bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of a Novel G3P[3] Rotavirus Isolated from a Lesser Horseshoe Bat: a Distant Relative of Feline/Canine Rotaviruses
Authors: He Biao , Yang Fanli , Yang Weihong , Zhang Yuzhen , Feng Yun , Zhou Jihua , Xie Jinxin , Feng Ye , Bao Xiaolei , Guo Huancheng , Li Yingying , Xia Lele , Li Nan , Matthijnssens Jelle , Zhang Hailin , Tu Changchun 
Published: September 2013

ABSTRACT

Bats are considered important animal reservoirs for many viruses pathogenic to humans. An approach based on viral metagenomics was used to study gut specimens from 78 insectivorous bats in Yunnan Province, China. Seventy-four reads were found to be related to group A rotavirus (RVA). Further reverse transcription-PCR screening and viral isolation on cell cultures confirmed the presence of a novel RVA strain, named RVA/Bat-tc/MSLH14/2012/G3P[3], in 1 (6%) of 16 lesser horseshoe bats. Full genomic sequencing analyses showed that MSLH14 possessed the genotype constellation G3-P[3]-I8-R3-C3-M3-A9-N3-T3-E3-H6, which is akin to human and animal rotaviruses believed to be of feline/canine origin. Phylogenetic analysis indicated that VP7 was most closely related to bovine RVA strains from India, whereas VP4 was most closely related to an unusual human RVA strain, CMH222, with animal characteristics isolated in Thailand. The remaining gene segments were only distantly related to a range of animal RVA strains, most of which are believed to be related to feline/canine RVAs. Experimental infection showed that bat RVA strain MSLH14 was highly pathogenic to suckling mice, causing 100% mortality when they were inoculated orally with a titer as low as 5 × 10
2
50% tissue culture infective doses. As this virus is not closely related to any known RVA strain, it is tempting to speculate that it is a true bat RVA strain rather than a virus transmitted between species. However, further screening of bat populations, preferably juvenile animals, will be crucial in determining whether or not this virus is widely distributed in the bat population.
Chimeric Exchange of Coronavirus nsp5 Proteases (3CLpro) Identifies Common and Divergent Regulatory Determinants of Protease Activity
Authors: Stobart Christopher C. , Sexton Nicole R. , Munjal Havisha , Lu Xiaotao , Molland Katrina L. , Tomar Sakshi , Mesecar Andrew D. , Denison Mark R. 
Published: September 2013

ABSTRACT
Human coronaviruses (CoVs) such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV) cause epidemics of severe human respiratory disease. A conserved step of CoV replication is the translation and processing of replicase polyproteins containing 16 nonstructural protein domains (nsp's 1 to 16). The CoV nsp5 protease (3CLpro; Mpro) processes nsp's at 11 cleavage sites and is essential for virus replication. CoV nsp5 has a conserved 3-domain structure and catalytic residues. However, the intra- and intermolecular determinants of nsp5 activity and their conservation across divergent CoVs are unknown, in part due to challenges in cultivating many human and zoonotic CoVs. To test for conservation of nsp5 structure-function determinants, we engineered chimeric betacoronavirus murine hepatitis virus (MHV) genomes encoding nsp5 proteases of human and bat alphacoronaviruses and betacoronaviruses. Exchange of nsp5 proteases from HCoV-HKU1 and HCoV-OC43, which share the same genogroup, genogroup 2a, with MHV, allowed for immediate viral recovery with efficient replication albeit with impaired fitness in direct competition with wild-type MHV. Introduction of MHV nsp5 temperature-sensitive mutations into chimeric HKU1 and OC43 nsp5 proteases resulted in clear differences in viability and temperature-sensitive phenotypes compared with MHV nsp5. These data indicate tight genetic linkage and coevolution between nsp5 protease and the genomic background and identify differences in intramolecular networks regulating nsp5 function. Our results also provide evidence that chimeric viruses within coronavirus genogroups can be used to test nsp5 determinants of function and inhibition in common isogenic backgrounds and cell types.
Involvement of the Rabies Virus Phosphoprotein Gene in Neuroinvasiveness
Authors: Yamaoka Satoko , Ito Naoto , Ohka Seii , Kaneda Shohei , Nakamura Hiroko , Agari Takahiro , Masatani Tatsunori , Nakagawa Keisuke , Okada Kazuma , Okadera Kota , Mitake Hiromichi , Fujii Teruo , Sugiyama Makoto 
Published: September 2013

ABSTRACT

Rabies virus (RABV), which is transmitted via a bite wound caused by a rabid animal, infects peripheral nerves and then spreads to the central nervous system (CNS) before causing severe neurological symptoms and death in the infected individual. Despite the importance of this ability of the virus to spread from a peripheral site to the CNS (neuroinvasiveness) in the pathogenesis of rabies, little is known about the mechanism underlying the neuroinvasiveness of RABV. In this study, to obtain insights into the mechanism, we conducted comparative analysis of two fixed RABV strains, Nishigahara and the derivative strain Ni-CE, which cause lethal and asymptomatic infections, respectively, in mice after intramuscular inoculation. Examination of a series of chimeric viruses harboring the respective genes from Nishigahara in the genetic background of Ni-CE revealed that the Nishigahara phosphoprotein (P) gene plays a major role in the neuroinvasiveness by mediating infection of peripheral nerves. The results obtained from both
in vivo
and
in vitro
experiments strongly suggested that the Nishigahara P gene, but not the Ni-CE P gene, is important for stable viral replication in muscle cells. Further investigation based on the previous finding that RABV phosphoprotein counteracts the host interferon (IFN) system demonstrated that the Nishigahara P gene, but not the Ni-CE P gene, functions to suppress expression of the beta interferon (IFN-β) gene (
Ifn
-β) and IFN-stimulated genes in muscle cells. In conclusion, we provide the first data strongly suggesting that RABV phosphoprotein assists viral replication in muscle cells by counteracting the host IFN system and, consequently, enhances infection of peripheral nerves.
Stress-Induced Cellular Transcription Factors Expressed in Trigeminal Ganglionic Neurons Stimulate the Herpes Simplex Virus 1 ICP0 Promoter
Authors: Sinani Devis , Cordes Ethan , Workman Aspen , Thunuguntia Prasanth , Jones Clinton 
Published: September 2013

ABSTRACTAlphaherpesvirinaefamily members can reactivate from latency following stress. The synthetic corticosteroid dexamethasone induces certain cellular transcription factors in murine and bovine trigeminal ganglionic neurons. Three dexamethasone-induced transcription factors, Krüppel-like factor 15, Slug, and SPDEF, stimulated the herpes simplex virus type 1-infected cell protein 0 (ICP0) promoter more than 150-fold. Conversely, other viral promoters (VP16 and ICP4) were not strongly stimulated, suggesting that the ICP0 promoter is preferentially activated by dexamethasone-simulated stress.
Systematic review of the application of the plan–do–study–act method to improve quality in healthcare
Authors: Taylor Michael J , McNicholas Chris , Nicolay Chris , Darzi Ara , Bell Derek , Reed Julie E 
Published: September 2013

BackgroundPlan–do–study–act (PDSA) cycles provide a structure for iterative testing of changes to improve quality of systems. The method is widely accepted in healthcare improvement; however there is little overarching evaluation of how the method is applied. This paper proposes a theoretical framework for assessing the quality of application of PDSA cycles and explores the consistency with which the method has been applied in peer-reviewed literature against this framework.MethodsNHS Evidence and Cochrane databases were searched by three independent reviewers. Empirical studies were included that reported application of the PDSA method in healthcare. Application of PDSA cycles was assessed against key features of the method, including documentation characteristics, use of iterative cycles, prediction-based testing of change, initial small-scale testing and use of data over time.Results73 of 409 individual articles identified met the inclusion criteria. Of the 73 articles, 47 documented PDSA cycles in sufficient detail for full analysis against the whole framework. Many of these studies reported application of the PDSA method that failed to accord with primary features of the method. Less than 20% (14/73) fully documented the application of a sequence of iterative cycles. Furthermore, a lack of adherence to the notion of small-scale change is apparent and only 15% (7/47) reported the use of quantitative data at monthly or more frequent data intervals to inform progression of cycles.DiscussionTo progress the development of the science of improvement, a greater understanding of the use of improvement methods, including PDSA, is essential to draw reliable conclusions about their effectiveness. This would be supported by the development of systematic and rigorous standards for the application and reporting of PDSAs.
The challenges in developing a finite element injury model of the neck to predict the penetration of explosively propelled projectiles
Authors: Breeze Johno , Newbery T , Pope D , Midwinter M J 
Published: September 2013

IntroductionNeck injuries sustained by UK service personnel serving on current operations from explosively propelled fragments result in significant mortality and long-term morbidity. Many of these injuries could potentially have been prevented had the soldiers been wearing their issued neck collars at the time of injury. The aim of this research is to develop an accurate method of predicting the resultant damage to cervical neurovascular structures from explosively propelled fragments.Current statusA finite element numerical model has been developed based on an anatomically accurate, anthropometrically representative 3D mathematical mesh of cervical neurovascular structures. Currently, the model simulates the passage of a fragment simulating projectile through all anatomical components of the neck using material models based upon 20% ballistic gelatin on the simplification that all tissue types act like homogenous muscle.Future researchThe material models used to define the properties of each element within the model will be sequentially replaced by ones specific to each individual tissue within an anatomical structure. However, the cumulative effect of so many additional variables will necessitate experimental validation against both animal models and post-mortem human subjects to improve the credibility of any predictions made by the model. We believe this approach will in the future have the potential to enable objective comparisons between the mitigative effects of different body armour systems to be made with resultant time and financial savings.
CXCR4, but not CXCR7, Discriminates Metastatic Behavior in Non–Small Cell Lung Cancer Cells
Authors: Choi Young H. , Burdick Marie D. , Strieter Brett A. , Mehrad Borna , Strieter Robert M. 
Published: September 2013

Abstract
Chemokines have been implicated as key contributors of non–small cell lung cancer (NSCLC) metastasis. However, the role of CXCR7, a recently discovered receptor for CXCL12 ligand, in the pathogenesis of NSCLC is unknown. To define the relative contribution of chemokine receptors to migration and metastasis, we generated human lung A549 and H157 cell lines with stable knockdown of CXCR4, CXCR7, or both. Cancer cells exhibited chemotaxis to CXCL12 that was enhanced under hypoxic conditions, associated with a parallel induction of CXCR4, but not CXCR7. Interestingly, neither knockdown cell line differed in the rate of proliferation, apoptosis, or cell adherence; however, in both cell lines, CXCL12-induced migration was abolished when CXCR4 signaling was abrogated. In contrast, inhibition of CXCR7 signaling did not alter cellular migration to CXCL12. In an in vivo heterotropic xenograft model using A549 cells, expression of CXCR4, but not CXCR7, on cancer cells was necessary for the development of metastases. In addition, cancer cells knocked down for CXCR4 (or both CXCR4 and CXCR7) produced larger and more vascular tumors as compared with wild-type or CXCR7 knockdown tumors, an effect that was attributable to cancer cell–derived CXCR4 out competing endothelial cells for available CXCL12 in the tumor microenvironment. These results indicate that CXCR4, not CXCR7, expression engages CXCL12 to mediate NSCLC metastatic behavior.
Implications: Targeting CXCR4-mediated migration and metastasis may be a viable therapeutic option in NSCLC. Mol Cancer Res; 12(1); 38–47. ©2013 AACR.
Androgen Receptor Signaling Regulates DNA Repair in Prostate Cancers
Authors: Polkinghorn William R. , Parker Joel S. , Lee Man X. , Kass Elizabeth M. , Spratt Daniel E. , Iaquinta Phillip J. , Arora Vivek K. , Yen Wei-Feng , Cai Ling , Zheng Deyou , Carver Brett S. , Chen Yu , Watson Philip A. , Shah Neel P. , Fujisawa Sho , Goglia Alexander G. , Gopalan Anuradha , Hieronymus Haley , Wongvipat John , Scardino Peter T. , Zelefsky Michael J. , Jasin Maria , Chaudhuri Jayanta , Powell Simon N. , Sawyers Charles L. 
Published: September 2013

Abstract
We demonstrate that the androgen receptor (AR) regulates a transcriptional program of DNA repair genes that promotes prostate cancer radioresistance, providing a potential mechanism by which androgen deprivation therapy synergizes with ionizing radiation. Using a model of castration-resistant prostate cancer, we show that second-generation antiandrogen therapy results in downregulation of DNA repair genes. Next, we demonstrate that primary prostate cancers display a significant spectrum of AR transcriptional output, which correlates with expression of a set of DNA repair genes. Using RNA-seq and ChIP-seq, we define which of these DNA repair genes are both induced by androgen and represent direct AR targets. We establish that prostate cancer cells treated with ionizing radiation plus androgen demonstrate enhanced DNA repair and decreased DNA damage and furthermore that antiandrogen treatment causes increased DNA damage and decreased clonogenic survival. Finally, we demonstrate that antiandrogen treatment results in decreased classical nonhomologous end-joining.
Significance: We demonstrate that the AR regulates a network of DNA repair genes, providing a potential mechanism by which androgen deprivation synergizes with radiotherapy for prostate cancer. Cancer Discov; 3(11); 1245–53. ©2013 AACR.
See related commentary by Bartek et al., p. 1222
This article is highlighted in the In This Issue feature, p. 1207
Red cell-derived microparticles (RMP) as haemostatic agent
Authors: Johansen Max E. , Bidot Carlos , Horstman Lawrence L. , Ahn Yeon S. , Jy Wenche 
Published: September 2013

SummaryAmong circulating cell-derived microparticles, those derived from red cells (RMP) have been least well investigated. To exploit potential haemostatic benefit of RMP, we developed a method of producing them in quantity, and here report on their haemostatic properties. High-pressure extrusion of washed RBC was employed to generate RMP. RMP were identified and enumerated by flow cytometry. Their size distribution was assessed by Doppler electrophoretic light scattering analysis (DELSA). Interaction with platelets was studied by platelet aggregometry, and shear-dependent adhesion by Diamed IMPACT-R. Thrombin generation and tissue factor (TF) expression was also measured. The effect of RMP on blood samples of patients with bleeding disorders was investigated ex vivo by thromboelastography (TEG). Haemostatic efficacy in vivo was assessed by measuring reduction of blood loss and bleeding time in rats and rabbits. RMP have mean diameter of 0.45 μm and 50% of them exhibit annexin V binding, a proxy for procoagulant phospholipids (PL). No TF could be detected by flow cytometry. At saturating concentrations of MPs, RMP generated thrombin robustly but after longer delay compared to PMP and EMP. RMP enhanced platelet adhesion and aggregation induced by low-dose ADP or AA. In TEG study, RMP corrected or improved haemostatic defects in blood of patients with platelet and coagulation disorders. RMP reduced bleeding time and blood loss in thrombocytopenic rabbits (busulfan-treated) and in Plavix-treated rats. In conclusion, RMP has broad haemostatic activity, enhancing both primary (platelet) and secondary (coagulation) haemostasis, suggesting potential use as haemostatic agent for treatment of bleeding.
C1q/Tumor Necrosis Factor–Related Protein-9, a Novel Adipocyte-Derived Cytokine, Attenuates Adverse Remodeling in the Ischemic Mouse Heart via Protein Kinase A Activation
Authors: Sun Yang , Yi Wei , Yuan Yuexing , Lau Wayne Bond , Yi Dinghua , Wang Xiaoliang , Wang Yajing , Su Hui , Wang Xiaoming , Gao Erhe , Koch Walter J. , Ma Xin-Liang 
Published: September 2013

Background—
C1q/tumor necrosis factor–related protein-9 (CTRP9) is a newly identified adiponectin paralog with established metabolic regulatory properties. However, the role of CTRP9 in postmyocardial infarction remodeling remains completely unknown. This study determined whether CTRP9 may regulate cardiac remodeling after acute myocardial infarction (AMI) and elucidated the underlying mechanisms.

Methods and Results—

Male adult mice were subject to AMI by left anterior descending coronary artery ligation or sham surgery and treated with saline (vehicle) or globular CTRP9 via peritoneal implant osmotic pumps for 6 weeks. H9C2 cardiac cell lines were used in vitro for determining underlying mechanisms. Adipocyte CTRP9 expression and plasma CTRP9 levels were both significantly reduced after AMI. Compared with vehicle, CTRP9 treatment improved animal survival rate (
P
<0.05), restored cardiac function (
P
<0.05), attenuated adverse remodeling (
P
<0.01), and ameliorated cardiomyocyte apoptosis and fibrosis after AMI (
P
<0.01). Among the multiple antiremodeling molecules determined, AMP-activated protein kinase, protein kinase A (PKA), and Akt were significantly activated in CTRP9-treated heart. Surprisingly, CTRP9 remains cardioprotective in mice with cardiomyocyte-specific overexpression of a mutant AMP-activated protein kinase α2 subunit (AMPK-DN). Additional in vitro experiments demonstrated that administration of either PKA inhibitor or PKA-specific small interfering RNA virtually abolished the antiapoptotic effect of CTRP9 (
P
<0.05), whereas inhibition of Akt is less effective in blocking CTRP9 cardioprotection. Finally, CTRP9 phosphorylates BCL-2-associated agonist of cell death at its multiple antiapoptotic sites, an effect blocked by PKA inhibitor.

Conclusions—
We demonstrate that adipokine CTRP9 attenuates adverse cardiac remodeling after AMI, largely via a PKA-dependent pathway.
Toll-Like Receptor 4–Dependent Microglial Activation Mediates Spinal Cord Ischemia–Reperfusion Injury
Authors: Bell Marshall T. , Puskas Ferenc , Agoston Viktor A. , Cleveland Joseph C. , Freeman Kirsten A. , Gamboni Fabia , Herson Paco S. , Meng Xianzhong , Smith Phillip D. , Weyant Michael J. , Fullerton David A. , Reece T. Brett 
Published: September 2013

Background—
Paraplegia continues to complicate thoracoabdominal aortic interventions. The elusive mechanism of spinal cord ischemia–reperfusion injury has delayed the development of pharmacological adjuncts. Microglia, the resident macrophages of the central nervous system, can have pathological responses after a variety of insults. This can occur through toll-like receptor 4 (TLR-4) in stroke models. We hypothesize that spinal cord ischemia–reperfusion injury after aortic occlusion results from TLR-4–mediated microglial activation in mice.

Methods and Results—
TLR-4 mutant and wild-type mice underwent aortic occlusion for 5 minutes, followed by 60 hours of reperfusion when spinal cords were removed for analysis. Spinal cord cytokine production and microglial activation were assessed at 6 and 36 hours after surgery. Isolated microglia from mutant and wild-type mice were subjected to oxygen and glucose deprivation for 24 hours, after which the expression of TLR-4 and proinflammatory cytokines was analyzed. Mice without functional TLR-4 demonstrated decreased microglial activation and cytokine production and had preserved functional outcomes and neuronal viability after thoracic aortic occlusion. After oxygen and glucose deprivation, wild-type microglia had increased TLR-4 expression and production of proinflammatory cytokines.

Conclusions—
The absence of functional TLR-4 attenuated neuronal injury and microglial activation after thoracic aortic occlusion in mice. Furthermore, microglial upregulation of TLR-4 occurred after oxygen and glucose deprivation, and the absence of functional TLR-4 significantly attenuated the production of proinflammatory cytokines. In conclusion, TLR-4–mediated microglia activation in the spinal cord after aortic occlusion is critical in the mechanism of paraplegia after aortic cross-clamping and may provide targets for pharmacological intervention.
Relationship Between Mitochondrial Matrix Volume and Cellular Volume in Response to Stress and the Role of ATP-Sensitive Potassium Channel
Authors: Anastacio Melissa M. , Kanter Evelyn M. , Makepeace Carol M. , Keith Angela D. , Zhang Haixia , Schuessler Richard B. , Nichols Colin G. , Lawton Jennifer S. 
Published: September 2013

Background—
Cardiac myocytes demonstrate significant swelling and associated reduced contractility in response to stress that is prevented by the ATP-sensitive potassium channel opener, diazoxide (DZX) via an unknown mechanism. One proposed mechanism of cardioprotection is mitochondrial matrix swelling. To establish the relationship between mitochondrial and cellular volume during stress, this study examined the effect of DZX on mitochondrial volume.

Methods and Results—

Isolated mouse mitochondria were exposed to the following solutions: Tyrode, isolation buffer, cardioplegia (CPG)±DZX±ATP-sensitive potassium channel inhibitor, 5-hydroxydecanoate, and metabolic inhibition (MI)±DZX±5-hydroxydecanoate. Mitochondrial volume was measured. DZX resulted in significant mitochondrial swelling (
P
<0.0001 versus Tyrode). MI and CPG resulted in significant mitochondrial swelling compared with baseline volume. The addition of DZX did not alter the response of mitochondrial volume to CPG (
P
=0.912) but increased swelling in response to MI (
P
=0.036). The addition of 5-hydroxydecanoate to MI+DZX or CPG+DZX significantly reduced mitochondrial swelling (
P
<0.003 MI+DZX versus MI+DZX+5HD;
P
<0.001 CPG+DZX versus CPG+DZX+5HD).

Conclusions—
Both cellular and mitochondrial volume increased during exposure to MI and CPG. DZX did not alter mitochondrial volume during CPG; however, it was associated with an increase in mitochondrial volume during MI. 5-Hydroxydecanoate reduced mitochondrial volume during exposure to both stresses with DZX, supporting a role for a mitochondrial ATP-sensitive potassium channel in the mechanism of cardioprotection by DZX.