71(14); 4955–67. ©2011 AACR.
Cancer Stem Cells and Chemosensitivity
Authors: Maugeri-Saccà Marcello , Vigneri Paolo , De Maria Ruggero 
Published: May 2011

Abstract
Cancer lethality is mainly due to the onset of distant metastases and refractoriness to chemotherapy. Thus, the development of molecular targeted agents that can restore or increase chemosensitivity will provide valuable therapeutic options for cancer patients. Growing evidence indicates that a cellular subpopulation with stem cell–like features, commonly referred to as cancer stem cells (CSCs), is critical for tumor generation and maintenance. Recent advances in stem cell biology are revealing that this cellular fraction shares many properties with normal adult stem cells and is able to propagate the parental tumor in animal models. CSCs seem to be protected against widely used chemotherapeutic agents by means of different mechanisms, such as a marked proficiency in DNA damage repair, high expression of ATP-binding cassette drug transporters, and activation of PI3K/AKT and Wnt pathways. Moreover, microenvironmental stimuli such as those involved in the epithelial-mesenchymal transition and hypoxia indirectly contribute to chemoresistance by inducing in cancer cells a stem-like phenotype. Understanding how CSCs overcome chemotherapy-induced death stimuli, and integrating such knowledge into clinical research methodology, has become a priority in the process of identifying innovative therapeutic strategies aimed at improving the outcome of cancer patients. Clin Cancer Res; 17(15); 4942–7. ©2011 AACR.
Impact of Clinical and Pathologic Features on Tumor-Infiltrating Lymphocyte Expansion from Surgically Excised Melanoma Metastases for Adoptive T-cell Therapy
Authors: Joseph Richard W. , Peddareddigari Vijay R. , Liu Ping , Miller Priscilla W. , Overwijk Willem W. , Bekele Nebiyou B. , Ross Merrick I. , Lee Jeffrey E. , Gershenwald Jeffrey E. , Lucci Anthony , Prieto Victor G. , McMannis John D. , Papadopoulos Nicholas , Kim Kevin , Homsi Jade , Bedikian Agop , Hwu Wen-Jen , Hwu Patrick , Radvanyi Laszlo G. 
Published: June 2011

Abstract
Purpose: Clinical trials on adoptive T-cell therapy (ACT) using expanded tumor-infiltrating lymphocytes (TIL) have shown response rates of over 50% in refractory melanoma. However, little is known how clinical and pathologic features impact TIL outgrowth isolated from metastatic melanoma tumors.
Experimental Design: We analyzed the impact of clinical and pathologic features on initial TIL outgrowth in 226 consecutive patients undergoing tumor resection. Successful initial TIL outgrowth was defined as ≥40 million viable lymphocytes harvested from all tumor fragments in a 5-week culture. To normalize for the different size of resected tumors and thus available tumor fragments, we divided the number of expanded TIL by the starting number of tumor fragments (TIL/fragment).
Results: Overall, initial TIL outgrowth was successful in 62% of patients, with patients ≤30 years of age (94%; P = 0.01) and female patients (71% vs. 57% for males; P = 0.04) having the highest rate of success. Systemic therapy 30 days before tumor harvest negatively impacted initial TIL outgrowth compared to patients who never received systemic therapy (47% vs. 71%, P = 0.02). Biochemotherapy within 0 to 60 days of tumor harvest negatively impacted the initial TIL outgrowth with a success rate of only 16% (P &lt; 0.0001).
Conclusion: Parameters such as age, sex, and the type and timing of prior systemic therapy significantly affect the success rate of the initial TIL outgrowth from tumor fragments for ACT; these parameters may be helpful in selecting patients for melanoma ACT. Clin Cancer Res; 17(14); 4882–91. ©2011 AACR.
Brivanib, a Dual FGF/VEGF Inhibitor, Is Active Both First and Second Line against Mouse Pancreatic Neuroendocrine Tumors Developing Adaptive/Evasive Resistance to VEGF Inhibition
Authors: Allen Elizabeth , Walters Ian B. , Hanahan Douglas 
Published: May 2011

Abstract
Purpose: Preclinical trials of a mouse model of pancreatic neuroendocrine tumors (PNET) were conducted to determine whether dual FGF/VEGF pathway inhibition with brivanib can improve first-line efficacy in comparison with VEGF inhibitors lacking fibroblast growth factor (FGF)-inhibitory activity and to characterize second-line brivanib activity before and after the onset of evasive resistance to VEGF-selective therapy.
Experimental Design: An anti-VEGFR2 monoclonal antibody (DC101), an inhibitor of FGF signaling (FGF ligand trap), sorafenib, and brivanib were comparatively evaluated in first-line monotherapy in short and longer term fixed endpoint intervention trials in the RIP-Tag2 mouse model of PNET. Brivanib was also tested second line aiming to block adaptive resistance to selective VEGF therapies, assessing tumor growth, vascularity, hypoxia, invasion, and metastasis. The effects of initiating second-line brivanib therapy prior to or following overt relapse on sorafenib therapy were compared in overall survival trials to first-line therapies.
Results: Brivanib produced enduring tumor stasis and angiogenic blockade, both first and second line following the failure of DC101 or sorafenib. Overall survival was significantly extended by brivanib versus sorafenib, both first-line and when second-line therapy was initiated prior to sorafenib failure; second-line brivanib was less beneficial when initiated later, after the initiation of revascularization and incipient tumor progression.
Conclusions: Brivanib holds promise and deserves consideration for clinical evaluation as an antiangiogenic therapy, both in the context of impending failures of VEGF-selective therapy and in a first-line setting aiming to limit the adaptive response to VEGF inhibitors that results in evasive resistance. Clin Cancer Res; 17(16); 5299–310. ©2011 AACR.
FGFR-4 Arg388 Enhances Prostate Cancer Progression via Extracellular Signal–Related Kinase and Serum Response Factor Signaling
Authors: Yu Wendong , Feng Shu , Dakhova Olga , Creighton Chad J. , Cai Yi , Wang Jianghua , Li Rile , Frolov Anna , Ayala Gustavo , Ittmann Michael 
Published: May 2011

Abstract
Purpose: Increased expression of FGFR-4 and its ligands have been linked to lethal prostate cancer (PCa). Furthermore, a germ line polymorphism in the FGFR-4 gene, resulting in arginine at codon 388 (Arg388) instead of glycine (Gly388), is associated with aggressive disease. The FGFR-4 Arg388 variant results in increased receptor stability, sustained receptor activation, and increased motility and invasion compared with Gly388. However, the impact of sustained signaling on cellular signal transduction pathways is unknown.
Experimental Design: Expression microarray analysis of immortalized prostatic epithelial cells lines expressing FGFR-4 Arg388 or Gly388 was used to establish a gene signature associated with FGFR-4 Arg388 expression. Transient transfection of reporters and inhibitors was used to establish the pathways activated by FGFR-4 Arg388 expression. The impact of pathway knockdown in vitro and in an orthotopic model was assessed using inhibitors and/or short hairpin RNA (shRNA).
Results: Expression of the FGFR-4 Arg388 protein leads to increased activity of the extracellular signal–related kinase (ERK) pathway, increased activity of serum response factor (SRF) and AP1, and transcription of multiple genes that are correlated with aggressive clinical behavior in PCa. Increased expression of SRF is associated with biochemical recurrence in men undergoing radical prostatectomy. Consistent with these observations, knockdown of FGFR-4 Arg388 in PCa cells decreases proliferation and invasion in vitro and primary tumor growth and metastasis in vivo.
Conclusions: These studies define a signal transduction pathway downstream of FGFR-4 Arg388 that acts via ERK and SRF to promote PCa progression. Clin Cancer Res; 17(13); 4355–66. ©2011 AACR.